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1.
J Bone Miner Res ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32176830

RESUMO

OBJECTIVES: Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB) but little is known about the clinical characteristics of those with early disease. METHODS: Radionuclide bone scans, biochemical markers of bone turnover and clinical characteristics were analysed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. RESULTS: We studied 222 individuals of whom 54.9% were female with average (± sem) age of 50.1± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu which was present in 141/222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%) of which 9 (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 vs. 49.8 ± 8.9, p=0.07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years vs. 59 years, p=0.25). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalised to the upper limit of normal in each centre were higher in those with lesions (0.75 ± 0.69 vs 0.42 ± 0.29; p<0.0001). Similar findings were observed for other biochemical markers of bone turnover but the sensitivity of ALP and other markers in detecting lesions was poor. CONCLUSIONS: Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow up of this cohort will provide important information on the natural history of early PDB and its response to treatment. This article is protected by copyright. All rights reserved.

2.
Endocr Connect ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31961795

RESUMO

Hypoparathyroidism is genetically heterogeneous and characterized by low plasma calcium and parathyroid hormone (PTH) concentrations. X-linked hypoparathyroidism (XLHPT) in two American families, is associated with interstitial deletion-insertions involving deletions of chromosome Xq27.1 downstream of SOX3 and insertions of predominantly non-coding DNA from chromosome 2p25.3. These could result in loss, gain, or movement of regulatory elements, which include ultraconserved element uc482, that could alter SOX3 expression,. To investigate this, we analysed SOX3 expression in EBV-transformed lymphoblastoid cells from 3 affected males, 3 unaffected males, and 4 carrier females from one XLHPT family. SOX3 expression was similar in all individuals, indicating that the spatiotemporal effect of the interstitial deletion-insertion on SOX3 expression postulated to occur in developing parathyroids did not manifest in lymphoblastoids. Expression of SNTG2, which is duplicated and inserted into the X chromosome, and ATP11C, which is moved telomerically, were also similarly expressed in all individuals. Investigation of male hemizygous (Sox3-/Y and uc482-/Y) and female heterozygous (Sox3+/- and uc482+/-) knock-out mice, together with wild-type littermates (male Sox3+/Y and uc482+/Y, and female Sox3+/+ and uc482+/+), revealed Sox3-/Y, Sox3+/-, uc482-/Y, and uc482+/- mice to have normal plasma biochemistry, compared to their respective wild-type littermates. When challenged with a low calcium diet, all mice had hypocalcaemia, and elevated plasma PTH concentrations and alkaline phosphatase activities, and Sox3-/Y, Sox3+/-, uc482-/Y, and uc482+/- mice had similar plasma biochemistry, compared to wild-type littermates. Thus, these results indicate that absence of Sox3 or uc482 does not cause hypoparathyroidism, and that XLHPT likely reflects a more complex mechanism.

3.
Calcif Tissue Int ; 106(1): 3-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31741016

RESUMO

The demand for measurement of vitamin D metabolites for clinical diagnosis and to advance our understanding of the role of vitamin D in human health has significantly increased in the last decade. New developments in technologies employed have enabled the separation and quantification of additional metabolites and interferences. Also, developments of immunoassays have changed the landscape. Programmes and materials for assay standardisation, harmonisation and the expansion of the vitamin D external quality assurance scheme (DEQAS) with the provision of target values as measured by a reference measurement procedure have improved standardisation, quality assurance and comparability of measurements. In this article, we describe developments in the measurement of the commonly analysed vitamin D metabolites in clinical and research practice. We describe current analytical approaches, discuss differences between assays, their origin, and how these may be influenced by physiological and experimental conditions. The value of measuring metabolites beyond 25 hydroxyvitamin D (25(OH)D), the marker of vitamin D status, in routine clinical practice is not yet confirmed. Here we provide an overview of the value and application of the measurement of 1,25 dihydroxyvitamin D, 24,25 dihydroxyvitamin D and free 25OHD in the diagnosis of patients with abnormalities in vitamin D metabolism and for research purposes.

4.
Am J Clin Nutr ; 111(1): 98-109, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31559434

RESUMO

BACKGROUND: Mediterranean diets limit red meat consumption and increase intakes of high-phytate foods, a combination that could reduce iron status. Conversely, higher intakes of fish, a good source of selenium, could increase selenium status. OBJECTIVES: A 1-y randomized controlled trial [New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE)] was carried out in older Europeans to investigate the effects of consuming a Mediterranean-style diet on indices of inflammation and changes in nutritional status. METHODS: Selenium and iron intakes and status biomarkers were measured at baseline and after 1 y in 1294 people aged 65-79 y from 5 European countries (France, Italy, the Netherlands, Poland, and the United Kingdom) who had been randomly allocated either to a Mediterranean-style diet or to remain on their habitual, Western diet. RESULTS: Estimated selenium intakes increased significantly with the intervention group (P < 0.01), but were not accompanied by changes in serum selenium concentrations. Iron intakes also increased (P < 0.001), but there was no change in iron status. However, when stratified by study center, there were positive effects of the intervention on iron status for serum ferritin for participants in Italy (P = 0.04) and France (P = 0.04) and on soluble transferrin receptor (sTfR) for participants in Poland (P < 0.01). Meat intake decreased and fish intake increased to a greater degree in the intervention group, relative to the controls (P < 0.01 for both), but the overall effects of the intervention on meat and fish intakes were mainly driven by data from Poland and France. Changes in serum selenium in the intervention group were associated with greater changes in serum ferritin (P = 0.01) and body iron (P = 0.01), but not sTfR (P = 0.73); there were no study center × selenium status interactions for the iron biomarkers. CONCLUSIONS: Consuming a Mediterranean-style diet for 1 y had no overall effect on iron or selenium status, although there were positive effects on biomarkers of iron status in some countries. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.

5.
Pediatr Obes ; 15(3): e12587, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31845502

RESUMO

BACKGROUND: Though the physiological roles of adipokines in metabolism, insulin resistance and satiety are clear, literature regarding associations between cord blood adipokine levels and childhood adiposity is equivocal. OBJECTIVES: To determine whether cord blood levels of leptin and adiponectin are associated with adiposity in children 2 to 5 years of age, and whether such associations are modified by sex. METHODS: Leptin and adiponectin levels were measured in cord blood and anthropometric measures were completed on 550 children enrolled in the Maternal-Infant Research on Environmental Chemicals Child Development Plus study (MIREC-CD Plus). We used multivariable linear and Poisson regression models to determine associations between cord blood adipokine levels and child body mass index (BMI), triceps and subscapular skinfold thickness and risk of overweight/obesity and to assess effect modification by child sex. RESULTS: Cord blood adiponectin was significantly associated with modest increases in BMI and the sum of triceps and subscapular skinfold z-scores in boys but not girls. A doubling of adiponectin levels was associated with a 30% increased risk of overweight/obesity in boys (RR = 1.30; 95% CI: 1.02, 1.64). Leptin was not associated with anthropometric measures in either sex. CONCLUSIONS: The observed associations between adiponectin and adiposity in boys were statistically significant, of moderate magnitude, and underscore the value of considering sex-specific patterns.

6.
Clin Endocrinol (Oxf) ; 92(1): 29-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31667854

RESUMO

OBJECTIVE: Bone turnover, which regulates bone mass, may exert metabolic consequences, particularly on markers of glucose metabolism and adiposity. To better understand these relationships, we examined cross-sectional associations between bone turnover markers (BTMs) and metabolic traits in a population with high bone mass (HBM, BMD Z-score ≥+3.2). DESIGN: ß-C-terminal telopeptide of type-I collagen (ß-CTX), procollagen type-1 amino-terminal propeptide (P1NP) and osteocalcin were assessed by electrochemiluminescence immunoassays. Metabolic traits, including lipids and glycolysis-related metabolites, were measured using nuclear magnetic resonance spectroscopy. Associations of BTMs with metabolic traits were assessed using generalized estimating equation linear regression, accounting for within-family correlation, adjusting for potential confounders (age, sex, height, weight, menopause, bisphosphonate and oral glucocorticoid use). RESULTS: A total of 198 adults with HBM had complete data, mean [SD] age 61.6 [13.7] years; 77% were female. Of 23 summary metabolic traits, citrate was positively related to all BTMs: adjusted ßß-CTX  = 0.050 (95% CI 0.024, 0.076), P = 1.71 × 10-4 , ßosteocalcin  = 6.54 × 10-4 (1.87 × 10-4 , 0.001), P = .006 and ßP1NP  = 2.40 × 10-4 (6.49 × 10-5 , 4.14 × 10-4 ), P = .007 (ß = increase in citrate (mmol/L) per 1 µg/L BTM increase). Inverse relationships of ß-CTX (ß = -0.276 [-0.434, -0.118], P = 6.03 × 10-4 ) and osteocalcin (-0.004 [-0.007, -0.001], P = .020) with triglycerides were also identified. We explored the generalizability of these associations in 3664 perimenopausal women (age 47.9 [4.4] years) from a UK family cohort. We confirmed a positive, albeit lower magnitude, association between ß-CTX and citrate (adjusted ßwomen  = 0.020 [0.013, 0.026], P = 1.95 × 10-9 ) and an inverse association of similar magnitude between ß-CTX and triglycerides (ß = -0.354 [-0.471, -0.237], P = 3.03 × 10-9 ). CONCLUSIONS: Bone resorption is positively related to circulating citrate and inversely related to triglycerides. Further studies are justified to determine whether plasma citrate or triglyceride concentrations are altered by factors known to modulate bone resorption, such as bisphosphonates.

7.
J Dev Orig Health Dis ; : 1-11, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679538

RESUMO

Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22-3.06; aOR2 = 2.05, 95% CI: 1.33-3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30-3.11; aOR2 = 2.51, 95% CI: 1.69-3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03-2.45; aOR2 = 1.99, 95% CI: 1.05-3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.

9.
BMJ Open ; 9(9): e030689, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31488492

RESUMO

INTRODUCTION: Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. METHODS AND ANALYSIS: People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events. ETHICS AND DISSEMINATION: The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

10.
Heliyon ; 5(8): e02150, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31453391

RESUMO

HPV vaccination efficacy has been shown in clinical trials but it is important to verify population level vaccine effectiveness (VE). We aimed to explore VE and herd effect using HPV infection data from a cohort study of Canadian pregnant women. We analyzed the baseline data of the HERITAGE study, which includes pregnant women recruited in Montreal between 2010-2012 and 2015-2016. Cervicovaginal samples self-collected in the first trimester were tested for 36 HPV types. Vaccination status was self-reported. VE and 95% confidence intervals (CI) were estimated by comparing the prevalence of HPV between vaccinated and unvaccinated women. Herd effect was explored by comparing HPV prevalence in unvaccinated women between the 2 recruitment periods. Adjusted ORs (95%CI) were estimated using exact logistic regression. The proportion of vaccinated women with at least one dose of 4vHPV was 7.5%. Although most of them were vaccinated after the onset of sexual activity, a high VE was found for HPV-16/18 (86.1% (95%CI: 15.0-99.7)). For HPV-6/11/16/18 and for HPV-31/33/45, VE was 61.9% (-23.5-92.6) and 57.0% (-47.7-92.0%), respectively. We also observed a non-statistically significant reduction in the prevalence of HPV-6/11/16/18 and HPV-31/33/45 among unvaccinated women recruited during the second recruitment period (adjusted OR: 0.8 (0.4-1.8) and 0.8 (0.3-1.7), respectively).

11.
Environ Res ; 177: 108593, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357157

RESUMO

Anogenital distance (AGD) has been used as a marker of fetal androgen action to identify endocrine disrupting chemicals. A US study (TIDES) has reported that the association between some phthalates and reduced AGD in males was only apparent in sons of mothers reporting no stressful life events (SLEs) during pregnancy. The objective of the current study was to examine the potential modifying effect of SLEs and their subjective impact on associations between prenatal phthalates and AGD. First trimester urines from the MIREC Study were analysed for phthalate metabolites and AGD was measured in neonates. Post-delivery, the women answered questions on SLEs during the pregnancy. Women reporting 1 or more SLEs during pregnancy were considered a "higher stressor" group, whereas women reporting no SLEs or who reported a SLE that was perceived as not at all stressful were considered a "lower stressor" group. Multivariable linear regression models were fit stratified by stressor group. Maternal stressor, AGD and phthalates results were available for 153 females and 147 males. A summary measure of androgen-disrupting phthalates (Σ AD) was associated with significantly longer AGDs in females from the higher stressor group. These effect sizes were increased when the perceived impact was restricted to moderately or very much stressful. In males, all phthalates were associated with longer anopenile distance (APD), regardless of stressor group; however, higher Σ AD was associated with significantly longer APD in the lower stressor group. In contrast to the TIDES study, we did not observe shorter AGDs in male infants prenatally exposed to di-(2-ethylhexyl) phthalates, regardless of maternal stressor level. In conclusion, we were unable to replicate the findings of the TIDES study, but did find some evidence that prenatal SLEs may modify associations between phthalates and female AGD. Further research with other populations and measures of prenatal stress may shed more light on whether prenatal stress is an important effect modifier of associations between phthalates (or other chemicals) and anogenital distance.

12.
Proc Natl Acad Sci U S A ; 116(21): 10463-10472, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31036632

RESUMO

Paget's disease of bone (PDB) is a chronic skeletal disorder that can affect one or several bones in individuals older than 55 y of age. PDB-like changes have been reported in archaeological remains as old as Roman, although accurate diagnosis and natural history of the disease is lacking. Six skeletons from a collection of 130 excavated at Norton Priory in the North West of England, which dates to medieval times, show atypical and extensive pathological changes resembling contemporary PDB affecting as many as 75% of individual skeletons. Disease prevalence in the remaining collection is high, at least 16% of adults, with age at death estimations as low as 35 y. Despite these atypical features, paleoproteomic analysis identified sequestosome 1 (SQSTM1) or p62, a protein central to the pathological milieu of PDB, as one of the few noncollagenous human sequences preserved in skeletal samples. Targeted proteomic analysis detected >60% of the ancient p62 primary sequence, with Western blotting indicating p62 abnormalities, including in dentition. Direct sequencing of ancient DNA excluded contemporary PDB-associated SQSTM1 mutations. Our observations indicate that the ancient p62 protein is likely modified within its C-terminal ubiquitin-associated domain. Ancient miRNAs were remarkably preserved in an osteosarcoma from a skeleton with extensive disease, with miR-16 expression consistent with that reported in contemporary PDB-associated bone tumors. Our work displays the use of proteomics to inform diagnosis of ancient diseases such as atypical PDB, which has unusual features presumably potentiated by yet-unidentified environmental or genetic factors.

13.
Bone ; 125: 54-60, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31077851

RESUMO

PURPOSE: Short periods of basic military training increase the density and size of the tibia, but the adaptive response of bone microarchitecture, a key component of bone strength, is not fully understood. METHODS: Tibial volumetric bone mineral density (vBMD), geometry, microarchitecture and mechanical properties were measured using high-resolution peripheral quantitative computed tomography in 43 male British Army infantry recruits (mean ±â€¯SD, age 21 ±â€¯3 years, height 1.76 ±â€¯0.06 m, body mass 76.5 ±â€¯9.4 kg). Bilateral scans were performed at the distal tibia at the start (week 1) and end (week 13) of basic military training. Concurrent measures were obtained for whole-body areal bone mineral density (aBMD) using DXA, and markers of bone metabolism (ßCTX, P1NP, PTH, total 25(OH)D and ACa) from venous blood. RESULTS: Training increased areal BMD for total body (1.4%) and arms (5.2%) (P ≤ 0.031), but not legs and trunk (P ≥ 0.094). Training increased trabecular (1.3 to 1.9%) and cortical vBMD (0.6 to 0.9%), trabecular volume (1.3 to 1.9%), cortical thickness (3.2 to 5.2%) and cortical area (2.6 to 2.8%), and reduced trabecular area (-0.4 to -0.5%) in both legs (P < 0.001). No changes in trabecular number, thickness and separation, cortical porosity, stiffness or failure load were observed (P ≥ 0.188). ßCTX decreased (-0.11 µg∙l-1, P < 0.001) and total 25(OH)D increased (9.4 nmol∙l-1, P = 0.029), but no differences in P1NP, PTH or ACa were observed between timepoints (P ≥ 0.233). CONCLUSION: A short period of basic military training increased density and altered geometry of the distal tibia in male military recruits. The osteogenic effects of basic military training are likely due to an increase in unaccustomed, dynamic and high-impact loading.

14.
Sci Rep ; 9(1): 6974, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31061425

RESUMO

Vitamin D status, assessed by serum concentration of 25(OH)D, is the prime candidate marker for many disease-association studies, but the interplay between the subsequent 1,25-dihydroxyvitamin D (1,25(OH)2D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) metabolites is unclear. In this study, we conducted an analysis from a large cohort of healthy, physically fit, young army recruits (n = 940). We found a significant, inverse relationship between serum 25(OH)D and 1,25(OH)2D:24,25(OH)2D vitamin D metabolite ratio (VMR) (r2Exp = 0.582, p < 0.0001), and demonstrated a significant association with increasing PTH concentration (p < 0.001). Circannual rhythms were evident for all vitamin D metabolites and VMRs except for 1,25(OH)2D when fitted to Cosinor curves. We estimated 1,25(OH)2D:24,25(OH)2D VMR of ≥35 to be the threshold value for vitamin D insufficiency, and ≥51 to be predictive of vitamin D deficiency. Our three-dimensional model provides mechanistic insight into the vitamin D-PTH endocrine system, and further substantiates the role of 24,25(OH)2D in human physiology. The model sets a new paradigm for vitamin D treatment strategy, and may help the establishment of vitamin D-adjusted PTH reference intervals. The study was approved by the UK Ministry of Defence research ethics committee (MODREC 165/Gen/10 and 692/MoDREC/15). ClinicalTrials.gov Identifier NCT02416895.

15.
Environ Res ; 172: 454-461, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30831435

RESUMO

BACKGROUND: Bisphenol A (BPA) is a high production volume chemical and because of its use in many consumer products, exposure is ubiquitous. Gestational BPA exposure has been associated with excess adiposity in rodent studies, but not consistently in human studies. We investigated the relation between gestational BPA exposure and early childhood adiposity in a prospective cohort study of 719 mother-child pairs. METHODS: We used data from the MIREC Study, a prospective Pan-Canadian pregnancy and birth cohort study. We measured BPA in urine samples collected at an average of 12.1 weeks (range: 6.3-15 weeks) gestation and measured children's weight, height, waist/hip circumference, and subscapular/triceps skinfold thickness at an average age of 3.5 years (range: 1.9-6.2). We estimated covariate-adjusted associations of log2-transformed BPA concentrations with child adiposity measures and examined whether these associations differed in boys and girls. RESULTS: Median BPA concentrations were 0.8 ng/mL (IQR: 0.5-1.4). Among both boys and girls, each 2-fold increase in BPA concentrations was associated with higher waist-to-hip ratio (ß: 0.003; 95% CI: 0.001, 0.005). The association of BPA with waist circumference and subscapular skinfold thickness was modified by sex (sex x BPA interaction p-values<0.2). In girls, each 2-fold increase in BPA concentrations was associated with a 0.2 cm (95% CI: 0.0, 0.5) and 0.15 mm (95% CI: 0.01, 0.30) increase in waist circumference and subscapular skinfolds, respectively. Associations were generally null or slightly inverse in boys. CONCLUSIONS: In this cohort, gestational urinary BPA concentrations were associated with subtle increases in girl's central adiposity during early childhood.


Assuntos
Adiposidade , Compostos Benzidrílicos , Fenóis , Compostos Benzidrílicos/urina , Canadá , Pré-Escolar , Estudos de Coortes , Exposição Dietética/efeitos adversos , Exposição Dietética/estatística & dados numéricos , Feminino , Humanos , Masculino , Exposição Materna/efeitos adversos , Exposição Materna/estatística & dados numéricos , Fenóis/urina , Gravidez , Estudos Prospectivos
16.
Diabetes Care ; 42(5): 964-971, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30833369

RESUMO

OBJECTIVE: Fetal excessive exposure to glucocorticoids may program cardiometabolic risk. Placental 11 ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2) serves as a barrier to prevent fetal overexposure to maternal glucocorticoids. It has not been explored whether placental 11ß-HSD2 levels are associated with cardiometabolic health in postnatal life. RESEARCH DESIGN AND METHODS: In a prospective birth cohort study of 246 mother-infant pairs, we measured placental 11ß-HSD2 expression and maternal (32-35 weeks of gestation) and cord plasma cortisol concentrations. The primary outcomes were HOMA of insulin resistance (IR) and blood pressure (BP) in infants at age 1 year. Other outcomes included fasting insulin, HOMA ß-cell function, carotid intima-media thickness, weight z score, and skinfold thickness (triceps and subscapular) at age 1 year. RESULTS: Placental 11ß-HSD2 expression was negatively correlated with HOMA-IR (r = -0.17, P = 0.021) and fasting insulin (r = -0.18, P = 0.017) and marginally negatively correlated with systolic BP (r = -0.16, P = 0.057) but was not correlated with HOMA of ß-cell function, diastolic BP, carotid intima-media thickness, and skinfold thickness (all P > 0.1) in infants at age 1 year. Cord plasma cortisol was negatively correlated to skinfold thickness (r = -0.20, P = 0007) but was not correlated with other outcomes at age 1 year. Maternal plasma cortisol was positively correlated with maximal carotid intima-media thickness (r = 0.20, P = 0.03) but was not correlated with other outcomes. Adjusting for maternal and infant characteristics, the associations were similar. CONCLUSIONS: The study is the first to show that higher placental 11ß-HSD2 expression is associated with lower IR in infancy. Independent cohort studies are required to confirm this novel finding.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Biomarcadores/metabolismo , Doenças Cardiovasculares/diagnóstico , Saúde do Lactente , Doenças Metabólicas/diagnóstico , Placenta/metabolismo , Adulto , Biomarcadores/análise , Doenças Cardiovasculares/metabolismo , Espessura Intima-Media Carotídea , Desenvolvimento Infantil/fisiologia , Estudos de Coortes , Feminino , Indicadores Básicos de Saúde , Humanos , Hidrocortisona/sangue , Lactente , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/metabolismo , Resistência à Insulina/fisiologia , Masculino , Doenças Metabólicas/metabolismo , Placenta/enzimologia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/metabolismo , Estudos Prospectivos
17.
J Bone Miner Res ; 34(7): 1306-1313, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30882941

RESUMO

Observations that insulin and adiponectin levels are related to cortical bone size in adolescents, independently of body composition, suggest factors related to fat metabolism directly influence skeletal development. To explore this question, we examined associations between a metabolic screen focusing on fat metabolism, and peripheral quantitative computed tomography (pQCT) measures of the mid-tibia, in 15-year-olds from the Avon Longitudinal Study of Parents and Children. Metabolic profiles were generated by proton nuclear magnetic resonance spectroscopy, from blood samples obtained at the same time as pQCT scans. Ordinary least squares linear regression was used to investigate relationships between metabolic measures and periosteal circumference (PC), cortical thickness (CT), and cortical bone mineral density (BMDC ). Metabolic profiles yielded 22 independent components following principal component analysis (PCA), giving a Bonferroni-adjusted threshold for statistical significance of p = 0.002. Data were available in 1121 subjects (487 males), mean age 15 years. Several metabolites related to lipid and cholesterol metabolism were associated with PC, CT, and BMDC after adjustment for age, sex, and Tanner stage. After additional adjustment for height, fat, and lean mass, only the association between citrate and BMDC remained below the Bonferroni-significant threshold (ß = -0.14 [-0.18, -0.09]) (ß represents a standardized coefficient). Citrate also showed evidence of association with PC (ß = 0.06 [0.03, 0.10]) and strength strain index (SSI; ß = 0.04 [0.01, 0.08]). Subsequently, we investigated whether these relationships were explained by increased bone resorption. Citrate was strongly related to serum ß-C-telopeptides of type I collagen (ß-CTX) (ß = 0.20 [0.16, 0.23]). After additional adjustment for ß-CTX the above associations between citrate and BMDC (ß = -0.04 [-0.08, 0.01]), PC (ß = 0.03 [-0.01, 0.07]) and SSI (ß = 0.03 [-0.01, 0.07]) were no longer observed. We conclude that in adolescents, circulating levels of citrate are inversely related to BMDC and positively related to PC, reflecting associations with higher bone turnover. Further studies are justified to elucidate possible contributions of citrate, a constituent of bone matrix, to bone resorption and cortical density. © 2019 American Society for Bone and Mineral Research.

18.
Amino Acids ; 51(4): 691-704, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30783776

RESUMO

This study examined whether consuming collagen peptides (CP) before and after strenuous exercise alters markers of muscle damage, inflammation and bone turnover. Using a double-blind, independent group's design, 24 recreationally active males consumed either 20 g day-1 of CP or a placebo control (CON) for 7 days before and 2 days after performing 150 drop jumps. Maximal isometric voluntary contractions, countermovement jumps (CMJ), muscle soreness (200 mm visual analogue scale), pressure pain threshold, Brief Assessment of Mood Adapted (BAM +) and a range of blood markers associated with muscle damage, inflammation and bone turnover C-terminal telopeptide of type 1 collagen (ß-CTX) and N-terminal propeptides of type 1 pro-collagen (P1NP) were measured before supplementation (baseline; BL), pre, post, 1.5, 24 and 48 h post-exercise. Muscle soreness was not significantly different in CP and CON (P = 0.071) but a large effect size was evident at 48 h post-exercise, indicative of lower soreness in the CP group (90.42 ± 45.33 mm vs. CON 125.67 ± 36.50 mm; ES = 2.64). CMJ height recovered quicker with CP than CON at 48 h (P = 0.050; CP 89.96 ± 12.85 vs. CON 78.67 ± 14.41% of baseline values; ES = 0.55). There were no statistically significant effects for the other dependent variables (P > 0.05). ß-CTX and P1NP were unaffected by CP supplementation (P > 0.05). In conclusion, CP had moderate benefits for the recovery of CMJ and muscle soreness but had no influence on inflammation and bone collagen synthesis.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Colágeno/administração & dosagem , Exercício , Inflamação/prevenção & controle , Músculo Esquelético/fisiologia , Mialgia/tratamento farmacológico , Fragmentos de Peptídeos/administração & dosagem , Adulto , Estudos de Casos e Controles , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Masculino , Músculo Esquelético/efeitos dos fármacos , Mialgia/etiologia , Limiar da Dor , Adulto Jovem
19.
J Bone Miner Res ; 34(4): 579-604, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803025

RESUMO

An evidence-based clinical guideline for the diagnosis and management of Paget's disease of bone (PDB) was developed using GRADE methodology, by a Guideline Development Group (GDG) led by the Paget's Association (UK). A systematic review of diagnostic tests and pharmacological and nonpharmacological treatment options was conducted that sought to address several key questions of clinical relevance. Twelve recommendations and five conditional recommendations were made, but there was insufficient evidence to address eight of the questions posed. The following recommendations were identified as the most important: 1) Radionuclide bone scans, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of metabolically active disease in patients with PDB. 2) Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB. 3) Bisphosphonates are recommended for the treatment of bone pain associated with PDB. Zoledronic acid is recommended as the bisphosphonate most likely to give a favorable pain response. 4) Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalizing total ALP in PDB. 5) Total hip or knee replacements are recommended for patients with PDB who develop osteoarthritis in whom medical treatment is inadequate. There is insufficient information to recommend one type of surgical approach over another. The guideline was endorsed by the European Calcified Tissues Society, the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the Bone Research Society (UK), and the British Geriatric Society. The GDG noted that there had been a lack of research on patient-focused clinical outcomes in PDB and identified several areas where further research was needed. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

20.
Artigo em Inglês | MEDLINE | ID: mdl-30764478

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3⁻4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008⁻2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3⁻4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children's reciprocal social and repetitive behaviours and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no evidence of an association between plasma PCB concentrations and autistic behaviour. However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest category of plasma PCB concentrations compared with the lowest category; for instance, an average increase of 1.4 (95%PCI: -0.4, 3.2) in the mean SRS (exposure contrast highest versus lowest PCB category) for PCB138 translated to an odds ratio of 1.8 (95%PCI: 1.0, 2.9). Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.


Assuntos
Transtorno do Espectro Autista/induzido quimicamente , Poluentes Ambientais/sangue , Exposição Materna/efeitos adversos , Bifenilos Policlorados/sangue , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Transtorno do Espectro Autista/sangue , Teorema de Bayes , Canadá , Estudos de Casos e Controles , Pré-Escolar , Monitoramento Ambiental , Feminino , Humanos , Masculino , Razão de Chances , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Fatores de Risco
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