Prediction and primary prevention of pre-eclampsia

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Thangaratinam, Shakila; Langenveld, Josie; Mol, Ben W.; Khan, Khalid S.

2011-01-01

Pre-eclampsia is associated with increased maternal and perinatal mortality and morbidity. Early recognition of women at risk of pre-eclampsia will enable the identification of high-risk women who may benefit from enhanced surveillance and prophylaxis. In this chapter, we summarise the accuracy of

Old and new aspects in the pathophysiology of pre-eclampsia

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Federico Prefumo

2007-12-01

Full Text Available Pre-eclampsia is a condition affecting the feto-placental unit and the mother. Three to five percent of pregnancies are complicated by pre-eclampsia, a multisystem disorder characterized by hypertension and proteinuria that occurs after 20 weeks of pregnancy. Pre-eclampsia is associated with substantial risks. For the fetus, these include intrauterine growth restriction, death, and prematurity with attendant complications, whereas the mother is at risk for complications of widespread alterations in endothelial function such as seizures (eclampsia, renal failure, pulmonary edema, stroke, and death. The establishment of pathological uterine perfusion raises the problem of stage two. The problem at stage three describes pre-eclampsia as a syndrome with the global maternal endothelial damage as the central pathophysiological feature.\tIt has been suggested that the pathophysiology of pre-eclampsia can be thought of as a ‘three-stage problem’, where each stage generates one, so far unsolved problem. An impaired trophoblast invasion is thought to be the central factor (first step regarding the etiology of pre-eclampsia. An increased uterine artery Doppler findings (PI, RI, lower maternal serum PAPP-A and free ßhCG levels, ischaemia modified albumin (IMA may be associated with pre-eclampsia.

Is human placenta proteoglycan remodeling involved in pre-eclampsia?

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Warda, Mohamad; Zhang, Fuming; Radwan, Moustafa; Zhang, Zhenqing; Kim, Nari; Kim, Young Nam; Linhardt, Robert J.; Han, Jin

2007-01-01

Impaired placento-fetal communication is a coherent symptom of exaggerated pre-eclampsia. The impact of the cellular expression of different glycosaminoglycans (GAGs) in this event on the placenta in pre-eclampsia is still obscure. This is the first study aimed at discovering the relationship between structural alterations of different sulfated GAGs at the molecular level and the development of pre-eclampsia in inflicted placenta. Sulfated GAGs were isolated and purified from control and pre-...

Periodontal disease and pre-eclampsia : a systematic review

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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,

Cognitive function after pre-eclampsia: an explorative study.

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Baecke, M.; Spaanderman, M.E.A.; Werf, S.P. van der

2009-01-01

BACKGROUND: Pre-eclampsia and eclampsia relate to cerebral damage. Memory and concentration problems are frequently reported after these pregnancy-related vascular complications. We tested the hypothesis that in formerly pre-eclamptic women cognitive functioning is impaired as compared with healthy

Correlating telomere length and radiosensitivity in cancer patients

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Sprung, C.N.; Davey, D.S.P.; McKay, M.J.

2003-01-01

Approximately three percent of cancer patients suffer from significant side effects in normal tissue exposed to ionising radiation during radiotherapy (RT). Although RT is an effective therapy for cancer treatment, the treatment dose intensity is generally restricted to minimize the incidence of these severe reactions. This imposes tumour control limitations on most patients. A major goal of radiation biology research is to develop efficient predictive assays that could identify these hyper-radiosensitive (hRS) individuals prior to treatment. This predictive ability would enable the individualisation of RT doses, which should result in improvement of tumour control rates and a reduction in the incidence of RT side effects. Recent studies have reported a correlation between cellular and organismal RS and shortened telomeres. Interestingly, a number of DNA repair proteins have been found to be associated with telomeres. Additionally, individuals with cancer-proneness and RS syndromes, such as ataxia telangiectasia and Fanconi anemia, have shortened telomeres. In animal models, mutations in DNA repair genes such as Ku, has resulted in shortened telomeres. We have a unique bank of blood samples and lymphoblastoid cell lines (LCLs) from over 50 hRS patients. We have used traditional methods of telomere length assessment and a clinically relevant method, flow cytometry fluorescence in situ hybridisation (flow-FISH) to determine the telomere length in both LCLs and peripheral blood mononuclear cells from the hRS patients. Results from the screening of these samples will be presented. If clinical hRS can be correlated with shortened telomeres in some patients, flow-FISH may have utility as part of a pre-treatment hRS assay for use in the clinic

Assessing Telomere Length Using Surface Enhanced Raman Scattering

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Zong, Shenfei; Wang, Zhuyuan; Chen, Hui; Cui, Yiping

2014-11-01

Telomere length can provide valuable insight into telomeres and telomerase related diseases, including cancer. Here, we present a brand-new optical telomere length measurement protocol using surface enhanced Raman scattering (SERS). In this protocol, two single strand DNA are used as SERS probes. They are labeled with two different Raman molecules and can specifically hybridize with telomeres and centromere, respectively. First, genome DNA is extracted from cells. Then the telomere and centromere SERS probes are added into the genome DNA. After hybridization with genome DNA, excess SERS probes are removed by magnetic capturing nanoparticles. Finally, the genome DNA with SERS probes attached is dropped onto a SERS substrate and subjected to SERS measurement. Longer telomeres result in more attached telomere probes, thus a stronger SERS signal. Consequently, SERS signal can be used as an indicator of telomere length. Centromere is used as the inner control. By calibrating the SERS intensity of telomere probe with that of the centromere probe, SERS based telomere measurement is realized. This protocol does not require polymerase chain reaction (PCR) or electrophoresis procedures, which greatly simplifies the detection process. We anticipate that this easy-operation and cost-effective protocol is a fine alternative for the assessment of telomere length.

Working hours and risk of gestational hypertension and pre-eclampsia.

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Chang, Pei-Jen; Chu, Li-Ching; Hsieh, Wu-Shiun; Chuang, Yi-Li; Lin, Shio-Jean; Chen, Pau-Chung

2010-01-01

The potential impact of employment on maternal health, particularly in relation to gestational hypertension and pre-eclampsia, has been subject to research. However, there is limited evidence on associations between shift work and long working hours on the incidence of these conditions. To evaluate potential associations between maternal shift work and long working hours during pregnancy and gestational hypertension or pre-eclampsia. Multistage stratified systematic sampling was used to recruit 24 200 post-partum women from the Taiwan national birth registration database in 2005. Subjects underwent home interview 6 months after their deliveries by structured questionnaire to obtain characteristics of maternal employment and potential confounders. Diagnosis of gestational hypertension and pre-eclampsia was obtained from the birth registration. There was no association between employment status and gestational hypertension or pre-eclampsia. Also, no significant association between gestational hypertension or pre-eclampsia and maternal shift work or long working hours during pregnancy was found in all or primiparous women. There was no convincing evidence that maternal shift work or long working hours had a higher risk of gestational hypertension or pre-eclampsia. However, further research is warranted to confirm these negative findings.

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...

The telomere length dynamic and methods of its assessment.

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Lin, Kah-Wai; Yan, Ju

2005-01-01

Human telomeres are composed of long repeating sequences of TTAGGG, associated with a variety of telomere-binding proteins. Its function as an end-protector of chromosomes prevents the chromosome from end-to-end fusion, recombination and degradation. Telomerase acts as reverse transcriptase in the elongation of telomeres, which prevent the loss of telomeres due to the end replication problems. However, telomerase activity is detected at low level in somatic cells and high level in embryonic stem cells and tumor cells. It confers immortality to embryonic stem cells and tumor cells. In most tumor cells, telomeres are extremely short and stable. Telomere length is an important indicator of the telomerase activity in tumor cells and it may be used in the prognosis of malignancy. Thus, the assessment of telomeres length is of great experimental and clinical significance. This review describes the role of telomere and telomerase in cancer pathogenesis and the dynamics of the telomeres length in different cell types. The various methods of measurement of telomeres length, i.e. southern blot, hybridization protection assay, fluorescence in situ hybridization, primed in situ, quantitative PCR and single telomere length analysis are discussed. The principle and comparative evaluation of these methods are reviewed. The detection of G-strand overhang by telomeric-oligonucleotide ligation assay, primer extension/nick translation assay and electron microscopy are briefly discussed.

Telomere Length Reprogramming in Embryos and Stem Cells

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Keri Kalmbach

2014-01-01

Full Text Available Telomeres protect and cap linear chromosome ends, yet these genomic buffers erode over an organism’s lifespan. Short telomeres have been associated with many age-related conditions in humans, and genetic mutations resulting in short telomeres in humans manifest as syndromes of precocious aging. In women, telomere length limits a fertilized egg’s capacity to develop into a healthy embryo. Thus, telomere length must be reset with each subsequent generation. Although telomerase is purportedly responsible for restoring telomere DNA, recent studies have elucidated the role of alternative telomeres lengthening mechanisms in the reprogramming of early embryos and stem cells, which we review here.

Cardiovascular risk factor assessment after pre-eclampsia in primary care

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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.

Telomere Length – a New Biomarker in Medicine

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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.

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

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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.

Cardiac diastolic function after recovery from pre-eclampsia.

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Soma-Pillay, P; Louw, M C; Adeyemo, A O; Makin, J; Pattinson, R C

Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks' gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11-10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

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.

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

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

2015-10-01

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 known about the cost effectiveness of these and other tests for pre-eclampsia, mainly because there is no clear treatment path. The aim of this study was to provide a comprehensive overview of the existing evidence on the health economics of screening, diagnosis and treatment options in pre-eclampsia. We searched three electronic databases (PubMed, EMBASE and the Cochrane Library) for studies on screening, diagnosis, treatment or prevention of pre-eclampsia, published between 1994 and 2014. Only full papers written in English containing complete economic assessments in pre-eclampsia were included. From an initial total of 138 references, six papers fulfilled the inclusion criteria. Three studies were on the cost effectiveness of treatment of pre-eclampsia, two of which evaluated magnesium sulphate for prevention of seizures and the third evaluated the cost effectiveness of induction of labour versus expectant monitoring. The other three studies were aimed at screening and diagnosis, in combination with subsequent preventive measures. The two studies on magnesium sulphate were equivocal on the cost effectiveness in non-severe cases, and the other study suggested that induction of labour in term pre-eclampsia was more cost effective than expectant monitoring. The screening studies were quite diverse in their objectives as well as in their conclusions. One study concluded that screening is probably not worthwhile, while two other studies stated that in certain scenarios it may be cost effective to screen all pregnant women and prophylactically treat those who are found to be at high risk of developing pre-eclampsia. This study is the first to provide a comprehensive overview

Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis

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Eric Le Balc’h

2017-08-01

Full Text Available All tumors have in common to reactivate a telomere maintenance mechanism to allow for unlimited proliferation. On the other hand, genetic instability found in some tumors can result from the loss of telomeres. Here, we measured telomere length in colorectal cancers (CRCs using TRF (Telomere Restriction Fragment analysis. Telomeric DNA content was also quantified as the ratio of total telomeric (TTAGGG sequences over that of the invariable Alu sequences. In most of the 125 CRCs analyzed, there was a significant diminution in telomere length compared with that in control healthy tissue. Only 34 tumors exhibited no telomere erosion and, in some cases, a slight telomere lengthening. Telomere length did not correlate with age, gender, tumor stage, tumor localization or stage of tumor differentiation. In addition, while telomere length did not correlate with the presence of a mutation in BRAF (V-raf murine sarcoma viral oncogene homolog B, PIK3CA (phosphatidylinositol 3-kinase catalytic subunit, or MSI status, it was significantly associated with the occurrence of a mutation in KRAS. Interestingly, we found that the shorter the telomeres in healthy tissue of a patient, the larger an increase in telomere length in the tumor. Our study points to the existence of two types of CRCs based on telomere length and reveals that telomere length in healthy tissue might influence telomere maintenance mechanisms in the tumor.

Cardiovascular mortality after pre-eclampsia in one child mothers: prospective, population based cohort study.

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Skjaerven, Rolv; Wilcox, Allen J; Klungsøyr, Kari; Irgens, Lorentz M; Vikse, Bjørn Egil; Vatten, Lars J; Lie, Rolv Terje

2012-11-27

To assess the association of pre-eclampsia with later cardiovascular death in mothers according to their lifetime number of pregnancies, and particularly after only one child. Prospective, population based cohort study. Medical Birth Registry of Norway. We followed 836,147 Norwegian women with a first singleton birth between 1967 and 2002 for cardiovascular mortality through linkage to the national Cause of Death Registry. About 23,000 women died by 2009, of whom 3891 died from cardiovascular causes. Associations between pre-eclampsia and cardiovascular death were assessed by hazard ratios, estimated by Cox regression analyses. Hazard ratios were adjusted for maternal education (three categories), maternal age at first birth, and year of first birth The rate of cardiovascular mortality among women with preterm pre-eclampsia was 9.2% after having only one child, falling to 1.1% for those with two or more children. With term pre-eclampsia, the rates were 2.8% and 1.1%, respectively. Women with pre-eclampsia in their first pregnancy had higher rates of cardiovascular death than those who did not have the condition at first birth (adjusted hazard ratio 1.6 (95% confidence interval 1.4 to 2.0) after term pre-eclampsia; 3.7 (2.7 to 4.8) after preterm pre-eclampsia). Among women with only one lifetime pregnancy, the increase in risk of cardiovascular death was higher than for those with two or more children (3.4 (2.6 to 4.6) after term pre-eclampsia; 9.4 (6.5 to 13.7) after preterm pre-eclampsia). The risk of cardiovascular death was only moderately elevated among women with pre-eclamptic first pregnancies who went on to have additional children (1.5 (1.2 to 2.0) after term pre-eclampsia; 2.4 (1.5 to 3.9) after preterm pre-eclampsia). There was little evidence of additional risk after recurrent pre-eclampsia. All cause mortality for women with two or more lifetime births, who had pre-eclampsia in first pregnancy, was not elevated, even with preterm pre-eclampsia in first

Leukocyte Telomere Length in the Neonatal Offspring of Mothers with Gestational and Pre-Gestational Diabetes.

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Gilfillan, Christopher; Naidu, Pratyusha; Gunawan, Florence; Hassan, Fadwa; Tian, Pei; Elwood, Ngaire

2016-01-01

Telomeres undergo shortening with cell division, accelerated by increased oxidative stress. We aimed to demonstrate shortened telomeres in the offspring of mothers who have diabetes as a consequence of exposure to increased oxidative stress during intrauterine development. We examined the level of glycaemia (glucose, HbA1c, fructosamine), oxidative stress (lipid peroxidation) and the levels of antioxidant enzymes (Superoxide dismutase (SOD) and Selenium dependent glutathione peroxidase) and correlate these findings with mean telomere length (TL) in maternal and foetal blood in groups of pregnant women with pre-gestational diabetes (PGD), gestational diabetes (GD) and a euglycaemic control group. Foetal and maternal glucose, maternal HbA1c, and foetal insulin and C-peptide were higher in the PGD group with the GD group being intermediate. Markers of oxidative stress did not vary between groups with the exception of foetal SOD activity that was highest in the GD group. There were no detectable differences in maternal or foetal TL between study groups. An exploratory analysis looking at correlations between glycaemic and oxidative stress parameters and TL revealed a negative correlation between maternal and foetal glucose and TL across the whole study population. This relationship held for the short-term marker of glycaemic control, fructosamine. We were unable to show significant telomere shortening in the offspring of mothers with PGD or GD. Exploratory analysis revealed a relationship between foetal TL and short-term glycaemia particularly in PGD. It is possible that increased telomerase activity can compensate for long-term increased oxidative stress but not for short-term dysglycaemia.

Pre-eclampsia: Factores de riesgo. Estudio en el Hospital Nacional Cayetano Heredia.

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Salviz Salhuana, Manuel; Cordero Muñoz, Luis; Saona Ugarte, Pedro

1996-01-01

Objetivo: El objetivo fue evaluar los factores de riesgo asociados a pre-eclampsia en nuestro hospital. Material y métodos: Se realizó un estudio prospectivo, de tipo caso-control concurrente en 88 pacientes con pre-eclampsia e igual número de controles. El trabajo se llevó a cabo en el Servicio de Obstetricia del Hospital Nacional Cayetano Heredia entre los meses de marzo a agosto de 1993. Resultados: Los factores asociados a pre-eclampsia fueron el antecedente previo a pre-eclampsia (OR:17)...

Diagnostic criteria and reporting procedures for pre-eclampsia

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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...

Serum magnesium levels in patients with pre-eclampsia and eclampsia with different regimens of magnesium sulphate

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Arpita Singh

2013-01-01

Full Text Available Background Pre-eclampsia and the subsequent eclampsia account for a common cause of maternal mortality worldwide and efforts aimed at reducing its menace are vital. Objective To estimate the serum magnesium levels in pre-eclampsia and eclampsia and to study the effect of using different regimens of magnesium sulphate. Methods 70 cases of pre-eclampsia and eclampsia and 35 normal pregnant women as controls were studied. Serum magnesium levels were estimated using Atomic Absorption Spectrophotometer (Model AAS-4139 at baseline and at frequent intervals during gestation and the overall parameters were meticulously observed. Results Majority(60%ofstudiedcaseswasnulliparawithgestationageof36-40 weeks. Statistically significant reduction of mean diastolic blood pressure and protein-urea was observed after using both intramuscular and intravenous regimens of magnesium sulphate. Mean initial serum magnesium level (mg/dl±SD was 1.81±0.58 in group A,1.55±0.41 in group B and 1.49±0.41 in group C. Mean serum magnesium levels during first 4 hours after therapy were statistically significant between intramuscular and intravenous regimen groups while same were statistically insignificant at 8,12,16,24 and 32 hours. Besides, few minor side effects including headache, vomiting, reduced tendon reflexes and thrombocytopenia, no severe side effects and no maternal mortality were seen. Conclusion Hypomagnesemia occurs during states of preeclampsia and eclampsia, and, administration of magnesium sulphate is effective and safe in preventing maternal mortality.

Serum magnesium levels in patients with pre-eclampsia and eclampsia with different regimens of magnesium sulphate

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Arpita Singh

2013-03-01

Full Text Available Background Pre-eclampsia and the subsequent eclampsia account for a common cause of maternal mortality worldwide and efforts aimed at reducing its menace are vital. Objective To estimate the serum magnesium levels in pre-eclampsia and eclampsia and to study the effect of using different regimens of magnesium sulphate. Methods 70 cases of pre-eclampsia and eclampsia and 35 normal pregnant women as controls were studied. Serum magnesium levels were estimated using Atomic Absorption Spectrophotometer (Model AAS-4139 at baseline and at frequent intervals during gestation and the overall parameters were meticulously observed. Results Majority (60% of studied cases was nullipara with gestation age of 36-40 weeks. Statistically significant reduction of mean diastolic blood pressure and protein-urea was observed after using both intramuscular and intravenous regimens of magnesium sulphate. Mean initial serum magnesium level (mg/dl±SD was 1.81±0.58 in group A,1.55±0.41 in group B and 1.49±0.41 in group C. Mean serum magnesium levels during first 4 hours after therapy were statistically significant between intramuscular and intravenous regimen groups while same were statistically insignificant at 8,12,16,24 and 32 hours. Besides, few minor side effects including headache, vomiting, reduced tendon reflexes and thrombocytopenia, no severe side effects and no maternal mortality were seen. Conclusion Hypomagnesemia occurs during states of preeclampsia and eclampsia, and, administration of magnesium sulphate is effective and safe in preventing maternal mortality.

Does Reproductive Investment Decrease Telomere Length in Menidia menidia?

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Jin Gao

Full Text Available Given finite resources, intense investment in one life history trait is expected to reduce investment in others. Although telomere length appears to be strongly tied to age in many taxa, telomere maintenance requires energy. We therefore hypothesize that telomere maintenance may trade off against other life history characters. We used natural variation in laboratory populations of Atlantic silversides (Menidia menidia to study the relationship between growth, fecundity, life expectancy, and relative telomere length. In keeping with several other studies on fishes, we found no clear dependence of telomere length on age. However, we did find that more fecund fish tended to have both reduced life expectancy and shorter telomeres. This result is consistent with the hypothesis that there is a trade-off between telomere maintenance and reproductive output.

ASSOCIATION OF ANGIOTENSINOGEN GENE M235T VARIANT IN PRE-ECLAMPSIA

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MAREI, E.S.; SAUDI, A.KH.; ANEES, L.M.; MOHAMMED, S.K.

2007-01-01

Pre-eclampsia (PE) is multisystem and multifactorial complication of pregnancy. The precise cause of pre-eclampsia has not been determined but mal adoption of the rennin and angiotensinogen (AGT) system may play a role. The products of genes involving the components of this system may be potential candidates for pre-eclampsia and hypertension related to pregnancy. This study was designed to determine whether the M235T variants of AGT gene were associated with the prevalence of pre-eclampsia and also to evaluate the role of plasma AGT in the development of the disease. Hence, developed, rapid and reliable PCR based assay was used to screen individuals for the M235T alleles. This assay was also used to genotype prospectively both recruited pregnant women with pre-eclampsia (n=24) and controls (n=11). Plasma AGT was determined by radioimmunoassay (RIA). The results of the PCR based assay revealed a significant association of 235T allele with the prevalence of all pre-eclamptic patients, Chi-square (x2) = 3.714, P 0.05). Also, pre-eclamptic women exhibited significant higher levels of plasma AGT (52.15 ± 1.63) versus controls (44.76 ± 4.6) with P value < 0.001. This gave clear evidence that T235T allele and plasma AGT contributed to the development of pre-eclampsia with pregnancy and correlated with severity of the disease

Childhood socioeconomic status, telomere length, and susceptibility to upper respiratory infection.

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Cohen, Sheldon; Janicki-Deverts, Denise; Turner, Ronald B; Marsland, Anna L; Casselbrant, Margaretha L; Li-Korotky, Ha-Sheng; Epel, Elissa S; Doyle, William J

2013-11-01

Low socioeconomic status (SES) during childhood and adolescence has been found to predict greater susceptibility to common cold viruses in adults. Here, we test whether low childhood SES is associated with shorter leukocyte telomere length in adulthood, and whether telomere length mediates the association between childhood SES and susceptibility to acute upper respiratory disease in adulthood. At baseline, 196 healthy volunteers reported whether they currently owned their home and, for each year of their childhood, whether their parents owned the family home. Volunteers also had blood drawn for assessment of specific antibody to the challenge virus, and for CD8+ CD28- T-lymphocyte telomere length (in a subset, n=135). They were subsequently quarantined in a hotel, exposed to a virus (rhinovirus [RV] 39) that causes a common cold and followed for infection and illness (clinical cold) over five post-exposure days. Lower childhood SES as measured by fewer years of parental home ownership was associated with shorter adult CD8+ CD28- telomere length and with an increased probability of developing infection and clinical illness when exposed to a common cold virus in adulthood. These associations were independent of adult SES, age, sex, race, body mass, neuroticism, and childhood family characteristics. Associations with infections and colds were also independent of pre-challenge viral-specific antibody and season. Further analyses do not support mediating roles for smoking, alcohol consumption or physical activity but suggest that CD8+ CD28- cell telomere length may act as a partial mediator of the associations between childhood SES and infection and childhood SES and colds. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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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

Telomere Length and the Cancer-Atherosclerosis Trade-Off.

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Rivka C Stone

2016-07-01

Full Text Available 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.

Telomere length maintenance--an ALTernative mechanism.

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Royle, N J; Foxon, J; Jeyapalan, J N; Mendez-Bermudez, A; Novo, C L; Williams, J; Cotton, V E

2008-01-01

The Alternative Lengthening of Telomeres (ALT) mechanism is utilised by approximately 10% of human tumours and a higher proportion of some types of sarcomas. ALT+ cell lines and tumours show heterogeneous telomere length, extra-chromosomal circular and linear telomeric DNA, ALT associated promyelocytic bodies (APBs), a high frequency of post-replication exchanges in telomeres (designated as telomere-sister chromatid exchanges, T-SCE) and high instability at a GC-rich minisatellite, MS32 (D1S8). It is clear that there is a link between the minisatellite instability and the mechanism that underpins ALT, however currently the nature of this relationship is uncertain. Single molecule analysis of telomeric DNA from ALT+ cell lines and tumours has revealed complex telomere mutations that have not been seen in cell lines or tumours that express telomerase. These complex telomere mutations cannot be explained by T-SCE but must arise by another inter-molecular process. The break-induced replication (BIR) model that may explain the observed high frequency of T-SCE and the presence of complex telomere mutations is reviewed. Copyright 2008 S. Karger AG, Basel.

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

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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.

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

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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

Utility of telomere length measurements for age determination of humpback whales

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Morten Tange Olsen

2014-12-01

Full Text Available This study examines the applicability of telomere length measurements by quantitative PCR as a tool for minimally invasive age determination of free-ranging cetaceans. We analysed telomere length in skin samples from 28 North Atlantic humpback whales (Megaptera novaeangliae, ranging from 0 to 26 years of age. The results suggested a significant correlation between telomere length and age in humpback whales. However, telomere length was highly variable among individuals of similar age, suggesting that telomere length measured by quantitative PCR is an imprecise determinant of age in humpback whales. The observed variation in individual telomere length was found to be a function of both experimental and biological variability, with the latter perhaps reflecting patterns of inheritance, resource allocation trade-offs, and stochasticity of the marine environment.

Pre-eclampsia: Factores de riesgo. Estudio en el Hospital Nacional Cayetano Heredia.

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Manuel Salviz Salhuana

1996-01-01

Full Text Available Objetivo: El objetivo fue evaluar los factores de riesgo asociados a pre-eclampsia en nuestro hospital. Material y métodos: Se realizó un estudio prospectivo, de tipo caso-control concurrente en 88 pacientes con pre-eclampsia e igual número de controles. El trabajo se llevó a cabo en el Servicio de Obstetricia del Hospital Nacional Cayetano Heredia entre los meses de marzo a agosto de 1993. Resultados: Los factores asociados a pre-eclampsia fueron el antecedente previo a pre-eclampsia (OR:17, el índice de masa corporal elevado (OR:9.6, la raza predominantemente blanca (OR:6.4, el antecedente familiar de hipertensión arterial (OR: 5.2, la falta de control pre-natal y la nuliparidad (OR: 2.5. La incidencia de pre-eclampsia fue 4.11%, y requirieron parto por cesárea el 69.3% de las pacientes. Presentaron complicaciones en el puerperio inmediato 28.4% de los casos, siendo más frecuentes las infecciones. (Rev Med Hered 1996; 7: 24-31.

Telomere length in normal and neoplastic canine tissues.

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Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

2007-12-01

To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

Risk factors of pre-eclampsia/eclampsia and its adverse outcomes in low- and middle-income countries: a WHO secondary analysis.

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Ver Luanni Bilano

Full Text Available Pre-eclampsia has an immense adverse impact on maternal and perinatal health especially in low- and middle-income settings. We aimed to estimate the associations between pre-eclampsia/eclampsia and its risk factors, and adverse maternal and perinatal outcomes.We performed a secondary analysis of the WHO Global Survey on Maternal and Perinatal Health. The survey was a multi-country, facility-based cross-sectional study. A global sample consisting of 24 countries from three regions and 373 health facilities was obtained via a stratified multi-stage cluster sampling design. Maternal and offspring data were extracted from records using standardized questionnaires. Multi-level logistic regression modelling was conducted with random effects at the individual, facility and country levels.Data for 276,388 mothers and their infants was analysed. The prevalence of pre-eclampsia/eclampsia in the study population was 10,754 (4%. At the individual level, sociodemographic characteristics of maternal age ≥30 years and low educational attainment were significantly associated with higher risk of pre-eclampsia/eclampsia. As for clinical and obstetric variables, high body mass index (BMI, nulliparity (AOR: 2.04; 95%CI 1.92-2.16, absence of antenatal care (AOR: 1.41; 95%CI 1.26-1.57, chronic hypertension (AOR: 7.75; 95%CI 6.77-8.87, gestational diabetes (AOR: 2.00; 95%CI 1.63-2.45, cardiac or renal disease (AOR: 2.38; 95%CI 1.86-3.05, pyelonephritis or urinary tract infection (AOR: 1.13; 95%CI 1.03-1.24 and severe anemia (AOR: 2.98; 95%CI 2.47-3.61 were found to be significant risk factors, while having >8 visits of antenatal care was protective (AOR: 0.90; 95%CI 0.83-0.98. Pre-eclampsia/eclampsia was found to be a significant risk factor for maternal death, perinatal death, preterm birth and low birthweight.Chronic hypertension, obesity and severe anemia were the highest risk factors of preeclampsia/eclampsia. Implementation of effective interventions

Short fetal leukocyte telomere length and preterm prelabor rupture of the membranes.

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Ramkumar Menon

Full Text Available BACKGROUND: Rupture of the fetal membranes is a common harbinger of imminent labor and delivery. Telomere shortening is a surrogate for oxidative stress (OS and senescence. Fetal leukocyte and placental membrane DNA telomere lengths were evaluated to determine their association with preterm prelabor rupture of the membranes (pPROM or spontaneous preterm births with intact membranes (PTB, compared to term birth. METHODS: Telomere lengths were quantified in cord blood leukocytes (n = 133 from three major groups: 1 pPROM (n = 28, 2 PTB (n = 69 and 3 uncomplicated full term births (controls, n = 35, using real-time quantitative PCR. Placental membrane specimens (n = 18 were used to correlate fetal leukocyte and placental telomere lengths. Telomere length differences among the groups were analyzed by ANOVA. Pearson correlation coefficients determined relationships between leukocyte and placental membrane telomere lengths. RESULTS: In pregnancies with intact membranes, fetal leukocyte telomere length was inversely proportional to gestational age. The mean telomere length decreased as gestation progressed, with the shortest at term. pPROM had telomere lengths (9962 ± 3124 bp that were significantly shorter than gestational age-matched PTB (11546 ± 4348 bp, p = 0.04, but comparable to term births (9011 ± 2497 bp, p = 0.31. Secondary analyses revealed no effects of race (African American vs. Caucasian or intraamniotic infection on telomere length. A strong Pearson's correlation was noted between fetal leukocyte and placental membrane telomere lengths (ρ = 0.77; p<0.01. CONCLUSIONS: Fetal leukocyte telomere length is reduced in pPROM compared to PTB but is similar to term births. pPROM represents a placental membrane disease likely mediated by OS-induced senescence.

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

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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

Acute maternal infection and risk of pre-eclampsia: a population-based case-control study.

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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

Television Watching and Telomere Length Among Adults in Southwest China.

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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.

Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case–control study

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Ye, Yunzhen; Zhou, Qiongjie; Feng, Liping; Wu, Jiangnan; Xiong, Yu; Li, Xiaotian

2017-01-01

Abstract Background Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. Methods We conducted a nested case–control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16–20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. Results BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42–49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). Conclusions These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia. PMID:29186464

Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case-control study.

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Ye, Yunzhen; Zhou, Qiongjie; Feng, Liping; Wu, Jiangnan; Xiong, Yu; Li, Xiaotian

2017-12-01

Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. We conducted a nested case-control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16-20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42-49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association.

Clinical accuracy of inflationary oscillometry in pregnancy and pre-eclampsia: Omron-MIT Elite.

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Chung, Y; Brochut, M C; de Greeff, A; Shennan, A H

2012-10-01

To evaluate the accuracy of the Omron MIT Elite in pregnancy and pre-eclampsia according to the British Hypertension Society protocol (BHS). Prospective observational study. Antenatal clinics and wards at St. Thomas' Hospital (London, UK). Forty-five pregnant women including 15 with pre-eclampsia. Nine sequential same arm blood pressure (BP) measurements were taken from each woman by trained observers, alternating between mercury sphygmomanometry and the test device. Grading criteria of the BHS protocol (A/B grade=pass; C/D=fail). The Omron MIT Elite achieved a grade A/A in both pregnancy and pre-eclampsia. The mean difference (SD) between the mercury standard and the device in pregnancy was -1.1 (5.2)mmHg and 1.5 (4.8)mmHg for systolic and diastolic BP respectively compared to 0.2 (5.3)mmHg and 2.2 (5.5)mmHg in pre-eclampsia. The Omron MIT Elite can be recommended for use in pregnancy and pre-eclampsia according to the BHS protocol. To date, this is the most accurate automated BP device validated in pre-eclampsia. Copyright © 2012. Published by Elsevier B.V.

Silica inhalation altered telomere length and gene expression of telomere regulatory proteins in lung tissue of rats.

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Shoeb, Mohammad; Joseph, Pius; Kodali, Vamsi; Mustafa, Gul; Farris, Breanne Y; Umbright, Christina; Roberts, Jenny R; Erdely, Aaron; Antonini, James M

2017-12-11

Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT. Lung tissues and blood samples were collected from rats at 4, 32, and 44 wk after exposure to 15 mg/m 3 of silica × 6 h/d × 5 d. Controls were exposed to air. At all-time points, RTEL1 expression was significantly decreased in lung tissue of the silica-exposed animals compared to controls. Also, significant increases in telomere length and TERT were observed in the silica group at 4 and 32 wk. Telomere length, RTEL1 and TERT expression may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung disease and tumorigeneses.

Relationship between leukocyte telomere length and personality traits in healthy subjects.

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Sadahiro, R; Suzuki, A; Enokido, M; Matsumoto, Y; Shibuya, N; Kamata, M; Goto, K; Otani, K

2015-02-01

It has been shown that certain personality traits are related to mortality and disease morbidity, but the biological mechanism linking them remains unclear. Telomeres are tandem repeat DNA sequences located at the ends of chromosomes, and shorter telomere length is a predictor of mortality and late-life disease morbidity. Thus, it is possible that personality traits influence telomere length. In the present study, we examined the relationship of leukocyte telomere length with personality traits in healthy subjects. The subjects were 209 unrelated healthy Japanese who were recruited from medical students at 4th-5th grade. Assessment of personality traits was performed by the Revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI). Leukocyte relative telomere length was determined by a quantitative real-time PCR method for a ratio of telomere/single copy gene. In the stepwise multiple regression analysis, shorter telomere length was related to lower scores of neuroticism (Ppersonality traits, and this association may be implicated in the relationship between personality traits and mortality. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

FTO associations with obesity and telomere length.

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Zhou, Yuling; Hambly, Brett D; McLachlan, Craig S

2017-09-01

This review examines the biology of the Fat mass- and obesity-associated gene (FTO), and the implications of genetic association of FTO SNPs with obesity and genetic aging. Notably, we focus on the role of FTO in the regulation of methylation status as possible regulators of weight gain and genetic aging. We present a theoretical review of the FTO gene with a particular emphasis on associations with UCP2, AMPK, RBL2, IRX3, CUX1, mTORC1 and hormones involved in hunger regulation. These associations are important for dietary behavior regulation and cellular nutrient sensing via amino acids. We suggest that these pathways may also influence telomere regulation. Telomere length (TL) attrition may be influenced by obesity-related inflammation and oxidative stress, and FTO gene-involved pathways. There is additional emerging evidence to suggest that telomere length and obesity are bi-directionally associated. However, the role of obesity risk-related genotypes and associations with TL are not well understood. The FTO gene may influence pathways implicated in regulation of TL, which could help to explain some of the non-consistent relationship between weight phenotype and telomere length that is observed in population studies investigating obesity.

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

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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.

A meta-analysis of the relationship between anxiety and telomere length.

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Malouff, John M; Schutte, Nicola S

2017-05-01

Telomeres are protective caps at the ends of chromosomes, and shorter telomeres are associated with poor physical health. The present study set out to consolidate the varying effect sizes found so far in studies of anxiety and telomere length. A meta-analytic investigation of the relationship between anxiety and telomere length used information from 17 different samples comprising a total of 19,424 participants. The results showed a small but significant association, r = -.06, between higher anxiety and shorter telomeres. Studies comparing individuals diagnosed with an anxiety disorder with other individuals had a significant effect size, and studies that did not use this comparison threshold did not have a significant effect size. Anxiety is associated with an important biomarker related to health. Future experimental studies that examine the impact of interventions intended to reduce anxiety in conjunction with measurement of telomere length can further clarify the impact of anxiety on telomere length.

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...

Parental care influences leukocyte telomere length with gender specificity in parents and offsprings.

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Enokido, Masanori; Suzuki, Akihito; Sadahiro, Ryoichi; Matsumoto, Yoshihiko; Kuwahata, Fumikazu; Takahashi, Nana; Goto, Kaoru; Otani, Koichi

2014-10-03

There have been several reports suggesting that adverse childhood experiences such as physical maltreatment and long institutionalization influence telomere length. However, there has been no study examining the relationship of telomere length with variations in parental rearing. In the present study, we examined the relationship of leukocyte telomere length with parental rearing in healthy subjects. The subjects were 581 unrelated healthy Japanese subjects. Perceived parental rearing was assessed by the Parental Bonding Instrument consisting of the care and protection factors. Leukocyte relative telomere length was determined by a quantitative real-time PCR method for a ratio of telomere/single copy gene. In the multiple regression analyses, shorter telomere length in males was related to lower scores of paternal care (β = 0.139, p care (β = 0.195, p parental care and telomere length which covers both lower and higher ends of parental care, and that the effects of parental care on telomere length are gender-specific in parents and offsprings.

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

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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.

Role of nutrition in pre-eclampsia and eclampsia cases, a case control study

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Punyatoya Bej

2014-12-01

Full Text Available Background: Preeclampsia and eclampsia during pregnancy contribute to maternal and fetal morbidity as well as mortality. The identification of the role of maternal nutrition during pregnancy will help in reducing morbidity and mortality. Aims & Objective: The objective of this study is to find out the role of nutrition, in the form of total calorie, protein, fruits, iron, folic acid and calcium intake in the development of preeclampsia and eclampsia among pregnant women in a tertiary level hospital. Material Methods: After ethical approval and informed consent, 122 women who delivered beyond 22 weeks of gestation and diagnosed as preeclampsia or eclampsia were selected. Simultaneously, 122 controls with no diagnosis of preeclampsia or eclampsia were selected from the post natal ward. Cases and controls were administered the same pre-tested questionnaire containing questions related to food and micronutrient intake by cases and control. Results: Logistic regression was applied in the statistical analysis. The factors that were found to be significant predictors of risk for development of preeclampsia and eclampsia were higher calorie intake (adjusted Odds Ratio (OR 14.12 [6.41-43.23] P < 0.001, less protein intake (adjusted OR 3.87 [1.97-8.01] P < 0.001 during pregnancy. Fruits intake in both cases and controls were similar. 77.9% of cases and 84.4% of controls had taken iron tablets during their antenatal period. 75.4% of cases and 82.8% of controls had taken calcium tablets during their antenatal period. Iron and calcium intake is not significantly associated with development of preeclampsia and eclampsia. Conclusion: Higher calorie intake and less protein intake during pregnancy were associated with development of preeclampsia and eclampsia. Fruits intake, iron and calcium intake were not associated with development of preeclampsia and eclampsia

Telomere length and early severe social deprivation: linking early adversity and cellular aging

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Drury, SS; Theall, K; Gleason, MM; Smyke, AT; De Vivo, I; Wong, JYY; Fox, NA; Zeanah, CH; Nelson, CA

2012-01-01

Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity. PMID:21577215

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

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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

Telomeres and replicative senescence: Is it only length that counts?

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von Zglinicki, T

2001-07-26

Telomeres are well established as a major 'replicometer', counting the population doublings in primary human cell cultures and ultimately triggering replicative senescence. However, neither is the pace of this biological clock inert, nor is there a fixed threshold telomere length acting as the universal trigger of replicative senescence. The available data suggest that opening of the telomeric loop and unscheduled exposure of the single-stranded G-rich telomeric overhang might act like a semaphore to signal senescent cell cycle arrest. Short telomere length, telomeric single-strand breaks, low levels of loop-stabilizing proteins, or other factors may trigger this opening of the loop. Thus, both telomere shortening and the ultimate signalling into senescence are able to integrate different environmental and genetic factors, especially oxidative stress-mediated damage, which might otherwise become a thread to genomic stability.

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.

Serial assessment of cardiovascular control shows early signs of developing pre-eclampsia

NARCIS (Netherlands)

Rang, Sasika; Wolf, H.; van Montfrans, G. A.; Karemaker, J. M.

2004-01-01

Purpose To evaluate whether differences in autonomic cardiovascular control between normal pregnant women and women who develop pre-eclampsia later in pregnancy can be detected even before or early in pregnancy. Design We studied 42 women, 21 multigravid with a history of pre-eclampsia and 21

A cross-sectional study to evaluate the cranial magnetic resonance imaging findings in eclampsia and severe pre-eclampsia patients and its clinical correlation

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Ruchi Saxena

2018-01-01

Full Text Available Background: Pre-eclampsia/eclampsia remains a high contributor towards maternal mortality and morbidity and also the poor perinatal outcome. Thus, timely prediction of the onset of eclampsia and starting appropriate treatment as early as possible is important for favourable maternal and perinatal outcome. However, there is a dearth of studies, especially in the Indian scenario which correlates the severity of pre-eclampsia/eclampsia and the cranial magnetic resonance imaging (MRI findings, therefore, this study was planned to fill the lacuna. Material and Methods: A total of forty patients admitted in the department, of forty, twenty patients were diagnosed with eclampsia and twenty patients with severe pre-eclampsia. MRI was performed in all these 40 patients and they were divided into two groups. Group I (MRI findings positive n = 17 and Group II (MRI findings negative n = 23, the patients once had agreed to (with consent were sent to MRI centre for MRI to be performed. All the data required along with the patients' sign and symptom were recorded in the pro foma designed for this study. Results: The difference in the study groups was statistically significant regarding headache, seizures, depression of consciousness and visual disorder (P = 0.0085, <0.0001, <0.0001, and <0.0001, respectively. In MRI positive findings patients, the occipital cortex was involved in 100% of patients, parietal cortex in 58.82%, frontal cortex in 58.82% and temporal cortex in only 11.77% of patients. Basal ganglia had an infarct in 11.77%. Conclusion: We have observed patients suffering from severe pre-eclampsia and having positive cerebral findings on MRI scan, However employing MRI for screening is not cost-effective and large-scale randomised control trials are needed to further confirm the role of MRI in severe pre-eclampsia.

Elevated circulating homocyst(e)ine levels in placental vascular disease and associated pre-eclampsia.

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Wang, J; Trudinger, B J; Duarte, N; Wilcken, D E; Wang, X L

2000-07-01

We examined the hypothesis that hyperhomocyst(e)inaemia in the maternal or fetal circulation is associated with placental vascular disease with either the maternal syndrome of pre-eclampsia and/or fetal syndrome of growth restriction. Maternal plasma homocyst(e)ine levels were significantly higher in pregnancies complicated by pre-eclampsia, pregnancies with evidence of umbilical placental vascular disease, and pregnancies with both complications compared with the normal pregnancy group. In the fetal circulation mean plasma homocyst(e)ine concentration was significantly higher in the pre-eclampsia group compared with the normal group. The results suggest that hyperhomocyst(e)inaemia may be a risk marker for placental vascular disease and maternal pre-eclampsia. The elevated fetal plasma homocyst(e)ine concentrations, found only in the group of pregnancies with pre-eclampsia in the absence of umbilical placental vascular disease, may be due to an effect of placental vascular disease on homocyst(e)ine transfer from the maternal to fetal circulation.

Large-scale parent-child comparison confirms a strong paternal influence on telomere length.

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Nordfjäll, Katarina; Svenson, Ulrika; Norrback, Karl-Fredrik; Adolfsson, Rolf; Roos, Göran

2010-03-01

Telomere length is documented to have a hereditary component, and both paternal and X-linked inheritance have been proposed. We investigated blood cell telomere length in 962 individuals with an age range between 0 and 102 years. Telomere length correlations were analyzed between parent-child pairs in different age groups and between grandparent-grandchild pairs. A highly significant correlation between the father's and the child's telomere length was observed (r=0.454, Pfather-son: r=0.465, Pfather-daughter: r=0.484, Pmothers, the correlations were weaker (mother-child: r=0.148, P=0.098; mother-son: r=0.080, P=0.561; mother-daughter: r=0.297, P=0.013). A positive telomere length correlation was also observed for grandparent-grandchild pairs (r=0.272, P=0.013). Our findings indicate that fathers contribute significantly stronger to the telomere length of the offspring compared with mothers (P=0.012), but we cannot exclude a maternal influence on the daughter's telomeres. Interestingly, the father-child correlations diminished with increasing age (P=0.022), suggesting that nonheritable factors have an impact on telomere length dynamics during life.

High-throughput telomere length quantification by FISH and its application to human population studies.

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Canela, Andrés; Vera, Elsa; Klatt, Peter; Blasco, María A

2007-03-27

A major limitation of studies of the relevance of telomere length to cancer and age-related diseases in human populations and to the development of telomere-based therapies has been the lack of suitable high-throughput (HT) assays to measure telomere length. We have developed an automated HT quantitative telomere FISH platform, HT quantitative FISH (Q-FISH), which allows the quantification of telomere length as well as percentage of short telomeres in large human sample sets. We show here that this technique provides the accuracy and sensitivity to uncover associations between telomere length and human disease.

Large-scale parent–child comparison confirms a strong paternal influence on telomere length

OpenAIRE

Nordfjäll, Katarina; Svenson, Ulrika; Norrback, Karl-Fredrik; Adolfsson, Rolf; Roos, Göran

2009-01-01

Telomere length is documented to have a hereditary component, and both paternal and X-linked inheritance have been proposed. We investigated blood cell telomere length in 962 individuals with an age range between 0 and 102 years. Telomere length correlations were analyzed between parent–child pairs in different age groups and between grandparent–grandchild pairs. A highly significant correlation between the father's and the child's telomere length was observed (r=0.454, P

Nature vs nurture: interplay between the genetic control of telomere length and environmental factors.

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Harari, Yaniv; Romano, Gal-Hagit; Ungar, Lior; Kupiec, Martin

2013-11-15

Telomeres are nucleoprotein structures that cap the ends of the linear eukaryotic chromosomes, thus protecting their stability and integrity. They play important roles in DNA replication and repair and are central to our understanding of aging and cancer development. In rapidly dividing cells, telomere length is maintained by the activity of telomerase. About 400 TLM (telomere length maintenance) genes have been identified in yeast, as participants of an intricate homeostasis network that keeps telomere length constant. Two papers have recently shown that despite this extremely complex control, telomere length can be manipulated by external stimuli. These results have profound implications for our understanding of cellular homeostatic systems in general and of telomere length maintenance in particular. In addition, they point to the possibility of developing aging and cancer therapies based on telomere length manipulation.

ASSESSMENT OF OXIDATIVE STRESS IN EARLY AND LATE ONSET PRE-ECLAMPSIA AMONG GHANAIAN WOMEN.

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Tetteh, P W; Adu-Bonsaffoh, K; Antwi-Boasiako, C; Antwi, D A; Gyan, B; Obed, S A

2015-01-01

Pre-eclampsia is a multisystem pregnancy-related disorder with multiple theories regarding its aetiology resulting in lack of reliable screening tests and well-established measures for primary prevention. However, oxidative stress is increasingly being implicated in the pathogenesi of pre-eclampsia although conflicting findings have been reported. To determine and compare the levels of oxidative stress in early and late onset pre-eclampsia by measuring urinary excretion of isoprostane and total antioxidant power (TAP) in a cohort of pre-eclamptic women at Korle Bu Teaching Hospital. This was a cross-sectional study conducted at Korle-Bu Teaching Hospital, Accra, Ghana involving pre-eclamptic women between the ages 18 and 45 years who gave written informed consent. Urinary isoprostane levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit whereas the Total Anti-oxidant Power in urine samples was determined using Total Antioxidant Power Colorimetric Microplate Assay kit. The data obtained were analyzed using MEGASTAT statistical software package. We included 102 pre-eclamptic women comprising 68 (66.7%) and 34 (33.3%) with early-onset and late-onset pre-eclampsia respectively. There were no statistically significant differences between the mean maternal age, haematological indices, serum ALT, AST, ALT, albumin, urea, creatinine uric acid and total protein at the time of diagnosis. The mean gestational age at diagnosis of early and late onset pre-eclampsia were 31.65 ± 0.41 and 38.03 ± 0.21 respectively (p ˂ 0.001). Also, there were statistically significant differences between the diastolic blood pressure (BP), systolic BP and mean arterial pressure (MAP) at diagnosis of pre-eclampsia in the two categories. The mean urinary Isoprostane excretion was significantly higher in the early onset pre-eclamptic group (3.04 ± 0.34 ng/mg Cr) compared to that of the late onset pre-eclamptic group (2.36 ± 0.45 ng/mg Cr), (p=0.019). Urinary total

Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

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Youichi Kawano

Full Text Available Along with the increasing need for living-donor liver transplantation (LDLT, the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH. The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038, demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001. Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

Impaired renal function and increased urinary isoprostane excretion in Ghanaian women with pre-eclampsia

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Tetteh PW

2013-06-01

Full Text Available Paul Winston Tetteh,1,4 Charles Antwi-Boasiako,1 Ben Gyan,3 Daniel Antwi,1 Festus Adzaku,1 Kwame Adu-Bonsaffoh,1,2 Samuel Obed21Department of Physiology, 2Department of Obstetrics and Gynecology, University of Ghana Medical School, Accra, Ghana; 3Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana; 4Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, Utrecht, The NetherlandsBackground: The cause of pre-eclampsia remains largely unknown, but oxidative stress (an imbalance favoring oxidant over antioxidant forces has been implicated in contributing to the clinical symptoms of hypertension and proteinuria. Assessment of oxidative stress in pre-eclampsia using urinary isoprostane has produced conflicting results, and it is likely that renal function may affect isoprostane excretion. The aim of this study was to determine the role of oxidative stress in the pathophysiology of pre-eclampsia and to assess the effect of renal function on isoprostane excretion in pre-eclampsia in the Ghanaian population.Methods: This was a case-controlled study, comprising 103 pre-eclamptic women and 107 normal pregnant controls and conducted at the Korle-Bu Teaching Hospital between December 2006 and May 2007. The study participants were enrolled in the study after meeting the inclusion criteria and signing their written informed consent. Oxidative stress was determined by measuring urinary excretion of isoprostane and total antioxidant capacity using an enzyme-linked immunosorbent assay technique. Renal function was assessed by calculating the estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula.Results: The pre-eclampsia group had significantly (P = 0.0006 higher urinary isoprostane excretion (2.81 ± 0.14 ng/mg creatinine than the control group (2.01 ± 0.18 ng/mg creatinine and a significantly (P = 0.0008 lower total antioxidant power (1

Genetic association of telomere length with hepatocellular carcinoma risk: A Mendelian randomization analysis.

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Cheng, Yue; Yu, Chengxiao; Huang, Mingtao; Du, Fangzhi; Song, Ci; Ma, Zijian; Zhai, Xiangjun; Yang, Yuan; Liu, Jibin; Bei, Jin-Xin; Jia, Weihua; Jin, Guangfu; Li, Shengping; Zhou, Weiping; Liu, Jianjun; Dai, Juncheng; Hu, Zhibin

2017-10-01

Observational studies show an association between telomere length and Hepatocellular carcinoma (HCC) risk, but the relationship is controversial. Particularly, it remains unclear whether the association is due to confounding or biases inherent in conventional epidemiological studies. Here, we applied Mendelian randomization approach to evaluate whether telomere length is causally associated with HCC risk. Individual-level data were from HBV-related HCC Genome-wide association studies (1,538 HBV positive HCC patients and 1,465 HBV positive controls). Genetic risk score, as proxy for actual measured telomere length, derived from nine telomere length-associated genetic variants was used to evaluate the effect of telomere length on HCC risk. We observed a significant risk signal between genetically increased telomere length and HBV-related HCC risk (OR=2.09, 95% CI 1.32-3.31, P=0.002). Furthermore, a U-shaped curve was fitted by the restricted cubic spline curve, which indicated that either short or long telomere length would increase HCC risk (P=0.0022 for non-linearity test). Subgroup analysis did not reveal significant heterogeneity between different age, gender, smoking status and drinking status groups. Our results indicated that a genetic background that favors longer or shorter telomere length may increase HBV-related HCC risk-a U-shaped association. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of Donor and Recipient Telomere Length with Clinical Outcomes following Lung Transplantation.

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Courtwright, Andrew M; Fried, Sabrina; Villalba, Julian A; Moniodis, Anna; Guleria, Indira; Wood, Isabelle; Milford, Edgar; Mallidi, Hari H; Hunninghake, Gary M; Raby, Benjamin A; Agarwal, Suneet; Camp, Philip C; Rosas, Ivan O; Goldberg, Hilary J; El-Chemaly, Souheil

2016-01-01

Patients with short telomere syndromes and pulmonary fibrosis have increased complications after lung transplant. However, the more general impact of donor and recipient telomere length in lung transplant has not been well characterized. This was an observational cohort study of patients who received lung transplant at a single center between January 1st 2012 and January 31st 2015. Relative donor lymphocyte telomere length was measured and classified into long (third tertile) and short (other tertiles). Relative recipient lung telomere length was measured and classified into short (first tertile) and long (other tertiles). Outcome data included survival, need for modification of immunosuppression, liver or kidney injury, cytomegalovirus reactivation, and acute rejection. Recipient lung tissue telomere lengths were measured for 54 of the 79 patients (68.3%) who underwent transplant during the study period. Donor lymphocyte telomeres were measured for 45 (83.3%) of these recipients. Neither long donor telomere length (hazard ratio [HR] = 0.58, 95% confidence interval [CI], 0.12-2.85, p = 0.50) nor short recipient telomere length (HR = 1.01, 95% CI = 0.50-2.05, p = 0.96) were associated with adjusted survival following lung transplant. Recipients with short telomeres were less likely to have acute cellular rejection (23.5% vs. 58.8%, p = 0.02) but were not more likely to have other organ dysfunction. In this small cohort, neither long donor lymphocyte telomeres nor short recipient lung tissue telomeres were associated with adjusted survival after lung transplantation. Larger studies are needed to confirm these findings.

The relationship between telomere length and mortality in chronic obstructive pulmonary disease (COPD.

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Jee Lee

Full Text Available Some have suggested that chronic obstructive pulmonary disease (COPD is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR, we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS. The subjects were followed for approximately 7.5 years during which time their vital status, FEV(1 and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy "mid-life" volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy "mid-life" volunteers (p<.001. Compared to individuals in the 4(th quartile of relative telomere length (i.e. longest telomere group, the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324 and total mortality (HR, 1.29; p = 0.0425. Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD.

Elucidating the Pathogenesis of Pre-eclampsia Using In Vitro Models of Spiral Uterine Artery Remodelling.

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McNally, Ross; Alqudah, Abdelrahim; Obradovic, Danilo; McClements, Lana

2017-10-23

The aim of the study is to perform a critical assessment of in vitro models of pre-eclampsia using complementary human and cell line-based studies. Molecular mechanisms involved in spiral uterine artery (SUA) remodelling and trophoblast functionality will also be discussed. A number of proteins and microRNAs have been implicated as key in SUA remodelling, which could be explored as early biomarkers or therapeutic targets for prevention of pre-eclampsia. Various 2D and 3D in vitro models involving trophoblast cells, endothelial cells, immune cells and placental tissue were discussed to elucidate the pathogenesis of pre-eclampsia. Nevertheless, pre-eclampsia is a multifactorial disease, and the mechanisms involved in its pathogenesis are complex and still largely unknown. Further studies are required to provide better understanding of the key processes leading to inappropriate placental development which is the root cause of pre-eclampsia. This new knowledge could identify novel biomarkers and treatment strategies.

Early life adversity and telomere length: a meta-analysis.

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Ridout, K K; Levandowski, M; Ridout, S J; Gantz, L; Goonan, K; Palermo, D; Price, L H; Tyrka, A R

2018-04-01

Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.

Telomere Length Dynamics and the Evolution of Cancer Genome Architecture

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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.

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

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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.

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

DEFF Research Database (Denmark)

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

2017-01-01

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......-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...

Pre-eclampsia: a Life-threatening Pregnancy Syndrom

Czech Academy of Sciences Publication Activity Database

Brázdová, A.; Keprová, Alena; Zídková, J.; Madar, J.

2014-01-01

Roč. 57, č. 5 (2014), s. 701-705 ISSN 1516-8913 Grant - others:GA AV ČR(CZ) IAA600110902 Program:IA Institutional support: RVO:61388963 Keywords : placenta * pre-eclampsia * pregnancy * oxidative stress Subject RIV: CE - Biochemistry Impact factor: 0.546, year: 2014

Soluble Endoglin as a new marker for prediction of pre-eclampsia in early pregnancy

Directory of Open Access Journals (Sweden)

Khaled Gaber

2010-01-01

Conclusion: Pregnant women who are at risk of developing pre-eclampsia can be offered measuring these markers as a screening method to point out those who are more likely to develop pre-eclampsia and warrant close observation and intervention.

Telomere Length in Circulating Lymphocytes: Association with Chromosomal Aberrations

Czech Academy of Sciences Publication Activity Database

Hemminki, K.; Rachakonda, S.; Musak, L.; Vymetálková, Veronika; Halasová, E.; Forsti,, A.; Vodičková, Ludmila; Buchancová, J.; Vodička, Pavel; Kumar, R.

2015-01-01

Roč. 54, č. 3 (2015), s. 194-196 ISSN 1045-2257 Institutional support: RVO:68378041 Keywords : structural chromosome aberrations * healthy subjects * relative telomere length * genotoxicity * telomere biology Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.960, year: 2015

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

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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.

High plasma folate is negatively associated with leukocyte telomere length in Framingham Offspring cohort.

Science.gov (United States)

Paul, Ligi; Jacques, Paul F; Aviv, Abraham; Vasan, Ramachandran S; D'Agostino, Ralph B; Levy, Daniel; Selhub, Jacob

2015-03-01

Shortening of telomeres, the protective structures at the ends of eukaryotic chromosomes, is associated with age-related pathologies. Telomere length is influenced by DNA integrity and DNA and histone methylation. Folate plays a role in providing precursors for nucleotides and methyl groups for methylation reactions and has the potential to influence telomere length. We determined the association between leukocyte telomere length and long-term plasma folate status (mean of 4 years) in Framingham Offspring Study (n = 1,044, females = 52.1 %, mean age 59 years) using data from samples collected before and after folic acid fortification. Leukocyte telomere length was determined by Southern analysis and fasting plasma folate concentration using microbiological assay. There was no significant positive association between long-term plasma folate and leukocyte telomere length among the Framingham Offspring Study participants perhaps due to their adequate folate status. While the leukocyte telomere length in the second quintile of plasma folate was longer than that in the first quintile, the difference was not statistically significant. The leukocyte telomere length of the individuals in the fifth quintile of plasma folate was shorter than that of those in the second quintile by 180 bp (P folate concentrations in the upper four quintiles of plasma folate (P for trend = 0.001). Multivitamin use was associated with shorter telomeres in this cohort (P = 0.015). High plasma folate status possibly resulting from high folic acid intake may interfere with the role of folate in maintaining telomere integrity.

The Functions of Microparticles in Pre-Eclampsia

NARCIS (Netherlands)

van der Post, Joris A. M.; Lok, Christianne A. R.; Boer, Kees; Sturk, Auguste; Sargent, Ian L.; Nieuwland, Rienk

2011-01-01

Pre-eclampsia (P-EC), a heterogenic multisystem disorder characterized by hypertension and proteinuria, usually develops in the second half of pregnancy. The incidence is 2 to 5%, and P-EC is therefore a major cause of maternal and perinatal morbidity and mortality. Although the exact etiology is

Insights into Cdc13 Dependent Telomere Length Regulation

Energy Technology Data Exchange (ETDEWEB)

M Mason; E Skordalakes

2011-12-31

Cdc13 is a single stranded telomere binding protein that specifically localizes to the telomere ends of budding yeasts and is essential for cell viability. It caps the ends of chromosomes thus preventing chromosome end-to-end fusions and exonucleolytic degradation, events that could lead to genomic instability and senescence, the hallmark of aging. Cdc13 is also involved in telomere length regulation by recruiting or preventing access of telomerase to the telomeric overhang. Recruitment of telomerase to the telomeres for G-strand extension is required for continuous cell division, while preventing its access to the telomeres through capping the chromosome ends prevents mitotic events that could lead to cell immortality, the hall mark of carcinogenesis. Cdc13 and its putative homologues human CTC1 and POT1 are therefore key to many biological processes directly associated with life extension and cancer prevention and can be viewed as an ideal target for cancer and age related therapies.

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

. Structural equation models revealed that a model including additive genetic effects and non-shared environment was the best fitting model and that telomere length was moderately heritable, with an estimate that was sensitive to the telomere length standardization procedure. Sex-specific analyses showed lower...... heritability in males, although not statistically significant, which is in line with our earlier finding of a sex difference in telomere dynamics among the elderly and oldest-old....

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 general population, older age is associated with short leukocyte telomere length and with high risk of infections. In a recent study of allogeneic hematopoietic cell transplantation for severe aplastic anemia, long donor leukocyte telomere length was associated with improved survival...

Magnesium sulphate and other anticonvulsants for women with pre-eclampsia.

Science.gov (United States)

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

Utility of telomere length measurements for age determination of humpback whales

NARCIS (Netherlands)

Olsen, Morten T.; Robbins, Jooke; Bérubé, Martine; Rew, Mary Beth; Palsboll, Per

2014-01-01

This study examines the applicability of telomere length measurements by quantitative PCR as a tool for minimally invasive age determination of free-ranging cetaceans. We analysed telomere length in skin samples from 28 North Atlantic humpback whales (Megaptera novaeangliae), ranging from 0 to 26

[Methods of measuring telomere length and telomerase activity--practice and problems].

Science.gov (United States)

Saito, Y; Suda, T; Hatakeyama, K

1998-05-01

The development of a highly sensitive method for detection of telomerase activity, telomeric repeat amplification protocol (TRAP), has provided knowledge on telomerase activity in normal and cancer tissues. Subsequent several modifications have been achieved, including an introduction of the internal standard and hybridization protection technique that leads to simplicity and improvement of reproducibility and linearity of this method, and application of TRAP to in situ analysis to identify the cells responsible for telomerase activity. As for measurement of telomere length, fluorescence in situ hybridization technique appeared to give an information of telomere length on an individual chromosome in contrast to analysis of terminal restriction fragment, a conventional method which can express mean telomere length of all chromosomes. Further methodological improvement in this field is ongoing and showing a new sight on cell mortality and immortality.

Association between objectively measured physical activity, chronic stress and leukocyte telomere length.

Science.gov (United States)

von Känel, Roland; Bruwer, Erna J; Hamer, Mark; de Ridder, J Hans; Malan, Leoné

2017-10-01

Physical activity (PA) attenuates chronic stress and age-related and cardiovascular disease risks, whereby potentially slowing telomere shortening. We aimed to study the association between seven-day objectively measured habitual PA, chronic stress and leukocyte telomere length. Study participants were African (N.=96) and Caucasian (N.=107) school teachers of the Sympathetic activity and Ambulatory Blood Pressure in Africans study. All lifestyle characteristics (including PA) were objectively measured. The general health questionnaire and serum cortisol were assessed as psychological and physical measures of chronic stress. Leukocyte telomere length was measured using the quantitative real-time polymerase chain reaction. Africans had significantly shorter telomeres (Pstress or telomere length. However, more time spent with light intensity PA time was significantly and independently correlated with lower waist circumference (r=-0.21, P=0.004); in turn, greater waist circumference was significantly associated shorter telomeres (β=-0.17 [-0.30, -0.03], P=0.017). Habitual PA of different intensity was not directly associated with markers of chronic stress and leukocyte telomere length in this biethnic cohort. However, our findings suggest that light intensity PA could contribute to lowered age-related disease risk and healthy ageing by facilitating maintenance of a normal waist circumference.

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. I 2 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.

Blood and dried blood spot telomere length measurement by qPCR: assay considerations.

Directory of Open Access Journals (Sweden)

DeAnna L Zanet

Full Text Available Measurement of telomere length is crucial for the study of telomere maintenance and its role in molecular pathophysiology of diseases and in aging. Several methods are used to measure telomere length, the choice of which usually depends on the type and size of sample to be assayed, as well as cost and throughput considerations. The goal of this study was to investigate the factors that may influence the reliability of qPCR-based relative telomere length measurements in whole blood. Day to day intra-individual variability, types of blood anticoagulant, sample storage conditions, processing and site of blood draw were investigated. Two qPCR-based methods to measure telomere length (monoplex vs. multiplex were also investigated and showed a strong correlation between them. Freezing and thawing of the blood and storage of the blood at 4°C for up to 4 days did not affect telomere length values. Telomere lengths in dried blood spots were significantly higher than both whole blood and peripheral mononuclear blood cells, and were highly correlated with both. We found that telomere length measurements were significantly higher in dried blood spots collected directly from fingertip prick compared to dried blood spots prepared with anticoagulated whole blood collected from the finger, and non-blotted whole blood taken from both finger and arm venipuncture. This suggests that DNA from cells blotted on paper is not equivalent to that collected from venipuncture whole blood, and caution should be taken when comparing between blood sample types.

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

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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.

Blood group AB and factor V Leiden as risk factors for pre-eclampsia: a population-based nested case-control study.

Science.gov (United States)

Hiltunen, Leena M; Laivuori, Hannele; Rautanen, Anna; Kaaja, Risto; Kere, Juha; Krusius, Tom; Paunio, Mikko; Rasi, Vesa

2009-06-01

Pre-eclampsia is an important cause of maternal morbidity and mortality. Its etiology is still unknown. Clinical symptoms correlate with activation of coagulation and inherited thrombophilia has been associated with pre-eclampsia. ABO blood group has been associated with thrombotic disorders and pre-eclampsia. We assessed ABO blood group, seven thrombophilia associated polymorphisms, and anti-beta2-glycoprotein I antibodies as risk factors for pre-eclampsia. We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers and medical records were reviewed. We studied 248 cases fulfilling strict criteria for pre-eclampsia and 679 controls. Severe pre-eclampsia, early pre-eclampsia, and pre-eclampsia with intra-uterine growth restriction (IUGR) were analyzed separately. Blood group AB increased the risk for pre-eclampsia as a whole (OR 2.1, 95% CI 1.3-3.5), and in the three subgroups (OR 2.3, 3.8, 3.4; 95% CI 1.3-3.9, 2.0-7.1, 1.6-7.1). FV Leiden increased the risk as a whole (OR 1.7, 95% CI 0.8-3.9), and in the three subgroups, although not statistically significantly. Anti-beta2-glycoprotein I antibodies were not associated with pre-eclampsia. High body mass index, diabetes, first pregnancy, and twin pregnancy increased the risk from 1.5-fold to 8.2-fold. Our results confirm and extend the prior observation of blood group AB being a risk factor for pre-eclampsia. ABO blood group is known from all pregnant women. The value of blood group as risk factor for pre-eclampsia should be further assessed in prospective studies. In this study, FV Leiden was not statistically significant risk factor.

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

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

Energy Technology Data Exchange (ETDEWEB)

Fillman, Toki, E-mail: tokif@humeco.m.u-tokyo.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan); Shimizu-Furusawa, Hana, E-mail: hana-shimizu@umin.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan); Ng, Chris Fook Sheng, E-mail: chrisng-tky@umin.ac.jp [Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki (Japan); Parajuli, Rajendra Prasad, E-mail: rp.parajuli@mcgill.ca [Basu Laboratory, CINE Building, Macdonald Campus, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec (Canada); Watanabe, Chiho, E-mail: chiho@humeco.m.u-tokyo.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan)

2016-08-15

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

International Nuclear Information System (INIS)

Fillman, Toki; Shimizu-Furusawa, Hana; Ng, Chris Fook Sheng; Parajuli, Rajendra Prasad; Watanabe, Chiho

2016-01-01

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater

Leukocyte Telomere Length and Cognitive Function in Older Adults

Directory of Open Access Journals (Sweden)

Emily Frith

2018-04-01

Full Text Available We evaluated the specific association between leukocyte telomere length and cognitive function among a national sample of the broader U.S. older adult population. Data from the 1999-2002 National Health and Nutrition Examination Survey (NHANES were used to identify 1,722 adults, between 60-85 years, with complete data on selected study variables. DNA was extracted from whole blood via the LTL assay, which is administered using quantitative polymerase chain reaction to measure telomere length relative to standard reference DNA (T/S ratio. Average telomere length was recorded, with two to three assays performed to control for individual variability. The DSST (Digit Symbol Substitution Test was used to assess participant executive cognitive functioning tasks of pairing and free recall. Individuals were excluded if they had been diagnosed with coronary artery disease, congestive heart failure, heart attack or stroke at the baseline assessment. Leukocyte telomere length was associated with higher cognitive performance, independent of gender, race-ethnicity, physical activity status, body mass index and other covariates. In this sample, there was a strong association between LTL and cognition; for every 1 T/S ratio increase in LTL, there was a corresponding 9.9 unit increase in the DSST (β = 9.9; 95% CI: 5.6-14.2; P [JCBPR 2018; 7(1.000: 14-18

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

The 3'-untranslated region of the HLA-G gene in relation to pre-eclampsia: revisited

DEFF Research Database (Denmark)

Larsen, M H; Hylenius, S; Andersen, Anne-Marie Nybo

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, P(C) = 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...

Telomere length is longer in women with late maternal age

DEFF Research Database (Denmark)

Fagan, Erin; Sun, Fangui; Bae, Harold

2017-01-01

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...... in the first tertile. CONCLUSIONS:: These findings show an association between longer leukocyte telomere length and a later maternal age at birth of last child, suggesting that extended maternal age at last childbirth may be a marker for longevity....

Determinants of magnesium sulphate use in women hospitalized at <29 weeks with severe or non-severe pre-eclampsia.

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Dane A De Silva

Full Text Available Magnesium sulphate is recommended by international guidelines to prevent eclampsia among women with pre-eclampsia, especially when it is severe, but fewer than 70% of such women receive magnesium sulphate. We aimed to identify variables that prompt Canadian physicians to administer magnesium sulphate to women with pre-eclampsia.Data were used from the Canadian Perinatal Network (2005-11 of women hospitalized at <29 weeks' who were thought to be at high risk of delivery due to pre-eclampsia (using broad Canadian definition. Unadjusted analyses of relative risks were estimated directly and population attributable risk percent (PAR% calculated to identify variables associated with magnesium sulphate use. A multivariable model was created and a generalized estimating equation was used to estimate the adjusted RR that explained magnesium sulphate use in pre-eclampsia. The adjusted PAR% was estimated by bootstrapping.Of 631 women with pre-eclampsia, 174 (30.1% had severe pre-eclampsia, of whom 131 (75.3% received magnesium sulphate. 457 (69.9% women had non-severe pre-eclamspia, of whom 291 (63.7% received magnesium sulphate. Use of magnesium sulphate among women with pre-eclampsia could be attributed to the following clinical factors (PAR%: delivery for 'adverse conditions' (48.7%, severe hypertension (21.9%, receipt of antenatal corticosteroids (20.0%, maternal transport prior to delivery (9.9%, heavy proteinuria (7.8%, and interventionist care (3.4%.Clinicians are more likely to administer magnesium sulphate for eclampsia prophylaxis in the presence of more severe maternal clinical features, in addition to concomitant antenatal corticosteroid administration, and shorter admission to delivery periods related to transport from another institution or plans for interventionist care.

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

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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.

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

Zen meditation, Length of Telomeres, and the Role of Experiential Avoidance and Compassion.

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Alda, Marta; Puebla-Guedea, Marta; Rodero, Baltasar; Demarzo, Marcelo; Montero-Marin, Jesus; Roca, Miquel; Garcia-Campayo, Javier

Mindfulness refers to an awareness that emerges by intentionally focusing on the present experience in a nonjudgmental or evaluative manner. Evidence regarding its efficacy has been increasing exponentially, and recent research suggests that the practice of meditation is associated with longer leukocyte telomere length. However, the psychological mechanisms underlying this potential relationship are unknown. We examined the telomere lengths of a group of 20 Zen meditation experts and another 20 healthy matched comparison participants who had not previously meditated. We also measured multiple psychological variables related to meditation practice. Genomic DNA was extracted for telomere measurement using a Life Length proprietary program. High-throughput quantitative fluorescence in situ hybridization (HT-Q-FISH) was used to measure the telomere length distribution and the median telomere length (MTL). The meditators group had a longer MTL ( p  = 0.005) and a lower percentage of short telomeres in individual cells ( p  = 0.007) than those in the comparison group. To determine which of the psychological variables contributed more to telomere maintenance, two regression analyses were conducted. In the first model, which applied to the MTL, the following three factors were significant: age, absence of experiential avoidance, and Common Humanity subscale of the Self Compassion Scale. Similarly, in the model that examined the percentage of short telomeres, the same factors were significant: age, absence of experiential avoidance, and Common Humanity subscale of the Self Compassion Scale. Although limited by a small sample size, these results suggest that the absence of experiential avoidance of negative emotions and thoughts is integral to the connection between meditation and telomeres.

n-3 Fatty Acid Supplementation and Leukocyte Telomere Length in Patients with Chronic Kidney Disease

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Anne Barden

2016-03-01

Full Text Available DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD. The effect of n-3 fatty acids and coenzyme Q10 (CoQ on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g; CoQ (200 mg; both supplements; or control (4 g olive oil, daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F2-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids (p = 0.015. Post-intervention plasma F2-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count (p = 0.025.The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients.

Criteria-based audit of quality of care to women with severe pre-eclampsia and eclampsia in a referral hospital in Accra, Ghana.

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Joyce L Browne

Full Text Available Severe pre-eclampsia and eclampsia are one of the major causes of maternal mortality globally. Reducing maternal morbidity and mortality demands optimizing quality of care. Criteria-based audits are a tool to define, assess and improve quality of care. The aim of this study was to determine applicability of a criteria-based audit to assess quality of care delivered to women with severe hypertensive disorders in pregnancy, and to assess adherence to protocols and quality of care provided at a regional hospital in Accra, Ghana.Checklists for management of severe preeclampsia, hypertensive emergency and eclampsia were developed in an audit cycle based on nine existing key clinical care protocols. Fifty cases were audited to assess quality of care, defined as adherence to protocols. Analysis was stratified for complicated cases, defined as (imminent eclampsia, perinatal mortality and/or one or more WHO maternal near miss C-criteria.Mean adherence to the nine protocols ranged from 15-85%. Protocols for 'plan for delivery' and 'magnesium sulphate administration' were best adhered to (85%, followed by adherence to protocols for 'eclampsia' (64%, 'severe pre-eclampsia at admission' (60%, 'severe pre-eclampsia ward follow-up' (53% and 'hypertensive emergency' (53%. Protocols for monitoring were least adhered to (15%. No difference was observed for severe disease. Increased awareness, protocol-based training of staff, and clear task assignment were identified as contributors to better adherence.A criteria-based audit is an effective tool to determine quality of care, identify gaps in standard of care, and allow for monitoring and evaluation in a health facility, ultimately resulting in improved quality of care provided and reduced maternal morbidity and mortality. In our audit, good adherence was observed for plan for delivery and treatment with magnesium sulphate. Substandard adherence to a number of protocols was identified, and points towards

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

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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

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

International Nuclear Information System (INIS)

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

2017-01-01

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. - Highlights: • This is the first study to investigate a clear association between indoor air pollution and leukocyte telomere length. • Chronic exposure to household solid fuel combustion and leukocyte telomere length presented a negative correlation. • Shortest leukocyte telomere length belonged to population cooking for longest time. • Education and occupation were remarkably associated with leukocyte telomere length via relating with indoor air pollution. - Long-term exposure to household solid fuel combustion is negatively associated with LTL.

Circulating vascular cell adhesion molecule-1 in pre-eclampsia, gestational hypertension, and normal pregnancy: evidence of selective dysregulation of vascular cell adhesion molecule-1 homeostasis in pre-eclampsia.

Science.gov (United States)

Higgins, J R; Papayianni, A; Brady, H R; Darling, M R; Walshe, J J

1998-08-01

Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

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.

Criteria-based audit of quality of care to women with severe pre-eclampsia and eclampsia in a referral hospital in Accra, Ghana

NARCIS (Netherlands)

Browne, Joyce L.; Van Nievelt, Sabine W.; Srofenyoh, Emmanuel K.; Grobbee, Diederick E.; Klipstein-Grobusch, Kerstin

2015-01-01

Objectives Severe pre-eclampsia and eclampsia are one of the major causes of maternal mortality globally. Reducing maternal morbidity and mortality demands optimizing quality of care. Criteria-based audits are a tool to define, assess and improve quality of care. The aim of this study was to

Sexual intimacy in couples is associated with longer telomere length.

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Cabeza de Baca, Tomás; Epel, Elissa S; Robles, Theodore F; Coccia, Michael; Gilbert, Amanda; Puterman, Eli; Prather, Aric A

2017-07-01

High-quality relationships have been shown to be beneficial for physical and mental health. This study examined overall relationship satisfaction and perceived stress as well as daily reports of partner support, partner conflict, and physical intimacy obtained over the course of one week in a sample of 129 high and low stress mothers. Telomere length was examined in whole blood, as well as the two cell subpopulations: peripheral blood mononuclear cells (PBMCs) and granulocytes. Telomerase activity was measured in PBMCs. Analyses revealed no statistically significant associations of telomere length with current relationship satisfaction, daily support or conflict, or perceived stress. In contrast, women who reported any sexual intimacy during the course of the week had significantly longer telomeres measured in whole blood and PBMCs, but not in granulocytes. These relationships held covarying for age, body mass index, perceived stress, the relationship indices, and caregiver status. Sexual intimacy was not significantly related to PBMC telomerase activity. These data provide preliminary data that sexual intimacy is associated with longer telomere length. Future studies investigating these associations are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

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...

Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for pre-eclampsia?

Science.gov (United States)

Rousseau, Aurélie; Favier, Rémi; Van Dreden, Patrick

2009-09-01

One of the most frequently proposed mechanisms for pre-eclampsia refers to uteroplacental thrombosis. However, the contribution of classical thrombotic risk factors remains questionable. The aims of this study were to investigate the activities of thrombomodulin, tissue factor and procoagulant phospholipids to assess endothelial cell injury in pregnant women with pre-eclampsia and to compare them with other classical markers of vascular injury and thrombotic risk. Using three new functional assays we studied the plasma levels of these new markers in 35 healthy women, 30 healthy pregnant women, and 35 women with pre-eclampsia. We found that plasma levels of thrombomodulin activity, tissue factor activity and procoagulant phospholipids were significantly elevated in women with pre-eclampsia versus normal pregnant and non-pregnant women. It is thus suggested that elevated levels of these parameters in pre-eclampsia may reflect vascular endothelium damage, and may be a more valuable biomarker than antigen for the assessment of endothelial damage in pre-eclampsia. The high increased levels of procoagulant phospholipids and tissue factor activities in pre-eclampsia could suggest that the procoagulant potential may be implicated in this complication and makes these markers very promising for the understanding, follow-up and therapeutic handling of complicated pregnancy.

Systematic correlation of environmental exposure and physiological and self-reported behaviour factors with leukocyte telomere length.

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Patel, Chirag J; Manrai, Arjun K; Corona, Erik; Kohane, Isaac S

2017-02-01

It is hypothesized that environmental exposures and behaviour influence telomere length, an indicator of cellular ageing. We systematically associated 461 indicators of environmental exposures, physiology and self-reported behaviour with telomere length in data from the US National Health and Nutrition Examination Survey (NHANES) in 1999-2002. Further, we tested whether factors identified in the NHANES participants are also correlated with gene expression of telomere length modifying genes. We correlated 461 environmental exposures, behaviours and clinical variables with telomere length, using survey-weighted linear regression, adjusting for sex, age, age squared, race/ethnicity, poverty level, education and born outside the USA, and estimated the false discovery rate to adjust for multiple hypotheses. We conducted a secondary analysis to investigate the correlation between identified environmental variables and gene expression levels of telomere-associated genes in publicly available gene expression samples. After correlating 461 variables with telomere length, we found 22 variables significantly associated with telomere length after adjustment for multiple hypotheses. Of these varaibales, 14 were associated with longer telomeres, including biomarkers of polychlorinated biphenyls([PCBs; 0.1 to 0.2 standard deviation (SD) increase for 1 SD increase in PCB level, P  environmental exposures and chronic disease-related risk factors may play a role in telomere length. Our secondary analysis found no evidence of association between PCBs/smoking and gene expression of telomere-associated genes. All correlations between exposures, behaviours and clinical factors and changes in telomere length will require further investigation regarding biological influence of exposure. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association

Community-based home-care program for the management of pre-eclampsia: an alternative.

OpenAIRE

Helewa, M; Heaman, M; Robinson, M A; Thompson, L

1993-01-01

OBJECTIVE: To evaluate the safety, acceptability and cost of a community-based home-care program for the management of mild pre-eclampsia. DESIGN: A descriptive study of outcomes between Apr. 1, 1985, and Dec. 31, 1989. SETTING: St. Boniface General Hospital, Winnipeg. PATIENTS: Urban Winnipeg residents between 27 and 40 weeks' gestation with mild pre-eclampsia who demonstrated acceptance and compliance with home-care management; 321 patients of 1330 were enrolled in the program. INTERVENTION...

Effects of brood size manipulation and common origin on phenotype and telomere length in nestling collared flycatchers

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Voillemot Marie

2012-08-01

Full Text Available Abstract Background Evidence is accumulating that telomere length is a good predictor of life expectancy, especially early in life, thus calling for determining the factors that affect telomere length at this stage. Here, we investigated the relative influence of early growth conditions and origin (genetics and early maternal effects on telomere length of collared flycatchers (Ficedula albicollis at fledging. We experimentally transferred hatchlings among brood triplets to create reduced, control (i.e. unchanged final nestling number and enlarged broods. Results Although our treatment significantly affected body mass at fledging, we found no evidence that increased sibling competition affected nestling tarsus length and telomere length. However, mixed models showed that brood triplets explained a significant part of the variance in body mass (18% and telomere length (19%, but not tarsus length (13%, emphasizing that unmanipulated early environmental factors influenced telomere length. These models also revealed low, but significant, heritability of telomere length (h2 = 0.09. For comparison, the heritability of nestling body mass and tarsus length was 0.36 and 0.39, respectively, which was in the range of previously published estimates for those two traits in this species. Conclusion Those findings in a wild bird population demonstrate that telomere length at the end of the growth period is weakly, but significantly, determined by genetic and/or maternal factors taking place before hatching. However, we found no evidence that the brood size manipulation experiment, and by extension the early growth conditions, influenced nestling telomere length. The weak heritability of telomere length suggests a close association with fitness in natural populations.

Measuring telomere length for the early detection of precursor lesions of esophageal squamous cell carcinoma

International Nuclear Information System (INIS)

Lin, Shih-Wen; Wang, Guo-Qing; Wei, Wen-Qiang; Lu, Ning; Taylor, Philip R; Qiao, You-Lin; Dawsey, Sanford M; Abnet, Christian C; Freedman, Neal D; Murphy, Gwen; Risques, Rosana; Prunkard, Donna; Rabinovitch, Peter; Pan, Qin-Jing; Roth, Mark J

2013-01-01

Esophageal cancer is the sixth leading cause of cancer death worldwide; current early detection screening tests are inadequate. Esophageal balloon cytology successfully retrieves exfoliated and scraped superficial esophageal epithelial cells, but cytologic reading of these cells has poor sensitivity and specificity for detecting esophageal squamous dysplasia (ESD), the precursor lesion of esophageal squamous cell carcinoma (ESCC). Measuring telomere length, a marker for chromosomal instability, may improve the utility of balloon cytology for detecting ESD and early ESCC. We examined balloon cytology specimens from 89 asymptomatic cases of ESD (37 low-grade and 52 high-grade) and 92 age- and sex-matched normal controls from an esophageal cancer early detection screening study. All subjects also underwent endoscopy and biopsy, and ESD was diagnosed histopathologically. DNA was extracted from the balloon cytology cells, and telomere length was measured by quantitative PCR. A receiver operating characteristic (ROC) curve was plotted for telomere length as a diagnostic marker for high-grade dysplasia. Telomere lengths were comparable among the low- and high-grade dysplasia cases and controls, with means of 0.96, 0.96, and 0.92, respectively. The area under the ROC curve was 0.55 for telomere length as a diagnostic marker for high-grade dysplasia. Further adjustment for subject characteristics, including sex, age, smoking, drinking, hypertension, and body mass index did not improve the use of telomere length as a marker for ESD. Telomere length of esophageal balloon cytology cells was not associated with ESCC precursor lesions. Therefore, telomere length shows little promise as an early detection marker for ESCC in esophageal balloon samples

Characteristics and outcomes of patients with eclampsia and severe pre-eclampsia in a rural hospital in Western Tanzania : a retrospective medical record study

NARCIS (Netherlands)

Mooij, Rob; Lugumila, Joseph; Mwashambwa, Masumbuko Y.; Mwampagatwa, Ipyana H.; van Dillen, Jeroen; Stekelenburg, Jelle

2015-01-01

Background: Eclampsia and pre-eclampsia are well-recognized causes of maternal and neonatal mortality in low income countries, but are never studied in a district hospital. In order to get reliable data to facilitate the hospital's obstetric audit a retrospective medical record study was performed

Gender and telomere length: Systematic review and meta-analysis☆

Science.gov (United States)

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

2015-01-01

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 association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Results Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p = 1.00) or cell type (p = 0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Conclusions Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. PMID:24365661

Influence of exposure to pesticides on telomere length in tobacco farmers: A biology system approach

Energy Technology Data Exchange (ETDEWEB)

Kahl, Vivian Francília Silva [Laboratory of Genetic Toxicology, PPGBioSaúde and PPGGTA, Lutheran University of Brazil (ULBRA), Canoas, RS (Brazil); Silva, Juliana da, E-mail: juliana.silva@ulbra.br [Laboratory of Genetic Toxicology, PPGBioSaúde and PPGGTA, Lutheran University of Brazil (ULBRA), Canoas, RS (Brazil); Rabaioli da Silva, Fernanda, E-mail: fernanda.silva@unilasalle.edu.br [Master’s Degree in Environmental Impact Evaluation, Centro Universitário La Salle, Canoas, RS (Brazil)

2016-09-15

Highlights: • Exposure to pesticides in tobacco fields is related to shorten telomere length. • The molecular mechanism of pesticide on telomere length is not fully understood. • Pesticides inhibit ubiquitin proteasome system. • Nicotine activates ubiquitin proteasome system. • Pesticides and nicotine regulate telomere length. - Abstract: Various pesticides in the form of mixtures must be used to keep tobacco crops pest-free. Recent studies have shown a link between occupational exposure to pesticides in tobacco crops and increased damage to the DNA, mononuclei, nuclear buds and binucleated cells in buccal cells as well as micronuclei in lymphocytes. Furthermore, pesticides used specifically for tobacco crops shorten telomere length (TL) significantly. However, the molecular mechanism of pesticide action on telomere length is not fully understood. Our study evaluated the interaction between a complex mixture of chemical compounds (tobacco cultivation pesticides plus nicotine) and proteins associated with maintaining TL, as well as the biological processes involved in this exposure by System Biology tools to provide insight regarding the influence of pesticide exposure on TL maintenance in tobacco farmers. Our analysis showed that one cluster was associated with TL proteins that act in bioprocesses such as (i) telomere maintenance via telomere lengthening; (ii) senescence; (iii) age-dependent telomere shortening; (iv) DNA repair (v) cellular response to stress and (vi) regulation of proteasome ubiquitin-dependent protein catabolic process. We also describe how pesticides and nicotine regulate telomere length. In addition, pesticides inhibit the ubiquitin proteasome system (UPS) and consequently increase proteins of the shelterin complex, avoiding the access of telomerase in telomere and, nicotine activates UPS mechanisms and promotes the degradation of human telomerase reverse transcriptase (hTERT), decreasing telomerase activity.

Influence of exposure to pesticides on telomere length in tobacco farmers: A biology system approach

International Nuclear Information System (INIS)

Kahl, Vivian Francília Silva; Silva, Juliana da; Rabaioli da Silva, Fernanda

2016-01-01

Highlights: • Exposure to pesticides in tobacco fields is related to shorten telomere length. • The molecular mechanism of pesticide on telomere length is not fully understood. • Pesticides inhibit ubiquitin proteasome system. • Nicotine activates ubiquitin proteasome system. • Pesticides and nicotine regulate telomere length. - Abstract: Various pesticides in the form of mixtures must be used to keep tobacco crops pest-free. Recent studies have shown a link between occupational exposure to pesticides in tobacco crops and increased damage to the DNA, mononuclei, nuclear buds and binucleated cells in buccal cells as well as micronuclei in lymphocytes. Furthermore, pesticides used specifically for tobacco crops shorten telomere length (TL) significantly. However, the molecular mechanism of pesticide action on telomere length is not fully understood. Our study evaluated the interaction between a complex mixture of chemical compounds (tobacco cultivation pesticides plus nicotine) and proteins associated with maintaining TL, as well as the biological processes involved in this exposure by System Biology tools to provide insight regarding the influence of pesticide exposure on TL maintenance in tobacco farmers. Our analysis showed that one cluster was associated with TL proteins that act in bioprocesses such as (i) telomere maintenance via telomere lengthening; (ii) senescence; (iii) age-dependent telomere shortening; (iv) DNA repair (v) cellular response to stress and (vi) regulation of proteasome ubiquitin-dependent protein catabolic process. We also describe how pesticides and nicotine regulate telomere length. In addition, pesticides inhibit the ubiquitin proteasome system (UPS) and consequently increase proteins of the shelterin complex, avoiding the access of telomerase in telomere and, nicotine activates UPS mechanisms and promotes the degradation of human telomerase reverse transcriptase (hTERT), decreasing telomerase activity.

Health system barriers to access and use of magnesium sulfate for women with severe pre-eclampsia and eclampsia in Pakistan: evidence for policy and practice.

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Maryam Bigdeli

Full Text Available Severe pre-eclampsia and eclampsia are rare but serious complications of pregnancy that threaten the lives of mothers during childbirth. Evidence supports the use of magnesium sulfate (MgSO4 as the first line treatment option for severe pre-eclampsia and eclampsia. Eclampsia is the third major cause of maternal mortality in Pakistan. As in many other Low- and Middle-Income Countries (LMIC, it is suspected that MgSO4 is critically under-utilized in the country. There is however a lack of information on context-specific health system barriers that prevent optimal use of this life-saving medicine in Pakistan. Combining quantitative and qualitative methods, namely policy document review, key informant interviews, focus group discussions and direct observation at health facility, we explored context-specific health system barriers and enablers that affect access and use of MgSO4 for severe pre-eclampsia and eclampsia in Pakistan. Our study finds that while international recommendations on MgSO4 have been adequately translated in national policies in Pakistan, the gap remains in implementation of national policies into practice. Barriers to access to and effective use of MgSO4 occur at health facility level where the medicine was not available and health staff was reluctant to use it. Low price of the medicine and the small market related to its narrow indications acted as disincentives for effective marketing. Results of our survey were further discussed in a multi-stakeholder round-table meeting and an action plan for increasing access to this life-saving medicine was identified.

Health system barriers to access and use of magnesium sulfate for women with severe pre-eclampsia and eclampsia in Pakistan: evidence for policy and practice.

Science.gov (United States)

Bigdeli, Maryam; Zafar, Shamsa; Assad, Hafeez; Ghaffar, Adbul

2013-01-01

Severe pre-eclampsia and eclampsia are rare but serious complications of pregnancy that threaten the lives of mothers during childbirth. Evidence supports the use of magnesium sulfate (MgSO4) as the first line treatment option for severe pre-eclampsia and eclampsia. Eclampsia is the third major cause of maternal mortality in Pakistan. As in many other Low- and Middle-Income Countries (LMIC), it is suspected that MgSO4 is critically under-utilized in the country. There is however a lack of information on context-specific health system barriers that prevent optimal use of this life-saving medicine in Pakistan. Combining quantitative and qualitative methods, namely policy document review, key informant interviews, focus group discussions and direct observation at health facility, we explored context-specific health system barriers and enablers that affect access and use of MgSO4 for severe pre-eclampsia and eclampsia in Pakistan. Our study finds that while international recommendations on MgSO4 have been adequately translated in national policies in Pakistan, the gap remains in implementation of national policies into practice. Barriers to access to and effective use of MgSO4 occur at health facility level where the medicine was not available and health staff was reluctant to use it. Low price of the medicine and the small market related to its narrow indications acted as disincentives for effective marketing. Results of our survey were further discussed in a multi-stakeholder round-table meeting and an action plan for increasing access to this life-saving medicine was identified.

Serum markers of macrophage activation in pre-eclampsia: no predictive value of soluble CD163 and neopterin

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Kronborg, Camilla S; Knudsen, Ulla Breth; Moestrup, Søren K

2007-01-01

BACKGROUND: Alternatively activated macrophages expressing the CD163 and CD206 surface receptors are the dominant immune-cell type found in the placenta. The placental number and distribution of macrophages is altered in pre-eclampsia, and the generalised inflammatory reaction associated with pre-eclampsia...... might lead to shedding of soluble CD163 into the circulation. METHODS: Serum samples from 18 women with pre-eclampsia and 90 normal pregnancies were obtained from a longitudinal study of 955 pregnant women at Randers County Hospital, Denmark. sCD163 and Neopterin were measured by ELISA on samples....... Neopterin increased throughout pregnancy in both healthy (from median 5.4 to 6.7 nmol/l, ppre-eclampsia...

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.

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

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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

Telomere length of anterior crucial ligament after rupture

DEFF Research Database (Denmark)

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

2011-01-01

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...... 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...... 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...

Leukocyte telomere length and late-life depression

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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

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...... of sports might have deleterious effects on muscle telomeres. Therefore, we aimed to compare telomere length of a group of power lifters (PL; N = 7) who trained for 8 +/- 3 yr against that of a group of healthy, active subjects (C; N = 7) with no history of strength training. METHODS: Muscle biopsies were...

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

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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

Aberrant leukocyte telomere length in Birdshot Uveitis.

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Vazirpanah, Nadia; Verhagen, Fleurieke H; Rothova, Anna; Missotten, Tom O A R; van Velthoven, Mirjam; Den Hollander, Anneke I; Hoyng, Carel B; Radstake, Timothy R D J; Broen, Jasper C A; Kuiper, Jonas J W

2017-01-01

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 (PRTEL1. These findings suggest that BU is accompanied by significantly longer LTL.

Association Between Leukocyte Telomere Length and the Risk of Incident Atrial Fibrillation

DEFF Research Database (Denmark)

Staerk, Laila; Wang, Biqi; Lunetta, Kathryn L

2017-01-01

BACKGROUND: Advancing age is a prominent risk factor for atrial fibrillation (AF). Shorter telomere length is a biomarker of biological aging, but the link between shorter telomere length and increased risk of AF remains unclear. We examined the association between shorter leukocyte telomere length...... at baseline was 6.95±0.57 kb. During 15.1±4.2 years mean follow-up, 184 participants (64 women) developed AF. Chronological age was associated with increased risk of AF (hazard ratio per 10-year increase, 2.16; 95% confidence interval, 1.71-2.72). There was no significant association between LTL and incident...... evidence for a significant association between LTL and risk of incident AF....

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...

Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

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Abalos, E; Cuesta, C; Carroli, G; Qureshi, Z; Widmer, M; Vogel, J P; Souza, J P

2014-03-01

To assess the incidence of hypertensive disorders of pregnancy and related severe complications, identify other associated factors and compare maternal and perinatal outcomes in women with and without these conditions. Secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health (WHOMCS) database. Cross-sectional study implemented at 357 health facilities conducting 1000 or more deliveries annually in 29 countries from Africa, Asia, Latin America and the Middle East. All women suffering from any hypertensive disorder during pregnancy, the intrapartum or early postpartum period in the participating hospitals during the study period. We calculated the proportion of the pre-specified outcomes in the study population and their distribution according to hypertensive disorders' severity. We estimated the association between them and maternal deaths, near-miss cases, and severe maternal complications using a multilevel logit model. Hypertensive disorders of pregnancy. Potentially life-threatening conditions among maternal near-miss cases, maternal deaths and cases without severe maternal outcomes. Overall, 8542 (2.73%) women suffered from hypertensive disorders. Incidences of pre-eclampsia, eclampsia and chronic hypertension were 2.16%, 0.28% and 0.29%, respectively. Maternal near-miss cases were eight times more frequent in women with pre-eclampsia, and increased to up to 60 times more frequent in women with eclampsia, when compared with women without these conditions. The analysis of this large database provides estimates of the global distribution of the incidence of hypertensive disorders of pregnancy. The information on the most frequent complications related to pre-eclampsia and eclampsia could be of interest to inform policies for health systems organisation. © 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

Age-related declines and disease-associated variation in immune cell telomere length in a wild mammal.

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Christopher Beirne

Full Text Available Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes ('immune cells', stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles. Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations.

Reliability and short-term intra-individual variability of telomere length measurement using monochrome multiplexing quantitative PCR.

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Sangmi Kim

Full Text Available Studies examining the association between telomere length and cancer risk have often relied on measurement of telomere length from a single blood draw using a real-time PCR technique. We examined the reliability of telomere length measurement using sequential samples collected over a 9-month period.Relative telomere length in peripheral blood was estimated using a single tube monochrome multiplex quantitative PCR assay in blood DNA samples from 27 non-pregnant adult women (aged 35 to 74 years collected in 7 visits over a 9-month period. A linear mixed model was used to estimate the components of variance for telomere length measurements attributed to variation among women and variation between time points within women. Mean telomere length measurement at any single visit was not significantly different from the average of 7 visits. Plates had a significant systematic influence on telomere length measurements, although measurements between different plates were highly correlated. After controlling for plate effects, 64% of the remaining variance was estimated to be accounted for by variance due to subject. Variance explained by time of visit within a subject was minor, contributing 5% of the remaining variance.Our data demonstrate good short-term reliability of telomere length measurement using blood from a single draw. However, the existence of technical variability, particularly plate effects, reinforces the need for technical replicates and balancing of case and control samples across plates.

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

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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.

Comparison of serum trace element levels in patients with or without pre-eclampsia

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Leila Farzin

2012-01-01

Full Text Available Objective: In developing countries, nutritional deficiency of essential trace elements is a common health problem, particularly among pregnant women because of increased requirements of various nutrients. Accordingly, this study was initiated to compare trace elements status in women with or without pre-eclampsia. Materials and Methods: In this study, serum trace elements including zinc (Zn, selenium (Se, copper (Cu, calcium (Ca and magnesium (Mg were determined by using atomic absorption spectrometry (AAS in 60 patients and 60 healthy subjects. Results: There was no significant difference in the values of Cu between two groups (P > 0.05. A significant difference in Zn, Se, Ca and Mg levels were observed between patients with pre-eclampsia and control group (P 0.05. Conclusion: Our findings indicate that the levels of Zn, Se, Ca and Mg are significantly altered in pregnant women with pre-eclampsia. This research shows that these deficiencies can not due to hemodilution.

Neighborhood Disadvantage and Telomere Length: Results from the Fragile Families Study

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Douglas S. Massey

2018-04-01

Full Text Available Telomeres are repetitive nucleotide sequences located at the ends of chromosomes that protect genetic material. We use data from the Fragile Families and Child Wellbeing Study to analyze the relationship between exposure to spatially concentrated disadvantage and telomere length for white and black mothers. We find that neighborhood disadvantage is associated with shorter telomere length for mothers of both races. This finding highlights a potential mechanism through which the unique spatially concentrated disadvantage faced by African Americans contributes to racial health disparities. We conclude that equalizing the health and socioeconomic status of black and white Americans will be very difficult without reducing levels of residential segregation in the United States.

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

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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.

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

Science.gov (United States)

Kjaer, T W; Faurholt-Jepsen, D; Mehta, K M; Christensen, V B; Epel, E; Lin, J; Blackburn, E; Wojcicki, J M

2018-04-01

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% of the relationship between excessive sugar-sweetened beverage consumption and obesity. Shorter leukocyte telomere length may be an indicator of future obesity risk in high-risk populations as it is particularly sensitive to damage from oxidative stress exposure, including those from sugar-sweetened beverages. © 2017 World Obesity Federation.

The association between intelligence and telomere length: a longitudinal population based study.

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Eva M Kingma

Full Text Available Low intelligence has been associated with poor health and mortality, but underlying mechanisms remain obscure. We hypothesized that low intelligence is associated with accelerated biological ageing as reflected by telomere length; we suggested potential mediation of this association by unhealthy behaviors and low socioeconomic position. The study was performed in a longitudinal population-based cohort study of 895 participants (46.8% males. Intelligence was measured with the Generalized Aptitude-Test Battery at mean age 52.8 years (33-79 years, SD=11.3. Leukocyte telomere length was measured by PCR. Lifestyle and socioeconomic factors were assessed using written self-report measures. Linear regression analyses, adjusted for age, sex, and telomere length measured at the first assessment wave (T1, showed that low intelligence was associated with shorter leukocyte telomere length at approximately 2 years follow-up (beta= .081, t=2.160, p= .031. Nearly 40% of this association was explained by an unhealthy lifestyle, while low socioeconomic position did not add any significant mediation. Low intelligence may be a risk factor for accelerated biological ageing, thereby providing an explanation for its association with poor health and mortality.

Prediction of pre-eclampsia by maternal characteristics : A case-controlled validation study of a Bayesian network model for risk identification of pre-eclampsia

NARCIS (Netherlands)

Meurs, van A.; Velikova, M.; van der Hout, Beatrijs; Vermeulen-Giovagnoli, Barbara; Oei, S G

2014-01-01

Brief Introduction: Pre-eclampsia (PE) is worldwide a leading and rising cause of maternal and perinatal morbidity and mortality. As PE remains a serious and poorly understood complication of pregnancy, it is necessary to recognize the disease before it threatens the survival of mother and fetus. A

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...

Development of software and modification of Q-FISH protocol for estimation of individual telomere length in immunopathology.

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Barkovskaya, M Sh; Bogomolov, A G; Knauer, N Yu; Rubtsov, N B; Kozlov, V A

2017-04-01

Telomere length is an important indicator of proliferative cell history and potential. Decreasing telomere length in the cells of an immune system can indicate immune aging in immune-mediated and chronic inflammatory diseases. Quantitative fluorescent in situ hybridization (Q-FISH) of a labeled (C 3 TA[Formula: see text] peptide nucleic acid probe onto fixed metaphase cells followed by digital image microscopy allows the evaluation of telomere length in the arms of individual chromosomes. Computer-assisted analysis of microscopic images can provide quantitative information on the number of telomeric repeats in individual telomeres. We developed new software to estimate telomere length. The MeTeLen software contains new options that can be used to solve some Q-FISH and microscopy problems, including correction of irregular light effects and elimination of background fluorescence. The identification and description of chromosomes and chromosome regions are essential to the Q-FISH technique. To improve the quality of cytogenetic analysis after Q-FISH, we optimized the temperature and time of DNA-denaturation to get better DAPI-banding of metaphase chromosomes. MeTeLen was tested by comparing telomere length estimations for sister chromatids, background fluorescence estimations, and correction of nonuniform light effects. The application of the developed software for analysis of telomere length in patients with rheumatoid arthritis was demonstrated.

Evaluation of biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes mellitus: A systematic review.

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

2016-07-01

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes. To undertake a systematic review to identify potential biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes. We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL SELECTION CRITERIA: Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta-analysis could not be performed, due to high study heterogeneity. A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful. Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

Father Loss and Child Telomere Length.

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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.

Localization of hyaluronan with a hyaluronan-specific hyaluronic acid binding protein in the placenta in pre-eclampsia.

Science.gov (United States)

Matejevic, D; Neudeck, H; Graf, R; Müller, T; Dietl, J

2001-01-01

Hyaluronan (HA), a high molecular weight polysaccharide, is a major component of connective tissue and is thus present in the extracellular matrix of most tissues. Increased serum concentrations have been reported in association with pre-eclampsia and liver malfunction, amongst other disorders. We have performed histochemical investigations with a HA-specific hyaluronic acid binding protein in placentas from uncomplicated pregnancies and from patients with pre-eclampsia. Staining for HA was found in the stroma and blood vessel walls of stem villi in all the placentas investigated. The syncytiotrophoblast and cytotrophoblast cells usually remained unstained. In addition, reactivity for HA was found within and on the surface of intervillous and perivillous fibrinoid deposits. Since fibrinoid deposits are increased in pre-eclampsia, our findings suggest that the increased HA serum concentrations in cases of pre-eclampsia could result from the stroma of the infarcted villi and from the fibrinoid deposits. HA may reach the maternal blood through fibrinoid gaps. Copyright 2001 S. Karger AG, Basel

Aspirin In The Prevention Of Pre-Eclampsia: Where Are We Now?

LENUS (Irish Health Repository)

2018-03-01

Pre-eclampsia is a pregnancy specific multi-systemic disorder that causes maternal and perinatal morbidity and mortality worldwide. It is estimated to complicate between three to five percent of pregnancies and contributes to 8 to 10% of all preterm births1,2. Aspirin inhibits cyclooxygenase in platelets and endothelium in a fashion that alters the balance between the vasoconstrictor thromboxane and the vasodilator prostacyclin. This potentiates vasodilatation and reduces platelet aggregation, contributors to the endothelial dysfunction seen in preeclampsia. Over 100 clinical trials have examined whether or not Aspirin, when prescribed from early pregnancy, can prevent pre-eclampsia, and the consensus is that it reduces the incidence by approximately 10 to 24 % in women that are deemed to be at risk3,4.

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

Science.gov (United States)

Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-12-01

Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. Copyright© Ferrata Storti Foundation.

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

Directory of Open Access Journals (Sweden)

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.

The Association of Telomere Length With Family Violence and Disruption

Science.gov (United States)

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

2014-01-01

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. PMID:24936002

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.

First trimester serum placental growth factor and hyperglycosylated human chorionic gonadotropin are associated with pre-eclampsia: a case control study.

Science.gov (United States)

Keikkala, Elina; Koskinen, Sini; Vuorela, Piia; Laivuori, Hannele; Romppanen, Jarkko; Heinonen, Seppo; Stenman, Ulf-Håkan

2016-11-25

To study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors. Gestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8-13 weeks of gestation. The case-control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls. Of 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis factors.

Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping.

Science.gov (United States)

Morgan, R Garrett; Ives, Stephen J; Walker, Ashley E; Cawthon, Richard M; Andtbacka, Robert H I; Noyes, Dirk; Lesniewski, Lisa A; Richardson, Russell S; Donato, Anthony J

2014-06-01

Telomere shortening in arteries could lead to telomere uncapping and cellular senescence, which in turn could promote the development of hypertension. To assess the novel role of arterial telomere dysfunction in hypertension, we compared mean telomere length (qPCR), telomere uncapping (serine 139 phosphorylated histone γ-H2A.X (γ-H2) localized to telomeres: ChIP), and tumor suppressor protein p53 (P53)/cyclin-dependent kinase inhibitor 1A (P21)-induced senescence (P53 bound to P21 gene promoter: ChIP) in arteries from 55 age-matched hypertensive and nonhypertensive individuals. Arterial mean telomere length was not different in hypertensive patients compared with nonhypertensive individuals (P = 0.29). Arterial telomere uncapping and P53/P21-induced senescence were two-fold greater in hypertensive patients compared with nonhypertensive individuals (P = 0.04 and P = 0.02, respectively). Arterial mean telomere length was not associated with telomere uncapping or P53/P21-induced senescence (r = -0.02, P = 0.44 and r = 0.01, P = 0.50, respectively), but telomere uncapping was a highly influential covariate for the hypertension group difference in P53/P21-induced senescence (r = 0.62, P hypertension status (P = 0.03), whereas mean telomere length was not (P = 0.68). Collectively, these findings demonstrate that arterial telomere uncapping and P53/P21-induced senescence are linked to hypertension independently of mean telomere length, and telomere uncapping influences hypertension status more than mean telomere length.

[Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction].

Science.gov (United States)

Valdés R, Enrique; Lattes A, Karina; Muñoz S, Hernán; Cumsille, Miguel Angel

2012-05-01

Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselected pregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls. Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively). Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.

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.

Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth

Science.gov (United States)

Law, Kai P.; Han, Ting-Li; Tong, Chao; Baker, Philip N.

2015-01-01

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. PMID:26006232

Management of pre-eclampsia/eclampsia.

Science.gov (United States)

Ababneh, Mo

2004-06-01

Preclampsia/eclampsia affects only a small proportion of all pregnancies, yet it is associated with significant morbidity and mortality for mother and baby, with post partum resolution. The disorder is triggered by a placental pathology followed by a wide spectrum of maternal systemic response. However, there remains controversy in practically every aspect of the condition. A full understanding of the condition, its variable presentation allows the consulting anesthetist to optimize a plan for anesthetic management.

Investigation of telomere length and psychological stress in rape victims.

Science.gov (United States)

Malan, Stefanie; Hemmings, Sian; Kidd, Martin; Martin, Lindi; Seedat, Soraya

2011-12-21

Women are at an increased risk of depression and other mental health problems following rape. Various etiological factors for depression, including predisposing genetic factors, have been identified. Telomeres are repetitive nucleoprotein structures located at chromosomal ends that protect them from premature degradation. Telomeres reduce in length with each cell division, resulting in cellular senescence and apoptosis. Relative quantification of telomeric repeats using qPCR was performed to investigate whether shorter relative leukocyte telomere length (LTL) in a cohort of 64 rape victims was associated with resilience, the development of rape trauma-related major depressive disorder (MDD) or the development of posttraumatic stress disorder (PTSD) after 3 months. Out of the 64 participants, 23 participants were diagnosed with MDD at baseline and 31 after 3 months. Nine participants were diagnosed with PTSD (MDD and PTSD specifically related to the trauma). No significant associations were observed between relative LTL and resilience or the development of MDD at either baseline or after 3 months in this cohort. However, a marginally significant association was evident between relative LTL and PTSD status. The significant association between relative LTL and PTSD suggests that shorter relative LTL might have acted as a predisposing factor in the development of PTSD after a severely traumatic event. The results of this study indicate that telomere shortening may be an important marker of PTSD risk, with implications for early intervention and timely treatment, and as such warrant replication in a larger cohort. © 2011 Wiley Periodicals, Inc.

Gender and telomere length

DEFF Research Database (Denmark)

Gardner, Michael; Bann, David; Wiley, Laura

2014-01-01

It is widely believed that females have longer telomeres than males, although results from studies have been contradictory.......It is widely believed that females have longer telomeres than males, although results from studies have been contradictory....

Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

DEFF Research Database (Denmark)

Kimura, Masayuki; Cherkas, Lynn F; Kato, Bernet S

2008-01-01

), 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......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...

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

Directory of Open Access Journals (Sweden)

Olivia I Okereke

Full Text Available 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-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.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.

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.

Reduced risk of pre-eclampsia with organic vegetable consumption: results from the prospective Norwegian Mother and Child Cohort Study.

Science.gov (United States)

Torjusen, Hanne; Brantsæter, Anne Lise; Haugen, Margaretha; Alexander, Jan; Bakketeig, Leiv S; Lieblein, Geir; Stigum, Hein; Næs, Tormod; Swartz, Jackie; Holmboe-Ottesen, Gerd; Roos, Gun; Meltzer, Helle Margrete

2014-09-10

Little is known about the potential health effects of eating organic food either in the general population or during pregnancy. The aim of this study was to examine associations between organic food consumption during pregnancy and the risk of pre-eclampsia among nulliparous Norwegian women. Prospective cohort study. Norway, years 2002-2008. 28 192 pregnant women (nulliparous, answered food frequency questionnaire and general health questionnaire in mid-pregnancy and no missing information on height, body weight or gestational weight gain). Relative risk was estimated as ORs by performing binary logistic regression with pre-eclampsia as the outcome and organic food consumption as the exposure. The prevalence of pre-eclampsia in the study sample was 5.3% (n=1491). Women who reported to have eaten organic vegetables 'often' or 'mostly' (n=2493, 8.8%) had lower risk of pre-eclampsia than those who reported 'never/rarely' or 'sometimes' (crude OR=0.76, 95% CI 0.61 to 0.96; adjusted OR=0.79, 95% CI 0.62 to 0.99). The lower risk associated with high organic vegetable consumption was evident also when adjusting for overall dietary quality, assessed as scores on a healthy food pattern derived by principal component analysis. No associations with pre-eclampsia were found for high intake of organic fruit, cereals, eggs or milk, or a combined index reflecting organic consumption. These results show that choosing organically grown vegetables during pregnancy was associated with reduced risk of pre-eclampsia. Possible explanations for an association between pre-eclampsia and use of organic vegetables could be that organic vegetables may change the exposure to pesticides, secondary plant metabolites and/or influence the composition of the gut microbiota. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Reduced risk of pre-eclampsia with organic vegetable consumption: results from the prospective Norwegian Mother and Child Cohort Study

Science.gov (United States)

Torjusen, Hanne; Brantsæter, Anne Lise; Haugen, Margaretha; Alexander, Jan; Bakketeig, Leiv S; Lieblein, Geir; Stigum, Hein; Næs, Tormod; Swartz, Jackie; Holmboe-Ottesen, Gerd; Roos, Gun; Meltzer, Helle Margrete

2014-01-01

Objective Little is known about the potential health effects of eating organic food either in the general population or during pregnancy. The aim of this study was to examine associations between organic food consumption during pregnancy and the risk of pre-eclampsia among nulliparous Norwegian women. Design Prospective cohort study. Setting Norway, years 2002–2008. Participants 28 192 pregnant women (nulliparous, answered food frequency questionnaire and general health questionnaire in mid-pregnancy and no missing information on height, body weight or gestational weight gain). Main outcome measure Relative risk was estimated as ORs by performing binary logistic regression with pre-eclampsia as the outcome and organic food consumption as the exposure. Results The prevalence of pre-eclampsia in the study sample was 5.3% (n=1491). Women who reported to have eaten organic vegetables ‘often’ or ‘mostly’ (n=2493, 8.8%) had lower risk of pre-eclampsia than those who reported ‘never/rarely’ or ‘sometimes’ (crude OR=0.76, 95% CI 0.61 to 0.96; adjusted OR=0.79, 95% CI 0.62 to 0.99). The lower risk associated with high organic vegetable consumption was evident also when adjusting for overall dietary quality, assessed as scores on a healthy food pattern derived by principal component analysis. No associations with pre-eclampsia were found for high intake of organic fruit, cereals, eggs or milk, or a combined index reflecting organic consumption. Conclusions These results show that choosing organically grown vegetables during pregnancy was associated with reduced risk of pre-eclampsia. Possible explanations for an association between pre-eclampsia and use of organic vegetables could be that organic vegetables may change the exposure to pesticides, secondary plant metabolites and/or influence the composition of the gut microbiota. PMID:25208850

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

The association of with severe early-onset pre-eclampsia

African Journals Online (AJOL)

however also found no differences in APA levels between patients with severe early-onset pre-eclampsia and controls."lO Further, Kilpatrick et a/.'°state that even Branch et a/. 6 found ACAs in only 16% of their patients. In the present study, both ACA and LAC levels were assayed, and all 4 patients had significantly raised ...

Telomere length and long-term endurance exercise: does exercise training affect biological age? A pilot study.

Directory of Open Access Journals (Sweden)

Ida Beate Ø Østhus

Full Text Available 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 (VO(2max are associated with improved survival, and dynamic effects of exercise are evident with ageing. However, the association of telomere length with exercise training and VO(2max has so far been inconsistent. Our aim was to assess whether muscle telomere length is associated with endurance exercise training and VO(2max in younger and older people. METHODS: Twenty men; 10 young (22-27 years and 10 old (66-77 years, were studied in this cross-sectional study. Five out of 10 young adults and 5 out of 10 older were endurance athletes, while other halves were exercising at a medium level of activity. Mean telomere length was measured as telomere/single copy gene-ratio (T/S-ratio using quantitative real time polymerase chain reaction. VO(2max was measured directly running on a treadmill. RESULTS: Older endurance trained athletes had longer telomere length compared with older people with medium activity levels (T/S ratio 1.12±0.1 vs. 0.92±0.2, p = 0.04. Telomere length of young endurance trained athletes was not different than young non-athletes (1.47±0.2 vs. 1.33±0.1, p = 0.12. Overall, there was a positive association between T/S ratio and VO(2max (r = 0.70, p = 0.001. Among endurance trained athletes, we found a strong correlation between VO(2max and T/S ratio (r = 0.78, p = 0.02. However, corresponding association among non-athlete participants was relatively weak (r = 0.58, p = 0.09. CONCLUSION: Our data suggest that VO(2max is positively associated with telomere length, and we found that long-term endurance exercise training may provide a protective effect on muscle telomere length in older people.

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.

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.

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

DEFF Research Database (Denmark)

Rode, Line; Bojesen, Stig Egil; 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)....

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 ...

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....

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.

Marital disruption is associated with shorter salivary telomere length in a probability sample of older adults.

Science.gov (United States)

Whisman, Mark A; Robustelli, Briana L; Sbarra, David A

2016-05-01

Marital disruption (i.e., marital separation, divorce) is associated with a wide range of poor mental and physical health outcomes, including increased risk for all-cause mortality. One biological intermediary that may help explain the association between marital disruption and poor health is accelerated cellular aging. This study examines the association between marital disruption and salivary telomere length in a United States probability sample of adults ≥50 years of age. Participants were 3526 individuals who participated in the 2008 wave of the Health and Retirement Study. Telomere length assays were performed using quantitative real-time polymerase chain reaction (qPCR) on DNA extracted from saliva samples. Health and lifestyle factors, traumatic and stressful life events, and neuroticism were assessed via self-report. Linear regression analyses were conducted to examine the associations between predictor variables and salivary telomere length. Based on their marital status data in the 2006 wave, people who were separated or divorced had shorter salivary telomeres than people who were continuously married or had never been married, and the association between marital disruption and salivary telomere length was not moderated by gender or neuroticism. Furthermore, the association between marital disruption and salivary telomere length remained statistically significant after adjusting for demographic and socioeconomic variables, neuroticism, cigarette use, body mass, traumatic life events, and other stressful life events. Additionally, results revealed that currently married adults with a history of divorce evidenced shorter salivary telomeres than people who were continuously married or never married. Accelerated cellular aging, as indexed by telomere shortening, may be one pathway through which marital disruption is associated with morbidity and mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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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.

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

-eclampsia/gestational hypertension); 33 reports were new to this review. For PTD, findings across a substantial evidence base were generally consistent, effectively ruling out large effects (eg, RR>1.2). Larger and higher quality studies were less positive, while meta-estimates of risk were smaller than in previous analyses......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...

Uterine artery Doppler screening as a predictor of pre-eclampsia

African Journals Online (AJOL)

Yasmin Casmod

Hypertensive disorders represent the second most common cause of maternal death, affecting 5e10% of .... screening in the prediction of pre-eclampsia. 2. Materials and methods ... presence of UA notching and a PI > 1.5 during the first ... occurring in another group. ... dependent variables as the uterine artery PI and notch-.

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.

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

Age and Heat Stress as Determinants of Telomere Length in a Long-Lived Fish, the Siberian Sturgeon.

Science.gov (United States)

Simide, Rémy; Angelier, Frédéric; Gaillard, Sandrine; Stier, Antoine

2016-01-01

Telomeres shorten at each cell division due to the end-replication problem but also in response to oxidative stress. Consequently, telomeres shorten with age in many endotherms, and this shortening is accelerated under stressful environmental conditions. Data in ectotherm vertebrates remain scarce so far, so our goal was to review existing data for fish and to test the influence of age and stress on telomere length in a very long-lived fish, the Siberian sturgeon (Acipenser baerii). Our review of the literature revealed age-related telomere shortening in approximately half of the published studies. In the Siberian sturgeon, we found a significant telomere shortening with age, both at the intraindividual level using red blood cells (-12.5% in 16 mo) and at the interindividual level using cross-sectional samples of fin over an age range of 8 yr. We also found that heat stress (30°C) significantly reduced telomere length by 15.0% after only 1 mo of exposure. Our results highlight that both age and stressful environmental conditions might be important determinants of telomere length in fish.

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.

Influence on pregestacional obesity on the pre-eclampsia/eclampsia risk

OpenAIRE

Suárez González, Juan Antonio; Preciado Guerrero, Richard; Gutiérrez Machado, Mario; Cabrera Delgado, María Rosa; Marín Tápanes, Yoani; Cairo González, Vivian

2013-01-01

Introducción: una de las condiciones maternas que con mayor frecuencia complica el periodo de gestación y el parto es la obesidad. Objetivo: determinar la influencia de la obesidad en los resultados maternos y perinatales de gestantes con riesgo de preeclampsia/eclampsia. Métodos: estudio analítico y ambispectivo en el Hospital Universitario Ginecobstétrico "Mariana Grajales" de Santa Clara, provincia de Villa Clara, en el año 2010 en un grupo de gestantes con riesgo de preeclampsia/eclampsia...

Cardiac telomere length in heart development, function, and disease.

Science.gov (United States)

Booth, S A; Charchar, F J

2017-07-01

Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

The association between post-traumatic stress disorder and shorter telomere length: A systematic review and meta-analysis.

Science.gov (United States)

Li, Xuemei; Wang, Jiang; Zhou, Jianghua; Huang, Pan; Li, Jiping

2017-08-15

Post-traumatic stress disorder (PTSD) is a common psychiatric disorder, which may accelerate aging. Many study have investigated the association between telomeres length and PTSD, but results from published studies are contradictory. Therefore, Meta-analysis approaches were conducted to give more precise estimate of relationship between telomere length and PTSD. We systematically reviewed the databases of PUBMED, PsycINFO, Medline(Ovid SP) and EMBASE for all articles on the association between telomere length and PTSD. Data were summarized by using random-effects in the meta-analysis. The heterogeneity among studies were examined by using Cochrane's Q statistic and I-squared. Five eligible studies containing 3851 participants were included in our meta-analysis. Shorten telomere length was significantly associated with PTSD with mean difference of -0.19( 95% CI: -0.27, -0.01; P<0.001) with I-square of 96%. The results from subgroup analysis demonstrated that shorter telomere length was significantly associated with PTSD across all gender groups, with mean difference of -0.15( 95% CI: -0.29, -0.01; P=0.04) for female, mean difference of -0.17( 95% CI: -0.19, -0.15; P<0.001) for male. Meanwhile, shorten telomere length was significantly associated with sexual assault(mean difference =-0.15, 95% CI: -0.29, -0.01), childhood trauma (mean difference =-0.08, 95% CI: -0.19, -0.07), but not combat (mean difference =-0.39, 95% CI: -0.83, 0.05). Compared to the individuals without PTSD, individuals with PTSD have shorter telomere length, which has implications for early intervention and timely treatment to prevent future adverse health outcomes. Copyright © 2017. Published by Elsevier B.V.

Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction

OpenAIRE

Valdés R, Enrique; Lattes A, Karina; Muñoz S, Hernán; Ángel Cumsille, Miguel

2012-01-01

Background: Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). Aim: To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Patients and Methods: Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselectedpregnant wome...

Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

Science.gov (United States)

Weiler, Jane; Tong, Stephen; Palmer, Kirsten R.

2011-01-01

Background Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. Methods and Findings We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). Conclusions The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population. PMID:22046419

A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

Science.gov (United States)

Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

2011-10-01

A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

Influence of exposure to pesticides on telomere length in tobacco farmers: A biology system approach.

Science.gov (United States)

Kahl, Vivian Francília Silva; da Silva, Juliana; da Silva, Fernanda Rabaioli

Various pesticides in the form of mixtures must be used to keep tobacco crops pest-free. Recent studies have shown a link between occupational exposure to pesticides in tobacco crops and increased damage to the DNA, mononuclei, nuclear buds and binucleated cells in buccal cells as well as micronuclei in lymphocytes. Furthermore, pesticides used specifically for tobacco crops shorten telomere length (TL) significantly. However, the molecular mechanism of pesticide action on telomere length is not fully understood. Our study evaluated the interaction between a complex mixture of chemical compounds (tobacco cultivation pesticides plus nicotine) and proteins associated with maintaining TL, as well as the biological processes involved in this exposure by System Biology tools to provide insight regarding the influence of pesticide exposure on TL maintenance in tobacco farmers. Our analysis showed that one cluster was associated with TL proteins that act in bioprocesses such as (i) telomere maintenance via telomere lengthening; (ii) senescence; (iii) age-dependent telomere shortening; (iv) DNA repair (v) cellular response to stress and (vi) regulation of proteasome ubiquitin-dependent protein catabolic process. We also describe how pesticides and nicotine regulate telomere length. In addition, pesticides inhibit the ubiquitin proteasome system (UPS) and consequently increase proteins of the shelterin complex, avoiding the access of telomerase in telomere and, nicotine activates UPS mechanisms and promotes the degradation of human telomerase reverse transcriptase (hTERT), decreasing telomerase activity. Copyright © 2016 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

Pawlas, Natalia; Płachetka, Anna; Kozłowska, Agnieszka; Broberg, Karin; Kasperczyk, Sławomir

2015-01-01

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 S = − 0.25, p = 0.013; in further analyses both log-transformed-univariate regression analysis β = − 0.13, p = 0.026, and R 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 2 adj 12%, p = 0.011). The effect of lead remained significant in children without prenatal tobacco exposure (N = 87, r S = − 0.24, p = 0.024; in further analyses, β = − 0.13, p = 0.029, and R 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 environmental lead exposure

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

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

2018-04-01

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.

Determination of risk factors for pre-eclampsia and eclampsia in a tertiary hospital of India: A case control study

Directory of Open Access Journals (Sweden)

Punyatoya Bej

2013-01-01

Full Text Available Background: Preeclampsia and eclampsia (PE are pregnancy specific syndromes that contribute to maternal and fetal morbidity and mortality. The identification of its predisposing factors in the pre-pregnancy and initial stage of pregnancy will help in reducing the morbidity and mortality. Aim: The aim of this study is to determine the risk factors for PE among pregnant women in a tertiary level hospital. Materials and Methods: In this study, 122 women who delivered beyond 22 weeks of gestation and diagnosed as preeclampsia or eclampsia were selected. Simultaneously, 122 controls with no diagnosis of preeclampsia or eclampsia were selected from the post natal ward. Cases and controls were administered the same pre-tested questionnaire containing different risk factors. Results and Conclusion: Logistic regression was applied in the statistical analysis. The factors that were found to be significant predictors of risk for development of PE were family history of preeclampsia (adjusted odds ratio [OR] 18.57 [1.93-178.16], P = 0.011, higher calorie intake (adjusted OR 14.12 [6.41-43.23] body mass index (adjusted P < 0.001, employment (adjusted OR 6.35 [1.56-25.82] P = 0.010], less protein intake (adjusted OR 3.87 [1.97-8.01] P < 0.001, increased OR 5.86 [02.48-13.8] P < 0.001, mild physical activities (adjusted OR 3.46 [1.06-11.24] P = 0.039. Past history of hypertension and diabetes mellitus were also associated with development of PE.

CTC1-STN1 coordinates G- and C-strand synthesis to regulate telomere length.

Science.gov (United States)

Gu, Peili; Jia, Shuting; Takasugi, Taylor; Smith, Eric; Nandakumar, Jayakrishnan; Hendrickson, Eric; Chang, Sandy

2018-05-17

Coats plus (CP) is a rare autosomal recessive disorder caused by mutations in CTC1, a component of the CST (CTC1, STN1, and TEN1) complex important for telomere length maintenance. The molecular basis of how CP mutations impact upon telomere length remains unclear. The CP CTC1 L1142H mutation has been previously shown to disrupt telomere maintenance. In this study, we used CRISPR/Cas9 to engineer this mutation into both alleles of HCT116 and RPE cells to demonstrate that CTC1:STN1 interaction is required to repress telomerase activity. CTC1 L1142H interacts poorly with STN1, leading to telomerase-mediated telomere elongation. Impaired interaction between CTC1 L1142H :STN1 and DNA Pol-α results in increased telomerase recruitment to telomeres and further telomere elongation, revealing that C:S binding to DNA Pol-α is required to fully repress telomerase activity. CP CTC1 mutants that fail to interact with DNA Pol-α resulted in loss of C-strand maintenance and catastrophic telomere shortening. Our findings place the CST complex as an important regulator of both G-strand extensions by telomerase and C-strand synthesis by DNA Pol-α. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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...... 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....... There was a decreasing trend (P = 0.01) in the incidence of 'severe pre-eclampsia/eclampsia/HELLP' with increasing dietary vitamin C intake; with an intake of 130-170 mg/day as reference, odds ratios ranged from 1.21 (95% confidence interval 0.83 to 1.75) for an intake below 70 mg/day to 0.70 (0.40 to 1...

Telomere length shortening is associated with treatment-free remission in chronic myeloid leukemia patients

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Giovanni Caocci

2016-07-01

Full Text Available Abstract We studied telomere length in 32 CML patients who discontinued imatinib after achieving complete molecular remission and 32 age-sex-matched controls. The relative telomere length (RTL was determined by q-PCR as the telomere to single copy gene (36B4 ratio normalized to a reference sample (K-562 DNA. Age-corrected RTL (acRTL was also obtained. The 36-month probability of treatment-free remission (TFR was 59.4 %. TFR patients showed shorter acRTL compared to relapsed (mean ± SD = 0.01 ± 0.14 vs 0.20 ± 0.21; p = 0.01. TFR was significantly higher in CML patients with acRTL ≤0.09 (78.9 vs 30.8 %, p = 0.002. CML stem cells harboring longer telomeres possibly maintain a proliferative potential after treatment discontinuation.

Role of cytokines in development of pre-eclampsia associated with periodontal disease - Cohort Study.

Science.gov (United States)

Kumar, Ashok; Begum, Nargis; Prasad, Sudha; Lamba, Arundeep K; Verma, Mahesh; Agarwal, Sarita; Sharma, Shashi

2014-04-01

The present study was designed to find any association of cytokines in women with periodontal disease and development of pre-eclampsia in North Indian population. A total of 504 consecutively registered primigravida with a single live pregnancy were recruited at 14-18 weeks of gestation from antenatal clinic of Maulana Azad Medical College & associated Lok Nayak Hospital and Maulana Azad Institute of Dental Sciences, New Delhi. One periodontist performed oral health examination of all patients at inclusion into study. Blood samples were collected to measure the level of cytokines IL-4, IL-10, TNF-α and IFN-γ. The profile of blood levels of cytokines from women with periodontal disease was observed. The log serum levels of TNF-α & IL-4 at 16-18 weeks of gestation were significantly higher in women with periodontal disease (4.13 ± 2.06; 0.47 ± 1.56 pg/ml respectively) than in women with healthy gums (2.16 ± 1.51; 0.02 ± 1.84 pg/ml respectively, p Periodontal disease is associated with log serum TNF-α levels at cut-off ≥14.43 pg/ml at sensitivity 71.2% and specificity 62% (OR = 4.04; 95%CI = 2.77-5.87). Woman with periodontal disease who later developed pre-eclampsia had lower levels of TNF-α (3.72 ± 1.33 pg/ml) than those with periodontal disease who did not develop pre-eclampsia (4.20 ± 2.15 pg/ml, p ≥ 0.05). Reduced TNF-α level secretion in the early second trimester in women with periodontal disease appears to be associated with the development of pre-eclampsia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

MRI and MRV in differentiation of posterior reversible encephalopathy syndrome and venous occlusion in patients with eclampsia or pre-eclampsia

International Nuclear Information System (INIS)

Xia Shuang; Liu Qingxian; Qi Ji

2009-01-01

Objective: To evaluate the role of MRV and MRI in the diagnosis of posterior encephalopathy syndrome (PRES) and venous sinus occlusion in patients with eclampsia or pre-eclampsia. Methods: We respectively studied the clinical and imaging data of 27 pre-eclampsia or eclampsia patients who occurred epilepsy, headache, and vision deficient during pregnancy or post partum. All patients underwent MRI and MRV examinations. The imaging protocol included coronal, sagittal, and axial T 1 WI, T 2 WI, FLAIR, DWI, and MRV. Results: 14 patients showed evidence of venous occlusion. Among them, 3 occurred in cortical vein, 4 in superior sagittal sinus, 2 in transverse sinus, l in sigmoid sinus, 2 in deep vein system, 3 in jugular vein, and 2 with complete sinus occlusion. Brain edema distributed in the corresponding area of occlusive sinus and 2 cases combined with secondary hemorrhage. 13 patients suffered from hypertensive encephalopathy. All of the lesions involved arcuate fibre in the bilateral parietal lobe (10 cases), right parietal lobe (2 cases), bilateral occipital lobe (7 cases), bilateral frontal lobe (6 cases), right frontal lobe (3 cases), bilateral temporal lobe (4 cases), left temporo-occipital lobe (1 case), splenium of corpus callosum (1 case), bilateral basal ganglia (2 cases), right basal ganglia (1 case), left centrum semiovale (1 case), and bilateral cerebellar hemisphere (1 case). Both of the lesions of PRES and venous occlusion showed hyperintensity on FLAIR and T 2 WI images, isointensity on DWI and hyperintensity on ADC, indicating vasogenic edema. Decreased lesion extent or completely disappeared was identified in 12 patients on follow-up scans. Conclusion: Lesions of PRES are usually located in the parietal and occipital lobes, especially in white matter. The lesion of venous occlusion usually occurs in the area of corresponding occlusive sinus. The MRV has an important value in diagnosis of PRES and venous sinus occlusion. (authors)

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.

Eclampsia - a method of management

African Journals Online (AJOL)

1983-04-02

Apr 2, 1983 ... A preliminary report ... Eight patients died from eclampsia during the period, a mortality ... Like pre-eclampsia, eclampsia is common- ... Only 3 patients experienced their initial convulsions in hospital,. 2 in the ... Level of consciousness at admission (Table IV). .... was used to provide postoperative analgesia.

Association between maternal symptoms of sleep disordered breathing and fetal telomere length.

Science.gov (United States)

Salihu, Hamisu M; King, Lindsey; Patel, Priyanshi; Paothong, Arnut; Pradhan, Anupam; Louis, Judette; Naik, Eknath; Marty, Phillip J; Whiteman, Valerie

2015-04-01

Our investigation aims to assess the impact of symptoms of maternal sleep-disordered breathing, specifically sleep apnea risk and daytime sleepiness, on fetal leukocyte telomere length. Pregnant women were recruited upon hospital delivery admission. Sleep exposure outcomes were measured using the Berlin Questionnaire to quantify sleep apnea and the Epworth Sleepiness Scale to measure daytime sleepiness. Participants were classified as "High Risk" or "Low Risk" for sleep apnea based on responses to the Berlin, while "Normal" or "Abnormal" daytime sleepiness was determined based on responses to the Epworth. Neonatal umbilical cord blood samples (N = 67) were collected and genomic DNA was isolated from cord blood leukocytes using Quantitative PCR. A ratio of relative telomere length was derived by telomere repeat copy number and single copy gene copy number (T/S ratio) and used to compare telomere lengths. Bootstrap and ANOVA statistical procedures were employed. On the Berlin, 68.7% of participants were classified as Low Risk while 31.3% were classified as High Risk for sleep apnea. According to the Epworth scale, 80.6% were determined to have Normal daytime sleepiness, and 19.4% were found to have Abnormal daytime sleepiness. The T/S ratio among pregnant women at High Risk for sleep apnea was significantly shorter than for those at Low Risk (P value sleep disordered breathing during pregnancy, and suggest sleep disordered breathing as a possible mechanism of accelerated chromosomal aging. © 2015 Associated Professional Sleep Societies, LLC.

Stress appraisals and cellular aging: A key role for anticipatory threat in the relationship between psychological stress and telomere length

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O’Donovan, Aoife; Tomiyama, A. Janet; Lin, Jue; Puterman, Eli; Adler, Nancy E.; Kemeny, Margaret; Wolkowitz, Owen M.; Blackburn, Elizabeth H.; Epel, Elissa S.

2012-01-01

Chronic psychological stressis a risk factor formultiple diseases of aging. Accelerated cellular aging as indexed by short telomere length has emerged as a potential common biological mechanism linking various forms of psychological stress and diseases of aging. Stress appraisals determine the degree and type of biological stress responses and altered stress appraisals may be a common psychological mechanism linking psychological stress and diseases of aging. However, no previous studies have examined the relationship between stress appraisals and telomere length. We exposed chronically stressed female caregivers and non-caregiving controls (N= 50; M age = 62.14±6.10) to a standardized acute laboratory stressor and measured their anticipatory and retrospective threat and challenge appraisals of the stressor. We hypothesized that threat and challenge appraisals would be associated with shorter and longer telomere length respectively, and that chronic care giving stress would influence telomere length through altered stress appraisals. Higher anticipatory threat appraisals were associated with shorter age-adjusted telomere length (β = −.32, p = .03), but challenge appraisals and retrospective threat appraisals showed no independent association with telomere length. Caregivers reported significantly higher anticipatory (β = −.36, p = .006)and retrospective (β = −.29, p = .03) threat appraisals than controls, but similar challenge appraisals. Although there was no significant main effect of caregiver status on telomere length, care giving had a significant indirect effect on telomere length through anticipatory threat appraisals. Exaggerated anticipatory threat appraisals may be a common and modifiable psychological mechanism of psychological stress effects on cellular aging. PMID:22293459

Comparison of telomere length in black and white teachers from South Africa: the sympathetic activity and ambulatory blood pressure in Africans study.

Science.gov (United States)

von Känel, Roland; Malan, Nico T; Hamer, Mark; Malan, Leoné

2015-01-01

Telomere length is a marker of biological aging that has been linked to cardiovascular disease risk. The black South African population is witnessing a tremendous increase in the prevalence of cardiovascular disease, part of which might be explained through urbanization. We compared telomere length between black South Africans and white South Africans and examined which biological and psychosocial variables played a role in ethnic difference in telomere length. We measured leukocyte telomere length in 161 black South African teachers and 180 white South African teachers aged 23 to 66 years without a history of atherothrombotic vascular disease. Age, sex, years having lived in the area, human immunodeficiency virus (HIV) infection, hypertension, body mass index, dyslipidemia, hemoglobin A1c, C-reactive protein, smoking, physical activity, alcohol abuse, depressive symptoms, psychological distress, and work stress were considered as covariates. Black participants had shorter (median, interquartile range) relative telomere length (0.79, 0.70-0.95) than did white participants (1.06, 0.87-1.21; p < .001), and this difference changed very little after adjusting for covariates. In fully adjusted models, age (p < .001), male sex (p = .011), and HIV positive status (p = .023) were associated with shorter telomere length. Ethnicity did not significantly interact with any covariates in determining telomere length, including psychosocial characteristics. Black South Africans showed markedly shorter telomeres than did white South African counterparts. Age, male sex, and HIV status were associated with shorter telomere length. No interactions between ethnicity and biomedical or psychosocial factors were found. Ethnic difference in telomere length might primarily be explained by genetic factors.

Ibuprofen versus acetaminophen as a post-partum analgesic for women with severe pre-eclampsia: randomized clinical study.

Science.gov (United States)

Vigil-De Gracia, Paulino; Solis, Valentin; Ortega, Nelson

2017-06-01

To compare differences in blood pressure levels between patients with severe post-partum pre-eclampsia using ibuprofen or acetaminophen. A randomized controlled trial was made in women with severe pre-eclampsia or superimposed pre-eclampsia after vaginal birth. The patient was randomly selected to receive either 400 mg of ibuprofen every 8 h or 1 g of acetaminophen every 6 h during the post-partum. The primary variable was systolic hypertension ≥150 mmHg and/or diastolic hypertension ≥100 mmHg after the first 24 h post-partum. Secondary variables were the arterial blood pressure readings at 24, 48, 72, and 96 h post-partum and maternal complications. A total of 113 patients were studied: 56 in the acetaminophen group and 57 in the ibuprofen group. With regard to the primary outcome, more cases were significantly hypertensive in the ibuprofen group (36/57; 63.1%) than in the acetaminophen group (16/56; 28.6%). Severe hypertension (≥160/110 mmHg) was not significantly different between the groups, 14.5% (acetaminophen) and 24.5% (ibuprofen). The levels of arterial blood pressure show a hammock-shaped curve independent of the drug used, however, is more noticeable with ibuprofen. This study shows that ibuprofen significantly elevates blood pressure in women with severe pre-eclampsia during the post-partum period.

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

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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.

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

were measured using Fluorescence In Situ Hybridization (Q-FISH). RESULTS: A telomere length pattern was found to exist in primary hMSC's as well as in hMSC-telo1. This pattern is similar to what was previously found in lymphocytes and fibroblasts. The cells were then exposed to a high dose of ionizing...... radiation. Irradiation caused profound changes in chromosome specific telomere lengths, effectively destroying the telomere length pattern. Following long term culturing after irradiation, a telomere length pattern was found to re-emerge. However, the new telomere length pattern did not resemble...

Polimorfismos genéticos asociados a pre-eclampsia

OpenAIRE

Baquero Mejía, Ingrid Carolina

2013-01-01

RESUMEN: La pre-eclampsia es un trastorno multisistémico del embarazo y del puerperio, que complica aproximadamente del 6 al 8% de todos los embarazos en los países desarrollados. Es considerada un problema de salud pública debido a su alta prevalencia. Es una de las causas más frecuentes de mortalidad materno-fetal en países en desarrollo, igualmente es causa de preocupación en los países desarrollados por su gran relación causal con el retraso de crecimiento intrauterino y partos prematuro...

The role of maternal serumbeta-HCG and PAPP-A levels at gestational weeks 10 to 14 in the prediction of pre-eclampsia

Science.gov (United States)

Ozdamar, Ozkan; Gun, Ismet; Keskin, Ugur; Kocak, Necmettin; Mungen, Ercument

2014-01-01

Objective: We aimed to detect whether maternal serum free β-hCG and PAPP-A levels and NT measurements vary between normal pregnancies and those that subsequently develop pre-eclampsia and to evaluate the role of these screening serum analytes in the prediction of pre-eclampsia. Methods: Using a case-control study design, we identified all women who had been screened by double test within 11+0 and 13+6 weeks of gestation and who had developed pre-eclampsia during the subsequent pregnancy course, over a 6-year period between January 2006 and December 2012 at two tertiary referral hospital. All women who had undergone a double test during that time, without a diagnosis of pre-eclampsia and who had not had any adverse obstetric outcomes, were also identified, and three women among them were randomly selected as controls for each case. Maternal and neonatal data were abstracted from the medical records and PAPP-A, β-hCG, NT and CRL MoM values were compared between the two groups. Results: Although β-hCG values show no statistically significant difference (p=0.882), PAPP-A levels were significantly reduced in the pre-eclampsia group compared to the control group (p<0.001). NT and CRL values showed no significant difference between the two groups (p=0.674 and p=0.558, respectively). Conclusion: Measuring PAPP-A in the first trimester may be useful in the prediction of pre-eclampsia. PMID:24948981

CORRELATION OF SPOT URINE ALBUMIN AND 12-HOUR URINE PROTEIN WITH 24-HOUR URINE PROTEIN IN PRE-ECLAMPSIA

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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.

Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis

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Langejans Marloes

2008-08-01

Full Text Available Abstract Background Reliable antenatal identification of pre-eclampsia and small for gestational age is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving maternal/perinatal outcome. The purpose of this systematic review was to determine the accuracy of five serum analytes used in Down's serum screening for prediction of pre-eclampsia and/or small for gestational age. Methods The data sources included Medline, Embase, Cochrane library, Medion (inception to February 2007, hand searching of relevant journals, reference list checking of included articles, contact with experts. Two reviewers independently selected the articles in which the accuracy of an analyte used in Downs's serum screening before the 25th gestational week was associated with the occurrence of pre-eclampsia and/or small for gestational age without language restrictions. Two authors independently extracted data on study characteristics, quality and results. Results Five serum screening markers were evaluated. 44 studies, testing 169,637 pregnant women (4376 pre-eclampsia cases and 86 studies, testing 382,005 women (20,339 fetal growth restriction cases met the selection criteria. The results showed low predictive accuracy overall. For pre-eclampsia the best predictor was inhibin A>2.79MoM positive likelihood ratio 19.52 (8.33,45.79 and negative likelihood ratio 0.30 (0.13,0.68 (single study. For small for gestational age it was AFP>2.0MoM to predict birth weight th centile with birth There were methodological and reporting limitations in the included studies thus studies were heterogeneous giving pooled results with wide confidence intervals. Conclusion Down's serum screening analytes have low predictive accuracy for pre-eclampsia and small for gestational age. They may be a useful means of risk assessment or of use in prediction when combined with other tests.

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, 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.

Shorter Leukocyte Telomere Length in Relation to Presumed Nonalcoholic Fatty Liver Disease in Mexican-American Men in NHANES 1999–2002

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Janet M. Wojcicki

2017-01-01

Full Text Available Leukocyte telomere length is shorter in response to chronic disease processes associated with inflammation such as diabetes mellitus and coronary artery disease. Data from the National Health and Nutrition Examination Survey (NHANES from 1999 to 2002 was used to explore the relationship between leukocyte telomere length and presumed NAFLD, as indicated by elevated serum alanine aminotransferase (ALT levels, obesity, or abdominal obesity. Logistic regression models were used to evaluate the relationship between telomere length and presumed markers of NAFLD adjusting for possible confounders. There was no relationship between elevated ALT levels, abdominal obesity, or obesity and telomere length in adjusted models in NHANES (OR 1.13, 95% CI 0.48–2.65; OR 1.17, 95% CI 0.52–2.62, resp.. Mexican-American men had shorter telomere length in relation to presumed NAFLD (OR 0.07, 95% CI 0.006–0.79 and using different indicators of NAFLD (OR 0.012, 95% CI 0.0006–0.24. Mexican origin with presumed NAFLD had shorter telomere length than men in other population groups. Longitudinal studies are necessary to evaluate the role of telomere length as a potential predictor to assess pathogenesis of NALFD in Mexicans.

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

International Nuclear Information System (INIS)

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

2014-01-01

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. (author)

Is telomere length a biomarker for aging: cross-sectional evidence from the west of Scotland?

Science.gov (United States)

Der, Geoff; Batty, G David; Benzeval, Michaela; Deary, Ian J; Green, Michael J; McGlynn, Liane; McIntyre, Alan; Robertson, Tony; Shiels, Paul G

2012-01-01

The search for biomarkers of aging (BoAs) has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure. Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites. Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area.

Is telomere length a biomarker for aging: cross-sectional evidence from the west of Scotland?

Directory of Open Access Journals (Sweden)

Geoff Der

Full Text Available BACKGROUND: The search for biomarkers of aging (BoAs has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure. METHODOLOGY/PRINCIPAL FINDINGS: Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites. CONCLUSIONS: Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area.

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

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 similar to 20 and 56 years. Leukocyte...... 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...... telomere length than men with positive change in cognitive performance (unadjusted difference beta = -0.09, 95% CI -0.16 to -0.02, p = 0.02). This association remained significant after adjusting for smoking, alcohol consumption, leisure time activity, body mass index (BMI) and cholesterol (adjusted...

Variants in TERT influencing telomere length are associated with paranoid schizophrenia risk.

Science.gov (United States)

Rao, Shuquan; Ye, Ning; Hu, Huiling; Shen, Yan; Xu, Qi

2016-04-01

Schizophrenia is one of the most severe psychiatric disorders, with a high heritability of up to 80%. Several studies have reported telomere dysfunction in schizophrenia, and common variants in the telomerase reverse transcriptase (TERT) gene. TERT is a key component of the telomerase complex that maintains telomere length by addition of telomere repeats to telomere ends, and has repeatedly shown association with mean lymphocyte telomere length (LTL). Thus, we hypothesized that TERT may be a novel susceptibility gene for schizophrenia. Using a Taqman protocol, we genotyped eight tag SNPs from the TERT locus in 1,072 patients with paranoid schizophrenia and 1,284 control subjects from a Chinese Han population. We also measured mean LTL in 98 cases and 109 controls using a quantitative PCR-based technique. Chi-square tests showed that two SNPs, rs2075786 (P = 0.0009, OR = 0.76, 95%CI = 0.65-0.90) and rs4975605 (P = 0.0026, OR = 0.73, 95%CI = 0.60-0.90), were associated with a protective effect, while rs10069690 was associated with risk of paranoid schizophrenia (P = 0.0044, OR = 1.23, 95%CI = 1.07-1.42). Additionally, the rs2736118-rs2075786 haplotype showed significant association with paranoid schizophrenia (P = 0.0013). Moreover, mean LTL correlated with rs2075786 genotypes was significantly shorter in the patient group than the control group. The present results suggest that the TERT gene may be a novel candidate involved in the development of paranoid schizophrenia. © 2016 Wiley Periodicals, Inc.

Poor periodontal health as a risk factor for development of pre-eclampsia in pregnant women

Directory of Open Access Journals (Sweden)

Shailesh Varshney

2014-01-01

Full Text Available Aims: Periodontal disease has been considered a systemic exposure implicated in a higher risk of adverse pregnancy outcomes. The aim of the present study was to determine whether maternal oral health is associated with an increased risk of pre-eclampsia. Subjects and Methods: A case-control study was conducted which included 40 pregnant women patients admitted to the Department of Obstetrics and Gynecology, J.N. Medical College, A.M.U, Aligarh. Pre-eclampsia was defined as classic triad of hypertension, proteinuria and symptoms such as swelling/edema esp. in hands and face, headache, visual changes etc., A periodontal examination was done during 48 h after child delivery. Maternal oral status was evaluated using gingival index by Loe and Silness, oral hygiene index (simplified by greene and vermillion and periodontal pockets and clinical attachment level (CAL. Statistical Analysis: Null hypothesis that no difference exist between the two groups (pre-eclamptic and non-pre-eclamptic Group was calculated using paired t-test, Chi-square and Mann-Whitney U statistical tests using SPSS 11.5 (Statistical Package for Social sciences, Chicago. P < 0.05 was considered to be statistically significant. Results: The amount of gingival inflammation, oral hygiene levels, pocket depth and CALs as measured by their respective indices were higher in the pre-eclamptic group when compared to non-pre-eclamptic group. Furthermore CAL was significantly increased in the test group. This study showed that pre-eclamptic cases were more likely to develop periodontal disease (P < 0.05. 30% of the test group and 65% of the case group had periodontal disease (P < 0.05 which had shown that pre-eclamptic cases were 4.33 times more likely to have periodontal disease (odds ratio = 4.33. Conclusions: Maternal oral status was determined to be associated with an increased risk of pre-eclampsia.

Eclampsia despite strict dietary sodium restriction.

NARCIS (Netherlands)

Delemarre, F.M.C.; Steegers, E.A.P.; Berendes, J.N.

2001-01-01

The classic indication for prescribing dietary sodium restriction in pregnancy has been the prevention of eclampsia. We describe a case of intrapartum eclampsia in a 24-year-old nulliparous woman. A strongly sodium restricted diet was prescribed because of pre-eclampsia. Compliance to the diet was

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.

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

Prenatal undernutrition and leukocyte telomere length in late adulthood: the Dutch famine birth cohort study

NARCIS (Netherlands)

de Rooij, Susanne R.; van Pelt, Ans M. M.; Ozanne, Susan E.; Korver, Cindy M.; van Daalen, Saskia K. M.; Painter, Rebecca C.; Schwab, Matthias; Viegas, Marcelo H.; Roseboom, Tessa J.

2015-01-01

Energy restriction in prenatal life has detrimental effects on later life health and longevity. Studies in rats have shown that the shortening of telomeres in key tissues plays an important role in this association. The aim of the current study was to investigate leukocyte telomere length in

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

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...... 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...... 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...

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

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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.

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

Setting the Trajectory: Racial Disparities in Newborn Telomere Length

Science.gov (United States)

Drury, Stacy S.; Esteves, Kyle; Hatch, Virginia; Woodbury, Margaret; Borne, Sophie; Adamski, Alys; Theall, Katherine P.

2015-01-01

Objective To explore racial differences in newborn telomere length (TL) and the effect moderation of the sex of the infant while establishing the methodology for the use of newborn blood spots for telomere length analyses. Study design Pregnant mothers were recruited from the Greater New Orleans area. TL was determined using MMQ-PCR on DNA extracted from infant blood spots. Demographic data and other covariates were obtained via maternal report prior to infant birth. Birth outcome data were obtained from medical records and maternal report. Results Black infants weighed significantly less than white infants at birth, and had significantly longer TL than White infants (p=0.0134), with the strongest effect observed in Black female infants. No significant differences in gestational age were present. Conclusions Significant racial differences in TL were present at birth in this sample, even after controlling for a range of birth outcomes and demographic factors. As longer initial TL is predictive of more rapid TL attrition across the life course, these findings provide evidence that, even at birth, biological vulnerability to early life stress may differ by race and sex. PMID:25681203

Educational attainment but not measures of current socioeconomic circumstances are associated with leukocyte telomere length in healthy older men and women.

Science.gov (United States)

Steptoe, Andrew; Hamer, Mark; Butcher, Lee; Lin, Jue; Brydon, Lena; Kivimäki, Mika; Marmot, Michael; Blackburn, Elizabeth; Erusalimsky, Jorge D

2011-10-01

Low socioeconomic status (SES) may be associated with accelerated biological aging, but findings relating SES with telomere length have been inconsistent. We tested the hypotheses that shorter telomere length and telomerase activity would be related more robustly to education, an early life indicator of socioeconomic position, than to current indicators of socioeconomic circumstances. Healthy men and women aged 53-76 years from the Whitehall II epidemiological cohort provided blood samples from which telomere length was assessed in 448 and telomerase activity in 416. Educational attainment was classified into four levels, while household income and grade of employment were measured as indicators of current socioeconomic circumstances. Age, gender, blood pressure, glycated hemoglobin, high density lipoprotein cholesterol, smoking, body mass index and physical activity were included as covariates. We found that lower educational attainment was associated with shorter telomere length after controlling statistically for biological and behavioral covariates. Neither household income nor employment grade was related to telomere length. The association between telomere length and education remained significant after adjusting for current socioeconomic circumstances. In men, highest levels of telomerase activity were found in the lowest education group. We conclude that low SES defined in terms of education but not current socioeconomic circumstances is associated with shortened telomeres. Low educational attainment may be an indicator of long-term SES trajectories, and be associated with accumulated allostatic load resulting in telomere shortening. Education may also promote problem-solving skills leading to reduced biological stress responsivity, with favorable consequences for biological aging. Copyright © 2011 Elsevier Inc. All rights reserved.

Serum Uric Acid as a Predictor of Perinatal Outcome in Women with Pre-Eclampsia

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Jwan Muhammad Zangana

2018-03-01

Full Text Available Background and objectives: Pre-eclampsia is one of the medical complication of pregnancy and contributes significantly to maternal and perinatal morbidity and mortality. Hyperuricemia is often associated with preeclampsia. The objective of this study was to assess serum uric acid in group of women with pre-eclampsia and to evaluate its diagnostic effect on perinatal outcome. Patients and methods: This is a hospital-based cross-sectional study conducted in Maternity Teaching Hospital in Erbil city, Iraq. Convenient sample size of 200 participants preeclamptic pregnant women with ≥ 34 weeks of gestation in different level of hypertension were included. After getting informed consent from participant who were diagnosed with pre-eclampsia (hypertension and proteinuria, all sociodemographic information was collected from 1st June 2017 to 19th January 2018. Blood samples were obtained to assess serum uric acid besides other investigation routinely done and fetal outcome (birth weight, gestational age, intrauterine death, Apgar score, admission to neonatal care unit, intrauterine growth restriction and early neonatal death was evaluated. Results: Serum uric acid was ≥ 6 mg/dL in 127 (63.5% among all pre-eclamptic women. There was positive significant association between means of serum uric acid at different levels of hypertension with p=0.000 in ANOVA and x2 test. This study revealed significant association between increased level of serum uric acid and bad fetal outcome (birth weight, gestational age, intrauterine death, Apgar score, admission to neonatal care unit, intrauterine growth restriction and early neonatal death and Apgar score in 1st minute. Conclusion: This study revealed significant raised level of serum uric acid among pre-eclamptic women and significant effect on fetal outcome and perinatal morbidity and mortality.

Intrauterine Exposure to Maternal Stress Alters Bdnf IV DNA Methylation and Telomere Length in the Brain of Adult Rat Offspring

Science.gov (United States)

Blaze, Jennifer; Asok, Arun; Borrelli, Kristyn; Tulbert, Christine; Bollinger, Justin; Ronca Finco, April E.; Roth, Tania L.

2017-01-01

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 contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavioral outcomes. 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 rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed controls. Further, prenatally-stressed males had shorter telomeres than controls in the mPFC. This study provides the first evidence in a rodent model of an association between prenatal stress exposure and subsequent shorter brain telomere length. Together findings indicate a long-term impact of prenatal stress on DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational epigenetic alterations and changes in telomere length.

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

Systemic lupus erythematosus and vitamin D deficiency are associated with shorter telomere length among African Americans: a case-control study.

Directory of Open Access Journals (Sweden)

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.

Analysis of the original causes of placental oxidative stress in normal pregnancy and pre-eclampsia: a hypothesis.

Science.gov (United States)

Yang, Xiang; Guo, Lili; Li, Huaifang; Chen, Xinliang; Tong, Xiaowen

2012-07-01

Pre-eclampsia (PE) and eclampsia remain enigmatic despite intensive research. Growing evidence suggests that placental oxidative stress (OS) is involved in the etiopathogenesis of pre-eclampsia. Reduced perfusion as a result of abnormal placentation was proposed to be responsible for placental OS in PE. However, placental OS was also observed in normal pregnancy. The exact differences and correlation of placental OS in PE and normal pregnancy remain elusive. In this review, we attempted to link both normal pregnancy and PE on the causes of placental OS and proposed a hypothesis that placental OS in normal pregnancy, plus the exploration of other placental and/or maternal factors, could provide a novel explanation of that in PE. We concluded that pregnancy, placental abnormality and preexisting maternal constitutional conditions are three principle factors that could contribute to placental OS in PE. The specific causes in each clinical case could be heterogeneous, which requires individual analysis.

Serum levels of activin A and inhibin A are not related to the increased susceptibility to pre-eclampsia in type I diabetic pregnancies

DEFF Research Database (Denmark)

Ekbom, Pia; Damm, Peter; Andersson, Anna-Maria

2006-01-01

Activin A and inhibin A have been found to be elevated in women without diabetes subsequently developing pre-eclampsia. The aim was to investigate whether activin A and inhibin A in serum were elevated in type I diabetic women after developing pre-eclampsia and, if so, were they clinically useful...

Telomere dynamics, end-to-end fusions and telomerase activation during the human fibroblast immortalization process.

Science.gov (United States)

Ducray, C; Pommier, J P; Martins, L; Boussin, F D; Sabatier, L

1999-07-22

Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been generally assumed that activation of telomerase prevents further telomere shortening and is essential for cell immortalization. In this study, we performed a detailed cytogenetic and molecular characterization of four SV40 transformed human fibroblastic cell lines by regularly monitoring the size distribution of terminal restriction fragments, telomerase activity and the associated chromosomal instability throughout immortalization. The mean TRF lengths progressively decreased in pre-crisis cells during the lifespan of the cultures. At crisis, telomeres reached a critical size, different among the cell lines, contributing to the peak of dicentric chromosomes, which resulted mostly from telomeric associations. We observed a direct correlation between short telomere length at crisis and chromosomal instability. In two immortal cell lines, although telomerase was detected, mean telomere length still continued to decrease whereas the number of dicentric chromosomes associated was stabilized. Thus telomerase could protect specifically telomeres which have reached a critical size against end-to-end dicentrics, while long telomeres continue to decrease, although at a slower rate as before crisis. This suggests a balance between elongation by telomerase and telomere shortening, towards a stabilized 'optimal' length.

Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control

Directory of Open Access Journals (Sweden)

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.

Normal telomere lengths in naive and memory CD4+ T cells in HIV type 1 infection: a mathematical interpretation

NARCIS (Netherlands)

Wolthers, K. C.; Noest, A. J.; Otto, S. A.; Miedema, F.; de Boer, R. J.

1999-01-01

To study CD4+ T cell productivity during HIV-1 infection, CD4+ T cell telomere lengths were measured. Cross-sectional and longitudinal analysis of HIV-1-infected individuals with CD4+ T cells counts >300 cells/mm3 showed normal average telomeric restriction fragment (TRF) length and normal

Normal telomere lengths in naive and memory CD4 T cells in HIV type 1 infection : a mathematical interpretation

NARCIS (Netherlands)

Wolthers, K.C.; Noest, A.J.; Otto, S.A.; Miedema, F.; Boer, R.J. de

1999-01-01

To study CD4+ T cell productivity during HIV-1 infection, CD4+ T cell telomere lengths were measured. Cross-sectional and longitudinal analysis of HIV-1-infected individuals with CD4+ T cells counts >300 cells/mm3 showed normal average telomeric restriction fragment (TRF) length and normal

Relationships of risk factors for pre-eclampsia with patterns of occurrence of isolated gestational proteinuria during normal term pregnancy.

Directory of Open Access Journals (Sweden)

Corrie Macdonald-Wallis

Full Text Available 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.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.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.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.

[Pre-eclampsia prevention in 2018 in general population and in lupic women: At the dawn of a personalized medicine?

Science.gov (United States)

de Moreuil, C; Fauchais, A-L; Merviel, P; Tremouilhac, C; Le Moigne, E; Pasquier, E; Pan-Petesch, B; Lacut, K

2018-06-19

Pre-eclampsia prevention represents a major public health issue, as this vasculo-placental disorder generates a great burden of foeto-maternal morbi-mortality. Aspirin has proved its efficacy in primary and secondary pre-eclampsia prevention, especially when it is given at 150mg per day bedtime before 15 weeks of gestation to high-risk women. In the English trial ASPRE, high-risk women were identified by an algorithm taking into account angiogenic biomarkers ascertained at the end of first trimester of pregnancy. This article focuses on physiopathological mechanisms and risk factors of pre-eclampsia and on the interest of early angiogenic biomarkers dosing during pregnancy, for the assessment of pre-eclampsia risk. Unlike Great Britain or Israel, cost-effectiveness of this algorithm in general population has not been assessed in France. Finally, systemic lupus erythematous is at high risk of vasculo-placental disorders. Although few studies of angiogenic biomarkers dosing during lupus pregnancies identified a correlation between high sFlt1 levels at the end of first trimester and subsequent onset of severe vasculo-placental disorders, with a very good negative predictive value of sFtl1. Angiogenic biomarkers ascertainment for screening of vasculo-placental disorders in pregnant women with systemic lupus erythematous could allow targeting at best women needing an aspirin treatment and a closer monitoring. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

First trimester serum afamin concentrations are associated with the development of pre-eclampsia and gestational diabetes mellitus in pregnant women.

Science.gov (United States)

Tramontana, Allessandra; Dieplinger, Benjamin; Stangl, Gerhard; Hafner, Erich; Dieplinger, Hans

2018-01-01

Aim of this study was to assess the prognostic capability of afamin to predict pregnancy complications. First-trimester screening was consecutively performed in 4948 pregnant women, of whom 474 women developed pregnancy complications [gestational hypertension (n=84), pre-eclampsia (n=30), intrauterine growth restriction (n=107), preterm birth (n=44), and gestational diabetes mellitus (n=209)]. To each woman with pregnancy complications an uncomplicated pregnancy was matched for body mass index. Afamin serum concentrations were measured in 948 pregnant women at the first-trimester screening. Median afamin concentrations were significantly higher in women developing pre-eclampsia or gestational diabetes mellitus when compared to women with uncomplicated pregnancies (76mg/L vs. 65mg/L, p=0.001 and 80mg/L vs. 69mg/L, p65mg/L) was a strong and independent predictor for the development of pre-eclampsia (risk ratio, 24.58; 95%CI, 2.82-214.12; p=0.004) as well as gestational diabetes mellitus (risk ratio, 2.07; 95%CI, 1.33-3.22; p=0.001). In this large nested case-control study increased afamin concentrations were a strong and independent predictor for pre-eclampsia and gestational diabetes mellitus, suggesting a potential role of afamin as predictive marker for pregnancy-related metabolic disorders. Copyright © 2017. Published by Elsevier B.V.

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

African Journals Online (AJOL)

group even though they all had access to the internet. It was found that ... In Sokoto, Nigeria6 159 relations of 56 patients brought to a referral hospital with eclampsia were interviewed about their beliefs about the causation of eclampsia. Only six of these relations associated high blood pressure with eclampsia. Seventy five ...

Experimental and Clinical Studies of Oxidative Stress in Pre-Eclampsia

OpenAIRE

Nash, Peppi

2007-01-01

Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of pre-eclampsia (PE). It has recently been pointed out that PE might be more than one disease and may have several different pathogeneses. This thesis describes a new animal model for PE and examines the role of oxidative stress in early respective late onset PE. The effects of Suramin injections on day 10 and 11 of pregnancy were investigated in normal and diabetic rats of two strains (U and H), ...

Telomere Restriction Fragment (TRF) Analysis.

Science.gov (United States)

Mender, Ilgen; Shay, Jerry W

2015-11-20

While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al. , 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al. , 1990; Ouellette et al. , 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

The effects of social status on biological aging as measured by white-blood-cell telomere length.

Science.gov (United States)

Cherkas, L F; Aviv, A; Valdes, A M; Hunkin, J L; Gardner, J P; Surdulescu, G L; Kimura, M; Spector, T D

2006-10-01

Low socio-economic status (SES) is associated with a shortened life expectancy, but its effect on aging is unknown. The rate of white-blood-cell (WBC) telomere attrition may be a biological indicator of human aging. We tested the hypothesis that SES is associated with telomere attrition independent of known risk factors influencing the aging process. We studied 1552 female twins. A venous blood sample was taken from each twin and isolated WBCs used for extraction of DNA. Terminal restriction fragment length (TRFL) was measured. Questionnaire data were collected on occupation, education, income, smoking, exercise, height and weight. Standard multiple linear regression and multivariate analyses of variance tested for associations between SES and TRFL, adjusting for covariates. A discordant twin analysis was conducted on a subset to verify findings. WBC telomere length was highly variable but significantly shorter in lower SES groups. The mean difference in TRFL between nonmanual and manual SES groups was 163.2 base pairs (bp) of which 22.9 bp (approximately 14%) was accounted for by body mass index, smoking and exercise. Comparison of TRFL in the 17 most discordant SES twin pairs confirmed this difference. Low SES, in addition to the harmful effects of smoking, obesity and lack of exercise, appears to have an impact on telomere length.

Endothelin type B (ETB) receptors: friend or foe in the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk?

Science.gov (United States)

Mirabito Colafella, Katrina M

2018-01-16

In a recent issue of Clinical Science, Stanhewicz et al. investigated persistent microvascular dysfunction in women up to 16 months postpartum. The authors found sensitivity to the pressor effects of endothelin-1 (ET-1) was enhanced when compared with women who had a normotensive pregnancy. Importantly, the authors demonstrated that this effect was mediated via the endothelin type B (ET B ) receptors. Therefore, the present study highlights the possibility that alterations in the localization of the ET B receptor contributes to the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk. Currently, there is great interest in the role of the endothelin system in pre-eclampsia. Targetting the endothelin system, potentially by modulating upstream pathways to prevent ET B receptor dysfunction, may improve health outcomes for women and their offspring during pre-eclampsia and later life. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

PCB153 reduces telomerase activity and telomere length in immortalized human skin keratinocytes (HaCaT) but not in human foreskin keratinocytes (NFK)

International Nuclear Information System (INIS)

Senthilkumar, P.K.; Robertson, L.W.; Ludewig, G.

2012-01-01

Polychlorinated biphenyls (PCBs), ubiquitous environmental pollutants, are characterized by long term-persistence in the environment, bioaccumulation, and biomagnification in the food chain. Exposure to PCBs may cause various diseases, affecting many cellular processes. Deregulation of the telomerase and the telomere complex leads to several biological disorders. We investigated the hypothesis that PCB153 modulates telomerase activity, telomeres and reactive oxygen species resulting in the deregulation of cell growth. Exponentially growing immortal human skin keratinocytes (HaCaT) and normal human foreskin keratinocytes (NFK) were incubated with PCB153 for 48 and 24 days, respectively, and telomerase activity, telomere length, superoxide level, cell growth, and cell cycle distribution were determined. In HaCaT cells exposure to PCB153 significantly reduced telomerase activity, telomere length, cell growth and increased intracellular superoxide levels from day 6 to day 48, suggesting that superoxide may be one of the factors regulating telomerase activity, telomere length and cell growth compared to untreated control cells. Results with NFK cells showed no shortening of telomere length but reduced cell growth and increased superoxide levels in PCB153-treated cells compared to untreated controls. As expected, basal levels of telomerase activity were almost undetectable, which made a quantitative comparison of treated and control groups impossible. The significant down regulation of telomerase activity and reduction of telomere length by PCB153 in HaCaT cells suggest that any cell type with significant telomerase activity, like stem cells, may be at risk of premature telomere shortening with potential adverse health effects for the affected organism. -- Highlights: ► Human immortal (HaCaT) and primary (NFK) keratinocytes were exposed to PCB153. ► PCB153 significantly reduced telomerase activity and telomere length in HaCaT. ► No effect on telomere length and

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; 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

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

Depressive symptoms are not associated with leukocyte telomere length: findings from the Nova Scotia Health Survey (NSHS95, a population-based study.

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Jonathan A Shaffer

Full Text Available Premature shortening of leukocyte telomere length has been proposed as a novel mechanism by which depression may confer increased risk of adverse cardiovascular events. Prior studies demonstrating associations of depression and depressive symptoms with shorter leukocyte telomere length were small, included selected psychiatric outpatients, were based on convenience samples, and/or adjusted for a limited number of possible confounding factors.We examined the associations of depressive symptoms, probable depressive disorder, and specific depressive symptom clusters, as assessed by the Center for Epidemiological Studies--Depression (CES-D scale, with leukocyte telomere length, measured by using a real-time PCR method, in 2,225 apparently healthy participants from the 1995 Nova Scotia Health Survey population-based study. The mean age was 48.2 ± 18.9 years; 49.9% of participants were female; and the mean CES-D score was 7.4 ± 7.9. The mean telomere length was 5,301 ± 587 base pairs. In an unadjusted model, depressive symptoms were significantly associated with longer leukocyte telomere length (B = 27.6 base pairs per standard deviation increase in CES-D, 95% confidence interval [CI] = 3.1-52.1, p = 0.027. This association was no longer significant after adjustment for age and sex (B = 9.5, 95% CI = -14.6-33.6, p = 0.44 or after further adjustment for body mass index, Framingham risk score and previous history of ischemic heart disease (all p's ≥ 0.37. Neither probable depressive disorder nor specific depressive symptom clusters were independently associated with leukocyte telomere length.Concurrent depressive symptoms were not associated with leukocyte telomere length in a large, representative, population-based study.

Risk factors for pre-eclampsia among women at antenatal booking in Kano, Northern Nigeria

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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.

Current employment status, occupational category, occupational hazard exposure, and job stress in relation to telomere length: The Multiethnic Study of Atherosclerosis (MESA)

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Fujishiro, Kaori; Diez-Roux, Ana V; Landsbergis, Paul; Jenny, Nancy Swords; Seeman, Teresa

2014-01-01

Objective Telomere length has been proposed as a biomarker of cell senescence, which is associated with a wide array of adverse health outcomes. While work is a major determinant of health, few studies have investigated the association of telomere length with various dimensions of occupation. Accelerated cellular aging could be a common pathway linking occupational exposure to several health outcomes. Methods Leukocyte telomere length was assessed using quantitative polymerase chain reaction (Q-PCR) in a community-based sample of 981 individuals (age: 45–84 years old). Questionnaires were used to collect information on current employment status, current or main occupation before retirement, and job strain. The O*NET (Occupational Resource Network) database was linked to the questionnaire data to create 5 exposure measures: physical activity on the job, physical hazard exposure, interpersonal stressors, job control, and job demands. Linear regression was used to estimate associations of occupational characteristics with telomere lengths after adjustment for age, sex, race, socioeconomic position, and several behavioral risk factors. Results There were no mean differences in telomere lengths across current employment status, occupational category, job strain categories or levels of most O*NET exposure measures. There was also no evidence that being in lower status occupational categories or being exposed to higher levels of adverse physical or psychosocial exposures accelerated the association between age and telomere shortening. Conclusions Cellular aging as reflected by shorter telomeres does not appear to be an important pathway linking occupation to various health outcomes. PMID:23686115

Telomere length in non-neoplastic gastric mucosa and its relationship to H. pylori infection, degree of gastritis, and NSAID use.

Science.gov (United States)

Tahara, Tomomitsu; Shibata, Tomoyuki; Kawamura, Tomohiko; Ishizuka, Takamitsu; Okubo, Masaaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Arisawa, Tomiyasu; Ohmiya, Naoki; Hirata, Ichiro

2016-02-01

Telomere shortening occurs with human aging in many organs and tissues and is accelerated by rapid cell turnover and oxidative injury. We measured average telomere length using quantitative real-time PCR in non-neoplastic gastric mucosa and assessed its relationship to H. pylori-related gastritis, DNA methylation, ulcer disease, and nonsteroidal anti-inflammatory drug (NSAID) usage. Gastric biopsies were obtained from 151 cancer-free subjects including 49 chronic NSAID users and 102 nonusers. Relative telomere length in genomic DNA was measured by real-time PCR. H. pylori infection status, histological severity of gastritis, and serum pepsinogens (PGs) were also investigated. E-cadherin (CDH1) methylation status was determined by methylation-specific PCR (MSP). Average relative telomere length of H. pylori-infected subjects was significantly shortened when compared to H. pylori-negative subjects (p = 0.002) and was closely associated with all histological parameter of gastritis (all p values gastritis and CDH1 methylation status. Also, telomere shortening is accelerated by NSAID usage especially in H. pylori-negative subjects.

Apoptosis Signaling Is Altered in CD4⁺CD25⁺FoxP3⁺ T Regulatory Lymphocytes in Pre-Eclampsia

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Jan Oleszczuk

2012-05-01

Full Text Available The aim of our study was to estimate the surface expressions of CD95 (APO-1/Fas antigen and the intracellular expressions of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in CD4⁺CD25⁺FoxP3⁺ T regulatory lymphocytes (Tregs as well as the percentage of CD8⁺CD28⁺ T cytotoxic cells in peripheral blood of patients with pre-eclampsia in comparison with healthy pregnant women in the third trimester of physiological pregnancy. Twenty-four women with pre-eclampsia and 20 normal third trimester pregnant women were included in the study. The lymphocytes were isolated from peripheral blood samples and labeled with monoclonal antibodies. The expressions of surface antigens and intracellular proteins were estimated using flow cytometry. The population of CD4⁺CD25⁺FoxP3⁺ Treg cells was significantly lower in peripheral blood of patients with pre-eclampsia when compared to normal third trimester pregnant women. The percentages of CD4⁺CD25⁺FoxP3⁺ Treg cells that express Bcl-2 protein were significantly lower in peripheral blood of patients with pre-eclampsia when compared to healthy pregnant women, whereas the percentages of CD4⁺CD25⁺FoxP3⁺ Treg cells with the expressions of Bax protein did not differ in both groups. Moreover, the mean fluorescence intensity (MFI of Bcl-2 protein in CD4⁺CD25⁺FoxP3⁺ Treg cells was significantly lower and MFI of Bax protein significantly higher in pre-eclampsia when compared to the control group. The percentage of CD8⁺CD28⁺ T cells did not differ in both studied groups but MFI of CD28 antigen on T CD8⁺ cells was significantly higher in pre-eclampsia when compared to the control group. The obtained results suggest that the deficit of CD4⁺CD25⁺FoxP3⁺ Treg

TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas.

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Gao, Ke; Li, Gang; Qu, Yiping; Wang, Maode; Cui, Bo; Ji, Meiju; Shi, Bingyin; Hou, Peng

2016-02-23

Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas.

Donor Telomere Length SAA

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A new NCI study has found that, among patients with severe aplastic anemia who received a hematopoietic cell transplant from an unrelated donor, those whose donor white blood cells had longer telomeres had higher survival rates five-years after transplant

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.

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

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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.

Telomere lengthening early in development.

Science.gov (United States)

Liu, Lin; Bailey, Susan M; Okuka, Maja; Muñoz, Purificación; Li, Chao; Zhou, Lingjun; Wu, Chao; Czerwiec, Eva; Sandler, Laurel; Seyfang, Andreas; Blasco, Maria A; Keefe, David L

2007-12-01

Stem cells and cancer cells maintain telomere length mostly through telomerase. Telomerase activity is high in male germ line and stem cells, but is low or absent in mature oocytes and cleavage stage embryos, and then high again in blastocysts. How early embryos reset telomere length remains poorly understood. Here, we show that oocytes actually have shorter telomeres than somatic cells, but their telomeres lengthen remarkably during early cleavage development. Moreover, parthenogenetically activated oocytes also lengthen their telomeres, thus the capacity to elongate telomeres must reside within oocytes themselves. Notably, telomeres also elongate in the early cleavage embryos of telomerase-null mice, demonstrating that telomerase is unlikely to be responsible for the abrupt lengthening of telomeres in these cells. Coincident with telomere lengthening, extensive telomere sister-chromatid exchange (T-SCE) and colocalization of the DNA recombination proteins Rad50 and TRF1 were observed in early cleavage embryos. Both T-SCE and DNA recombination proteins decrease in blastocyst stage embryos, whereas telomerase activity increases and telomeres elongate only slowly. We suggest that telomeres lengthen during the early cleavage cycles following fertilization through a recombination-based mechanism, and that from the blastocyst stage onwards, telomerase only maintains the telomere length established by this alternative mechanism.

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...

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...

Cancer telomeres and white crows.

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Meeker, Alan K

2018-01-01

This mini-review article discusses past and present prostate-focused research on telomere and telomerase biology conducted at Johns Hopkins, through the eyes of a Donald S Coffey trainee. Included are past discoveries of abnormalities in telomere biology in the context of prostate cancer and its pre-malignant precursor prostatic intraepithelial neoplasia (PIN); the finding that telomerase activity is androgen-regulated in the prostate, and the potential role of telomerase in prostate epithelial stem cells. Also reviewed are more recent results showing that in situ telomere length measurements in patient tissue specimens may have utility in risk assessment and as a prognostic biomarker. Highlighted throughout the article are some of the training and mentorship approaches employed by the late Dr. Coffey, former Director of Urologic Research at the Brady Urological Research Institute, which inspired new research ideas, team science, and discovery.

Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect

OpenAIRE

Oikemus, Sarah R.; McGinnis, Nadine; Queiroz-Machado, Joana; Tukachinsky, Hanna; Takada, Saeko; Sunkel, Claudio E.; Brodsky, Michael H.

2004-01-01

Terminal deletions of Drosophila chromosomes can be stably protected from end-to-end fusion despite the absence of all telomere-associated sequences. The sequence-independent protection of these telomeres suggests that recognition of chromosome ends might contribute to the epigenetic protection of telomeres. In mammals, Ataxia Telangiectasia Mutated (ATM) is activated by DNA damage and acts through an unknown, telomerase-independent mechanism to regulate telomere length and protection. We dem...

Acculturation Predicts Negative Affect and Shortened Telomere Length.

Science.gov (United States)

Ruiz, R Jeanne; Trzeciakowski, Jerome; Moore, Tiffany; Ayers, Kimberly S; Pickler, Rita H

2016-10-12

Chronic stress may accelerate cellular aging. Telomeres, protective "caps" at the end of chromosomes, modulate cellular aging and may be good biomarkers for the effects of chronic stress, including that associated with acculturation. The purpose of this analysis was to examine telomere length (TL) in acculturating Hispanic Mexican American women and to determine the associations among TL, acculturation, and psychological factors. As part of a larger cross-sectional study of 516 pregnant Hispanic Mexican American women, we analyzed DNA in blood samples (N = 56) collected at 22-24 weeks gestation for TL as an exploratory measure using monochrome multiplex quantitative telomere polymerase chain reaction (PCR). We measured acculturation with the Acculturation Rating Scale for Mexican Americans, depression with the Beck Depression Inventory, discrimination with the Experiences of Discrimination Scale, and stress with the Perceived Stress Scale. TL was negatively moderately correlated with two variables of acculturation: Anglo orientation and greater acculturation-level scores. We combined these scores for a latent variable, acculturation, and we combined depression, stress, and discrimination scores in another latent variable, "negative affectivity." Acculturation and negative affectivity were bidirectionally correlated. Acculturation significantly negatively predicted TL. Using structural equation modeling, we found the model had an excellent fit with the root mean square error of approximation estimate = .0001, comparative fit index = 1.0, Tucker-Lewis index = 1.0, and standardized root mean square residual = .05. The negative effects of acculturation on the health of Hispanic women have been previously demonstrated. Findings from this analysis suggest a link between acculturation and TL, which may indicate accelerated cellular aging associated with overall poor health outcomes. © The Author(s) 2016.

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...

Exposure to inorganic arsenic is associated with increased mitochondrial DNA copy number and longer telomere length in peripheral blood.

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Syeda Shegufta Ameer

2016-08-01

Full Text Available Background: Exposure to inorganic arsenic (iAs through drinking water causes cancer. Alterations in mitochondrial DNA copy number (mtDNAcn and telomere length in blood have been associated with cancer risk. We elucidated if arsenic exposure alters mtDNAcn and telomere length in individuals with different arsenic metabolizing capacity.Methods: We studied two groups in the Salta province, Argentina, one in the Puna area of the Andes (N=264, 89% females and one in Chaco (N=169, 75% females. We assessed arsenic exposure as the sum of arsenic metabolites [iAs, methylarsonic acid (MMA, dimethylarsinic acid (DMA] in urine (U-As using high-performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry. Efficiency of arsenic metabolism was expressed as percentage of urinary metabolites. MtDNAcn and telomere length were determined in blood by real-time PCR. Results: Median U-As was 196 (5 - 95 percentile: 21 - 537 µg/L in Andes and 80 (5 - 95 percentile: 15 - 1637 µg/L in Chaco. The latter study group had less-efficient metabolism, with higher %iAs and %MMA in urine compared with the Andean group. U-As was significantly associated with increased mtDNAcn (log2 transformed to improve linearity in Chaco (β=0.027 per 100 µg/L, p=0.0085; adjusted for age and sex, but not in Andes (β=0.025, p=0.24. U-As was also associated with longer telomere length in Chaco (β=0.016, p=0.0066 and Andes (β=0.0075, p=0.029. In both populations, individuals with above median %iAs showed significantly higher mtDNAcn and telomere length compared with individuals with below median %iAs. Conclusions: Arsenic was associated with increased mtDNAcn and telomere length, particularly in individuals with less-efficient arsenic metabolism, a group who may have increased risk for arsenic-related cancer.

Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation.

Science.gov (United States)

Witsenburg, C P J; Rosendaal, F R; Middeldorp, J M; Van der Meer, F J M; Scherjon, S A

2005-01-01

Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

OpenAIRE

Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

2014-01-01

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequentl...

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.

Polimorfismos genéticos do fator de crescimento do endotélio vascular na pré-eclâmpsia Genetic polymorphisms of vascular endothelial growth factor in pre-eclampsia

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Valquiria Maria de Paula Cunha

2011-07-01

with specific primers and polymorphism analysis of Restriction Fragment Length Polymorphism (RFLP were performed to identify polymorphisms. The statistical analysis was performedin a descriptive manner and using the test. The multiple logistic regression model was used to determine the effect of polymorphisms on pre-eclampsia. RESULTS:Ahigher frequency of the T allele of theVEGF +936C/T polymorphism was observedin patients with pre-eclampsia, but with no significant difference. The presence of allele A of the VEGF -2578C/A was significantly higher in the control group. CONCLUSIONS:No significant association was observed between VEGF +936C/Tpolymorphism andpre-eclampsia. For the VEGF -2578C/A polymorphism a significant differencewas observed between thecontrol and pre-eclampsia group, with allele A being the most frequent in the control, suggesting the possibility that carriers of allele A have lower susceptibility to the development of pre-eclampsia.

Low-molecular-weight heparin and aspirin in the prevention of recurrent early-onset pre-eclampsia in women with antiphospholipid antibodies : the FRUIT-RCT

NARCIS (Netherlands)

van Hoorn, Marion E.; Hague, William M.; Pampus , van Mariëlle G.; Bezemer, Dick; de Vries, Johanna I. P.

Objective: To examine whether combined treatment with low-molecular-weight heparin (LMWH) and aspirin reduces recurrent hypertensive disorders of pregnancy (HD: pre-eclampsia, eclampsia or HELLP syndrome) in women with antiphospholipid antibodies (aPLA) and a previous delivery for HD and/or

Physical activity and telomere length in U.S. men and women: An NHANES investigation.

Science.gov (United States)

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, Pactivity and those in the Sedentary, Low, and Moderate groups were 140, 137, and 111, respectively. Adults with High activity were estimated to have a biologic aging advantage of 9years (140 base pairs÷15.6) over Sedentary adults. The difference in cell aging between those with High and Low activity was also significant, 8.8years, as was the difference between those with High and Moderate PA (7.1years). Overall, PA was significantly and meaningfully associated with telomere length in U.S. men and women. Evidently, adults who participate in high levels of PA tend to have longer telomeres, accounting for years of reduced cellular aging compared to their more sedentary counterparts. Copyright © 2017 Elsevier Inc. All rights reserved.

Short telomere length is associated with impaired cognitive performance in European ancestry cohorts

NARCIS (Netherlands)

Hägg, S.; Zhan, Y.; Karlsson, Robert; Gerritsen, L.; Ploner, A.; Lee, J.S.; Broer, L.; Deelen, J.; Marioni, R.E.; Wong, A.|info:eu-repo/dai/nl/29867291X; Lundquist, A.; Zhu, G.; Hansell, N.K.; Sillanpää, E.; Fedko, I O; Amin, N.A.; Beekman, Jeffrey M.; de Craen, A.J.M.; Degerman, S.; Harris, S.E.; Kan, K.-J.; Martin-Ruiz, C.M.; Montgomery, Grant W.; Adolfsson, A.N.; Reynolds, Chandra A.; Samani, Nilesh J; Suchiman, H.E.D.; Viljanen, A.; Von Zglinicki, T.; Wright, M J; Hottenga, J.J.; Boomsma, Dorret I; Rantanen, T.; Kaprio, J.A.; Nyholt, D.R.; Martin, N.G.|info:eu-repo/dai/nl/314123083; Nyberg, Lars; Adolfsson, R.; Kuh, D.; Starr, John M; Deary, Ian J; Slagboom, P Eline; Van Duijn, C.M.|info:eu-repo/dai/nl/068368232; Codd, V.; Pedersen, Nancy L.

2017-01-01

The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR)

Cost effectiveness of medical devices to diagnose pre-eclampsia in low-resource settings

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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

The power of exercise: buffering the effect of chronic stress on telomere length.

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Eli Puterman

2010-05-01

Full Text Available 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. However, not all people under stress have distinctly short telomeres, and we examined whether exercise can serve a stress-buffering function. We predicted that chronic stress would be related to short telomere length (TL in sedentary individuals, whereas in those who exercise, stress would not have measurable effects on telomere shortening.63 healthy post-menopausal women underwent a fasting morning blood draw for whole blood TL analysis by a quantitative polymerase chain reaction method. Participants completed the Perceived Stress Scale (Cohen et al., 1983, and for three successive days reported daily minutes of vigorous activity. Participants were categorized into two groups-sedentary and active (those getting Centers for Disease Control-recommended daily amount of activity. The likelihood of having short versus long telomeres was calculated as a function of stress and exercise group, covarying age, BMI and education. Logistic regression analyses revealed a significant moderating effect of exercise. As predicted, among non-exercisers a one unit increase in the Perceived Stress Scale was related to a 15-fold increase in the odds of having short telomeres (p<.05, whereas in exercisers, perceived stress appears to be unrelated to TL (B = -.59, SE = .78, p = .45.Vigorous physical activity appears to protect those experiencing high stress by buffering its relationship with TL. We propose pathways through which physical activity acts to buffer stress effects.

Telomeric repeat factor 1 protein levels correlates with telomere length in colorectal cancer Los niveles proteicos del factor de repetición telomérico 1 se correlacionan con la longitud del telómero en el cáncer colorrectal

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Cristina Valls-Bautista

2012-11-01

Full Text Available Background: colorectal cancer is the third cancer cause of death in Spain. It is important to investigate new tumoral markers for early diagnosis, disease monitoring and prevention strategies. Telomeres protect the chromosome from degradation by nucleases and end-to-end fusion. The progressive loss of the telomeric ends of chromosomes is an important mechanism in the timing of human cellular aging. Telomeric Repeat Factor 1 (TRF1 is a protein that binds at telomere ends. Purpose: to measure the concentrations of TRF1 and the relationships among telomere length, telomerase activity, and TRF1 levels in tumor and normal colorectal mucosa. Method: from normal and tumoral samples of 83 patients who underwent surgery for colorectal cancer we analyzed TRF1 protein concentration by Western Blot, telomerase activity, by the fluorescent-telomeric repeat amplification protocol assay and telomere length by Southern Blot. Results: high levels of TRF1 were observed in 68.7% of tumor samples, while the majority of normal samples (59% showed negative or weak TRF1 concentrations. Among the tumor samples, telomere length was significantly associated with TRF1 protein levels (p = 0.023. Conclusions: a relationship was found between telomere length and TRF1 abundance protein in tumor samples, which means that TRF1 is an important factor in the tumor progression and maybe a diagnostic factor.

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

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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.

Quantitative fluorescence in situ hybridization measurement of telomere length in skin with/without sun exposure or actinic keratosis.

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Ikeda, Hiroyuki; Aida, Junko; Hatamochi, Atsushi; Hamasaki, Yoichiro; Izumiyama-Shimomura, Naotaka; Nakamura, Ken-Ichi; Ishikawa, Naoshi; Poon, Steven S; Fujiwara, Mutsunori; Tomita, Ken-Ichiro; Hiraishi, Naoki; Kuroiwa, Mie; Matsuura, Masaaki; Sanada, Yukihiro; Kawano, Youichi; Arai, Tomio; Takubo, Kaiyo

2014-03-01

Chromosomal and genomic instability due to telomere dysfunction is known to play an important role in carcinogenesis. To study telomere shortening in the epidermis surrounding actinic keratosis, we measured telomere lengths of basal, parabasal, and suprabasal cells in epidermis with actinic keratosis (actinic keratosis group, n = 18) and without actinic keratosis (sun-protected, n = 15, and sun-exposed, n = 13 groups) and in actinic keratosis itself as well as in dermal fibroblasts in the 3 groups, using quantitative fluorescence in situ hybridization. Among the 3 cell types, telomeres of basal cells were not always the longest, suggesting that tissue stem cells are not necessarily located among basal cells. Telomeres of basal cells in the sun-exposed group were shorter than those in the sun-protected group. Telomeres in the background of actinic keratosis and in actinic keratosis itself and those of fibroblasts in actinic keratosis were significantly shorter than those in the controls. Our findings demonstrate that sun exposure induces telomere shortening and that actinic keratosis arises from epidermis with shorter telomeres despite the absence of any histologic atypia. © 2014.

Tocotrienol-Rich Fraction Prevents Cell Cycle Arrest and Elongates Telomere Length in Senescent Human Diploid Fibroblasts

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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.

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

NARCIS (Netherlands)

Codd, V.; Nelson, C.P.; Albrecht, E.; Mangino, M.; Deelen, J.; Buxton, J.L.; Hottenga, J.J.; Fischer, K.; Esko, T.; Surakka, I.; Broer, L.; Nyholt, DR; Mateo Leach, I.; Salo, P.; Hägg, S.; Matthews, M.K.; Palmen, J.; Norata, G.D.; O'Reilly, P.F.; Saleheen, D.; Amin, N.; Balmforth, A.J.; Beekman, M.; de Boer, R.A.; Böhringer, S.; Braund, P.S.; Burton, P.R.; de Craen, A.J.; Denniff, M.; Dong, Y.; Douroudis, K.; Dubinina, E.; Eriksson, J.G.; Garlaschelli, K.; Guo, D.; Hartikainen, A.L.; Henders, A.K.; Houwing-Duistermaat, J.J.; Kananen, L.; Karssen, L.C.; Kettunen, J.; Klopp, N.; Lagou, V.; van Leeuwen, E.; Madden, P.A.; Mägi, R.; Magnusson, P.K.E.; Männistö, S.; McCarthy, M.I.; Medland, S.E.; Mihailov, E.; Montgomery, G.W.; Oostra, B.A.; Palotie, A.; Peters, A.; Pollard, H.; Pouta, A.; Prokopenko, I.; Ripatti, S.; Salomaa, V.; Suchiman, H.E.D.; Valdes, A.M.; Verweij, N.; Viñuela, A.; Wang, X.; Wichmann, H. E.; Widen, E.; Willemsen, G.; Wright, M.J.; Xia, K.; Xiao, X.; van Veldhuisen, D.J.; Catapano, A.L.; Tobin, M.D.; Hall, A.S.; Blakemore, A.I.F.; van Gilst, W.H.; Zhu, H.; Erdmann, J.; Reilly, M.P.; Kathiresan, S.; Schunkert, H.; Talmud, P.J.; Pedersen, N.L.; Perola, M.; Ouwehand, W.; Kaprio, J.; Martin, N.G.; van Duijn, C.M.; Hovatta, I.; Gieger, C.; Metspalu, A.; Boomsma, D.I.; Järvelin, M.R.; Slagboom, P.E.; Thompson, J.R.; Spector, T.D.; van der Harst, P.; Samani, N.J.

2013-01-01

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,

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; Verweij, Niek; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; van der Harst, Pim

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,

Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect.

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Oikemus, Sarah R; McGinnis, Nadine; Queiroz-Machado, Joana; Tukachinsky, Hanna; Takada, Saeko; Sunkel, Claudio E; Brodsky, Michael H

2004-08-01

Terminal deletions of Drosophila chromosomes can be stably protected from end-to-end fusion despite the absence of all telomere-associated sequences. The sequence-independent protection of these telomeres suggests that recognition of chromosome ends might contribute to the epigenetic protection of telomeres. In mammals, Ataxia Telangiectasia Mutated (ATM) is activated by DNA damage and acts through an unknown, telomerase-independent mechanism to regulate telomere length and protection. We demonstrate that the Drosophila homolog of ATM is encoded by the telomere fusion (tefu) gene. In the absence of ATM, telomere fusions occur even though telomere-specific Het-A sequences are still present. High levels of spontaneous apoptosis are observed in ATM-deficient tissues, indicating that telomere dysfunction induces apoptosis in Drosophila. Suppression of this apoptosis by p53 mutations suggests that loss of ATM activates apoptosis through a DNA damage-response mechanism. Loss of ATM reduces the levels of heterochromatin protein 1 (HP1) at telomeres and suppresses telomere position effect. We propose that recognition of chromosome ends by ATM prevents telomere fusion and apoptosis by recruiting chromatin-modifying complexes to telomeres.

Population-based estimate of sibling risk for preterm birth, preterm premature rupture of membranes, placental abruption and pre-eclampsia.

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Plunkett, Jevon; Borecki, Ingrid; Morgan, Thomas; Stamilio, David; Muglia, Louis J

2008-07-08

Adverse pregnancy outcomes, such as preterm birth, preeclampsia and placental abruption, are common, with acute and long-term complications for both the mother and infant. Etiologies underlying such adverse outcomes are not well understood. As maternal and fetal genetic factors may influence these outcomes, we estimated the magnitude of familial aggregation as one index of possible heritable contributions. Using the Missouri Department of Health's maternally-linked birth certificate database, we performed a retrospective population-based cohort study of births (1989-1997), designating an individual born from an affected pregnancy as the proband for each outcome studied. We estimated the increased risk to siblings compared to the population risk, using the sibling risk ratio, lambdas, and sibling-sibling odds ratio (sib-sib OR), for the adverse pregnancy outcomes of preterm birth, preterm premature rupture of membranes (PPROM), placental abruption, and pre-eclampsia. Risk to siblings of an affected individual was elevated above the population prevalence of a given disorder, as indicated by lambdaS (lambdaS (95% CI): 4.3 (4.0-4.6), 8.2 (6.5-9.9), 4.0 (2.6-5.3), and 4.5 (4.4-4.8), for preterm birth, PPROM, placental abruption, and pre-eclampsia, respectively). Risk to siblings of an affected individual was similarly elevated above that of siblings of unaffected individuals, as indicated by the sib-sib OR (sib-sib OR adjusted for known risk factors (95% CI): 4.2 (3.9-4.5), 9.6 (7.6-12.2), 3.8 (2.6-5.5), 8.1 (7.5-8.8) for preterm birth, PPROM, placental abruption, and pre-eclampsia, respectively). These results suggest that the adverse pregnancy outcomes of preterm birth, PPROM, placental abruption, and pre-eclampsia aggregate in families, which may be explained in part by genetics.

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout.

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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, R 2 =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/.

A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes

DEFF Research Database (Denmark)

Ringholm, L; Pedersen-Bjergaard, U; Thorsteinsson, B

2011-01-01

consecutive pregnant women with type 1 diabetes (median duration 16 years [range 1-36 years], HbA(1c) 6.6% [range 4.9-10.5%]) in early pregnancy. At 8, 14, 21, 27 and 33 weeks and once within 5 days postpartum, blood was sampled for measurements of prorenin, renin, angiotensinogen, ACE and SSAO. HbA(1c...... 4.4 [95% CI 1.5-13.0], p¿=¿0.007), i.e. an increase of prorenin of 100 ng angiotensin I ml(-1) h(-1) implies a 4.4 times higher risk of subsequent pre-eclampsia. CONCLUSIONS/INTERPRETATION: In type 1 diabetic women with pre-eclampsia, a higher concentration of prorenin in early pregnancy and higher......AIMS/HYPOTHESIS: The aim of this study was to investigate whether components of the renin-angiotensin system and semicarbazide-sensitive amine oxidase (SSAO) are associated with the development of pre-eclampsia in women with type 1 diabetes. METHODS: This was an observational study of 107...

Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence.

Science.gov (United States)

Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

2015-01-01

Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I.

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

Placental Growth Factor (PlGF in Women with Suspected Pre-Eclampsia Prior to 35 Weeks' Gestation: A Budget Impact Analysis.

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Suzy Duckworth

Full Text Available To model the resource implications of placental growth factor (PlGF testing in women with suspected pre-eclampsia prior to 35 weeks' gestation as part of a management algorithm, compared with current practice.Data on resource use from 132 women with suspected pre-eclampsia prior to 35 weeks' gestation, enrolled in a prospective observational cohort study evaluating PlGF measurement within antenatal assessment units within two UK consultant-led maternity units was extracted by case note review. A decision analytic model was developed using these data to establish the budget impact of managing women with suspected pre-eclampsia for two weeks from the date of PlGF testing, using a clinical management algorithm and reference cost tariffs. The main outcome measures of resource use (numbers of outpatient appointments, ultrasound investigations and hospital admissions were correlated to final diagnosis and used to calculate comparative management regimes.The mean cost saving associated with the PlGF test (in the PlGF plus management arm was £35,087 (95% CI -£33,181 to -£36,992 per 1,000 women. This equated to a saving of £582 (95% CI -552 to -£613 per woman tested. In 94% of iterations, PlGF testing was associated with cost saving compared to current practice.This analysis suggests PlGF used as part of a clinical management algorithm in women presenting with suspected pre-eclampsia prior to 35 weeks' gestation could provide cost savings by reducing unnecessary resource use. Introduction of PlGF testing could be used to direct appropriate resource allocation and overall would be cost saving.

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

Telomere Length in Peripheral Blood Leukocytes Is Associated with Severity of Biliary Atresia.

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Wanvisa Udomsinprasert

Full Text Available The purpose of this study was to investigate the association of telomere length in peripheral blood leukocytes with the severity of biliary atresia (BA.One hundred and fourteen BA patients and 114 age-matched healthy controls were enrolled. Relative telomere length (RTL was assessed using a quantitative real-time polymerase chain reaction. Multivariate regression analysis was used to estimate RTL as an independent risk factor of BA. Receiver operating characteristic curve analysis was used to calculate the accuracy of biomarkers in the prediction of liver cirrhosis.BA patients had significantly shorter telomeres than healthy controls (p < 0.0001. The RTL in BA patients with jaundice was considerably lower than that of patients without jaundice (p = 0.005. Moreover, RTL was markedly shorter in patients with cirrhosis (F4, as compared to patients with mild fibrosis (F2 and non-fibrosis (F0-F1, p < 0.0001. Logistic regression analysis indicated that short RTL was associated with a higher risk of liver cirrhosis in BA. Tertile analysis showed a dose-response effect for this association (p trend < 0.0001. Additionally, RTL in BA children revealed a negative correlation with age (r = -0.50, p < 0.001. We noted an association between reduction of RTL and liver stiffness scores, adjusted for age and gender (b = -0.01, p < 0.0001. Short RTL can be employed to distinguish cirrhosis patients from non-cirrhosis patients (AUC = 0.78. Further analysis showed a linear correlation between leukocyte RTL and liver RTL in BA patients (r = 0.83, p < 0.001.The findings of this study provide evidence that telomere shortening is associated with an elevated risk of liver cirrhosis in BA.

Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

Science.gov (United States)

Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

2016-04-07

Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. © 2016 by The American Society of Hematology.

Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence.

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Ryusaku Matsumoto

Full Text Available Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases.We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts.Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047. In addition, telomere length in acromegaly was negatively correlated with the disease duration (R2 = 0.210, P = 0.003. In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence.Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I.

Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence

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Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

2015-01-01

Objective Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. Methods We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Results Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R 2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Conclusion Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I. PMID:26448623

Sexual differences in telomere selection in the wild.

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Olsson, Mats; Pauliny, Angela; Wapstra, Erik; Uller, Tobias; Schwartz, Tonia; Miller, Emily; Blomqvist, Donald

2011-05-01

Telomere length is restored primarily through the action of the reverse transcriptase telomerase, which may contribute to a prolonged lifespan in some but not all species and may result in longer telomeres in one sex than the other. To what extent this is an effect of proximate mechanisms (e.g. higher stress in males, higher oestradiol/oestrogen levels in females), or is an evolved adaptation (stronger selection for telomere length in one sex), usually remains unknown. Sand lizard (Lacerta agilis) females have longer telomeres than males and better maintain telomere length through life than males do. We also show that telomere length more strongly contributes to life span and lifetime reproductive success in females than males and that telomere length is under sexually diversifying selection in the wild. Finally, we performed a selection analysis with number of recruited offspring into the adult population as a response variable with telomere length, life span and body size as predictor variables. This showed significant differences in selection pressures between the sexes with strong ongoing selection in females, with these three predictors explaining 63% of the variation in recruitment. Thus, the sexually dimorphic telomere dynamics with longer telomeres in females is a result of past and ongoing selection in sand lizards. Finally, we compared the results from our selection analyses based on Telometric-derived data to the results based on data generated by the software ImageJ. ImageJ resulted in shorter average telomere length, but this difference had virtually no qualitative effect on the patterns of ongoing selection. © 2011 Blackwell Publishing Ltd.

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

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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...

Salinity in Drinking Water and the Risk of (Pre)Eclampsia and Gestational Hypertension in Coastal Bangladesh: A Case-Control Study

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Khan, Aneire Ehmar; Scheelbeek, Pauline Franka Denise; Shilpi, Asma Begum; Chan, Queenie; Mojumder, Sontosh Kumar; Rahman, Atiq; Haines, Andy; Vineis, Paolo

2014-01-01

Background Hypertensive disorders in pregnancy are among the leading causes of maternal and perinatal death in low-income countries, but the aetiology remains unclear. We investigated the relationship between salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in a coastal community. Methods A population-based case-control study was conducted in Dacope, Bangladesh among 202 pregnant women with (pre)eclampsia or gestational hypertension, enrolled from the community served by the Upazilla Health Complex, Dacope and 1,006 matched controls from the same area. Epidemiological and clinical data were obtained from all participants. Urinary sodium and sodium levels in drinking water were measured. Logistic regression was used to calculate odds ratios, and 95% confidence intervals. Findings Drinking water sources had exceptionally high sodium levels (mean 516.6 mg/L, S.D 524.2). Women consuming tube-well (groundwater) were at a higher disease risk than rainwater users (psodium concentrations (300.01–600 mg/L, 600.1–900 mg/L, >900.01 mg/L, compared to <300 mg/L) in drinking water (ORs 3.30 [95% CI 2.00–5.51], 4.40 [2.70–7.25] and 5.48 [3.30–9.11] (p-trend<0.001). Significant associations were seen for both (pre)eclampsia and gestational hypertension separately. Interpretation Salinity in drinking water is associated with increased risk of (pre)eclampsia and gestational hypertension in this population. Given that coastal populations in countries such as Bangladesh are confronted with high salinity exposure, which is predicted to further increase as a result of sea level rise and other environmental influences, it is imperative to develop and evaluate affordable approaches to providing water with low salt content. PMID:25268785

Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia.

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Morgan, L; Crawshaw, S; Baker, P N; Brookfield, J F; Broughton Pipkin, F; Kalsheker, N

1998-01-01

OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region. RESULTS: Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission. CONCLUSION: Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion. PMID:9719367

Early Hits and Long-Term Consequences: Tracking the Lasting Impact of Prenatal Smoke Exposure on Telomere Length in Children

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McKasson, Sarah; Mabile, Emily; Dunaway, Lauren F.; Drury, Stacy S.

2013-01-01

We examined the association between telomere length and prenatal tobacco exposure (PTE) in 104 children aged 4 to 14 years. Salivary telomere length (STL) was determined from salivary DNA using quantitative polymerase chain reaction. Of the children, 18% had maternal reported PTE. Mean STL was significantly lower among children with PTE (6.4 vs 7.5, P < .05). Findings extend the literature demonstrating the negative long-term effects of PTE to include a cellular marker of aging linked to multiple negative health outcomes. PMID:23927510

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

Telomere length differences between subcutaneous and visceral adipose tissue in humans

International Nuclear Information System (INIS)

Lakowa, Nicole; Trieu, Nhu; Flehmig, Gesine; Lohmann, Tobias; Schön, Michael R.; Dietrich, Arne; Zeplin, Philip Helge; Langer, Stefan; Stumvoll, Michael; Blüher, Matthias; Klöting, Nora

2015-01-01

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

Risky family processes prospectively forecast shorter telomere length mediated through negative emotions.

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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).

Fetal sex-specific differences in gestational age at delivery in pre-eclampsia

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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...... fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59). Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences...

Deoxyribonucleic acid telomere length shortening can predict the incidence of non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus.

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Ping, Fan; Li, Zeng-Yi; Lv, Ke; Zhou, Mei-Cen; Dong, Ya-Xiu; Sun, Qi; Li, Yu-Xiu

2017-03-01

To investigate the effect of telomere shortening and other predictive factors of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus patients in a 6-year prospective cohort study. A total of 70 type 2 diabetes mellitus (mean age 57.8 ± 6.7 years) patients without NAFLD were included in the study, and 64 of them were successfully followed up 6 years later, excluding four cases with significant alcohol consumption. NAFLD was diagnosed by the hepatorenal ratio obtained by a quantitative ultrasound method using NIH image analysis software. The 39 individuals that developed NAFLD were allocated to group A, and the 21 individuals that did not develop NAFLD were allocated to group B. Fluorescent real-time quantitative polymerase chain reaction was used to measure telomere length. There was no significant difference between the two groups in baseline telomere length; however, at the end of the 6th year, telomere length had become shorter in group A compared with group B. There were significant differences between these two groups in baseline body mass index, waistline, systolic blood pressure, glycated hemoglobin and fasting C-peptide level. In addition, the estimated indices of baseline insulin resistance increased in group A. Fasting insulin level, body mass index, systolic blood pressure at baseline and the shortening of telomere length were independent risk factors of NAFLD in type 2 diabetes mellitus patients. Telomere length became shorter in type 2 diabetes mellitus patients who developed NAFLD over the course of 6 years. Type 2 diabetes mellitus patients who developed NAFLD had more serious insulin resistance compared with those who did not develop NAFLD a long time ago. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Ancestral telomere shortening: a countdown that will increase mean life span?

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Hertzog, Radu G

2006-01-01

Like cells, all mammals have a limited life span. Among cells there are a few exceptions (e.g., immortal cells), among mammals not, even if some of them live longer. Many in vitro and in vivo studies support the consensus that telomere length is strongly correlated with life span. At the somatic cellular level, long telomeres have been associated with longer life span. A different situation can be seen in immortal cells, such as cancer, germ and stem cells, where telomeres are maintained by telomerase, a specialized reverse transcriptase that is involved in synthesis of telomeres. Irrespective of telomere length, if telomerase is active, telomeres can be maintained at a sufficient length to ensure cell survival. To the contrary, telomeres shorten progressively with each cell division and when a critical telomere length (Hayflick limit) is reached, the cells undergo senescence and subsequently apoptosis. In mammals, those with the longest telomeres (e.g., mice) have the shortest life span. Furthermore, the shorter the mean telomere length, the longer the mean life span, as observed in humans (10-14 kpb) and bowhead-whales (undetermined telomere length), which have the longest mean life span among mammals. Over the past centuries, human average life span has increased. The hypothesis presented here suggests that this continual increase in the mean life span could be due to a decrease of mean telomere length over the last hundreds years. Actually, the life span is not directly influenced by length of telomeres, but rather by telomere length - dependent gene expression pattern. According to Greider, "rather than average telomere length, it is the shortest telomere length that makes the biggest difference to a cell". In the context of fast-growing global elderly population due to increase in life expectancy, it also seem to be an age related increase in cancer incidence. Nevertheless, extending healthy life span could depend on how good cells achieve, during the

Comparison of telomere length and association with progenitor cell markers in lacrimal gland between Sjögren syndrome and non-Sjögren syndrome dry eye patients.

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Kawashima, Motoko; Kawakita, Tetsuya; Maida, Yoshiko; Kamoi, Mizuka; Ogawa, Yoko; Shimmura, Shigeto; Masutomi, Kenkichi; Tsubota, Kazuo

2011-01-01

Indicators of aging such as disruption of telomeric function due to shortening may be more frequent in dysfunctional lacrimal gland. The aims of this study were to 1) determine the viability of quantitative fluorescence in situ hybridization of telomeres (telo-FISH) for the assessment of telomere length in lacrimal gland in Sjögren and non- Sjögren syndrome patients; and 2) investigate the relationship between progenitor cell markers and telomere length in both groups. Quantitative fluorescence in situ hybridization with a peptide nucleic acid probe complementary to the telomere repeat sequence was performed on frozen sections from human lacrimal gland tissues. The mean fluorescence intensity of telomere spots was automatically quantified by image analysis as relative telomere length in lacrimal gland epithelial cells. Immunostaining for p63, nucleostemin, ATP-binding cassette, sub-family G, member 2 (ABCG2), and nestin was also performed. Telomere intensity in the Sjögren syndrome group (6,785.0±455) was significantly lower than that in the non-Sjögren syndrome group (7,494.7±477; p=0.02). Among the samples from the non-Sjögren syndrome group, immunostaining revealed that p63 was expressed in 1-3 acinar cells in each acinar unit and continuously in the basal layer of duct cells. In contrast, in the Sjögren syndrome group, p63 and nucleostemin showed a lower level of expression. ABCG2 was expressed in acinar cells in both sjogren and non-Sjogren syndrome. The results of this study indicate that 1) telo-FISH is a viable method of assessing telomere length in lacrimal gland, and 2) telomere length in Sjögren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjögren syndrome.

Economic evaluation of Community Level Interventions for Pre-eclampsia (CLIP) in South Asian and African countries: a study protocol.

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Khowaja, Asif R; Mitton, Craig; Bryan, Stirling; Magee, Laura A; Bhutta, Zulfiqar A; von Dadelszen, Peter

2015-05-26

Globally, hypertensive disorders of pregnancy, particularly pre-eclampsia and eclampsia, are the leading cause of maternal and neonatal mortality, and impose substantial burdens on the families of pregnant women, their communities, and healthcare systems. The Community Level Interventions for Pre-eclampsia (CLIP) Trial evaluates a package of care applied at both community and primary health centres to reduce maternal and perinatal disabilities and deaths resulting from the failure to identify and manage pre-eclampsia at the community level. Economic evaluation of health interventions can play a pivotal role in priority setting and inform policy decisions for scale-up. At present, there is a paucity of published literature on the methodology of economic evaluation of large, multi-country, community-based interventions in the area of maternal and perinatal health. This study protocol describes the application of methodology for economic evaluation of the CLIP in South Asia and Africa. A mixed-design approach i.e. cost-effectiveness analysis (CEA) and qualitative thematic analysis will be used alongside the trial to prospectively evaluate the economic impact of CLIP from a societal perspective. Data on health resource utilization, costs, and pregnancy outcomes will be collected through structured questionnaires embedded into the pregnancy surveillance, cross-sectional survey and budgetary reviews. Qualitative data will be collected through focus groups (FGs) with pregnant women, household male-decision makers, care providers, and district level health decision makers. The incremental cost-effectiveness ratio will be calculated for healthcare system and societal perspectives, taking into account the country-specific model inputs (costs and outcome) from the CLIP Trial. Emerging themes from FGs will inform the design of the model, and help to interpret findings of the CEA. The World Health Organization (WHO) strongly recommends cost-effective interventions as a key

Direct comparison of flow-FISH and qPCR as diagnostic tests for telomere length measurement in humans.

Directory of Open Access Journals (Sweden)

Fernanda Gutierrez-Rodrigues

Full Text Available Telomere length measurement is an essential test for the diagnosis of telomeropathies, which are caused by excessive telomere erosion. Commonly used methods are terminal restriction fragment (TRF analysis by Southern blot, fluorescence in situ hybridization coupled with flow cytometry (flow-FISH, and quantitative PCR (qPCR. Although these methods have been used in the clinic, they have not been comprehensively compared. Here, we directly compared the performance of flow-FISH and qPCR to measure leukocytes' telomere length of healthy individuals and patients evaluated for telomeropathies, using TRF as standard. TRF and flow-FISH showed good agreement and correlation in the analysis of healthy subjects (R(2 = 0.60; p<0.0001 and patients (R(2 = 0.51; p<0.0001. In contrast, the comparison between TRF and qPCR yielded modest correlation for the analysis of samples of healthy individuals (R(2 = 0.35; p<0.0001 and low correlation for patients (R(2 = 0.20; p = 0.001; Bland-Altman analysis showed poor agreement between the two methods for both patients and controls. Quantitative PCR and flow-FISH modestly correlated in the analysis of healthy individuals (R(2 = 0.33; p<0.0001 and did not correlate in the comparison of patients' samples (R(2 = 0.1, p = 0.08. Intra-assay coefficient of variation (CV was similar for flow-FISH (10.8 ± 7.1% and qPCR (9.5 ± 7.4%; p = 0.35, but the inter-assay CV was lower for flow-FISH (9.6 ± 7.6% vs. 16 ± 19.5%; p = 0.02. Bland-Altman analysis indicated that flow-FISH was more precise and reproducible than qPCR. Flow-FISH and qPCR were sensitive (both 100% and specific (93% and 89%, respectively to distinguish very short telomeres. However, qPCR sensitivity (40% and specificity (63% to detect telomeres below the tenth percentile were lower compared to flow-FISH (80% sensitivity and 85% specificity. In the clinical setting, flow-FISH was more accurate, reproducible, sensitive, and specific in the measurement of human

Placental telomere shortening in stillbirth: a sign of premature senescence?

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Ferrari, Francesca; Facchinetti, Fabio; Saade, George; Menon, Ramkumar

2016-01-01

The objective of this study is to investigate placental telomere shortening in unexplained stillbirths (SBs) as an indication of premature senescence. Placentas were collected from 42 unexplained SB (>22 weeks), 43 term and 15 preterm live births, at the Policlinico Hospital of Modena (Italy). DNA extracted from placentae was studied for telomere length by real time PCR. Standard curves were generated for telomere lengths from single copy gene amplifications using a reference DNA. The telomere length for each sample was derived based on the ratio of telomere length between the sample and single copy gene standard (T/S ratio). The mean ratio of placental telomere in term live births was 5.181 ± 3.841. A twofold decrease in telomere length was seen in SBs (over all 2.455 ± 1.239; p PTBs) (6.382 ± 5.525; p < 0.01), whereas SBs telomere length were similar to those of preterm premature rupture of membranes (pPROM) (3.296 ± 3.599; p = ns). Substantial reduction in telomere length in SBs is indicative of placental senescence. These data provide mechanistic insights that premature aging may lead to placental dysfunction as an initiator of fetal demise in unexplained SBs.

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; 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

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...

Telomere stability and telomerase in mesenchymal stem cells

DEFF Research Database (Denmark)

Serakinci, Nedime; Graakjaer, Jesper; Kølvrå, Steen

2008-01-01

Telomeres are repetitive genetic material that cap and thereby protect the ends of chromosomes. Each time a cell divides, telomeres get shorter. Telomere length is mainly maintained by telomerase. This enzyme is present in high concentrations in the embryonic stem cells and in fast growing...... embryonic cells, and declines with age. It is still unclear to what extent there is telomerase in adult stem cells, but since these are the founder cells of cells of all the tissues in the body, understanding the telomere dynamics and expression of telomerase in adult stem cells is very important....... In the present communication we focus on telomere expression and telomere length in stem cells, with a special focus on mesenchymal stem cells. We consider different mechanisms by which stem cells can maintain telomeres and also focus on the dynamics of telomere length in mesenchymal stem cells, both the overall...

Evaluación de la globulina transportadora de hormonas esteroidales (SHBG) durante el embarazo como factor predictor de pre-eclampsia y restricción del crecimiento intrauterino

OpenAIRE

Valdés R,Enrique; Lattes A,Karina; Muñoz S,Hernán; Ángel Cumsille,Miguel

2012-01-01

Background: Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). Aim: To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Patients and Methods: Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselectedpregnant wome...

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.

A colorimetric platform for sensitively differentiating telomere DNA with different lengths, monitoring G-quadruplex and dsDNA based on silver nanoclusters and unmodified gold nanoparticles

Science.gov (United States)

Qu, Fei; Chen, Zeqiu; You, Jinmao; Song, Cuihua

2018-05-01

Human telomere DNA plays a vital role in genome integrity control and carcinogenesis as an indication for extensive cell proliferation. Herein, silver nanoclusters (Ag NCs) templated by polymer and unmodified gold nanoparticles (Au NPs) are designed as a new colorimetric platform for sensitively differentiating telomere DNA with different lengths, monitoring G-quadruplex and dsDNA. Ag NCs can produce the aggregation of Au NPs, so the color of Au NPs changes to blue and the absorption peak moves to 700 nm. While the telomere DNA can protect Au NPs from aggregation, the color turns to red again and the absorption band blue shift. Benefiting from the obvious color change, we can differentiate the length of telomere DNA by naked eyes. As the length of telomere DNA is longer, the variation of color becomes more noticeable. The detection limits of telomere DNA containing 10, 22, 40, 64 bases are estimated to be 1.41, 1.21, 0.23 and 0.22 nM, respectively. On the other hand, when telomere DNA forms G-quadruplex in the presence of K+, or dsDNA with complementary sequence, both G-quadruplex and dsDNA can protect Au NPs better than the unfolded telomere DNA. Hence, a new colorimetric platform for monitoring structure conversion of DNA is established by Ag NCs-Au NPs system, and to prove this type of application, a selective K+ sensor is developed.

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

Comparison of telomere length and association with progenitor cell markers in lacrimal gland between Sjögren syndrome and non-Sjögren syndrome dry eye patients

Science.gov (United States)

Kawashima, Motoko; Maida, Yoshiko; Kamoi, Mizuka; Ogawa, Yoko; Shimmura, Shigeto; Masutomi, Kenkichi; Tsubota, Kazuo

2011-01-01

Purpose Indicators of aging such as disruption of telomeric function due to shortening may be more frequent in dysfunctional lacrimal gland. The aims of this study were to 1) determine the viability of quantitative fluorescence in situ hybridization of telomeres (telo-FISH) for the assessment of telomere length in lacrimal gland in Sjögren and non- Sjögren syndrome patients; and 2) investigate the relationship between progenitor cell markers and telomere length in both groups. Methods Quantitative fluorescence in situ hybridization with a peptide nucleic acid probe complementary to the telomere repeat sequence was performed on frozen sections from human lacrimal gland tissues. The mean fluorescence intensity of telomere spots was automatically quantified by image analysis as relative telomere length in lacrimal gland epithelial cells. Immunostaining for p63, nucleostemin, ATP-binding cassette, sub-family G, member 2 (ABCG2), and nestin was also performed. Results Telomere intensity in the Sjögren syndrome group (6,785.0±455) was significantly lower than that in the non-Sjögren syndrome group (7,494.7±477; p=0.02). Among the samples from the non-Sjögren syndrome group, immunostaining revealed that p63 was expressed in 1–3 acinar cells in each acinar unit and continuously in the basal layer of duct cells. In contrast, in the Sjögren syndrome group, p63 and nucleostemin showed a lower level of expression. ABCG2 was expressed in acinar cells in both sjogren and non-Sjogren syndrome. Conclusions The results of this study indicate that 1) telo-FISH is a viable method of assessing telomere length in lacrimal gland, and 2) telomere length in Sjögren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjögren syndrome. PMID:21655359

Association of Leukocyte Telomere Length with Fatigue in Nondisabled Older Adults

DEFF Research Database (Denmark)

Bendix, Laila; Thinggaard, Mikael; Kimura, Masayuki

2014-01-01

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...

Tratamento da pré-eclâmpsia baseado em evidências Pre-eclampsia treatment according to scientific evidence

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Carlos Noronha Neto

2010-09-01

Full Text Available As síndromes hipertensivas na gestação merecem especial destaque no cenário da saúde pública mundial. Atualmente, respondem como terceira causa de mortalidade materna no mundo e primeira no Brasil. Do ponto de vista prático, a pré-eclâmpsia continua sendo uma síndrome que leva a graves repercussões maternas e fetais, conhecendo-se ainda pouco sobre sua etiologia. Atualmente, tem-se discutido a melhor terapêutica para os quadros de pré-eclâmpsia em diversos momentos do ciclo gravídico-puerperal, visando sempre à redução de altos índices de morbimortalidade materna e fetal. O parto, considerando-se a fisiopatologia do evento, representa a melhor forma de tratamento. O uso de sulfato de magnésio é recomendado em todos os casos de pré-eclâmpsia grave e eclâmpsia para prevenção e tratamento das crises convulsivas. Da mesma forma, o tratamento dos picos hipertensivos é recomendado. Hidralazina, nifedipina e labetalol têm sido as drogas mais utilizadas com essa finalidade, mas seu uso dependente da familiaridade do médico assistente. A corticoterapia antenatal está indicada sempre que existe risco iminente de prematuridade entre a 24º e 34º semana. Em contrapartida, não há evidências suficientes para recomendar repouso e administração de expansores plasmáticos de rotina, assim como há necessidade urgente de ensaios clínicos randomizados para determinar se o tratamento anti-hipertensivo de manutenção nas gestantes apresenta benefícios ou riscos para mães e fetos, em todas as formas clínicas da doença, em particular nos casos de pré-eclâmpsia pura.Hypertensive disorders in pregnancy deserve special attention in the setting of global public health. Currently, they represent the third cause of maternal mortality in the world and first in Brazil. From a practical standpoint, pre-eclampsia remains a syndrome that leads to serious repercussions on maternal and fetal mortality and its etiology is not well known

A dormant microbial component in the development of pre-eclampsia

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Douglas Bruce Kell

2016-11-01

Full Text Available Pre-eclampsia (PE is a complex, multi-system disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE, and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused.We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation is in fact microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS, also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, urinary tract infection and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of pre-eclampsia that we assessed has in fact also been shown to be raised in response to infection. An infectious component to PE fulfils the Bradford Hill criteria for ascribing a disease to an environmental cause, and suggests a number of treatments, some of which have in fact been shown to be successful.PE was classically referred to as endotoxaemia or toxaemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the aetiology of PE mirrors that for

Food Security and Leukocyte Telomere Length in Adult Americans

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Mohsen Mazidi

2017-01-01

Full Text Available Background and Purpose. 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. Methods. 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. Results. 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<0.001. Conclusion. The association between 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.

Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

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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.

Evidence of a normal mean telomere fragment length in patients with Ullrich-Turner syndrome

DEFF Research Database (Denmark)

Kveiborg, Marie; Gravholt, Claus Højbjerg; Kassem, M

2001-01-01

Clinical and epidemiological studies suggest that premature ageing and increased morbidity and mortality is present in Ullrich-Turner syndrome. We studied telomere restriction fragment length (TRFL) in 30 women with Ullrich-Turner syndrome and 30 age-matched control women. All Turner women had...... the 45,X karyotype verified by karyotyping. We found no difference in the mean TRFL in the young age group (TS: 7011+/-521 vs C: 7285+/-917 bp, P = 0.3), or in the older age group (TS: 7357+/-573 vs C: 7221+/-621 bp, P = 0.6). In conclusion, our data suggest that Ullrich-Turner syndrome is not associated...... with excessive telomere loss, at least when studied in peripheral blood leucocytes, and thus quite different from other premature ageing syndromes....

Leukocyte Telomere Length and Serum Levels of High-Molecular-Weight Adiponectin and Dehydroepiandrosterone-Sulfate Could Reflect Distinct Aspects of Longevity in Japanese Centenarians.

Science.gov (United States)

Aoki, Yuji; Aoki, Masato; Yamada, Kazuya

2017-01-01

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 r = .522, p r = -.574, p r = .530, p 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.

Telomere length and age in humpback whales (Megaptera novaeangliae)

NARCIS (Netherlands)

Olsen, Morten Tange; Bérubé, Martine; Robbins, Jooke; Rew, Mary Beth; Palsboll, Per

2009-01-01

Telomeres are DNA sequences situated at the end of chromosomes that play a key role in maintaining chromosome integrity and are crucial for normal cell function. In vertebrates, telomeres tend to shorten with age, ultimately reaching a threshold believed to trigger cellular and organismal

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,

Social isolation shortens telomeres in African Grey parrots (Psittacus erithacus erithacus.

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Denise Aydinonat

Full Text Available Telomeres, the caps of eukaryotic chromosomes, control chromosome stability and cellular senescence, but aging and exposure to chronic stress are suspected to cause attrition of telomere length. We investigated the effect of social isolation on telomere length in the highly social and intelligent African Grey parrot (Psittacus erithacus erithacus. Our study population consisted of single-housed (n = 26 and pair-housed (n = 19 captive individuals between 0.75 to 45 years of age. Relative telomere length of erythrocyte DNA was measured by quantitative real-time PCR. We found that telomere length declined with age (p<0.001, and socially isolated parrots had significantly shorter telomeres compared to pair-housed birds (p<0.001 - even among birds of similar ages. Our findings provide the first evidence that social isolation affects telomere length, which supports the hypothesis that telomeres provide a biomarker indicating exposure to chronic stress.

Telomere lengthening and other functions of telomerase.

Science.gov (United States)

Rubtsova, M P; Vasilkova, D P; Malyavko, A N; Naraikina, Yu V; Zvereva, M I; Dontsova, O A

2012-04-01

Telomerase is an enzyme that maintains the length of the telomere. The telomere length specifies the number of divisions a cell can undergo before it finally dies (i.e. the proliferative potential of cells). For example, telomerase is activated in embryonic cell lines and the telomere length is maintained at a constant level; therefore, these cells have an unlimited fission potential. Stem cells are characterized by a lower telomerase activity, which enables only partial compensation for the shortening of telomeres. Somatic cells are usually characterized by the absence of telomerase activity. Telomere shortening leads to the attainment of the Hayflick limit, the transition of cells to a state of senescence. The cells subsequently enter a state of crisis, accompanied by massive cell death. The surviving cells become cancer cells, which are capable both of dividing indefinitely and maintaining telomere length (usually with the aid of telomerase). Telomerase is a reverse transcriptase. It consists of two major components: telomerase RNA (TER) and reverse transcriptase (TERT). TER is a non-coding RNA, and it contains the region which serves as a template for telomere synthesis. An increasing number of articles focussing on the alternative functions of telomerase components have recently started appearing. The present review summarizes data on the structure, biogenesis, and functions of telomerase.

Pre-symptomatic increase in urine-orosomucoid excretion in pre-eclamptic women

DEFF Research Database (Denmark)

Kronborg, Camilla Skovhus; Allen, Jim; Vittinghus, Erik

2007-01-01

, 32 women developed pre-eclampsia, and 5 controls for every case of pre-eclampsia were found. Blood samples were collected 4 times and urine samples 6 times from the 18/19th week and throughout pregnancy. Orosomucoid and albumin in plasma were analysed by standard methods, and in urine by sandwich...... in orosomucoid. In the plasma samples, orosomucoid was significantly higher late in pre-eclamptic pregnancies (>or=36th week, p=0.0275). CONCLUSIONS: Pre-eclampsia is associated with a pre-symptomatic increase in the urine excretion of orosomucoid, and orosomucoid excretion precedes that of albumin. Orosomucoid...... excretion can probably be used as a prognostic tool in combination with other screening methods, and seems to be a more sensitive marker for evolving pre-eclampsia than albumin. Plasma orosomucoid is significantly increased late in pre-eclampsia. Thus, the increased excretion of orosomucoid must primarily...

Role of Peroxiredoxin III in the Pathogenesis of Pre-eclampsia as Evidenced in Mice

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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.

Salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in coastal Bangladesh: a case-control study.

Science.gov (United States)

Khan, Aneire Ehmar; Scheelbeek, Pauline Franka Denise; Shilpi, Asma Begum; Chan, Queenie; Mojumder, Sontosh Kumar; Rahman, Atiq; Haines, Andy; Vineis, Paolo

2014-01-01

Hypertensive disorders in pregnancy are among the leading causes of maternal and perinatal death in low-income countries, but the aetiology remains unclear. We investigated the relationship between salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in a coastal community. A population-based case-control study was conducted in Dacope, Bangladesh among 202 pregnant women with (pre)eclampsia or gestational hypertension, enrolled from the community served by the Upazilla Health Complex, Dacope and 1,006 matched controls from the same area. Epidemiological and clinical data were obtained from all participants. Urinary sodium and sodium levels in drinking water were measured. Logistic regression was used to calculate odds ratios, and 95% confidence intervals. Drinking water sources had exceptionally high sodium levels (mean 516.6 mg/L, S.D 524.2). Women consuming tube-well (groundwater) were at a higher disease risk than rainwater users (p900.01 mg/L, compared to water (ORs 3.30 [95% CI 2.00-5.51], 4.40 [2.70-7.25] and 5.48 [3.30-9.11] (p-trendwater is associated with increased risk of (pre)eclampsia and gestational hypertension in this population. Given that coastal populations in countries such as Bangladesh are confronted with high salinity exposure, which is predicted to further increase as a result of sea level rise and other environmental influences, it is imperative to develop and evaluate affordable approaches to providing water with low salt content.

The effect of CD34+ cell telomere length and hTERT expression on the outcome of autologous CD34+ cell transplantation in patients with chronic heart failure.

Science.gov (United States)

Rozman, Jasmina-Ziva; Perme, Maja Pohar; Jez, Mojca; Malicev, Elvira; Krasna, Metka; Novakovic, Srdjan; Vrtovec, Bojan; Rozman, Primoz

2017-09-01

Age-related telomere attrition in stem/progenitor cells may diminish their functional capacity and thereby impair the outcome of cell-based therapies. The aim of the present study was to investigate the effect of CD34 + cell telomere length and hTERT expression on the clinical outcome of autologous CD34 + cell transplantation. We studied 43 patients with cardiomyopathy. Their peripheral blood CD34 + cells were mobilized with granulocyte colony-stimulating factor, enriched by immunoselection and delivered transendocardially. Relative telomere length and expression levels of hTERT were measured using a real-time PCR assay. Immunoselected CD34 + cells had longer telomere length compared to leukocytes in leukapheresis products (p=0.001). In multivariate analysis, CD34 + cell telomere length was not associated with the clinical outcome (b=3.306, p=0.540). While hTERT expression was undetectable in all leukapheresis products, 94.4% of the CD34 + enriched cell products expressed hTERT. Higher CD34 + hTERT expression was associated with a better clinical outcome on univariate analysis (b=87.911, p=0.047). Our findings demonstrate that CD34 + cell telomere length may not influence the clinical outcome in cardiomyopathy patients treated with autologous CD34 + cell transplantation. Larger studies are needed to validate the impact of the CD34 + hTERT expression on the clinical outcome of autologous CD34 + cell transplantation. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of the severity of obstructive sleep apnea syndrome on telomere length.

Science.gov (United States)

Tempaku, Priscila Farias; Mazzotti, Diego Robles; Hirotsu, Camila; Andersen, Monica Levy; Xavier, Gabriela; Maurya, Pawan Kumar; Rizzo, Lucas Bortolotto; Brietzke, Elisa; Belangero, Sintia Iole; Bittencourt, Lia; Tufik, Sergio

2016-10-25

Aging is associated with an increase in the prevalence of obstructive sleep apnea syndrome (OSAS) as well as the shortening of telomeres. It is known that OSAS-related factors are stimuli that can contribute to the acceleration of cellular senescence. Thus, the present study aimed to compare the leukocyte telomere length (LTL) between OSAS patients and controls, as well as to verify the correlation between LTL and sleep parameters. We used DNA extracted of 928 individuals from EPISONO to measure the LTL by the quantitative real-time polymerase chain reaction. All individuals were subjected to one full-night polysomnography. LTL was significantly shorter in OSAS patients compared to controls. The results showed negative correlations between LTL and the following variables: apnea-hypopnea index, respiratory disturbance index, desaturation index and wake after sleep onset. LTL was positively correlated with sleep efficiency, total sleep time, basal, minimum and maximum oxygen saturation. Lastly, it was observed that OSAS severity was associated with shorter LTL even after adjusting for sex, age, years of schooling, body mass index, diabetes, stroke and heart attack. In conclusion, our study indicates the presence of an association between LTL and OSAS and a significant impact of severity of OSAS in telomeres shortening.

Telomere Maintenance Mechanisms in Cancer

OpenAIRE

Tiago Bordeira Gaspar; Ana Sá; José Manuel Lopes; Manuel Sobrinho-Simões; Paula Soares; João Vinagre

2018-01-01

Tumour cells can adopt telomere maintenance mechanisms (TMMs) to avoid telomere shortening, an inevitable process due to successive cell divisions. In most tumour cells, telomere length (TL) is maintained by reactivation of telomerase, while a small part acquires immortality through the telomerase-independent alternative lengthening of telomeres (ALT) mechanism. In the last years, a great amount of data was generated, and different TMMs were reported and explained in detail, benefiting from g...

Epigallocatechin gallate enhances treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia: A double-blind, randomized and placebo-controlled clinical study.

Science.gov (United States)

Shi, D-D; Guo, J-J; Zhou, L; Wang, N

2018-02-01

Oral nifedipine is commonly used to treat pre-eclampsia, one of the most severe complications during pregnancy, but its clinical efficacy is less than ideal. Epigallocatechin gallate (EGCG), a natural compound from green tea, could benefit cardiovascular health especially hypertension. We investigated the clinical efficacy of EGCG, when complemented with oral nifedipine, in treating pre-eclampsia. A total of 350 pregnant women with severe pre-eclampsia were recruited and randomized to receive oral nifedipine, together with placebo (NIF+placebo) or EGCG (NIF+EGCG). The primary treatment outcome was the time needed to control blood pressure and interval time before a new hypertensive crisis, whereas the secondary treatment outcome was the number of treatment doses to effectively control blood pressure, maternal adverse effects and neonatal complications. Comparing NIF+EGCG group to NIF+placebo group, the time needed to control blood pressure was significantly shorter (NIF+EGCG 31.2±16.7 minutes, NIF+placebo 45.3±21.9 minutes; 95% CI 9.7-18.5 minutes), whereas interval time before a new hypertensive crisis was significantly prolonged (NIF+EGCG 7.2±2.9 hours, NIF+placebo 4.1±3.7 hours; 95% CI 2.3-3.9 hours), and the number of treatment dosages needed to effectively control blood pressure was also lower. Between the two treatment groups, no differences in incidence rates of maternal adverse effects or neonatal complications were observed. EGCG is both safe and effective in enhancing treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia, but formal validation is required prior to its recommendation for use outside of clinical trials. © 2017 John Wiley & Sons Ltd.

Women born preterm or with inappropriate weight for gestational age are at risk of subsequent gestational diabetes and pre-eclampsia

DEFF Research Database (Denmark)

á Rogvi, Rasmus; Forman, Julie Lyng; Damm, Peter

2012-01-01

Low birthweight, which can be caused by inappropriate intrauterine growth or prematurity, is associated with development of gestational diabetes mellitus (GDM) as well as pre-eclampsia later in life, but the relative effects of prematurity and inappropriate intrauterine growth remain uncertain....

The association between dietary factors and gestational hypertension and pre-eclampsia: a systematic review and meta-analysis of observational studies

NARCIS (Netherlands)

Schoenaker, D.A.J.M.; Soedamah-Muthu, S.S.; Mishra, G.D.

2014-01-01

Background Dietary factors have been suggested to play a role in the prevention of hypertensive disorders of pregnancy (HDP), including gestational hypertension and pre-eclampsia, but inconsistent findings have been reported. A systematic review and meta-analyses were performed to synthesize

Leisure time physical activity and the risk of pre-eclampsia

DEFF Research Database (Denmark)

Wolf, H T; 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...... the association between LTPA before and/or during pregnancy and the risk of PE. A systematic search of the EMBASE and PUBMED databases from inception to November 17, 2011 was conducted by two independent reviewers. Only studies describing the association between the intensity or amount of LTPA before and....../or during pregnancy and the risk of PE were included. A narrative synthesis of the results was undertaken following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A quality assessment was performed using the Newcastle Ottawa Scale. Eleven studies were included. None...

Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia.

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Aparna Reddy

Full Text Available Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1, endoglin (sEng and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies.To assess the effects of labour, samples were taken from 10 normal pregnant (NP and 10 pre-eclamptic (PE women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively.The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase.Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum.

Erythrocytic cation transport receptor numbers and activity in pregnancies complicated by essential hypertension and pre-eclampsia.

OpenAIRE

Aronson, J K; Moore, M P; Redman, C W; Harper, C

1984-01-01

Various functions of erythrocytic cation transport were studied in normotensive and hypertensive pregnancy (women with pre-eclampsia and essential hypertension). The results showed that in pregnancy there is an increase in the number of erythrocytic glycoside binding sites accompanied by a proportional increase in the active inward transport of rubidium (used as a substitute for potassium). There was no evidence of an effect of pregnancy on intraerythrocytic sodium concentrations. These chang...

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

, and not in CD4+ T cells. In this double-blind placebo-controlled study, we investigated the effect of granulocyte colony stimulating factor (G-CSF) treatment combined with highly active antiretroviral therapy (HAART) on mean telomere length in peripheral blood mononuclear cells (PBMC). The terminal restriction...... fragment (TRF) length showed no changes during G-CSF treatment although the number of lymphocytes increased significantly. The mean TRF length correlated positively (R = 0.552, P = 0.009) and negatively (R = -0.503, P = 0.02) to the proportion of CD4+ memory and naïve cells, respectively. Our data suggest...

Telomeres and the natural lifespan limit in humans

DEFF Research Database (Denmark)

Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon

2017-01-01

An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal...... natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends...

Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries

DEFF Research Database (Denmark)

Urquia, Ml; Glazier, Rh; Gagnon, Aj

2014-01-01

% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native-born women, European and East Asian immigrants were at lower risk in most......OBJECTIVE: To assess disparities in preeclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries. DESIGN: Cross-country comparative study of linked population-based databases. SETTING: Provincial or regional obstetric delivery data from...... Australia, Canada, Spain and the USA and national data from Denmark and Sweden. POPULATION: All immigrant and non-immigrant women delivering in the six industrialised countries within the most recent 10-year period available to each participating centre (1995-2010). METHODS: Data was collected using...

T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover

NARCIS (Netherlands)

Wolthers, K. C.; Bea, G.; Wisman, A.; Otto, S. A.; de Roda Husman, A. M.; Schaft, N.; de Wolf, F.; Goudsmit, J.; Coutinho, R. A.; van der Zee, A. G.; Meyaard, L.; Miedema, F.

1996-01-01

Progression to acquired immunodeficiency syndrome (AIDS) has been related to exhaustion of the regenerative capacity of the immune system resulting from high T cell turnover. Analysis of telomeric terminal restriction fragment (TRF) length, a marker for cellular replicative history, showed that

Tumour-cell apoptosis after cisplatin treatment is not telomere dependent.

Science.gov (United States)

Jeyapalan, Jessie C; Saretzki, Gabriele; Leake, Alan; Tilby, Michael J; von Zglinicki, Thomas

2006-06-01

Cisplatin is a major chemotherapeutic agent, especially for the treatment of neuroblastoma. Telomeres with their sequence (TTAGGG)n are probable targets for cisplatin intrastrand cross-linking, but the role of telomeres in mediating cisplatin cytotoxicity is not clear. After exposure to cisplatin as single dose or continuous treatment, we found no loss of telomeres in either SHSY5Y neuroblastoma cells (telomere length, approximately 4 kbp), HeLa 229 cells (telomere length, 20 kbp) or in the acute lymphoblastic T cell line 1301 (telomere length, approximately 80 kbp). There was no induction of telomeric single strand breaks, telomeric overhangs were not degraded and telomerase activity was down-regulated only after massive onset of apoptosis. In contrast, cisplatin induced a delayed formation of DNA strand breaks and induced DNA damage foci containing gamma-H2A.X at nontelomeric sites. Interstitial DNA damage appears to be more important than telomere loss or telomeric damage as inducer of the signal pathway towards apoptosis and/or growth arrest in cisplatin-treated tumour cells.

Telomeres: Implications for Cancer Development

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Aina Bernal

2018-01-01

Full Text Available Telomeres facilitate the protection of natural ends of chromosomes from constitutive exposure to the DNA damage response (DDR. This is most likely achieved by a lariat structure that hides the linear telomeric DNA through protein-protein and protein-DNA interactions. The telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in unmasked telomeres. Then, the subsequent activation of the DDR will define the fate of cells according to the functionality of cell cycle checkpoints. Dysfunctional telomeres can suppress cancer development by engaging replicative senescence or apoptotic pathways, but they can also promote tumour initiation. Studies in telomere dynamics and karyotype analysis underpin telomere crisis as a key event driving genomic instability. Significant attainment of telomerase or alternative lengthening of telomeres (ALT-pathway to maintain telomere length may be permissive and required for clonal evolution of genomically-unstable cells during progression to malignancy. We summarise current knowledge of the role of telomeres in the maintenance of chromosomal stability and carcinogenesis.

Multiple measures of adiposity are associated with mean leukocyte telomere length in the northern Finland birth cohort 1966.

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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.

Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

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Phaedra M Tachtatzis

Full Text Available Chronic Hepatitis B virus (HBV infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase.Liver samples from patients with chronic HBV (n = 91, normal liver (n = 55 and regenerating liver (n = 15 were studied. Immunohistochemistry for cell cycle phase markers and HBV antigens was used to determine host cell cycle phase. Hepatocyte-specific telomere length was evaluated by quantitative fluorescent in-situ hybridization (Q-FISH in conjunction with hepatocyte nuclear area and HBV antigen expression. The effects of induced cell cycle arrest and induced cellular senescence on HBV production were assessed in vitro.13.7% hepatocytes in chronic HBV had entered cell cycle, but expression of markers for S, G2 and M phase was low compared with regenerating liver. Hepatocyte p21 expression was increased (10.9% in chronic HBV and correlated with liver fibrosis. Mean telomere length was reduced in chronic HBV compared to normal. However, within HBV-affected livers, hepatocytes expressing HBV antigens had longer telomeres. Telomere length declined and hepatocyte nuclear size increased as HBV core antigen (HBcAg expression shifted from the nucleus to cytoplasm. Nuclear co-expression of HBcAg and p21 was not observed. Cell cycle arrest induced in vitro was associated with increased HBV production, in contrast to in vitro induction of cellular senescence, which had no effect.Chronic HBV infection was associated with hepatocyte G1 cell cycle arrest and accelerated hepatocyte ageing, implying that HBV induced cellular senescence. However, HBV replication was confined to biologically younger hepatocytes. Changes in the cellular location of HBcAg may be related to the onset of cellular senescence.

Association of proteinuria threshold in pre-eclampsia with maternal and perinatal outcomes: a nested case control cohort of high risk women.

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Kate Bramham

Full Text Available To evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499 mg and ≥500 mg/24 hours in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension.Secondary analysis of the Vitamins in Pre-Eclampsia Trial.25 UK hospitals in ten geographical areas.946 women with pre-existing risk factors for pre-eclampsia.Women with pre-eclampsia and proteinuria 300-499 mg/24 h (PE300, referent group, n=60 or proteinuria ≥500 mg/24 h (PE500, n=161 were compared with two groups of non-proteinuric women with chronic hypertension (CHT, n=615 or gestational hypertension (GH, n=110.MATERNAL: progression to severe hypertension. Perinatal: small for gestational age (SGA <5(th centile, gestation at delivery.Severe hypertension occurred more frequently in PE500 (35% and PE300 (27% than CHT (5.9%; P≤0.01 and GH (10%; p≤0.001. Gestation at delivery was earlier in PE500 (33.2 w than PE300 (37.3 w; P≤0.001, and later in CHT (38.3 w; P≤0.05 and GH (39.1 w; P≤0.001. SGA infants were more frequent in PE300 (32% than in CHT (13.3%; P≤0.001 and GH (16.5%; P≤0.05. Women in PE500 were more likely to have a caesarean section than PE300 (78% vs. 48%; P≤0.001, and to receive magnesium sulphate (17% vs. 1.7%, P≤0.05.Women with PE300 have complication rates above those of women managed as out-patients (GH and CHT, meriting closer surveillance and confirming 300 mg/d as an appropriate threshold for determining in-patient management. Adverse perinatal outcomes are higher still in women with PE500.

Relationship of Reported Clinical Features of Pre-eclampsia and ...

African Journals Online (AJOL)

eclampsia assessed included headache, visual disturbance, urination, breathing, leg ... Conclusion: The high number of symptoms associated with preeclampsia among women with no formal education strongly supports the need for educational ...

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...

Telomeres and human health

DEFF Research Database (Denmark)

Bojesen, S E

2013-01-01

will be reviewed. In addition, technical difficulties and the reasons why measurement of telomeres has still not been introduced into routine clinical practice will be discussed. Findings from recent studies conducted in many thousands of individuals indicate that telomere length is not-or at best only marginally...

Telomeres, age and reproduction in a long-lived reptile.

Directory of Open Access Journals (Sweden)

Virginie Plot

Full Text Available A major interest has recently emerged in understanding how telomere shortening, mechanism triggering cell senescence, is linked to organism ageing and life history traits in wild species. However, the links between telomere length and key history traits such as reproductive performances have received little attention and remain unclear to date. The leatherback turtle Dermochelys coriacea is a long-lived species showing rapid growth at early stages of life, one of the highest reproductive outputs observed in vertebrates and a dichotomised reproductive pattern related to migrations lasting 2 or 3 years, supposedly associated with different environmental conditions. Here we tested the prediction of blood telomere shortening with age in this species and investigated the relationship between blood telomere length and reproductive performances in leatherback turtles nesting in French Guiana. We found that blood telomere length did not differ between hatchlings and adults. The absence of blood telomere shortening with age may be related to an early high telomerase activity. This telomere-restoring enzyme was formerly suggested to be involved in preventing early telomere attrition in early fast-growing and long-lived species, including squamate reptiles. We found that within one nesting cycle, adult females having performed shorter migrations prior to the considered nesting season had shorter blood telomeres and lower reproductive output. We propose that shorter blood telomeres may result from higher oxidative stress in individuals breeding more frequently (i.e., higher costs of reproduction and/or restoring more quickly their body reserves in cooler feeding areas during preceding migration (i.e., higher foraging costs. This first study on telomeres in the giant leatherback turtle suggests that blood telomere length predicts not only survival chances, but also reproductive performances. Telomeres may therefore be a promising new tool to evaluate

Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

Science.gov (United States)

Lawrie, Theresa A; Betrán, Ana Pilar; Singata-Madliki, Mandisa; Ciganda, Alvaro; Hofmeyr, G Justus; Belizán, José M; Purnat, Tina Dannemann; Manyame, Sarah; Parker, Catherine; Cormick, Gabriela

2017-10-26

The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low

Changes in the Expression of AQP4 and AQP9 in the Hippocampus Following Eclampsia-Like Seizure

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Xinjia Han

2018-01-01

Full Text Available Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of pre-eclampsia. Until now, the mechanisms underlying eclampsia were poorly understood. Brain edema is considered a leading cause of eclamptic seizures; aquaporins (AQP4 and AQP9, the glial water channel proteins mainly expressed in the nervous system, play an important role in brain edema. We studied AQP4 and AQP9 expression in the hippocampus of pre-eclamptic and eclamptic rats in order to explore the molecular mechanisms involved in brain edema. Using our previous animal models, we found several neuronal deaths in the hippocampal CA1 and CA3 regions after pre-eclampsia and that eclampsia induced more neuronal deaths in both areas by Nissl staining. In the current study, RT-PCR and Western blotting data showed significant upregulation of AQP4 and AQP9 mRNA and protein levels after eclamptic seizures in comparison to pre-eclampsia and at the same time AQP4 and AQP9 immunoreactivity also increased after eclampsia. These findings showed that eclamptic seizures induced cell death and that upregulation of AQP4 and AQP9 may play an important role in this pathophysiological process.

Ageing and the telomere connection: An intimate relationship with inflammation.

Science.gov (United States)

Zhang, Jingwen; Rane, Grishma; Dai, Xiaoyun; Shanmugam, Muthu K; Arfuso, Frank; Samy, Ramar Perumal; Lai, Mitchell Kim Peng; Kappei, Dennis; Kumar, Alan Prem; Sethi, Gautam

2016-01-01

Telomeres are the heterochromatic repeat regions at the ends of eukaryotic chromosomes, whose length is considered to be a determinant of biological ageing. Normal ageing itself is associated with telomere shortening. Here, critically short telomeres trigger senescence and eventually cell death. This shortening rate may be further increased by inflammation and oxidative stress and thus affect the ageing process. Apart from shortened or dysfunctional telomeres, cells undergoing senescence are also associated with hyperactivity of the transcription factor NF-κB and overexpression of inflammatory cytokines such as TNF-α, IL-6, and IFN-γ in circulating macrophages. Interestingly, telomerase, a reverse transcriptase that elongates telomeres, is involved in modulating NF-κB activity. Furthermore, inflammation and oxidative stress are implicated as pre-disease mechanisms for chronic diseases of ageing such as neurodegenerative diseases, cardiovascular disease, and cancer. To date, inflammation and telomere shortening have mostly been studied individually in terms of ageing and the associated disease phenotype. However, the interdependent nature of the two demands a more synergistic approach in understanding the ageing process itself and for developing new therapeutic approaches. In this review, we aim to summarize the intricate association between the various inflammatory molecules and telomeres that together contribute to the ageing process and related diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Significantly lengthened telomere in granulosa cells from women with polycystic ovarian syndrome (PCOS).

Science.gov (United States)

Wei, Duo; Xie, Juanke; Yin, Baoli; Hao, Haoying; Song, Xiaobing; Liu, Qi; Zhang, Cuilian; Sun, Yingpu

2017-07-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women at reproductive age. However, its etiology remains poorly understood. Recent studies indicated that telomere length was related to PCOS. However, the association between telomere length and PCOS has only been shown in leucocytes and remained controversial across different studies. To clarify the association between telomere length and PCOS, the current study interrogated telomere length not only in leucocytes, but also in follicular granulosa cells, which is essential for folliculogenesis and steroidogenesis. Seventy-five patients with PCOS and 81 controls with mechanical infertility undergoing their first in vitro fertilization cycle were enrolled. Their peripheral blood and granulosa cells were collected on the oocyte retrieval day. Telomere length of both leucocytes in the blood and granulosa cells was assayed by quantitative polymerase chain reaction. No significant difference was found in the leucocyte telomere length between controls and PCOS patients (0.99 ± 0.44 vs. 1.00 ± 0.38, p = 0.93). Interestingly, when comparing telomere length in granulosa cells between controls and PCOS subjects, significantly lengthened telomere length was found in PCOS subjects (1.00 ± 0.37 vs. 1.57±0.67, p < 0.0001). After adjustments for age and body mass index, the p value remained significant (p < 0.0001). This finding reinforced the association between telomere abnormalities and PCOS. Given the importance of telomere length in cellular proliferation, our findings provided novel insights into the pathophysiology of PCOS that abnormalities in telomere length possibly disturb folliculogenesis and subsequently result in PCOS.

The distribution pattern of critically short telomeres in human osteoarthritic knees

DEFF Research Database (Denmark)

Harbo, Maria; Bendix, Laila; Bay-Jensen, Anne Christine

2012-01-01

ABSTRACT: INTRODUCTION: Telomere shortening is associated with a number of common age-related diseases. A role of telomere shortening in osteoarthritis (OA) has been suggested, mainly based on the assessment of mean telomere length in ex vivo expanded chondrocytes. We addressed this role directly...... in vivo by using a newly developed assay, which measures specifically the load of ultra-short single telomeres (below 1,500 base pairs), that is, the telomere subpopulation believed to promote cellular senescence. METHODS: Samples were obtained from human OA knees at two distances from the central lesion...... site. Each sample was split into three: one was used for quantification of ultra-short single telomeres through the Universal single telomere length assay (STELA), one for histological Mankin grading of OA, and one for mean telomere length measurement through quantitative fluorescence in situ...

Within the genome, long telomeres are more informative than short telomeres with respect to fitness components in a long-lived seabird

NARCIS (Netherlands)

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

Telomeres, DNA-protein structures at chromosome ends, shorten with age, and telomere length has been linked to age-related diseases and survival. In vitro studies revealed that the shortest telomeres trigger cell senescence, but whether the shortest telomeres are also the best biomarker of ageing is

Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.

Science.gov (United States)

Lindqvist, Daniel; Epel, Elissa S; Mellon, Synthia H; Penninx, Brenda W; Révész, Dóra; Verhoeven, Josine E; Reus, Victor I; Lin, Jue; Mahan, Laura; Hough, Christina M; Rosser, Rebecca; Bersani, F Saverio; Blackburn, Elizabeth H; Wolkowitz, Owen M

2015-08-01

Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

Telomerase activity and telomere length in the colorectal polyp-carcinoma sequence Actividad de la telomerasa y longitud del telómero en la secuencia pólipo-carcinoma colorrectal

OpenAIRE

C. Valls Bautista; C. Piñol Felis; J. M. Reñe Espinet; J. Buenestado García; J. Viñas Salas

2009-01-01

Objective: the role of telomerase activity and telomere length in the adenoma-carcinoma sequence of colon carcinogenesis has not been well established. The objective of this study was to determine telomerase activity and telomere length patterns in patients with adenomatous polyps either associated or not with colorectal cancer, as well as the role of telomeric instability in the adenoma-carcinoma sequence. Patients and methods: we included in the study 14 patients who underwent surgery for c...

THE OCCURRENCE OF PRE-ECLAMPSIA IN WOMEN PREGNANT FOR THE FIRST TIME ATTENDING PRENATAL CARE CONSULTATION AT A UNIVERSITY HOSPITAL

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Thelma Spindola

2013-05-01

Objetivos. Conocer el  perfil de las gestantes primigestas atendidas en el pre-natal; identificar la incidencia de pre-eclampsia en gestantes primigestas atendidas en consultas del pre-natal y discutir la contribución del enfermero obstetra en la detección precoz de interconsultas durante el embarazo. Método: Estudio descriptivo, cuantitativo, retrospectivo, realizado en uno de los Hospitales Universitarios de Rio de Janeiro. Las historias clínicas de primigestas atendidas desde 2008 a 2009 fueron analizados con apoyo de la estadística descriptiva. Resultados: Fueron 264 (56,3% internaciones de primigestas, fueron parte del conjunto de muestra 105 historias clínicas.  En este grupo investigado, 43(40,9% gestantes no presentaron edema; 2 (1,9% tuvieron proteinuria e 29 (27,6 % no tuvieron anormalidades en los controles de presión arterial. Conclusión: En la muestra no hubo registro de pre-eclampsia, además 41 (38,9% mujeres presentaron alteraciones de presión arterial compatibles con  Enfermedad Hipertensiva Específica de la Gestación (EHEG. El enfermero tiene un papel importante en el equipo multi-profesional para la detección precoz de complicaciones en la gestación contribuyendo para la reducción de la incidencia de morbimortalidad.

Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis

NARCIS (Netherlands)

Cnossen, Jeltsje S.; Morris, Rachel K.; ter Riet, Gerben; Mol, Ben W. J.; van der Post, Joris A. M.; Coomarasamy, Arri; Zwinderman, Aeilko H.; Robson, Stephen C.; Bindels, Patrick J. E.; Kleijnen, Jos; Khan, Khalid S.

2008-01-01

BACKGROUND: Alterations in waveforms in the uterine artery are associated with the development of pre-eclampsia and intrauterine growth restriction. We investigated the predictive accuracy of all uterine artery Doppler indices for both conditions in the first and second trimesters. METHODS: We

Segregating YKU80 and TLC1 alleles underlying natural variation in telomere properties in wild yeast.

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Gianni Liti

2009-09-01

Full Text Available In yeast, as in humans, telomere length varies among individuals and is controlled by multiple loci. In a quest to define the extent of variation in telomere length, we screened 112 wild-type Saccharomyces sensu stricto isolates. We found extensive telomere length variation in S. paradoxus isolates. This phenotype correlated with their geographic origin: European strains were observed to have extremely short telomeres (400 bp. Insertions of a URA3 gene near telomeres allowed accurate analysis of individual telomere lengths and telomere position effect (TPE. Crossing the American and European strains resulted in F1 spores with a continuum of telomere lengths consistent with what would be predicted if many quantitative trait loci (QTLs were involved in length maintenance. Variation in TPE is similarly quantitative but only weakly correlated with telomere length. Genotyping F1 segregants indicated several QTLs associated with telomere length and silencing variation. These QTLs include likely candidate genes but also map to regions where there are no known genes involved in telomeric properties. We detected transgressive segregation for both phenotypes. We validated by reciprocal hemizygosity that YKU80 and TLC1 are telomere-length QTLs in the two S. paradoxus subpopulations. Furthermore, we propose that sequence divergence within the Ku heterodimer generates negative epistasis within one of the allelic combinations (American-YKU70 and European-YKU80 resulting in very short telomeres.

Segregating YKU80 and TLC1 alleles underlying natural variation in telomere properties in wild yeast.

Science.gov (United States)

Liti, Gianni; Haricharan, Svasti; Cubillos, Francisco A; Tierney, Anna L; Sharp, Sarah; Bertuch, Alison A; Parts, Leopold; Bailes, Elizabeth; Louis, Edward J

2009-09-01

In yeast, as in humans, telomere length varies among individuals and is controlled by multiple loci. In a quest to define the extent of variation in telomere length, we screened 112 wild-type Saccharomyces sensu stricto isolates. We found extensive telomere length variation in S. paradoxus isolates. This phenotype correlated with their geographic origin: European strains were observed to have extremely short telomeres (400 bp). Insertions of a URA3 gene near telomeres allowed accurate analysis of individual telomere lengths and telomere position effect (TPE). Crossing the American and European strains resulted in F1 spores with a continuum of telomere lengths consistent with what would be predicted if many quantitative trait loci (QTLs) were involved in length maintenance. Variation in TPE is similarly quantitative but only weakly correlated with telomere length. Genotyping F1 segregants indicated several QTLs associated with telomere length and silencing variation. These QTLs include likely candidate genes but also map to regions where there are no known genes involved in telomeric properties. We detected transgressive segregation for both phenotypes. We validated by reciprocal hemizygosity that YKU80 and TLC1 are telomere-length QTLs in the two S. paradoxus subpopulations. Furthermore, we propose that sequence divergence within the Ku heterodimer generates negative epistasis within one of the allelic combinations (American-YKU70 and European-YKU80) resulting in very short telomeres.

The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by alpha-T-catenin upregulation

NARCIS (Netherlands)

van Dijk, Marie; van Bezu, Jan; van Abel, Daan; Dunk, Caroline; Blankenstein, Marinus A.; Oudejans, Cees B. M.; Lye, Stephen J.

2010-01-01

By using complementary in vitro and ex vivo approaches, we show that the risk allele (Y153H) of the pre-eclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation of the cell-cell adhesion protein alpha-T-catenin (CTNNA3). This is effectuated at the crucial

Expectant management ofearly onset ofsevere pre-eclampsia in

African Journals Online (AJOL)

A diagnosis of eclampsia was made on readmission. (blood pressure =160/110 mmHg; proteinuria ++) and a live baby weighing 1 500 g was delivered by caesarean section. The second patient had requested a weekend's leave to attend to her domestic problems following a. 3-week stay in hospital. She did nor rerum after ...

High serum interleukin-8 levels in Afro-Caribbean women with pre-eclampsia. Relations with tumor necrosis factor-alpha, Duffy negative phenotype and von Willebrand factor

NARCIS (Netherlands)

Velzing-Aarts, FV; Muskiet, FAJ; van der Dijs, FPL; Duits, AJ

PROBLEM: Pre-eclampsia is characterized by neutrophil activation. Interleukin-8 (IL-8) is a strong neutrophil chemo-attractant and activator. METHOD OF STUDY: We measured serum IL-8 in 13 pre-eclamptic Afro-Caribbean women and 13 gestational age-, race- and parity-matched normotensive and

Telomeres, telomerase and premature ovarian failure

Directory of Open Access Journals (Sweden)

Renata Košir Pogačnik

2011-11-01

Full Text Available Telomeres are specialized structures at the ends of chromosomes, consisting of six repeated nucleotides in TTAGGG sequence. Genome stability is partly maintained by the architecture of telomeres and is gradually lost as telomeres progressively shorten with each cell replication. Critically shortened telomeres are recognized by DNA repair mechanisms as DNA damage and the cell replication cycle stops. The cell eventually dies or undergoes cell apoptosis. Telomere represents a cellular marker of biological age and are therefore also called cell mitotic clock. The enzyme that counteracts telomere shortening by adding nucleotides to the 3’ end of DNA strand is called telomerase. It is composed of the RNA subunit (TR, which is special type of messenger RNA (mRNA, the catalytic protein subunit (TERT, which works as a reverse transcriptase and numerous additional proteins. Telomerase is active in some germline, epithelial and haemopoietic cells, but in most somatic cells the activity is undetectable. In literature, the length of telomeres is closely connected with premature ovarian failure (POF. POF is generally defined as the onset of menopause before the age of 40. The causes of disease are genetical, autoimmune, iatrogenic or if we cannot establish the cause – idiopathic. A lot of studies examined correlation between idiopathic POF, length of telomeres and telomerase activity. The studies mostly show that women with POF have shortened telomeres and decreased activity of telomerase as compared to healthy women.

Age-dependent associations between telomere length and environmental conditions in roe deer.

Science.gov (United States)

Wilbourn, Rachael V; Froy, Hannah; McManus, Marie-Christina; Cheynel, Louise; Gaillard, Jean-Michel; Gilot-Fromont, Emmanuelle; Regis, Corinne; Rey, Benjamin; Pellerin, Maryline; Lemaître, Jean-François; Nussey, Daniel H

2017-09-01

Telomere length (TL) represents a promising biomarker of overall physiological state and of past environmental experiences, which could help us understand the drivers of life-history variation in natural populations. A growing number of studies in birds suggest that environmental stress or poor environmental conditions are associated with shortened TL, but studies of such relationships in wild mammals are lacking. Here, we compare leucocyte TL from cross-sectional samples collected from two French populations of roe deer which experience different environmental conditions. We found that, as predicted, TL was shorter in the population experiencing poor environmental conditions but that this difference was only significant in older individuals and was independent of sex and body mass. Unexpectedly, the difference was underpinned by a significant increase in TL with age in the population experiencing good environmental conditions, while there was no detectable relationship with age in poor conditions. These results demonstrate both the environmental sensitivity and complexity of telomere dynamics in natural mammal populations, and highlight the importance of longitudinal data to disentangle the within- and among-individual processes that generate them. © 2017 The Authors.

Fanconi anemia proteins in telomere maintenance.

Science.gov (United States)

Sarkar, Jaya; Liu, Yie

2016-07-01

Mammalian chromosome ends are protected by nucleoprotein structures called telomeres. Telomeres ensure genome stability by preventing chromosome termini from being recognized as DNA damage. Telomere length homeostasis is inevitable for telomere maintenance because critical shortening or over-lengthening of telomeres may lead to DNA damage response or delay in DNA replication, and hence genome instability. Due to their repetitive DNA sequence, unique architecture, bound shelterin proteins, and high propensity to form alternate/secondary DNA structures, telomeres are like common fragile sites and pose an inherent challenge to the progression of DNA replication, repair, and recombination apparatus. It is conceivable that longer the telomeres are, greater is the severity of such challenges. Recent studies have linked excessively long telomeres with increased tumorigenesis. Here we discuss telomere abnormalities in a rare recessive chromosomal instability disorder called Fanconi Anemia and the role of the Fanconi Anemia pathway in telomere biology. Reports suggest that Fanconi Anemia proteins play a role in maintaining long telomeres, including processing telomeric joint molecule intermediates. We speculate that ablation of the Fanconi Anemia pathway would lead to inadequate aberrant structural barrier resolution at excessively long telomeres, thereby causing replicative burden on the cell. Published by Elsevier B.V.

DNA-PKcs is critical for telomere capping

Energy Technology Data Exchange (ETDEWEB)

Gilley, David; Tanaka, Hiromi; Hande, M. Prakash; Kurimasa,Akihiro; Li, Gloria C.; Chen, David J.

2001-04-10

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is critical for DNA repair via the non-homologous end joining (NHEJ) pathway. Previously, it was reported that bone marrow cells and spontaneously transformed fibroblasts from SCID (severe combined immunodeficiency) mice have defects in telomere maintenance. The genetically defective SCID mouse arose spontaneously from its parental strain CB17. One known genomic alteration in SCID mice is a truncation of the extreme carboxyl-terminus of DNA-PKcs, but other as yet unidentified alterations may also exist. We have used a defined system, the DNA-PKcs knockout mouse, to investigate specifically the role DNA-PKcs specifically plays in telomere maintenance. We report that primary mouse embryonic fibroblasts (MEFs) and primary cultured kidney cells from 6-8 month old DNA-PKcs deficient mice accumulate a large number of telomere fusions, yet still retain wildtype telomere length. Thus, the phenotype of this defect separates the two-telomere related phenotypes, capping and length maintenance. DNA-PKcs deficient MEFs also exhibit elevated levels of chromosome fragments and breaks, which correlate with increased telomere fusions. Based on the high levels of telomere fusions observed in DNA-PKcs deficient cells, we conclude that DNA-PKcs plays an important capping role at the mammalian telomere.

Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia: Bivariate meta-analysis and decision analysis

NARCIS (Netherlands)

Koopmans, Corine M.; van Pampus, Maria G.; Groen, Henk; Aarnoudse, Jan G.; van den Berg, Paul P.; Mol, Ben W. J.

2009-01-01

The aim of this study is to determine the accuracy and clinical value of serum uric acid in predicting maternal complications in women with pre-eclampsia. An existing meta-analysis on the subject was updated. The accuracy of serum uric acid for the prediction of maternal complications was assessed

Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia : Bivariate meta-analysis and decision analysis

NARCIS (Netherlands)

Koopmans, C.M.; van Pampus, Maria; Groen, H.; Aarnoudse, J.G.; van den Berg, P.P.; Mol, B.W.J.

The aim of this study is to determine the accuracy and clinical value of serum uric acid in predicting maternal complications in women with pre-eclampsia. An existing meta-analysis on the subject was updated. The accuracy of serum uric acid for the prediction of maternal complications was assessed

Similarities between pre-eclampsia and atherosclerosis: a protective effect of physical exercise?

Science.gov (United States)

Belo, Luís; Santos-Silva, Alice; Quintanilha, Alexandre; Rebelo, Irene

2008-01-01

Pre-eclampsia (PE), a characteristic hypertensive disorder of human pregnancy and a leading cause of maternal and fetal mortality and morbidity worldwide, shares some similarities with atherosclerosis, namely the involvement of oxidative stress and of endothelial dysfunction in their pathophysiologies, the presence of similar typical lesions and of common risk factors. Although it is widely accepted that regular physical exercise protects against cardiovascular events, few studies have addressed the impact of physical activity in reducing PE risk. In this paper, similarities between atherosclerosis and PE, involving pathogenic mechanisms, are described. This paper also reviews the studies performed until now that evaluated the impact of regular physical exercise (prenataly or during pregnancy) in reducing risk of PE. The potential mechanisms underlying physical activity as a prophylactic approach of PE, as observed with cardiovascular diseases, are discussed.