Elevated plasma ceramide levels in post-menopausal women: a cross-sectional study.
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ABSTRACT:
SUBMITTER: Vozella V
PROVIDER: S-EPMC6339790 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:We developed and validated a hybrid risk classifier combining serum markers and epidemiologic risk factors to identify post-menopausal women at elevated risk for invasive fallopian tube, primary peritoneal, and ovarian epithelial carcinoma. METHODS:To select epidemiologic risk factors for use in the classifier, Cox proportional hazards analyses were conducted using 74,786 Women's Health Initiative (WHI) Observational Study (OS) participants. To construct a combination classifier, 210 WHI OS cases and 536 matched controls with serum marker measurements were analyzed; validation employed 143 cases and 725 matched controls from the WHI Clinical Trial (CT) with similar data. RESULTS:Analyses identified a combination risk classifier composed of two elevated-risk groups: 1) women with CA125 or HE4 exceeding a 98% specificity threshold; and 2) women with intact fallopian tubes, prior use of menopausal hormone therapy for at least two years, and either a first degree relative with breast or ovarian cancer or a personal history of breast cancer. In the WHI OS population, it classified 13% of women as elevated risk, identifying 30% of ovarian cancers diagnosed up to 7.8years post-enrollment (Hazard Ratio [HR]=2.6, p<0.001). In the WHI CT validation population, it classified 8% of women as elevated risk, identifying 31% of cancers diagnosed within 7years of enrollment (HR=4.6, p<0.001). CONCLUSION:CA125 and HE4 contributed significantly to a risk prediction classifier combining serum markers with epidemiologic risk factors. The hybrid risk classifier may be useful to identify post-menopausal women who would benefit from timely surgical intervention to prevent epithelial ovarian cancer.
| S-EPMC4664187 | biostudies-literature
Project description:ObjectiveBariatric surgery (BS) induces loss of body fat mass (FM) with an inexorable loss of lean mass (LM). Menopause leads to deleterious changes in body composition (BC) related to estrogen deficiency including LM loss and increase in total and visceral adipose tissue (VAT). This study aims to describe the long-term weight evolution of post-menopausal women after Roux-en-Y gastric bypass (RYGB) and to compare the BC between BS patients vs post-menopausal non-operated women.DesignCross-sectional study of 60 post-menopausal women who underwent RYGB ≥2 years prior to the study with nested case-control design.MethodsPost-menopausal BS women were matched for age and BMI with controls. Both groups underwent DXA scan, lipids and glucose metabolism markers assessment.ResultsMedian follow-up was 7.5 (2-18) years. Percentage of total weight loss (TWL%) was 28.5 ± 10%. After RYGB, LM percentage of body weight (LM%) was positively associated with TWL% and negatively associated with nadir weight. Forty-one post-BS women were age- and BMI-matched with controls. Post-BS patients showed higher LM% (57.7% (±8%) vs 52.5% (±5%), P = 0.001), reduced FM% (39.4% (±8.4%) vs 45.9% (±5.4%), P < 0.01) and lower VAT (750.6 g (±496) vs 1295.3 g (±688), P < 0.01) with no difference in absolute LM compared to controls. While post-BS women showed a better lipid profile compared to controls, no difference was found in glucose markers.ConclusionsPost-menopausal women after RYGB have a lower FM and VAT, preserved LM and a better lipid profile compared to controls. Weight loss after RYGB seems to have a persistent positive impact on metabolic health.
| S-EPMC8789027 | biostudies-literature
Project description:Water-soluble vitamins like B3 (nicotinamide), B6 (pyridoxine), and B9 (folic acid) are of utmost importance in human health and disease, as they are involved in numerous critical metabolic reactions. Not surprisingly, deficiencies of these vitamins have been linked to various disease states. Unfortunately, not much is known about the physiological levels of B6 vitamers and vitamin B3 in an ethnically isolated group (such as an Emirati population), as well as their relationship with obesity. The aim of the present study was to quantify various B6 vitamers, as well as B3, in the plasma of obese and healthy Emirati populations and to examine their correlation with obesity. A sensitive and robust HPLC-MS/MS-based method was developed for the simultaneous quantitation of five physiologically relevant forms of vitamin B6, namely pyridoxal, pyridoxine, pyridoxamine, pyridoxamine phosphate, and pyridoxal phosphate, as well as nicotinamide, in human plasma. This method was used to quantify the concentrations of these vitamers in the plasma of 57 healthy and 57 obese Emirati volunteers. Our analysis showed that the plasma concentrations of nicotinamide, pyridoxal, and pyridoxamine phosphate in the obese Emirati population were significantly higher than those in healthy volunteers (p < 0.0001, p = 0.0006, and p = 0.002, respectively). No significant differences were observed for the plasma concentrations of pyridoxine and pyridoxal phosphate. Furthermore, the concentrations of some of these vitamers in healthy Emirati volunteers were significantly different than those published in the literature for Western populations, such as American and European volunteers. This initial study underscores the need to quantify micronutrients in distinct ethnic groups, as well as people suffering from chronic metabolic disorders.
| S-EPMC7504312 | biostudies-literature
Project description:IntroductionOsteoporosis is a generalized skeletal disorder characterized by decreased bone mineral density and microarchitectural deterioration, resulting in increased susceptibility to fractures. The prevalence of osteoporosis in Lebanon, defined as T-score <-2.5 at the total hip using NHANES gender-specific database was estimated to be 31% among postmenopausal women.PurposeTo assess the general perception of osteoporosis among women in Lebanon as well as their general knowledge of its lifestyle, risk factors, diagnostic, preventive and therapeutic measures.MethodsA cross-sectional study was conducted in Lebanon between January and December 2017. Women above the age of 50 were invited to participate. A standardized questionnaire regarding the perception of personal risk of osteoporosis and fractures was used. Risk factors for osteoporosis, previous fractures or falls, family history of fracture, smoking, alcohol consumption, and secondary causes of osteoporosis were evaluated. Data were recorded on excel and analyzed on SPSS using variety of descriptive analysis, ANOVA tests, and others. P value <0.05 was considered to be statistically significant.ResultsFrom 396 interviewed women, 85% were in menopause and were more likely to be diagnosed with osteoporosis. 45% knew the true definition of osteoporosis and their most frequent source of information was doctors. Around 60% had heard of BMD screening but only 54.5% of those women actually did it.ConclusionThis study reveals that osteoporosis knowledge and perception is low among the Lebanese woman aged 50 years and older.
| S-EPMC6176852 | biostudies-literature
Project description:Background Elevated plasma ceramides are independent predictors of cardiovascular disease and mortality in patients with advanced epicardial coronary artery disease. Our understanding of plasma ceramides in early epicardial coronary artery disease, however, remains limited. We examined the role of plasma ceramides in early coronary atherosclerosis characterized by coronary endothelial dysfunction. Methods and Results Participants presenting with chest pain and nonobstructive epicardial coronary artery disease underwent coronary endothelial function. Patients (n=90) demonstrated abnormal coronary endothelial function with acetylcholine (≥20% decrease in coronary artery diameter or ≤50% increase in coronary blood flow). A total of 30 controls had normal coronary endothelial function. Concentrations of plasma ceramide 18:0 (P=0.038), 16:0 (P=0.021), and 24:0 (P=0.019) differed between participants with normal and abnormal coronary endothelial function. Ceramide 24:0 (odds ratio [OR], 2.23 [95% CI, 1.07-4.66]; P=0.033) and 16:0 (OR, 1.91×106 [95% CI, 11.93-3.07×1011]; P=0.018) were independently associated with coronary endothelial dysfunction. Among participants with endothelium-dependent coronary dysfunction (n=78), ceramides 16:0 (OR, 5.17×105 [95% CI, 2.83-9.44×1010]; P=0.033), 24:0 (OR, 2.98 [95% CI, 1.27-7.00]; P=0.012), and 24:1/24:0 (OR, 4.39×10-4 [95% CI, 4×10-7-0.48]; P=0.030) were more likely to be elevated. Conclusions The current study demonstrated an association between increased circulating ceramide levels and coronary endothelial dysfunction in the absence of epicardial coronary artery disease. This study supports the role of plasma ceramides as a potential biomarker or a therapeutic target for early coronary atherosclerosis in humans.
| S-EPMC9075496 | biostudies-literature
Project description:Context:Periodontitis is an inflammatory condition which is distinguished by the devastation of the supported tooth structures. In such inflammatory conditions, some biomarkers such as neopterin will be secreted and elevated in the body fluids, which can be used as a diagnostic marker for the present and future disease activity. Aims:Assessment of the neopterin as a biomarker in inflammatory conditions such as menopause and periodontitis. Settings and Design:A cross-sectional interventional study. Materials and Methods:Sixty female individuals with a mean age of 40-60 years with chronic periodontitis were included in this study. All were categorized into two groups of thirty each, depending on their menstrual history: Group I - thirty premenopausal women and Group II - thirty postmenopausal women. Urine and plasma were collected from both groups to estimate neopterin levels. ELISA kit was used to assess the neopterin levels at baseline and after 3 months of nonsurgical periodontal therapy (NSPT). Statistical Analysis Used:IBM SPSS version 21 software. Results:A significant depreciation in the mean values of all the parameters from baseline to 3 months (P < 0.001), in the intragroup analysis, was observed. Plasma (0.006) and urine (0.004) reduction was seen. Conclusions:In both the groups, in 3 months after NSPT, decreased neopterin levels were found, suggesting that the NSPT is the definitive therapy. Further, suggesting that, neopterin levels in the plasma and urine can be used as an index to identify the periodontal inflammation and destruction.
| S-EPMC5813341 | biostudies-literature
Project description:To examine associations between menopausal status and physical performance in middle-aged women from the Northeast region of Brazil.Cross-sectional study of women between 40 to 65 years old living in Parnamirim. Women were recruited by advertisements in primary care neighborhood centers across the city. Physical performance was assessed by grip strength, gait speed and chair stands. Menopausal status was determined using the Stages of Reproductive Aging Workshop classification and women were classified in: premenopausal, perimenopausal or postmenopausal. Multiple linear regression analyses were performed to model the effect of menopausal status on each physical performance measure, adjusting for covariates (age, family income, education, body mass index, parity and age at first birth).The premenopausal women were significantly stronger and performed better in chair stands than perimenopausal and postmenopausal women. Gait speed did not vary significantly by menopausal status. In multivariate analyses, menopausal status remained statistically significant only for grip strength. In fully adjusted analyses, premenopausal women had grip strength mean of 2.226 Kgf (95% CI: 0.361 - 4.091) higher than the postmenopausal group.This study provides further evidence for the associations between menopause and physical performance in middle-aged women, since grip strength is weaker in peri and postmenopausal women compared to premenopausal, even adjusted for age and other covariates.
| S-EPMC4378898 | biostudies-other
Project description:Background Muscle ageing contributes to both loss of functional autonomy and increased morbidity. Muscle atrophy accelerates after 50 years of age, but the mechanisms involved are complex and likely result from the alteration of a variety of interrelated functions. In order to better understand the molecular mechanisms underlying muscle chronological ageing in human, we have undertaken a top-down differential proteomic approach to identify novel biomarkers after the fifth decade of age. Results Muscle samples were compared between adult (56 years) and old (78 years) post-menopausal women. In addition to total muscle extracts, low-ionic strength extracts were investigated to remove high abundance myofibrillar proteins and improve the detection of low abundance proteins. Two-dimensional gel electrophoreses with overlapping IPGs were used to improve the separation of muscle proteins. Overall, 1919 protein spots were matched between all individuals, 95 were differentially expressed and identified by mass spectrometry, and they corresponded to 67 different proteins. Our results suggested important modifications in cytosolic, mitochondrial and lipid energy metabolism, which may relate to dysfunctions in old muscle force generation. A fraction of the differentially expressed proteins were linked to the sarcomere and cytoskeleton (myosin light-chains, troponin T, ankyrin repeat domain-containing protein-2, vinculin, four and a half LIM domain protein-3), which may account for alterations in contractile properties. In line with muscle contraction, we also identified proteins related to calcium signal transduction (calsequestrin-1, sarcalumenin, myozenin-1, annexins). Muscle ageing was further characterized by the differential regulation of several proteins implicated in cytoprotection (catalase, peroxiredoxins), ion homeostasis (carbonic anhydrases, selenium-binding protein 1) and detoxification (aldo-keto reductases, aldehyde dehydrogenases). Notably, many of the differentially expressed proteins were central for proteostasis, including heat shock proteins and proteins involved in proteolysis (valosin-containing protein, proteasome subunit beta type-4, mitochondrial elongation factor-Tu). Conclusions This study describes the most extensive proteomic analysis of muscle ageing in humans, and identified 34 new potential biomarkers. None of them were previously recognized as differentially expressed in old muscles, and each may represent a novel starting point to elucidate the mechanisms of muscle chronological ageing in humans.
2015-02-19 | PXD001527 | Pride
Project description:By the combination of meta-analysis, the data of the 1,000 Genomes Project Phase 3, and the promoter sequence of hepatic lipase (LIPC), we performed the cross-sectional study to explore the associations of four variants (rs1077835; rs1077834; rs1800588 [C-514T], and rs2070895 [G-250A]) in LIPC promoter with plasma lipid levels. Our results indicate that the first and the next three of the four SNPs are, respectively, reported to be associated with the decreased and increased HDL-c level. Meta-analysis of 87 studies with 101,988 participants indicates that HDL-c level in rs1800588 (C-514T) (pooled mean difference = 0.03, 95%CI (0.03, 0.04), p < .001) and rs2070895 (G-250A) (pooled mean difference = 0.07, 95%CI (0.05, 0.09), p < .001) is higher in allele T or A carriers. Similarly, LDL-c, TC, TG, and BMI levels are generally increased in T or A alleles carriers. We failed to conduct the meta-analysis of rs1077835 and rs1077834 due to the limited previous reports. Data from the 1,000 Genomes indicate that the allele frequencies of the four SNPs in total or subpopulations are almost equal to each other. The paired value r 2 and D' of the four SNPs are larger than 0.8, which indicate the linkage disequilibrium of the four variants. The analysis of LIPC promoter indicate that C-514T and G-250A are, respectively, located in transcriptional factor binding sites of USF1and Pbx1b, which may partly explain the effect of the two SNPs on the decreased LIPC activity in the alleles carriers and the corresponding increased plasma lipids hydrolyzed by LIPC. These results may help us to better understand the different effects of the four SNPs on the plasma lipid levels among subpopulations and offer clues for future clinical treatment of dyslipidemia-related diseases.
| S-EPMC7180388 | biostudies-literature
Project description:High blood concentrations of n-6 fatty acids (FAs) relative to n-3 FAs may lead to a "physiological switch" towards permanent low-grade inflammation, potentially influencing the onset of cardiovascular and inflammatory diseases, as well as cancer. To explore the potential effects of FA ratios prior to disease onset, we measured blood gene expression profiles and plasma FA ratios (linoleic acid/alpha-linolenic acid, LA/ALA; arachidonic acid/eicosapentaenoic acid, AA/EPA; and total n-6/n-3) in a cross-section of middle-aged Norwegian women (n = 227). After arranging samples from the highest values to the lowest for all three FA ratios (LA/ALA, AA/EPA and total n-6/n-3), the highest and lowest deciles of samples were compared. Differences in gene expression profiles were assessed by single-gene and pathway-level analyses. The LA/ALA ratio had the largest impact on gene expression profiles, with 135 differentially expressed genes, followed by the total n-6/n-3 ratio (125 genes) and the AA/EPA ratio (72 genes). All FA ratios were associated with genes related to immune processes, with a tendency for increased pro-inflammatory signaling in the highest FA ratio deciles. Lipid metabolism related to peroxisome proliferator-activated receptor γ (PPARγ) signaling was modified, with possible implications for foam cell formation and development of cardiovascular diseases. We identified higher expression levels of several autophagy marker genes, mainly in the lowest LA/ALA decile. This finding may point to the regulation of autophagy as a novel aspect of FA biology which warrants further study. Lastly, all FA ratios were associated with gene sets that included targets of specific microRNAs, and gene sets containing common promoter motifs that did not match any known transcription factors. We conclude that plasma FA ratios are associated with differences in blood gene expression profiles in this free-living population, and that affected genes and pathways may influence the onset and progression of disease.
| S-EPMC3692510 | biostudies-literature