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Sample records for telomere length pre-eclampsia

  1. Telomere Length and Mortality

    DEFF Research Database (Denmark)

    Kimura, Masayuki; Hjelmborg, Jacob V B; Gardner, Jeffrey P

    2008-01-01

    Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast imminent mortality in elderly people better than leukocyte telomere length. They performed mortality...... telomeres predicted the death of the first co-twin better than the mTRFL did (mTRFL: 0.56, 95% confidence interval (CI): 0.49, 0.63; mTRFL(50): 0.59, 95% CI: 0.52, 0.66; mTRFL(25): 0.59, 95% CI: 0.52, 0.66; MTRFL: 0.60, 95% CI: 0.53, 0.67). The telomere-mortality association was stronger in years 3-4 than...

  2. Telomere length and depression

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Rode, Line

    2017-01-01

    as prospectively and genetically. METHOD: Telomere length and three polymorphisms, TERT, TERC and OBFC1, were measured in 67 306 individuals aged 20-100 years from the Danish general population and associated with register-based attendance at hospital for depression and purchase of antidepressant medication.......0-21.5). The genetic analyses suggested that telomere length was not causally associated with attendance at hospital for depression or with purchase of antidepressant medication. CONCLUSIONS: Short telomeres were not associated with depression in prospective or in causal, genetic analyses.......BACKGROUND: Depression has been cross-sectionally associated with short telomeres as a measure of biological age. However, the direction and nature of the association is currently unclear. AIMS: We examined whether short telomere length is associated with depression cross-sectionally as well...

  3. Inheritance of telomere length in a bird.

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    Thorsten Horn

    Full Text Available Telomere dynamics are intensively studied in human ageing research and epidemiology, with many correlations reported between telomere length and age-related diseases, cancer and death. While telomere length is influenced by environmental factors there is also good evidence for a strong heritable component. In human, the mode of telomere length inheritance appears to be paternal and telomere length differs between sexes, with females having longer telomeres than males. Genetic factors, e.g. sex chromosomal inactivation, and non-genetic factors, e.g. antioxidant properties of oestrogen, have been suggested as possible explanations for these sex-specific telomere inheritance and telomere length differences. To test the influence of sex chromosomes on telomere length, we investigated inheritance and sex-specificity of telomere length in a bird species, the kakapo (Strigops habroptilus, in which females are the heterogametic sex (ZW and males are the homogametic (ZZ sex. We found that, contrary to findings in humans, telomere length was maternally inherited and also longer in males. These results argue against an effect of sex hormones on telomere length and suggest that factors associated with heterogamy may play a role in telomere inheritance and sex-specific differences in telomere length.

  4. Cytomegalovirus Infection and Pre-Eclampsia

    Directory of Open Access Journals (Sweden)

    Rădulescu Carmen

    2016-06-01

    Full Text Available Introduction: Pre-eclampsia is a pregnancy-specific disease characterized by hypertension after 20 weeks of gestation and proteinuria. It is a major cause of maternal and perinatal morbidity and mortality. The pathogenesis of pre-eclampsia is not completely understood. In our study we investigated if there is a potential link between cytomegalovirus infection and pre-eclampsia and if cytomegalovirus infection is the triggering factor of pre-eclampsia.

  5. Paternal age and telomere length in twins

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob B; Dalgård, Christine; Mangino, Massimo

    2015-01-01

    Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an 'epigenetic' mechanism through which paternal age plays a role in telomere length regulation in humans...

  6. Telomere length in early life predicts lifespan.

    Science.gov (United States)

    Heidinger, Britt J; Blount, Jonathan D; Boner, Winnie; Griffiths, Kate; Metcalfe, Neil B; Monaghan, Pat

    2012-01-31

    The attrition of telomeres, the ends of eukaryote chromosomes, is thought to play an important role in cell deterioration with advancing age. The observed variation in telomere length among individuals of the same age is therefore thought to be related to variation in potential longevity. Studies of this relationship are hampered by the time scale over which individuals need to be followed, particularly in long-lived species where lifespan variation is greatest. So far, data are based either on simple comparisons of telomere length among different age classes or on individuals whose telomere length is measured at most twice and whose subsequent survival is monitored for only a short proportion of the typical lifespan. Both approaches are subject to bias. Key studies, in which telomere length is tracked from early in life, and actual lifespan recorded, have been lacking. We measured telomere length in zebra finches (n = 99) from the nestling stage and at various points thereafter, and recorded their natural lifespan (which varied from less than 1 to almost 9 y). We found telomere length at 25 d to be a very strong predictor of realized lifespan (P telomeres at all points at which they were measured. Reproduction increased adult telomere loss, but this effect appeared transient and did not influence survival. Our results provide the strongest evidence available of the relationship between telomere length and lifespan and emphasize the importance of understanding factors that determine early life telomere length.

  7. Environmental stresses disrupt telomere length homeostasis.

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    Gal Hagit Romano

    Full Text Available Telomeres protect the chromosome ends from degradation and play crucial roles in cellular aging and disease. Recent studies have additionally found a correlation between psychological stress, telomere length, and health outcome in humans. However, studies have not yet explored the causal relationship between stress and telomere length, or the molecular mechanisms underlying that relationship. Using yeast as a model organism, we show that stresses may have very different outcomes: alcohol and acetic acid elongate telomeres, whereas caffeine and high temperatures shorten telomeres. Additional treatments, such as oxidative stress, show no effect. By combining genome-wide expression measurements with a systematic genetic screen, we identify the Rap1/Rif1 pathway as the central mediator of the telomeric response to environmental signals. These results demonstrate that telomere length can be manipulated, and that a carefully regulated homeostasis may become markedly deregulated in opposing directions in response to different environmental cues.

  8. Telomere Length in Elite Athletes.

    Science.gov (United States)

    Muniesa, Carlos A; Verde, Zoraida; Diaz-Ureña, Germán; Santiago, Catalina; Gutiérrez, Fernando; Díaz, Enrique; Gómez-Gallego, Félix; Pareja-Galeano, Helios; Soares-Miranda, Luisa; Lucia, Alejandro

    2017-08-01

    Growing evidence suggests that regular moderate-intensity physical activity is associated with an attenuation of leukocyte telomere length (LTL) shortening. However, more controversy exists regarding higher exercise loads such as those imposed by elite-sport participation. The authors investigated LTL differences between young elite athletes (n = 61, 54% men, age [mean ± SD] 27.2 ± 4.9 y) and healthy nonsmoker, physically inactive controls (n = 64, 52% men, 28.9 ± 6.3 y) using analysis of variance (ANOVA). Elite athletes had, on average, higher LTL than control subjects, 0.89 ± 0.26 vs 0.78 ± 0.31, P = .013 for the group effect, with no significant sex (P = .995) or age effect (P = .114). The results suggest that young elite athletes have longer telomeres than their inactive peers. Further research might assess the LTL of elite athletes of varying ages compared with both age-matched active and inactive individuals.

  9. Massive Ascites Complicating Pre-eclampsia

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    Ma-Lee Ko

    2005-09-01

    Conclusion: Clinicians should be aware of the possible presence of ascites in patients with severe pre-eclampsia. If the hypertension is controlled and the fetus is healthy, abdominal paracentesis without pregnancy termination is an efficacious procedure for the management of massive ascites complicating severe pre-eclampsia.

  10. Hemostasis in pre-eclampsia.

    LENUS (Irish Health Repository)

    Ismail, Siti Khadijah

    2012-01-31

    Pre-eclampsia (P-EC) is a multisystem disorder exclusive to pregnancy. It complicates ~2 to 8% of all pregnancies and remains a major cause of maternal mortality. P-EC is characterized by a profound hypercoagulable state. The delicate hemostatic balance that must be maintained in the uteroplacental circulation during pregnancy makes this system vulnerable to perturbation. An abnormal hemostatic pattern occurs within the uteroplacental circulation in P-EC compared with normal pregnancy. Much recent research has focused on the epidemiological link between inherited thrombophilia and P-EC. The data suggest a weak statistical association, indicating an improbable primary role in the pathogenesis. Without clear evidence, low molecular weight heparins have been widely used to reduce recurrence of P-EC in thrombophilia-positive women. This practice now should be reviewed. Future research needs to focus on improving our basic scientific understanding of the role of the hemostatic system in human placentation.

  11. Hemostasis in pre-eclampsia.

    LENUS (Irish Health Repository)

    Ismail, Siti Khadijah

    2011-03-01

    Pre-eclampsia (P-EC) is a multisystem disorder exclusive to pregnancy. It complicates ~2 to 8% of all pregnancies and remains a major cause of maternal mortality. P-EC is characterized by a profound hypercoagulable state. The delicate hemostatic balance that must be maintained in the uteroplacental circulation during pregnancy makes this system vulnerable to perturbation. An abnormal hemostatic pattern occurs within the uteroplacental circulation in P-EC compared with normal pregnancy. Much recent research has focused on the epidemiological link between inherited thrombophilia and P-EC. The data suggest a weak statistical association, indicating an improbable primary role in the pathogenesis. Without clear evidence, low molecular weight heparins have been widely used to reduce recurrence of P-EC in thrombophilia-positive women. This practice now should be reviewed. Future research needs to focus on improving our basic scientific understanding of the role of the hemostatic system in human placentation.

  12. Role of TERRA in the regulation of telomere length.

    Science.gov (United States)

    Wang, Caiqin; Zhao, Li; Lu, Shiming

    2015-01-01

    Telomere dysfunction is closely associated with human diseases such as cancer and ageing. Inappropriate changes in telomere length and/or structure result in telomere dysfunction. Telomeres have been considered to be transcriptionally silent, but it was recently demonstrated that mammalian telomeres are transcribed into telomeric repeat-containing RNA (TERRA). TERRA, a long non-coding RNA, participates in the regulation of telomere length, telomerase activity and heterochromatinization. The correct regulation of telomere length may be crucial to telomeric homeostasis and functions. Here, we summarize recent advances in our understanding of the crucial role of TERRA in the maintenance of telomere length, with focus on the variety of mechanisms by which TERRA is involved in the regulation of telomere length. This review aims to enable further understanding of how TERRA-targeted drugs can target telomere-related diseases.

  13. Telomere length in early life predicts lifespan

    OpenAIRE

    Heidinger, B. J.; Blount, J.D.; Boner, W.; Griffiths, K.; Metcalfe, N.B.; Monaghan, P.

    2012-01-01

    The attrition of telomeres, the ends of eukaryote chromosomes, is thought to play an important role in cell deterioration with advancing age. The observed variation in telomere length among individuals of the same age is therefore thought to be related to variation in potential longevity. Studies of this relationship are hampered by the time scale over which individuals need to be followed, particularly in long-lived species where lifespan variation is greatest. So far, data are based either ...

  14. Short Telomere Length and Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Madrid, Alexander Scheller; Rode, Line; Nordestgaard, Børge Grønne

    2016-01-01

    BACKGROUND: Short telomeres are associated with aging and have been associated with a high risk of ischemic heart disease in observational studies; however, the latter association could be due to residual confounding and/or reverse causation. We wanted to test the hypothesis that short telomeres...... are associated with high risk of ischemic heart disease using a Mendelian randomization approach free of reverse causation and of most confounding. METHODS: We genotyped 3 genetic variants in OBFC1 (oligonucleotide/oligosaccharide binding fold containing 1), TERT (telomerase reverse transcriptase), and TERC...... (telomerase RNA component), which code for proteins and RNA involved in telomere maintenance. We studied 105 055 individuals from Copenhagen; 17 235 of these individuals were diagnosed with ischemic heart disease between 1977 and 2013, and 66 618 had telomere length measured. For genetic studies, we further...

  15. Placental growth factor and pre-eclampsia

    Science.gov (United States)

    Chau, K; Hennessy, A; Makris, A

    2017-01-01

    Placental growth factor (PlGF) is an increasingly important molecule in the prediction, diagnosis and treatment of pre-eclampsia. It has pro-angiogenic effects on the feto-placental circulation and supports trophoblast growth. Mechanisms by which PlGF expression is regulated continue to be investigated. Low circulating PlGF precedes the manifestation of clinical disease in pre-eclamptic pregnancies and intrauterine growth restriction. This suggests that low PlGF is a marker of abnormal placentation, but it remains uncertain whether this is a cause or consequence. Prediction of pre-eclampsia using PlGF is promising and may assist in the targeting of resources to women at highest risk of adverse pregnancy outcomes. Promisingly, experimental animal models of pre-eclampsia have been successfully treated with supplemental PlGF. Treatment of pre-eclampsia with PlGF is a potential therapeutic option requiring further exploration. This review focuses specifically on the role of PlGF in normal and pathological placental development and in the clinical management of pre-eclampsia. PMID:29115294

  16. Paternal age and telomere length in twins

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob B; Dalgård, Christine; Mangino, Massimo

    2015-01-01

    . Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age...

  17. Twin correlations of telomere length metrics

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob B; Dalgård, Christine; Möller, Sören

    2015-01-01

    BACKGROUND: Leucocyte telomere length (LTL) is a complex trait associated with ageing and longevity. LTL dynamics are defined by LTL and its age-dependent attrition. Strong, but indirect evidence suggests that LTL at birth and its attrition during childhood largely explains interindividual LTL va...

  18. Neurologic Complications of Pre-eclampsia

    NARCIS (Netherlands)

    Zeeman, Gerda G.

    Pre-eclampsia is mainly responsible for the world's large maternal mortality rates, mostly due to acute cerebral complications. This review provides insight into the pathogenesis of the neurologic complications of hypertensive disease in pregnancy. In addition, practical relevance for clinical care

  19. risk factors for severe pre - eclampsia and eclampsia in mulago

    African Journals Online (AJOL)

    87 No. 10 October 2010. RISK FACTORS FOR SEVERE PRE ECLAMPSIA AND ECLAMPSIA IN MULAGO HOSPITAL, KAMPALA,. UGANDA ... Subject: One hundread and fourty three women with severe pre-eclampsia/ eclampsia and 500 women with normal delivery. ...... tertiary prevention of pre-eclampsia.Lancet 2001;.

  20. Telomere Length Correlates with Life Span of Dog Breeds

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    Laura J. Fick

    2012-12-01

    Full Text Available Telomeric DNA repeats are lost as normal somatic cells replicate. When telomeres reach a critically short length, a DNA damage signal is initiated, inducing cell senescence. Some studies have indicated that telomere length correlates with mortality, suggesting that telomere length contributes to human life span; however, other studies report no correlation, and thus the issue remains controversial. Domestic dogs show parallels in telomere biology to humans, with similar telomere length, telomere attrition, and absence of somatic cell telomerase activity. Using this model, we find that peripheral blood mononuclear cell (PBMC telomere length is a strong predictor of average life span among 15 different breeds (p < 0.0001, consistent with telomeres playing a role in life span determination. Dogs lose telomeric DNA ∼10-fold faster than humans, which is similar to the ratio of average life spans between these species. Breeds with shorter mean telomere lengths show an increased probability of death from cardiovascular disease, which was previously correlated with short telomere length in humans.

  1. Anticonvulsants for women with pre-eclampsia.

    Science.gov (United States)

    Duley, L; Gulmezoglu, A M; Henderson-Smart, D J

    2000-01-01

    Pre-eclampsia is a relatively common complication of pregnancy. Anticonvulsants are used in the belief they help prevent eclamptic fits and subsequent poor outcomes for mother and infant. The objective of this review was to assess the effects of anticonvulsants for women with pre-eclampsia on the women and their children. We searched the Cochrane Pregnancy and Childbirth Group trials register, and the Cochrane Controlled Trials Register, 1999 Issue 3. Randomised trials comparing anticonvulsants with placebo or no anticonvulsants or comparisons of different anticonvulsants in women with pre-eclampsia. Trial quality was assessed and data were extracted independently by two reviewers. Nine studies were included. Comparing magnesium sulphate with placebo/no anticonvulsant the relative risk (RR) of eclampsia was 0.33, 95% confidence interval (CI) 0.11 to 1.02. There was no significant difference detected in the risk of caesarean section (RR 1.04, 95% CI 0.92 to 1.17). Magnesium sulphate appeared to be better than phenytoin at reducing the risk of eclampsia (RR 0.05, 95% CI 0.00 to 0.84). However there was an increased risk of caesarean section with magnesium sulphate compared to phenytoin (RR 1.21, 95% CI 1.05 to 1. 41). No statistically significant differences were reported for any other clinically important outcomes. Studies comparing magnesium sulphate and diazepam were too small for any reliable conclusions. There is not enough evidence to establish the benefits and hazards of anticonvulsants for women with pre-eclampsia. If an anticonvulsant is used, magnesium sulphate appears to be the best choice.

  2. Telomere length alterations unique to invasive lobular carcinoma.

    Science.gov (United States)

    Heaphy, Christopher M; Asch-Kendrick, Rebecca; Argani, Pedram; Meeker, Alan K; Cimino-Mathews, Ashley

    2015-08-01

    Telomeres are nucleoprotein complexes located at the extreme ends of eukaryotic chromosomes and protect chromosomal ends from degradation and recombination. Dysfunctional telomeres contribute to genomic instability, promote tumorigenesis, and, in breast cancer, have been associated with increased cancer risk and poor prognosis. Short telomere lengths have been previously associated with triple-negative and human epidermal growth factor receptor (Her2)--positive ductal carcinomas. However, these investigations have not specifically assessed invasive lobular carcinomas (ILCs), which accounts for 5% to 15% of all invasive breast cancers. Here, we evaluate telomere lengths within 48 primary ILCs with complete characterization of estrogen receptor (ER), progesterone receptor (PR), and Her2 status, including 32 luminal/Her2- (ER+/PR+/Her2-), 8 luminal/Her2+ (ER+/PR+/Her2+), 3 Her2+ (ER-/PR-/Her2+), and 5 triple-negative (ER-/PR-/Her2-) carcinomas. A telomere-specific fluorescence in situ hybridization assay, which provides single-cell telomere length resolution, was used to evaluate telomere lengths and compare with standard clinicopathological markers. In contrast to breast ductal carcinoma, in which more than 85% of cases display abnormally short telomeres, approximately half (52%) of the ILCs displayed either normal or long telomeres. Short telomere length was associated with older patient age. Interestingly, 3 cases (6%) displayed a unique telomere pattern consisting of 1 or 2 bright telomere spots among the normal telomere signals within each individual cancer cell, a phenotype that has not been previously described. Additional studies are needed to further evaluate the significance of the unique bright telomere spot phenotype and the potential utility of telomere length as a prognostic marker in ILC. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Maternal lipids in pre-eclampsia: innocent bystander or culprit?

    Science.gov (United States)

    Barrett, Helen L; Dekker Nitert, Marloes; McIntyre, H David; Callaway, Leonie K

    2014-11-01

    Pre-eclampsia continues to be a challenge--to understand the underlying pathogenesis and to prevent or treat in the clinical setting. One area of potential therapies opening up is treatment of maternal lipids and clinical trials are underway using statins in early pre-eclampsia. At present, most potential therapies to treat lipids cannot be recommended for general use in pregnancy and if we were to target maternal lipids to reduce rates of pre-eclampsia, very large numbers of women may need to be treated. Prior to reaching that point, we first need to understand whether maternal lipids are pathogenic in the processes underlying pre-eclampsia. The aim of this review is to examine the role of lipids in the pathogenesis and outcomes of pre-eclampsia, how abnormal lipid genes may be implicated and consider whether treatment of hyperlipidemia has a more general place in the prevention or treatment of pre-eclampsia.

  4. Early pre-eclampsia unmasks underlying IgA nephropathy

    OpenAIRE

    Mona Singh; Akhenaton Pappoe; Burl R Don

    2010-01-01

    Mona Singh, Akhenaton Pappoe, Burl R DonDivision of Nephrology, University of California Davis Medical Center, Sacramento, CA, USAAbstract: Pre-eclampsia is the most ominous complication of pregnancy, and primary glomerular diseases can mimic pre-eclampsia in presentation. A patient presented at 21 weeks gestation with signs and symptoms of both pre-eclampsia and primary glomerular nephropathy. A critical clinical decision whether to continue or terminate the pregnancy was dependent on result...

  5. Father Loss and Child Telomere Length.

    Science.gov (United States)

    Mitchell, Colter; McLanahan, Sara; Schneper, Lisa; Garfinkel, Irv; Brooks-Gunn, Jeanne; Notterman, Daniel

    2017-08-01

    Father loss during childhood has negative health and behavioral consequences, but the biological consequences are unknown. Our goal was to examine how father loss (because of separation and/or divorce, death, or incarceration) is associated with cellular function as estimated by telomere length. Data come from the 9-year follow-up of the Fragile Families and Child Wellbeing Study, a birth cohort study of children in 20 large American cities (N = 2420). Principal measures are as follows: salivary telomere length (sTL), mother reports of father loss, and polymorphisms in genes related to serotonergic and dopaminergic signaling. At 9 years of age, children with father loss have significantly shorter telomeres (14% reduction). Paternal death has the largest association (16%), followed by incarceration (10%), and separation and/or divorce (6%). Changes in income partially mediate these associations (95% mediation for separation and/or divorce, 30% for incarceration, and 25% for death). Effects are 40% greater for boys and 90% greater for children with the most reactive alleles of the serotonin transporter genes when compared with those with the least reactive alleles. No differences were found by age at father loss or a child's race/ethnicity. Father loss has a significant association with children's sTL, with the death of a father showing the largest effect. Income loss explains most of the association between child sTL and separation and/or divorce but much less of the association with incarceration or death. This underscores the important role of fathers in the care and development of children and supplements evidence of the strong negative effects of parental incarceration. Copyright © 2017 by the American Academy of Pediatrics.

  6. Aberrant leukocyte telomere length in Birdshot Uveitis.

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    Nadia Vazirpanah

    Full Text Available Birdshot Uveitis (BU is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.To study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls.Although LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL = 4.87 (= 74131 base pair compared to 4.31 (= 20417 base pair in unaffected controls (P<0.0001. The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1.These findings suggest that BU is accompanied by significantly longer LTL.

  7. The yeast VPS genes affect telomere length regulation.

    Science.gov (United States)

    Rog, Ofer; Smolikov, Sarit; Krauskopf, Anat; Kupiec, Martin

    2005-01-01

    Eukaryotic cells invest a large proportion of their genome in maintaining telomere length homeostasis. Among the 173 non-essential yeast genes found to affect telomere length, a large proportion is involved in vacuolar traffic. When mutated, these vacuolar protein-sorting (VPS) genes lead to telomeres shorter than those observed in the wild type. Using genetic analysis, we characterized the pathway by which VPS15, VPS34, VPS22, VPS23 and VPS28 affect the telomeres. Our results indicate that these VPS genes affect telomere length through a single pathway and that this effect requires the activity of telomerase and the Ku heterodimer, but not the activity of Tel1p or Rif2p. We present models to explain the link between vacuolar traffic and telomere length homeostasis.

  8. Telomere Length Dynamics and the Evolution of Cancer Genome Architecture

    Directory of Open Access Journals (Sweden)

    Kez Cleal

    2018-02-01

    Full Text Available Telomeres are progressively eroded during repeated rounds of cell division due to the end replication problem but also undergo additional more substantial stochastic shortening events. In most cases, shortened telomeres induce a cell-cycle arrest or trigger apoptosis, although for those cells that bypass such signals during tumour progression, a critical length threshold is reached at which telomere dysfunction may ensue. Dysfunction of the telomere nucleoprotein complex can expose free chromosome ends to the DNA double-strand break (DSB repair machinery, leading to telomere fusion with both telomeric and non-telomeric loci. The consequences of telomere fusions in promoting genome instability have long been appreciated through the breakage–fusion–bridge (BFB cycle mechanism, although recent studies using high-throughput sequencing technologies have uncovered evidence of involvement in a wider spectrum of genomic rearrangements including chromothripsis. A critical step in cancer progression is the transition of a clone to immortality, through the stabilisation of the telomere repeat array. This can be achieved via the reactivation of telomerase, or the induction of the alternative lengthening of telomeres (ALT pathway. Whilst telomere dysfunction may promote genome instability and tumour progression, by limiting the replicative potential of a cell and enforcing senescence, telomere shortening can act as a tumour suppressor mechanism. However, the burden of senescent cells has also been implicated as a driver of ageing and age-related pathology, and in the promotion of cancer through inflammatory signalling. Considering the critical role of telomere length in governing cancer biology, we review questions related to the prognostic value of studying the dynamics of telomere shortening and fusion, and discuss mechanisms and consequences of telomere-induced genome rearrangements.

  9. Common variants near TERC are associated with mean telomere length

    NARCIS (Netherlands)

    Codd, Veryan; Mangino, Massimo; van der Harst, Pim; Braund, Peter S.; Kaiser, Michael; Beveridge, Alan J.; Rafelt, Suzanne; Moore, Jasbir; Nelson, Chris; Soranzo, Nicole; Zhai, Guangju; Valdes, Ana M.; Blackburn, Hannah; Mateo Leach, Irene; de Boer, Rudolf A.; Goodall, Alison H.; Ouwehand, Willem; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Navis, Gerjan; Burton, Paul R.; Tobin, Martin D.; Hall, Alistair S.; Thompson, John R.; Spector, Tim; Samani, Nilesh J.

    We conducted genome-wide association analyses of mean leukocyte telomere length in 2,917 individuals, with follow-up replication in 9,492 individuals. We identified an association with telomere length on 3q26 (rs12696304, combined P = 3.72 x 10(-14)) at a locus that includes TERC, which encodes the

  10. Telomere length modulation in human astroglial brain tumors.

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    Domenico La Torre

    Full Text Available BACKGROUND: Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP complex. OBJECTIVE: To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy. MATERIALS AND METHODS: Eight Low Grade Astrocytomas (LGA, 11 Anaplastic Astrocytomas (AA and 11 Glioblastoma Multiforme (GBM samples were analyzed. Three samples of normal brain tissue (NBT were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR. RESULTS: LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex. CONCLUSIONS: In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.

  11. Pre-eclampsia And Eclampsia: For The General Practitioner

    African Journals Online (AJOL)

    Vol. 10. No 1. Pre-eclampsia And Eclampsia: For The General Practitioner. LAR Mtimavalye. WHAT IS IT? Pre-eclampsia is peculiarly a pregnancy complication which occurs commonly during the second half of preg- nancy or within 48 hours of delivery. It is largely found in primiparous women but may also appear later in.

  12. Gene expression profiling of placentas affected by pre-eclampsia

    DEFF Research Database (Denmark)

    Hoegh, Anne Mette; Borup, Rehannah; Nielsen, Finn Cilius

    2010-01-01

    Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA...

  13. Reproductive outcome after early-onset pre-eclampsia

    NARCIS (Netherlands)

    Schaaf, Jelle M.; Bruinse, Hein W.; van der Leeuw-Harmsen, Loes; Groeneveld, Els; Koopman, Corine; Franx, Arie; van Rijn, Bas B.

    2011-01-01

    Early-onset pre-eclampsia is an important cause of maternal and neonatal morbidity and mortality and is believed to have a significant impact on future maternal physical and psychological health. However, structured follow-up data of women with a history of early-onset pre-eclampsia are lacking.

  14. Periodontal disease and pre-eclampsia : a systematic review

    NARCIS (Netherlands)

    Kunnen, Alina; van Doormaal, Jasper J.; Abbas, Frank; Aarnoudse, Jan G.; van Pampus, Maria; Faas, Marijke M.

    2010-01-01

    P>Aim This review evaluates the possible relationship between periodontal disease and pre-eclampsia, a major pregnancy complication. A generalized inflammatory response plays an important role in the pathogenesis of pre-eclampsia. Because periodontal disease is a low-grade inflammatory state,

  15. The heritability of leucocyte telomere length dynamics

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob B; Dalgård, Christine; Möller, Sören

    2015-01-01

    BACKGROUND: Leucocyte telomere length (LTL) is a complex trait associated with ageing and longevity. LTL dynamics are defined by LTL and its age-dependent attrition. Strong, but indirect evidence suggests that LTL at birth and its attrition during childhood largely explains interindividual LTL...... variation among adults. A number of studies have estimated the heritability of LTL, but none has assessed the heritability of age-dependent LTL attrition. METHODS: We examined the heritability of LTL dynamics based on a longitudinal evaluation (an average follow-up of 12 years) in 355 monozygotic and 297...... dizygotic same-sex twins (aged 19-64 years at baseline). RESULTS: Heritability of LTL at baseline was estimated at 64% (95% CI 39% to 83%) with 22% (95% CI 6% to 49%) of shared environmental effects. Heritability of age-dependent LTL attrition rate was estimated at 28% (95% CI 16% to 44%). Individually...

  16. Combined Screening for Early Detection of Pre-Eclampsia

    Directory of Open Access Journals (Sweden)

    Hee Jin Park

    2015-08-01

    Full Text Available Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers.

  17. Do Telomeres Adapt to Physiological Stress? Exploring the Effect of Exercise on Telomere Length and Telomere-Related Proteins

    Directory of Open Access Journals (Sweden)

    Andrew T. Ludlow

    2013-01-01

    Full Text Available Aging is associated with a tissue degeneration phenotype marked by a loss of tissue regenerative capacity. Regenerative capacity is dictated by environmental and genetic factors that govern the balance between damage and repair. The age-associated changes in the ability of tissues to replace lost or damaged cells is partly the cause of many age-related diseases such as Alzheimer's disease, cardiovascular disease, type II diabetes, and sarcopenia. A well-established marker of the aging process is the length of the protective cap at the ends of chromosomes, called telomeres. Telomeres shorten with each cell division and with increasing chronological age and short telomeres have been associated with a range of age-related diseases. Several studies have shown that chronic exposure to exercise (i.e., exercise training is associated with telomere length maintenance; however, recent evidence points out several controversial issues concerning tissue-specific telomere length responses. The goals of the review are to familiarize the reader with the current telomere dogma, review the literature exploring the interactions of exercise with telomere phenotypes, discuss the mechanistic research relating telomere dynamics to exercise stimuli, and finally propose future directions for work related to telomeres and physiological stress.

  18. Quantitative theory of telomere length regulation and cellular senescence.

    Science.gov (United States)

    Rodriguez-Brenes, Ignacio A; Peskin, Charles S

    2010-03-23

    In normal somatic cells, telomere length shortens with each cell replication. This progressive shortening is associated with cellular senescence and apoptosis. Germ cells, stem cells, and the majority of cancer cells express telomerase, an enzyme that extends telomere length and, when expressed at sufficient levels, can immortalize or extend the life span of a cell line. It is believed that telomeres switch between two states: capped and uncapped. The telomere state determines its accessibility to telomerase and also the onset of senescence. One hypothesis is that the t loop, a large lariat-like structure, represents the capped state. In this paper we model a telomere state on the basis of the biophysics of t-loop formation, allowing us to develop a single mathematical model that accounts for two processes: telomere length regulation for telomerase positive cells and cellular senescence in somatic cells. The model predicts the steady-state length distribution for telomerase positive cells, describes the time evolution of telomere length, and computes the life span of a cell line on the basis of the levels of TRF2 and telomerase expression. The model reproduces a wide range of experimental behavior and fits data from immortal cell lines (HeLa S3 and 293T) and somatic cells (human diploid fibroblasts) well. We conclude that the t loop as the capped state is a quantitatively reasonable model of telomere length regulation and cellular senescence.

  19. Telomere Length – a New Biomarker in Medicine

    Directory of Open Access Journals (Sweden)

    Agnieszka Kozłowska

    2015-12-01

    Full Text Available A number of xenobiotics in the environment and workplace influences on our health and life. Biomarkers are tools for measuring such exposures and their effects in the organism. Nowadays, telomere length, epigenetic changes, mutations and changes in gene expression pattern have become new molecular biomarkers. Telomeres play the role of molecular clock, which influences on expectancy of cell life and thus aging, the formation of damages, development diseases and carcinogenesis. The telomere length depends on mechanisms of replication and the activity of telomerase. Telomere length is currently used as a biomarker of susceptibility and/or exposure. This paper describes the role of telomere length as a biomarker of aging cells, oxidative stress, a marker of many diseases including cancer, and as a marker of environmental and occupational exposure.

  20. Telomere length elongation after weight loss intervention in obese adults.

    Science.gov (United States)

    Carulli, L; Anzivino, C; Baldelli, E; Zenobii, M F; Rocchi, M B L; Bertolotti, M

    2016-06-01

    Telomeres may be considered markers of biological aging, shorter telomere length is associated with some age-related diseases; in several studies short telomere length has also been associated to obesity in adults and adolescents. However the relationship between telomere complex functions and obesity is still not clear. Aim of the study was to assess telomere length (TL) in adults' obese subjects before and after weight loss obtained by placement of bioenteric intragastric balloon (BIB) for 6months. We enrolled 42 obese subjects before and after BIB placement as weight loss intervention. Blood samples were collected in order to obtain DNA from leukocyte to measure TL by quantitative PCR. Data were analyzed only in 37 subjects with complete data; all presented important body weight loss (124.06±26.7 vs 105.40±23.14, pweight loss (r=0.44, p=0.007) as well as an inverse correlation between TL at baseline and TL elongation (r=-0.35, p=0.03).The predictors of TL elongation were once again weight loss and short TL at baseline (respectively p=0.007 and p=0.003). Our study shows that weight loss is associated to telomere lengthening in a positive correlation: the greater weight loss the greater telomere lengthening; moreover telomere lengthening is more significant in those subjects with shortest telomeres at baseline. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The relationship between telomere length and beekeeping among Malaysians.

    Science.gov (United States)

    Nasir, Nurul Fatihah Mohamad; Kannan, Thirumulu Ponnuraj; Sulaiman, Siti Amrah; Shamsuddin, Shaharum; Azlina, Ahmad; Stangaciu, Stefan

    2015-06-01

    The belief that beekeepers live longer than anyone else is present since ages. However, no research has been done to explore the longevity of life in beekeepers. Here, we investigated the telomere length in 30 male beekeepers and 30 male non-beekeepers and associated them with the longevity of life using Southern analysis of terminal restriction fragments (TRFs) generated by Hinf I/Rsa I digestion of human genomic DNA using TeloTAGGG Telomere Length Assay. Interestingly, we found that the telomere length of male beekeepers was significantly longer than those of male non-beekeepers with a p value of less than 0.05, suggesting that beekeepers may have longer life compared to non-beekeepers. We further found that the consumption of bee products for a long period and frequent consumption of bee products per day are associated with telomere length. An increase of year in consuming bee products is associated with a mean increase in telomere length of 0.258 kbp. In addition, an increase in frequency of eating bee products per day was also associated with a mean increase of 2.66 kbp in telomere length. These results suggested that bee products might play some roles in telomere length maintenance.

  2. Serum inhibin and leptin: Risk factors for pre-eclampsia?

    Science.gov (United States)

    Chrelias, Georgios; Makris, Georgios-Marios; Papanota, Aristea-Maria; Spathis, Aris; Salamalekis, Georgios; Sergentanis, Theodoros N; Rizos, Demetrios; Karakitsos, Petros; Chrelias, Charalampos

    2016-12-01

    Pre-eclampsia and eclampsia are parts of the broader spectrum of hypertensive disorders complicating pregnancy. This study aims to examine the association between serum inhibin and leptin levels and pre-eclampsia. This study included 98 consecutive cases of pregnant women with pre-eclampsia, together with their 98 pregnant controls, matched for age, gestational week and time period of delivery. Maternal venous blood samples were obtained within 24h before delivery. In addition to serum inhibin and leptin, birth order, multiple pregnancy, maternal age, maternal overweight/obesity, maternal education, maternal smoking and family history of diabetes/hypertension, were examined as risk factors. Multivariate logistic regression analysis was performed. At the univariate analysis, serum inhibin and leptin levels were significantly higher in cases vs. Pre-eclampsia occurred more frequently in primiparous women, whereas overweight and obesity were also associated with pre-eclampsia. At the multivariate analysis, higher serum inhibin levels were associated with pre-eclampsia (multivariate OR=1.09, 95%CI: 1.03-1.17, p=0.004, increase per 0.1ng/mL). On the other hand, leptin was not independently associated with the occurrence of pre-eclampsia (multivariate OR=1.02, 95%CI: 0.95-1.09, p=0.631, increase per 10ng/mL). Elevated serum inhibin levels seem to be associated with pre-eclampsia, reflecting placental dysfunction. Increased serum leptin levels may merely reflect an elevated maternal body mass index, which is a well-known risk factor for pre-eclampsia. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Relationship between interpersonal sensitivity and leukocyte telomere length.

    Science.gov (United States)

    Suzuki, Akihito; Matsumoto, Yoshihiko; Enokido, Masanori; Shirata, Toshinori; Goto, Kaoru; Otani, Koichi

    2017-10-10

    Telomeres are repetitive DNA sequences located at the ends of chromosomes, and telomere length represents a biological marker for cellular aging. Interpersonal sensitivity, excessive sensitivity to the behavior and feelings of others, is one of the vulnerable factors to depression. In the present study, we examined the effect of interpersonal sensitivity on telomere length in healthy subjects. The subjects were 159 unrelated healthy Japanese volunteers. Mean age ± SD (range) of the subjects was 42.3 ± 7.8 (30-61) years. Interpersonal sensitivity was assessed by the Japanese version of the Interpersonal Sensitivity Measure (IPSM). Leukocyte telomere length was determined by a quantitative real-time PCR method. Higher scores of the total IPSM were significantly (β = -0.163, p = 0.038) related to shorter telomere length. In the sub-scale analysis, higher scores of timidity were significantly (β = -0.220, p = 0.044) associated with shorter telomere length. The present study suggests that subjects with higher interpersonal sensitivity have shorter leukocyte telomere length, implying that interpersonal sensitivity has an impact on cellular aging.

  4. Telomere length and cortisol reactivity in children of depressed mothers.

    Science.gov (United States)

    Gotlib, I H; LeMoult, J; Colich, N L; Foland-Ross, L C; Hallmayer, J; Joormann, J; Lin, J; Wolkowitz, O M

    2015-05-01

    A growing body of research demonstrates that individuals diagnosed with major depressive disorder (MDD) are characterized by shortened telomere length, which has been posited to underlie the association between depression and increased instances of medical illness. The temporal nature of the relation between MDD and shortened telomere length, however, is not clear. Importantly, both MDD and telomere length have been associated independently with high levels of stress, implicating dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and anomalous levels of cortisol secretion in this relation. Despite these associations, no study has assessed telomere length or its relation with HPA-axis activity in individuals at risk for depression, before the onset of disorder. In the present study, we assessed cortisol levels in response to a laboratory stressor and telomere length in 97 healthy young daughters of mothers either with recurrent episodes of depression (i.e., daughters at familial risk for depression) or with no history of psychopathology. We found that daughters of depressed mothers had shorter telomeres than did daughters of never-depressed mothers and, further, that shorter telomeres were associated with greater cortisol reactivity to stress. This study is the first to demonstrate that children at familial risk of developing MDD are characterized by accelerated biological aging, operationalized as shortened telomere length, before they had experienced an onset of depression; this may predispose them to develop not only MDD but also other age-related medical illnesses. It is critical, therefore, that we attempt to identify and distinguish genetic and environmental mechanisms that contribute to telomere shortening.

  5. Neurokinin B and pre-eclampsia: a decade of discovery

    Directory of Open Access Journals (Sweden)

    Page Nigel M

    2010-01-01

    Full Text Available Abstract At the start of the last decade, we provided evidence that levels of the peptide neurokinin B were highly elevated in pre-eclampsia. We hypothesized that elevated levels of neurokinin B may be an indicator of pre-eclampsia and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms. At the time of the original hypothesis many questions remained outstanding. These included - Does neurokinin B have any diagnostic value in the detection and diagnosis of pre-eclampsia? - What is the cause of the elevated levels of neurokinin B during pre-eclampsia? - What is the physiological significance of neurokinin B in the placenta? This review discusses the answers to these questions taking into account the subsequent developments of the past ten years and analyzing the plethora of discoveries that have arisen from those initial observations.

  6. Calcium supplementation to prevent pre-eclampsia - a systematic ...

    African Journals Online (AJOL)

    Calcium supplementation to prevent pre-eclampsia - a systematic review. ... To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child adverse ... Article Metrics.

  7. Gene expression profiling of placentas affected by pre-eclampsia

    DEFF Research Database (Denmark)

    Hoegh, Anne Mette; Borup, Rehannah; Nielsen, Finn Cilius

    2010-01-01

    Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA...... expression from pooled samples was analysed by microarrays. Verification of the expression of selected genes was performed using real-time PCR. A surprisingly low number of genes (21 out of 15,000) were identified as differentially expressed. Among these were genes not previously associated with pre-eclampsia...... as bradykinin B1 receptor and a 14-3-3 protein, but also genes that have already been connected with pre-eclampsia, for example, inhibin beta A subunit and leptin. A low number of genes were repeatedly identified as differentially expressed, because they may represent the endpoint of a cascade of events...

  8. Television Watching and Telomere Length Among Adults in Southwest China.

    Science.gov (United States)

    Xue, Hong-Mei; Liu, Qian-Qian; Tian, Guo; Quan, Li-Ming; Zhao, Yong; Cheng, Guo

    2017-09-01

    To explore the independent associations of sedentary behavior and physical activity with telomere length among Chinese adults. Data on total time of sedentary behavior, screen-based sedentary behavior (including television watching and computer or phone use), moderate to vigorous physical activity, and dietary intake of 518 adults in Chengdu, Guizhou, and Xiamen in China (54.25% women) aged 20 to 70 years were obtained between 2013 and 2015 through questionnaires. Height, weight, and waist circumference were measured to calculate body mass index and percentage of body fat. Telomere length was measured through Southern blot technique. Television watching was inversely related to adjusted telomere length (-71.75 base pair; SE = 34.40; P  = .04). Furthermore, a similar trend between telomere length and television watching was found in the group aged 20 to 40 years after adjusting for all covariates. Adults aged 20 to 40 years in the highest tertile of daily time spent on watching television had 4.0% shorter telomere length than adults in the lowest tertile (P = .03). Although the association is modest, television watching is inversely related to telomere length among Chinese adults, warranting further investigation in large prospective studies.

  9. Serious Visual (Ocular) Complications in Pre-eclampsia and Eclampsia.

    Science.gov (United States)

    Radha Bai Prabhu, Thangappah

    2017-10-01

    Complete loss of vision is an uncommon ocular complication of pre-eclampsia/eclampsia. The conditions which lead to visual loss in pre-eclampsia include cortical blindness, retinal detachment, retinal vascular thrombosis and optic nerve atrophy. The objective was to describe the cause, clinical course and prognosis in blindness complicating pre-eclampsia. This is a prospective observational study conducted at the Govt. Hospital for Women and Children, Chennai, from January 2006 to December 2010. Sixteen women who were diagnosed with blindness complicating pre-eclampsia were analysed for the cause of blindness, clinical details and prognosis. The incidence of blindness among women with pre-eclampsia and eclampsia was 0.17%. The cause of visual loss was cortical blindness in 14 patients and retinal detachment in two patients. Blindness manifested predominantly in the intrapartum and postpartum period in 13/16 cases (81.25%). Seven patients (43.75%) suffered from severe pre-eclampsia, and nine patients (56.25%) suffered from eclampsia. HELLP syndrome, gestational diabetes mellitus (GDM) and anaemia were seen in two patients each. Seven patients also presented with motor deficits. CT scan imaging showed cortical vein thrombosis in five cases, arterial infarcts in two cases, widespread hypodense areas in the occipito-parietal region in six cases. In patients with cortical blindness, recovery of vision occurred within 10 days. Cortical blindness and retinal detachment are rare complications of pre-eclampsia and eclampsia. The prognosis is usually good especially with cortical blindness where the loss of vision is transient. The mainstay of management is effective treatment of pre-eclampsia/eclampsia along with termination of pregnancy.

  10. Proteinuria as a predictor of complications of pre-eclampsia

    Directory of Open Access Journals (Sweden)

    Belfort Michael

    2009-03-01

    Full Text Available Abstract Proteinuria is a defining criterion for the diagnosis of pre-eclampsia. The amount of protein lost per day has been thought by some to predict both maternal and fetal outcome. The systematic review of 16 primary papers including over 6700 patients by Thangaratinam and colleagues published this month in BMC Medicine suggests otherwise. This finding may influence our management of pre-eclampsia.

  11. Telomere Length and the Cancer–Atherosclerosis Trade-Off

    Science.gov (United States)

    Stone, Rivka C.; Horvath, Kent; Kark, Jeremy D.; Susser, Ezra; Tishkoff, Sarah A.; Aviv, Abraham

    2016-01-01

    Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short-living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a) the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b) how cancer might have played a role in the evolution of telomere biology across mammals, (c) evidence that in modern humans telomere length is a determinant (rather than only a biomarker) of cancer and atherosclerosis, and (d) the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan. PMID:27386863

  12. Mathematical model of alternative mechanism of telomere length maintenance.

    Science.gov (United States)

    Kollár, Richard; Bod'ová, Katarína; Nosek, Jozef; Tomáška, L'ubomír

    2014-03-01

    Biopolymer length regulation is a complex process that involves a large number of biological, chemical, and physical subprocesses acting simultaneously across multiple spatial and temporal scales. An illustrative example important for genomic stability is the length regulation of telomeres-nucleoprotein structures at the ends of linear chromosomes consisting of tandemly repeated DNA sequences and a specialized set of proteins. Maintenance of telomeres is often facilitated by the enzyme telomerase but, particularly in telomerase-free systems, the maintenance of chromosomal termini depends on alternative lengthening of telomeres (ALT) mechanisms mediated by recombination. Various linear and circular DNA structures were identified to participate in ALT, however, dynamics of the whole process is still poorly understood. We propose a chemical kinetics model of ALT with kinetic rates systematically derived from the biophysics of DNA diffusion and looping. The reaction system is reduced to a coagulation-fragmentation system by quasi-steady-state approximation. The detailed treatment of kinetic rates yields explicit formulas for expected size distributions of telomeres that demonstrate the key role played by the J factor, a quantitative measure of bending of polymers. The results are in agreement with experimental data and point out interesting phenomena: an appearance of very long telomeric circles if the total telomere density exceeds a critical value (excess mass) and a nonlinear response of the telomere size distributions to the amount of telomeric DNA in the system. The results can be of general importance for understanding dynamics of telomeres in telomerase-independent systems as this mode of telomere maintenance is similar to the situation in tumor cells lacking telomerase activity. Furthermore, due to its universality, the model may also serve as a prototype of an interaction between linear and circular DNA structures in various settings.

  13. Childhood adversity, social support, and telomere length among perinatal women.

    Science.gov (United States)

    Mitchell, Amanda M; Kowalsky, Jennifer M; Epel, Elissa S; Lin, Jue; Christian, Lisa M

    2018-01-01

    Adverse perinatal health outcomes are heightened among women with psychosocial risk factors, including childhood adversity and a lack of social support. Biological aging could be one pathway by which such outcomes occur. However, data examining links between psychosocial factors and indicators of biological aging among perinatal women are limited. The current study examined the associations of childhood socioeconomic status (SES), childhood trauma, and current social support with telomere length in peripheral blood mononuclear cells (PBMCs) in a sample of 81 women assessed in early, mid, and late pregnancy as well as 7-11 weeks postpartum. Childhood SES was defined as perceived childhood social class and parental educational attainment. Measures included the Childhood Trauma Questionnaire, Center for Epidemiologic Studies-Depression Scale, Multidimensional Scale of Perceived Social Support, and average telomere length in PBMCs. Per a linear mixed model, telomere length did not change across pregnancy and postpartum visits; thus, subsequent analyses defined telomere length as the average across all available timepoints. ANCOVAs showed group differences by perceived childhood social class, maternal and paternal educational attainment, and current family social support, with lower values corresponding with shorter telomeres, after adjustment for possible confounds. No effects of childhood trauma or social support from significant others or friends on telomere length were observed. Findings demonstrate that while current SES was not related to telomeres, low childhood SES, independent of current SES, and low family social support were distinct risk factors for cellular aging in women. These data have relevance for understanding potential mechanisms by which early life deprivation of socioeconomic and relationship resources affect maternal health. In turn, this has potential significance for intergenerational transmission of telomere length. The predictive value of

  14. Diagnostic criteria and reporting procedures for pre-eclampsia

    DEFF Research Database (Denmark)

    Klemmensen, Ase K; Olsen, Sjurdur F.; Wengel, Christina M

    2005-01-01

    OBJECTIVE: A precondition for the rational use of obstetric databases in biomedical research is detailed knowledge on how data are being generated. We identified the diagnostic procedures and criteria for pre-eclampsia (PE) and assessed the level of obstetric training of the personnel responsible...... of pregnancy diagnoses to the National Patient Registry differed widely in training. For complicated pregnancies, departments ranged from having only specialists reporting all cases to secretaries reporting up to 50%. Cut off limits of blood pressure (BP) and protein loss used to diagnose pre-eclampsia showed...... large differences across departments. The diagnoses given to three case stories showed little correlation to the criteria the departments reported using. CONCLUSION: Even in a small country like Denmark with 34 obstetrical departments, there was little consensus on the diagnostic criteria for pre-eclampsia...

  15. Estimating telomere length from whole genome sequence data.

    Science.gov (United States)

    Ding, Zhihao; Mangino, Massimo; Aviv, Abraham; Spector, Tim; Durbin, Richard

    2014-05-01

    Telomeres play a key role in replicative ageing and undergo age-dependent attrition in vivo. Here, we report a novel method, TelSeq, to measure average telomere length from whole genome or exome shotgun sequence data. In 260 leukocyte samples, we show that TelSeq results correlate with Southern blot measurements of the mean length of terminal restriction fragments (mTRFs) and display age-dependent attrition comparably well as mTRFs. © The Author(s) 2014. Published by Oxford University Press [on behalf of insert name of society].

  16. Telomere lengths, pulmonary fibrosis and telomerase (TERT mutations.

    Directory of Open Access Journals (Sweden)

    Alberto Diaz de Leon

    2010-05-01

    Full Text Available Telomerase is an enzyme that catalyzes the addition of nucleotides on the ends of chromosomes. Rare loss of function mutations in the gene that encodes the protein component of telomerase (TERT have been described in patients with idiopathic pulmonary fibrosis (IPF. Here we examine the telomere lengths and pulmonary fibrosis phenotype seen in multiple kindreds with heterozygous TERT mutations.We have identified 134 individuals with heterozygous TERT mutations from 21 unrelated families. Available medical records, surgical lung biopsies and radiographs were evaluated retrospectively. Genomic DNA isolated from circulating leukocytes has been used to measure telomere lengths with a quantitative PCR assay. We find that telomere lengths of TERT mutation carriers decrease in an age-dependent manner and show progressive shortening with successive generations of mutation inheritance. Family members without TERT mutations have a shorter mean telomere length than normal, demonstrating epigenetic inheritance of shortened telomere lengths in the absence of an inherited TERT mutation. Pulmonary fibrosis is an age-dependent phenotype not seen in mutation carriers less than 40 years of age but found in 60% of men 60 years or older; its development is associated with environmental exposures including cigarette smoking. A radiographic CT pattern of usual interstitial pneumonia (UIP, which is consistent with a diagnosis of IPF, is seen in 74% of cases and a pathologic pattern of UIP is seen in 86% of surgical lung biopsies. Pulmonary fibrosis associated with TERT mutations is progressive and lethal with a mean survival of 3 years after diagnosis. Overall, TERT mutation carriers demonstrate reduced life expectancy, with a mean age of death of 58 and 67 years for males and females, respectively.A subset of pulmonary fibrosis, like dyskeratosis congenita, bone marrow failure, and liver disease, represents a "telomeropathy" caused by germline mutations in telomerase

  17. Association of Telomere Length with Breast Cancer Prognostic Factors.

    Directory of Open Access Journals (Sweden)

    Kaoutar Ennour-Idrissi

    Full Text Available Telomere length, a marker of cell aging, seems to be affected by the same factors thought to be associated with breast cancer prognosis.To examine associations of peripheral blood cell-measured telomere length with traditional and potential prognostic factors in breast cancer patients.We conducted a cross-sectional analysis of data collected before surgery from 162 breast cancer patients recruited consecutively between 01/2011 and 05/2012, at a breast cancer reference center. Data on the main lifestyle factors (smoking, alcohol consumption, physical activity were collected using standardized questionnaires. Anthropometric factors were measured. Tumor biological characteristics were extracted from pathology reports. Telomere length was measured using a highly reproducible quantitative PCR method in peripheral white blood cells. Spearman partial rank-order correlations and multivariate general linear models were used to evaluate relationships between telomere length and prognostic factors.Telomere length was positively associated with total physical activity (rs = 0.17, P = 0.033; Ptrend = 0.069, occupational physical activity (rs = 0.15, P = 0.054; Ptrend = 0.054 and transportation-related physical activity (rs = 0.19, P = 0.019; P = 0.005. Among post-menopausal women, telomere length remained positively associated with total physical activity (rs = 0.27, P = 0.016; Ptrend = 0.054 and occupational physical activity (rs = 0.26, P = 0.021; Ptrend = 0.056 and was only associated with transportation-related physical activity among pre-menopausal women (rs = 0.27, P = 0.015; P = 0.004. No association was observed between telomere length and recreational or household activities, other lifestyle factors or traditional prognostic factors.Telomeres are longer in more active breast cancer patients. Since white blood cells are involved in anticancer immune responses, these findings suggest that even regular low-intensity physical activity, such as that

  18. Mathematical model of alternative mechanism of telomere length maintenance

    CERN Document Server

    Kollár, Richard; Nosek, Jozef; Tomaska, Lubomir

    2014-01-01

    Biopolymer length regulation is a complex process that involves a large number of subprocesses acting simultaneously across multiple spatial and temporal scales. An illustrative example important for genomic stability is the length regulation of telomeres---nucleo-protein structures at the ends of linear chromosomes. Maintenance of telomeres is often facilitated by the enzyme telomerase but, particularly in telomerase-free systems, the maintenance of chromosomal termini depends on alternative lengthening of telomeres (ALT) mechanisms mediated by recombination. Various linear and circular DNA structures were identified to participate in ALT, however, dynamics of the whole process is still poorly understood. We propose a chemical kinetics model of ALT with kinetic rates systematically derived from the biophysics of DNA diffusion and looping. The reaction system is reduced to a coagulation-fragmentation system by quasi-steady state approximation. The detailed treatment of kinetic rates yields explicit formulae f...

  19. Short Telomere Load, Telomere Length, and Subclinical Atherosclerosis: The PESA Study.

    Science.gov (United States)

    Fernández-Alvira, Juan M; Fuster, Valentin; Dorado, Beatriz; Soberón, Nora; Flores, Ignacio; Gallardo, Mercedes; Pocock, Stuart; Blasco, María A; Andrés, Vicente

    2016-05-31

    Leucocyte telomere length (LTL) shortening is associated with cardiovascular ischemic events and mortality in humans, but data on its association with subclinical atherosclerosis are scarce. Whether the incidence and severity of subclinical atherosclerosis are associated with the abundance of critically short telomeres, a major trigger of cellular senescence, remains unknown. The authors conducted a cross-sectional exploration of the association between subclinical atherosclerosis burden and both average LTL and the abundance of short telomeres (%LTLSubclinical Atherosclerosis) study. Subclinical atherosclerosis was evaluated by coronary artery calcium scan and 2-dimensional/3-dimensional ultrasound in different aortic territories. Statistical significance of differences among multiple covariates was assessed with linear regression models. Independent associations of telomere parameters with plaque presence were evaluated using general linear models. In men and women, age was inversely associated with LTL (Pearson's r = -0.127, p subclinical atherosclerosis. Longitudinal follow-up of PESA participants will assess long-term associations between telomere length and progression of subclinical atherosclerosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  20. Leukocyte telomere length and late-life depression

    NARCIS (Netherlands)

    Schaakxs, R.; Verhoeven, J.E.; Oude Voshaar, R.C.; Comijs, H.C.; Penninx, B.W.

    2015-01-01

    OBJECTIVE: Depressive disorders have been associated with increased risk for aging-related diseases, possibly as a consequence of accelerated cellular aging. Cellular aging, indexed by telomere length (TL) shortening, has been linked to depression in adults younger than 60 years; however, it remains

  1. T cell renewal rates, telomerase, and telomere length shortening

    NARCIS (Netherlands)

    Boer, R.J. de; Noest, A.J.

    1998-01-01

    Measurements on the average telomere lengths of normal human naive and memory T cells suggested that 1) naive and memory human T cells have similar division rates, and 2) that the difference between naive and memory cells reflects the degree of clonal expansion during normal immune reactions. Here

  2. Longitudinal Changes in Leukocyte Telomere Length and Mortality in Humans

    DEFF Research Database (Denmark)

    Bendix, Laila; Thinggaard, Mikael; Fenger, Mogens

    2014-01-01

    Leukocyte telomere length (LTL) ostensibly shortens with age and has been moderately associated with mortality. In humans, these findings have come almost solely from cross-sectional studies. Only recently has LTL shortening within individuals been analyzed in longitudinal studies. Such studies...

  3. Maternal serum copeptin concentrations in early- and late-onset pre-eclampsia

    Directory of Open Access Journals (Sweden)

    Abdullah Tuten

    2015-08-01

    Conclusion: Our results suggest that copeptin levels might be useful in the evaluation of the severity of pre-eclampsia. However, copeptin might be involved in early- rather than late-onset pre-eclampsia.

  4. Expectant management ofearly onset ofsevere pre-eclampsia in

    African Journals Online (AJOL)

    and Davey7 for gestational ages of 30 weeks and more. Sibai et al.' also reported a high perinatal mortality rate of 250/1 000 deliveries (despite intensive treatment of severe hypertension in the mid-trimester). They reviewed pregnancy outcome over a 7-year period in 60 patients with severe pre-eclampsia between 18 and ...

  5. Gene Expression Profiling of Placentas Affected by Pre-Eclampsia

    Directory of Open Access Journals (Sweden)

    Anne Mette Hoegh

    2010-01-01

    Full Text Available Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA expression from pooled samples was analysed by microarrays. Verification of the expression of selected genes was performed using real-time PCR. A surprisingly low number of genes (21 out of 15,000 were identified as differentially expressed. Among these were genes not previously associated with pre-eclampsia as bradykinin B1 receptor and a 14-3-3 protein, but also genes that have already been connected with pre-eclampsia, for example, inhibin beta A subunit and leptin. A low number of genes were repeatedly identified as differentially expressed, because they may represent the endpoint of a cascade of events effectuated throughout gestation. They were associated with transcriptional regulation and vasoregulative pathways, along with a number of hypothetical proteins and gene sequences with unknown functions.

  6. Monocytes and macrophages in pregnancy and pre-eclampsia

    NARCIS (Netherlands)

    Faas, Marijke M.; Spaans, Floor; De Vos, Paul

    2014-01-01

    Preeclampsia is an important complication in pregnancy, characterized by hypertension and proteinuria in the second half of pregnancy. Generalized activation of the inflammatory response is thought to play a role in the pathogenesis of pre-eclampsia. Monocytes may play a central role in this

  7. Long-term cerebral imaging after pre-eclampsia

    NARCIS (Netherlands)

    Aukes, A. M.; De Groot, J. C.; Wiegman, M. J.; Aarnoudse, J. G.; Sanwikarja, G. S.; Zeeman, G. G.

    Please cite this paper as: Aukes A, De Groot J, Wiegman M, Aarnoudse J, Sanwikarja G, Zeeman G. Long-term cerebral imaging after pre-eclampsia. BJOG 2012;119:11171122. Objective Formerly eclamptic women demonstrate cerebral white matter lesions (WMLs) several years following the index pregnancy. The

  8. Pre-eclampsia And Eclampsia: For The General Practitioner

    African Journals Online (AJOL)

    WHAT IS IT? Pre-eclampsia is peculiarly a pregnancy complication which occurs commonly during the second half of preg- nancy or within 48 hours of delivery. It is largely found in primiparous women but may also appear later in reproductive life. It is made up of all or any two of the following: 1. A raised blood pressure; ...

  9. Review:The important epidemiology of pre-eclampsia | Richards ...

    African Journals Online (AJOL)

    Hypertensive disorders in pregnancy are responsible for significant mortality and morbidity of which pre-eclampsia is the greatest contributor. More than half of these deaths can be avoided by better understanding the important epidemiology of this disease. By intelligent revision of the final causes of hypertensive death, it is ...

  10. Maternal pre-pregnancy body mass index and newborn telomere length

    OpenAIRE

    Martens, Dries S.; Plusquin, Michelle; Gyselaers, Wilfried; De Vivo, Immaculata; Nawrot, Tim

    2016-01-01

    Background: Newborn telomere length sets telomere length for later life. At birth, telomere length is highly variable among newborns and the environmental factors during in utero life for this observation remain largely unidentified. Obesity during pregnancy might reflect an adverse nutritional status affecting pregnancy and offspring outcomes, but the association of maternal pre-pregnancy body mass index (BMI) with newborn telomere length, as a mechanism of maternal obesity, on the next gene...

  11. Telomere length as a potential biomarker of coronary artery disease

    Directory of Open Access Journals (Sweden)

    Joyeeta Bhattacharyya

    2017-01-01

    Full Text Available Coronary artery disease (CAD is a multifactorial disease whose prevalence remains unabated especially in developing countries. Both lifestyle factors and genetic predisposition contribute to this disorder. Though notable achievements have been made in the medical, interventional and surgical management of CAD, the need for its prevention is more important. Among other modalities, this calls for defining evidence-based new biomarkers, which on their own or in combination with other known biomarkers may predict the risk of CAD to enable institution of appropriate preventive strategies. In the present communication, we have discussed the usefulness of shortening of telomeres as a potential biomarker of CAD. Clinical research evidence in favour of telomere shortening in CAD is well documented in different ethnic populations of the world. Establishing a well-standardized and accurate method of evaluating telomere length is essential before its routine use in preventive cardiology.

  12. Dietary restraint and telomere length in pre- and postmenopausal women.

    Science.gov (United States)

    Kiefer, Amy; Lin, Jue; Blackburn, Elizabeth; Epel, Elissa

    2008-10-01

    Leukocyte telomere shortening can serve as a biomarker of aging, as telomere length (TL) can decline with age and shortening is positively associated with morbidity and mortality. It is therefore important to identify psychological and behavioral factors linked to accelerated telomere shortening. Stress and poorer metabolic health (greater adiposity, insulin resistance, and cortisol) correlate with shorter telomeres. Self-reported dietary restraint (DR), defined as chronic preoccupation with weight and attempts at restricting food intake, is linked to greater perceived stress, cortisol, and weight gain, when assessed in community studies (versus in weight loss programs). To test for an association between DR and TL in healthy women across a range of ages. We examined whether DR is linked to TL in two samples, one of premenopausal women (aged 20-50 years;N = 36) and one of postmenopausal women (aged 53-69 years; N = 20). In both samples, higher levels of DR were associated with shorter leukocyte TL, independent of body mass index, smoking, and age. Chronic DR, as assessed by self-report (i.e. not caloric restriction), may be a risk factor for premature telomere shortening. Potential mechanisms are discussed.

  13. Traffic noise exposure affects telomere length in nestling house sparrows.

    Science.gov (United States)

    Meillère, Alizée; Brischoux, François; Ribout, Cécile; Angelier, Frédéric

    2015-09-01

    In a consistently urbanizing world, anthropogenic noise has become almost omnipresent, and there are increasing evidence that high noise levels can have major impacts on wildlife. While the effects of anthropogenic noise exposure on adult animals have been widely studied, surprisingly, there has been little consideration of the effects of noise pollution on developing organisms. Yet, environmental conditions experienced in early life can have dramatic lifelong consequences for fitness. Here, we experimentally manipulated the acoustic environment of free-living house sparrows (Passer domesticus) breeding in nest boxes. We focused on the impact of such disturbance on nestlings' telomere length and fledging success, as telomeres (the protective ends of chromosomes) appear to be a promising predictor of longevity. We showed that despite the absence of any obvious immediate consequences (growth and fledging success), nestlings reared under traffic noise exposure exhibited reduced telomere lengths compared with their unexposed neighbours. Although the mechanisms responsible for this effect remain to be determined, our results provide the first experimental evidence that noise alone can affect a wild vertebrate's early-life telomere length. This suggests that noise exposure may entail important costs for developing organisms. © 2015 The Author(s).

  14. The association of telomere length with family violence and disruption.

    Science.gov (United States)

    Drury, Stacy S; Mabile, Emily; Brett, Zoë H; Esteves, Kyle; Jones, Edward; Shirtcliff, Elizabeth A; Theall, Katherine P

    2014-07-01

    To enhance the understanding of biological mechanisms connecting early adversity and negative health, we examine the association between family interpersonal violence and disruption and telomere length in youth. These specific exposures were selected because of their established links with negative health consequences across the life-course. Children, age 5 to 15, were recruited from the greater New Orleans area, and exposure to family disruption and violence was assessed through caregiver report. Telomere length, from buccal cell DNA (buccal telomere length [bTL]), was determined by using monochrome multiplex quantitative real-time polymerase chain reaction. The association between bTL and adversity exposure was tested (n = 80). Cumulative exposure to interpersonal violence and family disruption was correlated with bTL. Controlling for other sociodemographic factors, bTL was significantly shorter in children with higher exposure to family violence and disruption. Witnessing family violence exerted a particularly potent impact. A significant gender interaction was found (β = -0.0086, SE = 0.0031, z test= -2.79, P = .0053) and analysis revealed the effect only in girls. bTL is a molecular biomarker of adversity and allostatic load that is detectable in childhood. The present results extend previous studies by demonstrating that telomeres are sensitive to adversity within the overarching family domain. These findings suggest that the family ecology may be an important target for interventions to reduce the biological impact of adversity in the lives of children. Copyright © 2014 by the American Academy of Pediatrics.

  15. Accuracy of serum uric acid determination in predicting pre-eclampsia: a systematic review

    NARCIS (Netherlands)

    Cnossen, Jeltsje S.; de Ruyter-Hanhijärvi, Hanna; van der Post, Joris A. M.; Mol, Ben W. J.; Khan, Khalid S.; ter Riet, Gerben

    2006-01-01

    BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early prediction of pre-eclampsia may be used to target high-risk women for effective preventative treatments. Hyperuricemia is associated with pre-eclampsia and it has been tested in early pregnancy for

  16. Pre-eclampsia Diagnosis and Treatment Options : A Review of Published Economic Assessments

    NARCIS (Netherlands)

    Zakiyah, Neily; Postma, Maarten J.; Baker, Philip N.; van Asselt, Antoinette D. I.

    2015-01-01

    Pre-eclampsia is a pregnancy complication affecting both mother and fetus. Although there is no proven effective method to prevent pre-eclampsia, early identification of women at risk of pre-eclampsia could enhance appropriate application of antenatal care, management and treatment. Very little is

  17. Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.

    Directory of Open Access Journals (Sweden)

    Masayuki Kimura

    2008-02-01

    Full Text Available Leukocyte telomere length (LTL is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365, aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring, the NHLBI Family Heart Study (NHLBI-Heart, the Longitudinal Study of Aging Danish Twins (Danish Twins, and the UK Adult Twin Registry (UK Twins. Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (50 years donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.

  18. Diagnosis and management of pre-eclampsia: an update

    Directory of Open Access Journals (Sweden)

    Judi A Turner

    2010-09-01

    Full Text Available Judi A TurnerDepartment of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USAAbstract: Pre-eclampsia is a significant, multifactorial, multiorgan disease affecting 5%–8% of all pregnancies in the US where it is the third leading cause of maternal mortality. Despite improvements in the diagnosis and management of pre-eclampsia, severe complications can occur in both the mother and the fetus, and there is no effective method of prevention. Early detection and identification of pregnant women most at risk of developing the disease have proven challenging, but recent efforts combining biochemical and biophysical markers are promising. Efforts at prevention of pre-eclampsia with aspirin and calcium have had limited success, but research on modifiable risk factors, such as obesity surgery, are encouraging. Obstetric management of severe pre-eclampsia focuses on medical management of blood pressure and prevention of seizures using magnesium sulfate, but the ultimate cure remains delivery of the fetus and placenta. Timing of delivery depends on several factors, including gestational age, fetal lung maturity, and most importantly, disease severity. Anesthetic management includes regional anesthesia with careful evaluation of the patient’s airway, volume status, and coagulation status to reduce morbidity and mortality. The potential complications of general anesthesia, including intracranial hemorrhage, in these patients make regional anesthesia the preferred choice in many cases. Nevertheless, it is important to be aware of the contraindications to neuraxial anesthesia and to prepare always for the possibility of encountering a difficult airway.Keywords: pre-eclampsia, diagnosis, risk factors, complications, management, anesthesia, prevention

  19. The heritability of telomere length among the elderly and oldest-old

    DEFF Research Database (Denmark)

    Bischoff, Claus; Graakjaer, Jesper; Petersen, Hans Christian

    2005-01-01

    replication problem, explains why the telomere erodes at each cellular turnover. Telomere length is regulated by a number of associated proteins through a number of different signaling pathways. The determinants of telomere length were studied using whole blood samples from 287 twin pairs aged 73 to 95 years......A tight link exists between telomere length and both population doublings of a cell culture and age of a given organism. The more population doublings of the cell culture or the higher the age of the organism, the shorter the telomeres. The proposed model for telomere shortening, called the end...

  20. Telomere length of anterior crucial ligament after rupture

    DEFF Research Database (Denmark)

    Ponsot, Elodie; Langberg, Henning; Krogsgaard, Michael R

    2011-01-01

    of human anterior cruciate ligament (ACL) obtained during ACL reconstruction: the macroscopically injured proximal part and macroscopically noninjured mid- and distal portions in eight subjects (age 28 ± 8 years). The mean telomere length in ACL was within normal range of values usually reported for other......The regeneration of ligaments following injury is a slow process compared to the healing of many other tissues and the underlying mechanisms remain unknown. The purpose of the study was to evaluate the proliferative potential of ligaments by assessing telomere length within three distinct parts...... tissues indicating that the endogenous machinery responsible for the proliferative potential of ligament is not implicated in its poor healing capacity. The three ACL parts showed similar mean TRF lengths (distal part: 11.5 ± 0.8 kbp, mid-portion: 11.8 ± 1.2 kbp, proximal part: 11.9 ± 1.6 kbp...

  1. The Effect of Physical Activity agains the Telomere Length in the Leukocytes Cells of KONI Athletes

    Directory of Open Access Journals (Sweden)

    Endang Purwaningsih

    2017-07-01

    Full Text Available Telomeres are strands of non coding DNA at the ends of chromosomes that have the primary function to protect DNA from damage and maintain chromosomal stability. Physical exercise will increase the antioxidant activity can increase telomere proteins, lengthen telomeres and or protein networks associated with telomere so that the telomere remains long, or stopping telomere shortening. Telomere length was also associated with age. The purpose of the research was to determine telomere length of leukocyte cells in the KONI (Indonesian National Sports Committee athletes in Jakarta. The research method is descriptive, by measuring telomere length using quantitative PCR on leukocyte cells. Samples are KONI athletes from several sports, including men and women athletes, with ages between 15-20 years. Used a control group (not athletes is students of the Faculty of Medicine, University of YARSI. The results showed that there was no significant difference (p> 0.05 between telomere length group of athletes with the control group in both sexes. Similarly, telomere length between athlete male with female athletes also showed no significant difference (p> 0.05. It was concluded that physical exercise in athletes KONI at the age of 15- 20 years had no effect on telomere length in leukocytes. The results of this study provide information about the telomere length in Indonesian athletes at an early age.

  2. Telomere length is longer in women with late maternal age

    DEFF Research Database (Denmark)

    Fagan, Erin; Sun, Fangui; Bae, Harold

    2017-01-01

    years or less. METHODS:: A nested case control study was conducted using data from the Long Life Family Study. Three hundred eighty-seven women who gave birth to at least one child and lived to the top fifth percentile of their birth cohort, or died before the top fifth percentile of their birth cohort......OBJECTIVE:: Maternal age at birth of last child has been associated with maternal longevity. The aim of this study was to determine whether older women with a history of late maternal age at last childbirth had a longer leukocyte telomere length than those with maternal age at last childbirth of 29...... died, but were at least 70 years old, were studied. Logistic regression models using generalized estimating equations were used to determine the association between tertiles of telomere length and maternal age at last childbirth, adjusting for covariates. RESULTS:: Age at birth of the last child...

  3. Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data

    NARCIS (Netherlands)

    Farmery, James H. R.; Smith, Mike L.; Lynch, Andy G.; Huissoon, Aarnoud; Furnell, Abigail; Mead, Adam; Levine, Adam P.; Manzur, Adnan; Thrasher, Adrian; Greenhalgh, Alan; Parker, Alasdair; Sanchis-Juan, Alba; Richter, Alex; Gardham, Alice; Lawrie, Allan; Sohal, Aman; Creaser-Myers, Amanda; Frary, Amy; Greinacher, Andreas; Themistocleous, Andreas; Peacock, Andrew J.; Marshall, Andrew; Mumford, Andrew; Rice, Andrew; Webster, Andrew; Brady, Angie; Koziell, Ania; Manson, Ania; Chandra, Anita; Hensiek, Anke; Veld, Anna Huis In't; Maw, Anna; Kelly, Anne M.; Moore, Anthony; Vonk Noordegraaf, Anton; Attwood, Antony; Herwadkar, Archana; Ghofrani, Ardi; Houweling, Arjan C.; Girerd, Barbara; Furie, Bruce; Treacy, Carmen M.; Millar, Carolyn M.; Sewell, Carrock; Roughley, Catherine; Titterton, Catherine; Williamson, Catherine; Hadinnapola, Charaka; Deshpande, Charu; Toh, Cheng-Hock; Bacchelli, Chiara; Patch, Chris; Geet, Chris Van; Babbs, Christian; Bryson, Christine; Penkett, Christopher J.; Rhodes, Christopher J.; Watt, Christopher; Bethune, Claire; Booth, Claire; Lentaigne, Claire; McJannet, Coleen; Church, Colin; French, Courtney; Samarghitean, Crina; Halmagyi, Csaba; Gale, Daniel; Greene, Daniel; Hart, Daniel; Allsup, David; Bennett, David; Edgar, David; Kiely, David G.; Gosal, David; Perry, David J.; Keeling, David; Montani, David; Shipley, Debbie; Whitehorn, Deborah; Fletcher, Debra; Krishnakumar, Deepa; Grozeva, Detelina; Kumararatne, Dinakantha; Thompson, Dorothy; Josifova, Dragana; Maher, Eamonn; Wong, Edwin K. S.; Murphy, Elaine; Dewhurst, Eleanor; Louka, Eleni; Rosser, Elisabeth; Chalmers, Elizabeth; Colby, Elizabeth; Drewe, Elizabeth; McDermott, Elizabeth; Thomas, Ellen; Staples, Emily; Clement, Emma; Matthews, Emma; Wakeling, Emma; Oksenhendler, Eric; Turro, Ernest; Reid, Evan; Wassmer, Evangeline; Raymond, F. Lucy; Hu, Fengyuan; Kennedy, Fiona; Soubrier, Florent; Flinter, Frances; Kovacs, Gabor; Polwarth, Gary; Ambegaonkar, Gautum; Arno, Gavin; Hudson, Gavin; Woods, Geoff; Coghlan, Gerry; Hayman, Grant; Arumugakani, Gururaj; Schotte, Gwen; Cook, H. Terry; Alachkar, Hana; Lango Allen, Hana; Lango-Allen, Hana; Stark, Hannah; Stauss, Hans; Schulze, Harald; Boggard, Harm J.; Baxendale, Helen; Dolling, Helen; Firth, Helen; Gall, Henning; Watson, Henry; Longhurst, Hilary; Markus, Hugh S.; Watkins, Hugh; Simeoni, Ilenia; Emmerson, Ingrid; Roberts, Irene; Quinti, Isabella; Wanjiku, Ivy; Gibbs, J. Simon R.; Thaventhiran, James; Whitworth, James; Hurst, Jane; Collins, Janine; Suntharalingam, Jay; Payne, Jeanette; Thachil, Jecko; Martin, Jennifer M.; Martin, Jennifer; Carmichael, Jenny; Maimaris, Jesmeen; Paterson, Joan; Pepke-Zaba, Joanna; Heemskerk, Johan W. M.; Gebhart, Johanna; Davis, John; Pasi, John; Bradley, John R.; Wharton, John; Stephens, Jonathan; Rankin, Julia; Anderson, Julie; Vogt, Julie; von Ziegenweldt, Julie; Rehnstrom, Karola; Megy, Karyn; Talks, Kate; Peerlinck, Kathelijne; Yates, Katherine; Freson, Kathleen; Stirrups, Kathleen; Gomez, Keith; Smith, Kenneth G. C.; Carss, Keren; Rue-Albrecht, Kevin; Gilmour, Kimberley; Masati, Larahmie; Scelsi, Laura; Southgate, Laura; Ranganathan, Lavanya; Ginsberg, Lionel; Devlin, Lisa; Willcocks, Lisa; Ormondroyd, Liz; Lorenzo, Lorena; Harper, Lorraine; Allen, Louise; Daugherty, Louise; Chitre, Manali; Kurian, Manju; Humbert, Marc; Tischkowitz, Marc; Bitner-Glindzicz, Maria; Erwood, Marie; Scully, Marie; Veltman, Marijke; Caulfield, Mark; Layton, Mark; McCarthy, Mark; Ponsford, Mark; Toshner, Mark; Bleda, Marta; Wilkins, Martin; Mathias, Mary; Reilly, Mary; Afzal, Maryam; Brown, Matthew; Rondina, Matthew; Stubbs, Matthew; Haimel, Matthias; Lees, Melissa; Laffan, Michael A.; Browning, Michael; Gattens, Michael; Richards, Michael; Michaelides, Michel; Lambert, Michele P.; Makris, Mike; de Vries, Minka; Mahdi-Rogers, Mohamed; Saleem, Moin; Thomas, Moira; Holder, Muriel; Eyries, Mélanie; Clements-Brod, Naomi; Canham, Natalie; Dormand, Natalie; Zuydam, Natalie Van; Kingston, Nathalie; Ghali, Neeti; Cooper, Nichola; Morrell, Nicholas W.; Yeatman, Nigel; Roy, Noémi; Shamardina, Olga; Alavijeh, Omid S.; Gresele, Paolo; Nurden, Paquita; Chinnery, Patrick; Deegan, Patrick; Yong, Patrick; Man, Patrick Yu Wai; Corris, Paul A.; Calleja, Paul; Gissen, Paul; Bolton-Maggs, Paula; Rayner-Matthews, Paula; Ghataorhe, Pavandeep K.; Gordins, Pavel; Stein, Penelope; Collins, Peter; Dixon, Peter; Kelleher, Peter; Ancliff, Phil; Yu, Ping; Tait, R. Campbell; Linger, Rachel; Doffinger, Rainer; Machado, Rajiv; Kazmi, Rashid; Sargur, Ravishankar; Favier, Remi; Tan, Rhea; Liesner, Ri; Antrobus, Richard; Sandford, Richard; Scott, Richard; Trembath, Richard; Horvath, Rita; Hadden, Rob; MackenzieRoss, Rob V.; Henderson, Robert; MacLaren, Robert; James, Roger; Ghurye, Rohit; DaCosta, Rosa; Hague, Rosie; Mapeta, Rutendo; Armstrong, Ruth; Noorani, Sadia; Murng, Sai; Santra, Saikat; Tuna, Salih; Johnson, Sally; Chong, Sam; Lear, Sara; Walker, Sara; Goddard, Sarah; Mangles, Sarah; Westbury, Sarah; Mehta, Sarju; Hackett, Scott; Nejentsev, Sergey; Moledina, Shahin; Bibi, Shahnaz; Meehan, Sharon; Othman, Shokri; Revel-Vilk, Shoshana; Holden, Simon; McGowan, Simon; Staines, Simon; Savic, Sinisa; Burns, Siobhan; Grigoriadou, Sofia; Papadia, Sofia; Ashford, Sofie; Schulman, Sol; Ali, Sonia; Park, Soo-Mi; Davies, Sophie; Stock, Sophie; Ali, Souad; Deevi, Sri V. V.; Gräf, Stefan; Ghio, Stefano; Wort, Stephen J.; Jolles, Stephen; Austin, Steve; Welch, Steve; Meacham, Stuart; Rankin, Stuart; Walker, Suellen; Seneviratne, Suranjith; Holder, Susan; Sivapalaratnam, Suthesh; Richardson, Sylvia; Kuijpers, Taco; Bariana, Tadbir K.; Bakchoul, Tamam; Everington, Tamara; Renton, Tara; Young, Tim; Aitman, Timothy; Warner, Timothy Q.; Vale, Tom; Hammerton, Tracey; Pollock, Val; Matser, Vera; Cookson, Victoria; Clowes, Virginia; Qasim, Waseem; Wei, Wei; Erber, Wendy N.; Ouwehand, Willem H.; Astle, William; Egner, William; Turek, Wojciech; Henskens, Yvonne; Tan, Yvonne

    2018-01-01

    Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously

  4. Seasonal variation in telomere length of a hibernating rodent

    OpenAIRE

    Turbill, Christopher; Ruf, Thomas; Smith, Steve; Bieber, Claudia

    2013-01-01

    Small hibernating rodents have greater maximum lifespans and hence appear to age more slowly than similar-sized non-hibernators. We tested for a direct effect of hibernation on somatic maintenance and ageing by measuring seasonal changes in relative telomere length (RTL) in the edible dormouse Glis glis. Average RTL in our population did not change significantly over the hibernation season, and a regression model explaining individual variation in post-hibernation RTL suggested a significant ...

  5. Relationship between physical activity level, telomere length, and telomerase activity.

    Science.gov (United States)

    Ludlow, Andrew T; Zimmerman, Jo B; Witkowski, Sarah; Hearn, Joe W; Hatfield, Bradley D; Roth, Stephen M

    2008-10-01

    The purpose of this study was to examine the relationship of exercise energy expenditure (EEE) with both telomere length and telomerase activity in addition to accounting for hTERT C-1327T promoter genotype. Sixty-nine (n = 34 males; n = 35 females) participants 50-70 yr were assessed for weekly EEE level using the Yale Physical Activity Survey. Lifetime consistency of EEE was also determined. Subjects were recruited across a large range of EEE levels and separated into quartiles: 0-990, 991-2340, 2341-3540, and >3541 kcal x wk(-1). Relative telomere length and telomerase activity were measured in peripheral blood mononuclear cells (PBMC). The second EEE quartile exhibited significantly longer telomere lengths [1.12 +/- 0.03 relative units (RU)] than both the first and fourth EEE quartiles (0.94 +/- 0.03 and 0.96 +/- 0.03 RU, respectively; P EEE quartiles. An association was observed between telomerase enzyme activity and hTERT genotype with the TT genotype (1.0 x 10(-2) +/- 4.0 x 10(-3) attomoles (amol) per 10,000 cells; n = 19) having significantly greater telomerase enzyme activity than both the CT (1.3 x 10(-3) +/- 3.2 x 10(-3); n = 30) and CC groups (5.0 x 10(-4) +/- 3.9 x 10(-3); n = 20; P = 0.01). These results indicate that moderate physical activity levels may provide a protective effect on PBMC telomere length compared with both low and high EEE levels.

  6. Telomere length reflects phenotypic quality and costs of reproduction in a long-lived seabird

    OpenAIRE

    Bauch, Christina; Peter H. Becker; Verhulst, Simon

    2013-01-01

    Telomere length is associated with cellular senescence, lifestyle and ageing. Short telomeres indicate poor health in humans and reduced life expectancy in several bird species, but little is known about telomeres in relation to phenotypic quality in wild animals. We investigated telomere lengths in erythrocytes of known-age common terns (Sterna hirundo), a migratory seabird, in relation to arrival date and reproductive performance. Cross-sectional data revealed that, independent of age, indi...

  7. Screening for pre-eclampsia--lessons from aneuploidy screening.

    Science.gov (United States)

    Cuckle, H S

    2011-02-01

    Antenatal screening for aneuploidy is an established routine clinical practice worldwide. The same statistical methodology, developed and refined over three decades, might be adapted to screening for pre-eclampsia. The published literature is reviewed for evidence that the methodology is valid for pre-eclampsia using first trimester maternal serum PP13, PAPP-A, PlGF, ADAM12 and inhibin A, together with MAP and uterine artery Doppler PI. Risk is estimated for both early onset pre-eclampsia, requiring delivery before 34 weeks, or late onset disease. Prior risk from the background prevalence multiplied by likelihood ratios (LRs) for ethnicity, parity, adiposity and family history is multiplied by an LR from the screening marker profile. Markers are expressed in multiples of the gestation-specific median and adjusted for body mass, ethnicity and smoking status as appropriate. A standardized population with a fixed distribution of risk factors and a multi-variate Gaussian model of marker profiles is used to predict performance. There is sufficient published data to estimate individual risks reasonably well. Modeling predicts that using PAPP-A and one other serum marker, together with the physical markers more than two-thirds of early and one-third of late onset cases can be detected by classifying less than 2% of pregnancies as high risk; three-quarters of early case could be detected with a 5% high risk rate. Whilst more data on some markers is still required modeling so far suggests that extending first trimester aneuploidy screening programs to include pre-eclampsia screening would yield a high detection. However, prospective studies are needed to verify the model predictions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Progression of pre-eclampsia to eclampsia under spinal anaesthesia

    Directory of Open Access Journals (Sweden)

    Longinus N Ebirim

    2012-01-01

    Full Text Available Eclampsia remains a problem in the developing countries despite improvements in antenatal care and emergency obstetric facilities. It is an important cause of maternal morbidity and mortality in Nigeria. A 26-year-old primipara, residing in an urban city in Nigeria with antenatal care facilities, booked for antenatal care at 36 weeks of gestation and was then diagnosed with severe pre-eclampsia. She initially refused therapy and was later booked for an emergency cesarean section. She had eclamptic fits during cesarean section under spinal anesthesia, and the seizure was aborted with intravenous diazepam. The postoperative period was uneventful. Progression of pre-eclampsia to eclampsia during cesarean section under spinal anesthesia is rare, but it can occur. Early booking for antenatal care to enable an early diagnosis and treatment are necessary to prevent the progression of pre-eclampsia to eclampsia. There is need to educate the populace on the importance of ante natal care so as to improve its utilization.

  9. Management of pre-eclampsia: issues for anaesthetists.

    Science.gov (United States)

    Dennis, A T

    2012-09-01

    Pre-eclampsia is a leading cause of maternal morbidity and mortality. Substandard care is often present and many deaths are preventable. The aim of this review is to summarise the key management issues for anaesthetists in the light of the current literature. A systematic literature search of electronic databases was undertaken including MEDLINE, EMBASE and the Cochrane Library using the key words obstetrics, pregnancy, pregnancy complications, maternal, pre-eclampsia, preeclampsia, cardiac function, haemodynamics, haemolysis, elevated liver enzymes, low platelets (HELLP), eclampsia, anaesthesia, anesthesia, neuraxial. Relevant Colleges and Societies websites were examined for pertinent guidelines. The disease is defined within the context of hypertensive diseases, and early recognition of pre-eclampsia and its complications, as well as multidisciplinary expert team management is highlighted. Accurate monitoring and recording of observations including the use of transthoracic echocardiography is discussed. The importance of the treatment of systolic blood pressure>180 mmHg and the use of intravenous antihypertensive medication as well as the use of parenteral magnesium sulphate for the treatment and prevention of eclampsia is emphasised . Restricted intravenous fluid therapy and avoidance of ergometrine is discussed. Neuraxial analgesia and anaesthesia, and general anaesthesia for birth is summarised as well as postpartum management including analgesia, thromboprophylaxis, management of acute pulmonary oedema and the use of pharmacological agents in the setting of breastfeeding. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  10. Seasonal variation in telomere length of a hibernating rodent.

    Science.gov (United States)

    Turbill, Christopher; Ruf, Thomas; Smith, Steve; Bieber, Claudia

    2013-04-23

    Small hibernating rodents have greater maximum lifespans and hence appear to age more slowly than similar-sized non-hibernators. We tested for a direct effect of hibernation on somatic maintenance and ageing by measuring seasonal changes in relative telomere length (RTL) in the edible dormouse Glis glis. Average RTL in our population did not change significantly over the hibernation season, and a regression model explaining individual variation in post-hibernation RTL suggested a significant negative effect of the reduction in body mass over the inactive hibernation period (an index of time spent euthermic), supporting the idea that torpor slows ageing. Over the active season, RTL on average decreased in sub-adults but increased in adults, supporting previous findings of greater telomere shortening at younger ages. Telomere length increase might also have been associated with reproduction, which occurred only in adults. Our study reveals how seasonal changes in physiological state influence the progress of life-history traits, such as somatic maintenance and ageing, in a small hibernating rodent.

  11. Analysis of HLA-G gene polymorphisms in Slovak women with pre-eclampsia.

    Science.gov (United States)

    Durmanova, V; Drobny, J; Shawkatova, I; Dlhopolcek, J; Bucova, M

    2017-01-01

    To identify possible association between the selected HLA-G gene polymorphisms and risk of pre-eclampsia. Pre-eclampsia is a serious multisystem disorder that affects women during pregnancy. Despite many research studies, the pathology of pre-eclampsia is not fully understood. Human leukocyte antigen G (HLA-G) belongs to the molecules that induce fetal acceptance by the maternal immune system. HLA-G expression was found to be impaired in the women suffering from pre-eclampsia suggesting its involvement in the development of pre-eclampsia. 123 women with pre-eclampsia and 102 women with normotensive pregnancy were included in the study. HLA-G gene polymorphisms affecting its expression was determined, namely the HLA-G 14 bp insertion/deletion polymorphism in the 3'UTR and HLA-G 1597ΔC polymorphism tagging the HLA-G*01:05N null allele. Genotyping was performed by PCR and PCR-RFLP. No statistically significant differences in either allele or genotype frequencies between pre-eclampsia cases and control group have been observed (p > 0.05). Genetic predisposition of HLA-G to pre-eclampsia in Slovak women was examined for the first time. No association between analysed HLA-G gene polymorphisms and susceptibility to pre-eclampsia was observed. Further investigations are needed to determine the role of immunosuppressive molecule HLA-G in pre-eclampsia development (Tab. 5, Fig. 2, Ref. 37).

  12. Vitamin D, pre-eclampsia, and preterm birth among pregnancies at high risk for pre-eclampsia: an analysis of data from a low-dose aspirin trial.

    Science.gov (United States)

    Gernand, A D; Simhan, H N; Baca, K M; Caritis, S; Bodnar, L M

    2017-11-01

    To examine the relation between maternal vitamin D status and risk of pre-eclampsia and preterm birth in women at high risk for pre-eclampsia. Analysis of prospectively collected data and blood samples from a trial of prenatal low-dose aspirin. Thirteen sites across the USA. Women at high risk for pre-eclampsia. We measured 25-hydroxyvitamin D [25(OH)D] concentrations in stored maternal serum samples drawn at 12-26 weeks' gestation (n = 822). We used mixed effects models to examine the association between 25(OH)D and risk of pre-eclampsia and preterm birth, controlling for confounders including prepregnancy BMI and race. Pre-eclampsia and preterm birth. Twelve percent of women were vitamin D deficient [25(OH)D preterm birth at preterm births at preterm birth at preterm birth at preterm birth at <35 weeks in high-risk pregnancies. © 2016 Royal College of Obstetricians and Gynaecologists.

  13. Dynamics of telomere length in different age groups in a Latvian population.

    Science.gov (United States)

    Zole, Egija; Pliss, Liana; Ranka, Renate; Krumina, Astrida; Baumanis, Viesturs

    2013-12-01

    The shortening of telomeres with ageing is a well-documented observation; however, the reported number of nucleotides in telomeres varies between different laboratories and studies. Such variability is likely caused by ethnic differences between the populations studied. Until now, there were no studies that investigated the variability of telomere length in a senescent Latvian population of the most common mitochondrial haplogroups, defined as H (45%), U (25%), Y chromosomal N1c (40%) and R1a1 (40%). Telomere length was determined in 121 individuals in different age groups, including a control group containing individuals of 20-40 years old and groups of individuals between 60-70 years old, 71-80 years old, 81-90 years old, and above 90 years old. Telomere length was determined using the Southern blot telomeric restriction fragment assay (TRF). Decreased telomere length with ageing was confirmed, but a comparison of centenarians and individuals between 60-90 years of age did not demonstrate a significant difference in telomere length. However, significant variability in telomere length was observed in the control group, indicating probable rapid telomere shortening in some individuals that could lead up to development of health status decline appearing with ageing. Telomere length measured in mononuclear blood cells (MNC) was compared with the telomere length measured in whole peripheral white blood cells (WBC) using TRF. Telomere length in MNC was longer than in WBC for the control group with individuals 20 to 40 years old; in contrast, for the group of individuals aged 65 to 85 years old, measured telomere length was shorter in MNC when compared to WBC.

  14. Effects of donor cells' sex on nuclear transfer efficiency and telomere lengths of cloned goats.

    Science.gov (United States)

    Liu, H-J; Peng, H; Hu, C-C; Li, X-Y; Zhang, J-L; Zheng, Z; Zhang, W-C

    2016-10-01

    The aim of this study was to investigate the effects of donor cells' sex on nuclear transfer efficiency and telomere length of cloned goats from adult skin fibroblast cells. The telomere length of somatic cell cloned goats and their offspring was determined by measuring their mean terminal restriction fragment (TRF) length. The result showed that (i) reconstructed embryos with fibroblast cells from males Boer goats obtained significantly higher kids rate and rate of live kids than those of female embryos and (ii) the telomere lengths of four female cloned goats were shorter compared to their donor cells, but five male cloned goats had the same telomere length with their donor cells, mainly due to great variation existed among them. The offspring from female cloned goats had the same telomere length with their age-matched counterparts. In conclusion, the donor cells' sex had significant effects on nuclear transfer efficiency and telomere lengths of cloned goats. © 2016 Blackwell Verlag GmbH.

  15. Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Samassekou, Oumar [Manitoba Institute of Cell Biology, Cancer Care Manitoba, Department of Physiology, University of Manitoba, Winnipeg, Manitoba R3E 0V9 (Canada)

    2013-08-22

    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the t(9;22) translocation. As in most cancers, short telomeres are one of the features of CML cells, and telomere shortening accentuates as the disease progresses from the chronic phase to the blastic phase. Although most individual telomeres are short, some of them are lengthened, and long individual telomeres occur non-randomly and might be associated with clonal selection. Telomerase is the main mechanism used to maintain telomere lengths, and its activity increases when CML evolves toward advanced stages. ALT might be another mechanism employed by CML cells to sustain the homeostasis of their telomere lengths and this mechanism seems predominant at the early stage of leukemogenesis. Also, telomerase and ALT might jointly act to maintain telomere lengths at the chronic phase, and as CML progresses, telomerase becomes the major mechanism. Finally, CML cells display an altered nuclear organization of their telomeres which is characterized by the presence of high number of telomeric aggregates, a feature of genomic instability, and differential positioning of telomeres. CML represents a good model to study mechanisms responsible for dynamic changes of individual telomere lengths and the remodeling of telomeric nuclear organization throughout cancer progression.

  16. Human XPF controls TRF2 and telomere length maintenance through distinctive mechanisms.

    Science.gov (United States)

    Wu, Yili; Mitchell, Taylor R H; Zhu, Xu-Dong

    2008-10-01

    XPF-ERCC1, a structure-specific endonuclease, is involved in nucleotide excision repair, crosslink repair and homologous recombination. XPF-ERCC1 is also found to interact with TRF2, a duplex telomeric DNA binding protein. We have previously shown that XPF-ERCC1 is required for TRF2-promoted telomere shortening. However, whether XPF-ERCC1 by itself has a role in telomere length maintenance has not been determined. Here we report that overexpression of XPF induces telomere shortening in XPF-proficient cells whereas XPF complementation suppresses telomere lengthening in XPF-deficient cells. These results suggest that XPF-ERCC1 can function as a negative mediator of telomere length maintenance. In addition, we find that introduction of wild type XPF into XPF-deficient cells leads to over 40% reduction in TRF2 association with telomeric DNA, indicating that XPF-ERCC1 negatively regulates TRF2 binding to telomeric DNA. Furthermore, we show that XPF carrying mutations in the conserved nuclease domain fails to control TRF2 association with telomeric DNA but it is competent for modulating telomere length maintenance. These results imply that XPF-ERCC1 controls TRF2 and telomere length maintenance through two distinctive mechanisms, with the former requiring its nuclease activity. Our results further imply that TRF2 association with telomeres may be deregulated in cells derived from XPF patients.

  17. The Genetic Basis of Natural Variation in Caenorhabditis elegans Telomere Length.

    Science.gov (United States)

    Cook, Daniel E; Zdraljevic, Stefan; Tanny, Robyn E; Seo, Beomseok; Riccardi, David D; Noble, Luke M; Rockman, Matthew V; Alkema, Mark J; Braendle, Christian; Kammenga, Jan E; Wang, John; Kruglyak, Leonid; Félix, Marie-Anne; Lee, Junho; Andersen, Erik C

    2016-09-01

    Telomeres are involved in the maintenance of chromosomes and the prevention of genome instability. Despite this central importance, significant variation in telomere length has been observed in a variety of organisms. The genetic determinants of telomere-length variation and their effects on organismal fitness are largely unexplored. Here, we describe natural variation in telomere length across the Caenorhabditis elegans species. We identify a large-effect variant that contributes to differences in telomere length. The variant alters the conserved oligonucleotide/oligosaccharide-binding fold of protection of telomeres 2 (POT-2), a homolog of a human telomere-capping shelterin complex subunit. Mutations within this domain likely reduce the ability of POT-2 to bind telomeric DNA, thereby increasing telomere length. We find that telomere-length variation does not correlate with offspring production or longevity in C. elegans wild isolates, suggesting that naturally long telomeres play a limited role in modifying fitness phenotypes in C. elegans. Copyright © 2016 by the Genetics Society of America.

  18. Computel: computation of mean telomere length from whole-genome next-generation sequencing data.

    Directory of Open Access Journals (Sweden)

    Lilit Nersisyan

    Full Text Available Telomeres are the ends of eukaryotic chromosomes, consisting of consecutive short repeats that protect chromosome ends from degradation. Telomeres shorten with each cell division, leading to replicative cell senescence. Deregulation of telomere length homeostasis is associated with the development of various age-related diseases and cancers. A number of experimental techniques exist for telomere length measurement; however, until recently, the absence of tools for extracting telomere lengths from high-throughput sequencing data has significantly obscured the association of telomere length with molecular processes in normal and diseased conditions. We have developed Computel, a program in R for computing mean telomere length from whole-genome next-generation sequencing data. Computel is open source, and is freely available at https://github.com/lilit-nersisyan/computel. It utilizes a short-read alignment-based approach and integrates various popular tools for sequencing data analysis. We validated it with synthetic and experimental data, and compared its performance with the previously available software. The results have shown that Computel outperforms existing software in accuracy, independence of results from sequencing conditions, stability against inherent sequencing errors, and better ability to distinguish pure telomeric sequences from interstitial telomeric repeats. By providing a highly reliable methodology for determining telomere lengths from whole-genome sequencing data, Computel should help to elucidate the role of telomeres in cellular health and disease.

  19. Cockayne Syndrome group B protein interacts with TRF2 and regulates telomere length and stability.

    Science.gov (United States)

    Batenburg, Nicole L; Mitchell, Taylor R H; Leach, Derrik M; Rainbow, Andrew J; Zhu, Xu-Dong

    2012-10-01

    The majority of Cockayne syndrome (CS) patients carry a mutation in Cockayne Syndrome group B (CSB), a large nuclear protein implicated in DNA repair, transcription and chromatin remodeling. However, whether CSB may play a role in telomere metabolism has not yet been characterized. Here, we report that CSB physically interacts with TRF2, a duplex telomeric DNA binding protein essential for telomere protection. We find that CSB localizes at a small subset of human telomeres and that it is required for preventing the formation of telomere dysfunction-induced foci (TIF) in CS cells. We find that CS cells or CSB knockdown cells accumulate telomere doublets, the suppression of which requires CSB. We find that overexpression of CSB in CS cells promotes telomerase-dependent telomere lengthening, a phenotype that is associated with a decrease in the amount of telomere-bound TRF1, a negative mediator of telomere length maintenance. Furthermore, we show that CS cells or CSB knockdown cells exhibit misregulation of TERRA, a large non-coding telomere repeat-containing RNA important for telomere maintenance. Taken together, these results suggest that CSB is required for maintaining the homeostatic level of TERRA, telomere length and integrity. These results further imply that CS patients carrying CSB mutations may be defective in telomere maintenance.

  20. Longer leukocyte telomere length in Costa Rica's Nicoyan Peninsula: A population-based study

    Science.gov (United States)

    Rehkopf, David H; Dow, William H; Rosero-Bixby, Luis; Lin, Jue; Epel, Elissa S; Blackburn, Elizabeth H

    2013-01-01

    Studies in humans suggest that leukocyte telomere length may act as a marker of biological aging. We investigated whether individuals in the Nicoya region of Costa Rica, known for exceptional longevity, had longer telomere length than those in other parts of the country. After controlling for age, age squared, rurality, rainy season and gender, mean leukocyte telomere length in Nicoya was substantially longer (81 base pairs, pCosta Rica, providing evidence of a biological pathway to which this notable longevity may be related. This relationship remains unchanged (79 base pairs, p<0.05) after statistically controlling for nineteen potential biological, dietary and social and demographic mediators. Thus the difference in mean leukocyte telomere length that characterizes this unique region does not appear to be explainable by traditional behavioral and biological risk factors. More detailed examination of mean leukocyte telomere length by age shows that the regional telomere length difference declines at older ages. PMID:23988653

  1. Correlation of chromosomal instability, telomere length and telomere maintenance in microsatellite stable rectal cancer: a molecular subclass of rectal cancer.

    Science.gov (United States)

    Boardman, Lisa A; Johnson, Ruth A; Viker, Kimberly B; Hafner, Kari A; Jenkins, Robert B; Riegert-Johnson, Douglas L; Smyrk, Thomas C; Litzelman, Kristin; Seo, Songwon; Gangnon, Ronald E; Engelman, Corinne D; Rider, David N; Vanderboom, Russell J; Thibodeau, Stephen N; Petersen, Gloria M; Skinner, Halcyon G

    2013-01-01

    Colorectal cancer (CRC) tumor DNA is characterized by chromosomal damage termed chromosomal instability (CIN) and excessively shortened telomeres. Up to 80% of CRC is microsatellite stable (MSS) and is historically considered to be chromosomally unstable (CIN+). However, tumor phenotyping depicts some MSS CRC with little or no genetic changes, thus being chromosomally stable (CIN-). MSS CIN- tumors have not been assessed for telomere attrition. MSS rectal cancers from patients ≤50 years old with Stage II (B2 or higher) or Stage III disease were assessed for CIN, telomere length and telomere maintenance mechanism (telomerase activation [TA]; alternative lengthening of telomeres [ALT]). Relative telomere length was measured by qPCR in somatic epithelial and cancer DNA. TA was measured with the TRAPeze assay, and tumors were evaluated for the presence of C-circles indicative of ALT. p53 mutation status was assessed in all available samples. DNA copy number changes were evaluated with Spectral Genomics aCGH. Tumors were classified as chromosomally stable (CIN-) and chromosomally instable (CIN+) by degree of DNA copy number changes. CIN- tumors (35%; n=6) had fewer copy number changes (cancer appears to represent a heterogeneous group of tumors that may be categorized both on the basis of CIN status and telomere maintenance mechanism. MSS CIN- rectal cancers appear to have longer telomeres than those of MSS CIN+ rectal cancers and to utilize ALT rather than activation of telomerase.

  2. Correlation of chromosomal instability, telomere length and telomere maintenance in microsatellite stable rectal cancer: a molecular subclass of rectal cancer.

    Directory of Open Access Journals (Sweden)

    Lisa A Boardman

    Full Text Available Colorectal cancer (CRC tumor DNA is characterized by chromosomal damage termed chromosomal instability (CIN and excessively shortened telomeres. Up to 80% of CRC is microsatellite stable (MSS and is historically considered to be chromosomally unstable (CIN+. However, tumor phenotyping depicts some MSS CRC with little or no genetic changes, thus being chromosomally stable (CIN-. MSS CIN- tumors have not been assessed for telomere attrition.MSS rectal cancers from patients ≤50 years old with Stage II (B2 or higher or Stage III disease were assessed for CIN, telomere length and telomere maintenance mechanism (telomerase activation [TA]; alternative lengthening of telomeres [ALT]. Relative telomere length was measured by qPCR in somatic epithelial and cancer DNA. TA was measured with the TRAPeze assay, and tumors were evaluated for the presence of C-circles indicative of ALT. p53 mutation status was assessed in all available samples. DNA copy number changes were evaluated with Spectral Genomics aCGH.Tumors were classified as chromosomally stable (CIN- and chromosomally instable (CIN+ by degree of DNA copy number changes. CIN- tumors (35%; n=6 had fewer copy number changes (<17% of their clones with DNA copy number changes than CIN+ tumors (65%; n=13 which had high levels of copy number changes in 20% to 49% of clones. Telomere lengths were longer in CIN- compared to CIN+ tumors (p=0.0066 and in those in which telomerase was not activated (p=0.004. Tumors exhibiting activation of telomerase had shorter tumor telomeres (p=0.0040; and tended to be CIN+ (p=0.0949.MSS rectal cancer appears to represent a heterogeneous group of tumors that may be categorized both on the basis of CIN status and telomere maintenance mechanism. MSS CIN- rectal cancers appear to have longer telomeres than those of MSS CIN+ rectal cancers and to utilize ALT rather than activation of telomerase.

  3. Is mean platelet volume a better biomarker in pre-eclampsia?

    Science.gov (United States)

    Vilchez, Gustavo; Lagos, Moraima; Kumar, Komal; Argoti, Pedro

    2017-06-01

    Platelet activation and destruction is a well recognized feature of pre-eclampsia, but the current literature is contradictory regarding the role of mean platelet volume (MPV) in the diagnosis of this condition. We investigated whether MPV, compared with other routine laboratory markers such as platelet count, is a more significant biomarker of pre-eclampsia, giving special attention to the intrapartum period. Biochemical and hematological markers along pregnancy including MPV were compared retrospectively between pre-eclampsia and matched controls. Laboratory marker data were compared using independent t-test. A logistic regression model was used to compare the strength of the associations of MPV and other routine markers such as platelet count with pre-eclampsia. Receiver operating characteristic curves were plotted. There were a total of 150 cases of pre-eclampsia and 297 controls. In the pre-eclampsia group, there were 60 cases of mild pre-eclampsia (40.0%); 84, severe (56.0%); and six of eclampsia (4.0%). MPV was significantly higher in the pre-eclampsia than in the control group (11.3 ± 1.0 vs 10.1 ± 0.8 fL, P = 0.002). On multivariate analysis, MPV was the only statistically significant biomarker of pre-eclampsia (OR, 4.5; 95%CI: 1.5-13.7), and severe pre-eclampsia (OR, 6.2; 95%CI: 1.6-24.6); performing superiorly to platelet count. Mean platelet volume is a more significant biomarker of pre-eclampsia. It is more significantly associated with this condition than other routinely measured laboratory markers such as platelet count. MPV is routinely obtained on complete blood cell count and its utilization in the assessment of pre-eclampsia in a clinical setting should continue to be evaluated. © 2017 Japan Society of Obstetrics and Gynecology.

  4. Trends in the incidence of pre-eclampsia and eclampsia in Taiwan between 1998 and 2010

    Directory of Open Access Journals (Sweden)

    Te-Fu Chan

    2015-06-01

    Results: The incidence of pre-eclampsia increased significantly (from 0.87% to 1.21%, but the incidence of eclampsia did not change significantly (from 0.04% to 0.05% between 1998 and 2010. The incidence of pre-eclampsia in the 20–24-year age group was 0.60 ± 0.09%. The relative risk of pre-eclampsia in the different age groups was as follows: aged 35-year age groups.

  5. Short telomere length, cancer survival, and cancer risk in 47102 individuals

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Cawthon, Richard M

    2013-01-01

    Recent meta-analyses have suggested that short telomere length was associated with increased risk of cancer. We therefore tested the hypotheses that short telomere length was associated with increased risk of cancer and with increased risk of early death after cancer.......Recent meta-analyses have suggested that short telomere length was associated with increased risk of cancer. We therefore tested the hypotheses that short telomere length was associated with increased risk of cancer and with increased risk of early death after cancer....

  6. Pre-Eclampsia Placental Carbohydrate Metabolism Regulating Enzymes Activity

    OpenAIRE

    Oré, Raquel; Centro de Investigación en Bioquímica y Nutrición, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Suárez, Silvia; Centro de Investigación en Bioquímica y Nutrición, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Arnao, Inés; Centro de Investigación en Bioquímica y Nutrición, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    Pre eclampsia is one of the most frecuent pathologies during pregnancy. The placental tissue plays an important role in the development of the pathology. In this report we performed a study of the activities of two regulatory enzymes [ Phosphofructokinase I (E.C. 2.7.1.11) and Glucose 6-P-dehidrogenase (E.C. 1.1.1.49)] of the carbohydrate metabolism in both normal and pre emclampsia placental tissue. It has been found a pronounced decreased in both activities in the pathological tissue. We di...

  7. Association of telomere length in older men with mortality and midlife body mass index and smoking.

    Science.gov (United States)

    Strandberg, Timo E; Saijonmaa, Outi; Tilvis, Reijo S; Pitkälä, Kaisu H; Strandberg, Arto Y; Miettinen, Tatu A; Fyhrquist, Frej

    2011-07-01

    Leukocyte telomere length has been taken as a measure of biological age but several inconsistencies exist. We investigated associations between leukocyte telomere length in old age, midlife risk factors, and mortality. The Helsinki Businessmen Study (a cohort of mainly business executives, born 1919-1934) had baseline assessments of cardiovascular risk factors including body mass index between 1964 and 1973 at a mean age of 40. Leukocyte telomere length and proportion of short telomeres were measured from DNA samples collected in 2002-2003 (n = 622, mean age 78 years). Body mass index and smoking in old age were assessed from questionnaires. Total mortality was verified from registers through January 2010. Main outcome measures were relationships between telomeres, body mass index, smoking, and mortality. Leukocyte telomere length and notably proportion of short telomeres (associated with midlife overweight and smoking. The associations were independent of age and cardiovascular risk factors including postload glucose. Associations with body mass index and smoking were nonsignificant in old age, and telomere length did not predict 7-year total mortality. We conclude that smoking and overweight in midlife, irrespective of glucose, cholesterol and blood pressure, are related to shorter leukocyte telomeres in old men. Telomere length in old age did not predict total mortality possibly due to competing causes.

  8. Comparative analysis of whole genome sequencing-based telomere length measurement techniques.

    Science.gov (United States)

    Lee, Michael; Napier, Christine E; Yang, Sile F; Arthur, Jonathan W; Reddel, Roger R; Pickett, Hilda A

    2017-02-01

    Telomeres are regions of repetitive DNA at the ends of human chromosomes that function to maintain the integrity of the genome. Telomere attrition is associated with cellular ageing, whilst telomere maintenance is a prerequisite for malignant transformation. Whole genome sequencing (WGS) captures sequence information from the entire genome, including the telomeres, and is increasingly being applied in research and in the clinic. Several bioinformatics tools have been designed to determine telomere content and length from WGS data, and include Motif_counter, TelSeq, Computel, qMotif, and Telomerecat. These tools utilise different approaches to identify, quantify and normalise telomeric reads; however, it is not known how they compare to one another. Here we describe the details and utility of each tool, and directly compare WGS telomere length output with laboratory-based telomere length measurements. In addition, we evaluate the accessibility, practicality, speed, and additional features of each tool. Each tool was tested using a range of telomere read extraction criteria, to determine the optimal parameters for the specific WGS read length. The aim of this article is to improve the accessibility of WGS telomere length measurement tools, which have the potential to be applied to WGS cohorts for clinical as well as research benefit. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Paternal age and telomere length in twins: the germ stem cell selection paradigm

    Science.gov (United States)

    Hjelmborg, Jacob B; Dalgård, Christine; Mangino, Massimo; Spector, Tim D; Halekoh, Ulrich; Möller, Sören; Kimura, Masayuki; Horvath, Kent; Kark, Jeremy D; Christensen, Kaare; Kyvik, Kirsten O; Aviv, Abraham

    2015-01-01

    Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an ‘epigenetic’ mechanism through which paternal age plays a role in telomere length regulation in humans. Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age-dependent germ stem cell selection process, whereby the selected stem cells have longer telomeres, are more homogenous with respect to telomere length, and share resistance to aging. PMID:25865872

  10. Diet quality and telomere length in older Australian men and women.

    Science.gov (United States)

    Milte, Catherine M; Russell, Aaron P; Ball, Kylie; Crawford, David; Salmon, Jo; McNaughton, Sarah A

    2016-10-26

    Telomere length is a biomarker of cellular ageing, with longer telomeres associated with longevity and reduced risk of chronic disease in older age. Consumption of a healthy diet may contribute to longevity via its impact on cellular ageing, but studies on diet and telomere length to date have been limited and their findings equivocal. The aim of this study was to examine associations between three indices of diet quality and telomere length in older men and women. Adults aged 57-68 years participating in the Wellbeing, Eating and Exercise for a Long Life (WELL) study in Victoria, Australia (n = 679), completed a postal survey including an 111-item food frequency questionnaire in 2012. Diet quality was assessed via three indices: the Dietary Guideline Index, the Recommended Food Score, and the Mediterranean Diet Score. Relative telomere length was measured by quantitative polymerase chain reaction. Associations between diet quality and telomere length were assessed using linear regression adjusted for covariates. After adjustment for age, sex, education, smoking, physical activity, and body mass index (BMI), there were no significant associations between diet quality and relative telomere length. In a sample of older adults residing in Victoria, Australia, men and women aged 57-68 years with better-quality diets did not have longer telomeres. Further investigation in longitudinal studies will determine whether diet can influence telomere length over time in an ageing population.

  11. The role of invariant NKT cells in pre-eclampsia.

    Science.gov (United States)

    Miko, Eva; Szereday, Laszlo; Barakonyi, Aliz; Jarkovich, Andrea; Varga, Peter; Szekeres-Bartho, Julia

    2008-08-01

    Recent data suggest a dominant role of the innate, rather than the adaptive immune system in pregnancy-related immunoregulation. Invariant NKT (iNKT) cells represent a link between the innate and the acquired immune systems; however, little is known about how they function in pre-eclampsia. The aim of our study was to investigate the possible role of iNKT cells in the pathogenesis of pre-eclampsia. Human peripheral blood samples were obtained from pre-eclamptic, healthy pregnant- and non-pregnant women. Freshly separated peripheral blood mononuclear cells were immediately labeled with anti-perforin-, anti-CD69-, anti-CD95-, anti-NKG2A-, anti-NKG2D-, anti-IFN-gamma and anti iNKT antibodies and analyzed by flow cytometry. Pre-eclamptic patients demonstrated increased CD69, perforin and IFN-gamma expression, which could be explained by dysregulation of NK cell receptor expression. These Th1 polarized cells were less susceptible to apoptosis than iNKT cells from healthy pregnant women. Our data suggest that activated iNKT cells of pre-eclamptic women have an increased cytotoxic potential, which may be because of altered expression of NK cell inhibitory and activating receptors.

  12. Modified Terminal Restriction Fragment Analysis for Quantifying Telomere Length Using In-gel Hybridization.

    Science.gov (United States)

    Jenkins, Frank J; Kerr, Charles M; Fouquerel, Elise; Bovbjerg, Dana H; Opresko, Patricia L

    2017-07-10

    There are several different techniques for measuring telomere length, each with their own advantages and disadvantages. The traditional approach, Telomere Restriction Fragment (TRF) analysis, utilizes a DNA hybridization technique whereby genomic DNA samples are digested with restriction enzymes, leaving behind telomere DNA repeats and some sub-telomeric DNA. These are separated by agarose gel electrophoresis, transferred to a filter membrane and hybridized to oligonucleotide probes tagged with either chemiluminescence or radioactivity to visualize telomere restriction fragments. This approach, while requiring a larger quantity of DNA than other techniques such as PCR, can measure the telomere length distribution of a population of cells and allows measurement expressed in absolute kilobases. This manuscript demonstrates a modified DNA hybridization procedure for determining telomere length. Genomic DNA is first digested with restriction enzymes (that do not cut telomeres) and separated by agarose gel electrophoresis. The gel is then dried and the DNA is denatured and hybridized in situ to a radiolabeled oligonucleotide probe. This in situ hybridization avoids loss of telomere DNA and improves signal intensity. Following hybridization, the gels are imaged utilizing phosphor screens and the telomere length is quantified using a graphing program. This procedure was developed by the laboratories of Drs. Woodring Wright and Jerry Shay at the University of Texas Southwestern 1 , 2 . Here, we present a detailed description of this procedure, with some modifications.

  13. Maternal pre-pregnancy body mass index and newborn telomere length.

    Science.gov (United States)

    Martens, Dries S; Plusquin, Michelle; Gyselaers, Wilfried; De Vivo, Immaculata; Nawrot, Tim S

    2016-10-18

    Newborn telomere length sets telomere length for later life. At birth, telomere length is highly variable among newborns and the environmental factors during in utero life for this observation remain largely unidentified. Obesity during pregnancy might reflect an adverse nutritional status affecting pregnancy and offspring outcomes, but the association of maternal pre-pregnancy body mass index (BMI) with newborn telomere length, as a mechanism of maternal obesity, on the next generation has not been addressed. Average relative telomere lengths were measured in cord blood (n = 743) and placental tissue (n = 702) samples using a quantitative real-time PCR method from newborns from the ENVIRONAGE birth cohort in Belgium. By using univariate and multivariable adjusted linear regression models we addressed the associations between pre-pregnancy BMI and cord blood and placental telomere lengths. Maternal age was 29.1 years (range, 17-44) and mean (SD) pre-pregnancy BMI was 24.1 (4.1) kg/m(2). Decline in newborn telomere length occurred in parallel with higher maternal pre-pregnancy BMI. Independent of maternal and paternal age at birth, maternal education, gestational age, newborn gender, ethnicity, birthweight, maternal smoking status, parity, cesarean section, and pregnancy complications, each kg/m(2) increase in pre-pregnancy BMI was associated with a -0.50 % (95 % CI, -0.83 to -0.17 %; P = 0.003) shorter cord blood telomere length and a -0.66 % (95 % CI, -1.06 to -0.25 %; P = 0.002) shorter placental telomere length. Maternal pre-pregnancy BMI is associated with shorter newborn telomere lengths as reflected by cord blood and placental telomeres. These findings support the benefits of a pre-pregnancy healthy weight for promoting molecular longevity from early life onwards.

  14. Food Security and Leukocyte Telomere Length in Adult Americans.

    Science.gov (United States)

    Mazidi, Mohsen; Kengne, Andre Pascal; Vatanparast, Hassan

    2017-01-01

    Leukocyte telomere length (LTL) is a biomarker of biologic age. Whether food security status modulates LTL is still unknown. We investigated the association between food security and LTL in participants of the 1999-2002 US National Health and Nutrition Examination Survey (NHANES). Analysis of covariance (ANCOVA) was used to evaluate the association between food security categories and LTL controlling for sex, race, and education and accounting for the survey design and sample weights. We included 10,888 participants with 5228 (48.0%) being men. They were aged on average 44.1 years. In all, 2362 (21.7%) had less than high school, 2787 (25.6%) had achieved high school, while 5705 (52.5%) had done more than high school. In sex-, race-, and education-adjusted ANCOVA, average LTL (T/S ratio) for participants with high food security versus those with marginal, low, or very low food security was 1.32 versus 1.20 for the age group 25-35 years and 1.26 versus 1.11 for the 35-45 years, ( p food insecurity and LTL shortening in young adults suggest that some of the future effects of food insecurity on chronic disease risk in this population could be mediated by telomere shortening.

  15. Test anxiety and telomere length: Academic stress in adolescents may not cause rapid telomere erosion.

    Science.gov (United States)

    Zou, Yaru; Leong, Waiian; Yao, Mingling; Hu, Xuefei; Lu, Sixiao; Zhu, Xiaowei; Chen, Lianxiang; Tong, Jianjing; Shi, Jingyi; Gilson, Eric; Ye, Jing; Lu, Yiming

    2017-02-14

    Academic stress (AS) is one of the most important health problems experienced by students, but no biomarker of the potential psychological or physical problems associated with AS has yet been identified. As several cross-sectional studies have shown that psychiatric conditions accelerate aging and shorten telomere length (TL), we explored whether AS affected TL.Between June 2014 and July 2014, we recruited 200 junior high school students with imminent final examinations for participation in this study. The students were divided into three subgroups (mild, moderate, and severe anxiety) using the Sarason Test Anxiety Scale (TAS). Saliva samples were collected for TL measurement via quantitative polymerase chain reaction (qPCR).Students from both a specialized and a general school suffered from anxiety (p > 0.05). A total 35% had severe anxiety (score: 26.09±3.87), 33% had moderate anxiety (16.98±2.64), and 32% had mild anxiety (7.89±1.92). The TAS values differed significantly (p 0.05): 1.14±0.46 for those with severe anxiety, 1.02±0.40 for those with moderate anxiety, and 1.12±0.45 for those with mild anxiety.Previous reports have found that AS is very common in Asian adolescents. We found no immediate telomere shortening in adolescents with AS. Longitudinal observations are required to determine if TL is affected by AS.

  16. The Pre-Eclampsia Ontology: A Disease Ontology Representing the Domain Knowledge Specific to Pre-Eclampsia.

    Directory of Open Access Journals (Sweden)

    Satoshi Mizuno

    Full Text Available Pre-eclampsia (PE is a clinical syndrome characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation, and is a leading cause of maternal and perinatal morbidity and mortality. Previous studies have gathered abundant data about PE such as risk factors and pathological findings. However, most of these data are not semantically structured. Clinical data on PE patients are often generated with semantic heterogeneity such as using disparate terminology to describe the same phenomena. In clinical studies, interoperability of heterogenic clinical data is required in various situations. In such a situation, it is necessary to develop an interoperable and standardized semantic framework to research the pathology of PE more comprehensively and to achieve interoperability of heterogenic clinical data of PE patients. In this study, we developed an ontology representing clinical features, treatments, genetic factors, environmental factors, and other aspects of the current knowledge in the domain of PE. We call this pre-eclampsia ontology "PEO". To achieve interoperability with other ontologies, the core structure of PEO was compliant with the hierarchy of the Basic Formal Ontology (BFO. The PEO incorporates a wide range of key concepts and terms of PE from clinical and biomedical research in structuring the knowledge base that is specific to PE; therefore, PEO is expected to enhance PE-specific information retrieval and knowledge discovery in both clinical and biomedical research fields.

  17. Leukocyte telomere length and personality : Associations with the big five and type d personality traits

    NARCIS (Netherlands)

    Schoormans, D.; Verhoeven, J.E.; Denollet, J.; van de Poll-Franse, L.V.; Penninx, B.W.J.H.

    2018-01-01

    Accelerated cellular ageing, which can be examined by telomere length (TL), may be an overarching mechanism underlying the association between personality and adverse health outcomes. This 6-year longitudinal study examined the relation between personality and leukocyte telomere length (LTL) across

  18. Short telomere length, lung function and chronic obstructive pulmonary disease in 46 396 individuals

    DEFF Research Database (Denmark)

    Rode, Line; Bojesen, Stig E; Weischer, Maren

    2013-01-01

    A previous case-control study of 100 individuals found that short telomere length was associated with a 28-fold increased risk of chronic obstructive pulmonary disease (COPD).......A previous case-control study of 100 individuals found that short telomere length was associated with a 28-fold increased risk of chronic obstructive pulmonary disease (COPD)....

  19. Short Telomere Length, Myocardial Infarction, Ischemic Heart Disease, and Early Death

    DEFF Research Database (Denmark)

    Weischer, Maren; Bojesen, Stig E; Cawthon, Richard M

    2012-01-01

    OBJECTIVE: We tested the hypothesis that short telomere length is associated with increased risk of myocardial infarction, ischemic heart disease, and early death. METHODS AND RESULTS: We measured leukocyte telomere length in 2 prospective studies of 19 838 Danish general population participants ...

  20. Knowledge of pre-eclampsia in women living in Makole Ward ...

    African Journals Online (AJOL)

    Abstract. Background: Pre-eclampsia is a hypertensive disorder specific to pregnancy responsible for significant maternal morbidity and mortality in Africa. The majority of deaths related to pre-eclampsia could be avoided with timely and effective care. “Phase one delays” arise because of lack of knowledge. Objectives: This ...

  1. The association of with severe early-onset pre-eclampsia

    African Journals Online (AJOL)

    antibodies with early onset of severe pre-eclampsia before ... early-onset severe pre-eclampsia it is unlikely that they are .... HELLP syndrome. 33. 26. 3. 160/120. 12,6. 2,1. Preterm. Severe uncontrollable hypertension. ACA anticardiolipin antibody; LAC. lUpus anticoagulant; IUD - intra·uterine death; HELLP - haemolysis.

  2. Prediction of pre-eclampsia: a protocol for systematic reviews of test accuracy

    NARCIS (Netherlands)

    Cnossen, Jeltsje S.; van der Post, Joris A. M.; Mol, Ben W. J.; Khan, Khalid S.; Meads, Catherine A.; ter Riet, Gerben

    2006-01-01

    BACKGROUND: Pre-eclampsia, a syndrome of hypertension and proteinuria, is a major cause of maternal and perinatal morbidity and mortality. Accurate prediction of pre-eclampsia is important, since high risk women could benefit from intensive monitoring and preventive treatment. However, decision

  3. Risk factors for severe pre-eclampsia and eclamsia in Mulago ...

    African Journals Online (AJOL)

    Objective: To determine the risk factors for severe pre-eclampsia and eclampsia in Mulago Hospital, Kampala, Uganda. Design: A case control study. Setting: Mulago Hospital labour ward. Subject: One hundread and fourty three women with severe pre-eclampsia/ eclampsia and 500 women with normal delivery. Results: ...

  4. Are high uric acid levels in patients with early pre-eclampsia an ...

    African Journals Online (AJOL)

    Objective. To compare the perinatal mortality rates of pre-eclamptic patients with high, normal and low uric acid levels. Design. Prospective analytic study. Setting. Tertiary hospital to which many patients with severe pre-eclampsia are referred. Subjects. Two hundred and twenty-nine patients with severe pre-eclampsia.

  5. Are high uric acid levels in patients with early pre-eclampsia an ...

    African Journals Online (AJOL)

    Objective. To compare the perinatal mortality rates of pre- eclamptic patients with high, normal and low uric acid levels. Design. Prospective anaJytic study. Setting. Tertiary hospital to which many patients with severe pre-eclampsia are referred. Subjects. Two hundred and twenty-nine patients with severe pre-eclampsia.

  6. Managing pre-eclampsia and eclampsia in Dar es Salaam public ...

    African Journals Online (AJOL)

    Introduction: Severe pre-eclampsia and eclampsia (PE/E) is associated with high maternal and neonatal morbidity and mortality. Early detection and treatment of pre-eclampsia may prevent progression to severe PE/E. When severe PE/E occurs, timely use of anticonvulsants and antihypertensives (as part of emergency ...

  7. Knowledge of pre-eclampsia in women living in Makole Ward ...

    African Journals Online (AJOL)

    Background: Pre-eclampsia is a hypertensive disorder specific to pregnancy responsible for significant maternal morbidity and mortality in Africa. The majority of deaths related to pre-eclampsia could be avoided with timely and effective care. “Phase one delays” arise because of lack of knowledge. Objectives: This study ...

  8. Neighborhood characteristics and leukocyte telomere length: the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Needham, Belinda L; Carroll, Judith E; Diez Roux, Ana V; Fitzpatrick, Annette L; Moore, Kari; Seeman, Teresa E

    2014-07-01

    Telomeres are the protective caps at the ends of eukaryotic chromosomes. Telomeres get shorter each time a cell divides, and critically shortened telomeres trigger cellular senescence. Thus, telomere length is hypothesized to be a biological marker of aging. The purpose of this study was to examine the association between neighborhood characteristics and leukocyte telomere length. Using data from a subsample (n=978) of the Multi-Ethnic Study of Atherosclerosis, a population-based study of women and men aged 45-84, we found that neighborhood social environment (but not neighborhood socioeconomic disadvantage) was associated with telomere length. Respondents who lived in neighborhoods characterized by lower aesthetic quality, safety, and social cohesion had shorter telomeres than those who lived in neighborhoods with a more salutary social environment, even after adjusting for individual-level socioeconomic status and biomedical and lifestyle factors related to telomere length. Telomere length may be one biological mechanism by which neighborhood characteristics influence an individual׳s risk of disease and death. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Shorter leukocyte telomere length is associated with higher risk of infections

    DEFF Research Database (Denmark)

    Helby, Jens; Nordestgaard, Børge G; Benfield, Thomas

    2017-01-01

    in the recipients. These findings suggest that leukocyte telomere length could possibly be a marker of immune competence. Therefore, we tested the hypothesis that shorter leukocyte telomere length is associated with higher risk of infectious disease hospitalization and infection related death. Relative peripheral...... in 1508 individuals. Shorter telomere length was associated with higher risk of any infection (hazard ratio 1.05 per standard deviation shorter leukocyte telomere length; 95% confidence interval 1.03-1.07) and pneumonia (1.07;1.03-1.10) after adjustment for conventional infectious disease risk factors....... Corresponding hazard ratios for infection related death were 1.10 (1.04-1.16) for any infection and 1.11 (1.04-1.19) for pneumonia. Telomere length was not associated with risk of skin infection, urinary tract infection, sepsis, diarrhoeal disease, endocarditis, meningitis or other infections. In conclusion...

  10. Shorter preschool, leukocyte telomere length is associated with obesity at age 9 in Latino children

    DEFF Research Database (Denmark)

    Kjaer, Thora Wesenberg; Faurholt-Jepsen, D; Mehta, K M

    2018-01-01

    The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low-income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006-May 2007) was followed until age 9...... and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator...... of the relationship between excessive sugar-sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13-0.94) after adjustment for known risk factors. Telomere length mediated 11...

  11. Sex Ratio and Twinning in Women with Hyperemesis or Pre-eclampsia

    DEFF Research Database (Denmark)

    Basso, Olga; Olsen, Jørn

    2001-01-01

    We examined twinning and fetal gender in births of women with a hospital diagnosis of pre-eclampsia or hyperemesis. We also investigated sex ratio in infants whose mothers had had hyperemesis or pre-eclampsia in a different pregnancy. From all the hospitalized cases in Denmark between 1980 and 1996...... we extracted 6,227 births with hyperemesis and 24,764 with pre-eclampsia. Twins were more frequent in pregnancies with either condition. The male to female sex ratio was 1.04 (95%CI = 1.02-1.05) in the reference population, 0.87 (95% CI = 0.82-0.91) in births with hyperemesis, and 1.10 (95% CI = 1.......07-1.12) in births with pre-eclampsia. Women with pre-eclampsia had slightly more males also in non-affected pregnancies....

  12. Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings.

    Directory of Open Access Journals (Sweden)

    Owen M Wolkowitz

    2011-03-01

    Full Text Available Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of "accelerated aging" in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD, whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio and inflammation (IL-6. Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05. Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration was 281 base pairs shorter than that in controls (p<0.05, corresponding to approximately seven years of "accelerated cell aging." Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01 and in the controls (p<0.05 and with inflammation in the depressed subjects (p<0.05.These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening

  13. Telomere length and risk of developing gastric adenocarcinoma: The Singapore Chinese Health Study.

    Science.gov (United States)

    Wang, Zhensheng; Koh, Woon-Puay; Jin, Aizhen; Wang, Renwei; Yuan, Jian-Min

    2017-12-07

    Extreme telomere length has been previously reported to be associated with increased risk of gastric cancer. However, evidence from prospective studies on a relative large sample size with long-term follow-up to further corroborate previous study findings is meager. The association between peripheral blood leukocyte telomere length and risk of gastric adenocarcinoma was prospectively examined in a cohort of 26,540 middle-aged or older Chinese nested in the Singapore Chinese Health Study. Telomere length was determined using a validated qPCR-based method. The Cox proportional regression method was used to estimate hazard ratio (HR) and its 95% confidence interval (CI) of gastric adenocarcinoma associated with telomere length after adjustment for potential confounders. Restricted cubic spline analysis was applied to assess the nonlinear relationship between telomere length and gastric cancer risk. A U-shaped association was found between telomere length and risk of gastric adenocarcinoma (P nonlinearity = 0.020). Compared with the second quintile of telomere length, a statistically significant higher risk of gastric adenocarcinoma was associated with either the lowest quintile (HR = 1.63, 95% CI, 1.07-2.47) or the highest quintile (HR = 1.55, 95% CI, 0.97-2.47) of telomere length. This U-shaped relationship was more apparent in men and younger individuals. This is the first prospective study demonstrating a higher risk of gastric cancer to be associated with either extremely short or extremely long telomere length. Short and long telomere length may function differently in the early and late stages of gastric carcinogenesis.

  14. Maternal serum copeptin concentrations in early- and late-onset pre-eclampsia.

    Science.gov (United States)

    Tuten, Abdullah; Oncul, Mahmut; Kucur, Mine; Imamoglu, Metehan; Ekmekci, Ozlem Balcı; Acıkgoz, Abdullah Serdar; Cebe, Fatma Selcen; Yesilbas, Cengiz; Madazlı, Rıza

    2015-08-01

    Early-onset pre-eclampsia is primarily associated with placental dysfunction, whereas late-onset pre-eclampsia is defined as a maternal constitutional disorder. As a protein cosynthesized with vasopressin, copeptin is a potential marker of metabolic syndrome and insulin resistance, which shares similar risk factors with pre-eclampsia. The aim of this study was to investigate the copeptin levels in patients with early-onset and late-onset pre-eclampsia. A total of 80 pregnant women receiving antenatal and obstetric care were recruited. The patients were subdivided into four groups: Early-onset pre-eclampsia (n = 20), late-onset pre-eclampsia (n = 20), and two control groups of similar gestational ages for both pre-eclamptic groups (n = 20 in each group). The maternal serum copeptin levels were measured using an enzyme-linked immunosorbent assay. The mean copeptin levels were 0.92 ± 0.57 ng/mL and 1.65 ± 0.95 ng/mL in the early-onset and late-onset pre-eclampsia groups, respectively. These values were higher compared with the control groups (0.54 ± 0.25 ng/mL and 1.15 ± 0.94 ng/mL, respectively). However, the difference was only statistically significant in the early-onset pre-eclampsia group (p = 0.011). Copeptin levels were associated only with gestational age and systolic-diastolic blood pressure. Our results suggest that copeptin levels might be useful in the evaluation of the severity of pre-eclampsia. However, copeptin might be involved in early- rather than late-onset pre-eclampsia. Copyright © 2015. Published by Elsevier B.V.

  15. Pre-eclampsia increases the risk of postpartum haemorrhage: a nationwide cohort study in the Netherlands.

    Directory of Open Access Journals (Sweden)

    Joost F von Schmidt auf Altenstadt

    Full Text Available BACKGROUND: Postpartum haemorrhage is a leading cause of maternal morbidity and mortality worldwide. Identifying risk indicators for postpartum haemorrhage is crucial to predict this life threatening condition. Another major contributor to maternal morbidity and mortality is pre-eclampsia. Previous studies show conflicting results in the association between pre-eclampsia and postpartum haemorrhage. The primary objective of this study was to investigate the association between pre-eclampsia and postpartum haemorrhage. Our secondary objective was to identify other risk indicators for postpartum haemorrhage in the Netherlands. METHODS: A nationwide cohort was used, containing prospectively collected data of women giving birth after 19 completed weeks of gestation from January 2000 until January 2008 (n =  1,457,576. Data were extracted from the Netherlands Perinatal Registry, covering 96% of all deliveries in the Netherlands. The main outcome measure, postpartum haemorrhage, was defined as blood loss of ≥1000 ml in the 24 hours following delivery. The association between pre-eclampsia and postpartum haemorrhage was investigated with uni- and multivariable logistic regression analyses. RESULTS: Overall prevalence of postpartum haemorrhage was 4.3% and of pre-eclampsia 2.2%. From the 31 560 women with pre-eclampsia 2 347 (7.4% developed postpartum haemorrhage, compared to 60 517 (4.2% from the 1 426 016 women without pre-eclampsia (odds ratio 1.81; 95% CI 1.74 to 1.89. Risk of postpartum haemorrhage in women with pre-eclampsia remained increased after adjusting for confounders (adjusted odds ratio 1.53; 95% CI 1.46 to 1.60. CONCLUSION: Women with pre-eclampsia have a 1.53 fold increased risk for postpartum haemorrhage. Clinicians should be aware of this and use this knowledge in the management of pre-eclampsia and the third stage of labour in order to reach the fifth Millenium Developmental Goal of reducing maternal mortality ratios with 75% by

  16. The role of genetics in pre-eclampsia and potential pharmacogenomic interventions

    Directory of Open Access Journals (Sweden)

    Williams PJ

    2012-01-01

    Full Text Available Paula Juliet Williams, Linda MorganHuman Genetics Research Group, University of Nottingham, Nottingham, UKAbstract: The pregnancy-specific condition pre-eclampsia not only affects the health of mother and baby during pregnancy but also has long-term consequences, increasing the chances of cardiovascular disease in later life. It is accepted that pre-eclampsia has a placental origin, but the pathogenic mechanisms leading to the systemic endothelial dysfunction characteristic of the disorder remain to be determined. In this review we discuss some key factors regarded as important in the development of pre-eclampsia, including immune maladaptation, inadequate placentation, oxidative stress, and thrombosis. Genetic factors influence all of these proposed pathophysiological mechanisms. The inherited nature of pre-eclampsia has been known for many years, and extensive genetic studies have been undertaken in this area. Genetic research offers an attractive strategy for studying the pathogenesis of pre-eclampsia as it avoids the ethical and practical difficulties of conducting basic science research during the preclinical phase of pre-eclampsia when the underlying pathological changes occur. Although pharmacogenomic studies have not yet been conducted in pre-eclampsia, a number of studies investigating treatment for essential hypertension are of relevance to therapies used in pre-eclampsia. The pharmacogenomics of antiplatelet agents, alpha and beta blockers, calcium channel blockers, and magnesium sulfate are discussed in relation to the treatment and prevention of pre-eclampsia. Pharmacogenomics offers the prospect of individualized patient treatment, ensuring swift introduction of optimal treatment whilst minimizing the use of inappropriate or ineffective drugs, thereby reducing the risk of harmful effects to both mother and baby.Keywords: pre-eclampsia, pharmacogenetics, placenta, trophoblast, genetics

  17. Skin phenotypes can offer some insight about the association between telomere length and cancer susceptibility.

    Science.gov (United States)

    Ribero, S; Mangino, M; Bataille, V

    2016-12-01

    The role of telomere biology in cancer has been studied for a wide variety of different cancers but the association with telomere length has been controversial. This is because some cancers have been found to be associated with longer telomeres in circulating white cells whilst other cancer types are more common in individuals with shorter telomeres. Hence, there has been some skepticism as to whether telomere length may be helpful in estimating cancer risk. For melanoma, however, results have been fairly consistent showing that longer telomeres are associated with an increased risk. This link was first discovered because of a link between longer telomeres and a high number of naevi. In contrast, for cutaneous squamous cell carcinomas, the relationship is reversed with higher risk in individuals with shorter telomeres. Differences in skin phenotypes with the presence of high number of naevi versus photoageing with solar elastosis and solar keratoses have already been valuable for dermatologists as the former phenotype is associated with melanoma whilst the latter is more common in patients with squamous cell carcinoma of the skin. The hypothesis is that the differences in cutaneous phenotypes already observed by dermatologists for skin cancers may, in fact, be useful as well for cancer prediction in general as it may reflect underlying telomere biology. This manuscript will address the evidence for links between telomere biology, skin phenotypes and cancer risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Tired telomeres: Poor global sleep quality, perceived stress, and telomere length in immune cell subsets in obese men and women.

    Science.gov (United States)

    Prather, Aric A; Gurfein, Blake; Moran, Patricia; Daubenmier, Jennifer; Acree, Michael; Bacchetti, Peter; Sinclair, Elizabeth; Lin, Jue; Blackburn, Elizabeth; Hecht, Frederick M; Epel, Elissa S

    2015-07-01

    Poor sleep quality and short sleep duration are associated with increased incidence and progression of a number of chronic health conditions observed at greater frequency among the obese and those experiencing high levels of stress. Accelerated cellular aging, as indexed by telomere attrition in immune cells, is a plausible pathway linking sleep and disease risk. Prior studies linking sleep and telomere length are mixed. One factor may be reliance on leukocytes, which are composed of varied immune cell types, as the sole measure of telomere length. To better clarify these associations, we investigated the relationships of global sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), and diary-reported sleep duration with telomere length in different immune cell subsets, including granulocytes, peripheral blood mononuclear cells (PBMCs), CD8+ and CD4+ T lymphocytes, and B lymphocytes in a sample of 87 obese men and women (BMI mean=35.4, SD=3.6; 81.6% women; 62.8% Caucasian). Multiple linear regression analyses were performed adjusting for age, gender, race, education, BMI, sleep apnea risk, and perceived stress. Poorer PSQI global sleep quality was associated with statistically significantly shorter telomere length in lymphocytes but not granulocytes and in particular CD8+ T cells (b=-56.8 base pairs per one point increase in PSQI, SE=20.4, p=0.007) and CD4+ T cells (b=-37.2, SE=15.9, p=0.022). Among separate aspects of global sleep quality, low perceived sleep quality and decrements in daytime function were most related to shorter telomeres. In addition, perceived stress moderated the sleep-CD8+ telomere association. Poorer global sleep quality predicted shorter telomere length in CD8+ T cells among those with high perceived stress but not in low stress participants. These findings provide preliminary evidence that poorer global sleep quality is related to telomere length in several immune cell types, which may serve as a pathway linking sleep and

  19. No Association between Mean Telomere Length and Life Stress Observed in a 30 Year Birth Cohort

    OpenAIRE

    Sarah Jodczyk; Fergusson, David M; John Horwood, L.; Pearson, John F; Martin A Kennedy

    2014-01-01

    Telomeres are specialised structures that cap the ends of chromosomes. They shorten with each cell division and have been proposed as a marker of cellular aging. Previous studies suggest that early life stressors increase the rate of telomere shortening with potential impact on disease states and mortality later in life. This study examined the associations between telomere length and exposure to a number of stressors that arise during development from the antenatal/perinatal period through t...

  20. Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling

    NARCIS (Netherlands)

    Meads, C. A.; Cnossen, J. S.; Meher, S.; Juarez-Garcia, A.; ter Riet, G.; Duley, L.; Roberts, T. E.; Mol, B. W.; van der Post, J. A.; Leeflang, M. M.; Barton, P. M.; Hyde, C. J.; Gupta, J. K.; Khan, K. S.

    2008-01-01

    OBJECTIVES: To investigate the accuracy of predictive tests for pre-eclampsia and the effectiveness of preventative interventions for pre-eclampsia. Also to assess the cost-effectiveness of strategies (test-intervention combinations) to predict and prevent pre-eclampsia. DATA SOURCES: Major

  1. Emotions and family interactions in childhood: Associations with leukocyte telomere length emotions, family interactions, and telomere length.

    Science.gov (United States)

    Robles, Theodore F; Carroll, Judith E; Bai, Sunhye; Reynolds, Bridget M; Esquivel, Stephanie; Repetti, Rena L

    2016-01-01

    Conceptualizations of links between stress and cellular aging in childhood suggest that accumulating stress predicts shorter leukocyte telomere length (LTL). At the same time, several models suggest that emotional reactivity to stressors may play a key role in predicting cellular aging. Using intensive repeated measures, we tested whether exposure or emotional "reactivity" to conflict and warmth in the family were related to LTL. Children (N=39; 30 target children and 9 siblings) between 8 and 13 years of age completed daily diary questionnaires for 56 consecutive days assessing daily warmth and conflict in the marital and the parent-child dyad, and daily positive and negative mood. To assess exposure to conflict and warmth, diary scale scores were averaged over the 56 days. Mood "reactivity" was operationalized by using multilevel modeling to generate estimates of the slope of warmth or conflict scores (marital and parent-child, separately) predicting same-day mood for each individual child. After diary collection, a blood sample was collected to determine LTL. Among children aged 8-13 years, a stronger association between negative mood and marital conflict, suggesting greater negative mood reactivity to marital conflict, was related to shorter LTL (B=-1.51, paffection, suggesting positive mood reactivity, was related to longer LTL (B=1.15, pfamily and marital conflict and warmth, and positive and negative mood over a two-month period. To our knowledge, these findings, although cross-sectional, represent the first evidence showing that link between children's affective responses and daily family interactions may have implications for telomere length. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Cigarette smoking and telomere length: A systematic review of 84 studies and meta-analysis.

    Science.gov (United States)

    Astuti, Yuliana; Wardhana, Ardyan; Watkins, Johnathan; Wulaningsih, Wahyu

    2017-10-01

    Cigarette smoking is a risk factor for ageing-related disease, but its association with biological ageing, indicated by telomere length, is unclear. We systematically reviewed evidence evaluating association between smoking status and telomere length. Searches were performed in MEDLINE (Ovid) and EMBASE (Ovid) databases, combining variation of keywords "smoking" and "telomere". Data was extracted for study characteristics and estimates for association between smoking and telomere length. Quality of studies was assessed with a risk of bias score, and publication bias was assessed with a funnel plot. I2 test was used to observe heterogeneity. Meta-analysis was carried out to compare mean difference in telomere length by smoking status, and a dose-response approach was carried out for pack-years of smoking and telomere length. A sensitivity analysis was carried out to examine sources of heterogeneity. A total of 84 studies were included in the review, and 30 among them were included in our meta-analysis. Potential bias was addressed in half of included studies, and there was little evidence of small study bias. Telomere length was shorter among ever smokers compared to never smokers (summary standard mean difference [SMD]: -0.11 (95% CI -0.16 to -0.07)). Similarly, shorter telomere length was found among smokers compared to non-smokers, and among current smokers compared to never or former smokers. Dose-response meta-analysis suggested an inverse trend between pack-years of smoking and telomere length. However, heterogeneity among some analyses was observed. Shorter telomeres among ever smokers compared to those who never smoked may imply mechanisms linking tobacco smoke exposure to ageing-related disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Telomere length is an independent prognostic marker in MDS but not in de novo AML.

    Science.gov (United States)

    Williams, Jenna; Heppel, Nicole H; Britt-Compton, Bethan; Grimstead, Julia W; Jones, Rhiannon E; Tauro, Sudhir; Bowen, David T; Knapper, Steven; Groves, Michael; Hills, Robert K; Pepper, Chris; Baird, Duncan M; Fegan, Chris

    2017-07-01

    Telomere dysfunction is implicated in the generation of large-scale genomic rearrangements that drive progression to malignancy. In this study we used high-resolution single telomere length analysis (STELA) to examine the potential role of telomere dysfunction in 80 myelodysplastic syndrome (MDS) and 95 de novo acute myeloid leukaemia (AML) patients. Despite the MDS cohort being older, they had significantly longer telomeres than the AML cohort (P AML patients (age AML patients (P = 0·03). Using a previously determined telomere length threshold for telomere dysfunction (3·81 kb) did not provide prognostic resolution in AML [Hazard ratio (HR) = 0·68, P = 0·2]. In contrast, the same length threshold was highly prognostic for overall survival in the MDS cohort (HR = 5·0, P < 0·0001). Furthermore, this telomere length threshold was an independent parameter in multivariate analysis when adjusted for age, gender, cytogenetic risk group, number of cytopenias and International Prognostic Scoring System (IPSS) score (HR = 2·27, P < 0·0001). Therefore, telomere length should be assessed in a larger prospective study to confirm its prognostic role in MDS with a view to integrating this variable into a revised IPSS. © 2017 John Wiley & Sons Ltd.

  4. Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses' Health Study.

    Science.gov (United States)

    Liu, Jason J; Crous-Bou, Marta; Giovannucci, Edward; De Vivo, Immaculata

    2016-07-01

    Coffee is an important source of antioxidants, and consumption of this beverage is associated with many health conditions and a lower mortality risk. However, no study, to our knowledge, has examined whether varying coffee or caffeine consumption levels are associated with telomere length, a biomarker of aging whose shortening can be accelerated by oxidative stress. We performed a large comprehensive study on how coffee consumption is associated with telomere length. We used data from the Nurses' Health Study (NHS), a prospective cohort study of female nurses that began in 1976. We examined the cross-sectional association between coffee consumption and telomere length in 4780 women from the NHS. Coffee consumption information was obtained from validated food-frequency questionnaires, and relative telomere length was measured in peripheral blood leukocytes by the quantitative real-time polymerase chain reaction. Unconditional logistic regression was used to obtain ORs when the telomere length outcome was dichotomized at the median. Linear regression was used for tests of trend with coffee consumption and telomere length as continuous variables. Higher total coffee consumption was significantly associated with longer telomeres after potential confounding adjustment. Compared with non-coffee drinkers, multivariable ORs for those drinking 2 to coffee/d were, respectively, 1.29 (95% CI: 0.99, 1.68) and 1.36 (95% CI: 1.04, 1.78) (P-trend = 0.02). We found a significant linear association between caffeine consumption from all dietary sources and telomere length (P-trend = 0.02) after adjusting for potential confounders, but not after additionally adjusting for total coffee consumption (P-trend = 0.37). We found that higher coffee consumption is associated with longer telomeres among female nurses. Future studies are needed to better understand the influence of coffee consumption on telomeres, which may uncover new knowledge of how coffee consumption affects health and

  5. Body weight status and telomere length in U.S. middle-aged and older adults.

    Science.gov (United States)

    An, Ruopeng; Yan, Hai

    Telomere length has been proposed as a biomarker of biological aging. This study examined the relationship between body weight status and telomere length in U.S. middle-aged and older adults. Nationally representative data (N=2749) came from the Health and Retirement Study. Linear regressions were performed to examine the relationship between baseline body weight status reported in 1992 and telomere length measured in 2008 in the overall sample and by sex and racial/ethnic groups, adjusted for individual characteristics. Baseline overweight (25kg/m2≤body mass index [BMI]body weight status and telomere length found in this study was opposite to what existing biological model predicts, and could partially relate to the nonlinear relationship between body weight status and telomere length across age cohorts, and/or the lack of reliability of BMI as an indicator for adiposity in the older population. Large-scale longitudinal studies with baseline telomere length measures are warranted to replicate this study finding and explore the potential heterogeneous relationship between body weight status and telomere length. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  6. Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

    Science.gov (United States)

    Henje Blom, E; Han, L K M; Connolly, C G; Ho, T C; Lin, J; LeWinn, K Z; Simmons, A N; Sacchet, M D; Mobayed, N; Luna, M E; Paulus, M; Epel, E S; Blackburn, E H; Wolkowitz, O M; Yang, T T

    2015-11-10

    Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

  7. Lack of correlation between telomere length and telomerase activity and expression in leukemic cells.

    Science.gov (United States)

    Januszkiewicz, Danuta; Wysoki, Jacek; Lewandowski, Krzysztof; Pernak, Monika; Nowicka, Karina; Rembowska, Jolanta; Nowak, Jerzy

    2003-12-01

    The expression of three components of telomerase complex (hTR, hTERT, TP1) along with telomerase activity and telomere length in leukemic cells was investigated. Cells were isolated from peripheral blood and/or bone marrow of children with acute lymphoblastic (ALL) and non-lymphoblastic (ANLL) leukemia. Expression of three components of telomerase as well as telomerase activity was found in all leukemic cells. Chemiluminescent detection of terminal restriction fragments (TRF) from DNA isolated from ALL cells showed variable patterns expressing considerable heterogeneity of telomere length. The ALL cells appeared to have both long and short telomere lengths, in contrast to normal peripheral lymphocytes, which produced limited pattern of TRF. The ANLL cells produced predominantly short telomere pattern despite high telomerase activity and expression. It can be concluded that high telomerase activity and expression in leukemic cells is not always correlated with long telomeres (TRF pattern).

  8. Advances in the pathophysiology of pre-eclampsia and related podocyte injury.

    Science.gov (United States)

    Craici, Iasmina M; Wagner, Steven J; Weissgerber, Tracey L; Grande, Joseph P; Garovic, Vesna D

    2014-08-01

    Pre-eclampsia is a pregnancy-specific hypertensive disorder that may lead to serious maternal and fetal complications. It is a multisystem disease that is commonly, but not always, accompanied by proteinuria. Its cause(s) remain unknown, and delivery remains the only definitive treatment. It is increasingly recognized that many pathophysiological processes contribute to this syndrome, with different signaling pathways converging at the point of systemic endothelial dysfunction, hypertension, and proteinuria. Different animal models of pre-eclampsia have proven utility for specific aspects of pre-eclampsia research, and offer insights into pathophysiology and treatment possibilities. Therapeutic interventions that specifically target these pathways may optimize pre-eclampsia management and may improve fetal and maternal outcomes. In addition, recent findings regarding placental, endothelial, and podocyte pathophysiology in pre-eclampsia provide unique and exciting possibilities for improved diagnostic accuracy. Emerging evidence suggests that testing for urinary podocytes or their markers may facilitate the prediction and diagnosis of pre-eclampsia. In this review, we explore recent research regarding placental, endothelial, and podocyte pathophysiology. We further discuss new signaling and genetic pathways that may contribute to pre-eclampsia pathophysiology, emerging screening and diagnostic strategies, and potential targeted interventions.

  9. Potential New Non-Invasive Therapy Using Artificial Oxygen Carriers for Pre-Eclampsia.

    Science.gov (United States)

    Ohta, Hidenobu; Kaga, Maiko; Li, Heng; Sakai, Hiromi; Okamura, Kunihiro; Yaegashi, Nobuo

    2017-07-30

    The molecular mechanisms of pre-eclampsia are being increasingly clarified in animals and humans. With the uncovering of these mechanisms, preventive therapy strategies using chronic infusion of adrenomedullin, vascular endothelial growth factor-121 (VEGF-121), losartan, and sildenafil have been proposed to block narrow spiral artery formation in the placenta by suppressing related possible factors for pre-eclampsia. However, although such preventive treatments have been partly successful, they have failed in ameliorating fetal growth restriction and carry the risk of possible side-effects of drugs on pregnant mothers. In this study, we attempted to develop a new symptomatic treatment for pre-eclampsia by directly rescuing placental ischemia with artificial oxygen carriers (hemoglobin vesicles: HbV) since previous data indicate that placental ischemia/hypoxia may alone be sufficient to lead to pre-eclampsia through up-regulation of sFlt-1, one of the main candidate molecules for the cause of pre-eclampsia. Using a rat model, the present study demonstrated that a simple treatment using hemoglobin vesicles for placental ischemia rescues placental and fetal hypoxia, leading to appropriate fetal growth. The present study is the first to demonstrate hemoglobin vesicles successfully decreasing maternal plasma levels of sFlt-1 and ameliorating fetal growth restriction in the pre-eclampsia rat model (p pre-eclampsia.

  10. Telomere length reflects reproductive effort indicated by corticosterone levels in a long-lived seabird

    NARCIS (Netherlands)

    Bauch, Christina; Riechert, Juliane; Verhulst, Simon; Becker, Peter H.

    2016-01-01

    Telomere length (TL) is a candidate biomarker of ageing and phenotypic quality, but little is known of the (physiological) causes of TL variation. We previously showed that individual common terns Sterna hirundo with high reproductive success had short telomeres independent of age, and this pattern

  11. Influence of Amalaki Rasayana on telomerase activity and telomere length in human blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    Kanive P. Guruprasad

    2017-04-01

    Conclusion: The data indicate that the maintenance of telomere length is facilitated by an increase in telomerase activity upon rasayana administration in aged individuals and Amalaki Rasayana may prevent the erosion of telomeres over a period of time in aged individuals to promote healthy ageing.

  12. Does neuroticism make you old? Prospective associations between neuroticism and leukocyte telomere length

    NARCIS (Netherlands)

    van Ockenburg, S. L.; de Jonge, P.; van der Harst, P.; Ormel, J.; Rosmalen, J. G. M.

    Background Telomere attrition, causing accelerated aging, might be one of the mechanisms through which neuroticism leads to somatic disease and increased all-cause mortality. In the current study we investigated whether neuroticism is prospectively associated with shorter telomere length (TL), a

  13. The effect of regular strength training on telomere length in human skeletal muscle

    DEFF Research Database (Denmark)

    Kadi, F.; Ponsot, Elodie; Piehl-Aulin, Karin

    2008-01-01

    PURPOSE: The length of DNA telomeres is an important parameter of the proliferative potential of tissues. A recent study has reported abnormally short telomeres in skeletal muscle of athletes with exercise-associated fatigue. This important report raises the question of whether long-term practice...

  14. Age-dependence of relative telomere length profiles during spermatogenesis in man

    DEFF Research Database (Denmark)

    Jørgensen, Pernille Bach; Fedder, Jens; Koelvraa, Steen

    2013-01-01

    Telomeres, the protective structures at the outmost ends of chromosomes, shorten in all somatic cells with each cell-division and by cumulative oxidative damage. To counteract that these shortened telomeres are passed on to offspring, the telomeres are elongated by the enzyme, telomerase, during...... human spermatogenesis. A few groups have tried to elucidate this process by measuring telomerase activity in the various cell-types during spermatogenesis, but until now, no one has ever measured telomere length (TL) during these different stages in humans. Some groups have measured TL in spermatozoa...... by telomere QFISH. Our data revealed no difference in the TL profile during spermatogenesis between younger and older men. All men had a similar profile which strongly resembled the telomerase expression profile found by others. This indicates that the longer telomeres in older men are not caused by a wider...

  15. Gender and telomere length : Systematic review and meta-analysis

    NARCIS (Netherlands)

    Gardner, Michael; Bann, David; Wiley, Laura; Cooper, Rachel; Hardy, Rebecca; Nitsch, Dorothea; Martin-Ruiz, Carmen; Shiels, Paul; Sayer, Avan Aihie; Barbieri, Michelangela; Bekaert, Sofie; Bischoff, Claus; Brooks-Wilson, Angela; Chen, Wei; Cooper, Cyrus; Christensen, Kaare; De Meyer, Tim; Deary, Ian; Der, Geoff; Roux, Ana Diez; Fitzpatrick, Annette; Hajat, Anjum; Halaschek-Wiener, Julius; Harris, Sarah; Hunt, Steven C.; Jagger, Carol; Jeon, Hyo-Sung; Kaplan, Robert; Kimura, Masayuki; Lansdorp, Peter; Li, Changyong; Maeda, Toyoki; Mangino, Massimo; Nawrot, Tim S.; Nilsson, Peter; Nordfjall, Katarina; Paolisso, Giuseppe; Ren, Fu; Riabowol, Karl; Robertson, Tony; Roos, Goran; Staessen, Jan A.; Spector, Tim; Tang, Nelson; Unryn, Brad; van der Harst, Pim; Woo, Jean; Xing, Chao; Yadegarfar, Mohammad E.; Park, Jae Yong; Young, Neal; Kuh, Diana; von Zglinicki, Thomas; Ben-Shlomo, Yoav

    Background: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. Methods: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this

  16. Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle.

    Science.gov (United States)

    Graf, Marco; Bonetti, Diego; Lockhart, Arianna; Serhal, Kamar; Kellner, Vanessa; Maicher, André; Jolivet, Pascale; Teixeira, Maria Teresa; Luke, Brian

    2017-06-29

    Maintenance of a minimal telomere length is essential to prevent cellular senescence. When critically short telomeres arise in the absence of telomerase, they can be repaired by homology-directed repair (HDR) to prevent premature senescence onset. It is unclear why specifically the shortest telomeres are targeted for HDR. We demonstrate that the non-coding RNA TERRA accumulates as HDR-promoting RNA-DNA hybrids (R-loops) preferentially at very short telomeres. The increased level of TERRA and R-loops, exclusively at short telomeres, is due to a local defect in RNA degradation by the Rat1 and RNase H2 nucleases, respectively. Consequently, the coordination of TERRA degradation with telomere replication is altered at shortened telomeres. R-loop persistence at short telomeres contributes to activation of the DNA damage response (DDR) and promotes recruitment of the Rad51 recombinase. Thus, the telomere length-dependent regulation of TERRA and TERRA R-loops is a critical determinant of the rate of replicative senescence. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Time from pre-eclampsia diagnosis to delivery affects future health prospects of children.

    Science.gov (United States)

    Hollegaard, Birgitte; Lykke, Jacob A; Boomsma, Jacobus J

    2017-01-01

    Background and objectives: Pre-eclampsia often has detrimental health effects for pregnant women and their fetuses, but whether exposure in the womb has long-term health-consequences for children as they grow up remains poorly understood. We assessed overall morbidity of children following exposure to either mild or severe pre-eclampsia up to 30 years after birth and related disease risks to duration of exposure, i.e. the time from diagnosis to delivery. Methodology: We did a registry-based retrospective cohort study in Denmark covering the years 1979-2009, using the separate diagnoses of mild and severe pre-eclampsia and the duration of exposure as predictor variables for specific and overall risks of later disease. We analysed 3 537 525 diagnoses for 14 disease groups, accumulated by 758 524 singleton children, after subdividing deliveries in six gestational age categories, partialing out effects of eight potentially confounding factors. Results: Exposure to mild pre-eclampsia appeared to have consistent negative effects on health later in life, although only a few specific disease cases remained significant after corrections for multiple testing. Morbidity risks associated with mild pre-eclampsia were of similar magnitude as those associated with severe pre-eclampsia. Apart from this overall trend in number of diagnoses incurred across disease groups, hazard ratios for several disorders also increased with the duration of exposure, including disorders related to the metabolic syndrome. Conclusions and implications: Maternal pre-eclampsia has lasting effects on offspring health and differences between exposure to severe and mild pre-eclampsia appear to be less than previously assumed. Our results suggest that it would be prudent to include the long-term health prospects of children in the complex clinical management of mild pre-eclampsia.

  18. Telomere length and fetal programming: A review of recent scientific advances.

    Science.gov (United States)

    Whiteman, Valerie E; Goswami, Anjali; Salihu, Hamisu M

    2017-05-01

    We sought to synthesize a comprehensive literature review comprising recent research linking fetal programming to fetal telomere length. We also explored the potential effects fetal telomere length shortening has on fetal phenotypes. Utilizing the PubMed database as our primary search engine, we retrieved and reviewed 165 articles of published research. The inclusion criteria limited the articles to those that appeared within the last ten years, were pertinent to humans, and without restriction to language of publication. Our results showed that socio-demographic factors like age, sex, genetic inheritance, and acquired disease impact telomere length. Further, we found several maternal characteristics to be associated with fetal telomere length shortening, and these include maternal chemical exposure (eg, tobacco smoke), maternal stress during pregnancy, maternal nutritional and sleeping disorders during pregnancy as well as maternal disease status. Due to paucity of data, our review could not synthesize evidence directly linking fetal phenotypes to telomere length shortening. Although the research summarized in this review shows some association between determinants of intrauterine programming and fetal telomere length, there is still significant work that needs to be done to delineate the direct relationship of telomere attrition with specific fetal phenotypes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Telomere length, cardiovascular risk and arteriosclerosis in human kidneys: an observational cohort study.

    Science.gov (United States)

    De Vusser, Katrien; Pieters, Nicky; Janssen, Bram; Lerut, Evelyne; Kuypers, Dirk; Jochmans, Ina; Monbaliu, Diethard; Pirenne, Jacques; Nawrot, Tim; Naesens, Maarten

    2015-10-01

    Replicative senescence, associated with telomere shortening, plays an important role in aging and cardiovascular disease. The relation between telomere length, cardiovascular risk, and renal disease is unknown. Our study consisted of a cohort of 257 kidney donors for transplantation, divided into a test and a validation cohort. We used quantitative RT-PCR to measure relative telomere length (log T/S ratio) in peripheral blood leucocytes, and in kidney biopsies performed prior to implantation. The association between leucocyte and intrarenal telomere length, cardiovascular risk factors, and renal histology, was studied using multiple regression models, adjusted for calendar age, gender and other donor demographics. Subjects with intrarenal arteriosclerosis had significantly shorter leucocyte telomere length compared with patients without arteriosclerosis (log T/S ratio -0.3±0.4 vs. 0.1±0.2 with vs. without arteriosclerosis; p=0.0008). Intrarenal arteriosclerosis was associated with shorter telomere length, independent of gender, calendar age, history of hypertension and history of cardiovascular events. For each increase of one standard deviation of the log T/S ratio, the odds for intrarenal arteriosclerosis decreased with 64% (Odds ratio 0.36; 95% CI 0.17-0.77; p=0.02). In accordance with leucocyte telomere length, shorter intrarenal telomere length associated significantly with the presence of renal arteriosclerosis (log T/S ratio -0.04±0.06 vs. 0.08±0.01 with vs. without arteriosclerosis, p=0.007), and not with other histological lesions. We demonstrate that arteriosclerosis in smaller intrarenal arteries is associated with shorter telomere length. Our study suggests a central role of replicative senescence in the progression of renovascular disease, independent of calendar age.

  20. Telomere length in alcohol dependence: A role for impulsive choice and childhood maltreatment.

    Science.gov (United States)

    Kang, Jee In; Hwang, Syung Shick; Choi, Jong Rak; Lee, Seung-Tae; Kim, Jieun; Hwang, In Sik; Kim, Hae Won; Kim, Chan-Hyung; Kim, Se Joo

    2017-09-01

    Telomere shortening, a marker of cellular aging, has been considered to be linked with psychosocial stress as well as with chronic alcohol consumption, possibly mediated by oxidative stress and inflammatory response. Recent findings suggested that early life adversity on telomere dynamics may be related to impulsive choice. To further our understanding of the association of impulsive choice and childhood trauma on telomere length, we examined whether delayed discounting and childhood trauma or their interaction is related to leukocyte telomere length, while controlling for multiple potential confounding variables, in patients with alcohol dependence who are considered to have higher impulsive choice and shorter telomere length. We recruited 253 male patients with chronic alcohol dependence. All participants performed the delay discounting task, and the area under curve was used as a measure of delay discounting. Steeper delay discounting represents more impulsive choices. The modified Parent-Child Conflict Tactics Scale was used to measure childhood maltreatment. In addition, confounding factors, including socio-demographic characteristics, the Alcohol Use Disorders Identification Test, the Buss-Perry Aggression Questionnaire, the Resilience Quotient, the Beck Depression Inventory, and the Beck Anxiety Inventory, were also assessed. Hierarchical regression analyses showed a significant main effect of delay discounting (β=0.161, t=2.640, p=0.009), and an interaction effect between delay discounting and childhood maltreatment on leukocyte telomere length (β=0.173, t=2.138, p=0.034). In subsequent analyses stratified by childhood maltreatment, patients with alcohol dependence and high childhood trauma showed a significant relationship between delay discounting and leukocyte telomere length (β=0.279, t=3.183, p=0.002), while those with low trauma showed no association between them. Our findings suggest that higher impulsive choice is associated with shorter telomere

  1. Leukocyte telomere length: Effects of schizophrenia, age, and gender.

    Science.gov (United States)

    Wolkowitz, Owen M; Jeste, Dilip V; Martin, Averria Sirkin; Lin, Jue; Daly, Rebecca E; Reuter, Chase; Kraemer, Helena

    2017-02-01

    Schizophrenia is linked with early medical comorbidity and mortality. These observations indicate possible "accelerated biological aging" in schizophrenia, although prior findings are mixed, and few such studies have examined the role of gender. One putative marker of biological aging is leukocyte telomere length (LTL), which typically shortens with age. We assessed LTL in phenotypically well characterized 134 individuals with schizophrenia (60 women and 74 men) and 123 healthy comparison subjects (HCs) (66 women and 57 men), aged 26 to 65 years. Overall, LTL was inversely associated with age (t(249) = -6.2, p schizophrenia and HC groups (t(249) = 2.48, p = 0.014), with women having longer LTL than men, and a significant gender X diagnosis effect (t(249) = 2.43, p = 0.016) - at the average sample age, women with schizophrenia had shorter LTL than HC women. Gender, not the diagnosis of schizophrenia, was the major factor involved with LTL shortening across the age range studied. We discuss the constraints of a cross-sectional design and other methodological issues, and indicate future directions. Understanding the impact of schizophrenia on biological aging will require separate evaluations in men and women. Published by Elsevier Ltd.

  2. Leukocyte telomere length dynamics in women and men

    DEFF Research Database (Denmark)

    Dalgård, Christine; Benetos, Athanase; Verhulst, Simon

    2015-01-01

    BACKGROUND: A longer leukocyte telomere length (LTL) in women than men has been attributed to a slow rate of LTL attrition in women, perhaps due to high estrogen exposure during the premenopausal period. METHODS: To test this premise we performed a longitudinal study (an average follow-up of 12...... years) in a subset of the population-based Danish National Twin Registry. Participants consisted of 405 women, aged 37.5 (range 18.0-64.3) years, and 329 men, aged 38.8 (range 18.0-58.5) years, at baseline examination. RESULTS: Women showed a longer LTL [kb ± standard error(SE)] than men (baseline: 7.......01 ± 0.03 vs 6.87 ± 0.04; follow-up: 6.79 ± 0.03 vs 6.65 ± 0.03; both P = 0.005). Women displayed deceleration of LTL attrition (bp/years ± SE), as they transitioned from the premenopausal period (20.6 ± 1.0) through the perimenopausal period (16.5 ± 1.3) to the postmenopausal period (15.1 ± 1.7). Age...

  3. Maternal hypertrophy and diastolic disfunction and brain natriuretic peptide concentration in early and late Pre-Eclampsia.

    Science.gov (United States)

    Borges, V T M; Zanati, S G; PeraÇoli, M T S; Poiati, J R; Romão-Veiga, M; PeraÇoli, J C; Thilaganathan, B

    2017-04-23

    Pre-eclampsia is associated with maternal cardiac remodelling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and Brain Natriuretic Peptide (BNP) levels in women with early-onset pre-eclampsia (pre-eclampsia (≥34weeks of gestation). A prospective, cross-sectional observational study was performed in 30 women with early-onset pre-eclampsia, 32 with late-onset pre-eclampsia and 23 normotensive controls. Maternal cardiac structure and diastolic function as assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Pre-eclampsia was associated with an increased left ventricular mass index and relative wall thickness in early-onset pre-eclampsia compared with late-onset pre-eclampsia and normotensive controls. The prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher in early-onset pre-eclampsia than in late-onset pre-eclampsia (16% for both, all p pre-eclampsia (p pre-eclampsia has more severe cardiac impairment than late-onset pre-eclampsia as evidenced by increased prevalence of concentric hypertrophy, diastolic dysfunction and high concentrations BNP. These findings suggest that early-onset pre-eclampsia causes greater myocardial damage increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. This article is protected by copyright. All rights reserved.

  4. Cognitive Change during the Life Course and Leukocyte Telomere Length in Late Middle-Aged Men

    DEFF Research Database (Denmark)

    Rask, L.; Bendix, Laila; Harbo, Maria

    2016-01-01

    difference beta = -0.09, 95% CI -0.17 to -0.01, p = 0.02) but was non-significant after adjusting for smoking, alcohol consumption, leisure time activity, BMI, cholesterol, current cognitive function, depression and education (adjusted difference beta = -0.07, 95% CI -0.16 to -0.01, p = 0.08). Conclusion......, it is unclear whether there is an association between cognitive decline and leukocyte telomere length. Objective: To examine the association between changes in cognitive function during adult life and leukocyte telomere length after adjusting for confounding factors such as education, mental health and life...... telomere length at age similar to 58 was measured using qPCR. Linear regression models were used to investigate the association between cognitive function and leukocyte telomere length. Results: Men with negative change in cognitive performance during adult life had significantly shorter mean leukocyte...

  5. Mutations in TERT promoter and FGFR3 and telomere length in bladder cancer

    National Research Council Canada - National Science Library

    Hosen, Ismail; Rachakonda, P. Sivaramakrishna; Heidenreich, Barbara; de Verdier, Petra J; Ryk, Charlotta; Steineck, Gunnar; Hemminki, Kari; Kumar, Rajiv

    2015-01-01

    .... In this study, we screened DNA from 327 urothelial bladder carcinomas from well‐documented patients, with different stages and grades and known TERT promoter mutational status, for FGFR3 alterations and measured relative telomere length (RTL...

  6. Highly Aggressive Metastatic Melanoma Cells Unable to Maintain Telomere Length.

    Science.gov (United States)

    Viceconte, Nikenza; Dheur, Marie-Sophie; Majerova, Eva; Pierreux, Christophe E; Baurain, Jean-François; van Baren, Nicolas; Decottignies, Anabelle

    2017-06-20

    Unlimited replicative potential is one of the hallmarks of cancer cells. In melanoma, hTERT (telomerase reverse transcriptase) is frequently overexpressed because of activating mutations in its promoter, suggesting that telomerase is necessary for melanoma development. We observed, however, that a subset of melanoma metastases and derived cell lines had no telomere maintenance mechanism. Early passages of the latter displayed long telomeres that progressively shortened and fused before cell death. We propose that, during melanoma formation, oncogenic mutations occur in precursor melanocytes with long telomeres, providing cells with sufficient replicative potential, thereby bypassing the need to re-activate telomerase. Our data further support the emerging idea that long telomeres promote melanoma formation. These observations are important when considering anticancer therapies targeting telomerase. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Highly Aggressive Metastatic Melanoma Cells Unable to Maintain Telomere Length

    Directory of Open Access Journals (Sweden)

    Nikenza Viceconte

    2017-06-01

    Full Text Available Unlimited replicative potential is one of the hallmarks of cancer cells. In melanoma, hTERT (telomerase reverse transcriptase is frequently overexpressed because of activating mutations in its promoter, suggesting that telomerase is necessary for melanoma development. We observed, however, that a subset of melanoma metastases and derived cell lines had no telomere maintenance mechanism. Early passages of the latter displayed long telomeres that progressively shortened and fused before cell death. We propose that, during melanoma formation, oncogenic mutations occur in precursor melanocytes with long telomeres, providing cells with sufficient replicative potential, thereby bypassing the need to re-activate telomerase. Our data further support the emerging idea that long telomeres promote melanoma formation. These observations are important when considering anticancer therapies targeting telomerase.

  8. Telomere length reflects phenotypic quality and costs of reproduction in a long-lived seabird.

    Science.gov (United States)

    Bauch, Christina; Becker, Peter H; Verhulst, Simon

    2013-02-07

    Telomere length is associated with cellular senescence, lifestyle and ageing. Short telomeres indicate poor health in humans and reduced life expectancy in several bird species, but little is known about telomeres in relation to phenotypic quality in wild animals. We investigated telomere lengths in erythrocytes of known-age common terns (Sterna hirundo), a migratory seabird, in relation to arrival date and reproductive performance. Cross-sectional data revealed that, independent of age, individuals with short telomeres performed better: they arrived and reproduced earlier in the season and had more chicks in the nest. The latter effect was stronger the older the brood and stronger in males, which do most of the chick provisioning. Longitudinal data confirmed this pattern: compared with birds that lost their brood, birds that raised chicks beyond the 10th nestling day experienced higher telomere attrition from one year to the next. However, more detailed analysis revealed that the least and most successful individuals lost the fewest base pairs compared with birds with intermediate success. Our results suggest that reproductive success is achieved at the expense of telomeres, but that individual heterogeneity in susceptibility to such detrimental effects is important, as indicated by low telomere loss in the most successful birds.

  9. Is psychosocial stress in first ongoing pregnancies associated with pre-eclampsia and gestational hypertension?

    NARCIS (Netherlands)

    Vollebregt, K. C.; van der Wal, M. F.; Wolf, H.; Vrijkotte, T. G. M.; Boer, K.; Bonsel, G. J.

    2008-01-01

    OBJECTIVE: Investigating the association of pre-eclampsia and gestational hypertension with psychosocial stress in the first half of pregnancy. DESIGN: Prospective community-based cohort study. SETTING: Amsterdam, The Netherlands. POPULATION: Between January 2003 and March 2004, all pregnant

  10. Pre-eclampsia: Definitions, paternal contributions and a four stage model.

    Science.gov (United States)

    Redman, C W

    2011-01-01

    It is 40 years since I started researching pre-eclampsia. Much has changed but some old problems persist. These include the debate of how to define a syndrome, the inheritance and genetics of pre-eclampsia, why primiparae are so susceptible and is primipaternity important? If it is, in a multiparous pregnancy (after changing partners), the old hypothesis that pre-eclampsia is the outcome of failed maternal immunoregulation to accommodate nature's transplant - the fetus - must be confronted. These points are briefly reviewed and a four stage model of pre-eclampsia derived. Copyright © 2010 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  11. Pre-Eclampsia Increases the Risk of Postpartum Haemorrhage: A Nationwide Cohort Study in The Netherlands

    NARCIS (Netherlands)

    Altenstadt, J.F.V.A.; Hukkelhoven, C.W.P.M.; van Roosmalen, J.; Bloemenkamp, K.W.M.

    2013-01-01

    Background: Postpartum haemorrhage is a leading cause of maternal morbidity and mortality worldwide. Identifying risk indicators for postpartum haemorrhage is crucial to predict this life threatening condition. Another major contributor to maternal morbidity and mortality is pre-eclampsia. Previous

  12. Time from pre-eclampsia diagnosis to delivery affects future health prospects of children

    DEFF Research Database (Denmark)

    Hollegaard, Birgitte; Lykke, Jacob A; Boomsma, Jacobus Jan

    2017-01-01

    Background and objectives: Pre-eclampsia often has detrimental health effects for pregnant women and their fetuses, but whether exposure in the womb has long-term health-consequences for children as they grow up remains poorly understood. We assessed overall morbidity of children following exposu...... in the complex clinical management of mild pre-eclampsia.......Background and objectives: Pre-eclampsia often has detrimental health effects for pregnant women and their fetuses, but whether exposure in the womb has long-term health-consequences for children as they grow up remains poorly understood. We assessed overall morbidity of children following exposure...... to either mild or severe pre-eclampsia up to 30 years after birth and related disease risks to duration of exposure, i.e. the time from diagnosis to delivery. Methodology: We did a registry-based retrospective cohort study in Denmark covering the years 1979-2009, using the separate diagnoses of mild...

  13. Low vitamin C intake increases risk of pre-eclampsia in high pesticide exposure area

    Directory of Open Access Journals (Sweden)

    Rifatul Masrikhiyah

    2016-08-01

    Low vitamin C intake played the most important role toward pre-eclampsia. Greater caution is needed when issuing recommendations regarding the consumption of vitamin supplements in pregnancy, as high doses of some vitamins may be deleterious.

  14. Acute cortical blindness caused by pre-eclampsia in the antepartum ...

    African Journals Online (AJOL)

    We present a case report of a patient presenting posterior reversible encephalopathy syndrome (PRES), a rare acute neurological condition associated with pre-eclampsia. A possible common aetiology and successful clinical management approach is reported.

  15. InterPregGen:genetic studies of pre-eclampsia in three continents

    Directory of Open Access Journals (Sweden)

    Linda Morgan

    2014-12-01

    Full Text Available Pre-eclampsia is a major cause of maternal and fetal mortality in pregnancy. The identification of genetic variants which predispose to pre-eclampsia demands large DNA collections from affected mothers and babies and controls, with reliable supporting phenotypic data. The InterPregGen study has assembled a consortium of researchers from Europe, Central Asia and South America with the aim of elucidating the genetic architecture of pre-eclampsia. The MoBa collection is playing a vital role in this collaborative venture, which has the potential to provide new insights into the causes of pre-eclampsia, and provide a rational basis for novel approaches to prevention and treatment.

  16. Homeostasis of telomere length rather than telomere shortening after allogeneic peripheral blood stem cell transplantation

    NARCIS (Netherlands)

    Roelofs, Helene; de Pauw, Elmar S. D.; Zwinderman, Aeilko H.; Opdam, Sonja M.; Willemze, Roel; Tanke, Hans J.; Fibbe, Willem E.

    2003-01-01

    Hematopoietic reconstitution after stem cell transplantation requires excessive replicative activity because of the limited number of stem cells that are used for transplantation. Telomere shortening has been detected in hematopoietic cells after bone marrow transplantation. This has been thought to

  17. Effect of heartfulness meditation on burnout, emotional wellness, and telomere length in health care professionals

    OpenAIRE

    Thimmapuram, Jayaram; Pargament, Robert; Sibliss, Kedesha; Grim, Rodney; Risques, Rosana; Toorens, Erik

    2017-01-01

    ABSTRACT Background: Burnout poses significant challenges during training years in residency and later in the career. Meditation is a tool to treat stress-related conditions and promote wellness. Telomere length may be affected by burnout and stress. However, the benefits of meditation have not been fully demonstrated in health care professionals. Objective: We assessed the effects of a 12-week ?Heartfulness Meditation? program on burnout, emotional wellness, and telomere length in residents,...

  18. Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder

    OpenAIRE

    Blackburn, Elizabeth; Wolkowitz, Owen; Epel, Elissa; Yang, Tony; Blom, EH; Han, LKM; Connolly, CG; Ho, TC; Lin, J.; LeWinn, KZ; Simmons, AN; Sacchet, MD; Mobayed, N; Luna, ME

    2015-01-01

    Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered periphera...

  19. The relation between pre-eclampsia at term and neonatal encephalopathy

    OpenAIRE

    Impey, L; Greenwood, C; Sheil, O; MacQuillan, K; Reynolds, M.; Redman, C

    2001-01-01

    OBJECTIVES—To determine whether pre-eclampsia, hypothesised to be an inflammatory condition, is associated with fever in term labour, and confirm and examine the reported association of pre-eclampsia at term with neonatal encephalopathy.
DESIGN—Prospective cohort study.
SETTING—A Dublin teaching hospital.
PARTICIPANTS—6163 women in labour with singleton pregnancies at term at low risk for intrapartum hypoxia, recruited to a randomised trial examining the effect of admi...

  20. IL-6-induced pathophysiology during pre-eclampsia: potential therapeutic role for magnesium sulfate?

    OpenAIRE

    LaMarca, Babbette; Brewer, Justin; Wallace, Kedra

    2011-01-01

    Pre-eclampsia is defined as new onset hypertension with proteinuria during pregnancy. Pre-eclampsia is also characterized by endothelial cell activation and dysfunction and intrauterine growth restriction. Preeclamptic women display a chronic inflammatory response characterized by elevated inflammatory cytokines, circulating monocytes, neutrophils, and T and B lymphocytes secreting autoantibodies that activate the angiotensin II type I receptor (AT1-AA). Although the pathophysiology of pre-ec...

  1. Number of decidual natural killer cells & macrophages in pre-eclampsia.

    Science.gov (United States)

    Milosevic-Stevanovic, Jelena; Krstic, Miljan; Radovic-Janosevic, Dragana; Popovic, Jasmina; Tasic, Marija; Stojnev, Slavica

    2016-12-01

    The process of human placentation is complex and still not well understood. This study was aimed to examine the relationship between clinical features of pre-eclampsia and degree of trophoblastic invasion after its immunohistochemical visualization in the context of possible alterations in the number of natural killer (NK) cells and macrophages in the decidua. This prospective study included a study group comprising 30 pregnant women with pre-eclampsia delivered by caesarean section and a control group comprising 20 healthy pregnant women also delivered by caesarean section. Samples of placental bed obtained during caesarean section were analyzed after immunohistochemical labelling CD56 + NK cells, CD68 + macrophages and cytokeratin 7 trophoblastic cells. In pre-eclampsia, there was a significantly lower number of CD56 + NK cells in the decidua (P<0.001) and a higher number of CD68 + macrophages (P<0.001) compared to control group. In the subgroup of pre-eclampsia with intrauterine growth retardation (IUGR), a significantly greater number of NK cells (P<0.05) was recorded, as well as an increased number of macrophages, but not significantly compared to pre-eclampsia without IUGR. There was no significant difference in the distribution of these cells in the decidua in relation to the severity of pre-eclampsia. CD56 + NK cells were significantly less (P<0.05) and macrophages were more (P<0.05) in the group with poor trophoblastic invasion. Alterations in the number of immune cells in relation to the degree of trophoblastic invasion indicated their role in aetiopathogenesis of pre-eclampsia, while the direct association between their number and severity of pre-eclampsia was not confirmed.

  2. Number of decidual natural killer cells & macrophages in pre-eclampsia

    Directory of Open Access Journals (Sweden)

    Jelena Milosevic-Stevanovic

    2016-01-01

    Full Text Available Background & objectives: The process of human placentation is complex and still not well understood. This study was aimed to examine the relationship between clinical features of pre-eclampsia and degree of trophoblastic invasion after its immunohistochemical visualization in the context of possible alterations in the number of natural killer (NK cells and macrophages in the decidua. Methods: This prospective study included a study group comprising 30 pregnant women with pre-eclampsia delivered by caesarean section and a control group comprising 20 healthy pregnant women also delivered by caesarean section. Samples of placental bed obtained during caesarean section were analyzed after immunohistochemical labelling CD56 + NK cells, CD68 + macrophages and cytokeratin 7 trophoblastic cells. Results: In pre-eclampsia, there was a significantly lower number of CD56 + NK cells in the decidua (P<0.001 and a higher number of CD68 + macrophages (P<0.001 compared to control group. In the subgroup of pre-eclampsia with intrauterine growth retardation (IUGR, a significantly greater number of NK cells (P<0.05 was recorded, as well as an increased number of macrophages, but not significantly compared to pre-eclampsia without IUGR. There was no significant difference in the distribution of these cells in the decidua in relation to the severity of pre-eclampsia. CD56 + NK cells were significantly less (P<0.05 and macrophages were more (P<0.05 in the group with poor trophoblastic invasion. Interpretation & conclusions: Alterations in the number of immune cells in relation to the degree of trophoblastic invasion indicated their role in aetiopathogenesis of pre-eclampsia, while the direct association between their number and severity of pre-eclampsia was not confirmed.

  3. The Presence of Telomere Fusion in Sporadic Colon Cancer Independently of Disease Stage, TP53/KRAS Mutation Status, Mean Telomere Length, and Telomerase Activity

    Directory of Open Access Journals (Sweden)

    Hiromi Tanaka

    2014-10-01

    Full Text Available Defects in telomere maintenance can result in telomere fusions that likely play a causative role in carcinogenesis by promoting genomic instability. However, this proposition remains to be fully understood in human colon carcinogenesis. In the present study, the temporal sequence of telomere dysfunction dynamics was delineated by analyzing telomere fusion, telomere length, telomerase activity, hotspot mutations in KRAS or BRAF, and TP53 of tissue samples obtained from 18 colon cancer patients. Our results revealed that both the deficiency of p53 and the shortening of mean telomere length were not necessary for producing telomere fusions in colon tissue. In five cases, telomere fusion was observed even in tissue adjacent to cancerous lesions, suggesting that genomic instability is initiated in pathologically non-cancerous lesions. The extent of mean telomere attrition increased with lymph node invasiveness of tumors, implying that mean telomere shortening correlates with colon cancer progression. Telomerase activity was relatively higher in most cancer tissues containing mutation(s in KRAS or BRAF and/or TP53 compared to those without these hotspot mutations, suggesting that telomerase could become fully active at the late stage of colon cancer development. Interestingly, the majority of telomere fusion junctions in colon cancer appeared to be a chromatid-type containing chromosome 7q or 12q. In sum, this meticulous correlative study not only highlights the concept that telomere fusion is present in the early stages of cancer regardless of TP53/KRAS mutation status, mean telomere length, and telomerase activity, but also provides additional insights targeting key telomere fusion junctions which may have significant implications for colon cancer diagnoses.

  4. Telomere length reveals cumulative individual and transgenerational inbreeding effects in a passerine bird.

    Science.gov (United States)

    Bebbington, Kat; Spurgin, Lewis G; Fairfield, Eleanor A; Dugdale, Hannah L; Komdeur, Jan; Burke, Terry; Richardson, David S

    2016-06-01

    Inbreeding results in more homozygous offspring that should suffer reduced fitness, but it can be difficult to quantify these costs for several reasons. First, inbreeding depression may vary with ecological or physiological stress and only be detectable over long time periods. Second, parental homozygosity may indirectly affect offspring fitness, thus confounding analyses that consider offspring homozygosity alone. Finally, measurement of inbreeding coefficients, survival and reproductive success may often be too crude to detect inbreeding costs in wild populations. Telomere length provides a more precise measure of somatic costs, predicts survival in many species and should reflect differences in somatic condition that result from varying ability to cope with environmental stressors. We studied relative telomere length in a wild population of Seychelles warblers (Acrocephalus sechellensis) to assess the lifelong relationship between individual homozygosity, which reflects genome-wide inbreeding in this species, and telomere length. In juveniles, individual homozygosity was negatively associated with telomere length in poor seasons. In adults, individual homozygosity was consistently negatively related to telomere length, suggesting the accumulation of inbreeding depression during life. Maternal homozygosity also negatively predicted offspring telomere length. Our results show that somatic inbreeding costs are environmentally dependent at certain life stages but may accumulate throughout life. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  5. Birth weight and ponderal index in pre-eclampsia: a comparative study.

    Science.gov (United States)

    Obed, Sa; Patience, Aniteye

    2006-03-01

    To evaluate the effects of early-onset and late-onset pre-eclampsia on fetal growth. Longitudinal prospective analytical survey Obstetrics unit of Department of Obstetrics and Gynaecology in Korle Bu Teaching Hospital. 11,784 nulliparous women carrying singleton pregnancy were prospectively followed up based on a schedule of antenatal care from 14-16 weeks gestation till delivery. Exclusion criteria included obesity (BMI>30.0), underweight (BMIponderal index of each baby at birth was also computed. The incidence of pre-eclampsia in the 11,784 women was 7.03%. The babies delivered by mothers who had early-onset (ponderal indices (p=0.002 to p=0.02) at all gestational ages of delivery compared with babies of mothers who did not have pre-eclampsia. However, in late-onset (>/=37 weeks) pre-eclampsia, the birth weights and ponderal indice at all gestational ages were comparable to non-pre-eclamptics. These results support the hypothesis that pre-eclampsia is an aetiologically heterogenous disorder that occurs in at least two subsets: a late-onset pre-eclampsia with normal fetal growth denoting normal placental function and an early-onset type with fetal growth restriction implying placental dysfunction.

  6. A systematic review and meta-analysis of hypocalciuria in pre-eclampsia.

    Science.gov (United States)

    McMaster, Kristen M; Kaunitz, Andrew M; Burbano de Lara, Prardhana; Sanchez-Ramos, Luis

    2017-07-01

    Small observational studies have demonstrated that pre-eclampsia is associated with hypocalciuria. To compare urinary calcium excretion in pre-eclampsia, gestational hypertension, and chronic hypertension with that in normotensive pregnancies. Online databases were searched through February 2016 using medical subject headings "calcium homeostasis," "calcium excretion," "hypocalciuria," and "pre-eclampsia." Observational studies were included that evaluated calcium excretion with 24-hour urine collection in patients with pre-eclampsia compared with normotensive pregnant women. Data were extracted from identified studies. The primary outcome was 24-hour urinary calcium excretion. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated. Twenty-one studies were included. Urinary calcium excretion was lower among women with pre-eclampsia than among those with normotensive pregnancies (WMD -158.43, 95% CI -187.95 to -128.92) or chronic hypertension (WMD -92.92, 95% CI -100.55 to -85.29). Excretion was also reduced in severe versus mild pre-eclampsia (WMD -35.00, 95% CI -58.94 to -11.07) and gestational hypertension versus normotensive pregnancies (WMD -50.95, 95% CI -57.74 to -44.17). Calcium excretion was not significantly lower in chronic hypertension versus normotensive pregnancies (WMD -64.45, 95% CI -135.98 to 7.08). Urinary calcium excretion decreases with increasing severity of pregnancy-induced hypertensive disorders, but this trend is not observed in chronic hypertension. © 2017 International Federation of Gynecology and Obstetrics.

  7. Cardiovascular risk factor assessment after pre-eclampsia in primary care

    Directory of Open Access Journals (Sweden)

    Numans Mattijs E

    2009-12-01

    Full Text Available Abstract Background Pre-eclampsia is associated with an increased risk of development of cardiovascular disease later in life. It is not known how general practitioners in the Netherlands care for these women after delivery with respect to cardiovascular risk factor management. Methods Review of medical records of 1196 women in four primary health care centres, who were registered from January 2000 until July 2007 with an International Classification of Primary Care (ICPC code indicating pregnancy. Records were searched for indicators of pre-eclampsia. Of those who experienced pre-eclampsia and of a random sample of 150 women who did not, the following information on cardiovascular risk factor management after pregnancy was extracted from the records: frequency and timing of blood pressure, cholesterol and glucose measurements - and vascular diagnoses. Additionally the sensitivity and specificity of ICPC coding for pre-eclampsia were determined. Results 35 women experienced pre-eclampsia. Blood pressure was more often checked after pregnancy in these women than in controls (57.1% vs. 12.0%, p Conclusion Despite the evidence of increased risk of future cardiovascular disease in women with a history of pre-eclampsia, follow-up of these women is insufficient and undeveloped in primary care in the Netherlands.

  8. Pre-Eclampsia and Eclampsia: An Update on the Pharmacological Treatment Applied in Portugal

    Directory of Open Access Journals (Sweden)

    Gonçalo Miguel Peres

    2018-01-01

    Full Text Available Pre-eclampsia and eclampsia are two hypertensive disorders of pregnancy, considered major causes of maternal and perinatal death worldwide. Pre-eclampsia is a multisystemic disease characterized by the development of hypertension after 20 weeks of gestation, with the presence of proteinuria or, in its absence, of signs or symptoms indicative of target organ injury. Eclampsia represents the consequence of brain injuries caused by pre-eclampsia. The correct diagnosis and classification of the disease are essential, since the therapies for the mild and severe forms of pre-eclampsia are different. Thus, this review aims to describe the most advisable antepartum pharmacotherapy for pre-eclampsia and eclampsia applied in Portugal and based on several national and international available guidelines. Slow-release nifedipine is the most recommended drug for mild pre-eclampsia, and labetalol is the drug of choice for the severe form of the disease. Magnesium sulfate is used to prevent seizures caused by eclampsia. Corticosteroids are used for fetal lung maturation. Overall, the pharmacological prevention of these diseases is limited to low-dose aspirin, so it is important to establish the safest and most effective available treatment.

  9. Telomere length and type 2 diabetes in males, a premature aging syndrome.

    Science.gov (United States)

    Murillo-Ortiz, Blanca; Albarrán-Tamayo, Froylán; Arenas-Aranda, Diego; Benítez-Bribiesca, Luis; Malacara-Hernández, J M; Martínez-Garza, Sandra; Hernández-González, Martha; Solorio, Sergio; Garay-Sevilla, M E; Mora-Villalpando, Carmen

    2012-03-01

    Increased telomere shortening has been demonstrated in several diseases including type 2 diabetes. However, it is not known whether telomere length changes during the course of type 2 diabetes. To determine telomere length at different stages of type 2 diabetes, including early and late stages. A total of 93 males with type 2 diabetes and 10 years or more since original diagnosis; 96 males with less than one year of diagnosis; 98 age matched healthy males. Telomere length was estimated by means of real-time polymerase chain reaction. Fasting venous blood samples were obtained for measurement of lipid peroxidation and inflammation markers. We found a greater telomere shortening in group (A) with type 2 diabetes of 10 years or more since original diagnosis, compared with the control group (C) of healthy males (5.4 vs 9.6 Kb) (p = 0.04) and with group B (5.4 vs 8.7 kb) (p = 0.05). With regard to inflammatory markers TNF-α, malondialdehyde peroxidation and adiponectin we found significant differences. Telomere shortening increases with the duration of diabetes. The time of exhibition suggests in parallel that the progressive increase of inflammation and/or oxidative stress plays a direct role in telomere shortening.

  10. Paired assessment of liver telomere lengths in hepatocellular cancer is a reliable predictor of disease persistence.

    Science.gov (United States)

    Feng, Wendu; Yu, Decai; Li, Binghua; Luo, Ou-Yang; Xu, Tiancheng; Cao, Yajuan; Ding, Yitao

    2017-04-30

    In the present study, we used a small series of highly defined patients, where we had matched timed peripheral blood samples (PBS), as well as paired liver biopsies obtained during collection of blood samples from patients with diagnosed hepatocellular carcinoma (HCC) and compared the correlation between the changes of telomere lengths in these defined samples. Patients included had either HCC alone or in conjunction with either pre-existing hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. PCR-based assay incorporating primers to the telomeric hexamer repeats to polymerize and detect telomeric DNA was used. The average telomere length for each independent assessment was measured by seeing the differences in the intensity of the sample's telomere signal (T) to the signal from a single-copy gene (S-, β-globin) to estimate the standard ratio. Our results provide the first convincing evidence that PBS may be utilized to assay telomere shortening as a predictor for disease persistence in HCC resulting after HBV or HCV infection, but not in non-infectious cause-stimulated HCC. These findings provide incipient opportunity to develop telomere length assessment as a biomarker tool for prediction of HCC in patients with HBV or HCV infection, as well as to gauge responses to chemotherapy and other treatment modalities. © 2017 The Author(s).

  11. Leukocyte telomere length and coronary artery calcification in Palestinians.

    Science.gov (United States)

    Kark, Jeremy D; Nassar, Hisham; Shaham, Dorith; Sinnreich, Ronit; Goldberger, Nehama; Aboudi, Vartohi; Bogot, Naama R; Kimura, Masayuki; Aviv, Abraham

    2013-08-01

    Shorter leukocyte telomere length (LTL) is associated with higher incidence of coronary heart disease (CHD) and increased mortality. We examined the association of LTL with coronary artery calcification (CAC), which reflects the cumulative burden of coronary atherosclerosis, in an urban Arab sample of Palestinians, a population at high risk of CHD. Using a cross-sectional design, a random sample of East Jerusalem residents, comprising 250 men aged 45-77 and women aged 55-76 and free of CHD or past stroke, was drawn from the Israel national population register. LTL was measured by Southern blots. CAC was determined by 16-slice multidetector helical CT scanning using Agatston scoring. We applied multivariable logistic modeling to examine the association between sex-specific tertiles of LTL and CAC (comparing scores >100 vs. education and coronary risk factors. CAC, evident in 65% of men and 52% of women, was strongly associated with age (sex-adjusted Spearman's rho 0.495). The multivariable-adjusted odds ratios for CAC >100 (found in 30% of men and 29% of women) were 2.92 (95% CI 1.28-6.68) and 2.29 (0.99-5.30) for the lower and mid-tertiles of LTL vs. the upper tertile, respectively (Ptrend = 0.008). Findings were similar for CAC scores in the upper tertile (Ptrend = 0.006), and persisted after the exclusion of patients with diabetes or receiving statins. Shorter LTL was associated with a greater prevalence of asymptomatic coronary atherosclerosis in an urban Arab population-based sample. Mechanisms underlying this association should be sought. Copyright © 2013 [Author/Employing Institution]. Published by Elsevier Ireland Ltd.. All rights reserved.

  12. DCAF4, a novel gene associated with leucocyte telomere length

    Science.gov (United States)

    Mangino, Massimo; Christiansen, Lene; Stone, Rivka; Hunt, Steven C; Horvath, Kent; Eisenberg, Dan T A; Kimura, Masayuki; Petersen, Inge; Kark, Jeremy D; Herbig, Utz; Reiner, Alex P; Benetos, Athanase; Codd, Veryan; Nyholt, Dale R; Sinnreich, Ronit; Christensen, Kaare; Nassar, Hisham; Hwang, Shih-Jen; Levy, Daniel; Bataille, Veronique; Fitzpatrick, Annette L; Chen, Wei; Berenson, Gerald S; Samani, Nilesh J; Martin, Nicholas G; Tishkoff, Sarah; Schork, Nicholas J; Kyvik, Kirsten Ohm; Dalgård, Christine; Spector, Timothy D; Aviv, Abraham

    2015-01-01

    Background Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR). Results Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10−10) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10−3 and 2×10−3, respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (p<0.05, <0.01, <0.005, <0.001) in the LTL-GWA meta-analysis, these genes were jointly over-represented for melanoma at p values ranging from 1.97×10−169 to 3.42×10−24. Conclusions We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population. PMID:25624462

  13. Association between telomere length and diabetes mellitus: A meta-analysis.

    Science.gov (United States)

    Wang, Jianfei; Dong, Xu; Cao, Li; Sun, Yangyang; Qiu, Yu; Zhang, Yi; Cao, Ruoqiong; Covasa, Mihai; Zhong, Li

    2016-12-01

    Objective We investigated the relationship between diabetes and telomere length by meta-analysis. Methods We searched five popular databases for articles published between 1990 and 2015 using "diabetes" and "telomere" as search terms. Data were processed with RevMan5, and random- or fixed-effects meta-analysis was applied. The effects of geographical region, diabetes type, body mass index (BMI), age and sex were examined. Funnel plots were applied to evaluate publication bias. Results Seventeen articles were obtained from 571 references. We identified a significant association between telomere length and diabetes mellitus (standardized mean difference [SMD]: -3.41; 95% confidence interval [CI]: -4.01, -2.80; heterogeneity, I(2 )= 99%) by comparing 5575 patients with diabetes and 6349 healthy individuals. The pooled SMD by geographic region indicated a significant association between shortened telomere length and diabetes mellitus (SMD: -3.41; 95% CI: -4.01, -2.80; heterogeneity, I(2 )= 99%). In addition, telomere length was significantly associated with age (SMD: -3.41; 95% CI: -4.01, -2.80), diabetes type (SMD: -3.41; 95% CI: -4.01, -2.80), BMI (SMD: -1.61; 95% CI: -1.98, -1.23) and sex (SMD: -4.94; 95% CI: -9.47, -0.40). Conclusions The study demonstrated a close relationship between diabetes mellitus and telomere length, which was influenced by region, age, diabetes type, BMI and sex.

  14. Influence of Amalaki Rasayana on telomerase activity and telomere length in human blood mononuclear cells.

    Science.gov (United States)

    Guruprasad, Kanive P; Dash, Sweta; Shivakumar, Marigowda B; Shetty, Pavithra R; Raghu, Kothanahalli S; Shamprasad, Bhanuvalli R; Udupi, Vishwanatha; Acharya, Raviraj V; Vidya, Prasanna B; Nayak, Jayakrishna; Mana, Anandan E; Moni, Rajesh; Sankaran, Muraleedharan T; Satyamoorthy, Kapaettu

    Indian traditional medicine practices use defined rasayana preparations to improve the quality of life in aged individuals. Amalaki Rasayana is one such rasayana prepared from the fruits of Phyllanthus emblica and is popularly used to prevent or treat various age related health conditions. Telomerase activity in the cells maintains telomere length and is implicated in ageing and various diseases wherein the shortening of telomere during ageing is controlled chiefly by the telomerase activity. In the present study, we investigated telomerase activity and telomere length in the peripheral blood mononuclear cells of aged individuals administered with Amalaki Rasayana. Amalaki Rasayana was administered to healthy, aged (45-60 years) volunteers for 45 days after koshta shuddhi procedure. The telomerase activity and telomere length were analyzed on 0, 45th and 90th days of Amalaki Rasayana administration in peripheral blood mononuclear cells from these individuals and compared with age-matched placebo group and young volunteers (22-30 years). The data were compared between the groups. The results indicated an increase in telomerase activity with no discernible change in telomere length in the Amalaki administered participants. The comparison between young and aged participants revealed higher telomerase activity in young participants with no significant differences in telomere length. The data indicate that the maintenance of telomere length is facilitated by an increase in telomerase activity upon rasayana administration in aged individuals and Amalaki Rasayana may prevent the erosion of telomeres over a period of time in aged individuals to promote healthy ageing. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  15. Pre-eclampsia or chronic kidney disease? The flow hypothesis.

    Science.gov (United States)

    Piccoli, Giorgina B; Gaglioti, Pietro; Attini, Rossella; Parisi, Silvia; Bossotti, Carlotta; Olearo, Elena; Oberto, Manuela; Ferraresi, Martina; Rolfo, Alessandro; Versino, Elisabetta; Biolcati, Marilisa; Todros, Tullia

    2013-05-01

    Chronic kidney disease (CKD) and pre-eclampsia (PE) occur in 3-5% of pregnancies. They often share hypertension and proteinuria and a differential diagnosis may be impossible. However, in PE, the pathogenesis is related to abnormal placentation, which can be detected by abnormal uterine and umbilical Doppler flow velocities, while in CKD, an intrinsic kidney disease is present. We hypothesize that Doppler studies can help to differentiate PE from CKD, as the flow velocities are altered in PE and normal in CKD. We retrospectively selected patients who were followed in our Materno-Foetal Unit (2005-10) and had at least one flow measurement in our setting. CKD patients were included in the presence of proteinuria (≥ 300 mg/day) and hypertension, mimicking PE. The clinical charts were reviewed by the same operators; the clinical diagnoses were taken as reference. Three flow patterns were considered: alteration of both flow velocity waveforms (FVWs) (uterine and umbilical arteries), hypothesized as predictive of PE; normal FVWs at both levels, hypothesized as predictive of CKD; altered FVW in either artery, considered 'mixed'. Uterine FVWs were considered pathological according to the classical cut-point (RI > 0.58). Umbilical flows were evaluated according to standards adjusted for gestational age. Statistical analysis was performed in SPSS. The analysis included 61 cases. The presence of normal FVWs was significantly associated with the diagnosis of CKD (P = 0.0018). Conversely, the presence of both altered flows was significantly associated with PE (P = 0.0233). In the presence of proteinuria and hypertension, normal flows suggest CKD altered flows PE. Prospective studies are needed to refine this hypothesis based on the first Doppler criteria supporting the differential diagnosis between CKD and PE.

  16. SERUM LIPID CONCENTRATIONS IN PRE - ECLAMPSIA AND NORMAL PREGNANCY - A COMPARATIVE STUDY

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    Jishabai

    2015-08-01

    Full Text Available The association between pre - eclampsia and atherosclerosis is a much discussed topic. The changes in lipid profile observed during pregnancy have significant effects on woman’s long term health, because elevated serum triglycerides is an independent risk factor for coronar y artery disease. The aim of this study is to assess the lipid profile in pregnancy with pre - eclampsia and to compare that with normal pregnancy. METHOD: The study group consisted of 150 subjects in three groups of 50 each, selected according to the inclusion criteria. The groups were normotensive pregnant women, those with mild pre - eclampsia and severe pre - eclampsia. Blood samples were collected from all the subjects after 12hours of fasting, which was centrifuged at 3000rpm for 10 minutes and analyz ed for serum cholesterol, serum triglycerides, serum HDL, LDL and VLDL using an automatic analyzer. Data was analyzed using Chi square test and ANOVA using SPSS software version 16.0. A p value of <0.05 was considered significant. STUDY DESIGN: Cross secti onal study . STUDY SETTING: Department of Obstetrics and Gynaecology, Govt. Medical College, Kozhikode, Kerala, India. RESULTS : In this study, 48.7% of the subjects were in the age group of 18 - 25 years and 17.3%, above 30 years. The total cholesterol level was high in 54.7% of the entire subjects. The highest distribution were in the severe pre - eclampsia group with a significant p value of <0.001. The triglyceride values were high in 18% of normotensive subjects, while it was 46% and 80% in the mild and seve re pre - eclampsia groups respectively. HDL values were normal in the entire normotensive group. In the mild and severe pre - eclampsia groups, 96% and 86% had normal HDL values. High LDL values were seen in 8% of normotensive group, but it was 32% and 28% in the mild and severe pre - eclampsia group respectively, with a significant p value of <0.001. VLDL level was high in 18% of the normotensive group, while

  17. HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis.

    Science.gov (United States)

    Auld, Elizabeth; Lin, Jue; Chang, Emily; Byanyima, Patrick; Ayakaka, Irene; Musisi, Emmanuel; Worodria, William; Davis, J Lucian; Segal, Mark; Blackburn, Elizabeth; Huang, Laurence

    HIV infection is a risk factor for opportunistic pneumonias such as tuberculosis (TB) and for age-associated health complications. Short telomeres, markers of biological aging, are also associated with an increased risk of age-associated diseases and mortality. Our goals were to use a single cohort of HIV-infected and HIV-uninfected individuals hospitalized with pneumonia to assess whether shortened telomere length was associated with HIV infection, TB diagnosis, and 2-month mortality. This was a sub-study of the IHOP Study, a prospective observational study. Participants consisted of 184 adults admitted to Mulago Hospital in Kampala, Uganda who underwent evaluation for suspected TB and were followed for 2 months. Standardized questionnaires were administered to collect demographic and clinical data. PBMCs were isolated and analyzed using quantitative PCR to determine telomere length. The association between HIV infection, demographic and clinical characteristics, and telomere length was assessed, as were the associations between telomere length, TB diagnosis and 2-month mortality. Variables with a P≤0.2 in bivariate analysis were included in multivariate models. No significant demographic or clinical differences were observed between the HIV-infected and HIV-uninfected subjects. Older age (Paging and that shorter telomeres may be involved in age-associated health complications seen in this population. The findings indicate a need to further research the impact of HIV on aging.

  18. Cognitive Change During the Life Course and Leukocyte Telomere Length in Late Middle-aged Men.

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    Lene Rask

    2016-12-01

    Full Text Available AbstractImportance: Cognitive skills are known to decline through the lifespan with large individual differences. The molecular mechanisms for this decline are incompletely understood. Although leukocyte telomere length provides an index of cellular age that predicts the incidence of age-related diseases, it is unclear whether there is an association between cognitive decline and leukocyte telomere length. Objective: To examine the association between changes in cognitive function during adult life and leukocyte telomere length after adjusting for confounding factors such as education, mental health and life style. Design, setting and participants: Two groups of men with negative (n=97 and positive (n=93 change in cognitive performance were selected from a birth cohort of 1985 Danish men born in 1953. Cognitive performance of each individual was assessed at age ~20 and ~56 years. Leukocyte telomere length at age ~58 was measured using qPCR. Linear regression models were used to investigate the association between cognitive function and leukocyte telomere length. Results: Men with negative change in cognitive performance during adult life had significantly shorter mean leukocyte telomere length than men with positive change in cognitive performance (unadjusted difference β= - 0.09, 95% CI -0.16 - -0.02, p= 0.02. This association remained significant after adjusting for smoking, alcohol consumption, leisure time activity, body mass index and cholesterol (adjusted difference β= -0.09, 95% CI -0.17 - -0.01, p= 0.02 but was nonsignificant after adjusting for smoking, alcohol consumption, leisure time activity, body mass index cholesterol, current cognitive function, depression and education (adjusted difference β= -0.07, 95% CI -0.16 - -0.01, p= 0.08. Conclusion and relevance: Preclinical cognitive changes may be associated with leukocyte telomere length.

  19. Influence of Amalaki Rasayana on telomerase activity and telomere length in human blood mononuclear cells

    OpenAIRE

    Guruprasad, Kanive P.; Sweta Dash; Shivakumar, Marigowda B.; Pavithra R. Shetty; Kothanahalli S. Raghu; Shamprasad, Bhanuvalli R.; Vishwanatha Udupi; Acharya, Raviraj V.; Vidya, Prasanna B.; Jayakrishna Nayak; Anandan E. Mana; Rajesh Moni; Sankaran, Muraleedharan T.; Kapaettu Satyamoorthy

    2017-01-01

    Background: Indian traditional medicine practices use defined rasayana preparations to improve the quality of life in aged individuals. Amalaki Rasayana is one such rasayana prepared from the fruits of Phyllanthus emblica and is popularly used to prevent or treat various age related health conditions. Telomerase activity in the cells maintains telomere length and is implicated in ageing and various diseases wherein the shortening of telomere during ageing is controlled chiefly by the telomera...

  20. Extended interferon-alpha therapy accelerates telomere length loss in human peripheral blood T lymphocytes.

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    Joel M O'Bryan

    Full Text Available Type I interferons have pleiotropic effects on host cells, including inhibiting telomerase in lymphocytes and antiviral activity. We tested the hypothesis that long-term interferon treatment would result in significant reduction in average telomere length in peripheral blood T lymphocytes.Using a flow cytometry-based telomere length assay on peripheral blood mononuclear cell samples from the Hepatitis-C Antiviral Long-term Treatment against Cirrhosis (HALT-C study, we measured T cell telomere lengths at screening and at months 21 and 45 in 29 Hepatitis-C virus infected subjects. These subjects had failed to achieve a sustained virologic response following 24 weeks of pegylated-interferon-alpha plus ribavirin treatment and were subsequently randomized to either a no additional therapy group or a maintenance dose pegylated-IFNα group for an additional 3.5 years. Significant telomere loss in naïve T cells occurred in the first 21 months in the interferon-alpha group. Telomere losses were similar in both groups during the final two years. Expansion of CD8(+CD45RA(+CD57(+ memory T cells and an inverse correlation of alanine aminotransferase levels with naïve CD8(+ T cell telomere loss were observed in the control group but not in the interferon-alpha group. Telomere length at screening inversely correlated with Hepatitis-C viral load and body mass index.Sustained interferon-alpha treatment increased telomere loss in naïve T cells, and inhibited the accumulation of T cell memory expansions. The durability of this effect and consequences for immune senescence need to be defined.

  1. Association of biochemical markers with the severity of pre-eclampsia.

    Science.gov (United States)

    Maged, Ahmed M; Aid, Gamal; Bassiouny, Nehal; Eldin, Doaa S; Dahab, Sherif; Ghamry, Nevein K

    2017-02-01

    To assess the association between pre-eclampsia severity and biochemical and ultrasonography markers. A retrospective study was undertaken of women with severe pre-eclampsia (group 1, n=90), mild pre-eclampsia (group 2, n=90), or a normal pregnancy (group 3, n=90) who attended a hospital in Egypt in October 2013-April 2015. Associations between pre-eclampsia and biochemical, cardiotocography, and ultrasonography markers were investigated. There were significant differences between the groups in C-reactive protein (331.44±112.38, 251.43±59.05, and 23.81±16.19 nmol/L; P≤0.05 for all), platelet count (113.40±36.72, 172.93±57.60, and 212.68±70.00×10(9) /L; P≤0.05 for group 1 comparisons), alanine transaminase (52.24±14.83, 38.34±13.12, and 23.11±6.92 U/L; P≤0.05 for group 1 comparisons), and serum uric acid (600.80±117.19, 481.83±118.97, and 243.89±53.54 μmol/L; P=0.050 for group 3 comparisons). Cardiotocography score was worse among women with severe pre-eclampsia than among those in the other two groups (P=0.039 for both comparisons). Biophysical profile score and umbilical artery resistance index differed by group (P≤0.05 for all). Middle cerebral artery resistance index was lower among women with severe pre-eclampsia (P≤0.05). The levels of C-reactive protein, blood urea nitrogen, serum uric acid, and alanine transaminase, and the platelet count were linked with the presence and severity of pre-eclampsia. © 2016 International Federation of Gynecology and Obstetrics.

  2. Maternal and fetal outcome in pre-eclampsia in a secondary care hospital in South India

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    Parveen M Aabidha

    2015-01-01

    Full Text Available Background: Hypertensive disorders in pregnancy are one of the common causes for perinatal and maternal morbidity and mortality in developing countries. Pre-eclampsia is a condition which typically occurs after 20 weeks of gestation and has high blood pressure as the main contributing factor. The aim was to study the effects of pre-eclampsia on the mother and the fetus in rural South Indian population. Materials and Methods: This was a descriptive study conducted in a secondary level hospital in rural South India. A total of 1900 antenatal women were screened for pre-eclampsia during the period August 2010 to July 2011 to study the effects on the mother and fetus. Results: Of the 1900 women screened 93 were detected with pre-eclampsia in the study. Among these, 46.23% were primigravida, 30.1% belonged to socio-economic class 4 and 48.8% were among those with BMI 26-30. The incidence of severe pre-eclampsia was higher in the unregistered women. The most common maternal complication was antepartum hemorrhage (13.9% and the most common neonatal complication was prematurity (23.65%. Conclusions: Treating anemia and improving socioeconomic status will improve maternal and neonatal outcome in pre-eclampsia. Antenatal care and educating women on significance of symptoms will markedly improve perinatal morbidity and mortality. Prematurity, growth restriction and low birth weight are neonatal complications to be anticipated and dealt with when the mother has pre-eclampsia. A good neonatal intensive care unit will help improve neonatal outcomes.

  3. Reduced placental telomere length during pregnancies complicated by intrauterine growth restriction.

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    Jérôme Toutain

    Full Text Available OBJECTIVES: Recent studies have shown that telomere length was significantly reduced in placentas collected at delivery from pregnancies complicated by intrauterine growth restriction secondary to placental insufficiency. Placental telomere length measurement during ongoing pregnancies complicated by intrauterine growth restriction has never been reported. This was the main objective of our study. METHODS: In our center, late chorionic villus samplings were performed between 18 and 37 weeks of amenorrhea in 24 subjects with severe intrauterine growth restriction (cases and in 28 subjects with other indications for prenatal diagnosis (controls. Placental insufficiency was assessed by histo-pathological examination. Relative measurement of telomere length was carried out prospectively by quantitative Fluorescent In Situ Hybridization using fluorescent Peptide Nucleic Acid probes on interphase nuclei obtained from long-term cultured villi and with an automated epifluorescent microscope. A quantitative Polymerase Chain Reaction technique was performed to confirm the quantitative Fluorescent In Situ Hybridization results. The number of copies of gene loci encoding the RNA template (hTERC and the catalytic subunit (hTERT of the enzyme complex telomerase were also estimated in these placentas by Fluorescent In Situ Hybridization. RESULTS: Mean fluorescence intensity of telomere probes estimated by quantitative Fluorescent In Situ Hybridization was significantly less for cases compared to controls (p<0.001. This result indicated that mean telomere length was significantly reduced in placentas during pregnancies complicated by intrauterine growth restriction. Reduced telomere length was confirmed by the quantitative Polymerase Chain Reaction technique. No copy number variation of the hTERC and hTERT loci was noticed for cases, or for controls. CONCLUSION: This study clearly demonstrates a reduction of placental telomere length in ongoing pregnancies

  4. Experimentally increased reproductive effort alters telomere length in the blue tit (Cyanistes caeruleus).

    Science.gov (United States)

    Sudyka, J; Arct, A; Drobniak, S; Dubiec, A; Gustafsson, L; Cichoń, M

    2014-10-01

    Telomeres have recently been suggested to play important role in ageing and are considered to be a reliable ageing biomarkers. The life history theory predicts that costs of reproduction should be expressed in terms of accelerated senescence, and some empirical studies do confirm such presumption. Thus, a link between reproductive effort and telomere dynamics should be anticipated. Recent studies have indeed demonstrated that reproduction may trigger telomere loss, but actual impact of reproductive effort has not received adequate attention in experimental studies. Here, we experimentally manipulated reproductive effort by increasing the brood size in the wild blue tit (Cyanistes caeruleus). We show that parents attending enlarged broods experienced larger yearly telomere decay in comparison to control birds attending unaltered broods. In addition, we demonstrate that the change in telomere length differs between sexes, but this effect was independent from our treatment. To our knowledge, this is the first experimental study in the wild revealing that telomere dynamics may be linked to reproductive effort. Thus, telomere shortening may constitute one of the potential proximate mechanisms mediating the costs of reproduction. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  5. Leukocyte telomere length and hippocampus volume: a meta-analysis [version 1; referees: 2 approved

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    Gustav Nilsonne

    2015-10-01

    Full Text Available Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI -0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma.

  6. Low childhood subjective social status and telomere length in adulthood: The role of attachment orientations.

    Science.gov (United States)

    Murdock, Kyle W; Seiler, Annina; Chirinos, Diana A; Garcini, Luz M; Acebo, Sally L; Cohen, Sheldon; Fagundes, Christopher P

    2018-02-16

    Low subjective social status (SSS) in childhood places one at greater risk of a number of health problems in adulthood. Theoretical and empirical evidence indicates that exposure to supportive parenting may buffer the negative effects of low childhood SSS on adult health. Given the importance of supportive caregivers and close others for the development of attachment orientations throughout the lifespan, attachment theory may be important for understanding why some individuals are resilient to the negative effects of low childhood SSS on adult health while others are not. We examined if attachment anxiety and attachment avoidance altered the association between childhood subjective social status (SSS) and length of telomeres in white blood cells in adulthood. Shorter telomere length is associated with increased risk of age-related diseases including cancer, type 2 diabetes, and cardiovascular disease. Participants (N = 128) completed self-report measures of childhood SSS and attachment orientations, as well as a blood draw. We found that among those with low childhood SSS, low attachment anxiety was associated with longer telomere length in white blood cells in comparison to high attachment anxiety controlling for participant age, sex, race, body mass index, and adult SSS. Among those with high childhood SSS, low attachment anxiety was associated with a slight decrease in telomere length. Attachment avoidance was unrelated to length of telomeres. Such findings provide further evidence for the role that close relationships may have on buffering SSS related health disparities. © 2018 Wiley Periodicals, Inc.

  7. Prediction of pre-eclampsia: a protocol for systematic reviews of test accuracy

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    Khan Khalid S

    2006-10-01

    Full Text Available Abstract Background Pre-eclampsia, a syndrome of hypertension and proteinuria, is a major cause of maternal and perinatal morbidity and mortality. Accurate prediction of pre-eclampsia is important, since high risk women could benefit from intensive monitoring and preventive treatment. However, decision making is currently hampered due to lack of precise and up to date comprehensive evidence summaries on estimates of risk of developing pre-eclampsia. Methods/Design A series of systematic reviews and meta-analyses will be undertaken to determine, among women in early pregnancy, the accuracy of various tests (history, examinations and investigations for predicting pre-eclampsia. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Reviewers working independently will select studies, extract data, and assess study validity according to established criteria. Language restrictions will not be applied. Bivariate meta-analysis of sensitivity and specificity will be considered for tests whose studies allow generation of 2 × 2 tables. Discussion The results of the test accuracy reviews will be integrated with results of effectiveness reviews of preventive interventions to assess the impact of test-intervention combinations for prevention of pre-eclampsia.

  8. Oral nifedipine vs. intravenous labetalol for treatment of pregnancy-induced severe pre-eclampsia.

    Science.gov (United States)

    Shi, D-D; Yang, F-Z; Zhou, L; Wang, N

    2016-12-01

    Pre-eclampsia is one of the most challenging diseases of pregnancy. Both nifedipine and labetalol have been used for treatment of pregnancy-induced severe pre-eclampsia. In the present study, the efficacy and safety of oral nifedipine and intravenous labetalol for severe pre-eclampsia therapy were compared. Eligible pregnant women with severe pre-eclampsia (n = 147) were allocated to receive either oral nifedipine or intravenous labetalol. The primary endpoint of the study was the time needed to achieve target blood pressure. Secondary outcomes were the time interval before a new hypertensive crisis following effective blood pressure control, number of doses and adverse effects. We found that the time taken to achieve effective blood pressure control was 35 vs. 42 min for oral nifedipine and intravenous labetalol, respectively (P = 0·37). Compared with labetalol group, no significant difference was observed regarding time interval and drug dosages in nifedipine arm. Moreover, no serious side effects on maternal or perinatal were observed in either group. These findings suggest that both oral nifedipine and intravenous labetalol are effective for safely reducing blood pressure to target levels in patients with severe pre-eclampsia. © 2016 John Wiley & Sons Ltd.

  9. HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis.

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    Elizabeth Auld

    Full Text Available HIV infection is a risk factor for opportunistic pneumonias such as tuberculosis (TB and for age-associated health complications. Short telomeres, markers of biological aging, are also associated with an increased risk of age-associated diseases and mortality. Our goals were to use a single cohort of HIV-infected and HIV-uninfected individuals hospitalized with pneumonia to assess whether shortened telomere length was associated with HIV infection, TB diagnosis, and 2-month mortality.This was a sub-study of the IHOP Study, a prospective observational study. Participants consisted of 184 adults admitted to Mulago Hospital in Kampala, Uganda who underwent evaluation for suspected TB and were followed for 2 months. Standardized questionnaires were administered to collect demographic and clinical data. PBMCs were isolated and analyzed using quantitative PCR to determine telomere length. The association between HIV infection, demographic and clinical characteristics, and telomere length was assessed, as were the associations between telomere length, TB diagnosis and 2-month mortality. Variables with a P≤0.2 in bivariate analysis were included in multivariate models.No significant demographic or clinical differences were observed between the HIV-infected and HIV-uninfected subjects. Older age (P<0.0001, male gender (P = 0.04, total pack-years smoked (P<0.001, alcohol consumption in the past year (P = 0.12, and asthma (P = 0.08 were all associated (P≤0.2 with shorter telomere length in bivariate analysis. In multivariate analysis adjusting for these five variables, HIV-positive participants had significantly shorter telomeres than HIV-negative participants (β = -0.0621, 95% CI -0.113 to -0.011, P = 0.02. Shortened telomeres were not associated with TB or short-term mortality.The association between HIV infection and shorter telomeres suggests that HIV may play a role in cellular senescence and biological aging and that shorter telomeres may be

  10. Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes

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    Jue Lin

    2016-01-01

    Full Text Available Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. Leukocyte or peripheral blood mononuclear cell (PBMC telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. We examined the average telomere length (TL in CD4+, CD8+CD28+, and CD8+CD28− T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. We report that TL changes over 18 months were correlated among these three T cell types within the same participant. Additionally, PBMC TL change was also correlated with those of all three T cell types, and B cells. The rate of shortening for B cells was significantly greater than for the three T cell types. CD8+CD28− cells, despite having the shortest TL, showed significantly more rapid attrition when compared to CD8+CD28+ T cells. These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation.

  11. Synaptonemal complex extension from clustered telomeres mediates full-length chromosome pairing in Schmidtea mediterranea.

    Science.gov (United States)

    Xiang, Youbin; Miller, Danny E; Ross, Eric J; Sánchez Alvarado, Alejandro; Hawley, R Scott

    2014-12-02

    In the 1920s, József Gelei proposed that chromosome pairing in flatworms resulted from the formation of a telomere bouquet followed by the extension of synapsis from telomeres at the base of the bouquet, thus facilitating homolog pairing in a processive manner. A modern interpretation of Gelei's model postulates that the synaptonemal complex (SC) is nucleated close to the telomeres and then extends progressively along the full length of chromosome arms. We used the easily visible meiotic chromosomes, a well-characterized genome, and RNAi in the sexual biotype of the planarian Schmidtea mediterranea to test that hypothesis. By identifying and characterizing S. mediterranea homologs of genes encoding synaptonemal complex protein 1 (SYCP1), the topoisomerase-like protein SPO11, and RAD51, a key player in homologous recombination, we confirmed that SC formation begins near the telomeres and progresses along chromosome arms during zygotene. Although distal regions pair at the time of bouquet formation, pairing of a unique interstitial locus is not observed until the formation of full-length SC at pachytene. Moreover, neither full extension of the SC nor homologous pairing is dependent on the formation of double-strand breaks. These findings validate Gelei's speculation that full-length pairing of homologous chromosomes is mediated by the extension of the SC formed near the telomeres. S. mediterranea thus becomes the first organism described (to our knowledge) that forms a canonical telomere bouquet but does not require double-strand breaks for synapsis between homologous chromosomes. However, the initiation of SC formation at the base of the telomere bouquet, which then is followed by full-length homologous pairing in planarian spermatocytes, is not observed in other species and may not be conserved.

  12. Telomere length in Chernobyl accident recovery workers in the late period after the disaster.

    Science.gov (United States)

    Reste, Jelena; Zvigule, Gunda; Zvagule, Tija; Kurjane, Natalja; Eglite, Maija; Gabruseva, Natalija; Berzina, Dace; Plonis, Juris; Miklasevics, Edvins

    2014-11-01

    The outcome of the Chernobyl nuclear power plant (CNPP) accident was that a huge number of people were exposed to ionizing radiation. Previous studies of CNPP clean-up workers from Latvia revealed a high occurrence of age-associated degenerative diseases and cancer in young adults, as well as a high mortality as a result of cardiovascular disorders at age 45-54 years. DNA tandem repeats that cap chromosome ends, known as telomeres, are sensitive to oxidative damage and exposure to ionizing radiation. Telomeres are important in aging processes and carcinogenesis. The aim of this study was to investigate the long-term effect of protracted ionizing radiation exposure on telomere length in CNPP clean-up workers. Relative telomere length (RTL) was measured in peripheral blood leukocytes of 595 CNPP clean-up workers and 236 gender- and age-matched controls using real-time quantitative polymerase chain reaction (q-PCR). Close attention was paid to participation year and tasks performed during the worker's stay in Chernobyl, health status, and RTL differences between subgroups. Telomere shortening was not found in CNPP clean-up workers; on the contrary, their RTL was slightly greater than in controls (P = 0.001). Longer telomeres were found in people who worked during 1986, in those undertaking 'dirty' tasks (digging and deactivation), and in people with cancer. Shorter telomeres appeared frequently in those with cataract, osteoporosis, atherosclerosis, or coronary heart disease. We conclude that the longer telomeres revealed in people more heavily exposed to ionizing radiation probably indicate activation of telomerase as a chromosome healing mechanism following damage, and reflect defects in telomerase regulation that could potentiate carcinogenesis. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  13. Telomere length reflects phenotypic quality and costs of reproduction in a long-lived seabird : An evolutionary view on biological rhythms

    NARCIS (Netherlands)

    Bauch, Christina; Becker, Peter H.; Verhulst, Simon

    2013-01-01

    Telomere length is associated with cellular senescence, lifestyle and ageing. Short telomeres indicate poor health in humans and reduced life expectancy in several bird species, but little is known about telomeres in relation to phenotypic quality in wild animals. We investigated telomere lengths in

  14. Longitudinal Change in Telomere Length and the Chronic Stress Response in a Randomized Pilot Biobehavioral Clinical Study: Implications for Cancer Prevention

    OpenAIRE

    Biegler, K. A; Anderson, A. K. L; Wenzel, L. B; Osann, K; Nelson, E. L.

    2012-01-01

    Shortened telomere length is associated with increased cancer incidence and mortality. Populations experiencing chronic stress have accelerated telomere shortening. In this exploratory study, we examined associations between longitudinal changes in patient reported outcomes (PRO) of psychologic distress and peripheral blood mononuclear cell (PBMC) telomere length to test the hypothesis that modulation of the chronic stress response would also modulate telomere dynamics. Archived PBMC specimen...

  15. Cognitive Change during the Life Course and Leukocyte Telomere Length in Late Middle-Aged Men

    DEFF Research Database (Denmark)

    Rask, Lene; Bendix, Laila; Harbo, Maria

    2016-01-01

    Importance: Cognitive skills are known to decline through the lifespan with large individual differences. The molecular mechanisms for this decline are incompletely understood. Although leukocyte telomere length provides an index of cellular age that predicts the incidence of age-related diseases......, it is unclear whether there is an association between cognitive decline and leukocyte telomere length. Objective: To examine the association between changes in cognitive function during adult life and leukocyte telomere length after adjusting for confounding factors such as education, mental health and life......% CI −0.17 to −0.01, p = 0.02) but was non-significant after adjusting for smoking, alcohol consumption, leisure time activity, BMI, cholesterol, current cognitive function, depression and education (adjusted difference β = −0.07, 95% CI −0.16 to −0.01, p = 0.08). Conclusion and Relevance: Preclinical...

  16. Diet and Pre-eclampsia: A Prospective Multicentre Case-Control Study in Ethiopia.

    Science.gov (United States)

    Endeshaw, Mulualem; Abebe, Fantu; Bedimo, Melkamu; Asart, Anemaw

    2015-06-01

    Pre-eclampsia is one of the most commonly encountered hypertensive disorders of pregnancy that accounts for 20-80% of maternal mortality in developing countries, including Ethiopia. For many years, diet has been suggested to play a role in pre-eclampsia. However, the hypotheses have been diverse with inconsistent results across studies, and this has not been studied in Ethiopia. The objective of this study was to determine the effect of dietary habits on the incidence of pre-eclampsia in Bahir Dar, Ethiopia A prospective multicentre unmatched case-control study was conducted among 453 (151 cases and 302 controls) pregnant women attending antepartum or intrapartum care in public health facilities of Bahir Dar City from June to September 2014. The interviewer conducted a face-to-face interview, measured the mid-upper arm circumference (MUAC) and collected the mid-pregnancy haemoglobin level from clinical notes using a standardized and pretested questionnaire. Epi Info 3.5.3 was used for data entry and cleaning, while IBM SPSS Statistics 20 was used for data analysis. Backward stepwise unconditional logistic regression analysis was employed to determine the strength of association of predictive variables with the outcome variable and to control for the effect of confounding variables. A P-value ≤0.05 was considered statistically significant. For every 1-cm increase of MUAC, there was an increase in the incidence rate of pre-eclampsia by a factor of 1.35 (adjusted odds ratio (AOR)=1.35, 95% confidence interval (CI): 1.21, 1.51). A higher incidence of pre-eclampsia was found in women who reported to have consumed coffee daily during pregnancy (AOR=1.78, 95% CI: 1.20, 3.05). Similarly, for women who had anaemia during the first trimester, the incidence of pre-eclampsia was 2.5 times higher than their counterparts (AOR=2.47, 95% CI: 1.12, 7.61). This study also revealed consumption of fruit or vegetables at least three times a week during pregnancy to be protective

  17. Including ethical considerations in models for first-trimester screening for pre-eclampsia

    DEFF Research Database (Denmark)

    Jørgensen, Jennifer Maureen; Hedley, Paula L.; Gjerris, Mickey

    2014-01-01

    Recent efforts to develop reliable and efficient early pregnancy screening programmes for pre-eclampsia have focused on com-bining clinical, biochemical and biophysical markers. The same model has been used for first-trimester screening for fetal aneuploidies i.e. prenatal diagnosis (PD), which...... is routinely offered to all pregnant women in many developed countries. Some studies suggest combining PD and pre-eclampsia screening, so women can be offered testing for a number of conditions at the same clinical visit. A combination of these tests may be practical in terms of saving time and resources......; however, the combination raises ethical issues. First-trimester PD and pre-eclampsia screening entail qualitative differences which alter the requirements for disclosure, non-directedness and consent with regard to the informed consent process. This article explores the differences related to the ethical...

  18. Healthy lifestyle and leukocyte telomere length in U.S. women.

    Directory of Open Access Journals (Sweden)

    Qi Sun

    Full Text Available Whether a healthy lifestyle may be associated with longer telomere length is largely unknown.To examine healthy lifestyle practices, which are primary prevention measures against major age-related chronic diseases, in relation to leukocyte telomere length.Cross-sectional analysis in the Nurses' Health Study (NHS.The population consisted of 5,862 women who participated in multiple prospective case-control studies within the NHS cohort. Z scores of leukocyte telomere length were derived within each case-control study. Based on prior work, we defined low-risk or healthy categories for five major modifiable factors assessed in 1988 or 1990: non-current smoking, maintaining a healthy body weight (body mass index in 18.5-24.9 kg/m(2, engaging in regular moderate or vigorous physical activities (≥150 minutes/week, drinking alcohol in moderation (1 drink/week to <2 drinks/day, and eating a healthy diet (Alternate Healthy Eating Index score in top 50%. We calculated difference (% of the z scores contrasting low-risk groups with reference groups to evaluate the association of interest.Although none of the individual low-risk factors was significantly associated with larger leukocyte telomere length z scores, we observed a significant, positive relationship between the number of low-risk factors and the z scores. In comparison with women who had zero low-risk factors (1.9% of the total population and were, therefore, considered the least healthy group, the leukocyte telomere length z scores were 16.4%, 22.1%, 28.7%, 22.6%, and 31.2% (P for trend = 0.015 higher for women who had 1 to 5 low-risk factors, respectively.Adherence to a healthy lifestyle, defined by major modifiable risk factors, was associated with longer telomere length in leukocytes.

  19. Depression, anxiety and telomere length in young adults: evidence from the National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Needham, B L; Mezuk, B; Bareis, N; Lin, J; Blackburn, E H; Epel, E S

    2015-04-01

    Telomere length has been hypothesized to be a marker of cumulative exposure to stress, and stress is an established cause of depression and anxiety disorders. The aim of this study was to examine the relationship between depression, anxiety and telomere length, and to assess whether this relationship is moderated by race/ethnicity, gender and/or antidepressant use. Data were from the 1999-2002 National Health and Nutrition Examination Survey. Telomere length was assessed using the quantitative PCR method of telomere length relative to standard reference DNA. Past-year major depression (MD), generalized anxiety disorder (GAD) and panic disorder (PD), as well as depressed affect and anxious affect, were assessed using the Composite International Diagnostic Inventory (N=1290). Multiple linear regression was used to assess the relationship between depression and anxiety disorders and telomere length. Among women, those with GAD or PD had shorter telomeres than those with no anxious affect (β: -0.07, P0.05). Among respondents currently taking an antidepressant, those with MD had shorter telomeres than those without (β: -0.26, P0.05). Neither depressive nor anxiety disorders were directly associated with telomere length in young adults. There was suggestive evidence that pharmacologically treated MD is associated with shorter telomere length, likely reflecting the more severe nature of MD that has come to clinical attention.

  20. Telomere length is associated with ACE I/D polymorphism in hypertensive patients with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Fyhrquist, Frej; Eriksson, Anders; Saijonmaa, Outi

    2013-01-01

    INTRODUCTION: Short telomeres are often associated with cardiovascular risk factors and age-related diseases, while the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (DD, ID, II) has shown such associations less consistently. We hypothesized that telomere length...... and association of telomere length with cardiovascular risk is affected by ACE (I/D) genotype. METHODS: We measured leucocyte telomere length (LTL) by Southern blot and analysed ACE I/D genotypes in 1249 subjects with hypertension and left ventricular hypertrophy (LVH). We examined interactions of ACE I...

  1. Telomere Length and Long-Term Endurance Exercise: Does Exercise Training Affect Biological Age? A Pilot Study

    OpenAIRE

    Østhus, Ida Beate Øyen; Sgura, Antonella; Berardinelli, Francesco; Alsnes, Ingvild Vatten; Brønstad, Eivind; Rehn, Tommy Aune; Støbakk, Per Kristian; Hatle, Håvard; Wisløff, Ulrik; Nauman, Javaid

    2012-01-01

    Background: Telomeres are potential markers of mitotic cellular age and are associated with physical ageing process. Long-term endurance training and higher aerobic exercise capacity (VO2max) are associated with improved survival, and dynamic effects of exercise are evident with ageing. However, the association of telomere length with exercise training and VO2max has so far been inconsistent. Our aim was to assess whether muscle telomere length is associated with endurance exercise trainin...

  2. Single Stem Cell Imaging and Analysis Reveals Telomere Length Differences in Diseased Human and Mouse Skeletal Muscles

    OpenAIRE

    Tichy, Elisia D.; David K. Sidibe; Tierney, Matthew T.; Michael J. Stec; Sharifi-Sanjani, Maryam; Hosalkar, Harish; Mubarak, Scott; Johnson, F. Brad; Sacco, Alessandra; Mourkioti, Foteini

    2017-01-01

    Summary Muscle stem cells (MuSCs) contribute to muscle regeneration following injury. In many muscle disorders, the repeated cycles of damage and repair lead to stem cell dysfunction. While telomere attrition may contribute to aberrant stem cell functions, methods to accurately measure telomere length in stem cells from skeletal muscles have not been demonstrated. Here, we have optimized and validated such a method, named MuQ-FISH, for analyzing telomere length in MuSCs from either mice or hu...

  3. Catechol-O-methyltransferase Gene Polymorphism (Val158Met) and Development of Pre-eclampsia.

    Science.gov (United States)

    Taravati, Ali; Tohidi, Fatemeh; Moniri, Mehrnaz; Kamali, Kasra

    2017-02-01

    Catechol-O-methyltransferase (COMT) is a key enzyme in degradation pathways of estrogens and catecholamines. The present meta-analysis was done to elucidate the association of COMT Val158Met polymorphism with pre-eclampsia among pregnant women. A literature search was conducted in electronic databases including PubMed, Scopus, Elsevier, Springer and Google Scholar to find eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals were calculated under dominant, recessive, co-dominant, and allelic models. This meta-analysis included 6 eligible studies consisting 2596 cases and 4223 controls. The ORs for the COMT G472A polymorphism and pre-eclampsia were indicative of positive association under several genetic models. The results indicated that COMT Val158Met polymorphism was significantly associated with the increased risk of pre-eclampsia in recessive model (AA vs. AG + GG: OR = 1.522 [95% CI: 1.089-2.127]; p = 0.014), co-dominant model (AA vs. GG: OR = 1.605 [95% CI: 1.102-2.336]; p = 0.014), and allelic model (A vs. T: OR = 1.200 [95% CI: 1.021-1.402]; p = 0.021). In summary, COMT Val158Met polymorphism is positively associated with the increased risk of pre-eclampsia among pregnant women, especially the homozygous carriers. It could be of value to investigate its association with pre-eclampsia in combination with additional risk factors. However, very large studies with different ethnic population are required to accurately demonstrate the role of this candidate gene in development of pre-eclampsia. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  4. Pre-eclampsia research in the Norwegian Mother and Child Cohort Study

    Directory of Open Access Journals (Sweden)

    Per Magnus

    2014-12-01

    Full Text Available Pre-eclampsia is a pregnancy disorder of unknown origin. In Norway, pre-eclampsia is reported in 3 to 4 per cent of registered births. At present, November 2014, a series of investigations into the etiology of preeclampsia have been published internationally from the Norwegian Mother and Child Cohort Study (MoBa, and several studies are ongoing. The intention of this paper is to give a short summary of what has been accomplished, and to discuss future avenues of research concerning causes, mechanisms and consequences of pre-eclampsia. The papers that have been published up to now include seven that concern life-styles (physical activity, tobacco and diet, six that include prior pregnancies, infection, gestational weight gain, toxicants and tryptophan metabolism, and two studies concerning issues of selection and validity. Major findings are that tobacco smoking is only associated with reduced risk of pre-eclampsia when it occurs in the last trimester; that processed food and sugar-sweetened beverages are associated with increased risk while vegetables, vitamin D and probiotics are associated with reduced risk; and that prior induced abortions have the same risk-reducing effect as a prior pregnancy. For future studies, we suggest that better use should be made of the family structure built into MoBa. This includes better use of the discordant pregnancy design. A series of ongoing genetic studies, partly in international consortia, will hopefully open new etiological insights. The indications that pre-eclampsia is related to cardiovascular disease and other complex disorders should be further investigated through systematic follow-up of pre-eclamptic women and controls. Finally, MoBa is eminently suited to study the influences that pre-eclampsia can have on the growing child.

  5. High phobic anxiety is related to lower leukocyte telomere length in women.

    Science.gov (United States)

    Okereke, Olivia I; Prescott, Jennifer; Wong, Jason Y Y; Han, Jiali; Rexrode, Kathryn M; De Vivo, Immaculata

    2012-01-01

    Chronic psychological distress has been linked to shorter telomeres, an indication of accelerated aging. Yet, little is known about relations of anxiety to telomeres. We examined whether a typically chronic form of anxiety--phobic anxiety--is related to telomere length. Relative telomere lengths (RTLs) in peripheral blood leukocytes were measured by quantitative real-time polymerase chain reaction among 5,243 women (aged 42-69 years) who: were participants in the Nurses' Health Study; were controls in prior case-control studies of telomeres and disease, or randomly selected healthy participants in a cognitive function sub-study; had completed the Crown-Crisp phobic index proximal to blood collection. Adjusted least-squares mean RTLs (z-scores) were calculated across phobic categories. Higher phobic anxiety was generally associated with lower RTLs (age-adjusted p-trend = 0.09); this association was similar after adjustment for confounders--paternal age-at-birth, smoking, body mass index (BMI) and physical activity (p-trend = 0.15). Notably, a threshold was identified. Among women with Crown-Crispphobic women (Crown-Crisp ≥ 6), the multivariable-adjusted least-squares mean RTL z-score = -0.09 standard units (mean difference = -0.10 standard units; p = 0.02). The magnitude of this difference was comparable to that for women 6 years apart in age. Finally, effect modification by BMI, smoking and paternal age was observed: associations were stronger among highly phobic women with BMI ≥ 25 kg/m(2), without smoking history, or born to fathers aged ≥ 40 years. In this large, cross-sectional study high phobic anxiety was associated with shorter telomeres. These results point toward prospective investigations relating anxiety to telomere length change.

  6. High phobic anxiety is related to lower leukocyte telomere length in women.

    Directory of Open Access Journals (Sweden)

    Olivia I Okereke

    Full Text Available BACKGROUND: Chronic psychological distress has been linked to shorter telomeres, an indication of accelerated aging. Yet, little is known about relations of anxiety to telomeres. We examined whether a typically chronic form of anxiety--phobic anxiety--is related to telomere length. METHODOLOGY/PRINCIPAL FINDINGS: Relative telomere lengths (RTLs in peripheral blood leukocytes were measured by quantitative real-time polymerase chain reaction among 5,243 women (aged 42-69 years who: were participants in the Nurses' Health Study; were controls in prior case-control studies of telomeres and disease, or randomly selected healthy participants in a cognitive function sub-study; had completed the Crown-Crisp phobic index proximal to blood collection. Adjusted least-squares mean RTLs (z-scores were calculated across phobic categories. Higher phobic anxiety was generally associated with lower RTLs (age-adjusted p-trend = 0.09; this association was similar after adjustment for confounders--paternal age-at-birth, smoking, body mass index (BMI and physical activity (p-trend = 0.15. Notably, a threshold was identified. Among women with Crown-Crisp<6 points, the multivariable-adjusted least-squares mean RTL z-score = 0.02 standard units; however, among the most phobic women (Crown-Crisp ≥ 6, the multivariable-adjusted least-squares mean RTL z-score = -0.09 standard units (mean difference = -0.10 standard units; p = 0.02. The magnitude of this difference was comparable to that for women 6 years apart in age. Finally, effect modification by BMI, smoking and paternal age was observed: associations were stronger among highly phobic women with BMI ≥ 25 kg/m(2, without smoking history, or born to fathers aged ≥ 40 years. CONCLUSIONS/SIGNIFICANCE: In this large, cross-sectional study high phobic anxiety was associated with shorter telomeres. These results point toward prospective investigations relating anxiety to telomere length change.

  7. In young men sperm telomere length is related to sperm number and parental age.

    Science.gov (United States)

    Ferlin, A; Rampazzo, E; Rocca, M S; Keppel, S; Frigo, A C; De Rossi, A; Foresta, C

    2013-12-01

    What are the relationships between telomere lengths in leukocytes and sperm, sperm count and parents' age at conception in a group of apparently healthy subjects of the same age? Sperm telomere length (STL) is related to sperm count, it is lower in oligozoospermic than in normozoospermic men and it is directly related to parents' age at conception. Leukocyte telomere length (LTL) decreases with age but STL increases and offspring of older fathers tend to have longer leukocyte telomeres. Only one study analyzed STL in relation to male fertility, and reported shorter telomeres in infertile versus fertile men. No data have been reported on STL in relation to parents' age at conception. Prospective study conducted from January to December 2012 of 18-19-year-old high school students. The volunteers were 81 apparently healthy subjects, including 61 with normozoospermia and 20 with idiopathic oligozoospermia. Leukocyte and sperm telomere length were measured by real-time PCR. Data were analyzed for determining the relationships between LTL, STL, sperm count and parents' age at conception. Sperm and leukocyte telomere length were strongly correlated, but STL was significantly longer. A significant positive correlation between STL and total sperm number was found. STL was significantly lower in oligozoospermic than in normozoospermic men. Finally, we found a significant positive relationship between maternal age and both leukocyte and sperm telomere length and a significant positive relation between paternal age and STL in the offspring. The relative contributions of mothers' and fathers' ages to their offspring's telomere length could not be determined because of the high correlation between paternal and maternal ages. Although consistent with previous findings, this is the first study on telomere length in oligo- and normozoospermic men and included a relatively low number of subjects. Our study was also restricted to young (18-19 year old) men, so future studies should

  8. Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

    Directory of Open Access Journals (Sweden)

    Florencia M. Barbé-Tuana

    Full Text Available Objective: Bipolar disorder (BD has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls. Methods: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively. The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle. Conclusion: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD.

  9. Telomere Length in Elderly Caucasians Weakly Correlates with Blood Cell Counts

    Directory of Open Access Journals (Sweden)

    Ewa Gutmajster

    2013-01-01

    Full Text Available Background. Age-related decrease in bone marrow erythropoietic capacity is often accompanied by the telomere length shortening in peripheral white blood cells. However, limited and conflicting data hamper the conclusive opinion regarding this relationship. Therefore, the aim of this study was to assess an association between telomere length and peripheral blood cell count parameters in the Polish elderly population. Material and Methods. The substudy included 1573 of 4981 subjects aged 65 years or over, participants of the population-based PolSenior study. High-molecular-weight DNA was isolated from blood mononuclear cells. Telomere length (TL was measured by QRT-PCR as abundance of telomere template versus a single gene copy encoding acidic ribosomal phosphoprotein P0. Results. Only white blood count (WBC was significantly different in TL tertile subgroups in all subjects (P=0.02 and in men (P=0.01, but not in women. Merely in men significant but weak positive correlations were found between TL and WBC (r=0.11, P<0.05 and RBC (r=0.08, P<0.05. The multiple regression analysis models confirmed a weak, independent contribution of TL to both RBC and WBC. Conclusions. In the elderly, telomere shortening limits hematopoiesis capacity to a very limited extent.

  10. Work-related exhaustion and telomere length: a population-based study.

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    Kirsi Ahola

    Full Text Available Psychological stress is suggested to accelerate the rate of biological aging. We investigated whether work-related exhaustion, an indicator of prolonged work stress, is associated with accelerated biological aging, as indicated by shorter leukocyte telomeres, that is, the DNA-protein complexes that cap chromosomal ends in cells.We used data from a representative sample of the Finnish working-age population, the Health 2000 Study. Our sample consisted of 2911 men and women aged 30-64. Work-related exhaustion was assessed using the Maslach Burnout Inventory--General Survey. We determined relative leukocyte telomere length using a quantitative real-time polymerase chain reaction (PCR -based method.After adjustment for age and sex, individuals with severe exhaustion had leukocyte telomeres on average 0.043 relative units shorter (standard error of the mean 0.016 than those with no exhaustion (p = 0.009. The association between exhaustion and relative telomere length remained significant after additional adjustment for marital and socioeconomic status, smoking, body mass index, and morbidities (adjusted difference 0.044 relative units, standard error of the mean 0.017, p = 0.008.These data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging. This hypothesis awaits confirmation in a prospective study measuring changes in relative telomere length over time.

  11. Telomere length analysis in monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia Binet A

    Directory of Open Access Journals (Sweden)

    F.M. Furtado

    Full Text Available Monoclonal B-cell lymphocytosis (MBL is an asymptomatic clinical entity characterized by the proliferation of monoclonal B cells not meeting the diagnosis criteria for chronic lymphocytic leukemia (CLL. MBL may precede the development of CLL, but the molecular mechanisms responsible for disease progression and evolution are not completely known. Telomeres are usually short in CLL and their attrition may contribute to disease evolution. Here, we determined the telomere lengths of CD5+CD19+ cells in MBL, CLL, and healthy volunteers. Twenty-one CLL patients, 11 subjects with high-count MBL, and 6 with low-count MBL were enrolled. Two hundred and sixty-one healthy volunteers aged 0 to 88 years were studied as controls. After diagnosis confirmation, a flow cytometry CD19+CD5+-based cell sorting was performed for the study groups. Telomere length was determined by qPCR. Telomere length was similar in the 3 study groups but shorter in these groups compared to normal age-matched subjects that had been enrolled in a previous study from our group. These findings suggest that telomere shortening is an early event in CLL leukemogenesis.

  12. TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell lines

    Science.gov (United States)

    Schwartz, J. L.; Jordan, R.; Liber, H.; Murnane, J. P.; Evans, H. H.

    2001-01-01

    Telomere shortening in telomerase-negative somatic cells leads to the activation of the TP53 protein and the elimination of potentially unstable cells. We examined the effect of TP53 gene expression on both telomere metabolism and chromosome stability in immortal, telomerase-positive cell lines. Telomere length, telomerase activity, and chromosome instability were measured in multiple clones isolated from three related human B-lymphoblast cell lines that vary in TP53 expression; TK6 cells express wild-type TP53, WTK1 cells overexpress a mutant form of TP53, and NH32 cells express no TP53 protein. Clonal variations in both telomere length and chromosome stability were observed, and shorter telomeres were associated with higher levels of chromosome instability. The shortest telomeres were found in WTK1- and NH32-derived cells, and these cells had 5- to 10-fold higher levels of chromosome instability. The primary marker of instability was the presence of dicentric chromosomes. Aneuploidy and other stable chromosome alterations were also found in clones showing high levels of dicentrics. Polyploidy was found only in WTK1-derived cells. Both telomere length and chromosome instability fluctuated in the different cell populations with time in culture, presumably as unstable cells and cells with short telomeres were eliminated from the growing population. Our results suggest that transient reductions in telomere lengths may be common in immortal cell lines and that these alterations in telomere metabolism can have a profound effect on chromosome stability. Copyright 2000 Wiley-Liss, Inc.

  13. La aspirina es ineficaz en la prevención de la pre-eclampsia

    OpenAIRE

    Bustamante Rojas, Carlos

    2011-01-01

    Tres recientes estudios han confirmado que la aspirina no aporta ningún beneficio en la prevención de la pre-eclampsia o en reducir los efectos de esta en los recién nacidos. Sin embargo, y a pesar de la evidencia cada vez mayor de ineficacia, muchos continúan usándola de rutina con este fin. EI resultado de un primer ensayo clínico aleatorizado con 2.539 mujeres en alto riesgo para presentar pre-eclampsia, llevado a cabo en el National Institute of Child Health and Human Development en los E...

  14. Telomere length reflects reproductive effort indicated by corticosterone levels in a long-lived seabird.

    Science.gov (United States)

    Bauch, Christina; Riechert, Juliane; Verhulst, Simon; Becker, Peter H

    2016-11-01

    Telomere length (TL) is a candidate biomarker of ageing and phenotypic quality, but little is known of the (physiological) causes of TL variation. We previously showed that individual common terns Sterna hirundo with high reproductive success had short telomeres independent of age, and this pattern was particularly strong in the longer telomeres of the within-individual TL distribution. To test whether this relation can be attributed to effects of reproductive effort, we investigated baseline corticosterone in relation to reproductive success (number of fledglings) and TL. In this context, we assume that variation in baseline corticosterone can be interpreted as index of energy expenditure and allostatic load. Males with higher corticosterone levels during incubation, compared between and within individuals, achieved higher reproductive success and had shorter telomeres. The effect on telomeres was more pronounced in corticosterone measured later in incubation and in the longer telomeres of the within-individual TL distribution. Female corticosterone level during incubation was neither related to reproductive success nor to TL. That we observed these effects only in males mirrors different parental roles during reproduction in the common tern, where males do most of the chick provisioning. The negative association between reproductive success and TL suggests individual differences in reproductive effort as reflected in, or mediated by, baseline corticosterone. We see this result as a promising step towards unravelling the physiological causes of variation in TL and the costs of reproduction. © 2016 John Wiley & Sons Ltd.

  15. Telomere Length and Pulse Pressure in Newly Diagnosed, Antipsychotic-Naive Patients With Nonaffective Psychosis

    Science.gov (United States)

    Fernandez-Egea, Emilio; Bernardo, Miguel; Heaphy, Christopher M.; Griffith, Jeffrey K.; Parellada, Eduard; Esmatjes, Enric; Conget, Ignacio; Nguyen, Linh; George, Varghese; Stöppler, Hubert; Kirkpatrick, Brian

    2009-01-01

    Introduction: Recent studies suggest that in addition to factors such as treatment side effects, suicide, and poor health habits, people with schizophrenia may have an increased risk of diabetes prior to antipsychotic treatment. Diabetes is associated with an increased pulse pressure (PP) and a shortened telomere. We tested the hypothesis that prior to antipsychotic treatment, schizophrenia and related disorders are associated with a shortened telomere, as well as an increased PP. Methods: Telomere content (which is highly correlated with telomere length) and PP were measured in newly diagnosed, antipsychotic-naive patients with schizophrenia and related disorders on first clinical contact and in matched control subjects. Both groups were also administered an oral glucose tolerance test. Results: Compared with control subjects, the patients with psychosis had decreased telomere content and an increased PP. As previously reported, they also had increased glucose concentrations at 2 hours. These differences could not be attributed to differences in age, ethnicity, smoking, gender, body mass index, neighborhood of residence, socioeconomic status, aerobic conditioning, or an increased cortisol concentration in the psychotic subjects. Discussion: These results suggest that prior to antipsychotic use, nonaffective psychosis is associated with reduced telomere content and increased PP, indices that have been linked to an increased risk of diabetes and hypertension. PMID:19279086

  16. Is telomere length associated with mate choice in a songbird with a high rate of extra-pair paternity?

    Science.gov (United States)

    Johnsen, Arild; Pauliny, Angela; Lifjeld, Jan T; Blomqvist, Donald

    2017-01-01

    Telomere length is related to aging in many eukaryotes and the rate of telomere attrition has been suggested to reflect individual genetic quality. Telomere length could thus have implications for mate choice. We investigated telomere length variation in bluethroat Luscinia svecica families with mixed paternity, including social parents, extra-pair fathers and nestlings, testing whether telomere length is associated with social and/or extra-pair mate choice through assortative mating or selection of mates with relatively long telomeres. In adults, relative telomere length (rTL) did not differ between the sexes, nor between two age categories. In chicks, however, rTL decreased with body mass at sampling (an index of nestling age). We found a positive correlation between the rTL of social mates, suggesting assortative mating with respect to telomere length or a correlative thereof. However, extra-pair males did not differ from social mates in rTL, and accordingly there was also no difference between within- and extra-pair young (i.e. half-siblings) when controlling for the effect of mass. We found no relationships between telomere length, age and fitness-related traits in adults, but an intriguing year-difference in telomere length in both sexes. In conclusion, we found no support for the idea that females choose extra-pair males based on their telomere length, but social mate choice seems to be influenced by rTL, possibly through its co-variation with aspects reflecting individual quality, like early arrival at the breeding grounds.

  17. Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models

    NARCIS (Netherlands)

    Thangaratinam, Shakila; Allotey, John; Marlin, Nadine; Dodds, Julie; Cheong-See, Fiona; von Dadelszen, Peter; Ganzevoort, Wessel; Akkermans, Joost; Kerry, Sally; Mol, Ben W.; Moons, Karl G. M.; Riley, Richard D.; Khan, Khalid S.; Sundararajah, Raajkumar; Nejad, Avideah; Khan, Rehan; Burrell, Celia; Gupta, Manish; Oon, Vincent; Kadir, Rezan; Ramsey-Marcelle, Zeudi; Page, Louise; Thilaganathan, Baskaran; Martin, Bill; Bakour, Shagaf Haj; Morsi, Hassan; Churchill, David; O'Mahony, Fidelma; Powell, Karen; Srinivasan, Jayasree; Mohajer, Michele; Quenby, Siobhan; Thirumalaikumar, Lakshmi; Konje, Justin; Thornton, Jim; Bugg, George; Mackenzie, Shonag; Ullal, Aarti; Smith, Marie; Arya, Rita; Cunnigham, Simon; Walker, James; Simpson, Nigel; Page, Joanne; Oxby, Claire; Watkins, Karen; Tuffnell, Derek; Bober, S.; Wijesiriwardana, A.; Brandon, Helene; El-Badawy, Saif; Brigham, Sara; Shorinola, Lanre; Khunda, Aethele; Kalla, Shaku; Agha, Mohammed M. Abdullah; Poku, Stephen; Olawo, Ayo; Amu, Johnson; Banfield, Philip; Majoko, Franz; Alcide, Julia; Rajeswary, Jyothi; Salloum, Marwan; Rees, Alexandra; Oteri, Odiri; Ikhena, Sunday; Creswell, Janet; Dawood, Feroza; Agarwal, Umber

    2017-01-01

    Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required. Women with confirmed early onset pre-eclampsia were recruited from 53 maternity units in

  18. Prediction of complications in early-onset pre-eclampsia (PREP) : Development and external multinational validation of prognostic models

    NARCIS (Netherlands)

    Thangaratinam, Shakila; Allotey, John; Marlin, Nadine; Dodds, Julie; Cheong-See, Fiona; von Dadelszen, Peter; Ganzevoort, Wessel; Akkermans, Joost; Kerry, Sally; Mol, Ben W.; Moons, Karl G.M.; Riley, Richard D.; Khan, Khalid S.

    2017-01-01

    Background: Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required. Method: Women with confirmed early onset pre-eclampsia were recruited from 53

  19. Differential Gene Expression Analysis of Placentas with Increased Vascular Resistance and Pre-Eclampsia Using Whole-Genome Microarrays

    Directory of Open Access Journals (Sweden)

    M. Centlow

    2011-01-01

    Full Text Available Pre-eclampsia is a pregnancy complication characterized by hypertension and proteinuria. There are several factors associated with an increased risk of developing pre-eclampsia, one of which is increased uterine artery resistance, referred to as “notching”. However, some women do not progress into pre-eclampsia whereas others may have a higher risk of doing so. The placenta, central in pre-eclampsia pathology, may express genes associated with either protection or progression into pre-eclampsia. In order to search for genes associated with protection or progression, whole-genome profiling was performed. Placental tissue from 15 controls, 10 pre-eclamptic, 5 pre-eclampsia with notching, and 5 with notching only were analyzed using microarray and antibody microarrays to study some of the same gene product and functionally related ones. The microarray showed 148 genes to be significantly altered between the four groups. In the preeclamptic group compared to notch only, there was increased expression of genes related to chemotaxis and the NF-kappa B pathway and decreased expression of genes related to antigen processing and presentation, such as human leukocyte antigen B. Our results indicate that progression of pre-eclampsia from notching may involve the development of inflammation. Increased expression of antigen-presenting genes, as seen in the notch-only placenta, may prevent this inflammatory response and, thereby, protect the patient from developing pre-eclampsia.

  20. Maternal hypertrophy and diastolic disfunction and brain natriuretic peptide concentration in early and late Pre-Eclampsia.

    OpenAIRE

    Borges, VTM; Zanati, SG; PeraÇoli, MTS; Poiati, JR; Romão-Veiga, M; PeraÇoli, JC; Thilaganathan, B

    2017-01-01

    OBJECTIVE: Pre-eclampsia is associated with maternal cardiac remodelling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and Brain Natriuretic Peptide (BNP) levels in women with early-onset pre-eclampsia (

  1. Leukocyte Telomere Length in Healthy Caucasian and African-American Adolescents : Relationships with Race, Sex, Adiposity, Adipokines, and Physical Activity

    NARCIS (Netherlands)

    Zhu, Haidong; Wang, Xiaoling; Gutin, Bernard; Davis, Catherine L.; Keeton, Daniel; Thomas, Jeffrey; Stallmann-Jorgensen, Inger; Mooken, Grace; Bundy, Vanessa; Snieder, Harold; van der Harst, Pim; Dong, Yanbin

    Objective To examine the relationships of race, sex, adiposity, adipokines, and physical activity to telomere length in adolescents. Study design Leukocyte telomere length (T/S ratio) was assessed cross-sectionally in 667 adolescents (aged 14-18 years; 48% African-Americans; 51% girls) using a

  2. Depression and Leukocyte Telomere Length in Patients With Coronary Heart Disease : Data From The Heart and Soul Study

    NARCIS (Netherlands)

    Hoen, Petra W.; de Jonge, Peter; Na, Bee Ya; Farzaneh-Far, Ramin; Epel, Elissa; Lin, Jue; Blackburn, Elizabeth; Whooley, Mary A.

    Objective: Shortened telomere length has been associated with mortality in patients with coronary heart disease (CHD) and is considered as an emerging marker of biologic age. Whether depression is associated with telomere length or trajectory has not been evaluated in patients with CHD. Methods: In

  3. Does leisure time physical activity in early pregnancy protect against pre-eclampsia? Prospective cohort in Danish women

    DEFF Research Database (Denmark)

    Østerdal, M L; Strøm, M; Klemmensen, A K

    2008-01-01

    OBJECTIVE: To examine the association between physical activity in early pregnancy and risk of pre-eclampsia. DESIGN: Prospective cohort. SETTING: Denmark. POPULATION: A total of 85,139 pregnant Danish women, recruited between 1996 and 2002. METHODS: The authors assessed leisure time physical...... adjusted for by logistic regression. MAIN OUTCOME MEASURES: Pre-eclampsia and severe pre-eclampsia. RESULTS: The two highest physical activity levels were associated with increased risk of severe pre-eclampsia compared with the nonexercising group, with adjusted odds ratios of 1.65 (95% CI: 1.......11-2.43) and 1.78 (95% CI: 1.07-2.95), whereas more moderate levels of physical activity (1-270 minutes/week) had no statistically significant association with risk of pre-eclampsia (total n = 85,139). CONCLUSIONS: We were unable to document a protective effect of leisure time physical activity against pre...

  4. Identification of seven loci affecting mean telomere length and their association with disease

    NARCIS (Netherlands)

    Codd, Veryan; Nelson, Christopher P.; Albrecht, Eva; Mangino, Massimo; Deelen, Joris; Buxton, Jessica L.; Hottenga, Jouke Jan; Fischer, Krista; Esko, Tonu; Surakka, Ida; Broer, Linda; Nyholt, Dale R.; Mateo Leach, Irene; Salo, Perttu; Hagg, Sara; Matthews, Mary K.; Palmen, Jutta; Norata, Giuseppe D.; O'Reilly, Paul F.; Saleheen, Danish; Amin, Najaf; Balmforth, Anthony J.; Beekman, Marian; de Boer, Rudolf A.; Bohringer, Stefan; Braund, Peter S.; Burton, Paul R.; de Craen, Anton J. M.; Denniff, Matthew; Dong, Yanbin; Douroudis, Konstantinos; Dubinina, Elena; Eriksson, Johan G.; Garlaschelli, Katia; Guo, Dehuang; Hartikainen, Anna-Liisa; Henders, Anjali K.; Houwing-Duistermaat, Jeanine J.; Kananen, Laura; Karssen, Lennart C.; Kettunen, Johannes; Klopp, Norman; Lagou, Vasiliki; van Leeuwen, Elisabeth M.; Madden, Pamela A.; Maegi, Reedik; Magnusson, Patrik K. E.; Mannisto, Satu; McCarthy, Mark I.; Medland, Sarah E.; Mihailov, Evelin; Montgomery, Grant W.; Oostra, Ben A.; Palotie, Aarno; Peters, Annette; Pollard, Helen; Pouta, Anneli; Prokopenko, Inga; Ripatti, Samuli; Salomaa, Veikko; Suchiman, H. Eka D.; Valdes, Ana M.; Verweij, Niek; Vinuela, Ana; Wang, Xiaoling; Wichmann, H-Erich; Widen, Elisabeth; Willemsen, Gonneke; Wright, Margaret J.; Xia, Kai; Xiao, Xiangjun; van Veldhuisen, Dirk J.; Catapano, Alberico L.; Tobin, Martin D.; Hall, Alistair S.; Blakemore, Alexandra I. F.; van Gilst, Wiek H.; Zhu, Haidong; Erdmann, Jeanette; Reilly, Muredach P.; Kathiresan, Sekar; Schunkert, Heribert; Talmud, Philippa J.; Pedersen, Nancy L.; Perola, Markus; Ouwehand, Willem; Kaprio, Jaakko; Martin, Nicholas G.; van Duijn, Cornelia M.; Hovatta, Iris; Gieger, Christian; Metspalu, Andres; Boomsma, Dorret I.; Jarvelin, Marjo-Riitta; Slagboom, P. Eline; Thompson, John R.; Spector, Tim D.; van der Harst, Pim; Samani, Nilesh J.

    Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci,

  5. Alterations in leukocyte telomere length in workers occupationally exposed to Benzene

    NARCIS (Netherlands)

    Bassig, Bryan A.; Zhang, Luoping; Cawthon, Richard M.; Smith, Martyn T.; Yin, Songnian; Li, Guilan; Hu, Wei; Shen, Min; Rappaport, Stephen; Barone-Adesi, Francesco; Rothman, Nathaniel; Vermeulen, Roel; Lan, Qing

    2014-01-01

    Exposure to benzene, a known leukemogen and probable lymphomagen, has been demonstrated to result in oxidative stress, which has previously been associated with altered telomere length (TL). TL specifically has been associated with several health outcomes in epidemiologic studies, including cancer

  6. Effects of size at birth, childhood growth patterns and growth hormone treatment on leukocyte telomere length

    NARCIS (Netherlands)

    C.C.J. Smeets (Lin); V. Codd (Veryan); M. Denniff (Matthew); N.J. Samani (Nilesh); A.C.S. Hokken-Koelega (Anita)

    2017-01-01

    markdownabstract__Background__ Small size at birth and rapid growth in early life are associated with increased risk of cardiovascular disease in later life. Short children born small for gestational age (SGA) are treated with growth hormone (GH), inducing catch-up in length. Leukocyte telomere

  7. Increased Body Mass Index, Elevated C-reactive Protein, and Short Telomere Length

    DEFF Research Database (Denmark)

    Rode, Line; Nordestgaard, Børge G; Weischer, Maren

    2014-01-01

    -reactive protein. SETTING AND DESIGN: We studied 45,069 individuals from the Copenhagen General Population Study with measurements of leukocyte telomere length, BMI, and C-reactive protein in a Mendelian randomization study. Using the three obesity-associated polymorphisms FTO rs9939609, MC4R rs17782313, and TMEM...

  8. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

    NARCIS (Netherlands)

    Machiela, Mitchell J; Lan, Qing; Slager, Susan L; Vermeulen, Roel C H|info:eu-repo/dai/nl/216532620; Teras, Lauren R; Camp, Nicola J; Cerhan, James R; Spinelli, John J; Wang, Sophia S; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I W; Cox, David G; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R; De Roos, Anneclaire J; Brooks-Wilson, Angela R; Giles, Graham G; Melbye, Mads; Gu, Jian; Jackson, Rebecca D; Kane, Eleanor; Purdue, Mark P; Vajdic, Claire M; Albanes, Demetrius; Kelly, Rachel S; Zucca, Mariagrazia; Bertrand, Kimberly A; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M; Link, Brian K; Novak, Anne J; Dogan, Ahmet; Asmann, Yan W; Liebow, Mark; Thompson, Carrie A; Ansell, Stephen M; Witzig, Thomas E; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans-Olov; Roos, Göran; Bracci, Paige M; Riby, Jacques; Smith, Martyn T; Holly, Elizabeth A; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M; Severson, Richard K; Tinker, Lesley F; North, Kari E; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J; Villano, Danylo J; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R; Turner, Jenny; Southey, Melissa C; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Liang, Liming; Park, Ju-Hyun; Chung, Charles C; Weisenburger, Dennis D; Fraumeni, Joseph F; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E; de Sanjose, Silvia; Skibola, Christine F; Berndt, Sonja I; Birmann, Brenda M; Chanock, Stephen J; Rothman, Nathaniel

    2016-01-01

    Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might

  9. A genome-wide association scan (GWAS) for mean telomere length within the COGS project

    DEFF Research Database (Denmark)

    Pooley, Karen A; Bojesen, Stig E; Weischer, Maren

    2013-01-01

    Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the "iCOGS" custom genotyping array. All ∼...

  10. Telomere length and dynamics predict mortality in a wild longitudinal study

    NARCIS (Netherlands)

    Barrett, Emma L. B.; Burke, Terry A.; Hammers, Martijn; Komdeur, Jan; Richardson, David S.

    Explaining variation in life expectancy between individuals of the same age is fundamental to our understanding of population ecology and life history evolution. Variation in the length and rate of loss of the protective telomere chromosome caps has been linked to cellular lifespan. Yet, the extent

  11. Sex difference in leukocyte telomere length is ablated in opposite-sex co-twins

    NARCIS (Netherlands)

    Benetos, Athanase; Dalgard, Christine; Labat, Carlos; Kark, Jeremy D.; Verhulst, Simon; Christensen, Kaare; Kimura, Masayuki; Horvath, Kent; Kyvik, Kirsten Ohm; Aviv, Abraham

    2014-01-01

    Background: In eutherian mammals and in humans, the female fetus may be masculinized while sharing the intra-uterine environment with a male fetus. Telomere length (TL), as expressed in leukocytes, is heritable and is longer in women than in men. The main determinant of leukocyte TL (LTL) is LTL at

  12. Leukocyte telomere length dynamics in women and men : Menopause vs age effects

    NARCIS (Netherlands)

    Dalgard, Christine; Benetos, Athanase; Verhulst, Simon; Labat, Carlos; Kark, Jeremy D.; Christensen, Kaare; Kimura, Masayuki; Kyvik, Kirsten Ohm; Aviv, Abraham

    2015-01-01

    Background: A longer leukocyte telomere length (LTL) in women than men has been attributed to a slow rate of LTL attrition in women, perhaps due to high estrogen exposure during the premenopausal period. Methods: To test this premise we performed a longitudinal study (an average follow-up of 12

  13. Tracking and fixed ranking of leukocyte telomere length across the adult life course

    DEFF Research Database (Denmark)

    Benetos, Athanase; Kark, Jeremy D; Susser, Ezra

    2013-01-01

    Short leukocyte telomere length (LTL) is associated with atherosclerosis in adults and diminished survival in the elderly. LTL dynamics are defined by LTL at birth, which is highly variable, and its age-dependent attrition thereafter, which is rapid during the first 20 years of life. We examined ...

  14. DCAF4, a novel gene associated with leucocyte telomere length

    DEFF Research Database (Denmark)

    Mangino, Massimo; Christiansen, Lene; Stone, Rivka

    2015-01-01

    BACKGROUND: Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was t...

  15. Higher circulating levels of IGF-1 are associated with longer leukocyte telomere length in healthy subjects

    DEFF Research Database (Denmark)

    Barbieri, Michelangela; Paolisso, Giuseppe; Kimura, Masayuki

    2009-01-01

    Mutations that inhibit the insulin-like growth factor-1 (IGF-1) extend the lifespan of worms, flies and mice. However, it appears that relatively low circulating levels of IGF-1 in humans are associated with aging-related diseases and diminished longevity. As leukocyte telomere length (LTL) is os...

  16. No Association between Mean Telomere Length and Life Stress Observed in a 30 Year Birth Cohort

    Science.gov (United States)

    Jodczyk, Sarah; Fergusson, David M.; Horwood, L. John; Pearson, John F.; Kennedy, Martin A.

    2014-01-01

    Telomeres are specialised structures that cap the ends of chromosomes. They shorten with each cell division and have been proposed as a marker of cellular aging. Previous studies suggest that early life stressors increase the rate of telomere shortening with potential impact on disease states and mortality later in life. This study examined the associations between telomere length and exposure to a number of stressors that arise during development from the antenatal/perinatal period through to young adulthood. Participants were from the Christchurch Health and Development Study (CHDS), a New Zealand longitudinal birth cohort which has followed participants from birth until age 30. Telomere length was obtained on DNA from peripheral blood samples collected from consenting participants (n = 677) at age 28–30, using a quantitative PCR assay. These data were assessed for associations with 26 measures of life course adversity or stress which occurred prior to 25 years of age. No associations were found between telomere length measured at age 28–30 years and life course adversity or stress for specific measures and for the summary risk scores for each developmental domain. The correlations were very small ranging from −0.06 to 0.06 with a median of 0.01, and none were statistically significant. Our results in this well-studied birth cohort do not support prior reports of such associations, and underscore the need for more extensive replication of proposed links between stress and telomere biology in larger cohorts with appropriate phenotypic data. PMID:24816913

  17. No association between mean telomere length and life stress observed in a 30 year birth cohort.

    Directory of Open Access Journals (Sweden)

    Sarah Jodczyk

    Full Text Available Telomeres are specialised structures that cap the ends of chromosomes. They shorten with each cell division and have been proposed as a marker of cellular aging. Previous studies suggest that early life stressors increase the rate of telomere shortening with potential impact on disease states and mortality later in life. This study examined the associations between telomere length and exposure to a number of stressors that arise during development from the antenatal/perinatal period through to young adulthood. Participants were from the Christchurch Health and Development Study (CHDS, a New Zealand longitudinal birth cohort which has followed participants from birth until age 30. Telomere length was obtained on DNA from peripheral blood samples collected from consenting participants (n = 677 at age 28-30, using a quantitative PCR assay. These data were assessed for associations with 26 measures of life course adversity or stress which occurred prior to 25 years of age. No associations were found between telomere length measured at age 28-30 years and life course adversity or stress for specific measures and for the summary risk scores for each developmental domain. The correlations were very small ranging from -0.06 to 0.06 with a median of 0.01, and none were statistically significant. Our results in this well-studied birth cohort do not support prior reports of such associations, and underscore the need for more extensive replication of proposed links between stress and telomere biology in larger cohorts with appropriate phenotypic data.

  18. Accuracy of body mass index in predicting pre-eclampsia: bivariate meta-analysis

    NARCIS (Netherlands)

    Cnossen, J. S.; Leeflang, M. M. G.; de Haan, E. E. M.; Mol, B. W. J.; van der Post, J. A. M.; Khan, K. S.; ter Riet, G.

    2007-01-01

    OBJECTIVE: The objective of this study was to determine the accuracy of body mass index (BMI) (pre-pregnancy or at booking) in predicting pre-eclampsia and to explore its potential for clinical application. DESIGN: Systematic review and bivariate meta-analysis. SETTING: Medline, Embase, Cochrane

  19. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J.W.; Blankenstein, M.A.; Heijboer, A.C.; van Vugt, J.M.

    2011-01-01

    Objective: To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). Methods: PlGF concentration was retrospectively measured in first trimester

  20. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J. W. R.; Blankenstein, M. A.; Heijboer, A. C.; van Vugt, J. M. G.

    2011-01-01

    To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). PlGF concentration was retrospectively measured in first trimester serum specimens of 23

  1. Placental malaria and pre-eclampsia through the looking glass backwards?

    NARCIS (Netherlands)

    Brabin, Bernard J.; Johnson, Peter M.

    2005-01-01

    Placental malaria and pre-eclampsia occur frequently in women in developing countries and are leading causes of fetal growth restriction. Reduced placental perfusion, loss of placental integrity and endothelial cell dysfunction are characteristics of both conditions, and several common factors can

  2. Work activities and risk of prematurity, low birth weight and pre-eclampsia

    DEFF Research Database (Denmark)

    Palmer, Keith T; Bonzini, Matteo; Harris, E Clare

    2013-01-01

    Objectives We assessed the evidence relating preterm delivery (PTD), low birth weight, small for gestational age (SGA), pre-eclampsia and gestational hypertension to five occupational exposures (working hours, shift work, lifting, standing and physical workload). We conducted a systematic search...

  3. Prevention and management of severe pre-eclampsia/eclampsia in Afghanistan

    NARCIS (Netherlands)

    Kim, Y.M.; Ansari, N.; Kols, A.; Tappis, H.; Currie, S.; Zainullah, P.; Bailey, P.; van Roosmalen, J.; Stekelenburg, J.

    2013-01-01

    Background: An evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care

  4. The association between leisure time physical activity in the year before pregnancy and pre-eclampsia

    DEFF Research Database (Denmark)

    Hegaard, Hanne; Ottesen, Bent; Hedegaard, M

    2010-01-01

    In order to investigate the association between leisure time physical activity in the year before pregnancy and pre-eclampsia, stratifying for maternal BMI, a prospective study was carried out from 1996 to 1998. Pregnant women attending their first antenatal care visit, were invited to participate...

  5. Higher risk of pre-eclampsia after change of partner. An effect of longer interpregnancy intervals?

    DEFF Research Database (Denmark)

    Basso, Olga; Christensen, Kaare; Olsen, J.

    2001-01-01

    Epidemiologic studies have shown that pre-eclampsia is mainly a disease of first pregnancy, possibly associated with primipaternity. The interpregnancy interval, which is strongly associated with change of partner, has received little attention. In this study, based on Danish hospital records, we...

  6. Tests for predicting complications of pre-eclampsia: A protocol for systematic reviews

    Directory of Open Access Journals (Sweden)

    O'Brien Shaughn

    2008-08-01

    Full Text Available Abstract Background Pre-eclampsia is associated with several complications. Early prediction of complications and timely management is needed for clinical care of these patients to avert fetal and maternal mortality and morbidity. There is a need to identify best testing strategies in pre eclampsia to identify the women at increased risk of complications. We aim to determine the accuracy of various tests to predict complications of pre-eclampsia by systematic quantitative reviews. Method We performed extensive search in MEDLINE (1951–2004, EMBASE (1974–2004 and also will also include manual searches of bibliographies of primary and review articles. An initial search has revealed 19500 citations. Two reviewers will independently select studies and extract data on study characteristics, quality and accuracy. Accuracy data will be used to construct 2 × 2 tables. Data synthesis will involve assessment for heterogeneity and appropriately pooling of results to produce summary Receiver Operating Characteristics (ROC curve and summary likelihood ratios. Discussion This review will generate predictive information and integrate that with therapeutic effectiveness to determine the absolute benefit and harm of available therapy in reducing complications in women with pre-eclampsia.

  7. Psychological treatment of women with psychological complaints after pre-eclampsia

    NARCIS (Netherlands)

    Poel, D.M.; Swinkels, P.; de Vries, J.I.

    2009-01-01

    Aim. Pre-eclampsia (PE), eclampsia (E) and/or hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome cause major perinatal and maternal morbidity, mortality and have extensive psychosocial impact. The aim of this study is to describe psychological consequences, interventions and

  8. Knowledge of pre-eclampsia in women living in Makole Ward ...

    African Journals Online (AJOL)

    Knowledge of pre-eclampsia in women living in Makole Ward, Dodoma, Tanzania. Angela Ruth Savage1, Lujani Hoho2. 1. St John's University of Tanzania, Research, Consultancy and Postgraduate studies; St John's University of Tanzania,. DRCPGS. 2. St John's University of Tanzania, School of Nursing. Abstract.

  9. Leisure Time Physical Activity and the Risk of Pre-eclampsia

    DEFF Research Database (Denmark)

    Wolf, Hanne Trap; Owe, K M; Juhl, M

    2014-01-01

    Today, pre-eclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality. It has been proposed that leisure time physical activity (LTPA) is associated with a decreased risk of PE. The objective of this study was to perform a systematic literature review examining...

  10. Uterine artery Doppler screening as a predictor of pre-eclampsia ...

    African Journals Online (AJOL)

    Hypertensive disorders represent the second most common cause of maternal death, affecting 5-10% of pregnancies worldwide and accounting for 19% of maternal deaths in South Africa. Pre-eclampsia is believed to develop from inadequate trophoblast invasion of the maternal spiral arteries. Doppler imaging permits ...

  11. Expectant management of early onset of severe pre-eclampsia in ...

    African Journals Online (AJOL)

    Fifty patients with severe pre-eclampsia who presented before 32 weeks' gestation were managed conservatively (sedation, bed rest, antihypertensive therapy and intensive fetal and maternal monitoring) until intervention was indicated. Twelve patients presented before 26 weeks ofpregnancy and there were no fetal ...

  12. Evaluation of trace elements in pregnant women with pre-eclampsia ...

    African Journals Online (AJOL)

    The disturbance in the metabolism of these elements may be a contributing factor in the development of certain diseases such as pre-eclampsia. The aim of this study is to determine the status of these elements in pre-eclamptic pregnant women in Osogbo, Western Nigeria. Forty-nine pre-eclamptic patients and 40 ...

  13. Perinatal Outcome in Patients With Pre-Eclampsia in Benin City ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence of pre-eclampsia and examine its influence on perinatal outcome among Nigerian women. Methods: Among 3780 deliveries over a two-and-half year period, 212 singleton infants were born after preeclamptic pregnancies. We compared the perinatal outcome with those of 636 control ...

  14. Telomere length in children environmentally exposed to low-to-moderate levels of lead

    Energy Technology Data Exchange (ETDEWEB)

    Pawlas, Natalia, E-mail: n-pawlas@wp.pl [Institute of Occupational Medicine and Environmental Health, PL 41-200 Sosnowiec (Poland); Płachetka, Anna [Department of Animal Physiology and Ecotoxicology, University of Silesia, Bankowa str. 9, 40-007 Katowice (Poland); Kozłowska, Agnieszka [Institute of Occupational Medicine and Environmental Health, PL 41-200 Sosnowiec (Poland); Broberg, Karin [Institute of Environmental Medicine, Unit of Metals & Health, Box 210, SE-171 77 Stockholm (Sweden); Kasperczyk, Sławomir [Department of Biochemistry, Medical University of Silesia, Katowice, SMDZ in Zabrze, 41-808 Zabrze (Poland)

    2015-09-01

    Shorter relative telomere length in peripheral blood is a risk marker for some types of cancers and cardiovascular diseases. Several environmental hazards appear to shorten telomeres, and this shortening may predispose individuals to disease. The aim of the present cross-sectional study was to assess the effect of environmental exposure to lead on relative telomere length (rTL) in children. A cohort of 99 8-year-old children was enrolled from 2007–2010. Blood lead concentrations (B-Pb) were measured by graphite furnace atomic absorption spectrometry, and blood rTL was measured by quantitative PCR. The geometric mean of B-Pb was 3.28 μg/dl (range: 0.90–14.2), and the geometric mean of rTL was 1.08 (range: 0.49–2.09). B-Pb was significantly inversely associated with rTL in the children (r{sub S} = − 0.25, p = 0.013; in further analyses both log-transformed-univariate regression analysis β = − 0.13, p = 0.026, and R{sup 2}adj 4%; and β = − 0.12, p = 0.056 when adjusting for mothers' smoking during pregnancy, Apgar score, mother's and father's ages at delivery, sex and mother's education, R{sup 2}adj 12%, p = 0.011). The effect of lead remained significant in children without prenatal tobacco exposure (N = 87, r{sub S} = − 0.24, p = 0.024; in further analyses, β = − 0.13, p = 0.029, and R{sup 2}adj 4%). rTL was not affected by sex, the concentrations of other elements in the blood (i.e., cadmium and selenium concentrations), or oxidative injury parameters (total antioxidant status, 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances). Lead exposure in childhood appears to be associated with shorter telomeres, which might contribute to diseases, such as cardiovascular disease. The inverse association between blood lead level and the telomeres in children emphasizes the importance of further reducing lead levels in the environment. - Highlights: • This cross-sectional study analyzes the association between

  15. Studies suggest an association between maternal periodontal disease and pre-eclampsia.

    Science.gov (United States)

    Vergnes, Jean-Noel

    2008-01-01

    In this systematic review, several types of infections are identified and investigated: urinary tract infection, periodontal disease, Chlamydia pneumoniae infection, HIV infection, malaria and other persistent bacterial and viral infections. Separate analyses were conducted for each of them. This summary review will only focus on the link between pre-eclampsia and periodontitis, which was just a part of the original systematic review. MEDLINE, EMBASE, POPLINE, CINAHL, LILACS (all from inception to June 30, 2007), proceedings of international meetings on pre-eclampsia, bibliography of the retrieved articles, reviews, chapters in standard textbooks on hypertension in pregnancy, and contact with investigators involved in the field were used to identify relevant studies. No language restrictions were imposed. Cohort, case-control or cross-sectional studies with original data that evaluated the association between maternal periodontal disease and pre-eclampsia were included. Cases were defined as women suffering from hypertension plus proteinuria, after 20 weeks' gestation. Data were extracted from each study according to design, geographic location, sample size, gestational age when periodontal disease was diagnosed, definition and severity of pre-eclampsia, confounding factors controlled for, temporality of the association, and report of dose-response gradient. Studies included in the systematic review were also included in the meta-analysis if they reported Odds Ratio (OR) or Relative Risk (RR) estimates with their 95% Confidence Intervals (CIs), or provided the information necessary to calculate them. Results from different reports were combined to produce a pooled OR according to the Mantel-Haenszel method, using both fixed- and random-effects models. Heterogeneity was quantified with I(2) statistics. Studies were also quality assessed. Seven case-control studies and 2 cohort studies evaluated the association between periodontal disease and pre-eclampsia. Six

  16. Community perceptions of pre-eclampsia and eclampsia in Ogun State, Nigeria: a qualitative study.

    Science.gov (United States)

    Akeju, David O; Vidler, Marianne; Oladapo, Olufemi T; Sawchuck, Diane; Qureshi, Rahat; von Dadelszen, Peter; Adetoro, Olalekan O; Dada, Olukayode A

    2016-06-08

    Pre-eclampsia is a complication of pregnancy responsible for high rates of morbidity and mortality, particularly in sub-Saharan Africa. When undetected or poorly managed, it may progress to eclampsia which further worsens the prognosis. While most studies examining pre-eclampsia have used a bio-medical model, this study recognizes the role of the socio-cultural environment, in order to understand perceptions of pre-eclampsia within the community. The study was conducted in Ogun State, Nigeria in 2011-2012. Data were obtained through twenty-eight focus group discussions; seven with pregnant women (N = 80), eight with new mothers (N = 95), three with male decision-makers (N = 35), six with community leaders (N = 68), and three with traditional birth attendants (N = 36). Interviews were also conducted with the heads of the local traditional birth attendants (N = 4) and with community leaders (N = 5). Data were transcribed verbatim and analysed in NVivo 10 software. There was no terminology reportedly used for pre-eclampsia in the native language - Yoruba; however, hypertension has several terms independent of pregnancy status. Generally, 'gìrì âlábôyún' describes seizures specific to pregnancy. The cause of hypertension in pregnancy was thought to be due to depressive thoughts as a result of marital conflict and financial worries, while seizures in pregnancy were perceived to result from prolonged exposure to cold. There seemed to be no traditional treatment for hypertension. However for seizures the use of herbs, concoctions, incisions, and topical application of black soap were widespread. This study illustrates that knowledge of pre-eclampsia and eclampsia are limited amongst communities of Ogun State, Nigeria. Findings reveal that pre-eclampsia was perceived as a stress-induced condition, while eclampsia was perceived as a product of prolonged exposure to cold. Thus, heat-related local medicines and herbal concoctions were the

  17. Health care provider knowledge and routine management of pre-eclampsia in Pakistan.

    Science.gov (United States)

    Sheikh, Sana; Qureshi, Rahat Najam; Khowaja, Asif Raza; Salam, Rehana; Vidler, Marianne; Sawchuck, Diane; von Dadelszen, Peter; Zaidi, Shujat; Bhutta, Zulfiqar

    2016-09-30

    Maternal mortality ratio is 276 per 100,000 live births in Pakistan. Eclampsia is responsible for one in every ten maternal deaths despite the fact that management of this disease is inexpensive and has been available for decades. Many studies have shown that health care providers in low and middle-income countries have limited training to manage patients with eclampsia. Hence, we aimed to explore the knowledge of different cadres of health care providers regarding aetiology, diagnosis and treatment of pre-eclampsia and eclampsia and current management practices. We conducted a mixed method study in the districts of Hyderabad and Matiari in Sindh province, Pakistan. Focus group discussions and interviews were conducted with community health care providers, which included Lady Health Workers and their supervisors; traditional birth attendants and facility care providers. In total seven focus groups and 26 interviews were conducted. NVivo 10 was used for analysis and emerging themes and sub-themes were drawn. All participants were providing care for pregnant women for more than a decade except one traditional birth attendant and two doctors. The most common cause of pre-eclampsia mentioned by community health care providers was stress of daily life: the burden of care giving, physical workload, short birth spacing and financial constraints. All health care provider groups except traditional birth attendants correctly identified the signs, symptoms, and complications of pre-eclampsia and eclampsia and were referring such women to tertiary health facilities. Only doctors were aware that magnesium sulphate is recommended for eclampsia management and prevention; however, they expressed fears regarding its use at first and secondary level health facilities. This study found several gaps in knowledge regarding aetiology, diagnosis and treatment of pre-eclampsia among health care providers in Sindh. Findings suggest that lesser knowledge regarding management of pre-eclampsia

  18. IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia?

    Science.gov (United States)

    Redman, C W; Sargent, I L; Staff, A C

    2014-02-01

    Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as

  19. Effect of heartfulness meditation on burnout, emotional wellness, and telomere length in health care professionals.

    Science.gov (United States)

    Thimmapuram, Jayaram; Pargament, Robert; Sibliss, Kedesha; Grim, Rodney; Risques, Rosana; Toorens, Erik

    2017-01-01

    Background: Burnout poses significant challenges during training years in residency and later in the career. Meditation is a tool to treat stress-related conditions and promote wellness. Telomere length may be affected by burnout and stress. However, the benefits of meditation have not been fully demonstrated in health care professionals. Objective: We assessed the effects of a 12-week 'Heartfulness Meditation' program on burnout, emotional wellness, and telomere length in residents, faculty members, and nurses at a large community teaching hospital during the 2015-16 academic year. Methods: All subjects completed a baseline Maslach Burnout Inventory (MBI) and Emotional Wellness Assessment (EWA) at the beginning of the study. Meditators received instructions in Heartfulness Meditation. At week 12, subjects completed a follow up MBI and EWA scores. Salivary telomere length was measured at baseline and week 12. Results: Twenty-seven out of a total 155 residents (17.4%) along with eight faculty physicians and 12 nurses participated in the study. Thirty-five enrolled as meditators and 12 as controls. At 12 weeks, the meditators had statistically significant improvement in all measures of burnout and in nearly all attributes of EWA. Controls showed no statistically significant changes in either burnout or emotional wellness scores. Relative telomere length increased with statistical significance in a younger subset of meditators. Conclusion: Our results indicate that meditation offers an accessible and efficient method by which physician and nurse burnout can be ameliorated and wellness can be enhanced. The increased telomere length is an interesting finding but needs to be confirmed with further research. Abbreviations: EWA: Emotional wellness assessment; MBI: Maslach burnout inventory; EE: Emotional exhaustion; DP: Depersonalization; PA: Personal accomplishment; PI: Prinicipal investigator; JT: Jayaram Thimmapuram.

  20. Accumulative effects of indoor air pollution exposure on leukocyte telomere length among non-smokers.

    Science.gov (United States)

    Lin, Nan; Mu, Xinlin; Wang, Guilian; Ren, Yu'ang; Su, Shu; Li, Zhiwen; Wang, Bin; Tao, Shu

    2017-08-01

    Indoor air pollution is an important environmental factor that contributes to the burden of various diseases. Long-term exposure to ambient air pollution is associated with telomere shortening. However, the association between chronic indoor air pollution from household fuel combustion and leukocyte telomere length has not been studied. In our study, 137 cancer-free non-smokers were recruited. Their exposure levels to indoor air pollution from 1985 to 2014 were assessed using a face-to-face interview questionnaire, and leukocyte telomere length (LTL) was measured using a monochrome multiplex quantitative PCR method. Accumulative exposure to solid fuel usage for cooking was negatively correlated with LTL. The LTL of residents who were exposed to solid fuel combustion for three decades (LTL = 0.70 ± 0.17) was significantly shorter than that of other populations. In addition, education and occupation were related to both exposure to solid fuel and LTL. Sociodemographic factors may play a mediating role in the correlation between leukocyte telomere length and environmental exposure to indoor air pollution. In conclusion, long-term exposure to indoor air pollution may cause LTL dysfunction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Systematic review of the association between chronic social stress and telomere length: A life course perspective.

    Science.gov (United States)

    Oliveira, Bruna Silva; Zunzunegui, Maria Victoria; Quinlan, Jacklyn; Fahmi, Hassan; Tu, Mai Thanh; Guerra, Ricardo Oliveira

    2016-03-01

    Our aim was to examine whether chronic social stress is associated with telomere length throughout the life course, following our protocol published in 2014. Structured searches were conducted in MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and grey from their start date onwards. Reference lists of retrieved citations were hand searched for relevant studies. Eighteen studies published until May 1, 2015 investigating the association between chronic social stress (as defined by poverty, exposure to violence, or family caregiving) and telomere length in healthy or diseased adults and children were independently selected by 2 reviewers. Sixteen of those studies were cross-sectional and two had a longitudinal design. Studies differed in type of stress exposure, method to measure telomere length and cell type. As meta-analysis could not be conducted, the data were synthesized as a narrative review. Based on this comprehensive review, chronic social stress accompanies telomere shortening in both early and adult exposures, with most eligible studies showing a significant relationship. We discuss the significance of chronic stress of social origin and the potential for social interventions through public policies and we recommend methodological improvements that would allow for future meta-analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?

    Science.gov (United States)

    Ahmed, Asif; Ramma, Wenda

    2015-03-01

    Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the 'two-stage model' of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the 'accelerator'. The 'braking system' includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-γ-lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator-brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti-angiogenic factors sFlt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line. © 2014 The Authors. British Journal of Pharmacology published by John Wiley &. Sons Ltd on behalf of The British Pharmacological Society.

  3. Effects of reverse transcriptase inhibitors on telomere length and telomerase activity in two immortalized human cell lines.

    Science.gov (United States)

    Strahl, C; Blackburn, E H

    1996-01-01

    The ribonucleoprotein telomerase, a specialized cellular reverse transcriptase, synthesizes one strand of the telomeric DNA of eukaryotes. We analyzed telomere maintenance in two immortalized human cell lines: the B-cell line JY616 and the T-cell line Jurkat E6-1, and determined whether known inhibitors of retroviral reverse transcriptases could perturb telomere lengths and growth rates of these cells in culture. Dideoxyguanosine (ddG) caused reproducible, progressive telomere shortening over several weeks of passaging, after which the telomeres stabilized and remained short. However, the prolonged passaging in ddG caused no observable effects on cell population doubling rates or morphology. Azidothymidine (AZT) caused progressive telomere shortening in some but not all T- and B-cell cultures. Telomerase activity was present in both cell lines and was inhibited in vitro by ddGTP and AZT triphosphate. Prolonged passaging in arabinofuranyl-guanosine, dideoxyinosine (ddI), dideoxyadenosine (ddA), didehydrothymidine (d4T), or phosphonoformic acid (foscarnet) did not cause reproducible telomere shortening or decreased cell growth rates or viabilities. Combining AZT, foscarnet, and/or arabinofuranyl-guanosine with ddG did not significantly augment the effects of ddG alone. Strikingly, with or without inhibitors, telomere lengths were often highly unstable in both cell lines and varied between parallel cell cultures. We propose that telomere lengths in these T- and B-cell lines are determined by both telomerase and telomerase-independent mechanisms.

  4. Mesenchymal stem cells with high telomerase expression do not actively restore their chromosome arm specific telomere length pattern after exposure to ionizing radiation

    DEFF Research Database (Denmark)

    Graakjaer, Jesper; Christensen, Rikke; Kolvraa, Steen

    2007-01-01

    investigate the existence and maintenance of the telomere length pattern in stem cells. For this aim we studied telomere length in primary human mesenchymal stem cells (hMSC) and their telomerase-immortalised counterpart (hMSC-telo1) during extended proliferation as well as after irradiation. Telomere lengths...

  5. Telomere length is shorter in healthy offspring of subjects with coronary artery disease : support for the telomere hypothesis

    NARCIS (Netherlands)

    Brouilette, S. W.; Whittaker, A.; Stevens, S. E.; van der Harst, P.; Goodall, A. H.; Samani, N. J.

    Background: Telomeres are shorter in subjects with coronary artery disease (CAD) and may indicate premature biological ageing. However, whether shorter telomeres are a primary abnormality or secondary to the disease is unclear. Objective: To investigate whether shorter telomeres are a primary

  6. Effect of the anatomical site on telomere length and pref-1 gene expression in bovine adipose tissues

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Tomoya, E-mail: toyamada@affrc.go.jp; Higuchi, Mikito; Nakanishi, Naoto

    2015-08-07

    Adipose tissue growth is associated with preadipocyte proliferation and differentiation. Telomere length is a biological marker for cell proliferation. Preadipocyte factor-1 (pref-1) is specifically expressed in preadipocytes and acts as a molecular gatekeeper of adipogenesis. In the present study, we investigated the fat depot-specific differences in telomere length and pref-1 gene expression in various anatomical sites (subcutaneous, intramuscular and visceral) of fattening Wagyu cattle. Visceral adipose tissue expressed higher pref-1 mRNA than did subcutaneous and intramuscular adipose tissues. The telomere length in visceral adipose tissue tended to be longer than that of subcutaneous and intramuscular adipose tissues. The telomere length of adipose tissue was not associated with adipocyte size from three anatomical sites. No significant correlation was found between the pref-1 mRNA level and the subcutaneous adipocyte size. In contrast, the pref-1 mRNA level was negatively correlated with the intramuscular and visceral adipocyte size. These results suggest that anatomical sites of adipose tissue affect the telomere length and expression pattern of the pref-1 gene in a fat depot-specific manner. - Highlights: • Visceral adipose tissue express higher pref-1 mRNA than other anatomical sites. • Telomere length in visceral adipose tissue is longer than other anatomical sites. • Telomere length of adipose tissue is not associated with adipocyte size. • Pref-1 mRNA is negatively correlated with intramuscular and visceral adipocyte size.

  7. Assessment of the diagnostic value of a urinary adipsin rapid strip test for pre-eclampsia: A prospective multicenter study.

    Science.gov (United States)

    Peng, Bing; Zhang, Li; Yan, Jianying; Qi, Hongbo; Zhang, Weiyuan; Fan, Ling; Hu, Yayi; Lin, Li; Li, Xiaotian; Hu, Rong; Xie, Lan; Zhang, Jianping; Wu, Yanqiao; Li, Li; Zhou, Rong

    2017-01-01

    The purpose of the present study was to evaluate the clinical value of the rapid strip test of urinary adipsin for the quick diagnosis of pre-eclampsia. In a multicenter diagnostic test study, we studied the diagnostic accuracy of the rapid strip test of urinary adipsin in women presenting with pre-eclampsia. A total of 204 pre-eclampsia patients and 254 healthy pregnant women were recruited for this study, respectively. The rapid strip test of urinary adipsin was used to detect the adipsin in the urine of each patient. The diagnostic value of the rapid strip test of urinary adipsin for pre-eclampsia was demonstrated by its high sensitivity and specificity (95.10% and 97.64%, respectively). The diagnostic accuracy was 96.51%. The consistency analysis showed that the kappa value was 0.93 compared with the gold standard diagnosis of pre-eclampsia. The rapid strip test of urinary adipsin is a non-invasive test for the diagnosis of pre-eclampsia with high sensitivity and specificity. It could help the quick diagnosis of pre-eclampsia in clinical practice greatly. © 2016 Japan Society of Obstetrics and Gynecology.

  8. Women in southern Nigeria with change in paternity do not have increased incidence of pre-eclampsia.

    Science.gov (United States)

    Chigbu, C O; Okezie, O A; Odugu, B U

    2009-02-01

    This was a prospective cohort study of women in their second pregnancies aimed at determining if there was a difference in the incidence of pre-eclampsia between those with changed paternity and those without change in paternity in an entirely black African population. Women in their second pregnancies receiving antenatal care between September 2006 and August 2007 were recruited into the study between 10 and 20 weeks' gestational age and followed up until 37 weeks' gestation. The main outcome measures included incidence of pre-eclampsia in relation to change in paternity at second pregnancy, incidence of pre-eclampsia in relation to duration of sexual cohabitation among those with changed paternity and inter-pregnancy interval. There was no significant difference in the incidence of pre-eclampsia between women who had changed paternity and those without change in paternity (3.5% vs 3.1%, p=0.835). The inter-pregnancy interval was also similar in both groups. The mean duration of sexual cohabitation was similar between women who had changed paternity that developed pre-eclampsia and those that did not develop pre-eclampsia (7.9+/-1.3 vs 7.5+/-2.1 months, p=0.531). It was concluded that Southern Nigerian women with change in paternity in their second pregnancies do not have increased incidence of pre-eclampsia.

  9. Urinary antimony and leukocyte telomere length: An analysis of NHANES 1999-2002.

    Science.gov (United States)

    Scinicariello, Franco; Buser, Melanie C

    2016-10-01

    Telomeres are repetitive DNA sequences (TTAGGG) at the end of chromosomes. Cells with critically short telomeres enter replicative senescence and apoptosis. Several in vitro studies report that antimony causes cell apoptosis in human leukocyte cell lines. The goal of this analysis was to investigate whether there is an association between antimony exposure and leukocyte telomere length (LTL) among US adults aged 20 and older based on the National Health and Nutrition Examination Survey (NHANES) 1999-2002. We used multivariate linear regression to analyze the association of urinary antimony with LTL. LTL was log-natural transformed and the results were re-transformed and presented as percent differences. After adjustment for potential confounders, individuals in the 3rd and 4th quartiles of urinary antimony had statistically significantly shorter LTL (-4.78%, 95% CI: -8.42,-0.90; and -6.11%, 95% CI: -11.04,-1.00, respectively) compared to the lowest referent quartile, with evidence of a dose-response relationship (p-value for trend =0.03). Shorter LTL with antimony was driven by middle aged (40-59 years) and older (60-85 years) adult groups. The association may be biologically plausible because of reported oxidative stress and apoptosis effects of antimony on blood cells, effects known to shorten telomere length. Published by Elsevier Inc.

  10. A prospective study of leukocyte telomere length and risk of phobic anxiety among women.

    Science.gov (United States)

    Ramin, Cody; Wang, Wei; Prescott, Jennifer; Rosner, Bernard; Simon, Naomi M; De Vivo, Immaculata; Okereke, Olivia I

    2015-12-15

    We prospectively examined the relation of relative telomere lengths (RTLs), a marker of biological aging, to phobic anxiety in later-life. RTLs in peripheral blood leukocytes were measured among 3194 women in the Nurses' Health Study who provided blood samples in 1989/90. The Crown-Crisp Phobic Index (CCI, range=0–16) was assessed in 1988 and 2004. Only participants with CCI≤3 (consistent with no meaningful anxiety symptoms) in 1988 were included. We related baseline RTLs to odds ratios (ORs) of incident high phobic anxiety symptoms (CCI≥6). To enhance clinical relevance, we used finite mixture modeling (FMM) to relate baseline RTLs to latent classes of CCI in 2004. RTLs were not significantly associated with high phobic anxiety symptoms after 16 years of follow-up. However, FMM identified 3 groups of phobic symptoms in later-life: severe, minimal/intermediate, and non-anxious. The severe group had non-significantly shorter multivariable-adjusted mean RTLs than the minimal/intermediate and non-anxious groups. Women with shorter telomeres vs. longest telomeres had non-significantly higher likelihood of being in the severe vs. non-anxious group. Overall, there was no significant association between RTLs and incident phobic anxiety symptoms. Further work is required to explore potential connections of telomere length and emergence of severe phobic anxiety symptoms during later-life.

  11. Caffeine consumption and telomere length in men and women of the National Health and Nutrition Examination Survey (NHANES).

    Science.gov (United States)

    Tucker, Larry A

    2017-01-01

    The investigation evaluated the relationship between caffeine intake and coffee consumption and leukocyte telomere length, a biomarker of the senescence of cells. A total of 5826 adults from the National Health and Nutrition Examination Survey (NHANES) were studied cross-sectionally. Using the quantitative polymerase chain reaction method, telomere length was compared to standard reference DNA. Caffeine intake from foods and beverages and coffee consumption were measured using a validated, multi-pass, computer-assisted, 24-h recall system administered by NHANES interviewers. The following covariates were controlled: age, gender, race, marital status, education, housing, smoking, BMI, physical activity, alcohol use, and coffee intake (or caffeine consumption). Caffeine consumption was inversely related to telomere length (F = 15.1, P = 0.0005). For each 100 mg of caffeine consumed, telomeres were 35.4 base pairs shorter, after adjusting for the covariates. For each 100 mg of caffeine consumed among coffee drinkers only, telomeres were 36.7 base pairs shorter (F = 9.0, P = 0.0054), and among non-coffee drinkers only, 40.0 base pairs shorter (F = 8.5, P = 0.0067). Conversely, coffee intake was positively related to telomere length (F = 12.6, P = 0.0013), independent of the covariates. Results suggest that caffeine consumption accounts for shorter telomeres in U.S. adults, independent of numerous covariates, whereas coffee intake predicts longer telomeres.

  12. Genetic variation in TERT and TERC and human leukocyte telomere length and longevity: a cross-sectional and longitudinal analysis

    DEFF Research Database (Denmark)

    Sørensen, Mette; Thinggaard, Mikael; Nygaard, Marianne

    2012-01-01

    Telomerase is of key importance for telomere maintenance, and variants of the genes encoding its major subunits, telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC), are candidates for interindividual variation in telomere length. Recently, the two SNPs rs3772190 and rs...

  13. Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort.

    Science.gov (United States)

    Skjaerven, Rolv; Vatten, Lars J; Wilcox, Allen J; Rønning, Thorbjørn; Irgens, Lorentz M; Lie, Rolv Terje

    2005-10-15

    To assess the impact on risk of pre-eclampsia of genes that work through the mother, and genes of paternal origin that work through the fetus. Population based cohort study. Registry data from Norway. Linked generational data from the medical birth registry of Norway (1967-2003): 438,597 mother-offspring units and 286,945 father-offspring units. Pre-eclampsia in the second generation. The daughters of women who had pre-eclampsia during pregnancy had more than twice the risk of pre-eclampsia themselves (odds ratio 2.2, 95% confidence interval 2.0 to 2.4) compared with other women. Men born after a pregnancy complicated by pre-eclampsia had a moderately increased risk of fathering a pre-eclamptic pregnancy (1.5, 1.3 to 1.7). Sisters of affected men or women, who were themselves born after pregnancies not complicated by pre-eclampsia, also had an increased risk (2.0, 1.7 to 2.3). Women and men born after pre-eclamptic pregnancies were more likely to trigger severe pre-eclampsia in their own (or their partner's) pregnancy (3.0, 2.4 to 3.7, for mothers and 1.9, 1.4 to 2.5, for fathers). Maternal genes and fetal genes from either the mother or father may trigger pre-eclampsia. The maternal association is stronger than the fetal association. The familial association predicts more severe pre-eclampsia.

  14. Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction

    Directory of Open Access Journals (Sweden)

    Kurahashi Hiroki

    2011-08-01

    Full Text Available Abstract Background It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR. Methods We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8 and normotensive pregnancies with or (n = 8 without FGR (n = 8 using a microarray method. Results A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels. Conclusions Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia.

  15. Exploring knowledge of pre-eclampsia and views on a potential screening test in women with type 1 diabetes.

    Science.gov (United States)

    Wotherspoon, Amy C; Young, Ian S; McCance, David R; Holmes, Valerie A

    2017-07-01

    to explore knowledge of pre-eclampsia and opinions on potential screening tests for pre-eclampsia in women with type 1 diabetes. a qualitative study using semi-structured interviews of women planning a pregnancy, currently pregnant or post-partum with experience of pre-eclampsia. SETTING, PARTICIPANTS AND METHODS: eleven women with type 1 diabetes were recruited from a pre-pregnancy planning clinic or antenatal clinic. Semi-structured interviews were conducted with the women, asking a series of open-ended questions about their current knowledge of pre-eclampsia and their views on screening for pre-eclampsia. Data analysis was conducted using inductive thematic analysis. four main themes were identified: Information, sources of stress, awareness and acceptability of screening. Generally, women's knowledge of pre-eclampsia was limited. Most did not appear to be aware of their increased risk of developing the disease. Similarly, the majority of women were unaware as to why their blood pressure and urine were checked regularly. The introduction of a screening test for pre-eclampsia was favoured, with only a small number of women raising concerns related to the screening tests. health care professionals need to raise awareness of pre-eclampsia in this high risk group. The introduction of a screening test for pre-eclampsia appears to be acceptable in this population, however, further research is required to validate these findings and also to explore the views of women in other high risk groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Serious maternal complications in relation to severe pre-eclampsia: a retrospective cohort study of the impact of hospital volume.

    Science.gov (United States)

    Ananth, C V; Lavery, J A; Friedman, A M; Wapner, R J; Wright, J D

    2017-07-01

    We examined rates of serious maternal complications in relation to severe pre-eclampsia based on the delivering hospital's annualised volume. Retrospective cohort study. Singleton deliveries (n = 25 782 235) in 439 hospitals in the USA. Annualised hospital volume was categorised as 25-500, 501-1000, 1001-2000 and >2000. Rates of in-hospital maternal death and serious maternal complications, including puerperal cerebrovascular disorders, pulmonary oedema, disseminated intravascular coagulation, acute renal, heart and liver failure, sepsis, haemorrhage and intubation in relation to severe pre-eclampsia. We derived adjusted risk ratio (RR) and 95% confidence interval (CI), from hierarchical Poisson regression models. Severe pre-eclampsia was associated with an 8.7-fold (95% CI 7.6, 10.1) risk of composite maternal complications, with similar RRs across levels of hospital volumes. However, compared with hospitals with low annual volume (pre-eclampsia were lower in high volume hospitals. The rates of serious maternal complications were 410.7 per 10 000 to women who delivered in hospitals with a high rate of severe pre-eclampsia (≥2.12%) and 584.8 per 10 000 to women who delivered in hospitals with low severe pre-eclampsia rates (≤0.41; RR 1.75, 95% CI 1.24, 2.45). While the risks of serious maternal complications in relation to severe pre-eclampsia was similar across hospital delivery volume categories, deaths showed lower rates in large delivery volume hospitals than in smaller volume hospitals. The risk of complications was increased in hospitals with low compared with high severe pre-eclampsia rates. Hospital volume had little impact on the association between severe pre-eclampsia and maternal complications. © 2016 Royal College of Obstetricians and Gynaecologists.

  17. Telomere Length, Proviral Load and Neurologic Impairment in HTLV-1 and HTLV-2-Infected Subjects

    Directory of Open Access Journals (Sweden)

    Benjamin Usadi

    2016-08-01

    Full Text Available Short or damaged telomeres have been implicated in degenerative conditions. We hypothesized that analysis of telomere length (TL in human T-cell lymphotropic virus (HTLV infection and HTLV-associated neuropathy might provide clues to the etiology of HTLV-associated disease and viral dynamics. A subset of 45 human T-cell lymphotropic virus type 1 (HTLV-1, 45 human T-cell lymphotropic virus type 2 (HTLV-2, and 45 seronegative subjects was selected from the larger HTLV Outcomes Study (HOST cohort, matched on age, sex and race/ethnicity. Telomere-to-single-copy gene (T/S ratio (a measure of TL and HTLV-1 and HTLV-2 proviral loads were measured in peripheral blood mononuclear cells (PBMCs using quantitative PCR (qPCR. Vibration sensation measured by tuning fork during neurologic examinations performed as part of the HOST study allowed for an assessment of peripheral neuropathy. TL was compared between groups using t-tests, linear and logistic regression. Mean T/S ratio was 1.02 ± 0.16 in HTLV-1, 1.03 ± 0.17 in HTLV-2 and 0.99 ± 0.18 in HTLV seronegative subjects (p = 0.322. TL was not associated with HTLV-1 or -2 proviral load. Shorter TL was significantly associated with impaired vibration sense in the HTLV-2 positive group only. Overall, we found no evidence that telomere length was affected by chronic HTLV-1 and HTLV-2 infection. That TL was only associated with peripheral neuropathy in the HTLV-2-positive group is intriguing, but should be interpreted cautiously. Studies with larger sample size and telomere length measurement in lymphocyte subsets may clarify the relationship between TL and HTLV-infection.

  18. Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging.

    Science.gov (United States)

    Jones, Christopher W; Gambala, Cecilia; Esteves, Kyle C; Wallace, Maeve; Schlesinger, Reid; O'Quinn, Marguerite; Kidd, Laura; Theall, Katherine P; Drury, Stacy S

    2017-03-01

    Health disparities begin early in life and persist across the life course. Despite current efforts, black women exhibit greater risk for pregnancy complications and negative perinatal outcomes compared with white women. The placenta, which is a complex multi-tissue organ, serves as the primary transducer of bidirectional information between the mother and fetus. Altered placental function is linked to multiple racially disparate pregnancy complications; however, little is known about racial differences in molecular factors within the placenta. Several pregnancy complications, which include preeclampsia and fetal growth restriction, exhibit racial disparities and are associated with shorter placental telomere length, which is an indicator of cellular stress and aging. Cellular senescence and telomere dynamics are linked to the molecular mechanisms that are associated with the onset of labor and parturition. Further, racial differences in telomere length are found in a range of different peripheral tissues. Together these factors suggest that exploration of racial differences in telomere length of the placenta may provide novel mechanistic insight into racial disparities in birth outcomes. This study examined whether telomere length measured in 4 distinct fetally derived tissues were significantly different between black and white women. The study had 2 hypotheses: (1) that telomere length that is measured in different placental tissue types would be correlated and (2) that across all sampled tissues telomere length would differ by race. In a prospective study, placental tissue samples were collected from the amnion, chorion, villus, and umbilical cord from black and white singleton pregnancies (N=46). Telomere length was determined with the use of monochrome multiplex quantitative real-time polymerase chain reaction in each placental tissue. Demographic and pregnancy-related data were also collected. Descriptive statistics characterized the sample overall and among

  19. Augmented telomerase activity, reduced telomere length and the presence of alternative lengthening of telomere in renal cell carcinoma: plausible predictive and diagnostic markers.

    Science.gov (United States)

    Pal, Deeksha; Sharma, Ujjawal; Khajuria, Ragini; Singh, Shrawan Kumar; Kakkar, Nandita; Prasad, Rajendra

    2015-05-15

    In this study, we analyzed 100 cases of renal cell carcinoma (RCC) for telomerase activity, telomere length and alternative lengthening of telomeres (ALT) using the TRAP assay, TeloTTAGGG assay kit and immunohistochemical analysis of ALT associated promyelocytic leukemia (PML) bodies respectively. A significantly higher (P=0.000) telomerase activity was observed in 81 cases of RCC which was correlated with clinicopathological features of tumor for instance, stage (P=0.008) and grades (P=0.000) but not with the subtypes of RCC (P = 0.355). Notwithstanding, no correlation was found between telomerase activity and subtypes of RCC. Strikingly, the telomere length was found to be significantly shorter in RCC (P=0.000) to that of corresponding normal renal tissues and it is well correlated with grades (P=0.016) but not with stages (P=0.202) and subtypes (P=0.669) of RCC. In this study, telomere length was also negatively correlated with the age of patients (r(2)=0.528; P=0.000) which supports the notion that it could be used as a marker for biological aging. ALT associated PML bodies containing PML protein was found in telomerase negative cases of RCC. It suggests the presence of an ALT pathway mechanism to maintain the telomere length in telomerase negative RCC tissues which was associated with high stages of RCC, suggesting a prevalent mechanism for telomere maintenance in high stages. In conclusion, the telomerase activity and telomere length can be used as a diagnostic as well as a predictive marker in RCC. The prevalence of ALT mechanism in high stages of RCC is warranted for the development of anti-ALT inhibitors along with telomerase inhibitor against RCC as a therapeutic approach. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Early warning system hypertension thresholds to predict adverse outcomes in pre-eclampsia: A prospective cohort study.

    Science.gov (United States)

    Nathan, Hannah L; Seed, Paul T; Hezelgrave, Natasha L; De Greeff, Annemarie; Lawley, Elodie; Anthony, John; Hall, David R; Steyn, Wilhelm; Chappell, Lucy C; Shennan, Andrew H

    2017-11-21

    To evaluate the association between blood pressure (BP) measurements and adverse outcomes in women with pre-eclampsia. A prospective cohort study of women with pre-eclampsia admitted to three South African tertiary facilities. BP was measured using the CRADLE Vital Signs Alert (VSA), incorporated with a traffic light early warning system; green: systolic BP warning system, can identify women who are hypertensive, at increased risk of severe pre-eclampsia complications and in need of escalation of care. Women who triggered a red light were at increased risk of kidney injury, magnesium sulfate use and CCU admission. Copyright © 2017. Published by Elsevier B.V.

  1. Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review

    Directory of Open Access Journals (Sweden)

    Zamora Javier

    2009-03-01

    Full Text Available Abstract Background Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies. Methods We conducted electronic searches in MEDLINE (1951 to 2007, EMBASE (1980 to 2007, the Cochrane Library (2007 and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 × 2 tables with maternal and fetal complications as reference standards. Results Sixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7 and 0.53 (95% CI 0.27, 1 for stillbirths, 1.5 (95% CI 0.94, 2.4 and 0.73 (95% CI 0.39, 1.4 for neonatal deaths and 1.5 (95% 1, 2 and 0.78 (95% 0.64, 0.95 for Neonatal Intensive Care Unit admission. Conclusion Measure of proteinuria is a

  2. Empirical evaluation of humpback whale telomere length estimates : Quality control and factors causing variability in the singleplex and multiplex qPCR methods

    NARCIS (Netherlands)

    Olsen, Morten Tange; Berube, Martine; Robbins, Jooke; Palsboll, Per J.

    2012-01-01

    Background: Telomeres, the protective cap of chromosomes, have emerged as powerful markers of biological age and life history in model and non-model species. The qPCR method for telomere length estimation is one of the most common methods for telomere length estimation, but has received recent

  3. Development of mHealth applications for pre-eclampsia triage.

    Science.gov (United States)

    Dunsmuir, Dustin T; Payne, Beth A; Cloete, Garth; Petersen, Christian Leth; Görges, Matthias; Lim, Joanne; von Dadelszen, Peter; Dumont, Guy A; Ansermino, J Mark

    2014-11-01

    The development of mobile applications for the diagnosis and management of pregnant women with pre-eclampsia is described. These applications are designed for use by community-based health care providers (c-HCPs) in health facilities and during home visits to collect symptoms and perform clinical measurements (including pulse oximeter readings). The clinical data collected in women with pre-eclampsia are used as the inputs to a predictive model providing a risk score for the development of adverse outcomes. Based on this risk, the applications provide recommendations on treatment, referral, and reassessment. c-HCPs can access patient records across multiple visits, using multiple devices that are synchronized using a secure Research Electronic Data Capture server. A unique feature of these applications is the ability to measure oxygen saturation with a pulse oximeter connected to a smartphone (Phone Oximeter). The mobile health application development process, including challenges encountered and solutions are described.

  4. Associations of Leukocyte Telomere Length With Aerobic and Muscular Fitness in Young Adults.

    Science.gov (United States)

    Williams, Dylan M; Buxton, Jessica L; Kantomaa, Marko T; Tammelin, Tuija H; Blakemore, Alexandra I F; Järvelin, Marjo-Riitta

    2017-04-01

    Decline in both telomere length and physical fitness over the life course may contribute to increased risk of several chronic diseases. The relationship between telomere length and aerobic and muscular fitness is not well characterized. We examined whether there are cross-sectional associations of mean relative leukocyte telomere length (LTL) with objective measures of aerobic fitness, muscle strength, and muscle endurance, using data on 31-year-old participants of the Northern Finland Birth Cohort 1966 (n = 4,952-5,205, varying by exposure-outcome analysis). Aerobic fitness was assessed by means of heart rate measurement following a standardized submaximal step test; muscular fitness was assessed by means of a maximal isometric handgrip strength test and a test of lower-back trunk muscle endurance. Longer LTL was associated with higher aerobic fitness and better trunk muscle endurance in models including adjustment for age, sex, body mass index, socioeconomic position, diet, smoking, alcohol consumption, physical activity level, and C-reactive protein. In a sex-stratified analysis, LTL was not associated with handgrip strength in either men or women. LTL may relate to aspects of physical fitness in young adulthood, but replication of these findings is required, along with further studies to help assess directions and causality in these associations. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

  5. Leukocyte telomere length in HIV-infected and HIV-exposed uninfected children: shorter telomeres with uncontrolled HIV viremia.

    Directory of Open Access Journals (Sweden)

    Hélène C F Côté

    Full Text Available OBJECTIVES: Nucleoside reverse transcriptase inhibitors (NRTIs used in HIV antiretroviral therapy can inhibit human telomerase reverse transcriptase. We therefore investigated whether in utero or childhood exposure to NRTIs affects leukocyte telomere length (LTL, a marker of cellular aging. METHODS: In this cross-sectional CARMA cohort study, we investigated factors associated with LTL in HIV-1-infected (HIV(+ children (n = 94, HIV-1-exposed uninfected (HEU children who were exposed to antiretroviral therapy (ART perinatally (n = 177, and HIV-unexposed uninfected (HIV(- control children (n = 104 aged 0-19 years. Univariate followed by multivariate linear regression models were used to examine relationships of explanatory variables with LTL for: a all subjects, b HIV(+/HEU children only, and c HIV(+ children only. RESULTS: After adjusting for age and gender, there was no difference in LTL between the 3 groups, when considering children of all ages together. In multivariate models, older age and male gender were associated with shorter LTL. For the HIV(+ group alone, having a detectable HIV viral load was also strongly associated with shorter LTL (p = 0.007. CONCLUSIONS: In this large study, group rates of LTL attrition were similar for HIV(+, HEU and HIV(- children. No associations between children's LTL and their perinatal ART exposure or HIV status were seen in linear regression models. However, the association between having a detectable HIV viral load and shorter LTL suggests that uncontrolled HIV viremia rather than duration of ART exposure may be associated with acceleration of blood telomere attrition.

  6. Association between HLA-G genotype and risk of pre-eclampsia: a case-control study using family triads

    DEFF Research Database (Denmark)

    Hylenius, Sine; Andersen, Anne-Marie Nybo; Melbye, Mads

    2004-01-01

    Pre-eclampsia affects 2-7% of all pregnancies with varying severity and is a leading cause of maternal and fetal mortality and morbidity. The aetiology involves almost certainly a combination of genetic predisposition with maternal and fetal contributions and environmental factors. Research points...... towards pathologies in the placenta as the triggering factor which leads to systemic endothelial dysfunction in the mother, probably as the result of interaction with released placental factors circulating in the maternal blood. One prominent hypothesis regarding the aetiology of pre-eclampsia suggests......RNA splicing. The results may also indicate that combined mother-child HLA-G genotypes could influence the risk of developing pre-eclampsia. Overall, the study suggests that HLA-G genotypes and expression might have a significant influence on development of pre-eclampsia....

  7. Nursing care for women with pre-eclampsia and/or eclampsia: integrative review

    OpenAIRE

    Maria Beatriz Guimarães Ferreira; Caroline Freitas Silveira; Sueli Riul da Silva; Delvane José de Souza; Mariana Torreglosa Ruiz

    2016-01-01

    Abstract OBJECTIVE: To analyze the available evidence in the literature on nursing care for women with pre-eclampsia and/or eclampsia. METHODS: Integrative review searching for primary studies in the databases PubMed, CINAHL, LILACS and SciELO. RESULTS: The sample size consisted of 17 primary studies published between January 2000 and December 2014, grouped into four categories: standardizing blood pressure measurement technique; training with simulation; instruments for standardization ...

  8. Is there any relationship between ABO/Rh blood group and patients with pre-eclampsia?

    Science.gov (United States)

    Hentschke, Marta R; Caruso, Fernanda B; Paula, Letícia G; Medeiros, Augusto K; Gadonski, Giovani; Antonello, Ivan C; Mistry, Hiten D; Poli-de-Figueiredo, Carlos E; Pinheiro da Costa, Bartira E

    2014-04-01

    The purpose of the present study was to evaluate the association between pre-eclampsia and blood groups in a group of pregnant women hospitalized in a University Hospital in Porto Alegre, Brazil - Hospital São Lucas (HSL)/PUCRS. Our sample consisted of 10,040 pregnant women admitted to the maternity department of HSL between 2005 and 2010. The patients were reviewed retrospectively for inclusion. Medical records of 414 women were diagnosed as preeclampsia/eclampsia and 9611 women were identified to the control group. The patients were divided into two groups: the group with preeclampsia/eclampsia and the control group, and their blood groups were considered. Data were analyzed using SPSS for Windows version 17.0. Categorical data were summarized by counts and percentages, with the statistical significance evaluated by the Chi-square test. The null hypothesis was rejected when ppre-eclampsia, respectively, Systolic Blood Pressure (117±19.98 vs. 165±19.99); Diastolic Blood Pressure (73±14.23 vs. 106±14.24) and maternal weight at booking (73±33 vs. 83±33). For all data: mean+SD; pblood groups, firstly they were stratified by Rh and ABO phenotypes, separately. After that the groups were put together. No differences in blood group distribution were observed between controls and pre-eclampsia for any analysis. (p>0.05). When we adopted stricter criteria for pre-eclampsia and a large sample from the same region we noted that the results did not show any association between blood groups and the development of pre-eclampsia. Copyright © 2014 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  9. TERRA Expression Levels Do Not Correlate With Telomere Length and Radiation Sensitivity in Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Alexandra eSmirnova

    2013-05-01

    Full Text Available Mammalian telomeres are transcribed into long non-coding telomeric RNA molecules (TERRA that seem to play a role in the maintenance of telomere stability. In human cells, CpG island promoters drive TERRA transcription and are regulated by methylation. It was suggested that the amount of TERRA may be related to telomere length. To test this hypothesis we measured telomere length and TERRA levels in single clones isolated from five human cell lines: HeLa (cervical carcinoma, BRC-230 (breast cancer, AKG and GK2 (gastric cancers and GM847 (SV40 immortalized skin fibroblasts. We observed great clonal heterogeneity both in TRF (Terminal Restriction Fragment length and in TERRA levels. However, these two parameters did not correlate with each other. Moreover, cell survival to γ-rays did not show a significant variation among the clones, suggesting that, in this cellular system, the intra-population variability in telomere length and TERRA levels does not influence sensitivity to ionizing radiation. This conclusion was supported by the observation that in a cell line in which telomeres were greatly elongated by the ectopic expression of telomerase, TERRA expression levels and radiation sensitivity were similar to the parental HeLa cell line.

  10. Comparative proteomics analysis suggests that placental mitochondria are involved in the development of pre-eclampsia.

    Directory of Open Access Journals (Sweden)

    Zhonghua Shi

    Full Text Available INTRODUCTION: Pre-eclampsia (PE, a severe pregnancy-specific disease characterized by the new onset of hypertension, proteinuria, edema, and a series of other systematic disorders, is a state of widespread mitochondrial dysfunction of the placenta. METHODS: We compared the morphology of mitochondria in pre-eclamptic and normotensive placentae using electron microscopy. To reveal the systematic protein expression changes of placental mitochondria that might explain the pathogenesis of PE, we performed iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS on differentially expressed placental mitochondria proteins from 4 normotensive and 4 pre-eclamptic pregnancies. Bioinformatics analysis was used to find the relative processes that these differentially expressed proteins were involved in. Three differentially expressed proteins were chosen to confirm by Western blotting and immunohistochemistry. RESULTS: Morphological data demonstrated degenerative and apoptotic changes in the mitochondria of pre-eclamptic placentae. We found four proteins were upregulated and 22 proteins were downregulated in pre-eclamptic placentae compared with normotensive placentae. Bioinformatics analysis showed that these proteins were involved in many critical processes in the development of pre-eclampsia such as apoptosis, fatty acid oxidation, the respiratory chain, reactive oxygen species generation, the tricarboxylic acid cycle and oxidative stress. CONCLUSIONS: This preliminary work provides a better understanding of the proteomic alterations of mitochondria from pre-eclamptic placentae and may aid in our understanding of the importance of mitochondria in the development of pre-eclampsia.

  11. La aspirina es ineficaz en la prevención de la pre-eclampsia

    Directory of Open Access Journals (Sweden)

    Carlos Bustamante Rojas

    1998-10-01

    Full Text Available Tres recientes estudios han confirmado que la aspirina no aporta ningún beneficio en la prevención de la pre-eclampsia o en reducir los efectos de esta en los recién nacidos. Sin embargo, y a pesar de la evidencia cada vez mayor de ineficacia, muchos continúan usándola de rutina con este fin. EI resultado de un primer ensayo clínico aleatorizado con 2.539 mujeres en alto riesgo para presentar pre-eclampsia, llevado a cabo en el National Institute of Child Health and Human Development en los Estados Unidos, demostró categóricamente que el tratamiento preventivo con aspirina no sirve; las diferencias halladas frente al placebo no fueron estadísticamente significativas, tomando para el estudio mujeres con diabetes previa, hipertensión arterial, o antecedentes de pre-eclampsia. Tampoco hubo ninguna diferencia en cuanto al número de partos pretérmino, bajo peso para la edad gestacional y mortalidad.

  12. Nursing care for women with pre-eclampsia and/or eclampsia: integrative review

    Directory of Open Access Journals (Sweden)

    Maria Beatriz Guimarães Ferreira

    2016-04-01

    Full Text Available Abstract OBJECTIVE: To analyze the available evidence in the literature on nursing care for women with pre-eclampsia and/or eclampsia. METHODS: Integrative review searching for primary studies in the databases PubMed, CINAHL, LILACS and SciELO. RESULTS: The sample size consisted of 17 primary studies published between January 2000 and December 2014, grouped into four categories: standardizing blood pressure measurement technique; training with simulation; instruments for standardization of care and quality of care The main nursing actions were: physical examination, early detection of signs of pre-eclampsia/eclampsia, monitoring of laboratory tests, fetal assessment, qualification and training of professionals. We identified the need for standardization of care from instruments, protocols and blood pressure measurement technique, early identification and treatment of hypertensive crisis through institutional protocols and review of cases and work processes. CONCLUSION: Women with pre-eclampsia and/or eclampsia require specific nursing care, which must be guided by care protocols based on scientific evidence.

  13. [Care plan for women with cesarean section and pre-eclampsia].

    Science.gov (United States)

    Sabbagh-Sequera, Miriam; Loidi-García, Jose María; Romero-Vázquez, Gloria Maria

    2015-01-01

    Pregnancy pathologies in general, and pre-eclampsia in particular, are problems usually treated in post-anesthesia recovery and hospitalization units. Pre-eclampsia is the most frequent form of hypertension associated with pregnancy (50%). It affects from 7% to 10% of pregnant women. It is known as pregnancy and puerperium multisystem syndrome. It is due to a reduction of the systemic perfusion generated by the vasospasms and the activation of the coagulation systems. A clinical case is presented of the immediate post-surgery period of a patient, who has been operated on cesarean section after having been diagnosed with pre-eclampsia. A nursing care plan was prepared, based on Marjory Gordon functional patterns and guided by NANDA-NOC-NIC taxonomy, where 6 nursing diagnoses, which are the basis for the fulfillment of this nursing process, are identified: Risk of infection, excess fluid volume, risk of bleeding, insufficient knowledge about its pathological process, severe pain, and anxiety. The application of this care plan leads to an improvement in the patient care and in the work organization. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  14. Effects of G-CSF on telomere lengths in PBMCs from human immunodeficiency virus-infected patients

    DEFF Research Database (Denmark)

    Aladdin, H; Ullum, H; Schjerling, P

    2000-01-01

    Telomeres are unique terminal chromosomal structures, the length of which has been shown to decrease with cell division in vitro and with increased age in vivo for human somatic cells. In human immunodeficiency virus (HIV)-1 infection, decrease of telomere length is primarily found in CD8+ T cell...... that during G-CSF treatment lymphocytes are recruited by a combination of central and peripheral proliferation....

  15. Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction

    OpenAIRE

    Nishizawa, Haruki; Ota, Sayuri; Suzuki, Machiko; Kato, Takema; Sekiya, Takao; Kurahashi, Hiroki; Udagawa, Yasuhiro

    2011-01-01

    Background It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR. Methods We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8) and normotensive pregnancies with or (n = 8) without FGR (n = 8...

  16. Fetal sex and maternal risk of pre-eclampsia/eclampsia: a systematic review and meta-analysis.

    Science.gov (United States)

    Jaskolka, D; Retnakaran, R; Zinman, B; Kramer, C K

    2017-03-01

    A preponderance of male fetuses in pregnancies complicated by pre-eclampsia was described over 40 years ago. Since then, however, there has been conflicting evidence in the literature, with some studies supporting a male preponderance, some demonstrating no relationship with fetal sex, and others reporting increased risk in pregnancies bearing females. In this context, we sought to conduct a systematic review and meta-analysis to objectively evaluate the relationship between fetal sex and maternal risk of pre-eclampsia/eclampsia. Studies from January 1950 to April 2015 were identified from PUBMED and EMBASE. This systematic review and meta-analysis evaluated 22 articles reporting data on fetal sex and prevalence of pre-eclampsia/eclampsia. Data were extracted by two independent reviewers. Pooled estimates of the relative risk (RR) were calculated by random-effects model. Male fetus was considered the exposure and prevalence of maternal pre-eclampsia/eclampsia was the outcome of interest. We identified 534 studies through electronic searches and three studies through manual searches. Twenty-two studies fulfilled the inclusion criteria, yielding data on 3 163 735 women. Pooled analyses of these studies showed no association between male fetal sex and maternal risk of pre-eclampsia/eclampsia (RR 1.01; 95% confidence interval, 95% CI 0.97-1.05); however, a subgroup analysis including only studies that evaluated the non-Asian population (n = 2 931 771 women) demonstrated that male fetal sex was associated with increased maternal risk of pre-eclampsia/eclampsia (RR 1.05; 95% CI 1.03-1.06; I(2) = 10%; P = 0.33). Male fetal sex is associated with maternal risk of pre-eclampsia/eclampsia in the non-Asian population. Fetal sex is associated with maternal risk of pre-eclampsia/eclampsia in the non-Asian population. © 2016 Royal College of Obstetricians and Gynaecologists.

  17. Urinary albumin excretion and 24-hour blood pressure as predictors of pre-eclampsia in Type I diabetes

    DEFF Research Database (Denmark)

    Ekbom, P; Damm, P; Nøgaard, K

    2000-01-01

    To evaluate the value of 24-h blood pressure monitoring compared to office blood pressure and urinary albumin excretion in predicting pre-eclampsia in Type I (insulin-dependent) diabetes mellitus.......To evaluate the value of 24-h blood pressure monitoring compared to office blood pressure and urinary albumin excretion in predicting pre-eclampsia in Type I (insulin-dependent) diabetes mellitus....

  18. Telomere length is highly inherited and associated with hyperactivity-impulsivity in children with attention deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Danielle Souza Costa

    2015-07-01

    Full Text Available Telomere length (TL is highly heritable, and a shorter telomere at birth may increase the risk of age-related problems. Telomere length (TL is highly heritable, and a shorter telomere at birth may increase the risk of age-related problems. Additionally, a shorter TL may represent a biomarker of chronic stress and has been associated with psychiatric disorders. However, no study has explored whether there is an association between TL and the symptoms of one of the most common neurodevelopmental disorders in childhood: Attention Deficit/Hyperactive Disorder (ADHD. We evaluated 61 (range, 6-16 years ADHD children and their parents between 2012 and 2014. Telomere length was measured with a quantitative polymerase chain reaction method with telomere signal normalized to the signal from a single copy gene (36B4 to generate a T/S ratio. Family data was processed through a GEE model to determine the effect of parental TL on children TL. Inattentive and hyperactive-impulsive symptoms were also evaluated in relation to TL. For the first time, we found general heritability to be the major mechanism explaining interindividual telomere length variation in ADHD (father-child: 95%CI=0.35/0.91, p0.05. The ADHD inattentive dimension was not significant associated with TL in this study (p>0.05. TL was shown to be a potential biomarker of the ADHD symptoms burden in families affected by this neurodevelopmental disorder. However, it is crucial that future studies investigating the rate of telomere attrition in relation to psychiatric problems to consider the strong determination of telomere length at birth by inheritance.

  19. Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia.

    Science.gov (United States)

    Gadalla, Shahinaz M; Wang, Tao; Haagenson, Michael; Spellman, Stephen R; Lee, Stephanie J; Williams, Kirsten M; Wong, Jason Y; De Vivo, Immaculata; Savage, Sharon A

    2015-02-10

    Telomeres protect chromosome ends and are markers of cellular aging and replicative capacity. To evaluate the association between recipient and donor pretransplant leukocyte telomere length with outcomes after unrelated donor allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia. The study included 330 patients (235 acquired, 85 Fanconi anemia, and 10 Diamond-Blackfan anemia) and their unrelated donors who had pre-HCT blood samples and clinical and outcome data available at the Center for International Blood and Marrow Transplant Research. Patients underwent HCT between 1989 and 2007 in 84 centers and were followed-up to March 2013. Recipient and donor pre-HCT leukocyte telomere length classified into long (third tertile) and short (first and second tertiles combined) based on donor telomere length distribution. Overall survival, neutrophil recovery, and acute and chronic graft-vs-host disease, as ascertained by transplant centers through regular patient follow-up. Longer donor leukocyte telomere length was associated with higher survival probability (5-year overall survival, 56%; number at risk, 57; cumulative deaths, 50) than shorter donor leukocyte telomere length (5-year overall survival, 40%; number at risk, 71; cumulative deaths, 128; P = .009). The association remained statistically significant after adjusting for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race/ethnicity, and calendar year of transplant (hazard ratio [HR], 0.61; 95% CI, 0.44-0.86). Similar results were noted in analyses stratified on severe aplastic anemia subtype, recipient age, HLA matching, calendar year of transplant, and conditioning regimen. There was no association between donor telomere length and neutrophil engraftment at 28 days (cumulative incidence, 86% vs 85%; HR, 0.94; 95% CI, 0.73-1.22), acute graft-vs-host disease grades III-IV at 100 days (cumulative incidence

  20. A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

    Science.gov (United States)

    Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

    Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

  1. Psychological Profiles in the Prediction of Leukocyte Telomere Length in Healthy Individuals.

    Directory of Open Access Journals (Sweden)

    Louisia Starnino

    Full Text Available Shorter telomere length (TL may signal premature cellular aging and increased risk for disease. While depression and psychosocial stress have been associated with shorter telomeres, other psychological risk factors for cardiovascular disease have received less attention.To evaluate the association between TL and psychological risk factors (symptoms of anxiety and depression, hostility and defensiveness traits for heart disease, and to examine whether chronological age and sex moderate the associations observed.132 healthy men and women (Mage = 45.34 years completed the Marlowe-Crowne Social Desirability Scale, the Beck Depression Inventory II, The Beck Anxiety Inventory and the Cook-Medley Hostility Scale. Relative TL was measured by quantitative polymerase chain reaction (PCR of total genomic DNA samples. A series of hierarchical linear regressions were performed controlling for pertinent covariates.Shorter TL was observed among individuals high in defensiveness (β = -.221 and depressive symptoms (β = -.213, as well as in those with less hostility (β =.256 and anxiety (β =.220(all Ps<.05. Psychological variables explained 19% of the variance over and above that explained by covariates (age, sex, exercise, alcohol consumption, systemic inflammation, and 24-hr mean arterial pressure. Age moderated the relation between TL and defensiveness (β =.179, p =.03. Sex did not influence any of the relations.Telomere length is associated with psychological burden though the direction of effect differs depending on the psychological variables under study. Further research is needed to determine the reasons for and implications of these seemingly contradictory findings.

  2. TERRA Expression Levels Do Not Correlate with Telomere Length and Radiation Sensitivity in Human Cancer Cell Lines.

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    Smirnova, Alexandra; Gamba, Riccardo; Khoriauli, Lela; Vitelli, Valerio; Nergadze, Solomon G; Giulotto, Elena

    2013-01-01

    Mammalian telomeres are transcribed into long non-coding telomeric repeat-containing RNA (TERRA) molecules that seem to play a role in the maintenance of telomere stability. In human cells, CpG-island promoters drive TERRA transcription and are regulated by methylation. It was suggested that the amount of TERRA may be related to telomere length. To test this hypothesis we measured telomere length and TERRA levels in single clones isolated from five human cell lines: HeLa (cervical carcinoma), BRC-230 (breast cancer), AKG and GK2 (gastric cancers), and GM847 (SV40 immortalized skin fibroblasts). However, these two parameters did not correlate with each other. Moreover, cell survival to γ-rays did not show a significant variation among the clones, suggesting that, in this cellular system, the intra-population variability in telomere length and TERRA levels does not influence sensitivity to ionizing radiation. This conclusion was supported by the observation that in a cell line in which telomeres were greatly elongated by the ectopic expression of telomerase, TERRA expression levels and radiation sensitivity were similar to the parental HeLa cell line.

  3. Endothelial dysfunction in the pathogenesis of pre-eclampsia in Ghanaian women.

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    Adu-Bonsaffoh, Kwame; Antwi, Daniel Ansong; Gyan, Ben; Obed, Samuel Amenyi

    2017-03-29

    Pre-eclampsia (PE) remains a disease of theories despite extensive research into its etiology. Alteration in the production of vascular endothelial growth factor (VEGF), a biomarker of endothelial dysfunction, is associated with pre-eclampsia although conflicting reports have been reported. The aim of the study was to determine and compare maternal serum levels of VEGF among pre-eclamptics, normotensive non pregnant and pregnant women. This was a cross-sectional study involving 100 women with pre-eclampsia, 102 women with normotensive pregnancy and 75 normotensives who were not pregnant. The study was carried out at Korle Bu Teaching Hospital (KBTH) from April to June in 2011. Basic socio-demographic and obstetric data were obtained by means of structured questionnaire. Following venesection, about 5mls of blood was sampled from the participants for the various tests. Enzyme Linked Immunosorbent Assay was used to determine the maternal serum levels of free VEGF. Data analysis was performed using SPSS version 20. Significant reduction in median serum levels of free VEGF was seen in both, normal pregnant [84.06 pg/ml (IQR: 78.90-99.67)] and pre-eclamptic women [4.71 pg/ml, (IQR: 3.41-7.93)] compared to the non-pregnant (395.85 pg/ml, IQR 234.93-625) with p pre-eclamptic group compared to that of normotensive pregnant group (p pre-eclampsia had significantly more severe reduction in free VEGF levels (3.89, IQR: 2.60-5.67 pg/ml) compared to that of late onset PE (5.23, IQR: 3.78-16.97 pg/ml) with ppre-eclampsia as demonstrated by profound decrease in maternal serum VEGF levels in PE compared to normotensive pregnancy and non-pregnancy state. The pathophysiology of early-onset pre-eclampsia may be partly explained by marked reduction in free serum VEGF levels with resultant severe endothelial dysfunction.

  4. Community perceptions of pre-eclampsia and eclampsia in southern Mozambique.

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    Boene, Helena; Vidler, Marianne; Sacoor, Charfudin; Nhama, Abel; Nhacolo, Ariel; Bique, Cassimo; Alonso, Pedro; Sawchuck, Diane; Qureshi, Rahat; Macete, Eusébio; Menéndez, Clara; von Dadelszen, Peter; Sevene, Esperança; Munguambe, Khátia

    2016-06-08

    Sub-Saharan Africa has the highest maternal mortality ratio at 500 deaths per 100,000 live births. In Mozambique maternal mortality is estimated at 249-480 per 100,000 live births and eclampsia is the third leading cause of death. The objective of this study was to describe the community understanding of pre-eclampsia and eclampsia, as a crucial step to improve maternal and perinatal health in southern Mozambique. This qualitative study was conducted in Maputo and Gaza Provinces of southern Mozambique. Twenty focus groups were convened with pregnant women, partners and husbands, matrons and traditional birth attendants, and mothers and mothers-in-law. In addition, ten interviews were conducted with traditional healers, matrons, and a traditional birth attendant. All discussions were audio-recorded, translated from local language (Changana) to Portuguese and transcribed verbatim prior to analysis with QSR NVivo 10. A thematic analysis approach was taken. The conditions of "pre-eclampsia" and "eclampsia" were not known in these communities; however, participants were familiar with hypertension and seizures in pregnancy. Terms linked with the biomedical concept of pre-eclampsia were high blood pressure, fainting disease and illness of the heart, whereas illness of the moon, snake illness, falling disease, childhood illness, illness of scaresand epilepsy were used to characterizeeclampsia. The causes of hypertension in pregnancy were thought to include mistreatment by in-laws, marital problems, and excessive worrying. Seizures in pregnancy were believed to be caused by a snake living inside the woman's body. Warning signs thought to be common to both conditions were headache, chest pain, weakness, dizziness, fainting, sweating, and swollen feet. Local beliefs in southern Mozambique, regarding the causes, presentation, outcomes and treatment of pre-eclampsia and eclampsia were not aligned with the biomedical perspective. The community was often unaware of the link

  5. Physical activity and telomere length in U.S. men and women: An NHANES investigation.

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    Tucker, Larry A

    2017-07-01

    The principal objective was to determine the extent to which physical activity (PA) accounts for differences in leukocyte telomere length (LTL) in a large random sample of U.S. adults. Another purpose was to assess the extent to which multiple demographic and lifestyle covariates affect the relationship between PA and LTL. A total of 5823 adults from the National Health and Nutrition Examination Survey (NHANES 1999-2002) were studied cross-sectionally. Employing the quantitative polymerase chain reaction method, LTL was compared to standard reference DNA. PA was indexed using MET-minutes using self-reported frequency, intensity, and duration of participation in 62 physical activities. Covariates were controlled statistically. Telomeres were 15.6 base pairs shorter for each year of chronological age (F=723.2, Paccounting for years of reduced cellular aging compared to their more sedentary counterparts. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control

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    Kennedy Hugh

    2008-10-01

    Full Text Available Abstract Background Telomeres are DNA repeat sequences necessary for DNA replication which shorten at cell division at a rate directly related to levels of oxidative stress. Critical telomere shortening predisposes to cell senescence and to epithelial malignancies. Type 2 diabetes is characterised by increased oxidative DNA damage, telomere attrition, and an increased risk of colonic malignancy. We hypothesised that the colonic mucosa in Type 2 diabetes would be characterised by increased DNA damage and telomere shortening. Methods We examined telomere length (by flow fluorescent in situ hybridization and oxidative DNA damage (flow cytometry of 8 – oxoguanosine in the colonic mucosal cells of subjects with type 2 diabetes (n = 10; mean age 62.2 years, mean HbA1c 6.9% and 22 matched control subjects. No colonic pathology was apparent in these subjects at routine gastrointestinal investigations. Results Mean colonic epithelial telomere length in the diabetes group was not significantly different from controls (10.6 [3.6] vs. 12.1 [3.4] Molecular Equivalent of Soluble Fluorochrome Units [MESF]; P = 0.5. Levels of oxidative DNA damage were similar in both T2DM and control groups (2.6 [0.6] vs. 2.5 [0.6] Mean Fluorescent Intensity [MFI]; P = 0.7. There was no significant relationship between oxidative DNA damage and telomere length in either group (both p > 0.1. Conclusion Colonic epithelium in Type 2 diabetes does not differ significantly from control colonic epithelium in oxidative DNA damage or telomere length. There is no evidence in this study for increased oxidative DNA damage or significant telomere attrition in colonic mucosa as a carcinogenic mechanism.

  7. Associations Between Age, Psychosocial Work Conditions, Occupational Well-Being, and Telomere Length in Geriatric Care Professionals: A Mixed-Methods Study.

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    Chmelar, Caroline; Jörres, Rudolf A; Kronseder, Angelika; Müller, Andreas; Nowak, Dennis; Weigl, Matthias

    2017-10-01

    We identified associations between age, psychosocial work characteristics, occupational well-being, and-as a measure of biological age-leukocyte telomere length in geriatric care professionals. This is a multisource study of self-reports on psychosocial work characteristics, standardized physician's evaluations of health, and relative telomere length measures of peripheral blood leukocytes. We included 141 geriatric care professionals. Telomere length was assessed by an improved polymerase chain reaction (PCR)-based method. Increased depersonalization was associated with shorter telomeres. Their association with age was not moderated by psychosocial work conditions. There was, however, a significant three-way interaction of social support and work ability with the age-telomere association. Additionally, social support and adverse general health moderated the age-telomere length relationship. A supportive work environment and work-related health may influence the association between age and telomere length.

  8. Aspirin non-responsiveness in pregnant women at high-risk of pre-eclampsia.

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    Navaratnam, Kate; Alfirevic, Ana; Jorgensen, Andrea; Alfirevic, Zarko

    2018-02-01

    Low-dose aspirin is recommended for prevention of pre-eclampsia in high-risk pregnant women. Current doses provide a conservative risk reduction and some individuals demonstrate 'aspirin non-responsiveness', with insufficient antiplatelet effects. We aimed to determine if aspirin non-responsiveness could be identified in women at high risk of pre-eclampsia and assess for potential associations with placentally-mediated adverse outcomes. Prospective cohort study. 180 women at high-risk of pre-eclampsia, by NICE criteria, prescribed 75 mg dispersible aspirin daily were recruited from antenatal clinics of Liverpool Women's Hospital between 17/01/14 and 31/03/16. Platelet function (Multiplate™ impedance aggregometry, VerifyNow™ and 11-dehydrothromboxane B2) and aspirin metabolites (nuclear magnetic resonance and liquid chromatography mass spectrometry) were assessed at 5 + 0-20 + 6 and 33 + 0-35 + 6 weeks. Pearson's chi-square test was used to assess for associations between longitudinal response to aspirin and (1) any pre-eclampsia (2) composite adverse placentally-mediated outcome (one, or combination of pre-eclampsia, placental abruption, IUGR and perinatal mortality). A Bonferroni correction was applied to correct for multiple analyses. 180 women were recruited, there were 4 withdrawals and no women were lost to follow-up. After 15 women delivered prior to the completion of follow-up, sufficient sample volumes for longitudinal platelet function and aspirin adherence testing were obtained from 156 women. There were no consistent aspirin non-responders in the cohort. 59% (n = 92) women exhibited normal response to aspirin, 34% (n = 53) variable response (switching response status between study visits) and in 7% (n = 11) response could not be determined as they exhibited lack of platelet response on a background of undetectable aspirin metabolites. There was no significant association between indeterminate or inconsistent (variable or

  9. Acute maternal infection and risk of pre-eclampsia: a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Caroline Minassian

    Full Text Available Infection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection are associated with an increased risk of pre-eclampsia.We used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls. Cases (n=1533 were individually matched with up to ten controls (n=14236 on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14-1.44 and in women with urinary tract infection (adjusted odds ratio 1.22;1.03-1.45. We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72-1.16. Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings.Women who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying mechanism of this association and to determine

  10. Long term effects of radiation exposure on telomere lengths of leukocytes and its associated biomarkers among atomic-bomb survivors.

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    Lustig, Ana; Shterev, Ivo; Geyer, Susan; Shi, Alvin; Hu, Yiqun; Morishita, Yukari; Nagamura, Hiroko; Sasaki, Keiko; Maki, Mayumi; Hayashi, Ikue; Furukawa, Kyoji; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Ohishi, Waka; Nakachi, Kei; Weng, Nan-Ping; Hayashi, Tomonori

    2016-06-28

    Ionizing radiation (IR) is a major source of cellular damage and the immediate cellular response to IR has been well characterized. But the long-term impact of IR on cell function and its relationship with aging are not known. Here, we examined the IR effects on telomere length and other biomarkers 50 to 68 years post-exposure (two time points per person) in survivors of the atomic bombing at Hiroshima during WWII. We found that telomere length of leukocytes was inversely correlated with the dose of IR (p=0.008), and this effect was primarily found in survivors who were exposed at younger ages; specifically those <12 years old (p=0.0004). Although a dose-related retardation of telomere shortening with age was observed in the cross-sectional data, longitudinal follow-up after 11 years did not show IR exposure-related alteration of the rate of telomere shortening with age. In addition, IR diminished the associations between telomere length and selected aging biomarkers that were observed in survivors with no dose. These included uric acid metabolism, cytokines, and blood T cell counts. These findings showed long-lasting detrimental effects of IR on telomere length of leukocytes in both dose- and age-at-exposure dependent manner, and on alterations of biomarkers with aging.

  11. Telomere length and procedural justice predict stress reactivity responses to unfair outcomes in African Americans.

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    Lucas, Todd; Pierce, Jennifer; Lumley, Mark A; Granger, Douglas A; Lin, Jue; Epel, Elissa S

    2017-09-07

    This experiment demonstrates that chromosomal telomere length (TL) moderates response to injustice among African Americans. Based on worldview verification theory - an emerging psychosocial framework for understanding stress - we predicted that acute stress responses would be most pronounced when individual-level expectancies for justice were discordant with justice experiences. Healthy African Americans (N=118; 30% male; M age=31.63years) provided dried blood spot samples that were assayed for TL, and completed a social-evaluative stressor task during which high versus low levels of distributive (outcome) and procedural (decision process) justice were simultaneously manipulated. African Americans with longer telomeres appeared more resilient (in emotional and neuroendocrine response-higher DHEAs:cortisol) to receiving an unfair outcome when a fair decision process was used, whereas African Americans with shorter telomeres appeared more resilient when an unfair decision process was used. TL may indicate personal histories of adversity and associated stress-related expectancies that influence responses to injustice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A Network Mendelian Randomization Study.

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    Zhan, Yiqiang; Karlsson, Ida K; Karlsson, Robert; Tillander, Annika; Reynolds, Chandra A; Pedersen, Nancy L; Hägg, Sara

    2017-07-21

    Observational studies have found shorter leukocyte telomere length (TL) to be a risk factor for coronary heart disease (CHD), and recently the association was suggested to be causal. However, the relationship between TL and common metabolic risk factors for CHD is not well understood. Whether these risk factors could explain pathways from TL to CHD warrants further attention. To examine whether metabolic risk factors for CHD mediate the causal pathway from short TL to increased risk of CHD using a network Mendelian randomization design. Summary statistics from several genome-wide association studies were used in a 2-sample Mendelian randomization study design. Network Mendelian randomization analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality-was performed to examine the causal association between telomeres and CHD and metabolic risk factors. Summary statistics from the ENGAGE Telomere Consortium were used (n=37 684) as a TL genetic instrument, CARDIoGRAMplusC4D Consortium data were used (case=22 233 and control=64 762) for CHD, and other consortia data were used for metabolic traits (fasting insulin, triglyceride, total cholesterol, low-density lipoprotein cholesterol, fasting glucose, diabetes mellitus, glycohemoglobin, body mass index, waist circumference, and waist:hip ratio). One-unit increase of genetically determined TL was associated with -0.07 (95% confidence interval, -0.01 to -0.12; P=0.01) lower log-transformed fasting insulin (pmol/L) and 21% lower odds (95% confidence interval, 3-35; P=0.02) of CHD. Higher genetically determined log-transformed fasting insulin level was associated with higher CHD risk (odds ratio, 1.86; 95% confidence interval, 1.01-3.41; P=0.04). Overall, our findings support a role of insulin as a mediator on the causal pathway from shorter telomeres to CHD pathogenesis. © 2017 American Heart Association, Inc.

  13. Methylenetetrahydrofolate reductase gene C677T, A1298C polymorphisms and pre-eclampsia risk: a meta-analysis.

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    Li, Xing; Luo, Ya L; Zhang, Qiong H; Mao, Chen; Wang, Xi W; Liu, Shan; Chen, Qing

    2014-08-01

    To determine whether methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are associated with pre-eclampsia susceptibility. Literature searches of the Pubmed, Embase, BIOSIS Previews and Web of Science were conducted to identify all eligible articles up to January 18th, 2013. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) of five genetic models were calculated by fixed-effects or random-effects model. Publication bias, subgroup analysis, meta-regression and sensitivity analysis were also performed. A number of 49 studies including 51 samples consisted of 18,009 subjects (6,238 patients and 11,771 controls) were finally included. MTHFR C677T allele (TT or CT) carriers were 1.12 times more likely to develop pre-eclampsia (95% CI 1.04-1.21) compared with 677CC homozygous individuals. Similar results were obtained under other genetic models. Restricted to severe pre-eclampsia, there was an increased risk for 677TT homozygotes compared with 677CC homozygotes (OR 1.43; 95% CI 1.12-1.83). Subgroup analysis revealed a significant positive association between the C677T polymorphism (TT or CT) and pre-eclampsia in Asians (OR 1.41; 95% CI 1.11-1.79) and white population (OR 1.14; 95% CI 1.03-1.25). Meta-regression showed that study population, blinded genotyping, matching of cases and controls were not substantial sources of heterogeneity. For the MTHFR A1298C, ORs for all genetic models yielded a null association. This meta-analysis suggests that the MTHFR 677T allele might be associated with increased pre-eclampsia risk in Asian and white ethnicity and the subgroup of severe pre-eclampsia, while no association is observed between the MTHFR A1298C polymorphism and pre-eclampsia.

  14. Associations between pre-eclampsia and protein C and protein S levels among pregnant Nigerian women.

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    Okoye, Helen C; Eweputanna, Lisa I; Okpani, Anthony O U; Ejele, Oseikhuemen A

    2017-04-01

    To evaluate levels of protein C and free protein S among women with pre-eclampsia, and determine whether there is a relationship between deficiencies and pre-eclampsia. A cross-sectional study was conducted at a hospital in Nigeria from July 2013 to March 2014 among 90 pregnant women with pre-eclampsia (blood pressure ≥140/90 mm Hg, proteinuria ≥300 mg in 24 hours) and 90 normotensive pregnant women (control group). Plasma levels of protein C and free protein S were analyzed by enzyme-linked immunosorbent assay, and protein C activity by a chromogenic method. Mean protein C antigen and activity levels did not differ between groups (P=0.639 and P=0.444, respectively). The incidence of protein C antigen and activity deficiency also did not differ (P=0.288 and P>0.99, respectively). The mean free protein S antigen level was higher among women with pre-eclampsia (54.48%±19.58%) than in the control group (47.23%±10.27%; P=0.004). No woman in the control group had protein S deficiency, as compared with 2 (2%) of the women with pre-eclampsia (P=0.497). No association was found between deficiencies of these proteins and pre-eclampsia. Deficiencies of protein C and free protein S are unlikely to be etiopathogenetic for pre-eclampsia; therefore, therapeutic intervention should focus on other potential pathogenetic pathways. © 2016 International Federation of Gynecology and Obstetrics.

  15. Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial.

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    Rayman, Margaret P; Searle, Elizabeth; Kelly, Lynne; Johnsen, Sigurd; Bodman-Smith, Katherine; Bath, Sarah C; Mao, Jinyuan; Redman, Christopher W G

    2014-07-14

    Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 μg/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0·039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial.

  16. Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study.

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    Prescott, J; Du, M; Wong, J Y Y; Han, J; De Vivo, I

    2012-12-01

    Is the association between paternal age at birth and offspring leukocyte telomere length (LTL) an artifact of early life socioeconomic status (SES)? Indicators of early life SES did not alter the relationship between paternal age at birth and offspring LTL among a population of white female nurses. Telomere length is considered a highly heritable trait. Recent studies report a positive correlation between paternal age at birth and offspring LTL. Maternal age at birth has also been positively associated with offspring LTL, but may stem from the strong correlation with paternal age at birth. The Nurses' Health Study (NHS) is an ongoing prospective cohort study of 121 700 female registered nurses who were enrolled in 1976. Great effort goes into maintaining a high degree of follow-up among our cohort participants (>95% of potential person-years). In 1989-1990, a subset of 32 826 women provided blood samples from which we selected participants for several nested case-control studies of telomere length and incident chronic disease. We used existing LTL data on a total of 4250 disease-free women who also reported maternal and paternal age at birth for this study. Nested case-control studies of stroke, myocardial infarction, cancers of the breast, endometrium, skin, pancreas and colon, as well as colon adenoma, were conducted within the blood sub-cohort. Each study used the following study design: for each case of a disease diagnosed after blood collection, a risk-set sampling scheme was used to select from one to three controls from the remaining participants in the blood sub-cohort who were free of that disease when the case was diagnosed. Controls were matched to cases by age at blood collection (± 1 year), date of blood collection (± 3 months), menopausal status, recent postmenopausal hormone use at blood collection (within 3 months, except for the myocardial infarction case-control study), as well as other factors carefully chosen for each individual study. The

  17. Telomerase inhibition targets clonogenic multiple myeloma cells through telomere length-dependent and independent mechanisms.

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    Sarah K Brennan

    2010-09-01

    Full Text Available Plasma cells constitute the majority of tumor cells in multiple myeloma (MM but lack the potential for sustained clonogenic growth. In contrast, clonotypic B cells can engraft and recapitulate disease in immunodeficient mice suggesting they serve as the MM cancer stem cell (CSC. These tumor initiating B cells also share functional features with normal stem cells such as drug resistance and self-renewal potential. Therefore, the cellular processes that regulate normal stem cells may serve as therapeutic targets in MM. Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC. Moreover, we carried out both long and short-term inhibition studies to examine telomere length-dependent and independent activities.Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. In addition to these relatively long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth that was associated with MM CSC differentiation based on expression of the plasma cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term treatment of MM CSC also decreased the expression of genes typically expressed by stem cells (OCT3/4, SOX2, NANOG, and BMI1 as revealed by quantitative real-time PCR.Telomerase activity regulates the clonogenic growth of MM CSC. Moreover, reductions in MM growth following both long and short-term telomerase inhibition suggest that it impacts CSC through telomere length-dependent and independent mechanisms.

  18. Maternal adiposity and infancy growth predict later telomere length: a longitudinal cohort study.

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    Guzzardi, M A; Iozzo, P; Salonen, M K; Kajantie, E; Eriksson, J G

    2016-07-01

    Maternal overweight and obesity during pregnancy, and childhood growth patterns are risk factors influencing long-term health outcomes among the offspring. Furthermore, poor health condition has been associated with shorter leukocyte telomere length in adult subjects. We aimed to assess whether maternal adiposity during pregnancy and growth trajectory during infancy predict leukocyte telomere length (LTL) in later life. We studied a cohort of 1082 subjects belonging to the Helsinki Birth Cohort Study, born between 1934 and 1944. They underwent two clinical visits 10 years apart (2001-2004 and 2011-2013), during which LTL and anthropometrics were assessed. Birth records included birth weight, length, maternal body mass index (BMI) at the end of pregnancy. Serial measurements of height and weight from birth to 11 years were available. Higher maternal BMI was associated with shorter LTL in elderly women (r=-0.102, P=0.024) but not in men. Also, in women but not in men shorter LTL and greater telomere shortening over a 10-year interval were predicted by higher weight at 12 months of age (P=0.008 and P=0.029, respectively), and higher weight gain during the first 12 months of life (P=0.008 and P=0.006, respectively), particularly between 6 and 9 months of age (P=0.002 for both LTL and LTL shortening rate). A correlation between younger age at adiposity rebound and shorter LTL at 60 years (P=0.022) was also found. High maternal adiposity during pregnancy is associated with shorter LTL in elderly female offspring, but not in men. Moreover, higher weight and weight gain during the first year of life and younger age at adiposity rebound predict shorter LTL in older age in women, suggesting that rapid growth during the perinatal period accelerates cellular aging in late adulthood.

  19. Downregulation of Histone Methyltransferase Genes SUV39H1 and SUV39H2 Increases Telomere Length in Embryonic Stem-like Cells and Embryonic Fibroblasts in Pigs

    OpenAIRE

    DANG-NGUYEN, Thanh Quang; Haraguchi, Seiki; FURUSAWA, Tadashi; SOMFAI, Tamas; Kaneda, Masahiro; Watanabe, Shinya; AKAGI, Satoshi; KIKUCHI, Kazuhiro; Tajima, Atsushi; Nagai, Takashi

    2012-01-01

    Abstract Telomere is a nucleoprotein structure at the ends of chromosomes that helps to protect the ends of chromosomes from being fused with other chromosomes. Knockout of histone methyltransferases Suv39h1 and Suv39h2 increases the telomere length in murine cells, whereas downregulation of SUV39H1 and SUV39H2 genes decreases the telomere length in human cells, suggesting that telomere biology is different among mammalian species. However, epigenetic regulation of the telomere has not been s...

  20. Single Stem Cell Imaging and Analysis Reveals Telomere Length Differences in Diseased Human and Mouse Skeletal Muscles

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    Elisia D. Tichy

    2017-10-01

    Full Text Available Muscle stem cells (MuSCs contribute to muscle regeneration following injury. In many muscle disorders, the repeated cycles of damage and repair lead to stem cell dysfunction. While telomere attrition may contribute to aberrant stem cell functions, methods to accurately measure telomere length in stem cells from skeletal muscles have not been demonstrated. Here, we have optimized and validated such a method, named MuQ-FISH, for analyzing telomere length in MuSCs from either mice or humans. Our analysis showed no differences in telomere length between young and aged MuSCs from uninjured wild-type mice, but MuSCs isolated from young dystrophic mice exhibited significantly shortened telomeres. In corroboration, we demonstrated that telomere attrition is present in human dystrophic MuSCs, which underscores its importance in diseased regenerative failure. The robust technique described herein provides analysis at a single-cell resolution and may be utilized for other cell types, especially rare populations of cells.

  1. Single Stem Cell Imaging and Analysis Reveals Telomere Length Differences in Diseased Human and Mouse Skeletal Muscles.

    Science.gov (United States)

    Tichy, Elisia D; Sidibe, David K; Tierney, Matthew T; Stec, Michael J; Sharifi-Sanjani, Maryam; Hosalkar, Harish; Mubarak, Scott; Johnson, F Brad; Sacco, Alessandra; Mourkioti, Foteini

    2017-10-10

    Muscle stem cells (MuSCs) contribute to muscle regeneration following injury. In many muscle disorders, the repeated cycles of damage and repair lead to stem cell dysfunction. While telomere attrition may contribute to aberrant stem cell functions, methods to accurately measure telomere length in stem cells from skeletal muscles have not been demonstrated. Here, we have optimized and validated such a method, named MuQ-FISH, for analyzing telomere length in MuSCs from either mice or humans. Our analysis showed no differences in telomere length between young and aged MuSCs from uninjured wild-type mice, but MuSCs isolated from young dystrophic mice exhibited significantly shortened telomeres. In corroboration, we demonstrated that telomere attrition is present in human dystrophic MuSCs, which underscores its importance in diseased regenerative failure. The robust technique described herein provides analysis at a single-cell resolution and may be utilized for other cell types, especially rare populations of cells. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Leukocyte telomere length is inversely associated with post-load but not with fasting plasma glucose levels.

    Science.gov (United States)

    Khalangot, Mykola; Krasnienkov, Dmytro; Vaiserman, Alexander; Avilov, Ivan; Kovtun, Volodymir; Okhrimenko, Nadia; Koliada, Alexander; Kravchenko, Victor

    2017-04-01

    Type 2 diabetes mellitus is characterized by shorter leukocyte telomere length, but the relationship between leukocyte telomere length and type 2 diabetes mellitus development is rather questioned. Fasting and post-load glycaemia associated with different types of insulin resistance and their relation with leukocyte telomere length remains unknown. We compared leukocyte telomere length and fasting or post-load glucose levels in persons who do not receive glucose lowering treatment. For 82 randomly selected rural residents of Ukraine, aged 45+, not previously diagnosed with type 2 diabetes mellitus, the WHO oral glucose tolerance test and anthropometric measurements were performed. Leukocyte telomere length was measured by standardized method of quantitative monochrome multiplex polymerase chain reaction in real time. Spearman's or Pearson's rank correlation was used for correlation analysis between fasting plasma glucose or 2-h post-load plasma glucose levels and leukocyte telomere length. Logistical regression models were used to evaluate risks of finding short or long telomeres associated with fasting plasma glucose or 2-h post-load plasma glucose levels. No association of fasting plasma glucose and leukocyte telomere length was revealed, whereas 2-h post-load plasma glucose levels demonstrated a negative correlation ( P fasting plasma glucose and 2-h post-load plasma glucose (NGT, n = 33); diabetes mellitus (DM), n = 18 and impaired fasting glucose/tolerance (IFG/IGT, n = 31) levels. A correlation relationship between leukocyte telomere length and 2-h post-load plasma glucose level in NGT; IFG/IGT and DM groups ( P = 0.027; 0.029 and 0.049, respectively) was revealed; the association between leukocyte telomere length and fasting plasma glucose was confirmed in DM group only ( P = 0.009). Increase of 2-h post-load plasma glucose (but not fasting plasma glucose) level improves the chances of revealing short telomeres: OR 1.52 (95% CI 1

  3. The effects of vitamin C supplementation on pre-eclampsia in Mulago Hospital, Kampala, Uganda: a randomized placebo controlled clinical trial

    OpenAIRE

    Kiondo, Paul; Wamuyu-Maina, Gakenia; Wandabwa, Julius; Bimenya, Gabriel S; Tumwesigye, Nazarius Mbona; Okong, Pius

    2014-01-01

    Background Oxidative stress plays a role in the pathogenesis of pre-eclampsia. Supplementing women with antioxidants during pregnancy may reduce oxidative stress and thereby prevent or delay the onset pre-eclampsia. The objective of this study was to evaluate the effect of supplementing vitamin C in pregnancy on the incidence of pre-eclampsia, at Mulago hospital, Kampala, Uganda. Methods This was a (parallel, balanced randomization, 1:1) placebo randomized controlled trial conducted at Mulago...

  4. Mother–offspring and nest-mate resemblance but no heritability in early-life telomere length in white-throated dippers

    OpenAIRE

    Becker, Philipp J. J.; Reichert, Sophie; Zahn, Sandrine; Hegelbach, Johann; Massemin, Sylvie; Keller, Lukas F; Postma, Erik; Criscuolo, François

    2015-01-01

    Telomeres are protective DNA–protein complexes located at the ends of eukaryotic chromosomes, whose length has been shown to predict life-history parameters in various species. Although this suggests that telomere length is subject to natural selection, its evolutionary dynamics crucially depends on its heritability. Using pedigree data for a population of white-throated dippers (Cinclus cinclus), we test whether and how variation in early-life relative telomere length (RTL, measured as the n...

  5. Alternative magnesium sulphate regimens for women with pre-eclampsia and eclampsia.

    Science.gov (United States)

    Duley, Lelia; Matar, Hosam E; Almerie, Muhammad Qutayba; Hall, David R

    2010-08-04

    Magnesium sulphate remains the drug of choice for both prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but have not yet been formally evaluated. To assess the comparative effects of alternative regimens for the administration of magnesium sulphate when used for the care of women with pre-eclampsia or eclampsia, or both. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2010). Randomised trials comparing different regimens for administration of magnesium sulphate used for the care of women with pre-eclampsia or eclampsia, or both. All four review authors assessed trial quality and extracted data independently. We identified 17 studies of which six (866 women) met the inclusion criteria: two trials (451 women) compared regimens for women with eclampsia and four (415 women) for women with pre-eclampsia.Treatment of eclampsia: one trial compared loading dose alone with loading dose plus maintenance therapy for 24 hours (401 women). There was no clear difference between the groups in the risk ratio (RR) of recurrence of convulsions (RR 1.13, 95% confidence interval (CI) 0.42 to 3.05) or stillbirth (RR 1.13, 95% CI 0.66 to 1.92), and the CIs are wide. One trial compared a low dose regimen with a standard dose regimen over 24 hours (50 women). This study was too small for any reliable conclusions about the comparative effects.Prevention of eclampsia: one trial compared intravenous with intramuscular maintenance regimen for 24 hours (17 women). This trial was too small for any reliable conclusions. Three trials compared short maintenance regimens postpartum with continuing for 24 hours after the birth (398 women), even taken together these trials were too small for any reliable conclusions. Although strong evidence supports the use of magnesium sulphate for prevention and treatment of eclampsia, trials comparing alternative treatment regimens are too small for reliable

  6. Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth

    Directory of Open Access Journals (Sweden)

    Kai P. Law

    2015-05-01

    Full Text Available Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered.

  7. Can first trimester placental protein-13 and pregnancy-associated plasma protein-A predict pre-eclampsia in Turkish women?

    Science.gov (United States)

    Ceylan, N; Ozaksit, G; Unlu, B S; Yildiz, Y; Yilmaz, S; Agaca, F

    2014-08-01

    The aim of study was to evaluate placental protein-13 (PP-13) and pregnancy-associated plasma protein-A (PAPP-A) in first trimester maternal serum, for predicting pre-eclampsia. A prospective case-control study included 30 pre-eclampsia patients and 90 control pregnant women. Pre-eclampsia patients were divided into two subgroups: early- and late-onset (9 vs 21), and PP-13 and PAPP-A levels were compared between the groups and the comparison of risks for pre-eclampsia were calculated. Results showed that there was a significant inverse correlation between PAPP-A and late pre-eclampsia (p = 0.003), with a cut-off value of 0.805 (ROC analysis area under curve = 0.751). There was a significant reverse correlation between PAPP-A and early pre-eclampsia (p = 0.02). There was no significant relationship between PP-13 and early pre-eclampsia, nor with late pre-eclampsia (p = 0.7, p = 0.6, respectively). It was concluded that neither of these markers can serve as a sufficient and reliable screening test of pre-eclampsia because of inadequate sensitivity in the Turkish pregnant population.

  8. Isolated proteinuria is a risk factor for pre-eclampsia: a retrospective analysis of the maternal and neonatal outcomes in women presenting with isolated gestational proteinuria.

    Science.gov (United States)

    Shinar, S; Asher-Landsberg, J; Schwartz, A; Ram-Weiner, M; Kupferminc, M J; Many, A

    2016-01-01

    To examine maternal and neonatal outcomes of isolated proteinuria and define maternal characteristics for progression to pre-eclampsia. Retrospective cohort study. Data from all hospitalized pregnant women between 2009 and 2014 with new onset isolated proteinuria of over 300 mg/24 h at admission were obtained. Follow-up was performed from the time of admission to the hospital to the time of discharge postpartum. Obstetrical, maternal and neonatal outcomes were obtained. Ninety-five pregnant women diagnosed with new onset isolated proteinuria were followed to term. Thirteen women developed pre-eclampsia during pregnancy and eight developed pre-eclampsia postpartum. Maternal characteristics for progression to pre-eclampsia were greater maximal values of proteinuria. Earlier pre-eclampsia onset was associated with early-onset proteinuria and multiple gestation. Although greater values of proteinuria were associated with increased risk for intrauterine growth restriction and lower Apgar scores, maternal outcome was favorable, regardless of pre-eclampsia progression. Isolated proteinuria progressing to pre-eclampsia was associated with late pre-eclampsia onset and favorable maternal and neonatal outcomes. A significant proportion of women with new onset isolated proteinuria will develop pre-eclampsia. In these women, close follow-up is recommended until after delivery.

  9. C3F gene mutation is involved in the susceptibility to pre-eclampsia.

    Science.gov (United States)

    Rhim, Mohamed Salah; Meddeb, Sawsen; Kaabia, Ons; Jalloul, Mohamed; Sakouhi, Mohamed; Jrzad, Besma Bel Hadj; Felah, Raja

    2015-05-01

    The aim of this study was to analyze the functional polymorphism of exon 3 of the gene of complement component C3 (rs 2230199) to identify the potential involvement of the mutated gene C3F in the genesis of pre-eclampsia. It is a comparative case-control study conducted in the university center of maternity and neonatology of Monastir with collaboration of high institute of biotechnology (Tunisia) on a period of 2 years. Two hundred and fifty patients and 96 newborns divided into pre-eclampsia group (150 parturients with pre-eclampsia and 48 newborns) and control group (100 parturients with normal pregnancy and their 48 infants) are taken. Each patient and control were sampled for the phenotypic study and the molecular analysis. The ARMS-PCR (amplification refractory mutation system) was the standard procedure in our study. A simple observation let to distinguish three cases of genotypes: SS, FF and SF. In the control group, 56% of parturients had the genotype SS, 38%, the genotype SF and 6%, FF genotype. In the pre-eclamptic population, SS, SF, and FF genotypes were determined, respectively, 40, 45.30 and 14.60% of the patients. There is a sharp increase in the frequency of the FF genotype in pre-eclamptic patients compared to controls (14.60 vs. 6%). The difference was statistically significant (p = 0.01). The frequencies of C3S and alleles C3F determined in controls (respectively, 74 and 26%) were different from those identified in pre-eclamptic patients (respectively, 62.60 and 37.30%). This difference was statistically significant (p = 0.005). The C3S and C3F allele frequencies determined in control newborns (respectively, 83.33 and 16.66%) were slightly different from those identified in newborn issued from pre-eclamptic patients (respectively, 80.2 and 19.79%), but the difference was not statistically significant (p = 0.67). The gene polymorphism of complement component C3 was significantly associated with the onset of pre-eclampsia. These results should be

  10. Community health worker knowledge and management of pre-eclampsia in rural Karnataka State, India.

    Science.gov (United States)

    Ramadurg, Umesh; Vidler, Marianne; Charanthimath, Umesh; Katageri, Geetanjali; Bellad, Mrutyunjaya; Mallapur, Ashalata; Goudar, Shivaprasad; Bannale, Shashidhar; Karadiguddi, Chandrashekhar; Sawchuck, Diane; Qureshi, Rahat; von Dadelszen, Peter; Derman, Richard

    2016-09-30

    In India, the hypertensive disorders of pregnancy and postpartum haemorrhage are responsible for nearly 40 % of all maternal deaths. Most of these deaths occur in primary health settings which frequently lack essential equipment and medication, are understaffed, and have limited or no access to specialist care. Community health care workers are regarded as essential providers of basic maternity care; and the quality of care they provide is dependent on the level of knowledge and skills they possess. However, there is limited research regarding their ability to manage pregnancy complications. This study aims to describe the current state of knowledge regarding pre-eclampsia and eclampsia among community health care workers (auxiliary nurse midwives, accredited social health activists, staff nurses) in northern Karnataka, India. Furthermore, this study describes the treatment approaches used by various cadres of community health workers for these conditions. The findings of this study can help plan focussed training sessions to build upon their strengths and to address the identified gaps. Data were collected as part of a larger study aimed at assessing the feasibility of community-based treatment for pre-eclampsia. Eight focus group discussions were conducted in 2012-2013 in northern Karnataka State: four with staff nurses and auxiliary nurse midwives and four with accredited social health activists. In addition, twelve auxiliary nurse midwives and staff nurses completed questionnaires to explore their competence and self-efficacy in managing pre-eclampsia. Qualitative data were audio-recorded, transcribed verbatim and translated for thematic analysis using NVivo 10. Community health workers described their understanding of the origins of hypertension and seizures in pregnancy. Psychological explanations of hypertension were most commonly reported: stress, tension, and fear. The most common explanation for eclampsia was not receiving a tetanus vaccination. Despite

  11. Relation between Leukocyte Telomere Length and Incident Coronary Heart Disease Events (From the 1995 Canadian Nova Scotia Health Survey)

    Science.gov (United States)

    Ye, Siqin; Shaffer, Jonathan A.; Kang, Min Suk; Harlapur, Manjunath; Muntner, Paul; Epel, Elissa; Guernsey, Duane; Schwartz, Joseph E.; Davidson, Karina W.; Kirkland, Susan; Honig, Lawrence S.; Shimbo, Daichi

    2013-01-01

    Leukocyte telomere length has been proposed as a biomarker of cellular aging and atherosclerosis. We sought to determine whether leukocyte telomere length is independently associated with incident coronary heart disease (CHD) in the general population. Telomere length was measured using a polymerase chain reaction method for participants enrolled in the 1995 Nova Scotia Health Survey (n=1,917). The primary endpoint was first occurrence of fatal and non-fatal CHD events. During a mean follow-up of 8.7 years, 164 fatal or non-fatal CHD events occurred. Compared to participants in the longest tertile of telomere length, those in the middle and shortest tertiles had increased incidence of CHD events (6.2, 11.2 and 12.2 per 1000 person-years, respectively). After adjustment for demographics, traditional risk factors and inflammatory markers including hs-CRP, IL-6, and sICAM-1, those in the middle tertile had significantly elevated risk for incident CHD (hazard ratio [HR] 1.63, 95% CI 1.07–2.51, p=0.02) compared to the longest tertile, whereas the risk for those in the shortest tertile was non-significantly elevated (HR 1.25, 95% CI 0.82–1.90, p=0.30). In conclusion, these findings do not support a linear association between leukocyte telomere length and incident CHD risk in the general population. PMID:23375186

  12. Associations of cadmium and lead exposure with leukocyte telomere length: findings from National Health and Nutrition Examination Survey, 1999-2002

    National Research Council Canada - National Science Library

    Zota, Ami R; Needham, Belinda L; Blackburn, Elizabeth H; Lin, Jue; Park, Sung Kyun; Rehkopf, David H; Epel, Elissa S

    2015-01-01

    Cadmium and lead are ubiquitous environmental contaminants that might increase risks of cardiovascular disease and other aging-related diseases, but their relationships with leukocyte telomere length (LTL...

  13. Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout.

    Science.gov (United States)

    Vazirpanah, N; Kienhorst, L B E; Van Lochem, E; Wichers, C; Rossato, M; Shiels, P G; Dalbeth, N; Stamp, L K; Merriman, T R; Janssen, M; Radstake, T R D J; Broen, J Ca

    2017-07-01

    Chronic inflammation associates with increased senescence, which is a strong predictor for cardiovascular disease. We hypothesised that inflammation accelerates senescence and thereby enhances the risk of cardiovascular disease in gout. We assessed replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 Dutch patients with gout and 273 healthy individuals and validated our results in 474 patients with gout and 293 healthy participants from New Zealand. Subsequently, we investigated the effect of cardiovascular disease on TL of all participants. Also, we measured TL of CD4+ and CD8+ T lymphocytes, B lymphocytes, monocytes, natural killer cells and plasmacytoid dendritic cells. Additionally, we assessed the potential temporal difference in TL and telomerase activity. TL in PBMCs of healthy donors decreased over time, reflecting normal ageing. Patients with gout demonstrated shorter telomeres (p=0.001, R2=0.01873). In fact, the extent of telomere erosion in patients with gout was higher at any age compared with healthy counterparts at any age (pgout with cardiovascular disease had the shortest telomeres and TL was an independent risk factor for cardiovascular disease in patients with gout (p=0.001). TL was inversely associated with the number of gouty flares (p=0.005). Patients with gout have shorter telomeres than healthy participants, reflecting increased cellular senescence. Telomere shortening was associated with the number of flares and with cardiovascular disease in people with gout. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Risky family processes prospectively forecast shorter telomere length mediated through negative emotions.

    Science.gov (United States)

    Brody, Gene H; Yu, Tianyi; Shalev, Idan

    2017-05-01

    This study was designed to examine prospective associations of risky family environments with subsequent levels of negative emotions and peripheral blood mononuclear cell telomere length (TL), a marker of cellular aging. A second purpose was to determine whether negative emotions mediate the hypothesized link between risky family processes and diminished telomere length. Participants were 293 adolescents (age 17 years at the first assessment) and their primary caregivers. Caregivers provided data on risky family processes when the youths were age 17 years, youths reported their negative emotions at age 18 years, and youths' TL was assayed from a blood sample at age 22 years. The results revealed that (a) risky family processes forecast heightened negative emotions (β = .316, p emotions forecast shorter TL (β = -.187, p = .012), and (c) negative emotions served as a mediator connecting risky family processes with diminished TL (indirect effect = -0.012, 95% CI [-0.036, -0.002]). These findings are consistent with the hypothesis that risky family processes presage premature cellular aging through effects on negative emotions, with potential implications for lifelong health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. Genomics, Telomere Length, Epigenetics, and Metabolomics in the Nurses' Health Studies.

    Science.gov (United States)

    Townsend, Mary K; Aschard, Hugues; De Vivo, Immaculata; Michels, Karin B; Kraft, Peter

    2016-09-01

    To review the contribution of the Nurses' Health Study (NHS) and NHS II to genomics, epigenetics, and metabolomics research. We performed a narrative review of the publications of the NHS and NHS II between 1990 and 2016 based on biospecimens, including blood and tumor tissue, collected from participants. The NHS has contributed to the discovery of genetic loci influencing more than 45 complex human phenotypes, including cancers, diabetes, cardiovascular disease, reproductive characteristics, and anthropometric traits. The combination of genomewide genotype data with extensive exposure and lifestyle data has enabled the evaluation of gene-environment interactions. Furthermore, data suggest that longer telomere length increases risk of cancers not related to smoking, and that modifiable factors (e.g., diet) may have an impact on telomere length. "Omics" research in the NHS continues to expand, with epigenetics and metabolomics becoming greater areas of focus. The combination of prospective biomarker data and broad exposure information has enabled the NHS to participate in a variety of "omics" research, contributing to understanding of the epidemiology and biology of multiple complex diseases.

  16. Telomere length is associated with sleep duration but not sleep quality in adults with human immunodeficiency virus.

    Science.gov (United States)

    Lee, Kathryn A; Gay, Caryl; Humphreys, Janice; Portillo, Carmen J; Pullinger, Clive R; Aouizerat, Bradley E

    2014-01-01

    Telomere length provides an estimate of cellular aging and is influenced by oxidative stress and health behaviors such as diet and exercise. This article describes relationships between telomere length and sleep parameters that included total sleep time (TST), wake after sleep onset (WASO), and self-reported sleep quality in a sample of adults with chronic illness. Cross-sectional study of 283 adults (74% male, 42% Caucasian) infected with human immunodeficiency virus (HIV) while living in the San Francisco Bay area, CA, USA. Ages ranged from 22-77 y. TST and WASO were estimated with wrist actigraphy across 72 h; self-reported sleep quality was assessed with the Pittsburgh Sleep Quality Index. Relative telomere length (RTL) in leukocytes was estimated by quantitative polymerase chain reaction assays. Shorter RTL was associated with older age, and RTL was shorter in males than females. RTL was unrelated to HIV disease characteristics. RTL was not associated with WASO or self-reported sleep quality. Participants with at least 7 h sleep had longer RTL than those with less than 7 h, even after controlling for the effects of age, sex, race, education, body mass index, metabolic hormones (i.e., leptin, ghrelin, adiponectin, and resistin), depression and anxiety, and sleep quality. Results suggest that sleep duration is associated with preserving telomere length in a population of human immunodeficiency virus-infected adults. Getting at least 7 hours of sleep at night may either protect telomeres from damage or restore them on a nightly basis.

  17. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

    Science.gov (United States)

    Walsh, Kyle M.; Codd, Veryan; Rice, Terri; Nelson, Christopher P.; Smirnov, Ivan V.; McCoy, Lucie S.; Hansen, Helen M.; Elhauge, Edward; Ojha, Juhi; Francis, Stephen S.; Madsen, Nils R.; Bracci, Paige M.; Pico, Alexander R.; Molinaro, Annette M.; Tihan, Tarik; Berger, Mitchel S.; Chang, Susan M.; Prados, Michael D.; Jenkins, Robert B.; Wiemels, Joseph L.; Samani, Nilesh J.; Wiencke, John K.; Wrensch, Margaret R.

    2015-01-01

    Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82×10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48×10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83×10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis. PMID:26646793

  18. Telomerase activity is increased and telomere length shortened in T cells from blood of patients with atopic dermatitis and psoriasis

    DEFF Research Database (Denmark)

    Wu, Kehuai; Higashi, H; Hansen, E R

    2000-01-01

    We studied telomerase activity and telomere length in PBMC and purified CD4(+) and CD8(+) T cells from blood obtained from a total of 32 patients with atopic dermatitis, 16 patients with psoriasis, and 30 normal controls. The telomerase activity was significantly increased in PBMC from the patients...... compared with PBMC from normal donors. This increase was most pronounced in the subpopulation of CD4(+) T cells, which were significantly above the activity of the CD8(+) T cells in atopic dermatitis, psoriasis patients, and control persons. The telomere length was significantly reduced in all T cell...... subsets from both atopic dermatitis and psoriasis patients compared with normal individuals. Furthermore, the telomere length was found to be significantly shorter in CD4(+) memory T cells compared with the CD4(+) naive T cells, and both of the cell subsets from diseases were shown to be of significantly...

  19. Intake of vitamin C and E in pregnancy and risk of pre-eclampsia: prospective study among 57 346 women

    DEFF Research Database (Denmark)

    Klemmensen, Ak; Tabor, A; Østerdal, M L

    2009-01-01

    OBJECTIVE: It has been suggested that vitamin C, alone or in combination with vitamin E, may protect against pre-eclampsia, whereas the safety of high-dose vitamin E supplements has been questioned. We investigated dietary intakes of vitamins C and E to see if they correlated with the incidence...... of pre-eclampsia. DESIGN: Prospective cohort study. SETTING: The Danish National Birth Cohort; a population-based pregnancy cohort; analyses were based on 57 346 pregnancies. METHODS: Vitamin intake was estimated from a food frequency questionnaire completed in gestational week 25, recording intake from...... OUTCOME MEASURES: A small increase in the incidence of severe disease was also seen in the group of women (64, n = 49 373) with a high intake of vitamin E from supplements and dietary sources. RESULTS: The incidence of 'pre-eclampsia (all types)' did not correlate with dietary vitamin C and E intake...

  20. [Long noncoding RNA HOTAIR modulates the function of trophoblast cells in pre-eclampsia].

    Science.gov (United States)

    Zou, Yan-fen; Sun, Li-zhou

    2015-01-01

    To investigate the expression of long noncoding RNA (lncRNA) HOTAIR in pre-eclampsia (PE) placentas and its effect on trophoblast cells proliferation, invasion, and apoptosis. The expression of HOTAIR was determined by qPCR for 23 severe PE and 23 normal pregnant women. qRT-PCR was used to detect the efficiency of overexpression and knock-down after the HTR-8/SVneo cells were transfected with HOTAIR overexpression and siRNAs targeting HOTAIR for 24-48 h, respectively. MTT and colony formation assays were used to test the proliferation of HTR-8/SVneo cells transfected. Transwell assay was used to show the migration and invasion ability of HTR-8/SVneo cells transfected. Flow cytometry assay was used to detect the cell apoptosis rate after treatment. Western blot assay was applied to detect the expression level of apoptotic proteins Caspase-3 and BCL-2. The level of HOTAIR in severe pre-eclampsia groups was significantly increased compared to normal pregnant placentas (Papoptosis rate in cells transfected with HOTAIR overexpression was apparently more than that of control, while less in cells treated with si-HOTAIR. Western blot assay showed that the Caspase-3 showed an obvious increase in HOTAIR overexpression group while decreased in si-HOTAIR group. And BCL-2 presented an opposite trend. HOTAIR is probably involved in the onset of preeclampsia by regulating proliferation, invasion and apoptosis of trophoblast cells.

  1. Risk factors for pre-eclampsia/eclampsia among working women in Mexico City.

    Science.gov (United States)

    Cerón-Mireles, P; Harlow, S D; Sánchez-Carrillo, C I; Núñez, R M

    2001-01-01

    This study examined risk factors for pre-eclampsia/eclampsia in a population-based sample of pregnant working women in Mexico City. Over a 3-month period, all women who gave birth at three major hospitals and who had worked for at least 3 months during pregnancy were interviewed. After excluding mothers with multiple gestations or infants with birth defects, and previous diagnoses of hypertension, chronic renal disease or diabetes, 131 of 2,436 women (5.4%) had been diagnosed with pre-eclampsia and/or eclampsia. The frequency was much higher among women of low socio-economic status: 12% of uninsured women (SSA) compared with 4.2% of private sector employees (IMSS) and 1.3% of public sector employees (ISSSTE). After adjusting for education, women working in services (OR = 1.68, 95% CI = 1.01, 2.81) and in retail (OR = 1.99, 95% CI = 1.18, 3.37), primiparae (OR = 2.64, 95% CI = 1.65, 4.21) and women whose pregestational weight was > or = 55 kg (OR = 2.02, 95% CI = 1.34, 3.04) were at increased risk. Efforts to develop and evaluate intervention programmes should target hospitals serving the uninsured (SSA) if reduction in the number of preventable maternal deaths in Mexico is to be achieved. Such programmes should also target service and retail workers and identify women with poor glycaemic control early in pregnancy.

  2. Wiedemann-Rautenstrauch (neonatal progeroid) syndrome: new case with normal telomere length in skin fibroblasts.

    Science.gov (United States)

    Korniszewski, L; Nowak, R; Oknińska-Hoffmann, E; Skórka, A; Gieruszczak-Białek, D; Sawadro-Rochowska, M

    2001-10-01

    Wiedemann-Rautenstrauch (neonatal progeroid) syndrome is an autosomal recessive condition with characteristic appearance of premature aging present at birth (aged face, natal teeth, and wrinkled skin). Other features of the syndrome are generalized lipoatrophy with specific fat accumulation in the lateral suprabuttock region, hypotrichosis, macrocephaly (pseudohydrocephalus), and mental retardation. We report on a new case that demonstrates all typical features of the syndrome. The girl is now 16 years and 10 months old and has had follow-up from birth. We measured terminal restriction fragment (TRF) length to evaluate whether the patient's premature aging process is accompanied by shortening of telomere length in her cultured fibroblasts. Mean TRF of 13.5 kb found in our patient's fibroblasts is not shortened as compared to that of normal fibroblasts. Our results differ from those observed in Hutchinson-Gilford progeria. Copyright 2001 Wiley-Liss, Inc.

  3. A COMPARATIVE STUDY OF PERINATAL OUTCOME IN WOMEN WITH RECURRENT PREECLAMPSIA TO WOMEN WITH PRE-ECLAMPSIA WHO WERE NORMOTENSIVE DURING THEIR PREVIOUS PREGNANCIES

    Directory of Open Access Journals (Sweden)

    Beena Guhan

    2016-08-01

    Full Text Available BACKGROUND AND OBJECTIVE Pre-eclampsia is a systemic syndrome that occurs in 3-5% of the pregnant women and is the leading cause of maternal/neonatal morbidity and mortality. We designed a study to compare perinatal outcome in women with recurrent preeclampsia to women with women with pre-eclampsia who were normotensive during their previous pregnancies. MATERIALS AND METHODS This study was conducted in Dept. of Obstetrics and Gynaecology, Institute of Maternal and Child Health, Government Medical College, Kozhikode for a period of 1 year from March 2013 to February 2014. We conducted this study in multiparous women who developed pre-eclampsia in index pregnancy (n=110. Among these, women who had pre-eclampsia in previous pregnancies (n=55 were compared to those who remained normotensive during their prior pregnancies (n=55. Maternal and foetal variables were compared. Multivariate logistic analyses were performed to examine the impact of pre-eclampsia on foetal outcome, preterm delivery, IUGR, still births adjusted for confounding variables. RESULTS No statistical significant difference was observed between the 2 groups in terms of age, gravida, parity. Women who experienced recurrent pre-eclampsia were at elevated risk for early onset of pre-eclampsia, deranged laboratory investigations (Hepatic and Renal parameters, Coagulation Profile, higher chances of maternal complications, foetal mortality and morbidity (Statistically significant P <0.05. Foetal loss was higher in women with recurrent pre-eclampsia (14.5% than in women with pre-eclampsia who had normotensive pregnancy history (1.8%. CONCLUSION Women with recurrent pre-eclampsia had a higher rate of perinatal loss compared to women with pre-eclampsia who were normotensive in their prior pregnancies.

  4. Short communication: Telomere lengths in different tissues of dairy cows during early and late lactation.

    Science.gov (United States)

    Laubenthal, L; Hoelker, M; Frahm, J; Dänicke, S; Gerlach, K; Südekum, K-H; Sauerwein, H; Häussler, S

    2016-06-01

    Telomeres create a protective cap on the ends of chromosomes that shorten with cell division and are influenced by stressful conditions. With the onset of lactation, high-yielding dairy cows are exposed to metabolic stress. In the present study, we aimed to analyze telomere length (TL) in key metabolic organs, such as liver, subcutaneous (sc) adipose tissue (AT), and mammary gland, as well as in peripheral blood cells during early and late lactation in German Holstein cows (n=21). Animals were fed according to their requirement, and biopsies from scAT, liver, and mammary gland as well as blood cells were collected in early and late lactation. The relative quantity of telomere products (qT), which is proportional to the average TL, was determined in genomic DNA by multiplex quantitative PCR. In this study, relative qT varied widely in the investigated tissues and blood. In late lactation, slowly proliferating tissues, such as liver and scAT, had the highest qT, whereas peripheral blood cells and in the mammary gland had the lowest qT. Comparing early with late lactation, relative qT attrition was limited to blood and mammary gland. Relationships between relative qT in blood, mammary gland, scAT, and liver suggest that blood qT might serve as a surrogate marker for tissue-specific qT. Cows with high initial qT in tissues and blood in early lactation had greater qT attrition during the course of lactation than cows with lower qT. The determination of qT could be included when phenotyping dairy cattle to test for associations with performance and fitness traits. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. A common variant in the telomerase RNA component is associated with short telomere length.

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    Omer T Njajou

    2010-09-01

    Full Text Available Telomeres shorten as cells divide. This shortening is compensated by the enzyme telomerase. We evaluated the effect of common variants in the telomerase RNA component (TERC gene on telomere length (TL in the population-based Health Aging and Body Composition (Health ABC Study and in two replication samples (the TwinsUK Study and the Amish Family Osteoporosis Study, AFOS.Five variants were identified in the TERC region by sequence analysis and only one SNP was common (rs2293607, G/A. The frequency of the G allele was 0.26 and 0.07 in white and black, respectively. Testing for association between TL and rs2293607 was performed using linear regression models or variance component analysis conditioning on relatedness among subjects.The adjusted mean TL was significantly shorter in 665 white carriers of the G allele compared to 887 non-carriers from the Health ABC Study (4.69±0.05 kbp vs. 4.86±0.04 kbp, measured by quantitative PCR, p = 0.005. This association was replicated in another white sample from the TwinsUK Study (6.90±0.03 kbp in 301 carriers compared to 7.06±0.03 kbp in 395 non-carriers, measured by Southern blots, p = 0.009. A similar pattern of association was observed in whites from the family-based AFOS and blacks from the Health ABC cohort, although not statistically significant, possibly due to the lower allele frequency in these populations. Combined analysis using 2,953 white subjects from 3 studies showed a significant association between TL and rs2293607 (β = -0.19±0.04 kbp, p = 0.001.Our study shows a significant association between a common variant in TERC and TL in humans, suggesting that TERC may play a role in telomere homeostasis.

  6. Divergence of sperm and leukocyte age-dependent telomere dynamics: implications for male-driven evolution of telomere length in humans

    OpenAIRE

    Aston, Kenneth I; Hunt, Steven C.; Susser, Ezra; Kimura, Masayuki; Factor-Litvak, Pam; Carrell, Douglas; Aviv, Abraham

    2012-01-01

    Telomere length (TL) dynamics in vivo are defined by TL and its age-dependent change, brought about by cell replication. Leukocyte TL (LTL), which reflects TL in hematopoietic stem cells (HSCs), becomes shorter with age. In contrast, sperm TL, which reflects TL in the male germ cells, becomes longer with age. Moreover, offspring of older fathers display longer LTL. Thus far, no study has examined LTL and sperm TL relations with age in the same individuals, nor considered their implications fo...

  7. Health workers' knowledge on future vascular disease risk in women with pre-eclampsia in south western Nigeria.

    Science.gov (United States)

    Adekanle, D A; Adeyemi, A S; Olowookere, S A; Akinleye, C A

    2015-10-16

    Pre-eclampsia progressing to eclampsia is one of the major causes of maternal death in Nigeria. Since there is long term association of pre-eclampsia with cardiovascular disease, cerebrovascular disease, renal disease, short life expectancy and mortality, it is essential to obtain obstetric history for better counseling and long term monitoring. The study assessed the knowledge of health workers about the association of pre-eclampsia with future cardiovascular disease and offering any risk-reduction counseling to women with pre-eclampsia. During a training workshop, a validated questionnaire on the association between pre-eclampsia and cardiovascular risk was distributed among health care workers working at the infant welfare and family planning clinics in Osun State. Data were analysed using descriptive and inferential statistics. One hundred and forty-six out of 150 health workers approached participated in the study (response rate 97.3%). Mean age of respondents was 35.6 ± 9.1 years. Median age of practice was 7 years, ranging from 1-40 years. They were medical doctors (60.3%), community health workers (26.7%) and nurses/midwives (13.0%). Most participants had good knowledge on future cardiovascular risk of pre-eclampsia. The medical doctors had better knowledge compared to nurses/midwives and community health workers (78.4 vs. 57.9 vs. 53.8%; p workers. Risk reduction counseling was quite low across all the health workers. There is need for continuous medical education and possible review of the training curriculum of the lower cadres of health workers.

  8. Telomerase activity is increased and telomere length shortened in T cells from blood of patients with atopic dermatitis and psoriasis

    DEFF Research Database (Denmark)

    Wu, Kehuai; Higashi, N; Hansen, E R

    2000-01-01

    We studied telomerase activity and telomere length in PBMC and purified CD4(+) and CD8(+) T cells from blood obtained from a total of 32 patients with atopic dermatitis, 16 patients with psoriasis, and 30 normal controls. The telomerase activity was significantly increased in PBMC from the patients......(+) T cell subsets from normal donors. In conclusion, the increased telomerase activity and shortened telomere length indicates that T lymphocytes in atopic dermatitis and psoriasis are chronically stimulated and have an increased cellular turnover in vivo....

  9. Telomere length differences between subcutaneous and visceral adipose tissue in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lakowa, Nicole; Trieu, Nhu; Flehmig, Gesine [Department of Medicine, University of Leipzig, Leipzig (Germany); Lohmann, Tobias [Municipal Clinic Dresden-Neustadt, Dresden (Germany); Schön, Michael R. [Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe (Germany); Dietrich, Arne [Department of Surgery, University of Leipzig, Leipzig (Germany); IFB AdiposityDiseases, University of Leipzig, Leipzig (Germany); Zeplin, Philip Helge; Langer, Stefan [Department of Orthopaedics, Traumatology and Plastic Surgery, University of Leipzig, Leipzig (Germany); Stumvoll, Michael; Blüher, Matthias [Department of Medicine, University of Leipzig, Leipzig (Germany); Klöting, Nora, E-mail: nora.kloeting@medizin.uni-leipzig.de [IFB AdiposityDiseases, Junior Research Group 2 “Animal Models of Obesity”, University of Leipzig, Leipzig (Germany)

    2015-02-13

    Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF). We further asked whether AT TL is related to age, anthropometric and metabolic traits. TL was analyzed by quantitative PCR in total human genomic DNA isolated from paired subcutaneous and visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in isolated small and large adipocytes and SVF cells. We find significantly shorter TL in subcutaneous compared to visceral AT (P < 0.001) which is consistent in men and subgroups of lean and obese, and individuals with or without type 2 diabetes (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to visceral AT (P < 0.01). SAT TL is most strongly correlated with age (r = −0.205, P < 0.05) and independently of age with HbA1c (r = −0.5, P < 0.05). We found significant TL differences between superficial SAT of lean and obese as well as between individuals with our without T2D, but not between the two layers of SAT. Our data indicate that fat depot differences in TL mainly reflect shorter TL of SVF cells. In addition, we found an age and BMI-independent relationship between shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the regenerative capacity of AT more strongly than obesity alone. - Highlights: • Telomere lengths (TL) differ between fat depots mainly due to different lengths in SVF. • TL is not associated with gender, BMI and T2D. • The tendency for

  10. The relationship between leukocyte mitochondrial DNA copy number and telomere length in community-dwelling elderly women.

    Directory of Open Access Journals (Sweden)

    Jung-Ha Kim

    Full Text Available PURPOSE: Both telomere length and mitochondrial function are accepted as reflective indices of aging. Recent studies have shown that telomere dysfunction may influence impaired mitochondrial biogenesis and function. However, there has been no study regarding the possible association between telomere and mitochondrial function in humans. Therefore, the purpose of the study was to identify any relationships between mitochondrial and telomere function. METHODS: The present study included 129 community-dwelling, elderly women. The leukocyte mitochondrial DNA copy number and telomere length were measured using a quantitative real-time polymerase chain reaction method. Anthropometric measurement, biochemical blood testing, a depression screening questionnaire using a 15-question geriatric depression scale (GDS-15, and a cognitive function test using the Korean version of the mini mental state examination (K-MMSE were performed. RESULTS: Leukocyte mtDNA copy number was positively associated with telomere length (r=0.39, p=<0.0001 and K-MMSE score (r=0.06, p=0.02. Additionally, leukocyte mtDNA copy number was negatively correlated with GDS-15 score (r=-0.17, p=0.04. Age (r=-0.15, p=0.09, waist circumference (r=-0.16, p=0.07, and serum ferritin level (r=-0.13, p=0.07 tended to be inversely correlated with leukocyte mtDNA copy number. With a stepwise multiple regression analysis, telomere length was found to be an independent factor associated with leukocyte mtDNA copy number after adjustment for confounding variables including age, body mass index, waist circumference, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, hs-CRP, serum ferritin, HOMA-IR, K-MMSE, GDS-15, hypertension, diabetes, dyslipidemia, currently smoking, alcohol drinking, and regular exercise. CONCLUSIONS: This study showed that leukocyte mtDNA copy number was positively correlated with leukocyte telomere length in community-dwelling elderly women. Our findings suggest

  11. Telomerase inhibitor imetelstat has preclinical activity across the spectrum of non-small cell lung cancer oncogenotypes in a telomere length dependent manner.

    Science.gov (United States)

    Frink, Robin E; Peyton, Michael; Schiller, Joan H; Gazdar, Adi F; Shay, Jerry W; Minna, John D

    2016-05-31

    Telomerase was evaluated as a therapeutic oncotarget by studying the efficacy of the telomerase inhibitor imetelstat in non-small cell lung cancer (NSCLC) cell lines to determine the range of response phenotypes and identify potential biomarkers of response. A panel of 63 NSCLC cell lines was studied for telomere length and imetelstat efficacy in inhibiting colony formation and no correlation was found with patient characteristics, tumor histology, and oncogenotypes. While there was no overall correlation between imetelstat efficacy with initial telomere length (ranging from 1.5 to 20 kb), the quartile of NSCLC lines with the shortest telomeres was more sensitive than the quartile with the longest telomeres. Continuous long-term treatment with imetelstat resulted in sustained telomerase inhibition, progressive telomere shortening and eventual growth inhibition in a telomere-length dependent manner. Cessation of imetelstat therapy before growth inhibition was followed by telomere regrowth. Likewise, in vivo imetelstat treatment caused tumor xenograft growth inhibition in a telomere-length dependent manner. We conclude from these preclinical studies of telomerase as an oncotarget tested by imetelstat response that imetelstat has efficacy across the entire oncogenotype spectrum of NSCLC, continuous therapy is necessary to prevent telomere regrowth, and short telomeres appears to be the best treatment biomarker.

  12. Diagnostic criteria and reporting procedures for pre-eclampsia: a national survey among obstetrical departments in Denmark

    DEFF Research Database (Denmark)

    Klemmensen, Åse Kathrine; Olsen, SF; Wengel, CM

    2005-01-01

    OBJECTIVE: A precondition for the rational use of obstetric databases in biomedical research is detailed knowledge on how data are being generated. We identified the diagnostic procedures and criteria for pre-eclampsia (PE) and assessed the level of obstetric training of the personnel responsible...... of pregnancy diagnoses to the National Patient Registry differed widely in training. For complicated pregnancies, departments ranged from having only specialists reporting all cases to secretaries reporting up to 50%. Cut off limits of blood pressure (BP) and protein loss used to diagnose pre-eclampsia showed...

  13. Assessment of serum lipids in pregnant women aged over 35 years and their relation with pre-eclampsia

    Directory of Open Access Journals (Sweden)

    Umberto Gazi Lippi

    2008-03-01

    Full Text Available Objective: To assess serum total cholesterol, low density lipoproteincholesterol, high density lipoprotein cholesterol, very low densitylipoprotein cholesterol and triglyceride levels in pregnant womenaged over 35 years during the first and second trimesters ofpregnancy, and to relate theses values with the diagnosis ofpre-eclampsia in the 3rd trimester of pregnancy. Methods: Fiftythreepregnant women were divided into two groups, one withno pre-eclampsia and another diagnosed with pre-eclampsia.Five pregnant women were excluded due to miscarriages. Serumtotal cholesterol, low density lipoprotein cholesterol, high densitylipoprotein cholesterol, very low density lipoprotein cholesteroland triglyceride levels were measured in all pregnant womenduring the first and second trimesters of pregnancy. Results:Thirty-nine pregnant women had no pre-eclampsia and nine werediagnosed with pre-eclampsia. Serum total cholesterol, low densitylipoprotein cholesterol and triglyceride levels were similar inboth groups during the first and second trimesters of pregnancy(p = 0.25, p = 0.71 and p = 0.30, respectively. However,serum total cholesterol, low density lipoprotein cholesterol andtriglyceride levels were significantly higher during the secondtrimester compared to the first trimester in both groups (p < 0.001,p < 0.005 and p < 0.001, respectively. Serum high densitylipoprotein cholesterol and very low density lipoprotein cholesterollevels were similar in both groups during the first trimester(p = 0.21 and p = 0.38, respectively; during the second trimester,however, these levels were significantly higher in the pre-eclampsiagroup compared to the group with no pre-eclampsia (p = 0.005 andp = 0.003, respectively. Furthermore, serum high density lipoproteincholesterol levels in the pre-eclampsia group were significantlyhigher during the second trimester compared to the first trimesterin the same groups, and serum very low density lipoproteincholesterol levels in

  14. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.

    Science.gov (United States)

    Haycock, Philip C; Burgess, Stephen; Nounu, Aayah; Zheng, Jie; Okoli, George N; Bowden, Jack; Wade, Kaitlin Hazel; Timpson, Nicholas J; Evans, David M; Willeit, Peter; Aviv, Abraham; Gaunt, Tom R; Hemani, Gibran; Mangino, Massimo; Ellis, Hayley Patricia; Kurian, Kathreena M; Pooley, Karen A; Eeles, Rosalind A; Lee, Jeffrey E; Fang, Shenying; Chen, Wei V; Law, Matthew H; Bowdler, Lisa M; Iles, Mark M; Yang, Qiong; Worrall, Bradford B; Markus, Hugh Stephen; Hung, Rayjean J; Amos, Chris I; Spurdle, Amanda B; Thompson, Deborah J; O'Mara, Tracy A; Wolpin, Brian; Amundadottir, Laufey; Stolzenberg-Solomon, Rachael; Trichopoulou, Antonia; Onland-Moret, N Charlotte; Lund, Eiliv; Duell, Eric J; Canzian, Federico; Severi, Gianluca; Overvad, Kim; Gunter, Marc J; Tumino, Rosario; Svenson, Ulrika; van Rij, Andre; Baas, Annette F; Bown, Matthew J; Samani, Nilesh J; van t'Hof, Femke N G; Tromp, Gerard; Jones, Gregory T; Kuivaniemi, Helena; Elmore, James R; Johansson, Mattias; Mckay, James; Scelo, Ghislaine; Carreras-Torres, Robert; Gaborieau, Valerie; Brennan, Paul; Bracci, Paige M; Neale, Rachel E; Olson, Sara H; Gallinger, Steven; Li, Donghui; Petersen, Gloria M; Risch, Harvey A; Klein, Alison P; Han, Jiali; Abnet, Christian C; Freedman, Neal D; Taylor, Philip R; Maris, John M; Aben, Katja K; Kiemeney, Lambertus A; Vermeulen, Sita H; Wiencke, John K; Walsh, Kyle M; Wrensch, Margaret; Rice, Terri; Turnbull, Clare; Litchfield, Kevin; Paternoster, Lavinia; Standl, Marie; Abecasis, Gonçalo R; SanGiovanni, John Paul; Li, Yong; Mijatovic, Vladan; Sapkota, Yadav; Low, Siew-Kee; Zondervan, Krina T; Montgomery, Grant W; Nyholt, Dale R; van Heel, David A; Hunt, Karen; Arking, Dan E; Ashar, Foram N; Sotoodehnia, Nona; Woo, Daniel; Rosand, Jonathan; Comeau, Mary E; Brown, W Mark; Silverman, Edwin K; Hokanson, John E; Cho, Michael H; Hui, Jennie; Ferreira, Manuel A; Thompson, Philip J; Morrison, Alanna C; Felix, Janine F; Smith, Nicholas L; Christiano, Angela M; Petukhova, Lynn; Betz, Regina C; Fan, Xing; Zhang, Xuejun; Zhu, Caihong; Langefeld, Carl D; Thompson, Susan D; Wang, Feijie; Lin, Xu; Schwartz, David A; Fingerlin, Tasha; Rotter, Jerome I; Cotch, Mary Frances; Jensen, Richard A; Munz, Matthias; Dommisch, Henrik; Schaefer, Arne S; Han, Fang; Ollila, Hanna M; Hillary, Ryan P; Albagha, Omar; Ralston, Stuart H; Zeng, Chenjie; Zheng, Wei; Shu, Xiao-Ou; Reis, Andre; Uebe, Steffen; Hüffmeier, Ulrike; Kawamura, Yoshiya; Otowa, Takeshi; Sasaki, Tsukasa; Hibberd, Martin Lloyd; Davila, Sonia; Xie, Gang; Siminovitch, Katherine; Bei, Jin-Xin; Zeng, Yi-Xin; Försti, Asta; Chen, Bowang; Landi, Stefano; Franke, Andre; Fischer, Annegret; Ellinghaus, David; Flores, Carlos; Noth, Imre; Ma, Shwu-Fan; Foo, Jia Nee; Liu, Jianjun; Kim, Jong-Won; Cox, David G; Delattre, Olivier; Mirabeau, Olivier; Skibola, Christine F; Tang, Clara S; Garcia-Barcelo, Merce; Chang, Kai-Ping; Su, Wen-Hui; Chang, Yu-Sun; Martin, Nicholas G; Gordon, Scott; Wade, Tracey D; Lee, Chaeyoung; Kubo, Michiaki; Cha, Pei-Chieng; Nakamura, Yusuke; Levy, Daniel; Kimura, Masayuki; Hwang, Shih-Jen; Hunt, Steven; Spector, Tim; Soranzo, Nicole; Manichaikul, Ani W; Barr, R Graham; Kahali, Bratati; Speliotes, Elizabeth; Yerges-Armstrong, Laura M; Cheng, Ching-Yu; Jonas, Jost B; Wong, Tien Yin; Fogh, Isabella; Lin, Kuang; Powell, John F; Rice, Kenneth; Relton, Caroline L; Martin, Richard M; Davey Smith, George

    2017-05-01

    The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Genomewide association studies (GWAS) published up to January 15, 2015. GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of

  15. Mutations in TERT promoter and FGFR3 and telomere length in bladder cancer.

    Science.gov (United States)

    Hosen, Ismail; Rachakonda, P Sivaramakrishna; Heidenreich, Barbara; de Verdier, Petra J; Ryk, Charlotta; Steineck, Gunnar; Hemminki, Kari; Kumar, Rajiv

    2015-10-01

    Mutations in the promoter of the telomerase reverse transcriptase (TERT) and fibroblast growth factor receptor 3 (FGFR3) genes constitute the most recurrent somatic alterations in urothelial carcinoma of bladder. In this study, we screened DNA from 327 urothelial bladder carcinomas from well-documented patients, with different stages and grades and known TERT promoter mutational status, for FGFR3 alterations and measured relative telomere length (RTL). Although, the frequency of the TERT promoter mutations was higher than those in FGFR3; however, the alterations at the two loci occurred together more frequently than per chance [Odds ratio (OR) = 4.93, 95% CI = 2.72-8.92, p FGFR3 mutations had shorter RTL than those without mutations (p FGFR3 mutations than without mutations implies mechanistic relevance of telomere biology in cancer progression. The observed association with recurrence and survival shows that the TERT promoter mutations can potentially be used as markers to refine selection of patients for different treatments. The overwhelming frequency of the TERT promoter mutations also represents a case for development of an eventual therapeutic target. © 2015 UICC.

  16. Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study.

    Science.gov (United States)

    Du, Mengmeng; Prescott, Jennifer; Cornelis, Marilyn C; Hankinson, Susan E; Giovannucci, Edward; Kraft, Peter; De Vivo, Immaculata

    2013-01-01

    Although cross-sectional studies have linked higher body mass index (BMI) and type 2 diabetes (T2D) to shortened telomeres, whether these metabolic conditions play a causal role in telomere biology is unknown. We therefore examined whether genetic predisposition to higher BMI or T2D was associated with shortened leukocyte telomere length (LTL). We conducted an analysis of 3,968 women of European ancestry aged 43-70 years from the Nurses' Health Study, who were selected as cases or controls in genome-wide association studies and studies of telomeres and disease. Pre-diagnostic relative telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative PCR. We combined information from multiple risk variants by calculating genetic risk scores based on 32 polymorphisms near 32 loci for BMI, and 36 polymorphisms near 35 loci for T2D. After adjustment for age and case-control status, there was no association between the BMI genetic risk score and LTL (β per standard deviation increase: -0.01; SE: 0.02; P = 0.52). Similarly, the T2D genetic score was not associated with LTL (β per standard deviation increase: -0.006; SE: 0.02; P = 0.69). In this population of middle-aged and older women of European ancestry, those genetically predisposed to higher BMI or T2D did not possess shortened telomeres. Although we cannot exclude weak or modest effects, our findings do not support a causal relation of strong magnitude between these metabolic conditions and telomere dynamics.

  17. Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Although cross-sectional studies have linked higher body mass index (BMI and type 2 diabetes (T2D to shortened telomeres, whether these metabolic conditions play a causal role in telomere biology is unknown. We therefore examined whether genetic predisposition to higher BMI or T2D was associated with shortened leukocyte telomere length (LTL.We conducted an analysis of 3,968 women of European ancestry aged 43-70 years from the Nurses' Health Study, who were selected as cases or controls in genome-wide association studies and studies of telomeres and disease. Pre-diagnostic relative telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative PCR. We combined information from multiple risk variants by calculating genetic risk scores based on 32 polymorphisms near 32 loci for BMI, and 36 polymorphisms near 35 loci for T2D.After adjustment for age and case-control status, there was no association between the BMI genetic risk score and LTL (β per standard deviation increase: -0.01; SE: 0.02; P = 0.52. Similarly, the T2D genetic score was not associated with LTL (β per standard deviation increase: -0.006; SE: 0.02; P = 0.69.In this population of middle-aged and older women of European ancestry, those genetically predisposed to higher BMI or T2D did not possess shortened telomeres. Although we cannot exclude weak or modest effects, our findings do not support a causal relation of strong magnitude between these metabolic conditions and telomere dynamics.

  18. Nursing care for women with pre-eclampsia and/or eclampsia: integrative review.

    Science.gov (United States)

    Ferreira, Maria Beatriz Guimarães; Silveira, Caroline Freitas; Silva, Sueli Riul da; Souza, Delvane José de; Ruiz, Mariana Torreglosa

    2016-04-01

    To analyze the available evidence in the literature on nursing care for women with pre-eclampsia and/or eclampsia. Integrative review searching for primary studies in the databases PubMed, CINAHL, LILACS and SciELO. The sample size consisted of 17 primary studies published between January 2000 and December 2014, grouped into four categories: standardizing blood pressure measurement technique; training with simulation; instruments for standardization of care and quality of care The main nursing actions were: physical examination, early detection of signs of pre-eclampsia/eclampsia, monitoring of laboratory tests, fetal assessment, qualification and training of professionals. We identified the need for standardization of care from instruments, protocols and blood pressure measurement technique, early identification and treatment of hypertensive crisis through institutional protocols and review of cases and work processes. Women with pre-eclampsia and/or eclampsia require specific nursing care, which must be guided by care protocols based on scientific evidence. Analisar as evidências disponíveis na literatura sobre assistência de enfermagem às mulheres com pré-eclâmpsia e/ou eclâmpsia. Revisão integrativa cuja busca dos estudos primários foi realizada nas bases de dados PubMed, CINAHL, LILACS e SciELO. Amostra foi composta por 17 estudos primários, publicados entre janeiro de 2000 e dezembro de 2014, agrupados em quatro categorias: padronização da técnica de mensuração da pressão arterial; treinamentos com simulação; instrumentos para padronização da assistência e qualidade da assistência As principais ações de enfermagem foram: exame físico, identificação precoce de sinais de pré-eclâmpsia/eclâmpsia, acompanhamento de exames laboratoriais, avaliação fetal, capacitação e treinamento dos profissionais. Identificou-se a necessidade de padronização do atendimento a partir de instrumentos e protocolos e da técnica de aferição da

  19. Cost effectiveness of medical devices to diagnose pre-eclampsia in low-resource settings

    Directory of Open Access Journals (Sweden)

    Zoë M. McLaren

    Full Text Available Background: Maternal mortality remains a major health challenge facing developing countries, with pre-eclampsia accounting for up to 17% of maternal deaths. Diagnosis requires skilled health providers and devices that are appropriate for low-resource settings. This study presents the first cost-effectiveness analysis of multiple medical devices used to diagnose pre-eclampsia in low- and middle-income countries (LMICs. Methods: Blood pressure and proteinuria measurement devices, identified from compendia for LMICs, were included. We developed a decision tree framework to assess the cost-effectiveness of each device using parameter values that reflect the general standard of care based on a survey of relevant literature and expert opinion. We examined the sensitivity of our results using one-way and second-order probabilistic multivariate analyses. Results: Because the disability-adjusted life years (DALYs averted for each device were very similar, the results were influenced by the per-use cost ranking. The most cost-effective device combination was a semi-automatic blood pressure measurement device and visually read urine strip test with the lowest combined per-use cost of $0.2004 and an incremental cost effectiveness ratio of $93.6 per DALY gained relative to a baseline with no access to diagnostic devices. When access to treatment is limited, it is more cost-effective to improve access to treatment than to increase testing rates or diagnostic device sensitivity. Conclusions: Our findings were not sensitive to changes in device sensitivity, however they were sensitive to changes in the testing rate and treatment rate. Furthermore, our results suggest that simple devices are more cost-effective than complex devices. The results underscore the desirability of two design features for LMICs: ease of use and accuracy without calibration. Our findings have important implications for policy makers, health economists, health care providers and

  20. Cost and resource implications with serum angiogenic factor estimation in the triage of pre-eclampsia.

    Science.gov (United States)

    Schnettler, W T; Dukhovny, D; Wenger, J; Salahuddin, S; Ralston, S J; Rana, S

    2013-09-01

    To analyse the economic and resource implications of using plasma soluble fms-like tyrosine kinase-1 s(Flt1) and placenta growth factor (PlGF) measurements in pre-eclampsia evaluation and management. Retrospective cost analysis of our prospective cohort study. Boston, Massachusetts (USA). Women (n = 176) presenting to the hospital at pre-eclampsia during 2009-10. Cases without complete cost or outcome data (n = 9) and re-enrolments (n = 18) were excluded. Modelled comparisons between the standard approach (combination of blood pressure, urinary protein excretion, alanine aminotransferase and platelet counts) and a novel approach (ratio of plasma sFlt1 and PlGF) using actual hospital data converted to 2012 US dollars in accordance with the Centers for Medicare and Medicaid Services. Direct 2-week costs and resource use by groups having true or false positive and negative test results for adverse outcomes according to approach. The improved specificity of the novel approach decreased the proportion of women falsely labelled as test-positive from 42.3% (34.4-50.2%) to 4.0% (0.85-7.15%) and increased the proportion correctly labelled as test-negative from 23.5% (16.7-30.3%) to 61.7% (53.9-69.5%). This could potentially reduce average per-patient costs by $1215. Substantial quantities of resources [47.2% (35.7-58.7%) of antenatal admissions and 72.5% (68.0-77.0%) of tests for fetal wellbeing] were unnecessarily used for women who were truly negative. A proportion of iatrogenic preterm deliveries among women with negative results was potentially avoidable representing further cost and resource savings. Clinical use of the plasma sFlt1 and PlGF ratio improves risk stratification among women presenting for pre-eclampsia evaluation and has the potential to reduce costs and resource use. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

  1. Sex difference in leukocyte telomere length is ablated in opposite-sex co-twins

    DEFF Research Database (Denmark)

    Benetos, Athanase; Dalgård, Christine; Labat, Carlos

    2014-01-01

    BACKGROUND: In eutherian mammals and in humans, the female fetus may be masculinized while sharing the intra-uterine environment with a male fetus. Telomere length (TL), as expressed in leukocytes, is heritable and is longer in women than in men. The main determinant of leukocyte TL (LTL) is LTL...... at birth. However, LTL is modified by age-dependent attrition. METHODS: We studied LTL dynamics (LTL and its attrition) in adult same-sex (monozygotic, n = 268; dizygotic, n = 308) twins and opposite-sex (n = 144) twins. LTL was measured by Southern blots of the terminal restriction fragments. RESULTS: We...... male LTL was not affected. Findings were similar when the comparison was restricted to opposite-sex and same-sex dizygotic twins (females relative to males: same-sex: 188 ± 90 bp, P masculinization of the female...

  2. Telomere length shows no association with BRCA1 and BRCA2 mutation status

    DEFF Research Database (Denmark)

    Killick, Emma; Tymrakiewicz, Malgorzata; Cieza-Borrella, Clara

    2014-01-01

    This study aimed to determine whether telomere length (TL) is a marker of cancer risk or genetic status amongst two cohorts of BRCA1 and BRCA2 mutation carriers and controls. The first group was a prospective set of 665 male BRCA1/2 mutation carriers and controls (mean age 53 years), all healthy...... at time of enrollment and blood donation, 21 of whom have developed prostate cancer whilst on study. The second group consisted of 283 female BRCA1/2 mutation carriers and controls (mean age 48 years), half of whom had been diagnosed with breast cancer prior to enrollment. TL was quantified by qPCR from...... DNA extracted from peripheral blood lymphocytes. Weighted and unweighted Cox regressions and linear regression analyses were used to assess whether TL was associated with BRCA1/2 mutation status or cancer risk. We found no evidence for association between developing cancer or being a BRCA1 or BRCA2...

  3. A short leucocyte telomere length is associated with development of insulin resistance

    DEFF Research Database (Denmark)

    Verhulst, Simon; Dalgård, Christine; Labat, Carlos

    2016-01-01

    AIMS/HYPOTHESIS: A number of studies have shown that leucocyte telomere length (LTL) is inversely associated with insulin resistance and type 2 diabetes mellitus. The aim of the present longitudinal cohort study, utilising a twin design, was to assess whether shorter LTL predicts insulin resistance...... and insulin resistance over an average of 12 years were performed in a subset of the Registry consisting of 338 (184 monozygotic and 154 dizygotic) same-sex twin pairs. RESULTS: Age at baseline examination was 37.4 ± 9.6 (mean ± SD) years. Baseline insulin resistance was not associated with age......-dependent changes in LTL (attrition) over the follow-up period, whereas baseline LTL was associated with changes in insulin resistance during this period. The shorter the LTL at baseline, the more pronounced was the increase in insulin resistance over the follow-up period (p 

  4. Sociodemographic correlates and family aggregation of leukocyte telomere length in adults and children from Mesoamerica.

    Science.gov (United States)

    Flannagan, Kerry S; Jansen, Erica C; Rozek, Laura S; Rentschler, Katie M; Roman, Ana Victoria; Ramirez-Zea, Manuel; Villamor, Eduardo

    2017-05-06

    Telomere length is a biomarker of cumulative stress and inflammation related to chronic disease risk. We examined the associations of leukocyte telomere length (LTL) with sociodemographic and anthropometric variables and estimated LTL family aggregation in Central America, a region with a high burden of chronic disease where LTL has not been studied. We conducted a cross-sectional study of 174 school age children and their parents in the capital cities of Belize, Honduras, Nicaragua, Costa Rica, Panama, and the city of Tuxtla-Gutierrez in Mexico. We measured LTL by quantitative PCR in DNA extracted from whole blood. We compared the distribution of LTL by categories of sociodemographic and anthropometric characteristics using linear regression. Family aggregation was estimated with correlation coefficients and intraclass correlations. In mothers, LTL was inversely associated with age (P, trend < .0001) and positively associated with height (P = .0002). Among fathers, LTL was inversely associated with food insecurity (P, trend = .0004). In children, boys had 0.10 log units shorter LTL than girls (95% CI: -0.17, -0.03; P = .004). LTL was inversely associated with parental education (P, trend = .01) and positively associated with paternal age at birth (P, trend < .0001), maternal LTL (P, trend = .007), and paternal LTL (P, trend = .02). LTL varied significantly by country of origin among all family members. Aggregation was greatest between children and their mothers, and mostly occurred at the country, rather than family, level. LTL is associated with age and height in women; food insecurity in men; and sex, parental education, parental LTL, and paternal age at birth among children. © 2016 Wiley Periodicals, Inc.

  5. Leukocyte telomere length and personality: associations with the Big Five and Type D personality traits.

    Science.gov (United States)

    Schoormans, D; Verhoeven, J E; Denollet, J; van de Poll-Franse, L; Penninx, B W J H

    2017-09-11

    Backgrounds Accelerated cellular ageing, which can be examined by telomere length (TL), may be an overarching mechanism underlying the association between personality and adverse health outcomes. This 6-year longitudinal study examined the relation between personality and leukocyte telomere length (LTL) across time among adults with a wide age-range. Data from the Netherlands Study of Depression and Anxiety were used and included patients with a depression and/or anxiety disorder and healthy controls. Overall, 2936 persons (18-65 years, 66% female) had data on LTL at baseline and 1883 persons had LTL at 6-year follow-up. The Big Five personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) and Type D personality were assessed. Neuroticism was negatively (B = -2.11, p = 0.03) and agreeableness was positively (B = 3.84, p = 0.03) related to LTL measured across two time points, which became just non-significant after adjusting for somatic health, lifestyle factors, and recent life stress (B = -1.99, p = 0.06; and B = 3.01, p = 0.10). Type D personality was negatively (B = -50.16, p Big Five traits high neuroticism and low agreeableness, and Type D personality were associated with shorter LTL measured across a 6-year period. Associations with the Big Five traits became non-significant after controlling for somatic health, lifestyle factors, and recent life stress, yet similar trends were observed. Type D personality remained independently associated with shorter LTL after full adjustment.

  6. Validity of pre-eclampsia registration in the medical birth registry of norway for women participating in the norwegian mother and child cohort study, 1999-2010.

    Science.gov (United States)

    Klungsøyr, Kari; Harmon, Quaker E; Skard, Linn B; Simonsen, Ingeborg; Austvoll, Elise T; Alsaker, Elin R; Starling, Anne; Trogstad, Lill; Magnus, Per; Engel, Stephanie M

    2014-09-01

    The Norwegian Mother and Child Cohort Study (MoBa), a prospective population-based pregnancy cohort, is a valuable database for studying causes of pre-eclampsia. Pre-eclampsia data in MoBa come from the Medical Birth Registry of Norway (MBRN); thus, we wanted to study the validity of MBRN pre-eclampsia registration for MoBa women. We selected all MoBa pregnancies with pre-eclampsia registered in the MBRN (n = 4081) and a random control group (n = 2000) without pre-eclampsia registrations. After excluding two delivery units not participating in MoBa and one no longer operating, units were asked to provide copies of antenatal charts with blood pressure and urinary measurements from all antenatal visits during pregnancy, and hospital discharge codes from the delivery stay. We received data for 5340 pregnancies delivered 1999-2010 (87% of all eligible). We calculated positive predictive value (PPV), and sensitivity and specificity of MBRN registration, using hypertension and proteinuria on the antenatal charts and/or hospital discharge codes indicating pre-eclampsia as gold standard. Overall PPV was 83.9% [95% CI 82.7, 85.1] and was higher when women were primiparous, or delivered preterm or low birthweight infants. Severe pre-eclampsia in the MBRN was found to be a true severe pre-eclampsia in 70% of cases. Extrapolating to the total MoBa population, the estimated sensitivity was low - 43.0% (38.7, 48.2) - while specificity was high - 99.2% (99.2, 99.3). False negative cases seemed to have mild forms of pre-eclampsia. PPV and specificity of pre-eclampsia registration in the MBRN during 1999-2010 was satisfactory, while sensitivity was low. © 2014 John Wiley & Sons Ltd.

  7. Accuracy of angiogenic biomarkers at ⩽20weeks' gestation in predicting the risk of pre-eclampsia: A WHO multicentre study.

    Science.gov (United States)

    Widmer, Mariana; Cuesta, Cristina; Khan, Khalid S; Conde-Agudelo, Agustin; Carroli, Guillermo; Fusey, Shalini; Karumanchi, S Ananth; Lapaire, Olav; Lumbiganon, Pisake; Sequeira, Evan; Zavaleta, Nelly; Frusca, Tiziana; Gülmezoglu, A Metin; Lindheimer, Marshall D

    2015-10-01

    To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia. Prospective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20, 23-27 and 32-35weeks' gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure ⩾140mmHg and/or diastolic blood pressure ⩾90mmHg, and proteinuria (protein/creatinine ratio ⩾0.3, protein ⩾1g/l, or one dipstick measurement ⩾2+) appearing after 20weeks' gestation. Early pre-eclampsia was defined when these signs appeared ⩽34weeks' gestation. Pre-eclampsia. Pre-eclampsia was diagnosed in 198 of 5121 women tested (3.9%) of whom 47 (0.9%) developed it early. The median maternal serum concentrations of index tests were significantly altered in women who subsequently developed pre-eclampsia than in those who did not. However, the area under receiver operating characteristics curve at ⩽20weeks' gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at ⩽34weeks' gestation. The corresponding sensitivity, specificity and likelihood ratios were poor. Multivariable models combining sEng with clinical features slightly improved the prediction capability. Angiogenic biomarkers in first half of pregnancy do not perform well enough in predicting the later development of pre-eclampsia. Copyright © 2015. Published by Elsevier B.V.

  8. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

    NARCIS (Netherlands)

    Boks, Marco P.; van Mierlo, Hans C.; Rutten, Bart P. F.; Radstake, Timothy R. D. J.; De Witte, Lot; Geuze, Elbert; Horvath, Steve; Schalkwyk, Leonard C.; Vinkers, Christiaan H.; Broen, Jasper C. A.; Vermetten, Eric

    Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA

  9. Realizing the Translational Potential of Telomere Length Variation as a Tissue Based Prognostic Marker for Prostate Cancer

    Science.gov (United States)

    2016-10-01

    pathologic prognostic factors are imperfect predictors of outcome in the men with clinically localized prostate cancer, the majority of men diagnosed...E, De Vivo I, Platz EA. Circulating leukocyte telomere length and risk of overall and aggressive prostate cancer. Br J Cancer. 2015 Feb 17;112(4

  10. Realizing the Translational Potential of Telomere Length Variation as a Tissue-Based Prognostic Marker for Prostate Cancer

    Science.gov (United States)

    2015-10-01

    488/Cy2, Alexa 568/Cy3, and Alexa 633/Cy5. The system contains an ultra -precise motorized stage for 8 slides for high throughput scanning. In addition...Kulac I, Graham MK , Joshu CE, De Marzo AM, Platz EA, Meeker AK. Tissue-based telomere length measurements as a biomarker for individualized prostate

  11. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

    NARCIS (Netherlands)

    Haycock, P.C.; Burgess, S.; Nounu, A.; Zheng, J.; Okoli, G.N.; Bowden, J.; Wade, K.H.; Timpson, N.J.; Evans, D.M.; Willeit, P.; Aviv, A.; Gaunt, T.R.; Hemani, G.; Mangino, M.; Ellis, H.P.; Kurian, K.M.; Pooley, K.A.; Eeles, R.A.; Lee, J.E.; Fang, S.; Chen, W.V.; Law, M.H.; Bowdler, L.M.; Iles, M.M.; Yang, Q.; Worrall, B.B.; Markus, H.S.; Hung, R.J.; Amos, C.I.; Spurdle, A.B.; Thompson, D.J.; O'Mara, T.A.; Wolpin, B.; Amundadottir, L.; Stolzenberg-Solomon, R.; Trichopoulou, A.; Onland-Moret, N.C.; Lund, E.; Duell, E.J.; Canzian, F.; Severi, G.; Overvad, K.; Gunter, M.J.; Tumino, R.; Svenson, U.; Rij, A. van; Baas, A.F.; Bown, M.J.; Samani, N.J.; t'Hof, F.N.G. van; Tromp, G.; Jones, G.T.; Kuivaniemi, H.; Elmore, J.R.; Johansson, M.; McKay, J.; Scelo, G.; Carreras-Torres, R.; Gaborieau, V.; Brennan, P.; Bracci, P.M.; Neale, R.E.; Olson, S.H.; Gallinger, S.; Li, D.; Petersen, G.M.; Risch, H.A.; Klein, A.P.; Han, J.; Abnet, C.C.; Freedman, N.D.; Taylor, P.R.; Maris, J.M.; Aben, K.K.H.; Kiemeney, L.A.; Vermeulen, S.H.; Wiencke, J.K.; Walsh, K.M.; Wrensch, M.; Rice, T.; Turnbull, C.; Litchfield, K.; Paternoster, L.; Standl, M.; Abecasis, G.R.; SanGiovanni, J.P.; Li, Y.; Mijatovic, V.; Sapkota, Y.; Low, S.K.; Zondervan, K.T.; Montgomery, G.W.; Nyholt, D.R.; Heel, D.A. van; Hunt, K.; Arking, D.E.; Ashar, F.N.; Sotoodehnia, N.; Woo, D.; et al.,

    2017-01-01

    Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study,

  12. Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis

    NARCIS (Netherlands)

    Cnossen, Jeltsje S.; Vollebregt, Karlijn C.; de Vrieze, Nynke; ter Riet, Gerben; Mol, Ben W. J.; Franx, Arie; Khan, Khalid S.; van der Post, Joris A. M.

    2008-01-01

    Objective To determine the accuracy of using systolic and diastolic blood pressure, mean arterial pressure, and increase of blood pressure to predict pre-eclampsia. Design Systematic review with meta-analysis of data on test accuracy. Data sources Medline, Embase, Cochrane Library, Medion, checking

  13. Women with a recent history of early-onset pre-eclampsia have a worse periodontal condition

    NARCIS (Netherlands)

    Kunnen, Alina; Blaauw, Judith; van Doormaal, Jasper J.; van Pampus, Maria G.; van der Schans, Cees P.; Aarnoudse, Jan G.; van Winkelhoff, Arie J.; Abbas, Frank

    Objective: Pre-eclampsia is a complication of pregnancy characterized by systemic vascular dysfunction and pathological changes in placental arteries. Growing evidence of chronic infection as an aetiological factor in vascular diseases prompted us to study maternal periodontal disease in subjects

  14. Placental leptin mRNA expression and serum leptin levels in pre-eclampsia associated with HIV infection.

    Science.gov (United States)

    Haffejee, Firoza; Naicker, Thajasvarie; Singh, Moganavelli; Kharsany, Ayesha B M; Adhikari, Miriam; Singh, Ravesh; Maharaj, Niren; Moodley, Jagidesa

    2017-01-01

    Leptin, primarily produced by adipocytes, is implicated in the development of pre-eclampsia. This study examines placental leptin production and serum leptin levels in HIV infected and uninfected normotensive and pre-eclamptic pregnancies. Placental leptin production was analysed by RT-PCR and serum leptin levels by ELISA in normotensive (n = 90) and pre-eclamptic (n = 90) pregnancies which were further stratified by HIV status. Placental leptin production was higher in pre-eclampsia compared to normotensive pregnancies irrespective of HIV status (p = .04). Serum leptin was non-significantly raised in HIV uninfected (p = .42) but lower in HIV-infected (p = .03) pre-eclampsia. The latter had lower BMI (p = .007) and triceps skin-fold thickness (p leptin and triceps skin-fold thickness (p leptin. Thus, serum leptin levels are not indicative of increased placental production when pre-eclampsia is associated with HIV infection.

  15. Morbidity and development in childhood of infants born after temporising treatment of early onset pre-eclampsia.

    NARCIS (Netherlands)

    Withagen, M.I.J.; Wallenburg, H.C.S.; Steegers, E.A.P.; Hop, W.C.J.; Visser, W. de

    2005-01-01

    OBJECTIVE: To assess morbidity and development in childhood of infants born after temporising management of severe early onset pre-eclampsia. DESIGN: Cohort study with matched controls. SETTING: University centre for high risk obstetrics. SAMPLES: Three groups of neonates matched for gender and year

  16. The 3’-untranslated region of the HLA-G gene in relation to pre-eclampsia

    DEFF Research Database (Denmark)

    Larsen, M. H.; Hylenius, S.; Nybo Andersen, A.-M.

    2010-01-01

    Abnormal human leukocyte antigen G (HLA-G) expression may be involved in pre-eclampsia. A 14 bp insertion/deletion polymorphism exists in exon 8 of the HLA-G gene. Fetal +14/+14 bp HLA-G genotype may predispose to pre-eclampsia in the mother. Other polymorphisms, besides the 14 bp polymorphism (rs......66554220), in the 3′-untranslated region (3′-UTR) (exon 8) of the HLA-G gene might be associated with severe pre-eclampsia, especially in primiparas. By haplotype-specific polymerase chain reaction amplification and DNA sequence analysis in the offspring from 50 pre-eclamptic cases and 85 controls (35.......008, PC = 0.04) were significantly associated with severe pre-eclampsia in primiparas. In conclusion, this study indicates that the +14 bp HLA-G allele defines a nearly unique exon 8 haplotype, and fetuses homozygous for this haplotype [SNP 2995(C)/SNP 3127(G)/SNP 3172(A)/SNP 3181(G)/+14 bp...

  17. Fetal sex-specific differences in gestational age at delivery in pre-eclampsia

    DEFF Research Database (Denmark)

    Schalekamp-Timmermans, Sarah; Arends, Lidia R.; Alsaker, Elin

    2017-01-01

    Background: Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother,placenta and fetus. This may lead to different adaptive mechanisms during pregnancy. Methods: We performed an individual...... participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating...... in a worldwide consortium of international research groups focusing on pregnancy. Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered >= 37...

  18. Uterine artery Doppler screening as a predictor of pre-eclampsia

    Directory of Open Access Journals (Sweden)

    Yasmin Casmod

    2016-10-01

    A prospective quantitative experimental study tested the hypothesis that uterine artery (UA spectral Doppler screening is able to identify patients at risk for developing preeclampsia. Convenience sampling allowed for the recruitment of 144 patients (11–14 weeks gestation who attended the antenatal clinic at Rahima Moosa Mother and Child Hospital between November 2008 and July 2010. A complete record of 121 participants was available for the final analysis. The results of this study revealed that 7 (5.8% participants developed pre-eclampsia. Race was identified as the most significant independent variable with an odds ratio of 1.5; 26 and 9 to 1 for developing PET in the 1st, 2nd and 3rd trimesters respectively. Uterine Artery Doppler is promising. An ultrasound screening programme in high risk pregnant women would offer clinicians the opportunity to pre-empt the disease before it manifests clinically.

  19. Role of Peroxiredoxin III in the Pathogenesis of Pre-eclampsia as Evidenced in Mice

    Directory of Open Access Journals (Sweden)

    Lianqin Li

    2010-01-01

    Full Text Available As a member of peroxiredoxin (Prx family, PrxIII has been demonstrated to play an important role in scavenging intracellular reactive oxygen species (ROS. Since PrxIII knockout mice exhibited oxidative stress in placentas resembling pathophysiologic changes in placentas of human pre-eclampsia, we measured blood pressure through the carotid artery and detected oxidative status by western blotting in pregnant mice. We did not notice hypertension in pregnant PrxIII knockout mice as compared with wild-type littermates, although endothelin-1 was overexpressed in PrxIII-deficient placentas. Our results indicate that PrxIII is not involved in pre-eclamptic development. Instead, PrxIII is an indispensable antioxidant in placentas where oxidative stress exists.

  20. Leukocyte Telomere Length, Breast Cancer Risk in the Offspring: The Relations with Father’s Age at Birth

    OpenAIRE

    Arbeev, Konstantin G.; Hunt, Steven C.; Kimura, Masayuki; Aviv, Abraham; Yashin, Anatoliy I.

    2011-01-01

    Recent studies have reported that leukocyte telomere length (LTL) is longer in offspring of older fathers. Longer telomeres might increase cancer risk. We examined the relation of father’s age at the birth of the offspring (FAB) with LTL in the offspring in 2177 participants of the Family Heart Study and the probability of developing breast cancer in 1405 women from the Framingham Heart Study (offspring cohort). For each year of increase in FAB (adjusted for mother’s age at birth), LTLs in th...

  1. Risk factors for pre-eclampsia among women at antenatal booking in Kano, Northern Nigeria

    Directory of Open Access Journals (Sweden)

    Ibrahim A. Yakasai

    2013-05-01

    Full Text Available Pre-eclampsia (PE is an important cause of maternal mortality. There have been several studies on risk factors assessment with conflicting reports across the globe on this disease; however, rigorous recent evaluation of these factors is uncommon in this region. The aim of the present study was to determine the risks factors in the early-onset PE in Aminu Kano Teaching Hospital (AKTH, Kano (Northern Nigeria. We conducted a case-control study in Nigeria between April 2009 and January 2010 to identify the risk factors associated with the early-onset PE in women attending antenatal clinic in AKTH. Information on socio-cultural characteristics, medical history, previous obstetrics history, level of stress at home, and type of family were obtained and recorded in a proforma designed for the study. Multiple logistic regression analysis was used to determine the risk factors for PE at 95% confidence level. Pregnant women with early-onset PE (150 in each case and control group. Risk factors associated with increased risk of early-onset PE were: history of pre-eclampsia/eclampsia (PE/E in a previous pregnancy [adjusted odds ratio (AOR 2.09]; exposure to passive smoking (AOR 1.34; inadequate antenatal supervision (AOR 15.21; family history of hypertension in one or more 1st-degree relative (AOR 8.92; living in a joint family (AOR 6.93; overweight (120% to 150% of pre-pregnancy ideal body weight, AOR 4.65. Risk factors among women in Northern Nigeria are similar to those reported from other studies. Good antenatal cares, early detection, reduction of stressful conditions at home are the most important preventive measures of early-onset severe PE among these women.

  2. Clinical management of pregnant women with the risk of pre-eclampsia developing

    Directory of Open Access Journals (Sweden)

    Loskutova T.O.

    2015-03-01

    Full Text Available Hypertensive disorders in pregnancy remain important problem of modern obstetrics, their frequency being 2-8% with no tendency of decreasing. To identify pregnant women with high risk and to conduct preventive treatment is very important for the practitioner. The aim of the study was to develop and justify differential management of pregnants depending on the risk of preeclampsia. 131 pregnant women in I trimester were tested to determine the risk of hypertensive disorders. Prediction model allows to identify pregnant women with risk of hypertensive disorders according to the results of testing thrombophilia genes (presence of 455G → A polymorphism in the gene for fibrinogen β and 4G/5G in gene of plasminogen activator inhibitor - type 1, the level of antibodies to β2 glycoprotein-1, the level of D-dimer and the value of atherogenicity coefficient. Pregnant women with high risk of hypertensive disorders, received prophylactic treatment complex. This complex included antiplatelet therapy, correction of hyperho¬mo¬cysteinemia and hypercholesterolemia levels. Etio-pathogenic concept of prediction and prevention of pre-eclampsia associated with thrombophilia was proposed. The proposed scheme of preventive treatment allowed to normalize blood clotting parameters, lipid metabolism, to reduce the number of thrombophilia markers. The necessity of early and long-term administration of prophylactic complex was proved. This management prevents endothelial damage and deve¬lopment of pathological range of pre-eclampsia. The results of prophylactic treatment were the reduction of preeclampsia cases by 6,5 times (p < 0.05, number of complicated deliveries by 3 times (p <0.05, number of preterm birth by 6,57 times (p <0.05, cases of growth retardation by 9,8 times (p = 0.003, increase of newborns’ weight by 1,24 times (p = 0.02.

  3. CORRELATION OF SPOT URINE ALBUMIN AND 12-HOUR URINE PROTEIN WITH 24-HOUR URINE PROTEIN IN PRE-ECLAMPSIA

    Directory of Open Access Journals (Sweden)

    S. Vinayachandran

    2017-11-01

    Full Text Available BACKGROUND Pre-eclampsia is defined as the development of new-onset hypertension in the second half of pregnancy often accompanied by new-onset proteinuria with other signs and symptoms. Proteinuria is defined by the excretion of 300 mg or more of protein in a 24-hour urine collection. To avoid time consumed in collection of 24-hour urine specimens, efforts have been made to develop faster methods to determine concentration of urine protein. Preliminary studies have suggested that 12-hour urine protein collection maybe adequate for evaluation of pre-eclampsia with advantage of early diagnosis and treatment of pre-eclampsia as well as potential for early hospital discharge and increased compliance with specimen collection. The aim of the study is to evaluate and correlate spot urine albumin and 12-hour urine protein with 24-hour urine protein in pre-eclampsia. MATERIALS AND METHODS A diagnostic evaluation study- a 24-hour urine protein, 12-hour urine protein and spot urine albumin results are analysed. Correlation of 12-hour urine protein and spot urine albumin with 24-hour urine protein is analysed using SPSS software. The strength of correlation was measured by Pearson’s correlation coefficient (r. Student’s t-test and Chi-square tests were used to compare patients with and without 24-hour urine protein ≥300 mg. Probability value of 165 mg with 24-hour urine protein ≥300 mg suggest that this test has role in the evaluation of women with suspected pre-eclampsia and could be substituted for 24-hour urine protein as a simple, faster and cheaper method.

  4. Strong inhibitory effect of pre-eclampsia serum on angiogenesis detected in vitro by human cell-based angiogenesis tests.

    Science.gov (United States)

    Virtanen, Anita; Toimela, Tarja; Tihtonen, Kati; Sarkanen, Jertta-Riina; Huttala, Outi; Heinonen, Tuula; Uotila, Jukka

    2016-10-01

    To explore in vitro angiogenic properties of maternal and umbilical cord blood sera from women with symptomatic pre-eclampsia in comparison with sera from women with normotensive pregnancies. Maternal and umbilical blood serum samples were collected from eleven primiparous women with pre-eclampsia and ten healthy gestational-age-matched primiparous controls. The samples were tested for tubule formation in two different types of in vitro angiogenesis tests. The first test (fibroblast-HUVEC) showed effects on angiogenesis and the second test (hASC-HUVEC), in addition to angiogenesis, also showed effects on vasculogenesis. The pro-angiogenic and inhibitory properties of the samples were microscopically quantified after immunostaining tubular structures, using markers for von Willebrand factor (vWf) and collagen IV. Serum samples from pre-eclamptic women inhibited tubule formation in both models, while those from normal pregnancy didn't. Umbilical blood samples were inhibitory both after pre-eclampsia and normal pregnancy. In the fibroblast-HUVEC model the inhibition was stronger after preeclampsia pregnancy, and the difference between groups was statistically significant. In the pre-eclampsia group a correlation between the inhibitory effect of umbilical blood and birth weight adjusted to gestational age was found. No clear correlation between sera from pregnant women and corresponding umbilical sera was found. The strong inhibitory effect of maternal serum samples on tubule formation reflects the anti-angiogenic state that is present in pre-eclampsia. Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  5. Telomere length, ATM mutation status and cancer risk in Ataxia-Telangiectasia families.

    Science.gov (United States)

    Renault, Anne-Laure; Mebirouk, Noura; Cavaciuti, Eve; Le Gal, Dorothée; Lecarpentier, Julie; d'Enghien, Catherine Dubois; Laugé, Anthony; Dondon, Marie-Gabrielle; Labbé, Martine; Lesca, Gaetan; Leroux, Dominique; Gladieff, Laurence; Adenis, Claude; Faivre, Laurence; Gilbert-Dussardier, Brigitte; Lortholary, Alain; Fricker, Jean-Pierre; Dahan, Karin; Bay, Jacques-Olivier; Longy, Michel; Buecher, Bruno; Janin, Nicolas; Zattara, Hélène; Berthet, Pascaline; Combès, Audrey; Coupier, Isabelle; Hall, Janet; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Lesueur, Fabienne

    2017-10-01

    Recent studies have linked constitutive telomere length (TL) to aging-related diseases including cancer at different sites. ATM participates in the signaling of telomere erosion, and inherited mutations in ATM have been associated with increased risk of cancer, particularly breast cancer. The goal of this study was to investigate whether carriage of an ATM mutation and TL interplay to modify cancer risk in ataxia-telangiectasia (A-T) families.The study population consisted of 284 heterozygous ATM mutation carriers (HetAT) and 174 non-carriers (non-HetAT) from 103 A-T families. Forty-eight HetAT and 14 non-HetAT individuals had cancer, among them 25 HetAT and 6 non-HetAT were diagnosed after blood sample collection. We measured mean TL using a quantitative PCR assay and genotyped seven single-nucleotide polymorphisms (SNPs) recurrently associated with TL in large population-based studies.HetAT individuals were at increased risk of cancer (OR = 2.3, 95%CI = 1.2-4.4, P = 0.01), and particularly of breast cancer for women (OR = 2.9, 95%CI = 1.2-7.1, P = 0.02), in comparison to their non-HetAT relatives. HetAT individuals had longer telomeres than non-HetAT individuals (P = 0.0008) but TL was not associated with cancer risk, and no significant interaction was observed between ATM mutation status and TL. Furthermore, rs9257445 (ZNF311) was associated with TL in HetAT subjects and rs6060627 (BCL2L1) modified cancer risk in HetAT and non-HetAT women.Our findings suggest that carriage of an ATM mutation impacts on the age-related TL shortening and that TL per se is not related to cancer risk in ATM carriers. TL measurement alone is not a good marker for predicting cancer risk in A-T families. © The Author 2017. Published by Oxford University Press.

  6. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    Science.gov (United States)

    Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L; French, Juliet D; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F; Maranian, Melanie J; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A; Álvarez, Nuria; Larson, Melissa C; Fridley, Brooke L; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S; Peto, Julian; Kalli, Kimberly R; Broeks, Annegien; Armasu, Sebastian M; Schmidt, Marjanka K; Braaf, Linde M; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L; Garcia, Joaquin J; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J; Haiman, Christopher A; Wang-Gohrke, Shan; Andrulis, Irene L; Moysich, Kirsten B; Hopper, John L; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A; Carney, Michael E; Radice, Paolo; Wilkens, Lynne R; Swerdlow, Anthony; Goodman, Marc T; Brauch, Hiltrud; García-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V; Dörk, Thilo; Pelttari, Liisa M; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H; Kristensen, Vessela; Ness, Roberta B; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A; Nordestgaard, Børge G; Flyger, Henrik; Vachon, Celine; Olson, Janet E; Wang, Xianshu; Levine, Douglas A; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M; Silva, Isabel Dos Santos; Cramer, Daniel W; Gibson, Lorna; Terry, Kathryn L; Fletcher, Olivia; Vitonis, Allison F; van der Schoot, C Ellen; Poole, Elizabeth M; Hogervorst, Frans B L; Tworoger, Shelley S; Liu, Jianjun; Bandera, Elisa V; Li, Jingmei; Olson, Sara H; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B; Muranen, Taru A; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K; Wildiers, Hans; Kiemeney, Lambertus A; Mulot, Claire; Aben, Katja K; Laurent-Puig, Pierre; van Altena, Anne M; Truong, Thérèse; Massuger, Leon F A G; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M Pilar; Cook, Linda S; Balasubramanian, Sabapathy P; Kelemen, Linda E; Schneeweiss, Andreas; Le, Nhu D; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A; Høgdall, Claus K; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C; Jager, Agnes; van den Ouweland, Ans M W; Brown, Robert; Martens, John W M; Flanagan, James M; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Müller, Heiko; Arndt, Volker; Labrèche, France; Gao, Yu-Tang; Goldberg, Mark S; Yang, Gong; Dumont, Martine; McLaughlin, John R; Hartmann, Arndt; Ekici, Arif B; Beckmann, Matthias W; Phelan, Catherine M; Lux, Michael P; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J; Orr, Nick; Menon, Usha; Pearce, Celeste L; Brüning, Thomas; Pike, Malcolm C; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K; Pylkäs, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A E M; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O; van den Berg, David; Yip, Cheng Har; Ikram, M Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R; Piedmonte, Marion; Singer, Christian F; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V O; Neuhausen, Susan L; Szabo, Csilla I; Blanco, Ignacio; Garber, Judy; Narod, Steven A; Weitzel, Jeffrey N; Montagna, Marco; Olah, Edith; Godwin, Andrew K; Yannoukakos, Drakoulis; Goldgar, David E; Caldes, Trinidad; Imyanitov, Evgeny N; Tihomirova, Laima; Arun, Banu K; Campbell, Ian; Mensenkamp, Arjen R; van Asperen, Christi J; van Roozendaal, Kees E P; Meijers-Heijboer, Hanne; Collée, J Margriet; Oosterwijk, Jan C; Hooning, Maartje J; Rookus, Matti A; van der Luijt, Rob B; van Os, Theo A M; Evans, D Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D; Cole, Trevor; Paillerets, Brigitte Bressac-de; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Plendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Åke; Melin, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L; Domchek, Susan M; Rodriguez, Gustavo C; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A; Lester, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B; Olswold, Curtis; Cunningham, Julie M; Slager, Susan; Pankratz, Vernon S; Dicks, Ed; Lakhani, Sunil R; Couch, Fergus J; Hall, Per; Monteiro, Alvaro N A; Gayther, Simon A; Pharoah, Paul D P; Reddel, Roger R; Goode, Ellen L; Greene, Mark H; Easton, Douglas F; Berchuck, Andrew; Antoniou, Antonis C; Chenevix-Trench, Georgia; Dunning, Alison M

    2013-01-01

    TERT-locus single nucleotide polymorphisms (SNPs) and leucocyte telomere measures are reportedly associated with risks of multiple cancers. Using the iCOGs chip, we analysed ~480 TERT-locus SNPs in breast (n=103,991), ovarian (n=39,774) and BRCA1 mutation carrier (11,705) cancer cases and controls. 53,724 participants have leucocyte telomere measures. Most associations cluster into three independent peaks. Peak 1 SNP rs2736108 minor allele associates with longer telomeres (P=5.8×10−7), reduced estrogen receptor negative (ER-negative) (P=1.0×10−8) and BRCA1 mutation carrier (P=1.1×10−5) breast cancer risks, and altered promoter-assay signal. Peak 2 SNP rs7705526 minor allele associates with longer telomeres (P=2.3×10−14), increased low malignant potential ovarian cancer risk (P=1.3×10−15) and increased promoter activity. Peak 3 SNPs rs10069690 and rs2242652 minor alleles increase ER-negative (P=1.2×10−12) and BRCA1 mutation carrier (P=1.6×10−14) breast and invasive ovarian (P=1.3×10−11) cancer risks, but not via altered telomere length. The cancer-risk alleles of rs2242652 and rs10069690 respectively increase silencing and generate a truncated TERT splice-variant. PMID:23535731

  7. Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

    Science.gov (United States)

    Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

    2015-01-01

    In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

  8. Physical Activity, Physical Fitness and Leukocyte Telomere Length: the Cardiovascular Health Study.

    Science.gov (United States)

    Soares-Miranda, Luisa; Imamura, Fumiaki; Siscovick, David; Jenny, Nancy Swords; Fitzpatrick, Annette L; Mozaffarian, Dariush

    2015-01-01

    Introduction The influence of physical activity (PA) and physical fitness (PF) at older ages on changes in telomere length (TL), repetitive DNA sequences that may mark biologic aging, is not well-established. Few prior studies have been conducted in older adults, these were mainly cross-sectional, and few evaluated PF. Methods We investigated cross-sectional and prospective associations of PA and PF with leukocyte TL among 582 older adults (age 73±5 y at baseline) in the Cardiovascular Health Study, having serial TL measures and PA and PF assessed multiple times. Cross-sectional associations were assessed using multivariable repeated-measures regression, in which cumulatively averaged PA and PF measures were related to TL. Longitudinal analyses assessed cumulatively averaged PA and PF against later changes in TL; and changes in cumulatively averaged PA and PF against changes in TL. Results Cross-sectionally, greater walking distance and chair test performance, but not other PA and PF measures, were each associated with longer TL (p-trend=0.007, 0.04 respectively). In longitudinal analyses, no significant associations of baseline PA and PF with change in TL were observed. In contrast, changes in leisure-time activity and chair test performance were each inversely associated with changes in TL. Conclusions Cross-sectional analyses suggest that greater PA and PF are associated with longer TL. Prospective analyses show that changes in PA and PF are associated with differences in changes in TL. Even later in life, changes in certain PA and PF measures are associated with changes in TL, suggesting that leisure-time activity and fitness could reduce leukocyte telomere attrition among older adults. PMID:26083773

  9. Longitudinal change in telomere length and the chronic stress response in a randomized pilot biobehavioral clinical study: implications for cancer prevention.

    Science.gov (United States)

    Biegler, Kelly A; Anderson, Amanda K L; Wenzel, Lari B; Osann, Kathryn; Nelson, Edward L

    2012-10-01

    Shortened telomere length is associated with increased cancer incidence and mortality. Populations experiencing chronic stress have accelerated telomere shortening. In this exploratory study, we examined associations between longitudinal changes in patient reported outcomes (PRO) of psychologic distress and peripheral blood mononuclear cell (PBMC) telomere length to test the hypothesis that modulation of the chronic stress response would also modulate telomere dynamics. Archived PBMC specimens (N = 22) were analyzed from a completed and reported randomized, longitudinal trial that showed a psychosocial telephone counseling intervention improved quality of life (QOL) and modulated stress-associated biomarkers in cervical cancer survivors. PROs and biospecimens were collected at baseline and 4 months postenrollment. Telomere length of archived PBMCs was evaluated using the flow-FISH assay. Longitudinal changes in psychologic distress, measured by the Brief Symptom Inventory-18, were significantly associated with increased telomere length within the CD14(+) (monocyte) population (r = -0.46, P = 0.043); a similar trend was observed for the CD14(-) population. Longitudinal changes in telomere length of the CD14(-) subset, primarily T lymphocytes, were associated with longitudinal increases in the naive T-cell population (r = 0.49, P = 0.052). Alterations in the chronic stress response were associated with modulation of telomere length in PBMCs, with evidence for mobilization of "younger" cells from progenitor populations. These data provide preliminary support for the (i) capacity to modulate the chronic stress response and the associated accelerated telomere shortening, (ii) inclusion of telomere length in the biobehavioral paradigm, and (iii) potential link between the chronic stress response and biologic mechanisms responsible for genomic integrity and carcinogenesis.

  10. Empirical evaluation of humpback whale telomere length estimates; quality control and factors causing variability in the singleplex and multiplex qPCR methods.

    Science.gov (United States)

    Olsen, Morten Tange; Bérubé, Martine; Robbins, Jooke; Palsbøll, Per J

    2012-09-06

    Telomeres, the protective cap of chromosomes, have emerged as powerful markers of biological age and life history in model and non-model species. The qPCR method for telomere length estimation is one of the most common methods for telomere length estimation, but has received recent critique for being too error-prone and yielding unreliable results. This critique coincides with an increasing awareness of the potentials and limitations of the qPCR technique in general and the proposal of a general set of guidelines (MIQE) for standardization of experimental, analytical, and reporting steps of qPCR. In order to evaluate the utility of the qPCR method for telomere length estimation in non-model species, we carried out four different qPCR assays directed at humpback whale telomeres, and subsequently performed a rigorous quality control to evaluate the performance of each assay. Performance differed substantially among assays and only one assay was found useful for telomere length estimation in humpback whales. The most notable factors causing these inter-assay differences were primer design and choice of using singleplex or multiplex assays. Inferred amplification efficiencies differed by up to 40% depending on assay and quantification method, however this variation only affected telomere length estimates in the worst performing assays. Our results suggest that seemingly well performing qPCR assays may contain biases that will only be detected by extensive quality control. Moreover, we show that the qPCR method for telomere length estimation can be highly precise and accurate, and thus suitable for telomere measurement in non-model species, if effort is devoted to optimization at all experimental and analytical steps. We conclude by highlighting a set of quality controls which may serve for further standardization of the qPCR method for telomere length estimation, and discuss some of the factors that may cause variation in qPCR experiments.

  11. Empirical evaluation of humpback whale telomere length estimates; quality control and factors causing variability in the singleplex and multiplex qPCR methods

    Directory of Open Access Journals (Sweden)

    Olsen Morten

    2012-09-01

    Full Text Available Abstract Background Telomeres, the protective cap of chromosomes, have emerged as powerful markers of biological age and life history in model and non-model species. The qPCR method for telomere length estimation is one of the most common methods for telomere length estimation, but has received recent critique for being too error-prone and yielding unreliable results. This critique coincides with an increasing awareness of the potentials and limitations of the qPCR technique in general and the proposal of a general set of guidelines (MIQE for standardization of experimental, analytical, and reporting steps of qPCR. In order to evaluate the utility of the qPCR method for telomere length estimation in non-model species, we carried out four different qPCR assays directed at humpback whale telomeres, and subsequently performed a rigorous quality control to evaluate the performance of each assay. Results Performance differed substantially among assays and only one assay was found useful for telomere length estimation in humpback whales. The most notable factors causing these inter-assay differences were primer design and choice of using singleplex or multiplex assays. Inferred amplification efficiencies differed by up to 40% depending on assay and quantification method, however this variation only affected telomere length estimates in the worst performing assays. Conclusion Our results suggest that seemingly well performing qPCR assays may contain biases that will only be detected by extensive quality control. Moreover, we show that the qPCR method for telomere length estimation can be highly precise and accurate, and thus suitable for telomere measurement in non-model species, if effort is devoted to optimization at all experimental and analytical steps. We conclude by highlighting a set of quality controls which may serve for further standardization of the qPCR method for telomere length estimation, and discuss some of the factors that may cause

  12. Birth outcomes of newborns after folic Acid supplementation in pregnant women with early and late pre-eclampsia: a population-based study.

    Science.gov (United States)

    Bánhidy, Ferenc; Dakhlaoui, Abdallah; Dudás, István; Czeizel, Andrew E

    2011-01-01

    Objective. To evaluate the rate of preterm birth and low birth weight in the newborns of pregnant women with early and late onset pre-eclampsia according to folic acid supplementation. Study design. Birth outcomes of newborns were evaluated in 1,017 (2.7%) pregnant women with medically recorded pre-eclampsia and 37,134 pregnant women without pre-eclampsia as reference in the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996, in addition these study groups were differentiated according to the supplementation of high dose of folic acid alone from early pregnancy. Results. Pregnant women with pre-eclampsia associated with a higher rate of preterm birth (10.2% versus 9.1%) and low birthweight (7.9% versus 5.6%). There was a lower risk of preterm birth (6.8%) of newborn infants born to pregnant women with early onset pre-eclampsia after folic acid supplementation from early pregnancy though the rate of low birthweight was not reduced significantly. There was no significant reduction in the rate of preterm birth and low birthweight in pregnant women with late onset pre-eclampsia after folic acid supplementation. Conclusion. The rate of preterm birth in pregnant women with early onset pre-eclampsia was reduced moderately by high doses of folic acid supplementation from early pregnancy.

  13. Childhood growth, IQ and education as predictors of white blood cell telomere length at age 49-51 years: the Newcastle Thousand Families Study.

    Directory of Open Access Journals (Sweden)

    Mark S Pearce

    Full Text Available BACKGROUND: Telomere length is emerging as a potential factor in the pathogenesis of cardiovascular disease. We investigated whether birth weight, infant growth, childhood cognition and adult height, as well as a range of lifestyle, socio-economic and educational factors, were associated with white blood cell telomere length at age 49-51 years. METHODS: The study included 318 members of the Newcastle Thousand Families Study, a prospectively followed birth cohort which includes all individuals born in Newcastle, England in May and June 1947, who attended for clinical examination at age 49-51 years, and had telomere length successfully measured using real-time PCR analyses of DNA extracted from peripheral blood mononuclear cells. RESULTS: No association was found between birth weight and later telomere length. However, associations were seen with other factors from early life. Education level was the only predictor in males, while telomere length in females was associated with gestational age at birth, childhood growth and childhood IQ. CONCLUSIONS: While these findings may be due to chance, in particular where differing associations were seen between males and females, they do provide evidence of early life associations with telomere length much later in life. Our findings of sex differences in the education association may reflect the sex differences in achieved education levels in this generation where few women went to university regardless of their intelligence. Our findings do not support the concept of telomere length being on the pathway between very early growth and later disease risk.

  14. Childhood growth, IQ and education as predictors of white blood cell telomere length at age 49-51 years: the Newcastle Thousand Families Study.

    Science.gov (United States)

    Pearce, Mark S; Mann, Kay D; Martin-Ruiz, Carmen; Parker, Louise; White, Martin; von Zglinicki, Thomas; Adams, Jean

    2012-01-01

    Telomere length is emerging as a potential factor in the pathogenesis of cardiovascular disease. We investigated whether birth weight, infant growth, childhood cognition and adult height, as well as a range of lifestyle, socio-economic and educational factors, were associated with white blood cell telomere length at age 49-51 years. The study included 318 members of the Newcastle Thousand Families Study, a prospectively followed birth cohort which includes all individuals born in Newcastle, England in May and June 1947, who attended for clinical examination at age 49-51 years, and had telomere length successfully measured using real-time PCR analyses of DNA extracted from peripheral blood mononuclear cells. No association was found between birth weight and later telomere length. However, associations were seen with other factors from early life. Education level was the only predictor in males, while telomere length in females was associated with gestational age at birth, childhood growth and childhood IQ. While these findings may be due to chance, in particular where differing associations were seen between males and females, they do provide evidence of early life associations with telomere length much later in life. Our findings of sex differences in the education association may reflect the sex differences in achieved education levels in this generation where few women went to university regardless of their intelligence. Our findings do not support the concept of telomere length being on the pathway between very early growth and later disease risk.

  15. Race, Ethnicity, Psychosocial Factors, and Telomere Length in a Multicenter Setting.

    Directory of Open Access Journals (Sweden)

    Shannon M Lynch

    Full Text Available Leukocyte telomere length(LTL has been associated with age, self-reported race/ethnicity, gender, education, and psychosocial factors, including perceived stress, and depression. However, inconsistencies in associations of LTL with disease and other phenotypes exist across studies. Population characteristics, including race/ethnicity, laboratory methods, and statistical approaches in LTL have not been comprehensively studied and could explain inconsistent LTL associations.LTL was measured using Southern Blot in 1510 participants from a multi-ethnic, multi-center study combining data from 3 centers with different population characteristics and laboratory processing methods. Main associations between LTL and psychosocial factors and LTL and race/ethnicity were evaluated and then compared across generalized estimating equations(GEE and linear regression models. Statistical models were adjusted for factors typically associated with LTL(age, gender, cancer status and also accounted for factors related to center differences, including laboratory methods(i.e., DNA extraction. Associations between LTL and psychosocial factors were also evaluated within race/ethnicity subgroups (Non-hispanic Whites, African Americans, and Hispanics.Beyond adjustment for age, gender, and cancer status, additional adjustments for DNA extraction and clustering by center were needed given their effects on LTL measurements. In adjusted GEE models, longer LTL was associated with African American race (Beta(β(standard error(SE = 0.09(0.04, p-value = 0.04 and Hispanic ethnicity (β(SE = 0.06(0.01, p-value = 0.02 compared to Non-Hispanic Whites. Longer LTL was also associated with less than a high school education compared to having greater than a high school education (β(SE = 0.06(0.02, p-value = 0.04. LTL was inversely related to perceived stress (β(SE = -0.02(0.003, p<0.001. In subgroup analyses, there was a negative association with LTL in African Americans with a high

  16. sFlt-1/PlGF ratio test for pre-eclampsia: an economic assessment for the UK.

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    Vatish, M; Strunz-McKendry, T; Hund, M; Allegranza, D; Wolf, C; Smare, C

    2016-12-01

    To assess the economic impact of introducing into clinical practice in the UK the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test for guiding the management of pre-eclampsia. We used an economic model estimating the incremental value of information, from a UK National Health Service payer's perspective, generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. The economic model estimated costs associated with the diagnosis and management of pre-eclampsia in pregnant women between 24 + 0 and 36 + 6 weeks' gestation, managed in either a 'test' scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a 'no-test' scenario in which clinical decisions are based on current diagnostic procedures alone. Test characteristics and resource use were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of pre-eclampsia. The main outcome measure from the economic model was the cost per patient per episode of care, from first suspicion of pre-eclampsia to birth. Introduction of the sFlt-1/PlGF ratio test into clinical practice is expected to result in cost savings of £344 per patient compared with a no-test scenario. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalization. Introducing the sFlt-1/PlGF ratio test into clinical practice in the UK was shown to be cost-saving by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia. In addition, the test ensures that those women at higher risk are identified and managed appropriately. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology

  17. [Effect of hydrogen peroxide on human leukocyte antigen-G expression in placental trophoblasts in pre-eclampsia].

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    Zhou, Xue; Sun, Li-zhou; Yin, Yin

    2010-05-01

    To explore the effect of hydrogen peroxide (H2O2) on the expression of human leukocyte antigen-G (HLA-G) in placental trophoblasts in pregnant women with pre-eclampsia. Forty pregnant women, delivered through cesarean section in the Department of Obstetrics of and Gynecology, the First Affiliated Hospital of Nanjing Medical University from October 2008 to October 2009, were enrolled, including 20 women with pre-eclampsia and 20 healthy gravidas (control group). Colorimetry and western blot were applied, respectively, to determine the level of H2O2 and the expression of HLA-G protein in placental tissues and the correlation between them were analyzed. After 24 hours of seeding, JEG-3 cells (the HLA-G positive cell line of choriocarcinoma) were divided into two groups: intervention group (exposure to 175 micromol/L H2O2) and control group (without H2O2). Immunofluorescence and western blot were used to investigate the expression of HLA-G protein in JEG-3 cells at 24 hours and 48 hours after incubation. (1) The level of H2O2 in placenta in the pre-eclampsia group was significantly higher than that in control group [(105+/-13) nmolxmg(-1)xprot(-1) vs (62+/-18) nmol.mg(-1)xprot(-1), PHLA-G protein in placenta of the pre-eclampsia group was reduced by 88% compared with that of the control (0.20+/-0.08 vs 1.67+/-0.65, PHLA-G level and H2O2 expression in the placenta in both groups (r=-0.895, P=0.000). (4) Compared with the control group, the expression of HLA-G protein in JEG-3 cells, after 24 hours and 48 hours exposure to H2O2, reduced by 39% and 80%, respectively, (3.21+/-0.33 vs 1.95+/-0.25 and 0.65+/-0.08, PHLA-G in JEG-E cells in the intervention group at 48 hours compared to the control group (PHLA-G expression in the placental trophoblasts in pre-eclampsia which may be involved in the pathogenesis of pre-eclampsia.

  18. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia.

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    Duley, Lelia; Gülmezoglu, A Metin; Henderson-Smart, David J; Chou, Doris

    2010-11-10

    Eclampsia, the occurrence of a seizure (fit) in association with pre-eclampsia, is rare but potentially life-threatening. Magnesium sulphate is the drug of choice for treating eclampsia. This review assesses its use for preventing eclampsia. To assess the effects of magnesium sulphate, and other anticonvulsants, for prevention of eclampsia. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (4 June 2010), and the Cochrane Central Register of Controlled Trials Register (The Cochrane Library 2010, Issue 3). Randomised trials comparing anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs, for pre-eclampsia. Two authors assessed trial quality and extracted data independently. We included 15 trials. Six (11,444 women) compared magnesium sulphate with placebo or no anticonvulsant: magnesium sulphate more than a halved the risk of eclampsia (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; number needed to treat for an additional beneficial outcome (NNTB) 100, 95% CI 50 to 100), with a non-significant reduction in maternal death (RR 0.54, 95% CI 0.26 to 1.10) but no clear difference in serious maternal morbidity (RR 1.08, 95% CI 0.89 to 1.32). It reduced the risk of placental abruption (RR 0.64, 95% CI 0.50 to 0.83; NNTB 100, 95% CI 50 to 1000), and increased caesarean section (RR 1.05, 95% CI 1.01 to 1.10). There was no clear difference in stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15). Side effects, primarily flushing, were more common with magnesium sulphate (24% versus 5%; RR 5.26, 95% CI 4.59 to 6.03; number need to treat for an additional harmful outcome (NNTH) 6, 95% CI 5 to 6).Follow-up was reported by one trial comparing magnesium sulphate with placebo: for 3375 women there was no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53) or morbidity potentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26) (median follow-up 26 months); for 3283 children exposed in utero

  19. Effects of size at birth, childhood growth patterns and growth hormone treatment on leukocyte telomere length.

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    Carolina C J Smeets

    Full Text Available Small size at birth and rapid growth in early life are associated with increased risk of cardiovascular disease in later life. Short children born small for gestational age (SGA are treated with growth hormone (GH, inducing catch-up in length. Leukocyte telomere length (LTL is a marker of biological age and shorter LTL is associated with increased risk of cardiovascular disease.To investigate whether LTL is influenced by birth size, childhood growth and long-term GH treatment.We analyzed LTL in 545 young adults with differences in birth size and childhood growth patterns. Previously GH-treated young adults born SGA (SGA-GH were compared to untreated short SGA (SGA-S, SGA with spontaneous catch-up to a normal body size (SGA-CU, and appropriate for gestational age with a normal body size (AGA-NS. LTL was measured using a quantitative PCR assay.We found a positive association between birth length and LTL (p = 0.04, and a trend towards a positive association between birth weight and LTL (p = 0.08, after adjustments for gender, age, gestational age and adult body size. Weight gain during infancy and childhood and fat mass percentage were not associated with LTL. Female gender and gestational age were positively associated with LTL, and smoking negatively. After adjustments for gender, age and gestational age, SGA-GH had a similar LTL as SGA-S (p = 0.11, SGA-CU (p = 0.80, and AGA-NS (p = 0.30.Larger size at birth is positively associated with LTL in young adulthood. Growth patterns during infancy and childhood are not associated with LTL. Previously GH-treated young adults born SGA have similar LTL as untreated short SGA, SGA with spontaneous catch-up and AGA born controls, indicating no adverse effects of GH-induced catch-up in height on LTL.

  20. Genetic association study of selected candidate genes (ApoB, LPL, Leptin and telomere length in obese and hypertensive individuals

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    Saini Divyalakshmi

    2009-09-01

    Full Text Available Abstract Background A genetic study was carried out among obese and hypertensive individuals from India to assess allelic association, if any, at three candidate loci: Apolipoprotein B (ApoB minisatellite and two tetranucleotide repeat loci; LPL (Lipoprotein lipase and Leptin. Attempt has also been made to find out whether telomere length attrition is associated with hypertension and obese individuals. Methods Venous blood samples were collected from 37 normal, 35 obese and 47 hypertensive individuals. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMC and PCR amplifications were achieved using locus specific primers. Genotyping of ApoB minisatellite was performed using 4% polyacrylamide gel electrophoresis (PAGE followed by silver staining, whereas LPL and Leptin loci were genotyped using ALF Express™ DNA sequencer. Telomere length was determined using a recently developed real time based quantitative PCR, where the relative telomere length was determined by calculating the relative ratio of telomere (T and single copy gene (S PCR products which is expressed as T/S ratio. Results All the three loci are highly polymorphic, display high heterozygosity and conform to Hardy-Weinberg's equilibrium expectations. ApoB minisatellite displayed 14 alleles, whereas LPL and Leptin tetranucleotide loci were having 9 and 17 alleles, respectively. Interestingly two new alleles (9 and 11 repeats were detected at ApoB locus for the first time. The alleles at Leptin locus were classified as Class I (lower alleles: 149-200 bp and Class II alleles (higher alleles: >217 bp. Higher alleles at ApoB (>39 repeats, predominant allele 9 at LPL and alleles 164 bp and 224 bp at Leptin loci have shown allelic association with hypertensive individuals. After adjusting the influence of age and gender, the analysis of co-variance (ANCOVA revealed the relative telomere length (T/S ratio in hypertensive individuals to be (1.01 ± 0.021, which was

  1. Relative Leukocyte Telomere Length, Hematological Parameters and Anemia - Data from the Berlin Aging Study II (BASE-II).

    Science.gov (United States)

    Meyer, Antje; Salewsky, Bastian; Buchmann, Nikolaus; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

    2016-01-01

    The length of the chromosome ends, telomeres, is widely accepted as a biomarker of aging. However, the dynamic of the relationship between telomere length and hematopoietic parameters in the normal aging process, which is of particular interest with respect to age-related anemia, is not well understood. We have analyzed the relationship between relative leukocyte telomere length (rLTL) and several hematological parameters in the older group of the Berlin Aging Study II (BASE-II) participants. This paper also compares rLTL between both BASE-II age groups (22-37 and 60-83 years). Genomic DNA was extracted from peripheral blood leukocytes of BASE-II participants and used to determine rLTL by a quantitative PCR protocol. Standard methods were used to determine blood parameters, and the WHO criteria were used to identify anemic participants. Telomere length data were available for 444 younger participants (28.4 ± 3.1 years old; 52% women) and 1,460 older participants (68.2 ± 3.7 years old; 49.4% women). rLTL was significantly shorter in BASE-II participants of the older group (p = 3.7 × 10-12) and in women (p = 4.2 × 10-31). rLTL of older men exhibited a statistically significant, positive partial correlation with mean corpuscular hemoglobin (MCH; p = 0.012) and MCH concentration (p = 0.002). While these correlations were only observed in men, the rLTL of older women was negatively correlated with the number of thrombocytes (p = 0.015) in the same type of analysis. Among all older participants, 6% met the criteria to be categorized as 'anemic'; however, there was no association between anemia and rLTL. In the present study, we have detected isolated correlations between rLTL and hematological parameters; however, in all cases, rLTL explained only a small part of the variation of the analyzed parameters. In disagreement with some other studies showing similar data, we interpret the association between rLTL and some of the hematological parameters studied here to be

  2. Systemic lupus erythematosus and vitamin D deficiency are associated with shorter telomere length among African Americans: a case-control study.

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    Brett M Hoffecker

    Full Text Available Systemic lupus erythematosus (SLE is a chronic systemic autoimmune disease that disproportionately affects African American females. The causes of SLE are unknown but postulated to be a combination of genetic predisposition and environmental triggers. Vitamin D deficiency is one of the possible environmental triggers. In this study we evaluated relationships between vitamin D status, cellular aging (telomere length and anti-telomere antibodies among African American Gullah women with SLE. The study population included African American female SLE patients and unaffected controls from the Sea Island region of South Carolina. Serum 25-hydroxyvitamin D levels were measured using a nonchromatographic radioimmunoassay. Telomere length was measured in genomic DNA of peripheral blood mononuclear cells (PBMCs by monochrome multiplex quantitative PCR. Anti-telomere antibody levels were measured by enzyme-linked immunosorbent assay (ELISA. Patients with SLE had significantly shorter telomeres and higher anti-telomere antibody titers compared to age- and gender-matched unaffected controls. There was a positive correlation between anti-telomere antibody levels and disease activity among patients and a significant correlation of shorter telomeres with lower 25-hydroxyvitamin D levels in both patients and controls. In follow-up examination of a subset of the patients, the patients who remained vitamin D deficient tended to have shorter telomeres than those patients whose 25-hydroxyvitamin D levels were repleted. Increasing 25-hydroxyvitamin D levels in African American patients with SLE may be beneficial in maintaining telomere length and preventing cellular aging. Moreover, anti-telomere antibody levels may be a promising biomarker of SLE status and disease activity.

  3. Downregulation of histone methyltransferase genes SUV39H1 and SUV39H2 increases telomere length in embryonic stem-like cells and embryonic fibroblasts in pigs.

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    Dang-Nguyen, Thanh Quang; Haraguchi, Seiki; Furusawa, Tadashi; Somfai, Tamas; Kaneda, Masahiro; Watanabe, Shinya; Akagi, Satoshi; Kikuchi, Kazuhiro; Tajima, Atsushi; Nagai, Takashi

    2013-01-01

    Telomere is a nucleoprotein structure at the ends of chromosomes that helps to protect the ends of chromosomes from being fused with other chromosomes. Knockout of histone methyltransferases Suv39h1 and Suv39h2 increases the telomere length in murine cells, whereas downregulation of SUV39H1 and SUV39H2 genes decreases the telomere length in human cells, suggesting that telomere biology is different among mammalian species. However, epigenetic regulation of the telomere has not been studied in mammals other than the human and mouse. In the present study, the effect of knockdown of SUV39H1 and SUV39H2 genes on telomere length was examined in porcine embryonic stem-like cells (pESLCs) and porcine embryonic fibroblasts (PEFs). The telomeres in SUV39H1 and SUV39H2 knockdown (SUV39KD) pESLCs (37.1 ± 0.9 kb) were longer (Ptelomeres (22.1 ± 0.4 kb; Ptelomere elongation in SUV39KD pESLCs and SUV39KD PEFs. Relative levels of trimethylation of histone H3 lysine 9 and expressions of DNMT1, DNMT3A and DNMT3B were decreased in SUV39KD cells, suggesting that telomere lengthening in SUV39KD pESLCs and SUV39KD PEFs might be not only related to the loss of histone modification marks but also linked to the decrease in DNA methyltransferase in pigs.

  4. Community perceptions of pre-eclampsia in rural Karnataka State, India: a qualitative study.

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    Vidler, Marianne; Charantimath, Umesh; Katageri, Geetanjali; Ramadurg, Umesh; Karadiguddi, Chandrashekhar; Sawchuck, Diane; Qureshi, Rahat; Dharamsi, Shafik; von Dadelszen, Peter; Derman, Richard; Goudar, Shivaprasad; Mallapur, Ashalata; Bellad, Mrutyunjaya

    2016-06-08

    Maternal deaths have been attributed in large part to delays in recognition of illness, timely transport to facility, and timely treatment once there. As community perceptions of pregnancy and their complications are critical to averting maternal morbidity and mortality, this study sought to contribute to the literature and explore community-based understandings of pre-eclampsia and eclampsia. The study was conducted in rural Karnataka State, India, in 2012-2013. Fourteen focus groups were held with the following community stakeholders: three with community leaders (n = 27), two with male decision-makers (n = 19), three with female decision-makers (n = 41), and six with reproductive age women (n = 132). Focus groups were facilitated by local researchers with clinical and research expertise. Discussions were audio-recorded, transcribed verbatim and translated to English for thematic analysis using NVivo 10. Terminology exists in the local language (Kannada) to describe convulsions and hypertension, but there were no terms that are specific to pregnancy. Community participants perceived stress, tension and poor diet to be precipitants of hypertension in pregnancy. Seizures in pregnancy were thought to be brought on by anaemia, poor medical adherence, lack of tetanus toxoid immunization, and exposure in pregnancy to fire or water. Sweating, fatigue, dizziness-unsteadiness, swelling, and irritability were perceived to be signs of hypertension, which was recognized to have the potential to lead to eclampsia or death. Home remedies, such as providing the smell of onion, placing an iron object in the hands, or squeezing the fingers and toes, were all used regularly to treat seizures prior to accessing facility-based care although transport is not delayed. It is evident that 'pre-eclampsia' and 'eclampsia' are not well-known; instead hypertension and seizures are perceived as conditions that may occur during or outside pregnancy. Improving community

  5. Consumption of Nuts and Seeds and Telomere Length in 5,582 Men and Women of the National Health and Nutrition Examination Survey (NHANES).

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    Tucker, L A

    2017-01-01

    Consumption of nuts and seeds is associated favorably with all-cause mortality. Nuts and seeds could reduce disease and prolong life by influencing telomeres. Telomere length is a good indicator of the senescence of cells. The purpose of the present study was to determine the relationship between nuts and seeds intake and leukocyte telomere length, a biomarker of biologic aging. Cross-sectional. A total of 5,582 randomly selected men and women from the National Health and Nutrition Examination Survey (NHANES), 1999-2002, were studied. DNA was obtained via blood samples. Telomere length was assessed using the quantitative polymerase chain reaction method. A validated, multi-pass, 24-h recall dietary assessment, administered by NHANES, was employed to quantify consumption of nuts and seeds. Nuts and seeds intake was positively and linearly associated with telomere length. For each 1-percent of total energy derived from nuts and seeds, telomere length was 5 base pairs longer (F=8.6, P=0.0065). Given the age-related rate of telomere shortening was 15.4 base pairs per year (F=581.1, Pseeds. Consumption of nuts and seeds accounts for meaningful decreases in biologic aging and cell senescence. The findings reinforce the recommendations of the 2015-2020 Dietary Guidelines for Americans, which encourage the consumption of nuts and seeds as part of a healthy diet.

  6. Leukocyte Telomere Length and Serum Levels of High-Molecular-Weight Adiponectin and Dehydroepiandrosterone-Sulfate Could Reflect Distinct Aspects of Longevity in Japanese Centenarians

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    Yuji Aoki MD, PhD

    2017-03-01

    Full Text Available Leukocyte telomere length and serum levels of high-molecular-weight adiponectin and dehydroepiandrosterone-sulfate (DHEA-S were assessed in association with nutrition and performance status (PS in Japanese centenarians. Twenty-three centenarians (five men, 18 women were classified according to their PS 1 (nearly fully ambulatory, n = 2, 2 (in bed less than 50% of daytime, n = 10, 3 (in bed greater than 50%, n = 6, and 4 (completely bedridden, n = 5. Leukocyte telomere length was determined by the hybridization protection assay, and the adiponectin and DHEA-S levels were measured by chemiluminescent enzyme immunoassay. Among variables of PS, body mass index (BMI, albumin, adiponectin, DHEA-S, and telomere length, there were significant correlations between PS and albumin ( r = −.694, p < .01, between telomere length and BMI ( r = .522, p < .05, between adiponectin and BMI ( r = −.574, p < .01, and between DHEA-S and albumin ( r = .530, p < .01. When excluding two cancer-bearing centenarians with short telomere, telomere length significantly correlated with PS ( r = −.632, p < .01. It was indicated that the short leukocyte telomere was associated with poor PS and cancer development and that the adiponectin or DHEA-S was associated with adiposity or nutritional status. Despite a small number of subjects, these biomarkers seemed to reflect distinct aspects of longevity in Japanese centenarians.

  7. Diurnal and stress-reactive dehydroepiandrosterone levels and telomere length in youth

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    Andrew R Dismukes

    2016-05-01

    Full Text Available The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA and telomere length (TL in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C. TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05, while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging.

  8. Short leukocyte telomere length is associated with obesity in American Indians: The strong heart family study

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    Chen, Shufeng; Yeh, Fawn; Lin, Jue; Matsuguchi, Tet; Blackburn, Elizabeth; Lee, Elisa T.; Howard, Barbara V.; Zhao, Jinying

    2014-01-01

    Shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders including cardiovascular disease (CVD) and diabetes. Obesity is an important risk factor for CVD and diabetes. The association of LTL with obesity is not well understood. This study for the first time examines the association of LTL with obesity indices including body mass index, waist circumference, percent body fat, waist-to-hip ratio, and waist-to-height ratio in 3,256 American Indians (14-93 years old, 60% women) participating in the Strong Heart Family Study. Association of LTL with each adiposity index was examined using multivariate generalized linear mixed model, adjusting for chronological age, sex, study center, education, lifestyle (smoking, alcohol consumption, and total energy intake), high-sensitivity C-reactive protein, hypertension and diabetes. Results show that obese participants had significantly shorter LTL than non-obese individuals (age-adjusted P=0.0002). Multivariate analyses demonstrate that LTL was significantly and inversely associated with all of the studied obesity parameters. Our results may shed light on the potential role of biological aging in pathogenesis of obesity and its comorbidities. PMID:24861044

  9. Alterations in leukocyte telomere length in workers occupationally exposed to benzene.

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    Bassig, Bryan A; Zhang, Luoping; Cawthon, Richard M; Smith, Martyn T; Yin, Songnian; Li, Guilan; Hu, Wei; Shen, Min; Rappaport, Stephen; Barone-Adesi, Francesco; Rothman, Nathaniel; Vermeulen, Roel; Lan, Qing

    2014-10-01

    Exposure to benzene, a known leukemogen and probable lymphomagen, has been demonstrated to result in oxidative stress, which has previously been associated with altered telomere length (TL). TL specifically has been associated with several health outcomes in epidemiologic studies, including cancer risk, and has been demonstrated to be altered following exposure to a variety of chemical agents. To evaluate the association between benzene exposure and TL, we measured TL by monochrome multiplex quantitative PCR in 43 workers exposed to high levels of benzene and 43 age and sex-matched unexposed workers in Shanghai, China. Benzene exposure levels were monitored using organic vapor passive dosimetry badges before phlebotomy. The median benzene exposure level in exposed workers was 31 ppm. The mean TL in controls, workers exposed to levels of benzene below the median (≤31 ppm), and above the median (>31 ppm) was 1.26 ± 0.17, 1.25 ± 0.16, and 1.37 ± 0.23, respectively. Mean TL was significantly elevated in workers exposed to >31 ppm of benzene compared with controls (P = 0.03). Our findings provide evidence that high levels of occupational benzene exposure are associated with TL. Environ. Published [2014]. This article is a U.S. Government work and is in the public domain in the USA.

  10. Association of Leukocyte Telomere Length with Fatigue in Nondisabled Older Adults

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    Laila Bendix

    2014-01-01

    Full Text Available Introduction. Fatigue is often present in older adults with no identified underlying cause. The accruing burden of oxidative stress and inflammation might be underlying factors of fatigue. We therefore hypothesized that leukocyte telomere length (LTL is relatively short in older adults who experience fatigue. Materials and Methods. We assessed 439 older nondisabled Danish twins. LTL was measured using Southern blots of terminal restriction fragments. Fatigue was measured by the Mob-T Scale based on questions on whether the respondents felt fatigued after performing six mobility items. Results. LTL was significantly associated with fatigue (P=0.023, showing an increase of 0.038 kb/fatigue score unit. Aging-related diseases and mental health did not explain the association, while lifestyle factors slightly attenuated the estimates. Conclusion. Our results support an association between LTL and fatigue. Further studies are required to confirm this finding and the link of LTL with oxidative stress/inflammation over the life course.

  11. Inflammatory Long Pentraxin 3 is Associated with Leukocyte Telomere Length in Night-Shift Workers

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    Sofia Pavanello

    2017-05-01

    Full Text Available Aging is an emerging worldwide threat to public health, even in the workplace, as it links with risk of illness and death. Bewildered inflammatory responses and stressful conditions associate with age-related disorders. Additionally, circadian rhythm disruption, a critical health issue in night-shift workers, correlates with premature aging. We investigated the hypothesis of a link between altered inflammatory response, detected by plasmatic long pentraxin 3 (PTX3, and biological aging, measured by leukocyte telomere length (LTL, attrition, and possibly induced by night-shift work. Within the framework of a cross-sectional study, such possible relationships were appraised by simultaneous equation model (SEM technique among day and night-shift hospital workers. PTX3 levels, modulated by several aging conditions [i.e., body mass index (BMI (beta = −0.22; p = 0.022, C-reactive protein (CRP (beta = −0.07; p = 0.000, and cardiovascular diseases with hypertension included (CVD (beta = −0.12; p = 0.000], positively associate with LTL (coefficient = 0.15; p = 0.033. LTL, in turn is reduced by CVD (beta = −0.15; p = 0.000, binge drinking (beta = −0.10; p = 0.004, and CRP (beta = −0.05; p = 0.026. On the other hand, night-shift work, found to be remarkably free from aging risk factors [i.e., age (beta = −0.13; p = 0.017, BMI (beta = −0.17; p = 0.030, CVD (beta = −0.14; p = 0.000, and binge drinking (beta = −0.13; p = 0.000], does associate almost significantly with reversed PTX3 (coefficient = −0.09; p = 0.089 and even with CRP (beta = 0.17; p = 0.000. In conclusion, the SEM analysis indicates that PTX3 is positively linked to LTL. The finding suggests a possible new role of this long pentraxin that, by orchestrating an efficient governance of inflammatory processes, may protect telomere from attrition, ensuring therefore the

  12. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder.

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    Boks, Marco P; van Mierlo, Hans C; Rutten, Bart P F; Radstake, Timothy R D J; De Witte, Lot; Geuze, Elbert; Horvath, Steve; Schalkwyk, Leonard C; Vinkers, Christiaan H; Broen, Jasper C A; Vermetten, Eric

    2015-01-01

    Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out. From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure. The association of trauma with telomere length was in the expected direction but not significant (B=-10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid early life trauma exposure did not

  13. Ethanol-Associated Cardiomyocyte Apoptosis and Left Ventricular Dilation Are Unrelated to Changes in Myocardial Telomere Length in Rats.

    Science.gov (United States)

    Raymond, Andrew R; Becker, Jason; Woodiwiss, Angela J; Booysen, Hendrik L; Norton, Gavin R; Brooksbank, Richard L

    2016-04-01

    The aim of this work was to determine whether ethanol-associated myocardial apoptosis and cardiac dilation are related to myocardial telomere shortening in rats. Sprague-Dawley (SD) rats received either drinking water with (ethanol: n = 19) or without (control: n = 19) 5% (v/v) ethanol ad libitum, for 4 months. Left ventricular (LV) dimensions and function (echocardiography and isolated perfused heart preparations), cardiomyocyte apoptosis (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling), and leukocyte and myocardial telomere length (real-time polymerase chain reaction) were determined at the end of the study. Ethanol administration resulted in a marked increase in cardiomyocyte apoptosis (ethanol 0.85 ± 0.13% vs control 0.36 ± 0.06%; P = .0021) and LV dilation (LV end-diastolic diameter: ethanol 8.20 ± 0.14 mm vs control 7.56 ± 0.11 mm [P = .0014]; volume intercept at 0 mm Hg (V0) of the LV end-diastolic pressure-volume relationship: ethanol 0.40 ± 0.03 mL vs control 0.31 ± 0.02 mL [P = .020]). However, there were no changes in systolic chamber function as indexed by LV endocardial fractional shortening or the slope of the LV systolic pressure-volume relationship (end systolic elastance). The percentage of myocardial apoptosis was correlated with the degree of LV dilation (% apoptosis vs LV EDD: r = 0.39; n = 38; P = .021; vs V0: r = 0.44; n = 19; P = .046). No differences in leukocyte or cardiac telomere length were noted between the ethanol and control groups. Furthermore, cardiac telomere length was not associated with indexes of LV dilation (LVEDD and V0) or cardiomyocyte apoptosis. Chronic ethanol-associated myocardial apoptosis and adverse remodeling occurs independently from changes in cardiac telomere length. Telomere shortening may not be a critical mechanism responsible for cardiomyocyte apoptosis and adverse cardiac remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Where You Live May Make You Old: The Association between Perceived Poor Neighborhood Quality and Leukocyte Telomere Length.

    Science.gov (United States)

    Park, Mijung; Verhoeven, Josine E; Cuijpers, Pim; Reynolds, Charles F; Penninx, Brenda W J H

    2015-01-01

    Strong evidence supports that living in disadvantaged neighborhoods has direct unfavorable impact on mental and physical health. However, whether it also has direct impact on cellular health is largely unknown. Thus we examined whether neighborhood quality was associated with leukocyte telomere length, an indicator of cellular aging. In May 2014, we extracted and analyzed baseline data from the Netherlands Study of Depression and Anxiety (NESDA), a large epidemiological study of individuals age between 18-65 years (n=2902). Telomere length was determined using quantitative polymerase chain reaction. Neighborhood quality was assessed using modified measures of perceived neighborhood disorder, fear of crime, and noise. We used multivariable linear regression models to examine association between perceived neighborhood quality and telomere length with comprehensive adjustment for individual and community characteristics related to socioeconomic and demographic status, urbanization level, mental and physical health, and lifestyle. Compared to individuals who reported good neighborhood quality, the mean telomere length of those who reported moderate neighborhood quality was approximately 69 base pair shorter (β =-69.33, 95% CI: -119.49, -19.17, p= 0.007), and that of those who reported poor neighborhood quality were 174 base pair shorter (β =-173.80, 95% CI: -298.80, -49.01, p=0.006). For illustrative purposes, one could extrapolate these outcomes to 8.7 and 11.9 years in chronological age, respectively. We have established an association between perceived neighborhood quality and cellular aging over and above a range of individual attributes. Biological aging processes may be impacted by socioeconomic milieu.

  15. Where You Live May Make You Old: The Association between Perceived Poor Neighborhood Quality and Leukocyte Telomere Length.

    Directory of Open Access Journals (Sweden)

    Mijung Park

    Full Text Available Strong evidence supports that living in disadvantaged neighborhoods has direct unfavorable impact on mental and physical health. However, whether it also has direct impact on cellular health is largely unknown. Thus we examined whether neighborhood quality was associated with leukocyte telomere length, an indicator of cellular aging.In May 2014, we extracted and analyzed baseline data from the Netherlands Study of Depression and Anxiety (NESDA, a large epidemiological study of individuals age between 18-65 years (n=2902. Telomere length was determined using quantitative polymerase chain reaction. Neighborhood quality was assessed using modified measures of perceived neighborhood disorder, fear of crime, and noise. We used multivariable linear regression models to examine association between perceived neighborhood quality and telomere length with comprehensive adjustment for individual and community characteristics related to socioeconomic and demographic status, urbanization level, mental and physical health, and lifestyle.Compared to individuals who reported good neighborhood quality, the mean telomere length of those who reported moderate neighborhood quality was approximately 69 base pair shorter (β =-69.33, 95% CI: -119.49, -19.17, p= 0.007, and that of those who reported poor neighborhood quality were 174 base pair shorter (β =-173.80, 95% CI: -298.80, -49.01, p=0.006. For illustrative purposes, one could extrapolate these outcomes to 8.7 and 11.9 years in chronological age, respectively.We have established an association between perceived neighborhood quality and cellular aging over and above a range of individual attributes. Biological aging processes may be impacted by socioeconomic milieu.

  16. Relationships of Risk Factors for Pre-Eclampsia with Patterns of Occurrence of Isolated Gestational Proteinuria during Normal Term Pregnancy

    Science.gov (United States)

    Macdonald-Wallis, Corrie; Lawlor, Debbie A.; Heron, Jon; Fraser, Abigail; Nelson, Scott M.; Tilling, Kate

    2011-01-01

    Background Isolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept. Methods Data from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy. Results Higher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (≤20 weeks gestation), and onset at 21–28 weeks, 29–32 weeks, 33–36 weeks and ≥37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy. Conclusions Established pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of pre-eclampsia. PMID:21789220

  17. Restraint of Trophoblast Invasion of the Uterus by Decorin: Role in Pre-eclampsia.

    Science.gov (United States)

    Nandi, Pinki; Siddiqui, Mohammad Fyyaz; Lala, Peeyush K

    2016-03-01

    Decorin (DCN) is a leucine-rich, TGF-β binding proteoglycan produced by mesenchymal cells including chondrocytes, dermal fibroblasts, and uterine decidual cells. It exerts multiple physiological functions including collagen fibrillogenesis, myogenesis, angiostasis, and restraining placental invasiveness. We discovered that decidua-derived DCN restrains proliferation, migration, and invasion of extravillous trophoblast (EVT) cells of the human placenta in a TGF-β-independent manner. These functions were differentially mediated by binding of DCN to multiple tyrosine kinase receptors (TKR) including EGFR, IGFR1, and VEGFR2. DCN blocked VEGFR-2 dependent EVT cell migration and endovascular differentiation by inhibiting P38MAPK and ERK1/2 pathways.We identified the avid VEGFR2 binding site in DCN protein as a 12 amino acids (LGTNPLKSSGIE) span in the Leucine-rich-repeat (LRR) 5 region of domain III. A single amino acid mutation (substitution of K to A) of DCN at this site abrogated VEGFR-2- dependent DCN actions. Also, DCN mRNA expression, measured with in situ hybridization, was selectively upregulated in decidual cells in placentas from mothers suffering from pre-eclampsia (PE), whereas the expression levels remained unchanged in chorionic villus mesenchymal cells. This difference between PE and control placentas was present at all gestational ages, indicating the pathogenic role of DCN in PE. We hypothesize that increased blood DCN levels could be a candidate biomarker for PE. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Maternal venous Doppler characteristics are abnormal in pre-eclampsia but not in gestational hypertension.

    Science.gov (United States)

    Gyselaers, W; Staelens, A; Mesens, T; Tomsin, K; Oben, J; Vonck, S; Verresen, L; Molenberghs, G

    2015-04-01

    To compare functional characteristics of maternal thoraco-abdominal arteries and veins in proteinuric and non-proteinuric hypertension in pregnancy. This retrospective study included women with singleton pregnancies during the third trimester, which were either uncomplicated or complicated with different clinical types of hypertension: non-proteinuric gestational hypertension (GH), early-onset pre-eclampsia (PE) diagnosed 150 pregnancies were evaluated: 22 with uncomplicated pregnancy, 41 GH, 31 early PE and 56 late PE. Aortic VI and ACI were lower in GH, early PE and late PE than in uncomplicated pregnancy. Both early PE and late PE differed from GH by having shorter APTT in the uterine arcuate arteries and higher RIVI. Hemodynamic abnormalities were most pronounced in early PE, during which uterine arcuate artery RI was higher and VPTT in kidneys was shorter than in late PE. There was a significant correlation between degree of proteinuria and RIVI for the left (r = 0.381) and right (r = 0.347) kidney in late PE, but this was not true for early PE. There is a gradient of worsening arterial and venous hemodynamic abnormalities from GH to late PE and then to early PE. Venous hemodynamic abnormalities are present only in PE, with a linear correlation between proteinuria and RIVI in late PE. The role of the maternal venous compartment in the pathophysiology and etiology of PE-related symptoms may be much more important than considered at present. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  19. Syncytiotrophoblast Extracellular Vesicles from Pre-Eclampsia Placentas Differentially Affect Platelet Function.

    Directory of Open Access Journals (Sweden)

    Dionne S Tannetta

    Full Text Available Pre-eclampsia (PE complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition.

  20. Dydrogesterone support following assisted reproductive technique (ART) reduces the risk of pre-eclampsia.

    Science.gov (United States)

    Ali, Anizah Bt; Ahmad, Mohd Faizal B; Kwang, Ng Beng; Shan, Lim Pei; Shafie, Nasir Mohamed; Omar, Mohd Hashim

    2016-09-01

    Pre-eclampsia (PE) contributes to poor maternal morbidity and mortality. Progesterone is hypothesised to reduce the risk of PE. To determine the effect of progestogen supplementation during assisted reproductive technique (ART) in reducing the incidence of PE. A retrospective comparative analysis among 1140 pregnancies between January 2006 and March 2015 conducted in a tertiary centre. A total of 570 pregnancies who conceived following ART with progesterone supplementation (study group) and an age-matched spontaneous pregnancies, without progesterone supplementation (control group, n=570) were included in the analysis. The study group received progesterone support following ART or intrauterine insemination (IUI) until 14-16 weeks' gestation. The rate of PE was significantly lower in the study group compared to control group (8.4% vs. 14.2%, p<0.05). Women supplemented with dydrogesterone only showed a lower PE incidence as compared to women received a combination of dydrogesterone and hydroxyprogesterone caproate, however, it was not statistically significant (6.9% vs. 9.9%; 6.9%; p=0.2).

  1. Syncytiotrophoblast Extracellular Vesicles from Pre-Eclampsia Placentas Differentially Affect Platelet Function.

    Science.gov (United States)

    Tannetta, Dionne S; Hunt, Kathryn; Jones, Chris I; Davidson, Naomi; Coxon, Carmen H; Ferguson, David; Redman, Christopher W; Gibbins, Jonathan M; Sargent, Ian L; Tucker, Katherine L

    2015-01-01

    Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition.

  2. Association between nephrinuria, podocyturia, and proteinuria in women with pre-eclampsia.

    Science.gov (United States)

    Furuta, Itsuko; Zhai, Tianyue; Ishikawa, Satoshi; Umazume, Takeshi; Nakagawa, Kinuko; Yamada, Takahiro; Morikawa, Mamoru; Minakami, Hisanori

    2017-01-01

    Podocyte depletion in the kidney is associated with end-stage kidney disease (ESKD). Pre-eclampsia (PE) increases the risk of ESKD in later life. This study was performed to determine whether nephrinuria (soluble nephrin in the urine) is correlated with proteinuria and/or podocyturia (podocytes in the urine) in PE women. Eighty-three urine samples, consisting of 45 and 38 samples from 27 normotensive and nine PE women, respectively, underwent simultaneous determination of nephrin, protein, and creatinine concentrations in the urine supernatant and quantitative analysis of podocyte-specific protein mRNA expression. This included podocin (Pod-mRNA) and nephrin (Nep-mRNA), using real-time polymerase chain reaction in the pelleted urine. Nephrinuria and proteinuria were corrected by creatinine concentration. Pod- and Nep-mRNA expression levels were corrected by GAPDH. Nephrinuria, proteinuria, Pod-mRNA expression, and Nep-mRNA expression all increased with advancing gestation in PE women, while not in normotensive women. The nephrinuria was strongly correlated with proteinuria (R = 0.901, P proteinuria alone (R  =  0.419, P proteinuria and podocyturia in PE women. This suggested that increased nephrinuria/proteinuria was associated with podocyte loss in the kidneys of PE women. © 2016 Japan Society of Obstetrics and Gynecology.

  3. Choroidal changes in pre-eclampsia during pregnancy and the postpartum period: comparison with healthy pregnancy

    Directory of Open Access Journals (Sweden)

    Necati Duru

    2016-06-01

    Full Text Available ABSTRACT Purpose: To investigate subfoveal choroidal thickness (SFCT in patients with pre-eclampsia using enhanced depth imaging optical coherence tomography (EDI-OCT. Methods: A sample of 73 pregnant women was studied over 28 weeks of gestation. The sample was divided into two groups: one comprising pre-eclamptic pregnant women (n=32, and the other comprising healthy pregnant women (n=41. The SFCT was determined for all patients using EDI-OCT during pregnancy and at the third month of the postpartum period. Results: The SFCTs in pre-eclamptic pregnant women were 351.97 ± 22.44 and 332.28 ± 20.32 µm during the pregnancy and postpartum periods (p<0.001, respectively, whereas these values in healthy pregnant women were 389.73 ± 49.64 and 329.78 ± 22.36 µm (p<0.001, respectively. During pregnancy SFCT in pre-eclamptic pregnant women was significantly thinner than that in healthy pregnant women (p<0.001. However, there was no statistically significant difference during the postpartum period (p=0.623. Conclusions: The results suggest that SFCT is significantly decreased in pre-eclamptic pregnant women than in healthy pregnant women, despite no statistically significant difference in SFCT existing between the groups during the postpartum period.

  4. Reduction of telomeric length and c-erbB-2 gene amplification in human breast cancer, fibroadenoma, and gynecomastia. Relationship to histologic grade and clinical parameters

    National Research Council Canada - National Science Library

    Odagiri, E; Kanada, N; Jibiki, K; Demura, R; Aikawa, E; Demura, H

    1994-01-01

    .... The Southern blot analysis was used to measure telomeric length as well as the c-erbB-2 gene amplification of breast carcinomas, adjacent normal breast tissues, fibroadenomas, and cases of gynecomastia...

  5. Soda and cell aging: associations between sugar-sweetened beverage consumption and leukocyte telomere length in healthy adults from the National Health and Nutrition Examination Surveys

    National Research Council Canada - National Science Library

    Leung, Cindy W; Laraia, Barbara A; Needham, Belinda L; Rehkopf, David H; Adler, Nancy E; Lin, Jue; Blackburn, Elizabeth H; Epel, Elissa S

    2014-01-01

    ...) consumption and the risk of cardiometabolic disease. We examined cross-sectional associations between the consumption of SSBs, diet soda, and fruit juice and telomere length in a nationally representative sample of healthy adults...

  6. The power of exercise: buffering the effect of chronic stress on telomere length

    National Research Council Canada - National Science Library

    Puterman, Eli; Lin, Jue; Blackburn, Elizabeth; O'Donovan, Aoife; Adler, Nancy; Epel, Elissa

    2010-01-01

    Chronic psychological stress is associated with detrimental effects on physical health, and may operate in part through accelerated cell aging, as indexed by shorter telomeres at the ends of chromosomes...

  7. Identification of New Genes that Regulate Telomerase and Telomere Length in Budding Yeast

    National Research Council Canada - National Science Library

    Pennock, Erin

    2001-01-01

    ... of telomerase to the chromosome end. The exact molecular mechanism by which Cdc13 protects the telomere has not been elucidated, although Stn1, a protein previously shown to interact with Cdc13, may contribute to end protection...

  8. Identification of New Genes that Regulate Telomerase and Telomere Length in Budding Yeast

    National Research Council Canada - National Science Library

    Otero, Joel

    2003-01-01

    In budding yeast, Cdc13 has both an essential function in chromosome end protection as well as a non-essential role in telomere replication, by mediating recruitment of telomerase to the chromosome end...

  9. sFlt-1/PlGF for prediction of early-onset pre-eclampsia: STEPS (Study of Early Pre-eclampsia in Spain).

    Science.gov (United States)

    Perales, A; Delgado, J L; de la Calle, M; García-Hernández, J A; Escudero, A I; Campillos, J M; Sarabia, M D; Laíz, B; Duque, M; Navarro, M; Calmarza, P; Hund, M; Álvarez, F V

    2017-09-01

    A high ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) has been linked to pre-eclampsia (PE). We evaluated the sFlt-1/PlGF ratio as a predictive marker for early-onset PE in women at risk of PE. This prospective, Spanish, multicenter study included pregnant women with a risk factor for PE, including intrauterine growth restriction, PE, eclampsia or hemolysis, elevated liver enzymes and low platelet count syndrome in previous pregnancy, pregestational diabetes or abnormal uterine artery Doppler. The primary objective was to show that the sFlt-1/PlGF ratio at 20, 24 and 28 weeks' gestation was predictive of early-onset PE (< 34 + 0 weeks). Serum sFlt-1 and PlGF were measured at 20, 24 and 28 weeks. Multivariate logistic regression was used to develop a predictive model. A total of 819 women were enrolled, of which 729 were suitable for analysis. Of these, 78 (10.7%) women developed PE (24 early onset and 54 late onset). Median sFlt-1/PlGF ratio at 20, 24 and 28 weeks was 6.3 (interquartile range (IQR), 4.1-9.3), 4.0 (IQR, 2.6-6.3) and 3.3 (IQR, 2.0-5.9), respectively, for women who did not develop PE (controls); 14.5 (IQR, 5.5-43.7), 18.4 (IQR, 8.2-57.9) and 51.9 (IQR, 11.5-145.6) for women with early-onset PE; and 6.7 (IQR, 4.6-9.9), 4.7 (IQR, 2.8-7.2) and 6.0 (IQR, 3.8-10.5) for women with late-onset PE. Compared with early-onset PE, the sFlt-1/PlGF ratio was significantly lower in controls (P < 0.001 at each timepoint) and in women with chronic hypertension (P < 0.001 at each timepoint), gestational hypertension (P < 0.001 at each timepoint) and late-onset PE (P < 0.001 at each timepoint). A prediction model for early-onset PE was developed, which included the sFlt-1/PlGF ratio plus mean arterial pressure, being parous and previous PE, with areas under the receiver-operating characteristics curves of 0.86 (95% CI, 0.77-0.95), 0.91 (95% CI, 0.85-0.97) and 0.93 (95% CI, 0.86-0.99) at 20, 24 and 28 weeks, respectively, and was

  10. Childhood Physical and Sexual Abuse History and Leukocyte Telomere Length among Women in Middle Adulthood

    OpenAIRE

    Mason, Susan M.; Jennifer Prescott; Tworoger, Shelley S.; Immaculata DeVivo; Rich-Edwards, Janet W.

    2015-01-01

    Objective: Abuse victimization in childhood is associated with a variety of age-related cardiometabolic diseases, but the mechanisms remain unknown. Telomeres, which form the protective caps at the ends of chromosomes, have been proposed as measures of biological age, and a growing body of research suggests that telomere attrition may help to explain relationships between stress and cardiometabolic degradation. We examined the association between childhood abuse victimization and leukocyte te...

  11. Empirical evaluation of humpback whale telomere length estimates; quality control and factors causing variability in the singleplex and multiplex qPCR methods

    DEFF Research Database (Denmark)

    Olsen, Morten Tange; Bérubé, Martine; Robbins, Jooke

    2012-01-01

    steps of qPCR. In order to evaluate the utility of the qPCR method for telomere length estimation in non-model species, we carried out four different qPCR assays directed at humpback whale telomeres, and subsequently performed a rigorous quality control to evaluate the performance of each assay. RESULTS......:Performance differed substantially among assays and only one assay was found useful for telomere length estimation in humpback whales. The most notable factors causing these inter-assay differences were primer design and choice of using singleplex or multiplex assays. Inferred amplification efficiencies differed by up...

  12. Effects of Intentional Weight Loss on Markers of Oxidative Stress, DNA Repair and Telomere Length - a Systematic Review.

    Science.gov (United States)

    Himbert, Caroline; Thompson, Henry; Ulrich, Cornelia M

    2017-12-14

    Altered levels of markers of oxidative stress, DNA repair, and telomere integrity have been detected in obese individuals and may underlie the pathogenesis of obesity-related diseases. However, whether or not such effects are reversed by intentional weight loss has not been systematically reviewed. A literature search in PubMed/Medline identified 2,388 articles of which 21 studies (randomized controlled trial (RCT) (n = 10) and non-randomized intervention studies (n = 11)) were classified as testing the effects of intentional weight loss on i) oxidative stress (n = 15), ii) DNA repair (n = 2), and iii) telomere length (n = 4). Across a broad range of intervention designs, diet-, exercise-, surgery-, balloon-induced weight loss regimens decreased oxidative stress measures. Studies investigating DNA repair capacity or telomere length as endpoints after weight loss were less common in number and yielded null or inconsistent results, respectively. While this systematic review supports a role for intentional weight loss in reducing obesity-associated oxidative stress, it is not clear whether the effects are primary outcomes or secondary to improvement in obesity-associated insulin resistance and/or chronic inflammation. Although the lack of effect of intentional weight loss on DNA repair capacity might be anticipated given that oxidative stress is reduced, additional studies are needed. The inconsistent effects of weight loss on telomere length or DNA repair suggest the need for a re-assessment of intervention designs and assay methodology to definitively address this topic. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

  13. Association of human telomerase reverse transcriptase gene polymorphisms, serum levels, and telomere length with renal cell carcinoma risk and pathology.

    Science.gov (United States)

    de Martino, Michela; Taus, Christopher; Lucca, Ilaria; Hofbauer, Sebastian L; Haitel, Andrea; Shariat, Shahrokh F; Klatte, Tobias

    2016-10-01

    Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the human telomerase and plays a key role in telomere restitution and gene regulation. Evidence suggests that hTERT is linked with the risk and progression of several malignancies, but there are no comprehensive data in renal cell carcinoma (RCC). In this case-control study, we assessed seven polymorphic hTERT gene variants (MNS16A, rs2736100, rs2736098, rs7726159, rs2853677, rs13172201, and rs10069690), hTERT serum levels, and the telomere length of 663 individuals, including 243 with clear cell RCC and 420 age- and gender-matched healthy controls. The SL and SS genotypes of MNS16A were associated with a decreased risk for RCC on the multivariable logistic regression analysis (SL-OR 0.72, SS-OR 0.37, P < 0.001). The GG genotype of rs2736098 was associated with a decreased risk for RCC compared with AA (OR 0.18, P < 0.001). Both telomere length and hTERT serum levels increased with every G allele in rs2736098 (P = 0.008). Pretherapeutic hTERT serum levels were higher in patients with advanced tumor stages (P = 0.037) and distant metastases (P = 0.006). Rs2736100, rs7726159, rs2853677, rs13172201, and rs10069690 were not linked with RCC risk, and none of the polymorphisms was associated with RCC pathology. In conclusion, the polymorphic number of tandem repeats in hTERT (MNS16A) and rs2736098 may be linked with the risk for RCC. Rs2736098 may have an important role in telomere length restitution and serum hTERT levels may represent a novel biomarker for RCC. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  14. Telomere length in blood cells is related to the chronicity, severity, and recurrence rate of schizophrenia

    Directory of Open Access Journals (Sweden)

    Pawelczyk T

    2015-06-01

    Full Text Available Tomasz Pawelczyk,1 Bozena Szymanska,2 Marta Grancow-Grabka,3 Magdalena Kotlicka-Antczak,1 Agnieszka Pawelczyk1 1Department of Affective and Psychotic Disorders, Medical University of Lodz, Czechoslowacka, Lodz, Poland; 2Central Scientific Laboratory, Medical University of Lodz, Mazowiecka, Lodz, Poland; 3Central Teaching Hospital, Medical University of Lodz, Czechoslowacka, Lodz, PolandIntroduction: Telomere shortening is strongly associated with higher mortality rates and has been shown in a number of age-related diseases, such as cardiovascular disorders, diabetes mellitus, Alzheimer’s disease, and psychiatric disorders. Oxidative stress is known to induce DNA breaks and genome instability. Telomeric DNA rich in guanosine is particularly sensitive to such oxidative damages. Psychosis is associated with a disequilibrium between free radical production and antioxidative defense. Although telomere attrition has been demonstrated in schizophrenia, no relationship has been reported between telomere length and severity of schizophrenia.Aim: The aim of the present study was to identify differences in telomere length in peripheral blood cells between patients with chronic schizophrenia (C-SCZ and early schizophrenia (E-SCZ and to identify any relationship between telomere length and disease chronicity and severity.Methods: Relative average telomere lengths were determined using qPCR assay in patients with E-SCZ (n=42 and C-SCZ (n=44 hospitalized due to schizophrenia exacerbation. E-SCZ was diagnosed when less than 2 years had passed since the beginning of psychotic symptoms. The severity of symptoms was assessed using appropriate scales.Results: The severity of schizophrenia symptoms, as well as the number of psychotic episodes and hospital admissions, correlated significantly with telomere length in univariate analyses. Regression analysis revealed that a model incorporating study group (E-SCZ or C-ECZ, sex, and age, as well as the combined

  15. Buccal telomere length and its associations with cortisol, heart rate variability, heart rate, and blood pressure responses to an acute social evaluative stressor in college students.

    Science.gov (United States)

    Woody, Alex; Hamilton, Katrina; Livitz, Irina E; Figueroa, Wilson S; Zoccola, Peggy M

    2017-05-01

    Understanding the relationship between stress and telomere length (a marker of cellular aging) is of great interest for reducing aging-related disease and death. One important aspect of acute stress exposure that may underlie detrimental effects on health is physiological reactivity to the stressor. This study tested the relationship between buccal telomere length and physiological reactivity (salivary cortisol reactivity and total output, heart rate (HR) variability, blood pressure, and HR) to an acute psychosocial stressor in a sample of 77 (53% male) healthy young adults. Consistent with predictions, greater reductions in HR variability (HRV) in response to a stressor and greater cortisol output during the study session were associated with shorter relative buccal telomere length (i.e. greater cellular aging). However, the relationship between cortisol output and buccal telomere length became non-significant when adjusting for medication use. Contrary to past findings and study hypotheses, associations between cortisol, blood pressure, and HR reactivity and relative buccal telomere length were not significant. Overall, these findings may indicate there are limited and mixed associations between stress reactivity and telomere length across physiological systems.

  16. Multiple measures of adiposity are associated with mean leukocyte telomere length in the northern Finland birth cohort 1966.

    Directory of Open Access Journals (Sweden)

    Jessica L Buxton

    Full Text Available Studies of leukocyte telomere length (LTL and adiposity have produced conflicting results, and the relationship between body mass index (BMI and telomere length throughout life remains unclear. We therefore tested association of adult LTL measured in 5,598 participants with: i childhood growth measures (BMI and age at adiposity rebound (AR; ii change in BMI from childhood to adulthood and iii adult BMI, waist-to-hip ratio (WHR, body adiposity index (BAI. Childhood BMI at AR was positively associated with LTL at 31 years in women (P = 0.041. Adult BMI and WHR in both men (P = 0.025 and P = 0.049, respectively and women (P = 0.029 and P = 0.008, respectively, and BAI in women (P = 0.021 were inversely associated with LTL at 31 years. An increase in standardised BMI between early childhood and adulthood was associated with shorter adult LTL in women (P = 0.008. We show that LTL is inversely associated with multiple measures of adiposity in both men and women. Additionally, BMI increase in women from childhood to adulthood is associated with shorter telomeres at age 31, potentially indicating accelerated biological ageing.

  17. Multiple measures of adiposity are associated with mean leukocyte telomere length in the northern Finland birth cohort 1966.

    Science.gov (United States)

    Buxton, Jessica L; Das, Shikta; Rodriguez, Alina; Kaakinen, Marika; Couto Alves, Alexessander; Sebert, Sylvain; Millwood, Iona Y; Laitinen, Jaana; O'Reilly, Paul F; Jarvelin, Marjo-Riitta; Blakemore, Alexandra I F

    2014-01-01

    Studies of leukocyte telomere length (LTL) and adiposity have produced conflicting results, and the relationship between body mass index (BMI) and telomere length throughout life remains unclear. We therefore tested association of adult LTL measured in 5,598 participants with: i) childhood growth measures (BMI and age at adiposity rebound (AR)); ii) change in BMI from childhood to adulthood and iii) adult BMI, waist-to-hip ratio (WHR), body adiposity index (BAI). Childhood BMI at AR was positively associated with LTL at 31 years in women (P = 0.041). Adult BMI and WHR in both men (P = 0.025 and P = 0.049, respectively) and women (P = 0.029 and P = 0.008, respectively), and BAI in women (P = 0.021) were inversely associated with LTL at 31 years. An increase in standardised BMI between early childhood and adulthood was associated with shorter adult LTL in women (P = 0.008). We show that LTL is inversely associated with multiple measures of adiposity in both men and women. Additionally, BMI increase in women from childhood to adulthood is associated with shorter telomeres at age 31, potentially indicating accelerated biological ageing.

  18. Tocotrienol-Rich Fraction Prevents Cell Cycle Arrest and Elongates Telomere Length in Senescent Human Diploid Fibroblasts

    Directory of Open Access Journals (Sweden)

    Suzana Makpol

    2011-01-01

    Full Text Available This study determined the molecular mechanisms of tocotrienol-rich fraction (TRF in preventing cellular senescence of human diploid fibroblasts (HDFs. Primary culture of HDFs at various passages were incubated with 0.5 mg/mL TRF for 24 h. Telomere shortening with decreased telomerase activity was observed in senescent HDFs while the levels of damaged DNA and number of cells in G0/G1 phase were increased and S phase cells were decreased. Incubation with TRF reversed the morphology of senescent HDFs to resemble that of young cells with decreased activity of SA-β-gal, damaged DNA, and cells in G0/G1 phase while cells in the S phase were increased. Elongated telomere length and restoration of telomerase activity were observed in TRF-treated senescent HDFs. These findings confirmed the ability of tocotrienol-rich fraction in preventing HDFs cellular ageing by restoring telomere length and telomerase activity, reducing damaged DNA, and reversing cell cycle arrest associated with senescence.

  19. Leukocyte telomere length is associated with advanced age-related macular degeneration in the Han Chinese population.

    Science.gov (United States)

    Weng, Xiaoling; Zhang, Hong; Kan, Mengyuan; Ye, Junyi; Liu, Fatao; Wang, Ting; Deng, Jiaying; Tan, Yanfang; He, Lin; Liu, Yun

    2015-09-01

    Telomeres located at the ends of chromosomes are involved in genomic stability and play a key role in various cancers and age-related diseases. Age-related macular degeneration (AMD) is a late-onset, age-associated progressive neurodegenerative disease, which includes the geographic atrophy (GA) subtype and the choroidal neovascularization (CNV) subtype. To better understand how leukocyte telomere length (LTL) is related to AMD, we conducted an association study in 197 AMD patients and 259 healthy controls using the established quantitative PCR technique. Logistic regression was performed to evaluate the association of LTL and AMD with the age-adjusted ratio of the telomere length to the copy number of a single-copy gene (T/S). Notably, we found a significant association between AMD and LTL (OR=2.24; 95% CI=1.68-3.07; P=0.0001) after adjusting for age and sex. Furthermore, the results showed a strongly significant association between the GA subtype and the LTL (OR=4.81; 95% CI=3.15-7.82; P=0.0001) after adjusting for age and sex. Our findings provide evidence of the role that LTL plays in the pathological mechanisms of AMD, mainly in the GA subgroup but not the CNV subgroup. Copyright © 2015. Published by Elsevier Inc.

  20. Association between genetic risk score for telomere length and risk of breast cancer.

    Science.gov (United States)

    Luu, Hung N; Long, Jirong; Wen, Wanqing; Zheng, Ying; Cai, Qiuyin; Gao, Yu-Tang; Zheng, Wei; Shu, Xiao-Ou

    2016-10-01

    While leukocyte telomere length (TL) has been associated with breast cancer risk, limited information is available regarding the role of genetically-determined TL on breast cancer risk. We investigated whether aggregated TL-associated variants are associated with the risk of breast cancer in 2,865 breast cancer cases and 2,285 controls from the Shanghai Breast Cancer Genetics Study. Six genetic variants, identified through a genome-wide association study (GWAS) of TL in European-ancestry participants, were included in the study. A separate sample [n = 1,536, from the Shanghai Women's Health Study (SWHS), for whom information on both phenotypical leukocyte TL and genetic information was collected] was used to evaluate the association of six variants with TL in Asians. Three genetic risk scores (GRSs), based on the number of alleles associated with shorter TL that each individual carries for the six variants, were derived for the study: un-weighted, internally weighted (from the SWHS), and externally weighted (from the European-ancestry GWAS study), and evaluated for their association with breast cancer risk by applying logistic regression analysis. Both internally and externally weighted GRSs were significantly associated with a decreased risk of breast cancer (OR 0.83, 95 % CI 0.72-0.95 and OR 0.84, 95 % CI 0.74-0.96, respectively, for tertile 3 vs. tertile 1). Non-genetic risk factors for breast cancer (i.e., age, years of menstruation/reproduction, oral contraceptive usage, and BMI) did not modify the association between GRSs and the risk of breast cancer. Our results suggest that short TL, determined by genetic factors, may be associated with a reduced susceptibility to breast cancer.

  1. Number of Children and Telomere Length in Women: A Prospective, Longitudinal Evaluation.

    Science.gov (United States)

    Barha, Cindy K; Hanna, Courtney W; Salvante, Katrina G; Wilson, Samantha L; Robinson, Wendy P; Altman, Rachel M; Nepomnaschy, Pablo A

    2016-01-01

    Life history theory (LHT) predicts a trade-off between reproductive effort and the pace of biological aging. Energy invested in reproduction is not available for tissue maintenance, thus having more offspring is expected to lead to accelerated senescence. Studies conducted in a variety of non-human species are consistent with this LHT prediction. Here we investigate the relationship between the number of surviving children born to a woman and telomere length (TL, a marker of cellular aging) over 13 years in a group of 75 Kaqchikel Mayan women. Contrary to LHT's prediction, women who had fewer children exhibited shorter TLs than those who had more children (p = 0.045) after controlling for TL at the onset of the 13-year study period. An "ultimate" explanation for this apparently protective effect of having more children may lay with human's cooperative-breeding strategy. In a number of socio-economic and cultural contexts, having more chilren appears to be linked to an increase in social support for mothers (e.g., allomaternal care). Higher social support, has been argued to reduce the costs of further reproduction. Lower reproductive costs may make more metabolic energy available for tissue maintenance, resulting in a slower pace of cellular aging. At a "proximate" level, mechanisms involved may include the actions of the gonadal steroid estradiol, which increases dramatically during pregnancy. Estradiol is known to protect TL from the effects of oxidative stress as well as increase telomerase activity, an enzyme that maintains TL. Future research should explore the potential role of social support as well as that of estradiol and other potential biological pathways in the trade-offs between reproductive effort and the pace of cellular aging within and among human as well as in non-human populations.

  2. Number of Children and Telomere Length in Women: A Prospective, Longitudinal Evaluation.

    Directory of Open Access Journals (Sweden)

    Cindy K Barha

    Full Text Available Life history theory (LHT predicts a trade-off between reproductive effort and the pace of biological aging. Energy invested in reproduction is not available for tissue maintenance, thus having more offspring is expected to lead to accelerated senescence. Studies conducted in a variety of non-human species are consistent with this LHT prediction. Here we investigate the relationship between the number of surviving children born to a woman and telomere length (TL, a marker of cellular aging over 13 years in a group of 75 Kaqchikel Mayan women. Contrary to LHT's prediction, women who had fewer children exhibited shorter TLs than those who had more children (p = 0.045 after controlling for TL at the onset of the 13-year study period. An "ultimate" explanation for this apparently protective effect of having more children may lay with human's cooperative-breeding strategy. In a number of socio-economic and cultural contexts, having more chilren appears to be linked to an increase in social support for mothers (e.g., allomaternal care. Higher social support, has been argued to reduce the costs of further reproduction. Lower reproductive costs may make more metabolic energy available for tissue maintenance, resulting in a slower pace of cellular aging. At a "proximate" level, mechanisms involved may include the actions of the gonadal steroid estradiol, which increases dramatically during pregnancy. Estradiol is known to protect TL from the effects of oxidative stress as well as increase telomerase activity, an enzyme that maintains TL. Future research should explore the potential role of social support as well as that of estradiol and other potential biological pathways in the trade-offs between reproductive effort and the pace of cellular aging within and among human as well as in non-human populations.

  3. Interaction between Obstructive Sleep Apnea and Shortened Telomere Length on Brain White Matter Abnormality.

    Science.gov (United States)

    Choi, Kyung-Mee; Thomas, Robert J; Yoon, Dai Wui; Lee, Seung Ku; Baik, Inkyung; Shin, Chol

    2016-09-01

    Age-related brain white matter changes (WMC) have been associated separately with obstructive sleep apnea (OSA) and short telomere length (TL). No studies have examined their interaction effect on WMC. This is a cross-sectional study with a community-based sample of 420 participants (mean age, 61.3 ± 7.2) from the Korean Genome and Epidemiology Study during 2011-2012. An overnight fasted blood sample was taken to determine glucose and blood lipid levels at the sleep laboratory of Korea University Ansan Hospital. The status of brain WMC was determined using structural magnetic resonance imaging at 1.5 Tesla. Overnight polysomnography was performed, and leukocyte TL was measured. OSA was determined based on apnea-hypopnea index, and short TL was defined as the lowest quartile of the study participants. Adjusting for age, sex, BMI, smoking, drinking, snoring, and hypertension, odds ratio (OR) of brain WMC was estimated using multivariate logistic regression. The odds ratio was significant for cardiovascular disease (OR, 4.5; 95% CI, 1.2-16.3) and OSA (OR, 4.0; 95% CI, 1.0-15.2) among those with short TL; and for diabetes (OR, 3.0; 95% CI, 1.3-13.0) and age (OR, 1.1; 95% CI, 1.0-1.1) among those with longer TL. Interaction effect of OSA and short TL (OR, 4.3; 95% CI, 1.4-13.8) was significant, compared to those with neither OSA nor short TL. This study provides a first evidence of mediated interaction of short TL with OSA on brain WMC in a community-based sample. The results generate new hypotheses regarding mechanisms of impaired brain health in sleep apnea. © 2016 Associated Professional Sleep Societies, LLC.

  4. Number of Children and Telomere Length in Women: A Prospective, Longitudinal Evaluation

    Science.gov (United States)

    Barha, Cindy K.; Hanna, Courtney W.; Salvante, Katrina G.; Wilson, Samantha L.; Robinson, Wendy P.; Altman, Rachel M.; Nepomnaschy, Pablo A.

    2016-01-01

    Life history theory (LHT) predicts a trade-off between reproductive effort and the pace of biological aging. Energy invested in reproduction is not available for tissue maintenance, thus having more offspring is expected to lead to accelerated senescence. Studies conducted in a variety of non-human species are consistent with this LHT prediction. Here we investigate the relationship between the number of surviving children born to a woman and telomere length (TL, a marker of cellular aging) over 13 years in a group of 75 Kaqchikel Mayan women. Contrary to LHT’s prediction, women who had fewer children exhibited shorter TLs than those who had more children (p = 0.045) after controlling for TL at the onset of the 13-year study period. An “ultimate” explanation for this apparently protective effect of having more children may lay with human’s cooperative-breeding strategy. In a number of socio-economic and cultural contexts, having more chilren appears to be linked to an increase in social support for mothers (e.g., allomaternal care). Higher social support, has been argued to reduce the costs of further reproduction. Lower reproductive costs may make more metabolic energy available for tissue maintenance, resulting in a slower pace of cellular aging. At a “proximate” level, mechanisms involved may include the actions of the gonadal steroid estradiol, which increases dramatically during pregnancy. Estradiol is known to protect TL from the effects of oxidative stress as well as increase telomerase activity, an enzyme that maintains TL. Future research should explore the potential role of social support as well as that of estradiol and other potential biological pathways in the trade-offs between reproductive effort and the pace of cellular aging within and among human as well as in non-human populations. PMID:26731744

  5. Discrimination, racial bias, and telomere length in African-American men.

    Science.gov (United States)

    Chae, David H; Nuru-Jeter, Amani M; Adler, Nancy E; Brody, Gene H; Lin, Jue; Blackburn, Elizabeth H; Epel, Elissa S

    2014-02-01

    Leukocyte telomere length (LTL) is an indicator of general systemic aging, with shorter LTL being associated with several chronic diseases of aging and earlier mortality. Identifying factors related to LTL among African Americans may yield insights into mechanisms underlying racial disparities in health. To test whether the combination of more frequent reports of racial discrimination and holding a greater implicit anti-black racial bias is associated with shorter LTL among African-American men. Cross-sectional study of a community sample of 92 African-American men aged between 30 and 50 years. Participants were recruited from February to May 2010. Ordinary least squares regressions were used to examine LTL in kilobase pairs in relation to racial discrimination and implicit racial bias. Data analysis was completed in July 2013. After controlling for chronologic age and socioeconomic and health-related characteristics, the interaction between racial discrimination and implicit racial bias was significantly associated with LTL (b=-0.10, SE=0.04, p=0.02). Those demonstrating a stronger implicit anti-black bias and reporting higher levels of racial discrimination had the shortest LTL. Household income-to-poverty threshold ratio was also associated with LTL (b=0.05, SE=0.02, pracism, including interpersonal experiences of racial discrimination and the internalization of negative racial bias, operate jointly to accelerate biological aging among African-American men. Societal efforts to address racial discrimination in concert with efforts to promote positive in-group racial attitudes may protect against premature biological aging in this population. © 2013 American Journal of Preventive Medicine Published by American Journal of Preventive Medicine All rights reserved.

  6. Processed Meat, but Not Unprocessed Red Meat, Is Inversely Associated with Leukocyte Telomere Length in the Strong Heart Family Study.

    Science.gov (United States)

    Fretts, Amanda M; Howard, Barbara V; Siscovick, David S; Best, Lyle G; Beresford, Shirley Aa; Mete, Mihriye; Eilat-Adar, Sigal; Sotoodehnia, Nona; Zhao, Jinying

    2016-10-01

    Telomeres are repetitive nucleotide sequences (TTAGGG) and their associated proteins at the end of eukaryote chromosomes. Telomere length shortens throughout the lifespan with each cell division, and leukocyte telomere length (LTL) is often used as a biomarker of cellular aging. LTL is related to many chronic diseases, including cardiovascular disease and diabetes. However, to our knowledge, the relation between LTL and risk factors for cardiovascular disease and diabetes, such as dietary intake of processed meat and unprocessed red meat, is largely unknown. We examined the associations of processed meat intake and unprocessed red meat intake with LTL. This cross-sectional study comprised 2846 American Indians from the Strong Heart Family Study who participated in the 2001-2003 examination. Dietary factors, including past-year consumption of processed meat and unprocessed red meat, were assessed with the use of a 119-item Block Food-Frequency Questionnaire. LTL was measured with the use of quantitative polymerase chain reaction. Generalized estimating equations were used to examine the associations of intake of processed meat and unprocessed red meat with LTL. Consumption of processed meat was negatively associated with LTL after adjustment for age, sex, site, education, smoking, alcohol use, physical activity, and other dietary factors. For every additional daily serving of processed meat, LTL was 0.021 units (telomeric product-to-single-copy gene ratio) shorter (β ± SE = -0.021 ± 0.008, P = 0.009). No association was observed between the intake of unprocessed red meat and LTL (β ± SE = 0.008 ± 0.011, P = 0.46). In the Strong Heart Family Study, consumption of processed meat, but not unprocessed red meat, was associated with shorter LTL, a potential mediator for several age-related diseases. Further studies are needed to better understand the biological mechanism by which processed meat intake influences cellular aging. © 2016 American Society for Nutrition.

  7. Telomeres and human health

    DEFF Research Database (Denmark)

    Bojesen, S E

    2013-01-01

    Telomeres are the tips of chromosomes and consist of proteins and hexanucleotide tandem repeats of DNA. The DNA repeats are shortened at each mitotic division of normal cells, and the telomere length chronicles how many divisions the cell has undergone. Thus, telomere length is a marker of fundam...

  8. Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia.

    Science.gov (United States)

    Caniggia, I; Winter, J; Lye, S J; Post, M

    2000-01-01

    During early pregnancy, placentation occurs in a relatively hypoxic environment which is essential for appropriate embryonic development. Intervillous blood flow increases at around 10-12 weeks of gestation and results in exposure of the trophoblast to increased oxygen tension (PO2). Prior to this time, low oxygen appears to prevent trophoblast differentiation towards an invasive phenotype. In other mammalian systems, oxygen tension effects are mediated by hypoxia inducible factor-1 (HIF-1). We found that the ontogeny of HIF-1alpha subunit expression during the first trimester of gestation parallels that of transforming growth factor-beta3 (TGFbeta3), an inhibitor of early trophoblast differentiation. Expression of both molecules is high in early pregnancy and falls at around 10 weeks of gestation when placental PO2 levels are believed to increase. Antisense-induced inhibition of HIF-1alpha inhibited the expression of TGFbeta3, and stimulated extravillous trophoblast (EVT) outgrowth and invasion. Of clinical significance we found that TGFbeta3 expression was increased in pre-eclamptic placentae when compared to age-matched controls. Significantly, inhibition of TGFbeta3 by antisense oligonucleotides or antibodies restored the invasive capability to the trophoblast cells in pre-eclamptic explants. We speculate that if oxygen tension fails to increase, or trophoblasts do not detect this increase, HIF-1alpha and TGFbeta3 expression remain high, resulting in shallow trophoblast invasion and predisposing the pregnancy to pre-eclampsia. Effective fetal-maternal interactions during early placentation are critical for a successful pregnancy. Optimal placental perfusion requires the controlled invasion of trophoblast cells deep into the decidua to the spiral arteries. Trophoblast stem cells, also referred to as cytotrophoblast cells, reside in chorionic villi of two types, floating and anchoring villi. Floating villi, which represent the vast majority of chorionic villi

  9. Prevention and management of severe pre-eclampsia/eclampsia in Afghanistan

    Science.gov (United States)

    2013-01-01

    Background An evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care (EmONC) in Afghanistan have the capacity to manage severe PE/E cases. Methods A further analysis was conducted of the 2009–10 Afghanistan EmONC Needs Assessment. Assessors observed equipment and supplies available, and services provided at 78 of the 127 facilities offering comprehensive EmONC services and interviewed 224 providers. The providers also completed a written case scenario on severe PE/E. Descriptive statistics were used to summarize facility and provider characteristics. Student t-test, one-way ANOVA, and chi-square tests were performed to determine whether there were significant differences between facility types, doctors and midwives, and trained and untrained providers. Results The median number of severe PE/E cases in the past year was just 5 (range 0–42) at comprehensive health centers (CHCs) and district hospitals, compared with 44 (range 0–130) at provincial hospitals and 108 (range 32–540) at regional and specialized hospitals (p Afghanistan, but providers lack knowledge in some areas, especially concerning the use of MgSO4 and diazepam. Providers who have specialized training or work at larger facilities are better at managing cases of severe PE/E. The findings suggest a need to clarify service delivery guidelines, offer refresher training, and reinforce best practices with supervision and reinforcement. PMID:24119329

  10. Pre-eclampsia: an important risk factor for asymptomatic heart failure.

    Science.gov (United States)

    Ghossein-Doha, C; van Neer, J; Wissink, B; Breetveld, N M; de Windt, L J; van Dijk, A P J; van der Vlugt, M J; Janssen, M C H; Heidema, W M; Scholten, R R; Spaanderman, M E A

    2017-01-01

    Pre-eclampsia (PE) is associated with both postpartum structural asymptomatic heart disease (i.e. heart failure Stage B (HF-B)) and conventional cardiovascular (CV) risk factors. We aimed to evaluate the extent to which PE, adjusted for conventional CV risk factors, is associated independently with asymptomatic cardiac abnormalities postpartum. In this cross-sectional cohort study, 107 formerly pre-eclamptic women and 41 women with uneventful previous pregnancy (controls) were invited for CV risk assessment 4-10 years postpartum. This included cardiac ultrasound, blood pressure (BP) measurement and evaluation of metabolic syndrome determinants. Asymptomatic structural and functional cardiac abnormalities were classified as HF-B, according to the American Heart Association guidelines. Prehypertension was defined as systolic BP of 120-139 mmHg and/or diastolic BP of 80-89 mmHg. Univariate and multivariate regression analyses were performed to calculate associations of PE and conventional risk factors with HF-B. The prevalence of asymptomatic HF-B was approximately 3.5-fold higher in the PE group compared with controls (25% vs 7%, P < 0.01); 67% of this group had concentric remodeling and 22% had mildly impaired ejection fraction. After adjustment for postpartum interval, hypertension and high-density lipoprotein, PE was significantly associated with HF-B (adjusted odds ratio, 4.4 (95% CI, 1.0-19.1)). Moreover, in the formerly pre-eclamptic group, prehypertension was associated significantly with HF-B (odds ratio, 4.3 (95% CI, 1.4-12.7)), while metabol