Plasma levels of 24S-hydroxycholesterol reflect the balance between cerebral production and hepatic metabolism and are inversely related to body surface.

PubMed

Bretillon, L; Lütjohann, D; Ståhle, L; Widhe, T; Bindl, L; Eggertsen, G; Diczfalusy, U; Björkhem, I

2000-05-01

We have previously presented evidence that most of the 24S-hydroxycholesterol present in the circulation originates from the brain and that most of the elimination of this oxysterol occurs in the liver. Plasma 24S-hydroxycholesterol levels decline by a factor of about 5 during the first decades of life. The concentration of the enzyme cholesterol 24S-hydroxylase in the brain is, however, about constant from the first year of life, and reduced enzyme levels thus cannot explain the decreasing plasma levels during infancy. In the present work we tested the hypothesis that the plasma levels of 24S-hydroxycholesterol may reflect the size of the brain relative to the capacity of the liver to eliminate the substance. It is shown here that the age-dependent changes in absolute as well as cholesterol-related plasma level of 24S-hydroxycholesterol closely follow the changes in the ratio between estimated brain weight and estimated liver volume. The size of the brain is increased only about 50% whereas the size of the liver is increased by about 6-fold after the age of 1 year. Liver volume is known to be highly correlated to body surface, and in accordance with this the absolute as well as the cholesterol-related plasma level of 24S-hydroxycholesterol was found to be highly inversely correlated to body surface in 77 healthy subjects of varying ages (r(2) = 0.74). Two chondrodystrophic dwarves with normal size of the brain but with markedly reduced body area had increased levels of 24S-hydroxycholesterol when related to age but normal levels when related to body surface. It is concluded that the balance between cerebral production and hepatic metabolism is a critical determinant for plasma levels of 24S-hydroxycholesterol at different ages and that endocrinological factors are less important. The results are discussed in relation to the possibility to use 24S-hydroxycholesterol in the circulation as a marker for cholesterol homeostasis in the brain.

Upregulation of Aβ42 in the Brain and Bodily Fluids of Rhesus Monkeys with Aging.

PubMed

Zhao, Qiao; Lu, Jing; Yao, Zitong; Wang, Shubo; Zhu, Liming; Wang, Ju; Chen, Baian

2017-01-01

The cerebral accumulation of amyloid beta (Aβ) is one of the key pathological hallmarks of Alzheimer's disease (AD). Aβ is also found in bodily fluids such as the cerebrospinal fluid (CSF) and plasma. However, the significance of Aβ accumulation in the brain and different bodily pools, as well as its correlation with aging and cerebral amyloid pathology, is not completely understood. To better understand this question, we selected the rhesus monkey, which is phylogenetically and physiologically highly similar to the human, as a model to study. We quantified the levels of the two main Aβ isoforms (Aβ42 and Aβ40) in different sections of the brain (frontal cortex, temporal cortex, and hippocampus) and bodily fluids (CSF and plasma) of rhesus monkeys at different developmental phases (young, 5-9 years of age; mature, 10-19 years of age; and old, 21-24 years of age). We found that the levels of neuronal and insoluble Aβ42 increased significantly in the brain with aging, suggesting that this specific isoform might be directly involved in aging and AD-like pathophysiology. There was no significant change in the Aβ40 level in the brain with aging. In addition, the Aβ42 level, but not the Aβ40 level, in both the CSF and plasma increased with aging. We also identified a positive correlation between Aβ42 in the CSF and plasma and Aβ42 in the brain. Taken collectively, our results indicate that there is an association between Aβ accumulation and age. These results support the increased incidence of AD with aging.

Erythrocyte Sialic Acid Content during Aging in Humans: Correlation with Markers of Oxidative Stress

PubMed Central

Mehdi, Mohammad Murtaza; Singh, Prabhakar; Rizvi, Syed Ibrahim

2012-01-01

Sialic acids are substituted neuraminic acid derivatives which are typically found at the outermost end of glycan chains on the membrane in all cell types. The role of erythrocyte membrane sialic acids during aging has been established however the relationship between sialic acid and oxidative stress is not fully understood. The present work was undertaken to analyze the relationship between erythrocyte membrane sialic acid with its plasma level, membrane and plasma lipid hydroperoxide levels and plasma total antioxidant capacity. Results show that sialic acid content decreases significantly (P < 0.001) in RBC membrane (r = −0.901) and increases in plasma (r = 0.860) as a function of age in humans. Lipid peroxidation measured in the form of hydroperoxides increases significantly (P < 0.001) in plasma (r = 0.830) and RBC membranes (r = 0.875) with age in humans. The Trolox Equivalent Total Antioxidant Capacity (TETAC) of plasma was found to be significantly decreased (P < 0.001, r = −0.844). We observe significant correlations between decrease of erythrocyte membrane sialic acid and plasma lipid hydroperoxide and TETAC. Based on the observed correlations, we hypothesize that increase in oxidative stress during aging may influence the sialic acid decomposition from membrane thereby altering the membrane configuration affecting many enzymatic and transporter activities. Considering the importance of plasma sialic acid as a diagnostic parameter, it is important to establish age-dependent reference. PMID:22377734

Erythrocyte sialic acid content during aging in humans: correlation with markers of oxidative stress.

PubMed

Mehdi, Mohammad Murtaza; Singh, Prabhakar; Rizvi, Syed Ibrahim

2012-01-01

Sialic acids are substituted neuraminic acid derivatives which are typically found at the outermost end of glycan chains on the membrane in all cell types. The role of erythrocyte membrane sialic acids during aging has been established however the relationship between sialic acid and oxidative stress is not fully understood. The present work was undertaken to analyze the relationship between erythrocyte membrane sialic acid with its plasma level, membrane and plasma lipid hydroperoxide levels and plasma total antioxidant capacity. Results show that sialic acid content decreases significantly (P< 0.001) in RBC membrane (r= -0.901) and increases in plasma (r=0.860) as a function of age in humans. Lipid peroxidation measured in the form of hydroperoxides increases significantly (P<0.001) in plasma (r=0.830) and RBC membranes (r=0.875) with age in humans. The Trolox Equivalent Total Antioxidant Capacity (TETAC) of plasma was found to be significantly decreased (P< 0.001, r=-0.844). We observe significant correlations between decrease of erythrocyte membrane sialic acid and plasma lipid hydroperoxide and TETAC. Based on the observed correlations, we hypothesize that increase in oxidative stress during aging may influence the sialic acid decomposition from membrane thereby altering the membrane configuration affecting many enzymatic and transporter activities. Considering the importance of plasma sialic acid as a diagnostic parameter, it is important to establish age-dependent reference.

Klotho dysfunction: A pathway linking the aging process to bipolar disorder?

PubMed

Barbosa, Izabela Guimarães; Rocha, Natalia Pessoa; Alpak, Gokay; Vieira, Erica Leandro Marciano; Huguet, Rodrigo Barreto; Rocha, Fabio Lopes; de Oliveira Diniz, Breno Satler; Teixeira, Antonio Lucio

2017-12-01

Although accelerated aging profile has been described in bipolar disorder (BD), the biology linking BD and aging is still largely unknown. Reduced levels and/or activity of a protein named Klotho is associated with decreased life span, premature aging and occurrence of age-related diseases. Therefore, this study was designed to evaluate plasma levels of Klotho in BD patients and controls. Forty patients with type 1 BD and 30 controls were enrolled in this study. After clinical evaluation, peripheral blood samples were drawn and plasma levels of Klotho were measured using enzyme-linked immunosorbent assay. Patients with BD and controls presented similar age and sex distribution. The mean ± SD length of illness was 24.00 ± 12.75 years. BD patients presented increased frequency of clinical comorbidities in comparison with controls, mainly arterial hypertension, diabetes mellitus, and hypothyroidism. Both patients with BD in remission and in mania exhibited increased plasma levels of Klotho in comparison with controls. There was no significant difference between patients in mania and patients in remission regarding the levels of Klotho. Klotho-related pathway is altered in BD. Contrary to our original hypothesis, our sample of patients with BD presented increased plasma levels of Klotho in comparison with controls. Elevated levels of Klotho in long-term BD patients may be associated with the disorder progression. Further studies are needed to better understand the role of Klotho in BD and other mood disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamics of lipoprotein level in blood plasma of pregnant women as a function of gestational age according to FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Korolik, E. V.; Korolenko, E. A.; Tretinnikov, O. N.; Kozlyakova, O. V.; Korolik, A. K.; Kirkovskiy, V. V.

2013-01-01

Results of an IR spectroscopic investigation of films of blood plasma taken from women of reproductive age, pregnant women with positive and negative Rh factors, and Rh-immunized women were presented as a function of gestational age. It was found that the lipoprotein content in blood plasma of all groups of pregnant women increased during the early stages of pregnancy (17-23 weeks) irrespective of the Rh factor and attained its peak value by weeks 30-35. It was shown that the lipoprotein level in blood plasma as a function of gestational age was quantitatively the same for pregnant women with positive and negative Rh factors. It was established for the first time that this dependence for Rh-immunized women featured a considerable increase of lipoprotein content at gestational age 30-32 weeks and declined acutely by week 36.

Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from ZincAge study.

PubMed

Giacconi, R; Costarelli, L; Piacenza, F; Basso, A; Rink, L; Mariani, E; Fulop, T; Dedoussis, G; Herbein, G; Provinciali, M; Jajte, J; Lengyel, I; Mocchegiani, E; Malavolta, M

2017-12-01

Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual. It is therefore necessary to identify other determinants associated with plasma Zn to better understanding how physiopathological conditions during aging may affect the concentration of this metal. We have investigated the association between Zn levels and some biomarkers in 1090 healthy elderly from five European countries to increase the accuracy in the assessment of the Zn status. Stepwise multivariate linear regression models were used to analyze the influence of factors such as age, dietary intake, inflammatory mediators, laboratory parameters and polymorphisms previously associated with Zn homeostasis. Plasma Zn decrement was most strongly predicted by age, while positive correlations were found with albumin, RANTES and Zn intake after adjustment for multiple confounders. HSP70 +1267 AA genotype was an independent factor associated with Zn plasma concentrations. Cu/Zn ratio was positively associated with markers of systemic inflammation and age and negatively associated with albumin serum levels. Our findings show the most important independent determinants of plasma Zn concentration and Cu/Zn ratio variability in elderly population and suggest that the decline with age of Zn circulating levels is more dependent on physiopathological changes occurring with aging rather than to its nutritional intake.

Advanced glycation end products are elevated in cystic fibrosis-related diabetes and correlate with worse lung function.

PubMed

Hunt, William R; Helfman, Beth R; McCarty, Nael A; Hansen, Jason M

2016-09-01

The onset of cystic fibrosis-related diabetes (CFRD) exacerbates lung function decline and increases mortality. One pathway that may worsen the lung dysfunction associated with CFRD is that of the receptor for advanced glycation end products (RAGE) and its ligands. Human plasma was obtained from age-matched healthy, CF and CFRD patients. Plasma RAGE ligands (i.e. advanced glycation end products, S100A12, and high-mobility group protein B1) and soluble RAGE (sRAGE) levels were measured. CFRD patients had elevated plasma levels of AGEs and S100A12. Soluble RAGE, a RAGE ligand decoy receptor, was not significantly different between groups. Plasma AGE levels and S100A12 levels had significantly negative correlations with FEV1. AGEs are significantly elevated in CFRD and correlate negatively with FEV1. CFRD patients did not have significant increases in the decoy sRAGE, suggesting there may be heightened binding and activation of RAGE in CFRD exacerbating activation of proinflammatory pathways. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Postoperative plasma 8-iso-prostaglandin F2α levels are associated with delirium and cognitive dysfunction in elderly patients after hip fracture surgery.

PubMed

Zheng, Yuan-Bo; Ruan, Guo-Mo; Fu, Jia-Xing; Su, Zhong-Liang; Cheng, Peng; Lu, Jian-Zuo

2016-04-01

Oxidative stress may be involved in occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD). 8-iso-Prostaglandin F2α (8-iso-PGF2α), an isoprostane derived from arachidonic acid via lipid peroxidation, is considered a gold standard for measuring oxidative stress. The present study aimed to investigate the ability of postoperative plasma 8-iso-PGF2α levels to predict POD and POCD in elderly patients undergoing hip fracture surgery. Postoperative plasma 8-iso-PGF2α levels of 182 patients were measured by an enzyme-linked immunosorbent assay. We assessed the relationships between plasma 8-iso-PGF2α levels and the risk of POD and POCD using a multivariate analysis. Plasma 8-iso-PGF2α levels and age were identified as the independent predictors for POD and POCD. Based on areas under receiver operating characteristic curve, the predictive values of 8-iso-PGF2α were obviously higher than those of age for POD and POCD. In a combined logistic-regression model, 8-iso-PGF2α significantly enhanced the areas under curve of age for prediction of POD and POCD. Postoperative plasma 8-iso-PGF2α levels may have the potential to predict POD and POCD in elder patients undergoing hip fracture surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

Relationship between Lipids Levels of Serum and Seminal Plasma and Semen Parameters in 631 Chinese Subfertile Men

PubMed Central

Yao, Qi; Fan, Kai; Wang, Guo-Hong; Feng, Rui-Xiang; Liang, Yuan-Jiao; Chen, Li; Ge, Yi-Feng; Yao, Bing

2016-01-01

Objective This prospective study was designed to investigate the relationship between lipids levels in both serum and seminal plasma and semen parameters. Methods 631 subfertile men were enrolled. Their obesity-associated markers were measured, and semen parameters were analyzed. Also, seminal plasma and serum TC, TG, HDL and LDL and serum FFA, FSH, LH, total testosterone (TT), estradiol (E2) and SHBG levels were detected. Results Seminal plasma and serum TG, TC and LDL levels were positively related to age. Serum TC, TG and LDL were positively related to obesity-associated markers (P < 0.001), while only seminal plasma TG was positively related to them (P < 0.05). For lipids levels in serum and seminal plasma, only TG level had slightly positive correlation between them (r = 0.081, P = 0.042). There was no significant correlation between serum lipids levels and semen parameters. However, seminal plasma TG, TC, LDL and HDL levels were negatively related to one or several semen parameters, including semen volume (SV), sperm concentration (SC), total sperm count (TSC), sperm motility, progressive motility (PR) and total normal-progressively motile sperm counts (TNPMS). Moreover, seminal plasma TG, TC, LDL and HDL levels in patients with oligospermatism, asthenospermia and teratozoospermia were higher than those with normal sperm concentration, motility or morphology. After adjusting age and serum LH, FSH, TT, E2 and SHBG levels, linear regression analysis showed that SV was still significantly correlated with seminal plasma LDL (P = 0.012), both of SC and TSC with seminal plasma HDL (P = 0.028 and 0.002), and both of PR and sperm motility with seminal plasma TC (P = 0.012 and 0.051). Conclusion The abnormal metabolism of lipids in male reproductive system may contribute to male factor infertility. PMID:26726884

Plasma galanin is a biomarker for severity of major depressive disorder.

PubMed

Wang, Yong-Jun; Yang, Yu-Tao; Li, Hui; Liu, Po-Zi; Wang, Chuan-Yue; Xu, Zhi-Qing David

2014-01-01

This study investigated the association between plasma galanin level and depression severity. The severity of depression symptoms of 79 patients with major depressive disorder (MDD; 52 women and 27 men, 71 patients in onset, 8 in remission) was assessed using the 17-item Hamilton Depression Rating Scale. Venous fasting blood samples (5 mL) were taken from the 79 MDD patients, 35 healthy siblings, and 19 healthy controls, and plasma samples were prepared. Galanin levels in the plasma were measured by radioimmunoassay. Plasma galanin in MDD patients was significantly higher than that of remission patients, healthy siblings, or healthy controls (P < 0.05) There was no significant difference between the healthy sibling and healthy control groups (P = 0.924). Plasma galanin of remission patients was also significantly higher than that of healthy controls (P < 0.05). There was no significant correlation between age and galanin levels in the 79 patients (r = 0.053, P = 0.646), nor was there a correlation between age and galanin levels when patients were stratified by gender (P > 0.05). There was a significant positive correlation between plasma galanin levels and depression severity in women MDD patients (r = 0.329, df = 42, P = 0.020), but not in men patients. Plasma galanin levels may be an important biomarker for depression severity, especially in female patients.

[Physical activity in patients with symptoms of metabolic syndrome reduces the concentration of plasma antioxidant vitamins - protective effect of vitamin C].

PubMed

Godala, Małgorzata; Materek-Kuśmierkiewicz, Izabela; Moczulski, Dariusz; Rutkowski, Maciej; Szatko, Franciszek; Gaszyńska, Ewelina; Tokarski, Sławomir; Kowalski, Jan

2015-05-01

Patients with cardiovascular diseases, including those with the symptoms of metabolic syndrome (MS), are recommended regular exercise but many studies indicate its role in the production of reactive oxygen species. Vitamin C supplementation may enhance the antioxidant barrier in MS patients. The aim of the study was to assess the impact of regular physical activity (PA)and vitamin C supplementation on plasma vitamin A, C and E levels in patients with MS. The study included 62 patients with MS according to International Diabetes Federation criteria, 32 men and 30 women, aged 38-57 years (mean age 51,24 ± 5,29 years). The patients were divided in two groups: group I (MS+PA) - 31 patients with recommended regular physical activity; group II ( MS+PA+C) - 31 patients with recommended regular physical activity and vitamin C supplementation per os. The control group consisted of 23 healthy individuals without MS, 17 men and 6 women, aged 49-56 years (mean age 53,21 ± 3,6 years), who were not recommended any vitamin supplementation nor physical activity. Plasma vitamin A, C and E levels were estimated in MS patients with spectrophotometry using T60V spectrophotometer (PG Instruments) before and after regular exercise with and without vitamin C supplementation. In the control group plasma levels of antioxidant vitamins were assessed only once. The plasma vitamin A, C and E levels were significantly lower (p<0,05) in MS patients than in the control group. After 6 weeks of regular physical activity a significant fall in plasma levels of antioxidant vitamins was observed in MS patients. In the group of patients with regular physical activity and vitamin C supplementation there was detected a significant rise in the level of all the tested vitamins close to the levels in control group. Regular physical activity enhances the decrease in plasma antioxidant vitamin level in patients with MS. Vitamin C supplementation conducted in parallel with regular physical activity normalize plasma vitamin A, C and E levels in these patients. © 2015 MEDPRESS.

Human umbilical cord plasma proteins revitalize hippocampal function in aged mice

PubMed Central

Castellano, Joseph M.; Mosher, Kira I.; Abbey, Rachelle J.; McBride, Alisha A.; James, Michelle L.; Berdnik, Daniela; Shen, Jadon C.; Zou, Bende; Xie, Xinmin S.; Tingle, Martha; Hinkson, Izumi V.; Angst, Martin S.; Wyss-Coray, Tony

2017-01-01

Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation1, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation2, 3, 4 and downregulated in the aged brain5, 6, 7, 8. In addition to revitalizing other aged tissues9, 10, 11, 12, 13, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters14, 15, 16, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown17. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high translational value for targeting ageing- or disease-associated hippocampal dysfunction. PMID:28424512

Plasma testosterone levels in Alzheimer and Parkinson diseases.

PubMed

Okun, M S; DeLong, M R; Hanfelt, J; Gearing, M; Levey, A

2004-02-10

Testosterone deficiency, a treatable condition commonly seen in aging men, has been linked to Parkinson disease (PD) and Alzheimer disease (AD). In normal subjects, low testosterone levels are associated with cognitive and neuropsychiatric symptoms, yet the relationship between testosterone levels and cognitive function in PD and AD remains unclear. To examine the relationship of testosterone levels to age and cognitive function in PD and AD. Plasma testosterone levels were determined in men enrolled in a clinical registry of subjects with PD and AD, and neuropsychological testing was performed on subjects who consented. Testosterone levels in men with PD were compared with those in men with AD. In both groups, the relationship between testosterone levels and neuropsychological test scores was analyzed, adjusting for age and education. Linear regression analysis revealed that testosterone levels decreased with age in male PD patients (p < 0.03) and male AD patients (p < 0.07). The rate of decline was similar for the two groups. In PD patients, lower testosterone levels were associated with poorer performance on Trails B Seconds (p < 0.02). There is a similar age-related decline in plasma testosterone levels in men with either PD or AD. Previously described associations between low testosterone levels and frontal lobe dysfunction in normal aged men, together with these results, suggest that the hormonal deficiency may act as a "second hit" to impair cognitive function in neurodegenerative disease.

Breast milk provides better antioxidant power than does formula.

PubMed

Aycicek, Ali; Erel, Ozcan; Kocyigit, Abdurrahim; Selek, Sahbettin; Demirkol, Mehmet Resit

2006-06-01

We examined the effect of breast milk on plasma total antioxidant capacity (TAC), total peroxide (TP), and oxidative stress index (OSI), which are biomarkers of oxidative status. Fifty-four healthy term infants 3 to 6 mo of age were fed breast milk or a cow's milk modified formula. Plasma TAC, vitamin C, albumin, bilirubin, and uric acid levels were measured as indexes of antioxidative markers. Plasma TP levels were measured as an oxidative stress marker. The OSI was calculated to assess oxidative status. No significant differences were observed between groups with respect to growth or anthropometric measurements. Plasma uric acid, total protein, and albumin concentrations were slightly higher in the breast-fed group than in the formula-fed group. There was a positive correlation between infant's age and serum albumin levels; between TAC and plasma uric acid, albumin, and total bilirubin; and between plasma iron and TP levels in both groups (r > 0.256, P < 0.05). In addition, there was a negative correlation between plasma iron and TAC (r = -0.267, P = 0.01). Plasma TAC and vitamin C levels were significantly higher in the breast-fed group than in the formula-fed group (P < 0.05). Plasma TP levels and the OSI were higher in the formula-fed group than those in the breast-fed group (P < 0.05). Our data suggest that breast milk provides better antioxidant power than does formula.

Progranulin plasma levels predict the presence of GRN mutations in asymptomatic subjects and do not correlate with brain atrophy: results from the GENFI study.

PubMed

Galimberti, Daniela; Fumagalli, Giorgio G; Fenoglio, Chiara; Cioffi, Sara M G; Arighi, Andrea; Serpente, Maria; Borroni, Barbara; Padovani, Alessandro; Tagliavini, Fabrizio; Masellis, Mario; Tartaglia, Maria Carmela; van Swieten, John; Meeter, Lieke; Graff, Caroline; de Mendonça, Alexandre; Bocchetta, Martina; Rohrer, Jonathan D; Scarpini, Elio

2018-02-01

We investigated whether progranulin plasma levels are predictors of the presence of progranulin gene (GRN) null mutations or of the development of symptoms in asymptomatic at risk members participating in the Genetic Frontotemporal Dementia Initiative, including 19 patients, 64 asymptomatic carriers, and 77 noncarriers. In addition, we evaluated a possible role of TMEM106B rs1990622 as a genetic modifier and correlated progranulin plasma levels and gray-matter atrophy. Plasma progranulin mean ± SD plasma levels in patients and asymptomatic carriers were significantly decreased compared with noncarriers (30.5 ± 13.0 and 27.7 ± 7.5 versus 99.6 ± 24.8 ng/mL, p < 0.00001). Considering the threshold of >61.55 ng/mL, the test had a sensitivity of 98.8% and a specificity of 97.5% in predicting the presence of a mutation, independent of symptoms. No correlations were found between progranulin plasma levels and age, years from average age at onset in each family, or TMEM106B rs1990622 genotype (p > 0.05). Plasma progranulin levels did not correlate with brain atrophy. Plasma progranulin levels predict the presence of GRN null mutations independent of proximity to symptoms and brain atrophy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Relationship between functional capacity and body mass index with plasma coenzyme Q10 and oxidative damage in community-dwelling elderly-people.

PubMed

Del Pozo-Cruz, Jesús; Rodríguez-Bies, Elizabeth; Navas-Enamorado, Ignacio; Del Pozo-Cruz, Borja; Navas, Plácido; López-Lluch, Guillermo

2014-04-01

The impact of aging and physical capacity on coenzyme Q10 (Q10) levels in human blood is unknown. Plasma Q10 is an important factor in cardiovascular diseases. To understand how physical activity in the elderly affects endogenous Q10 levels in blood plasma, we studied a cohort of healthy community-dwelling people. Volunteers were subjected to different tests of the Functional Fitness Test Battery including handgrip strength, six-minute walk, 30 s chair to stand, and time up and go tests. Anthropometric characteristics, plasma Q10 and lipid peroxidation (MDA) levels were determined. Population was divided according to gender and fitness. We found that people showing higher levels of functional capacity presented lower levels of cholesterol and lipid peroxidation accompanied by higher levels of Q10 in plasma. The ratio Q10/cholesterol and Q10/LDL increased in these people. No relationship was found when correlated to muscle strength or agility. On the other hand, obesity was related to lower Q10 and higher MDA levels in plasma affecting women more significantly. Our data demonstrate for the first time that physical activity at advanced age can increase the levels of Q10 and lower the levels of lipid peroxidation in plasma, probably reducing the progression of cardiovascular diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Plasma levels of brain-derived neurotrophic factor and interleukin-6 in patients with dysthymic disorder: comparison with age- and sex-matched major depressed patients and healthy controls.

PubMed

Yoshimura, Reiji; Umene-Nakano, Wakako; Hoshuyama, Tsutomu; Ikenouchi-Sugita, Atsuko; Hori, Hikaru; Katsuki, Asuka; Hayashi, Kenji; Atake, Kiyokazu; Nakamura, Jun

2010-11-01

In the present study, we investigated the serum BDNF levels and plasma IL-6 levels in patients with dysthymic disorder, major depressive disorder and control subjects. Eighteen patients who met the DSM-IV criteria (American Psychiatric Association, 1994) for dysthymic disorder (male/female: 5/13; age: 36 ± 9 year) and 20 patients (male/female: 7/13; age: 38 ± 10 year) who met the criteria for major depressive disorder were enrolled. The serum BDNF levels in patients with dysthymic and major depressive disorder were significantly lower than those in the control subjects. However, no difference was found between the dysthymic group and major depression group. The plasma IL-6 levels in the dysthymic group and major depression group were significantly higher than those in the control group. No difference was observed in the plasma IL-6 levels between the dysthymic group and major depression group. These results suggest that the pathophysiology of dysthymic disorder and major depression might be similar in terms of the blood levels of BDNF and IL-6. Copyright © 2011 John Wiley & Sons, Ltd.

Mild hypercholesterolemia, normal plasma triglycerides, and normal glucose levels across dementia staging in Alzheimer's disease: a clinical setting-based retrospective study.

PubMed

Ramdane, Said; Daoudi-Gueddah, Doria

2011-08-01

We examined retrospectively the concurrent relationships between fasting plasma total cholesterol, triglycerides, and glucose levels, and Alzheimer's disease (AD), in a clinical setting-based study. Total cholesterol level was higher in patients with AD compared to elderly controls; triglycerides or glucose levels did not significantly differ between the 2 groups. Respective plotted trajectories of change in cholesterol level across age were fairly parallel. No significant difference in total cholesterol levels was recorded between patients with AD classified by the Clinical Dementia Rating (CDR) score subgroups. These results suggest that patients with AD have relative mild total hypercholesterolemia, normal triglyceridemia, and normal fasting plasma glucose level. Mild total hypercholesterolemia seems to be permanent across age, and across dementia severity staging, and fairly parallels the trajectory of age-related change in total cholesterolemia of healthy controls. We speculate that these biochemical parameters pattern may be present long before-a decade at least-the symptomatic onset of the disease.

Visceral fat area is a strong predictor of leukocyte cell-derived chemotaxin 2, a potential biomarker of dyslipidemia.

PubMed

Tanisawa, Kumpei; Taniguchi, Hirokazu; Sun, Xiaomin; Ito, Tomoko; Kawakami, Ryoko; Sakamoto, Shizuo; Higuchi, Mitsuru

2017-01-01

Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine linking obesity to skeletal muscle insulin resistance. Although previous studies reported that obesity was associated with high levels of circulating LECT2 in human, the associations of detailed body fat distribution with LECT2 levels have not been examined. Furthermore, although animal study suggested that exercise decreased circulating LECT2 levels, it remains unknown whether physical fitness is associated with LECT2 levels in human. We therefore examined the relationship of plasma LECT2 levels with various adiposity indices and cardiorespiratory fitness (CRF) in middle-aged and elderly Japanese men. Furthermore, we examined the relationship of LECT2 levels with the presence of metabolic syndrome, hypertension, insulin resistance and dyslipidemia to determine the clinical significance of measuring circulating LECT2. This was a cross-sectional study of 143 Japanese men (age: 30-79 years). Participants' plasma LECT2 levels were measured by an enzyme-linked immunosorbent assay. To assess their abdominal fat distributions, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using magnetic resonance imaging. CRF was assessed by measuring peak oxygen uptake ([Formula: see text]). All adiposity indices measured in this study were positively correlated with plasma LECT2 levels, while [Formula: see text] was negatively correlated with LECT2 levels after adjustment for age. The correlations, except for VFA were no longer significant with further adjustment for VFA. Stepwise multiple linear regression analysis revealed that VFA was the strongest predictor of plasma LECT2 levels. Plasma LECT2 levels differed based on the presence of metabolic syndrome and dyslipidemia, but not hypertension and insulin resistance. Logistic regression analyses revealed that plasma LECT2 levels were significantly associated with dyslipidemia independently of VFA; VFA was not significantly associated with dyslipidemia after adjustment for LECT2. VFA was the strongest predictor of plasma LECT2 that is a potential biomarker linking visceral obesity to dyslipidemia.

Effects of feeding level of milk replacer on body growth, plasma metabolite and insulin concentrations, and visceral organ growth of suckling calves.

PubMed

Kamiya, Mitsuru; Matsuzaki, Masatoshi; Orito, Hideki; Kamiya, Yuko; Nakamura, Yoshi-nori; Tsuneishi, Eisaku

2009-12-01

The objective was to evaluate effects of feeding level of milk replacer on body growth, plasma metabolite and insulin concentrations, and allometric growth of visceral organs in suckling calves. Holstein bull calves (n = 8; 3-4 days of age) were fed either a low amount (average 0.63 kgDM/day, LM) or high amount (average 1.15 kgDM/day, HM) of high protein milk replacer until they were slaughtered at 6 weeks of age. Body weight (BW) at 4, 5, and 6 weeks of age, feed intake, average daily gain, and feed efficiency were higher in the HM than LM calves. The HM group had higher plasma glucose at 3 and 4 weeks of age and insulin levels after the age of 4 weeks compared with LM calves whereas no effect was detected on plasma nonesterified fatty acid or urea nitrogen concentrations. The HM calves had greater empty body weight (EBW), viscera-free BW and most of the organs dissected than LM calves. Relative weights (% of EBW) of liver, spleen, kidneys, and internal fat were higher, whereas head and large intestine was lower in HM than LM calves. The results suggest that increased milk feeding levels would accelerate the growth of the body and specific organs.

Unique sex- and age-dependent effects in protective pathways in acute kidney injury.

PubMed

Boddu, Ravindra; Fan, Chunlan; Rangarajan, Sunil; Sunil, Bhuvana; Bolisetty, Subhashini; Curtis, Lisa M

2017-09-01

Sex and age influence susceptibility to acute kidney injury (AKI), with young females exhibiting lowest incidence. In these studies, we investigated mechanisms which may underlie the sex/age-based dissimilarities. Cisplatin (Cp)-induced AKI resulted in morphological evidence of injury in all groups. A minimal rise in plasma creatinine (PCr) was seen in Young Females, whereas in Aged Females, PCr rose precipitously. Relative to Young Males, Aged Males showed significantly, but temporally, comparably elevated PCr. Notably, Aged Females showed significantly greater mortality, whereas Young Females exhibited none. Tissue KIM-1 and plasma NGAL were significantly lower in Young Females than all others. IGFBP7 levels were modestly increased in both Young groups. IGFBP7 levels in Aged Females were significantly elevated at baseline relative to Aged Males, and increased linearly through day 3 , when these levels were comparable in both Aged groups. Plasma cytokine levels similarly showed a pattern of protective effects preferentially in Young Females. Expression of the drug transporter MATE2 did not explain the sex/age distinctions. Heme oxygenase-1 (HO-1) levels (~28-kDa species) showed elevation at day 1 in all groups with highest levels seen in Young Males. Exclusively in Young Females, these levels returned to baseline on day 3 , suggestive of a more efficient recovery. In aggregate, we demonstrate, for the first time, a distinctive pattern of response to AKI in Young Females relative to males which appears to be significantly altered in aging. These distinctions may offer novel targets to exploit therapeutically in both females and males in the treatment of AKI.

BMI, body fat mass and plasma leptin level in relation to cardiovascular diseases risk factors among adolescents in Taitung.

PubMed

Wu, Ya-Ke; Chu, Nain-Feng; Huang, Ya-Hsien; Syu, Jhu-Ting; Chang, Jin-Biou

2016-01-01

To investigate the risk factors associated with cardiovascular diseases and its relation to BMI, body fat mass and plasma leptin level among adolescents in Taitung, Taiwan. A cross-sectional Taitung Children Heart Study for 500 young adolescents between ages 13 and 15 was conducted. Gender-specific regression models were used to determine the associations between BMI, percentage of body fat mass, plasma leptin level and seven CVDs risk factors (systolic and diastolic blood pressure, mean arterial pressure, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol) before and after adjusting for weight status and age. After adjusting for weight status and age, BMI was positively associated with systolic BP, triglycerides, LDL-cholesterol levels but negatively associated with HDL-cholesterol level in boys while positively associated with systolic and diastolic BP, mean arterial pressure, and LDL-cholesterol level in girls. The percentage of body fat mass was positively associated with triglycerides, total cholesterol, and LDL-cholesterol in boys while positively associated with systolic BP, total cholesterol, and LDL-cholesterol in girls. Plasma leptin was positively associated with triglycerides, total cholesterol and LDL-cholesterol in boys but no statistically significant associations with CVDs risk factors in girls. A strong relationship between the percentage of body fat mass and plasma leptin appeared among all participants (r=0.59, p<0.01). BMI, body fat mass and plasma leptin level may be used to identify certain CVDs risk factors among Taitung adolescents. Future researches could consider measuring body fat mass in the relationship of CVDs risk factors instead of plasma leptin among young adolescents. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Association between obesity-related biomarkers and cognitive and motor development in infants.

PubMed

Camargos, Ana Cristina R; Mendonça, Vanessa A; Oliveira, Katherine S C; de Andrade, Camila Alves; Leite, Hércules Ribeiro; da Fonseca, Sueli Ferreira; Vieira, Erica Leandro Marciano; Teixeira Júnior, Antônio Lúcio; Lacerda, Ana Cristina Rodrigues

2017-05-15

This study aimed to verify the association between obesity-related biomarkers and cognitive and motor development in infants between 6 and 24 months of age. A cross-sectional study was conducted with 50 infants and plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2), chemokines, brain-derived neurotrophic factor (BDNF), serum cortisol and redox status were measured. The Bayley-III test was utilized to evaluate cognitive and motor development, and multiple linear stepwise regression models were performed to verify the association between selected biomarkers and cognitive and motor development. A significant association was found among plasma leptin and sTNFR1 levels with cognitive composite scores, and these two independents variables together explained 37% of the variability of cognitive composite scores (p=0.001). Only plasma sTNFR1 levels were associated and explained 24% of the variability of motor composite scores (p=0.003). Plasma levels of sTNFR1 were associated with the increase in cognitive and motor development scores in infants between 6 and 24 months of age through a mechanism not directly related to excess body weight. Moreover, increase in plasma levels of leptin reduced the cognitive development in this age range. Copyright © 2017 Elsevier B.V. All rights reserved.

Insulin-like growth factors (IGF-I, free IGF-I and IGF-II) and insulin-like growth factor binding proteins (IGFBP-2, IGFBP-3, IGFBP-6, and ALS) in blood circulation.

PubMed

Yu, H; Mistry, J; Nicar, M J; Khosravi, M J; Diamandis, A; van Doorn, J; Juul, A

1999-01-01

Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) play an important role in cell growth and differentiation. Clinical and epidemiological studies have indicated that measuring IGFs and IGFBPs in blood has potential implications in assessing growth-related abnormalities and risks of certain types of cancer. To facilitate the application, we reported a large collection of reference ranges of IGFs and IGFBPs in normal population and evaluations of these molecules in serum and plasma as well as the impact of freeze-thaw cycles on the measurement. IGF-I, IGFBP-3 andALS showed a similar pattern of change associated with age. Levels of these molecules were low at birth and increased with age through puberty. After puberty the levels declined slowly with age. Overall, IGF-I, IGFBP-3 and ALS were slightly higher in females than in males. Free IGF-I accounted for about 1% of the total IGF-I and its variation with age was similar to total IGF-I. IGF-II levels were also increased with age from birth to puberty, but became stable after puberty. There was little difference in IGF-II levels between genders. IGFBP-2 levels declined with age from birth to puberty. Levels of IGFBP-6 in contrast were increased with age. These IGF binding proteins were higher in males than in females. IGFs, IGFBP-3 and ALS were 5-10% higher in serum than in plasma. IGFBP-2 and IGFBP-6 differed substantially between serum and plasma. Freeze-thaw treatment up to five cycles had little impact on plasma levels of IGFs and IGFBP-3. Our observations suggest that levels of IGFs and their binding proteins are varied with age, gender, and types of specimen and that these variations need to be taken into consideration when IGFs and their binding proteins are utilized in clinic and research.

[Atorvastatin and oxidized low density lipoprotein antibody. Relationship to age].

PubMed

Sánchez Muñoz-Torrero, Juan Francisco; Crespo, Leandro; Fernández Pereira, Luis; Pereira, Gema; Cámara, Carmen; Costo, Alberto

2011-02-26

In hypercholesterolemic patients, we studied the relationships of plasma levels of LDLoxab with cardiovascular variables and its changes after treatment with atorvastatin. We studied, in 48 patients, the levels of LDLoxab, as well as lipid, oxidative stress and inflammatory biomarkers, at baseline and 24 weeks after treatment with 20mg of atorvastatin. Baseline: a correlation was observed between LDLoxab and age (r= 0.41, P=.03), waist (r=0.38, P=.04) and C reactive protein (r= 0.46, P=.02), but not with other variables. Atorvastatin treatment did not decrease LDLoxab;(mU/mL, median [CI 95%]: baseline: 413 [187-1,196] and 24 weeks: 349 [101-1559]). The percentage change at week 24, was negatively correlated with age (r=-0.37, P=.03) but not with other variables. In hypercholesterolemic subjects plasma LDLoxab levels were positively corelated with age, waist and C reactive protein. There were no changes in plasma levels of LDLoxab after treatment with atorvastatin, but the variation was associated with age, suggesting that the immunomodulatory actions may depend of this. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Plasma concentrations of lipids and lipoproteins in newborn kids and female Baladi goats during late pregnancy and onset of lactation.

PubMed

Hussein, S A; Azab, M E

1998-01-01

Concentrations of blood lipids and some lipoproteins were investigated in normal female Baladi goats during late pregnancy, parturition and onset of lactation as well as in their newborn kids during the first two weeks of life. A total number of 60 herparinized blood samples was collected from does at 4, 3, 2 and 1 weeks pre-partum, day of parturition and at 1, 2, 3 and 4 weeks postpartum. In addition, blood samples were also collected from their newborn kids during the first two weeks of life (day of birth, 1 and 2 weeks of age). Plasma was separated and analyzed for concentration of total lipid, total cholesterol, triacylglycerols, phospholipids, non esterified fatty acids (NEFA) and some lipoproteins as high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). The obtained results revealed that there was a significant decrease in plasma level of total lipids at one week after parturition. Plasma level of triaclyglycerols was significantly higher at 4, 3 and 2 weeks before parturition. This increase became very highly significant at one week before parturition. Meanwhile, plasma phospholipid concentrations showed a significant decrease at 3 weeks before parturition, followed by an significant increase at 2 and 3 weeks after parturition and highly significant increase at 4 weeks after parturition. The concentration of plasma NEFA showed a significant increase at 4 weeks before parturition followed by a very highly significant increase at 2 and 1 week before parturition. On the other hand plasma NEFA was non detected at 2, 3 and 4 weeks post-partum when compared with the value reported at day of parturition. Regarding plasma lipoprotein concentrations the obtained results showed that there was a significant increase in plasma HDL-C level at 2 and 3 weeks after parturition, followed by a very highly significant decrease at the fourth week post-partum. However, plasma LDL-C level showed a significant decrease at 3, 2 and 1 weeks before parturition, followed by a further highly significant decrease at 1 and 2 weeks post-partum. In newborn kids plasma concentrations of total lipids, total cholesterol, phospholipids, HDL-C and LDL-C were very markedly increased at 1 and 2 weeks of age. However, plasma triacylglycerol concentrations showed a highly significant decrease at 1 and 2 weeks of age. The concentration of plasma NEFA showed a very highly significant decrease at 2 weeks of age, whereas, at one week of age plasma NEFA were not detected in comparison with first day of life.

Binge drinking and total alcohol consumption from 16 to 43 years of age are associated with elevated fasting plasma glucose in women: results from the northern Swedish cohort study.

PubMed

Nygren, Karina; Hammarström, Anne; Rolandsson, Olov

2017-06-08

Studies have indicated that moderate alcohol consumption is associated with lower incidence of diabetes in women. However, not only the amount but also the drinking pattern could be of importance when assessing the longitudinal relation between alcohol and glucose. Also, there is a lack of studies on alcohol use beginning in adolescence on adult glucose levels. The aim was to examine the association between total alcohol consumption and binge drinking between ages 16 and 43 and fasting plasma glucose at age 43. Data were retrieved from a 27-year prospective cohort study, the Northern Swedish Cohort. In 1981, all 9th grade students (n = 1083) within a municipality in Sweden were invited to participate. There were re-assessments at ages 18, 21, 30 and 43. This particular study sample consisted of 897 participants (82.8%). Fasting plasma glucose (mmol/L) was measured at a health examination at age 43. Total alcohol consumption (in grams) and binge drinking were calculated from alcohol consumption data obtained from questionnaires. Descriptive analyses showed that men had higher levels of fasting plasma glucose as compared to women. Men also reported higher levels of alcohol consumption and binge drinking behavior. Linear regressions showed that total alcohol consumption in combination with binge drinking between ages 16 and 43 was associated with elevated fasting plasma glucose at age 43 in women (beta = 0.14, p = 0.003) but not in men after adjustment for BMI, hypertension and smoking at age 43. Our findings indicate that reducing binge drinking and alcohol consumption among young and middle-aged women with the highest consumption might be metabolically favorable for their future glucose metabolism.

Plasma signaling proteins in persons at genetic risk for Alzheimer disease: influence of APOE genotype.

PubMed

Ringman, John M; Elashoff, David; Geschwind, Daniel H; Welsh, Brian T; Gylys, Karen H; Lee, Cathy; Cummings, Jeffrey L; Cole, Greg M

2012-06-01

To study the effect of familial Alzheimer disease (FAD) mutations and APOE genotype on plasma signaling protein levels. Cross-sectional comparison of plasma levels of 77 proteins measured using multiplex immune assays. A tertiary referral dementia research center. Thirty-three persons from families harboring PSEN1 or APP mutations, aged 19 to 59 years. Protein levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs) and among APOE genotype groups, using multiple linear regression models. Twenty-one participants were FAD MCs and 12 were NCs. Six had the APOE ε2/3, 6 had the ε3/4, and 21 had the ε3/3 genotype. Levels of 17 proteins differed among APOE genotype groups, and there were significant interactions between age and APOE genotype for 12 proteins. Plasma levels of apolipoprotein E and superoxide dismutase 1 were highest in the ε2 carriers, lowest in ε4 carriers, and intermediate in the ε3 carriers. Levels of multiple interleukins showed the opposite pattern and, among the ε4 carriers, demonstrated significant negative correlations with age. Although there were no significant differences between FAD MCs and NCs, there were interactions between mutation status and APOE genotype for 13 proteins. We found different patterns of inflammatory markers in young and middle-aged persons among APOE genotype groups. The APOE ε4 carriers had the lowest levels of apolipoprotein E. Young ε4 carriers have increased inflammatory markers that diminish with age. We demonstrated altered inflammatory responses in young and middle adulthood in ε4 carriers that may relate to AD risk later in life.

Autoxidation products of both carbohydrates and lipids are increased in uremic plasma: is there oxidative stress in uremia?

PubMed

Miyata, T; Fu, M X; Kurokawa, K; van Ypersele de Strihou, C; Thorpe, S R; Baynes, J W

1998-10-01

Advanced glycation end products (AGEs), formed by non-enzymatic glycation and oxidation (glycoxidation) reactions, have been implicated in the pathogenesis of several diseases, including normoglycemic uremia. AGE research in uremia has focused on the accumulation of carbohydrate-derived adducts generated by the Maillard reaction. Recent studies, however, have demonstrated that one AGE, the glycoxidation product carboxymethyllysine (CML), could be derived not only from carbohydrates but also from oxidation of polyunsaturated fatty acids in vitro, raising the possibility that both carbohydrate and lipid autoxidation might be increased in uremia. To address this hypothesis, we applied gas chromatography-mass spectrometry and high performance liquid chromatography to measure protein adducts formed in uremic plasma by reactions between carbonyl compounds and protein amino groups: pentosidine derived from carbohydrate-derived carbonyls, malondialdehyde (MDA)-lysine derived from lipid-derived carbonyls, and CML originating possibly from both sources. All three adducts were elevated in uremic plasma. Plasma CML levels were mainly (>95%) albumin bound. Their levels were not correlated with fructoselysine levels and were similar in diabetic and non-diabetic patients on hemodialysis, indicating that their increase was not driven by glucose. Pentosidine and MDA-lysine were also increased in plasma to the same extent in diabetic and non-diabetic hemodialysis patients. Statistical analysis indicated that plasma levels of CML correlated weakly (P < 0.05) with those of pentosidine and MDA-lysine, but that pentosidine and MDA-lysine varied independently (P > 0.5). These data suggest that the increased levels of AGEs in blood, and probably in tissues, reported in uremia implicate a broad derangement in non-enzymatic biochemistry involving alterations in autoxidation of both carbohydrates and lipids.

Hematocrit and plasma osmolality values of young-of-year shortnose sturgeon following acute exposures to combinations of salinity and temperature

USGS Publications Warehouse

Ziegeweid, J.R.; Black, M.C.

2010-01-01

Little is known about the physiological capabilities of young-of-year (YOY) shortnose sturgeon. In this study, plasma osmolality and hematocrit values were measured for YOY shortnose sturgeon following 48-h exposures to 12 different combinations of salinity and temperature. Hematocrit levels varied significantly with temperature and age, and plasma osmolalities varied significantly with salinity and age. Plasma osmolality and hematocrit values were similar to previously published values for other sturgeons of similar age and size in similar treatment conditions. ?? 2010 Springer Science+Business Media B.V.

Reference values of amino acids and of common clinical chemistry in plasma of healthy infants aged 1 and 4 months.

PubMed

Haschke-Becher, Elisabeth; Kainz, Alexander; Bachmann, Claude

2016-01-01

To compare plasma levels of amino acids and clinical chemistry parameters in healthy infants at 1 and 4 months of age and to establish corresponding reference limits. Data of three multicenter studies assessing the safety of new infant formulas were used. During these studies infants of both age-groups were either breast-fed or received formulas of low or high protein content. All samples were analyzed centrally in the same accredited laboratory. Plasma was collected from 521 infants in total, 157 boys and 135 girls aged 1 month and 121 boys and 108 girls aged 4 months. At the age of 1 month, 62 infants had received exclusively breast milk, 198 exclusively formula, and 27 both; in the 4-months age group corresponding numbers were 49, 158 and 18, respectively; for 9 infants, diet was unknown. Concentrations of most amino acids and clinical chemistry parameters differed significantly between both ages. Regardless of age, most plasma amino acid levels were comparable or lower in breast-fed than in formula-fed infants whereas at 1 month of age most clinical chemistry parameters were higher. While in breast-fed infants the plasma urea concentration decreased over 4 months of age, it increased in formula-fed infants. There were significant differences between infants fed a low and high protein formula. At both ages, high protein formulas resulted in significantly higher threonine, 2-aminobutyrate, and urea concentrations. For clinical use, age- and diet specific reference limits in infants are warranted.

Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome.

PubMed

Cannizzaro, Luca; Rossoni, Giuseppe; Savi, Federica; Altomare, Alessandra; Marinello, Cristina; Saethang, Thammakorn; Carini, Marina; Payne, D Michael; Pisitkun, Trairak; Aldini, Giancarlo; Leelahavanichkul, Asada

2017-01-01

The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ). Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half. Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented. Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by PPARγ modulation.

Alpha-synuclein levels in blood plasma decline with healthy aging.

PubMed

Koehler, Niklas K U; Stransky, Elke; Meyer, Mirjam; Gaertner, Susanne; Shing, Mona; Schnaidt, Martina; Celej, Maria S; Jovin, Thomas M; Leyhe, Thomas; Laske, Christoph; Batra, Anil; Buchkremer, Gerhard; Fallgatter, Andreas J; Wernet, Dorothee; Richartz-Salzburger, Elke

2015-01-01

There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes or chaperone activity in older individuals. Our results support the concept that alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance of the proteostasis network, a key component of healthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.

Suppression of homocysteine levels by vitamin B12 and folates: age and gender dependency in the Jackson Heart Study.

PubMed

Henry, Olivia R; Benghuzzi, Hamed; Taylor, Herman A; Tucci, Michelle; Butler, Kenneth; Jones, Lynne

2012-08-01

To examine factors potentially contributing to premature cardiovascular disease mortality in African Americans (40% versus 20% all other populations), plasma homocysteine, serum vitamin B12 and folate levels were examined for African American participants in the Jackson Heart Study. Of 5192 African American Jackson Heart Study participants (21-94 years), 5064 (mean age, 55 ± 13 years; 63% female) had homocysteine levels measured via fasting blood samples, with further assessments of participants' vitamin B12 (n = 1790) and folate (n = 1788) levels. Regression analyses were used to examine age, gender, vitamin B12 and folate with homocysteine levels. Homocysteine levels, a purported surrogate risk factor for cardiovascular disease, increased with age, were inversely proportional to folate and vitamin B12 levels (P < 0.001) and were higher for men of all ages. The results show that, as with other populations, age, gender, vitamin B12 and folate may predict homocysteine levels for African Americans. Diet may be an important predictive factor as well, given the relationships that were observed between plasma homocysteine and serum B vitamin levels.

Plasma Levels of Folates, Riboflavin, Vitamin B6, and Ascorbate in Severely Disturbed Children.

ERIC Educational Resources Information Center

Sankar, D. V. Siva

1979-01-01

The plasma levels of folic acid, ascorbic acid, pyridoxine, and riboflavin were studied in 125 severely emotionally disturbed children (ages 5-16 years) to determine whether they had overt vitamin deficiencies. (Author/DLS)

Low plasma selenium concentration is associated with elevated risk to neoplastic polyps of the colon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, L.C.; Hixson, L.G.; Sampliner, R.E.

1991-03-11

A cross-sectional study was conducted to examine the relationship of selenium (Se) status and polyps incidence in a sequential series of 100 patients undergoing outpatient colonoscopies at the Tucson VA Hospital. Se was measured in plasma samples by electrothermal atomic absorption spectrophotometry with Zeeman background correction using a reduced palladium matrix modified. The activities of the Se-dependent enzyme glutathione peroxidase (SeGSHpx) were measured using H{sub 2}O{sub 2} as substrate in all plasma samples and in colonic mucosal biopsies obtained from some patients. The mean plasma Se concentration of patients without polyps was 134 ng/ml. Mean plasma Se levels of patientsmore » with only diminutive or large polyps were 127 ng/ml and 125 ng/ml; while patients with polyps of both sizes had a mean plasma Se level of 121 ng/ml. Patients with no reported history of cancer, neoplastic polyps or prior colonoscopy, showed an inverse association of plasma Se level and risk of benign colonic neoplasms. The age-adjusted odds ratio for neoplastic polyps was 3.8 for patients with plasma Se levels below vs. above the median value. This association was stronger for patients under 68 yrs of age than for older patients. Activities of SeGSHpx in plasma or colonic mucosa were not related to plasma Se level; however, smokers showed greater SeGSHpx activities than non-smokers. This study is the first to detect an association of Se status and risk to neoplastic polyps of the colon.« less

Impairment of liver synthetic function and the production of plasma proteins in primary breast cancer patients on doxorubicincyclophosphamide (AC) protocol.

PubMed

Saleem, Zikria; Ahmad, Mobasher; Hashmi, Furqan Khurshid; Saeed, Hamid; Aziz, Muhammad Tahir

2016-09-01

Doxorubicin and Cyclophosphamide (AC protocol) combination is usually considered as a first line therapy in newly diagnosed breast cancer patients. Thus, a retrospective observational study was conducted to monitor the effect of AC protocol on liver synthetic functions and production of plasma proteins in breast cancer patients, reporting to specialized cancer care hospital of Lahore, Pakistan. A total of 75 patients (n=75) on AC protocol with breast cancer were observed in this study. The patient data including age, gender, body surface area, dosage, disease status and laboratory biochemical values were recorded by reviewing historical treatment records. Pre-treatment values were taken as baseline values for albumin, globulin, blood urea nitrogen (BUN), albumin/globulin (A/G) ratio and total proteins. The baseline values were compared after each cycle of by applying ANOVA using statistical tool SPSS® version 21. The plasma levels of blood urea nitrogen (BUN), total protein and globulin dropped significantly (p<0.05) in patients of all age groups. However, the albumin levels were not significantly changed (p>0.05). The A/G ratio level increased (p<0.05) as a result of reduction in globulin levels. Significant changes in plasma protein levels were observed in the elderly patients (50 to 65 years) than patients between 20 to 50 years of age. AC protocol impairs liver synthetic functions as observed by decreased blood urea nitrogen (BUN) and plasma protein levels.

Optimal plasma progranulin cutoff value for predicting null progranulin mutations in neurodegenerative diseases: a multicenter Italian study.

PubMed

Ghidoni, Roberta; Stoppani, Elena; Rossi, Giacomina; Piccoli, Elena; Albertini, Valentina; Paterlini, Anna; Glionna, Michela; Pegoiani, Eleonora; Agnati, Luigi F; Fenoglio, Chiara; Scarpini, Elio; Galimberti, Daniela; Morbin, Michela; Tagliavini, Fabrizio; Binetti, Giuliano; Benussi, Luisa

2012-01-01

Recently, attention was drawn to a role for progranulin in the central nervous system with the identification of mutations in the progranulin gene (GRN) as an important cause of frontotemporal lobar degeneration. GRN mutations are associated with a strong reduction of circulating progranulin and widely variable clinical phenotypes: thus, the dosage of plasma progranulin is a useful tool for a quick and inexpensive large-scale screening of carriers of GRN mutations. To establish the best cutoff threshold for normal versus abnormal levels of plasma progranulin. 309 cognitively healthy controls (25-87 years of age), 72 affected and unaffected GRN+ null mutation carriers (24-86 years of age), 3 affected GRN missense mutation carriers, 342 patients with neurodegenerative diseases and 293 subjects with mild cognitive impairment were enrolled at the Memory Clinic, IRCCS S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy, and at the Alzheimer Unit, Ospedale Maggiore Policlinico and IRCCS Istituto Neurologico C. Besta, Milan, Italy. Plasma progranulin levels were measured using an ELISA kit (AdipoGen Inc., Seoul, Korea). Plasma progranulin did not correlate with age, gender or body mass index. We established a new plasma progranulin protein cutoff level of 61.55 ng/ml that identifies, with a specificity of 99.6% and a sensitivity of 95.8%, null mutation carriers among subjects attending to a memory clinic. Affected and unaffected GRN null mutation carriers did not differ in terms of circulating progranulin protein (p = 0.686). A significant disease anticipation was observed in GRN+ subjects with the lowest progranulin levels. We propose a new plasma progranulin protein cutoff level useful for clinical practice. Copyright © 2011 S. Karger AG, Basel.

Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study.

PubMed

Ameling, Sabine; Kacprowski, Tim; Chilukoti, Ravi Kumar; Malsch, Carolin; Liebscher, Volkmar; Suhre, Karsten; Pietzner, Maik; Friedrich, Nele; Homuth, Georg; Hammer, Elke; Völker, Uwe

2015-10-14

Non-cellular blood circulating microRNAs (plasma miRNAs) represent a promising source for the development of prognostic and diagnostic tools owing to their minimally invasive sampling, high stability, and simple quantification by standard techniques such as RT-qPCR. So far, the majority of association studies involving plasma miRNAs were disease-specific case-control analyses. In contrast, in the present study, plasma miRNAs were analysed in a sample of 372 individuals from a population-based cohort study, the Study of Health in Pomerania (SHIP). Quantification of miRNA levels was performed by RT-qPCR using the Exiqon Serum/Plasma Focus microRNA PCR Panel V3.M covering 179 different miRNAs. Of these, 155 were included in our analyses after quality-control. Associations between plasma miRNAs and the phenotypes age, body mass index (BMI), and sex were assessed via a two-step linear regression approach per miRNA. The first step regressed out the technical parameters and the second step determined the remaining associations between the respective plasma miRNA and the phenotypes of interest. After regressing out technical parameters and adjusting for the respective other two phenotypes, 7, 15, and 35 plasma miRNAs were significantly (q < 0.05) associated with age, BMI, and sex, respectively. Additional adjustment for the blood cell parameters identified 12 and 19 miRNAs to be significantly associated with age and BMI, respectively. Most of the BMI-associated miRNAs likely originate from liver. Sex-associated differences in miRNA levels were largely determined by differences in blood cell parameters. Thus, only 7 as compared to originally 35 sex-associated miRNAs displayed sex-specific differences after adjustment for blood cell parameters. These findings emphasize that circulating miRNAs are strongly impacted by age, BMI, and sex. Hence, these parameters should be considered as covariates in association studies based on plasma miRNA levels. The established experimental and computational workflow can now be used in future screening studies to determine associations of plasma miRNAs with defined disease phenotypes.

Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer's disease and down syndrome.

PubMed

Tatebe, Harutsugu; Kasai, Takashi; Ohmichi, Takuma; Kishi, Yusuke; Kakeya, Tomoshi; Waragai, Masaaki; Kondo, Masaki; Allsop, David; Tokuda, Takahiko

2017-09-04

There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer's disease (AD) pathology. This study is aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181) is informative in the diagnosis of AD. We have developed a novel ultrasensitive immunoassay to quantify plasma p-tau181, and measured the levels of plasma p-tau181 in three cohorts. In the first cohort composed of 20 AD patients and 15 age-matched controls, the plasma levels of p-tau181 were significantly higher in the AD patients than those in the controls (0.171 ± 0.166 pg/ml in AD versus 0.0405 ± 0.0756 pg/ml in controls, p = 0.0039). The percentage of the subjects whose levels of plasma p-tau181 exceeded the cut-off value (0.0921 pg/ml) was significantly higher in the AD group compared with the control group (60% in AD versus 16.7% in controls, p = 0.0090). In the second cohort composed of 20 patients with Down syndrome (DS) and 22 age-matched controls, the plasma concentrations of p-tau181 were significantly higher in the DS group (0.767 ± 1.26 pg/ml in DS versus 0.0415 ± 0.0710 pg/ml in controls, p = 0.0313). There was a significant correlation between the plasma levels of p-tau181 and age in the DS group (R 2  = 0.4451, p = 0.0013). All of the DS individuals showing an extremely high concentration of plasma p-tau181 (> 1.0 pg/ml) were older than the age of 40. In the third cohort composed of 8 AD patients and 3 patients with other neurological diseases, the levels of plasma p-tau181 significantly correlated with those of CSF p-tau181 (R 2  = 0.4525, p = 0.023). We report for the first time quantitative data on the plasma levels of p-tau181 in controls and patients with AD and DS, and these data suggest that the plasma p-tau181 is a promising blood biomarker for brain AD pathology. This exploratory pilot study warrants further large-scale and well-controlled studies to validate the usefulness of plasma p-tau181 as an urgently needed surrogate marker for the diagnosis and disease progression of AD.

Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease.

PubMed

Ramachandran, Surya; Venugopal, Anila; Kutty, V Raman; A, Vinitha; G, Divya; Chitrasree, V; Mullassari, Ajit; Pratapchandran, N S; Santosh, K R; Pillai, M Radhakrishna; Kartha, C C

2014-02-07

Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that Cyclophilin A is an inflammatory mediator in atherogenesis, the mechanistic role of cyclophilin A in diabetic vascular disease progression deserves detailed investigation.

Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease

PubMed Central

2014-01-01

Aims/hypothesis Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Methods Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Results Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Conclusions/interpretations Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that Cyclophilin A is an inflammatory mediator in atherogenesis, the mechanistic role of cyclophilin A in diabetic vascular disease progression deserves detailed investigation. PMID:24502618

Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging.

PubMed

Lin, Jonathan B; Sene, Abdoulaye; Santeford, Andrea; Fujiwara, Hideji; Sidhu, Rohini; Ligon, Marianne M; Shankar, Vikram A; Ban, Norimitsu; Mysorekar, Indira U; Ory, Daniel S; Apte, Rajendra S

2018-06-11

Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Plasma Signaling Proteins in Persons at Genetic Risk for Alzheimer Disease

PubMed Central

Ringman, John M.; Elashoff, David; Geschwind, Daniel H.; Welsh, Brian T.; Gylys, Karen H.; Lee, Cathy; Cummings, Jeffrey L.; Cole, Greg M.

2013-01-01

Objective To study the effect of familial Alzheimer disease (FAD) mutations and APOE genotype on plasma signaling protein levels. Design Cross-sectional comparison of plasma levels of 77 proteins measured using multiplex immune assays. Setting A tertiary referral dementia research center. Participants Thirty-three persons from families harboring PSEN1 or APP mutations, aged 19 to 59 years. Main Outcome Measures Protein levels were compared between FAD mutation carriers (MCs) and non-carriers (NCs) and among APOE genotype groups, using multiple linear regression models. Results Twenty-one participants were FAD MCs and 12 were NCs. Six had the APOE ε2/3, 6 had the ε3/4, and 21 had the ε3/3 genotype. Levels of 17 proteins differed among APOE genotype groups, and there were significant interactions between age and APOE genotype for 12 proteins. Plasma levels of apolipoprotein E and superoxide dismutase 1 were highest in the ε2 carriers, lowest in ε4 carriers, and intermediate in the ε3 carriers. Levels of multiple interleukins showed the opposite pattern and, among the ε4 carriers, demonstrated significant negative correlations with age. Although there were no significant differences between FAD MCs and NCs, there were interactions between mutation status and APOE genotype for 13 proteins. Conclusions We found different patterns of inflammatory markers in young and middle-aged persons among APOE genotype groups. The APOE ε4 carriers had the lowest levels of apolipoprotein E. Young ε4 carriers have increased inflammatory markers that diminish with age. We demonstrated altered inflammatory responses in young and middle adulthood in ε4 carriers that may relate to AD risk later in life. PMID:22689192

Age-specific oxidative status and the expression of pre- and postcopulatory sexually selected traits in male red junglefowl, Gallus gallus

PubMed Central

Noguera, Jose C; Dean, Rebecca; Isaksson, Caroline; Velando, Alberto; Pizzari, Tommaso

2012-01-01

Oxidative stress is emerging as a key factor underpinning life history and the expression of sexually selected traits. Resolving the role of oxidative stress in life history and sexual selection requires a pluralistic approach, which investigates how age affects the relationship between oxidative status (i.e., antioxidants and oxidative damage) and the multiple traits contributing to variation in reproductive success. Here, we investigate the relationship between oxidative status and the expression of multiple sexually selected traits in two-age classes of male red junglefowl, Gallus gallus, a species which displays marked male reproductive senescence. We found that, irrespective of male age, both male social status and comb size were strongly associated with plasma oxidative status, and there was a nonsignificant tendency for sperm motility to be associated with seminal oxidative status. Importantly, however, patterns of plasma and seminal antioxidant levels differed markedly in young and old males. While seminal antioxidants increased with plasma antioxidants in young males, the level of seminal antioxidants remained low and was independent of plasma levels in old males. In addition, old males also accumulated more oxidative damage in their sperm DNA. These results suggest that antioxidant allocation across different reproductive traits and somatic maintenance might change drastically as males age, leading to age-specific patterns of antioxidant investment. PMID:23139875

Plasma glial cell line-derived neurotrophic factor in patients with major depressive disorder: a preliminary study.

PubMed

Lee, Bun-Hee; Hong, Jin-Pyo; Hwang, Jung-A; Na, Kyoung-Sae; Kim, Won-Joong; Trigo, Jose; Kim, Yong-Ku

2016-02-01

Some clinical studies have reported reduced peripheral glial cell line-derived neurotrophic factor (GDNF) level in elderly patients with major depressive disorder (MDD). We verified whether a reduction in plasma GDNF level was associated with MDD. Plasma GDNF level was measured in 23 healthy control subjects and 23 MDD patients before and after 6 weeks of treatment. Plasma GDNF level in MDD patients at baseline did not differ from that in healthy controls. Plasma GDNF in MDD patients did not differ significantly from baseline to the end of treatment. GDNF level was significantly lower in recurrent-episode MDD patients than in first-episode patients before and after treatment. Our findings revealed significantly lower plasma GDNF level in recurrent-episode MDD patients, although plasma GDNF levels in MDD patients and healthy controls did not differ significantly. The discrepancy between our study and previous studies might arise from differences in the recurrence of depression or the ages of the MDD patients.

The relation between plasma α-synuclein level and clinical symptoms or signs of Parkinson's disease.

PubMed

Malec-Litwinowicz, Michalina; Plewka, Andrzej; Plewka, Danuta; Bogunia, Edyta; Morek, Michał; Szczudlik, Andrzej; Szubiga, Michał; Rudzińska-Bar, Monika

2018-03-01

Parkinson disease (PD) is the common neurodegenerative disease. α-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was found in peripheral fluids. Testing ASN in plasma is potential test for diagnose PD, but previous studies are controversial. The aim of this study was to investigate if plasma ASN level may be a valuable biomarker, is the level of plasma ASN concentration different in various motor subtypes of diseases, is there a relation between the level of plasma ASN and the severity of motor symptoms. Patients with PD hospitalized in Neurology Department, Medical College were performed sequencing the 8th and 9th exon of GBA gene. Next plasma ASN level was tested in 58 patients with sequenced GBA gene and in 38 healthy volunteers (HV), matched by the age (respectively 68.43 vs. 64.57 years of age) and sex (female %, respectively: 43.10 vs.44.74). Patients were assessed with the scales: UPDRS (II, III, IV), Hoehn-Yahr (HY) and qualified to PIGD or TD subtype. For homogeneity of the group patients with GBA mutation were excluded from the analysis. The ASN level did not differ between patients and HV (respectively: 4.53 vs. 3.73ng/ml) and between patients with different subtypes. There was inverse correlation between ASN and HY in PIGD subtype. Plasma ASN level is not valuable marker of the disease. It does not differ in subtypes of the disease. There is relation between plasma ASN level and the severity of the disease in PIGD subtype. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Evaluation of neutrophil gelatinase-associated lipocalin in pediatric patients with acute rotavirus gastroenteritis and dehydration.

PubMed

Çelik, Tanju; Altekin, Emel; İşgüder, Rana; Kenesari, Yasin; Duman, Murat; Arslan, Nur

2013-09-03

Dehydration caused by acute rotavirus gastroenteritis is a frequent finding in pediatric patients. The most important treatment modality in these patients is recognising and treating dehydration, electrolyte imbalance and acute kidney injury. Neutrophil gelatinase-associated lipocalin (NGAL) is used widely as a biomarker for the diagnosis of acute or chronic renal injury in numerous clinical studies. It is recognized as an early marker of acute renal failure before the elevation of routine biochemical tests such as creatinine. The aim of this study is to investigate the plasma and urine NGAL concentrations in mildly or moderately dehydrated patients with acute rotavirus gastroenteritis. A total of 30 patients (13 girls, mean age 62.5 ± 46.2 months) with diarrhea and mild/moderate dehydration and 35 healthy controls (17 girls, mean age 81.1 ± 41.8 months) were enrolled in the study. Plasma and urine NGAL levels of the two groups were compared. The mean age, gender and serum creatinine levels of the patients and healthy controls were similar. The mean plasma and urine NGAL levels of the patients were significantly higher than controls (plasma: 118.6 ± 81.2 vs. 66.5 ± 11.3, p = 0.001 and urine: 17.7 ± 17.5 vs. 10.6 ± 7.9, p = 0.035, respectively). Mildly or moderately dehydrated children have higher plasma and urine NGAL levels compared to control subjects. Plasma and/or urine NGAL levels can be used for the early prediction of renal impairment in children with mild or moderate dehydration.

[Plasma orexin-A level in patients with obstructive apnea-hypopnea syndrome].

PubMed

Yao, Xingqi; Yang, Hui; Zhang, Guifeng; Tang, Ying

2006-06-01

To investigate the effect of uvulopalatopharyngoplasty (UPPP) on changes of plasma orexin-A levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Fifty-four cases with OSAHS diagnosed by polysomnography were treated with uvulopalatopharyngoplasty and hyoid suspension. Plasma orexin-A levels in patients with OSAHS before and after surgical procedure 6 months, and in 20 healthy people with age,sex and BMI matched controls were measured by radioimmunoassay. The plasma was deproteinized by chromatography. Correlations between orexin-A levels and AHI, MAI and SaO2 min were analyzed. The plasma orexin-A levels in the OSAHS group was significantly higher than those in the control group (P < 0.01). Plasma orexin A levels in the patients with OSAHS correlated positively with the AHI (r < 0.658, P < 0.05) and MAI. (r = 0.464, P < 0.05) but correlated negatively with the SaO2 min. The plasma orexin-A levels of 54 responders after 6 months were significantly decreased (P < 0.01) than that of pre-operation, and there is no correlation between plasma orexin-A levels and BMI. The plasma orexin-A levels in the OSAHS patients are increased which may be caused by repeated nocturnal apnoea and hypoxia due to OSAHS. Surgical procedures may decreased the plasma orexin-A levels.

Expression of the androgen receptor in the testes and the concentrations of gonadotropins and sex steroid hormones in male turkeys (Meleagris gallopavo) during growth and development.

PubMed

Kiezun, J; Leska, A; Kaminska, B; Jankowski, J; Dusza, L

2015-04-01

Androgens, including testosterone (T) and androstenedione (A4), are essential for puberty, fertility and sexual functions. The biological activity of those hormones is mediated via the androgen receptor (AR). The regulation of androgen action in birds is poorly understood. Therefore, the present study analysed mRNA and protein expression of AR in the testes, plasma concentrations of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), T, A4 and oestradiol (E2), as well as the levels of T, A4 and E2 in testicular homogenates of male turkeys (Meleagris gallopavo) at the age of 4, 8, 12, 16, 20, 24 and 28weeks. Plasma concentrations of LH and FSH, as well as plasma and testicular levels of T and A4 began to increase at 20weeks of age. The lowest plasma levels of E2 were noted at 20weeks relative to other growth stages. The 20th week of life seems to be the key phase in the development of the reproductive system of turkeys. The AR protein was found in the nuclei of testicular cells in all examined growth stages. Higher expression of AR protein in the testes beginning at 20weeks of age was accompanied by high plasma concentrations of LH and high plasma and testicular levels of androgens. This relationship seems to be necessary to regulate male sexual function. Copyright © 2014 Elsevier Inc. All rights reserved.

Plasma Amino Acid Levels in Children with Autism and Their Families.

ERIC Educational Resources Information Center

Aldred, Sarah; Moore, Kieran M.; Fitzgerald, Michael; Waring, Rosemary H.

2003-01-01

Plasma amino acid levels were measured in autistic (n=12), Asperger syndrome (n=11) patients, their parents and siblings. Patients with autism or Asperger syndrome and their siblings and parents all had raised glutamic acid, phenyalanine, asparagine, tyrosine, alanine, and lysine levels than age-matched controls. Results suggest dysregulated amino…

Carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort

USDA-ARS?s Scientific Manuscript database

Diet may influence circulating adiponectin levels by improving insulin sensitivity. We examined the associations between carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults aged 26–81 y (n= 979 men and 1227 women). Dietary intakes were assessed using a FFQ. Fasting...

Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging.

PubMed

Gupta, V B; Laws, S M; Villemagne, V L; Ames, D; Bush, A I; Ellis, K A; Lui, J K; Masters, C; Rowe, C C; Szoeke, C; Taddei, K; Martins, R N

2011-03-22

There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which included both healthy controls and participants with early-stage AD. Total apoE and apoE4 were measured in 1,079 individuals drawn from the highly characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Total and isoform-specific plasma apoE levels were then compared with cerebral Aβ load, as assessed by PET using Pittsburgh compound B (PiB). Total apoE and apoE4 levels were found to be significantly lower in patients with AD in the entire cohort, and decrease with Aβ load in the PiB-PET subset. ApoE levels were significantly lower among ε4 homozygous individuals. In APOE ε3/ε4 heterozygote carriers, apoE4 levels decrease, indicating that apoE3 levels increase with disease. Analysis of cross-sectional data from the AIBL study indicates that plasma apoE levels are altered in AD and correlate with AD pathology level. The significance of these findings will be determined in the AIBL longitudinal study of aging. © 2011 by AAN Enterprises, Inc.

Suppression of Homocysteine Levels by Vitamin B12 and Folates: Age and Gender Dependency in the Jackson Heart Study

PubMed Central

Henry, Olivia R.; Benghuzzi, Hamed; Taylor, Herman A.; Tucci, Michelle; Butler, Kenneth; Jones, Lynne

2011-01-01

Objectives To examine factors potentially contributing to premature cardiovascular disease mortality in African Americans (40% versus 20% all other populations), plasma homocysteine, serum vitamin B12 and folate levels were examined for African American participants in the Jackson Heart Study. Methods Of 5,192 African American Jackson Heart Study participants (21–94 years), 5,064 (mean age, 55±13 years; 63% female) had homocysteine levels measured via fasting blood samples, with further assessments of participants’ vitamin B12 (n=1,790) and folate (n=1,788) levels. We used regression analyses to examine age, gender, vitamin B12, and folate with homocysteine levels. Results Homocysteine levels, a purported surrogate risk factor for cardiovascular disease, increased with age, were inversely proportional to folate and vitamin B12 levels (p<0.001), and higher for men of all ages. Conclusions Our results show that, as with other populations, age, gender, vitamin B12, and folate may predict homocysteine levels for African Americans. Diet may be an important predictive factor as well, given the relationships we observed between plasma homocysteine and serum B vitamin levels. PMID:22173042

Ghrelin and obestatin plasma levels and ghrelin/obestatin prepropeptide gene polymorphisms in small for gestational age infants.

PubMed

Zhang, Shulian; Zhai, Guanpeng; Zhang, Jinping; Zhou, Jianguo; Chen, Chao

2014-12-01

To investigate plasma ghrelin and obestatin levels, and ghrelin/obestatin prepropeptide gene polymorphisms, in sequentially enrolled small for gestational age (SGA) infants. Neonates were sequentially enrolled into this study and were then subdivided into different groups, according to different study aims and availability of study materials. Consequently, plasma ghrelin and obestatin levels were measured in term SGA, term appropriate for gestational age (AGA), term large for gestational age (LGA), preterm SGA and preterm AGA neonates. Levels of both peptides were also measured in AGA infants of different gestational ages, and in term AGA neonates at different days following birth. Three ghrelin/obestatin prepropeptide gene single nucleotide polymorphisms (SNPs), Arg51Gln, Leu72Met, and Gln90Leu, were measured in neonates. The study involved a total cohort of 581 neonates. Out of 150 neonates (30 term AGA, 30 term SGA, 30 term LGA, 30 preterm AGA, and 30 preterm SGA), plasma obestatin levels were significantly higher in term SGA versus term LGA neonates (0.21 ± 0.02 ng/ml versus 0.17 ± 0.01 ng/ml, respectively). Out of a wider cohort, there were no significant differences in genotypes and allele frequencies of Arg51Gln, Leu72Met, and Gln90Leu SNPs between term SGA and AGA neonates, or between preterm SGA and AGA neonates. Ghrelin/obestatin prepropeptide polymorphisms were not found to be associated with SGA status in neonates; however, ghrelin and obestatin levels may be involved in growth and development. Further studies are required to understand the relationship between ghrelin, obestatin and prenatal development. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Plasma and serum L-selectin and clinical and subclinical the Multi-Ethnic Study of Atherosclerosis (MESA)cardiovascular disease

PubMed Central

BERARDI, CECILIA; DECKER, PAUL A.; KIRSCH, PHILLIP S.; DE ANDRADE, MARIZA; TSAI, MICHAEL Y.; PANKOW, JAMES S.; SALE, MICHELE M.; SICOTTE, HUGUES; TANG, WEIHONG; HANSON, NAOMI; POLAK, JOSEPH F.; BIELINSKI, SUZETTE J.

2014-01-01

L-selectin has been suggested to play a role in atherosclerosis. Previous studies on cardiovascular disease (CVD) and serum or plasma L-selectin are inconsistent. The association of serum L-selectin (sL-selectin) with carotid intima-media thickness, coronary artery calcium, ankle-brachial index (subclinical CVD) and incident CVD was assessed within 2403 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Regression analysis and the Tobit model were used to study subclinical disease; Cox Proportional Hazards regression for incident CVD. Mean age was 63 ± 10, 47% were males; mean sL-selectin was significantly different across ethnicities. Within each race/ethnicity, sL-selectin was associated with age and sex; among Caucasians and African Americans, it was associated with smoking status and current alcohol use. sL-selectin levels did not predict subclinical or clinical CVD after correction for multiple comparisons. Conditional logistic regression models were used to study plasma L-selectin and CVD within 154 incident CVD cases, occurred in a median follow up of 8.5 years, and 306 age-, sex-, and ethnicity-matched controls. L-selectin levels in plasma were significantly lower than in serum and the overall concordance was low. Plasma levels were not associated with CVD. In conclusion, this large multi-ethnic population, soluble L-selectin levels did not predict clinical or subclinical CVD. PMID:24631064

Association between plasma kisspeptin levels and adolescent gynecomastia.

PubMed

Aluclu, Mustafa Arif; Sen, Selcuk; Cevik, Muazez

2016-01-01

Gynecomastia is defined as benign proliferation of male breast glandular tissue. To date, the pathophysiology of adolescent gynecomastia (AG) remains unclear. Kisspeptin is a polypeptide that plays an important role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis. In this study, we investigated whether there is a relationship between kisspeptin and AG. This study included 40 males between 9 and 18 years of age diagnosed with gynecomastia. The control group consisted of 30 young healthy males in the same age range. The participants were evaluated with respect to anthropometric measurements (age, height, body weight, body mass index, breast and pubic stages and testicular volume). The levels of kisspeptin, follicle-stimulating hormone, luteinizing hormone, estradiol (E2), testosterone (T), and ratio of E2 to T were measured in both groups. The mean age was 13.8 years. There were no differences between the groups in terms of anthropometric parameters, plasma gonadotropin levels, estrogen levels, and E2/T (P > 0.05). Plasma kisspeptin (0.77 and 0.54 ng/mL, P < 0.05) and T (253.9 ng/dL and 117.9 ng/dL) levels were significantly higher in the AG group than in the control group (P < 0.001). Kisspeptin levels are an important factor in AG.

Plasma and tissue oxidative stress index in patients with rheumatic and degenerative heart valve disease.

PubMed

Rabus, Murat; Demirbağ, Recep; Sezen, Yusuf; Konukoğlu, Oğuz; Yildiz, Ali; Erel, Ozcan; Zeybek, Rahmi; Yakut, Cevat

2008-12-01

We investigated whether patients with rheumatic and degenerative heart valve disease (HVD) differed with regard to plasma and tissue oxidative stress index (OSI). The study included 56 patients who underwent valve replacement due to rheumatic (n=32; 15 males; mean age 47+/-10 years) and degenerative (n=24; 13 males; mean age 55+/-12 years) HVD. Plasma and tissue total oxidative status (TOS) and total antioxidative capacity (TAC) levels were measured and OSI was calculated. Patients with degenerative HVD had significantly higher age, increased interventricular septum thickness, and higher frequency of aortic stenosis, whereas the incidence of mitral stenosis was higher in patients with rheumatic HVD (p<0.05). Plasma oxidative characteristics did not differ between the two HVD groups (p>0.05). Tissue TAC was significantly lower in patients with rheumatic HVD (p=0.027), whereas tissue TOS and OSI were similar between the two HVD groups (p>0.05). In bivariate analysis, plasma OSI did not show any correlation with clinical, laboratory, and echocardiographic variables (p>0.05). Our data show that plasma and tissue OSI levels are similar in patients with rheumatic and degenerative HVD.

Effects of changes in sodium balance on plasma and kidney angiotensin II levels in anesthetized and conscious Ren-2 transgenic rats.

PubMed

Husková, Zuzana; Kramer, Herbert J; Vanourková, Zdenka; Cervenka, Ludek

2006-03-01

Since there is as yet no general agreement regarding the role of plasma and kidney angiotensin II (ANG II) in the development of hypertension in Ren-2 transgenic rats (TGR), in the present study we evaluated plasma and kidney ANG II levels in anesthetized and conscious TGR and in normotensive Hannover-Sprague-Dawley rats (HanSD) fed a normal salt diet (NS). Given the importance of ANG II in the development of salt-sensitive hypertension, and the fact that hypertensinogenic actions of ANG II are mediated via ANG II type 1 (AT1) receptors, the effects of high salt (HS) intake and of sodium depletion on blood pressure (BP), ANG II levels and kidney AT1 receptor protein expression in TGR and HanSD were also examined. Rats were maintained on a NS diet (0.6% NaCl) or fed a HS diet (2% NaCl) for 4 days or were sodium depleted (40 mg/l furosemide for 1 day followed by 3 days of 0.01% NaCl diet). They were sacrificed either by an overdose of anesthetic (thiopental sodium) or by decapitation (without anesthetic) and plasma and kidney ANG II levels were determined by radioimmunoassay during the prehypertensive (32 days old), the early (52 days) and the maintenance (90 days) phases of hypertension. Total kidney AT1 receptor protein levels were assessed by Western blot analysis. In anesthetized animals fed the NS diet, plasma ANG II levels were lower in 32-day-old TGR than in HanSD, but at 52 and 90 days of age no significant differences were noted. ANG II concentrations in kidney tissue were similar in 32- and 90-day-old TGR and HanSD, but were higher in 52-day-old TGR than in HanSD. In contrast, in conscious animals immediately after decapitation, plasma and kidney ANG II levels were higher in TGR than in HanSD at all ages. HS diet did not change BP but suppressed ANG II levels in HanSD at all ages. In contrast, HS diet increased BP but did not decrease plasma and kidney ANG II levels in TGR at all ages. Sodium restriction did not alter BP and resulted in a marked increase in ANG II levels in HanSD, but caused a significant decrease in BP in TGR without altering plasma or tissue ANG II concentrations. There were no significant differences in renal AT1 receptor protein expression between HanSD and TGR at any age of any of the experimental groups. On the basis of our present results we conclude that TGR exhibit a disrupted interaction between sodium homeostasis and the regulation of the renin-angiotensin system (RAS) activity which results in the loss of BP regulation in this model.

Factors Associated with D-Dimer Levels in HIV-Infected Individuals

PubMed Central

Borges, Álvaro H.; O’Connor, Jemma L.; Phillips, Andrew N.; Baker, Jason V.; Vjecha, Michael J.; Losso, Marcelo H.; Klinker, Hartwig; Lopardo, Gustavo; Williams, Ian; Lundgren, Jens D.

2014-01-01

Background Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. Methods In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. Results Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. Conclusions D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels. PMID:24626096

Cord plasma insulin and in utero exposure to ambient air pollution.

PubMed

Madhloum, Narjes; Janssen, Bram G; Martens, Dries S; Saenen, Nelly D; Bijnens, Esmée; Gyselaers, Wilfried; Penders, Joris; Vanpoucke, Charlotte; Lefebvre, Wouter; Plusquin, Michelle; Nawrot, Tim S

2017-08-01

Cardio-metabolic risk factors including insulin levels are at young age barely perceived as harmful, but over time these risk factors may track and lead to higher risk of metabolic syndrome. Studies showed that exposure to air pollution is associated with an increased risk of insulin resistance in childhood. We determined whether the origin of type 2 diabetes can be found in the early childhood by examining the levels of insulin in the neonatal cord blood and whether this can be considered as a disease marker for later life. In the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort, we recruited 620 mother-infant pairs between February 2nd 2010 until August 12th 2014 at the East-Limburg Hospital in Genk, Belgium. We investigated in 590 newborns the association between cord plasma insulin levels and exposure to particulate matter (PM 2.5 and PM 10 ) and nitrogen dioxide (NO 2 ) in various exposure windows during pregnancy. Trimester-specific air pollutant exposure levels were estimated for each mother's home address using a spatiotemporal model. Cord plasma insulin levels averaged 33.1pmol/L (25-75th percentile: 20.1-53.5), while PM 2.5 exposure during pregnancy averaged (SD) 13.7μg/m 3 (2.4). Independent of maternal age, newborn's sex, birth weight, gestational age, parity, early-pregnancy BMI, ethnicity, smoking status, time of the day, maternal education, time of delivery, and season of delivery, cord plasma insulin levels increased with 15.8% (95% CI 7.8 to 24.4, p<0.0001) for each SD increment in PM 2.5 levels during the entire pregnancy and was most pronounced in the 2nd trimester (13.1%, 95% CI 3.4 to 23.7, p=0.007) of pregnancy. The results for PM 10 exposure were similar with those of PM 2.5 exposure but we did not observe an association between cord blood insulin levels and NO 2 exposure. Exposure to particulate air pollution during pregnancy is associated with increased levels of cord plasma insulin at birth. The public health relevance of this association is demonstrated by the fact that a 2.4μg/m 3 (SD) increase in PM 2.5 during pregnancy on cord plasma insulin levels corresponds to the effect-size of a 9kg/m 2 higher early-pregnancy BMI on cord plasma. Particulate air pollution induced changes in cord plasma insulin levels during early life and might be a risk factor in the development of metabolic disease, such as glucose intolerance or type 2 diabetes, later in life. Copyright © 2017. Published by Elsevier Ltd.

Influence of Clinical Status on the Association Between Plasma Total and Unbound Bilirubin and Death or Adverse Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants

PubMed Central

Oh, William; Stevenson, David K.; Tyson, Jon E.; Morris, Brenda H.; Ahlfors, Charles E.; Bender, G. Jesse; Wong, Ronald J.; Perritt, Rebecca; Vohr, Betty R.; Van Meurs, Krista P.; Vreman, Hendrik J.; Das, Abhik; Phelps, Dale L.; O’Shea, T. Michael; Higgins, Rosemary D.

2010-01-01

Objectives To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method Total plasma biirubin and unbound biirubin were measured in 1,101 extremely low birth weight infants at 5±1 day of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma and unbound bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants. PMID:20105142

Plasma antioxidant status and motor features in de novo Chinese Parkinson's disease patients.

PubMed

Yuan, Yongsheng; Tong, Qing; Zhang, Li; Jiang, Siming; Zhou, Hong; Zhang, Rui; Zhang, Shu; Xu, Qinrong; Li, Daqian; Zhou, Xiaobin; Ding, Jian; Zhang, Kezhong

2016-01-01

This study aimed to explore plasma antioxidant status in de novo Chinese Parkinson's disease (PD) patients and investigate its relationship with specific motor features of PD. Sixty-four de novo Chinese PD patients and 40 age- and sex-matched healthy controls were recruited. Each motor feature of PD patients was assessed by unified Parkinson's disease rating scale. Plasma antioxidant status, including plasma level of glutathione (GSH) and plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), was detected using enzyme-linked immunosorbent assay. The relationship between the plasma antioxidant status and motor features of PD was evaluated by Spearman's coefficient. Plasma GSH level and plasma activities of GSH-Px, CAT and SOD of PD patients were lower than those of healthy controls. Moreover, the declining activity of plasma CAT was related with the increasing mean postural instability and gait disorder (PIGD) score and growing age. In contrast, the severity of tremor was positively correlated with plasma SOD activity. Our study demonstrates that the plasma antioxidant status is impaired in de novo Chinese PD patients. The complex relationship between the plasma antioxidant status and different motor features indicates that the antioxidant mechanisms underlying tremor and PIGD of PD may be different.

Zinc Deficiency Is associated With Depressive Symptoms-Results From the Berlin Aging Study II.

PubMed

Jung, Alissa; Spira, Dominik; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja; Norman, Kristina

2017-08-01

Zinc plays an important role for behavioral and mental function, maintaining the correct functions of intracellular signal transduction, cellular and trans-membrane transport, protein synthesis, and antioxidant system. We investigated both dietary zinc intake and plasma zinc levels and the correlation with depressive symptoms in a large sample of community-dwelling old. One thousand five hundred fourteen older people (aged 60-84 years, 772 women) from the Berlin Aging Study II were included. Zinc intake was assessed by the EPIC Food Frequency Questionnaire. Plasma zinc levels were assessed with atomic-absorption spectrophotometry. Depressive symptoms were assessed with the "Center for Epidemiological Studies Depression Scale" and the "Geriatric Depression Scale." Zinc deficiency in blood plasma was found in 18.7% of participants, and depressive symptoms in 15.7%. Participants with depressive symptoms had lower energy-adjusted zinc intake (median 11.1 vs 11.6 µmol/L; p = .048) and lower plasma zinc levels (median 12.2 vs12.3 mg/dL; p = .037). Even after adjustment for known predictors of depression, plasma zinc deficiency remained significantly associated with depressive symptoms (odds ratio: 1.490, 95% confidence interval: 1.027-2.164; p = .036). In the multiple logistic regression model stratified by sex, we found that plasma zinc deficiency was strongly associated with a higher risk for depressive symptoms in women (odds ratio: 1.739, 95% confidence interval: 1.068-2.833; p = .026). Plasma zinc deficiency was common in our old study population. An increase in dietary zinc and higher plasma zinc levels may reduce the risk of depressive symptoms. A screening for reduced dietary zinc intake or plasma zinc deficiency might be beneficial in older people at risk of depressive symptoms. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Large –scale wheat flour folic acid fortification program increases plasma folate levels among women of reproductive age in urban Tanzania

PubMed Central

Abioye, Ajibola I.; Ulenga, Nzovu; Msham, Salum; Kaishozi, George; Gunaratna, Nilupa S; Mwiru, Ramadhani; Smith, Erin; Dhillon, Christina Nyhus; Spiegelman, Donna; Fawzi, Wafaie

2017-01-01

There is widespread vitamin and mineral deficiency problem in Tanzania with known deficiencies of at least vitamin A, iron, folate and zinc, resulting in lasting negative consequences especially on maternal health, cognitive development and thus the nation’s economic potential. Folate deficiency is associated with significant adverse health effects among women of reproductive age, including a higher risk of neural tube defects. Several countries, including Tanzania, have implemented mandatory fortification of wheat and maize flour but evidence on the effectiveness of these programs in developing countries remains limited. We evaluated the effectiveness of Tanzania’s food fortification program by examining folate levels for women of reproductive age, 18–49 years. A prospective cohort study with 600 non-pregnant women enrolled concurrent with the initiation of food fortification and followed up for 1 year thereafter. Blood samples, dietary intake and fortified foods consumption data were collected at baseline, and at 6 and 12 months. Plasma folate levels were determined using a competitive assay with folate binding protein. Using univariate and multivariate linear regression, we compared the change in plasma folate levels at six and twelve months of the program from baseline. We also assessed the relative risk of folate deficiency during follow-up using log-binomial regression. The mean (±SE) pre–fortification plasma folate level for the women was 5.44-ng/ml (±2.30) at baseline. These levels improved significantly at six months [difference: 4.57ng/ml (±2.89)] and 12 months [difference: 4.27ng/ml (±4.18)]. Based on plasma folate cut-off level of 4 ng/ml, the prevalence of folate deficiency was 26.9% at baseline, and 5% at twelve months. One ng/ml increase in plasma folate from baseline was associated with a 25% decreased risk of folate deficiency at 12 months [(RR = 0.75; 95% CI = 0.67–0.85, P<0.001]. In a setting where folate deficiency is high, food fortification program with folic acid resulted in significant improvements in folate status among women of reproductive age. PMID:28797054

Prospective study of plasma homocysteine level and risk of age-related macular degeneration in women.

PubMed

Christen, William G; Cook, Nancy R; Ridker, Paul M; Buring, Julie E

2015-04-01

Prospective data to examine the association of homocysteine with age-related macular degeneration (AMD) are limited. We examined the prospective relation of plasma homocysteine level and AMD in a large cohort of apparently healthy women. We evaluated the relationship between baseline levels of plasma homocysteine and incident AMD among 27,479 female health professionals aged 40 years or older. Main outcome measures were total AMD, defined as self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity 20/30 or worse attributable to this condition. During an average 10 years of follow-up, a total of 452 cases of AMD, including 182 cases of visually significant AMD, were documented. Women in the highest versus lowest quartile of plasma homocysteine had modestly, but statistically non-significant, increased risks of total AMD (hazard ratio, HR, 1.24, 95% confidence interval, CI, 0.95-1.63; p for trend 0.07) and visually significant AMD (HR 1.41, 95% CI 0.92-2.17; p for trend 0.052) in age- and treatment-adjusted analyses. These prospective data from a large cohort of apparently healthy women do not support a strong role for homocysteine in AMD occurrence.

Induction of a hypothyroid state during juvenile development delays pubertal reactivation of the neuroendocrine system governing luteinising hormone secretion in the male rhesus monkey (Macaca mulatta).

PubMed

Mann, D R; Bhat, G K; Stah, C D; Pohl, C R; Plant, T M

2006-09-01

The present study aimed to determine the influence of thyroid status on the timing of the pubertal resurgence in gonadotrophin-releasing hormone pulse generator activity [tracked by circulating luteinising hormone (LH) levels] in male rhesus monkeys. Six juvenile monkeys were orchidectomised and then treated with the antithyroid drug, methimazole, from 15-19 months until 36 months of age, at which time thyroxine (T(4)) replacement was initiated. Four additional agonadal monkeys served as controls. Blood samples were drawn weekly for hormonal assessments. Body weight, crown-rump length and bone age were monitored at regular intervals. By 8 weeks of methimazole treatment, plasma T(4) had fallen sharply, and the decline was associated with a plasma thyroid-stimulating hormone increase. In controls, plasma LH levels remained undetectable until the pubertal rise occurred at 29.3 +/- 0.2 months of age. This developmental event occurred in only half of the methimazole-treated animals before 36 months of age when T(4) replacement was initiated. The hypothyroid state was associated with a profound arrest of growth and bone maturation, but increased body mass indices and plasma leptin levels. T(4) replacement in methimazole-treated monkeys was associated with the pubertal rise in LH in the remaining three animals and accelerated somatic development in all six animals. Although pubertal resurgence in LH secretion occurred at a later chronological age in methimazole-treated animals compared to controls, bone age, crown-rump length and body weight at that time did not differ between groups. There were no long-term differences in plasma prolactin between groups. We conclude that juvenile hypothyroidism in male primates causes a marked delay in the pubertal resurgence of LH secretion, probably occasioned at the hypothalamic level. Whether this effect is meditated by an action of thyroid hormone directly on the hypothalamus or indirectly as a result of the concomitant deficit in somatic development remains to be determined.

Regulation of Peripheral Catecholamine Responses to Acute Stress in Young Adult and Aged F-344 Rats.

PubMed

McCarty; Pacak; Goldstein; Eisenhofer

1997-12-01

Young adult (3-month-old) and aged (24-month-old) Fischer-344 male rats received i.v. infusions of 3H-labeled norepinephrine (NE) and epinephrine (EPI) to examine the effects of aging on the neuronal uptake of NE and sympathoadrenal release of NE and EPI. Spillovers of NE and EPI into plasma and their clearance from the circulation were estimated from plasma concentrations of endogenous and 3H-labeled NE and EPI. The efficiency of neuronal uptake was assessed from changes in plasma clearance of NE and concentrations of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), during immobilization stress or neuronal uptake blockade with desipramine. Stress-induced increases in plasma NE and higher plasma NE concentrations in aged compared to young adult rats were due to both decreases in NE clearance and increases in NE spillover. EPI spillover and clearance were reduced in aged compared to young adult rats, so that plasma EPI levels did not differ between groups. Young adult and aged rats had similar desipramine-induced decreases in NE clearance, whereas desipramine-sensitive decreases and stress-induced increases in plasma DHPG were larger in aged rats. This indicates that neuronal uptake is intact and that increased NE spillover at rest and during stress in aged rats reflects increased NE release from sympathetic nerves. The results show that aging is associated with divergent decreases in EPI release from the adrenal medulla and increases in NE release from sympathetic nerves. Increased plasma concentrations of NE in aged compared to young adult rats also result from decreased circulatory clearance of NE, but this does not reflect any age-related impairment of NE reuptake.

Absolute versus relative measures of plasma fatty acids and health outcomes: example of phospholipid omega-3 and omega-6 fatty acids and all-cause mortality in women.

PubMed

Miura, Kyoko; Hughes, Maria Celia B; Ungerer, Jacobus P J; Smith, David D; Green, Adèle C

2018-03-01

In a well-characterised community-based prospective study, we aimed to systematically assess the differences in associations of plasma omega-3 and omega-6 fatty acid (FA) status with all-cause mortality when plasma FA status is expressed in absolute concentrations versus relative levels. In a community sample of 564 women aged 25-75 years in Queensland, Australia, baseline plasma phospholipid FA levels were measured using gas chromatography. Specific FAs analysed were eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, total long-chain omega-3 FAs, linoleic acid, arachidonic acid, and total omega-6 FAs. Levels of each FA were expressed in absolute amounts (µg/mL) and relative levels (% of total FAs) and divided into thirds. Deaths were monitored for 17 years and hazard ratios and 95% confidence intervals calculated to assess risk of death according to absolute versus relative plasma FA levels. In total 81 (14%) women died during follow-up. Agreement between absolute and relative measures of plasma FAs was higher in omega-3 than omega-6 FAs. The results of multivariate analyses for risk of all-cause mortality were generally similar with risk tending to inverse associations with plasma phospholipid omega-3 FAs and no association with omega-6 FAs. Sensitivity analyses examining effects of age and presence of serious medical conditions on risk of mortality did not alter findings. The directions and magnitude of associations with mortality of absolute versus relative FA levels were comparable. However, plasma FA expressed as absolute concentrations may be preferred for ease of comparison and since relative units can be deduced from absolute units.

Comparisons of the effect of naturally acquired maternal pertussis antibodies and antenatal vaccination induced maternal tetanus antibodies on infant's antibody secreting lymphocyte responses and circulating plasma antibody levels

PubMed Central

Ahmad, Shaikh Meshbahuddin; Alam, Md. Jahangir; Afsar, Md. Nure Alam; Huda, M. Nazmul; Kabir, Yearul; Qadri, Firdausi; Raqib, Rubhana; Stephensen, Charles B.

2016-01-01

ABSTRACT The goal of this study was to explore the effects of trans-placental tetanus toxoid (TT) and pertussis (PT) antibodies on an infant's response to vaccination in the context of antenatal immunization with tetanus but not with pertussis. 38 mothers received a single dose of TT vaccine during pregnancy. Infants received tetanus and pertussis vaccines at 6, 10 and 14 wk of age. TT and PT anti-IgG secretion by infant lymphocytes was measured at 15 wk. Plasma antibodies were measured at 6 wk (pre-vaccination), 15 wk and 1 y of age. Prior to vaccination, TT and PT antibody were detected in 94.6% and 15.2% of infants. At 15 wk anti-TT-IgG and anti-PT-IgG in plasma was increased by 7–9 fold over pre-vaccination levels, while at 1 y plasma anti-TT-IgG was decreased by approximately 5-fold from the peak and had returned to near the pre-vaccination level. At 1 y plasma anti-PT-IgG was decreased by 2-fold 1 yfrom the 15 wk level. However, 89.5% and 82.3% of infants at 1 y had protective levels of anti-TT and anti-PT IgG, respectively. Pre-vaccination plasma IgG levels were associated with lower vaccine-specific IgG secretion by infant lymphocytes at 15 wk (p < 0.10). This apparent inhibition was seen for anti-TT-IgG at both 15 wk (p < 0.05) and t 1 y (p < 0.10) of age. In summary, we report an apparent inhibitory effect of passively derived maternal antibody on an infants' own antibody response to the same vaccine. However, since the cut-off values for protective titers are low, infants had protective antibody levels throughout infancy. PMID:27176823

Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas.

PubMed

Goncharova, N D; Vengerin, A A; Khavinson, V Kh; Lapin, B A

2005-01-01

The purpose of this research was to study age-related changes in functioning of pineal and pancreatic glands of non-human primates, rhesus monkeys, and to elucidate the possibility of their corrections with the help of epitalon, a synthetic analogue of the pharmacopoeia drug epithalamin. In old (20-27 years) animals, the basal plasma levels of glucose and insulin were found to be higher, while the night melatonin level was lower in comparison with (6-8 years) young animals. After the glucose administration to old monkeys, a larger area under the curve of the plasma glucose response, a reduced glucose 'disappearance' rate, and a reduced insulin peak (5 min after the glucose administration) were observed in comparison with young animals in similar experiments. The epitalon administration to old monkeys caused the decrease in the basal levels of glucose and insulin and the increase in the basal night melatonin level. Additionally, in the case of old monkeys, epitalon decreased the area under the plasma glucose response curve, markedly increased the glucose 'disappearance' rate and normalized the plasma insulin dynamics in response to glucose administration. Yet, it has not affected the hormonal and metabolic changes in young animals. Thus, epitalon is a promising factor for restoring the age-related endocrine dysfunctions of primates.

Ten-year change in plasma amyloid beta levels and late-life cognitive decline.

PubMed

Okereke, Olivia I; Xia, Weiming; Selkoe, Dennis J; Grodstein, Francine

2009-10-01

Plasma levels of amyloid beta peptide (Abeta) are potential biomarkers of early cognitive impairment and decline and of Alzheimer disease risk. To relate midlife plasma Abeta measures and 10-year change in plasma Abeta measures since midlife to late-life cognitive decline. Prospective study of a population-based sample. Academic research. Plasma Abeta40 and Abeta42 levels were measured in 481 Nurses' Health Study participants in late midlife (mean age, 63.6 years) and again 10 years later (mean age, 74.6 years). Cognitive testing also began 10 years after the initial blood draw. Participants completed 3 repeated telephone-based assessments (mean span, 4.1 years). Multivariable linear mixed-effects models were used to estimate relations of midlife plasma Abeta40 to Abeta42 ratios and Abeta42 levels to late-life cognitive decline, as well as relations of 10-year change in Abeta40 to Abeta42 ratios and Abeta42 levels to cognitive decline. The 3 primary outcomes were the Telephone Interview for Cognitive Status (TICS) findings, a global score averaging the results of all tests (TICS, immediate and delayed verbal recall, category fluency, and attention), and a verbal memory score averaging the results of 4 tests of verbal recall. Higher midlife plasma Abeta40 to Abeta42 ratios were associated with worse late-life decline on the global score (P = .04 for trend). Furthermore, increase in Abeta40 to Abeta42 ratios since midlife predicted greater decline in the global score (P = .03 for trend) and in the TICS (P = .02 for trend). There was no association of cognitive decline with midlife plasma Abeta42 levels alone or with change in Abeta42 levels since midlife. In this large community-dwelling sample, higher plasma Abeta40 to Abeta42 ratios in late midlife and increases in Abeta40 to Abeta42 ratios 10 years later were significantly associated with greater decline in global cognition at late life.

Increased plasma chemokine levels in children with Prader-Willi syndrome.

PubMed

Butler, Merlin G; Hossain, Waheeda; Sulsona, Carlos; Driscoll, Daniel J; Manzardo, Ann M

2015-03-01

Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes from the 15q11-q13 region and reportedly rearranged as a cause of autism. Additionally, increased inflammatory markers and features of autism are reported in PWS. Cytokines encoded by genes involved with inflammation, cell proliferation, migration, and adhesion play a role in neurodevelopment and could be disturbed in PWS as abnormal plasma cytokine levels are reported in autism. We analyzed 41 plasma cytokines in a cohort of well-characterized children with PWS between 5 and 11 years of age and unaffected unrelated siblings using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Data were analyzed using ANOVA testing for effects of diagnosis, gender, body mass index (BMI) and age on the 24 cytokines meeting laboratory criteria for inclusion. No significant effects were observed for age, gender or BMI. The log-transformed levels of the 24 analyzable cytokines were examined simultaneously using MANOVA adjusting for age and gender and a main effect of diagnosis was found (P-value <0.03). Four of 24 plasma cytokine levels (MCP1, MDC, Eotaxin, RANTES) were significantly higher in children with PWS compared with controls and classified as bioinflammatory chemokines supporting a disturbed immune response unrelated to obesity status. BMI was not statistically different in the two subject groups (PWS or unaffected unrelated siblings) and chemokine levels were not correlated with percentage of total body fat. Additional studies are required to identify whether possible early immunological disturbances and chemokine inflammatory processes found in PWS may contribute to neurodevelopment and behavioral features. © 2015 Wiley Periodicals, Inc.

Plasma hepcidin levels and anemia in old age. The Leiden 85-Plus Study

PubMed Central

den Elzen, Wendy P.J.; de Craen, Anton J.M.; Wiegerinck, Erwin T.; Westendorp, Rudi G.J.; Swinkels, Dorine W.; Gussekloo, Jacobijn

2013-01-01

Hepcidin, an important regulator of iron homeostasis, is suggested to be causally related to anemia of inflammation. The aim of this study was to explore the role of plasma hepcidin in anemia among older persons from the general population. The Leiden 85-Plus Study is a population-based study of 85-year olds in Leiden, the Netherlands. Eighty-five-year old inhabitants of Leiden were enrolled between September 1997 and September 1999. At the age of 86, plasma hepcidin was determined with time of flight mass spectrometry in 490 participants [160 (32.7%) male, 114 (23.3%) with anemia]. Anemia was defined according to criteria of the World Health Organization (hemoglobin level <13 g/dL for men and hemoglobin <12 g/dL for women). The median plasma hepcidin level was 3.0 nM [interquartile range (IQR) 1.8–4.9]. We found strong correlations between plasma hepcidin and body iron status, C-reactive protein and erythropoietin levels. Significantly higher hepcidin levels were found in participants with anemia of inflammation (P<0.01), in participants with anemia of kidney disease (P=0.01), and in participants with unexplained anemia (P=0.01) than in participants without anemia. Participants with iron-deficiency anemia had significantly lower plasma hepcidin levels than participants without anemia (P<0.01). In conclusion, older persons with anemia of inflammation have higher hepcidin levels than their counterparts without anemia. The potential clinical value of hepcidin in future diagnostic algorithms for anemia has to be explored. PMID:23065507

Soluble sortilin is present in excess and positively correlates with progranulin in CSF of aging individuals.

PubMed

Molgaard, Simon; Demontis, Ditte; Nicholson, Alexandra M; Finch, Nicole A; Petersen, Ronald C; Petersen, Claus M; Rademakers, Rosa; Nykjaer, Anders; Glerup, Simon

2016-11-01

Mutations in progranulin are a major cause of frontotemporal lobe degeneration (FTLD). Hence, plasma progranulin is an attractive biomarker in FTLD but poorly reflects levels in cerebrospinal fluid (CSF), suggesting tissue-specific regulation of progranulin levels. Sortilin was recently identified as a progranulin scavenger receptor that destines it for lysosomal degradation. Proteolysis or alternative splicing generates soluble sortilin variants that retain progranulin binding and potentially functions as a decoy receptor. In the present study, we analyzed soluble sortilin and progranulin in plasma and CSF in 341 aging individuals. We found that soluble sortilin exists in CSF in ten-fold molar excess compared to progranulin and observed a highly significant positive correlation between soluble sortilin and progranulin levels in CSF but not in plasma. However, carriers of the minor allele of SNP rs646776 in SORT1 encoding sortilin displayed significantly increased soluble sortilin and reduced progranulin specifically in plasma but not in CSF. Taken together, our findings suggest that soluble sortilin may affect progranulin levels in both a tissue-specific and genotype-dependent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of plasma sRAGE, but not esRAGE with lung function impairment in COPD.

PubMed

Gopal, Poornima; Reynaert, Niki L; Scheijen, Jean L J M; Schalkwijk, Casper G; Franssen, Frits M E; Wouters, Emiel F M; Rutten, Erica P A

2014-02-25

Plasma soluble Receptor for Advanced Glycation End Product (sRAGE) is considered as a biomarker in COPD. The contribution of endogenous sRAGE (esRAGE) to the pool of plasma sRAGE and the implication of both markers in COPD pathogenesis is however not clear yet. The aim of the current study was therefore to measure plasma levels of esRAGE comparative to total sRAGE in patients with COPD and a control group. Further, we established the relations of esRAGE and total sRAGE with disease specific characteristics such as lung function and DLCO, and with different circulating AGEs. Plasma levels of esRAGE and sRAGE were measured in an 88 patients with COPD and in 55 healthy controls. FEV1 (%predicted) and FEV1/VC (%) were measured in both groups; DLCO (%predicted) was measured in patients only. In this study population we previously reported that the AGE Nϵ-(carboxymethyl) lysine (CML) was decreased, Nϵ-(carboxyethyl) lysine (CEL) increased and pentosidine was not different in plasma of COPD patients compared to controls. Plasma esRAGE (COPD: 533.9 ± 412.4, CONTROLS: 848.7 ± 690.3 pg/ml; p = 0.000) was decreased in COPD compared to controls. No significant correlations were observed between plasma esRAGE levels and lung function parameters or plasma AGEs. A positive correlation was present between esRAGE and total sRAGE levels in the circulation. Confirming previous findings, total sRAGE (COPD: 512.6 ± 403.8, CONTROLS: 1834 ± 804.2 pg/ml; p < 0.001) was lower in patients compared to controls and was positively correlated FEV1 (r = 0.235, p = 0.032), FEV1/VC (r = 0.218, p = 0.047), and DLCO (r = 0.308, p = 0.006). sRAGE furthermore did show a significant positive association with CML (r = 0.321, p = 0.003). Although plasma esRAGE is decreased in COPD patients compared to controls, only total sRAGE showed a significant and independent association with FEV1, FEV1/VC and DLCO, indicating that total sRAGE but not esRAGE may serve as marker of COPD disease state and severity.

Low plasma vitamin D levels and muscle-related adverse effects in statin users.

PubMed

Eisen, Alon; Lev, Eli; Iakobishvilli, Zaza; Porter, Avital; Brosh, David; Hasdai, David; Mager, Aviv

2014-01-01

Treatment with HMG-CoA reductase inhibitors (statins) is often complicated by muscle-related adverse effects (MAEs). Studies of the association between low plasma vitamin D levels and MAEs have yielded conflicting results. To determine if low plasma vitamin D level is a risk factorfor MAEs in statin users. Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007-2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database. The sample included 272 patients (141 men) aged 33-89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 +/- 20.5 versus 44.7 +/- 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 9 patients (3%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 +/- 17.7 versus 48.9 +/- 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 +/- 14.6 versus 47.8 +/- 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 +/- 15.0 versus 47.8 +/- 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L). There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.

Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study.

PubMed

Pinna, Antonio; Zinellu, Angelo; Tendas, Donatella; Blasetti, Francesco; Carru, Ciriaco; Castiglia, Paolo

2016-01-01

To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

Influence of insulin on beta-endorphin plasma levels in obese and normal weight subjects.

PubMed

Brunani, A; Pincelli, A I; Pasqualinotto, L; Tibaldi, A; Baldi, G; Scacchi, M; Fatti, L M; Cavagnini, F

1996-08-01

To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

Impact of Oxidative Stress Biomarkers and Carboxymethyllysine (An Advanced Glycation End Product) on Prostate Cancer: A Prospective Study

PubMed Central

Yang, Shuman; Pinney, Susan M.; Mallick, Palash; Ho, Shuk-Mei; Bracken, Bruce; Wu, Tianying

2015-01-01

Introduction Biomarkers of oxidative stress and advanced glycation end products (AGE) have been linked to the development of prostate cancer, but evidence from human studies is either scarce or controversial. Materials and Methods We conducted a prospective nested case-control study among 48 men (24 prostate cancer cases and 24 controls) aged 48–76 years at baseline. The participants of our study were a part of the Fernald Community Cohort (FCC). Prostate cancer cases and controls were matched individually on age (± 3 years) with 1:1 ratio. Biomarkers included urine F2-isoprostanes (markers of lipid oxidation), plasma fluorescent oxidation products (FlOPs; markers of global oxidation) and carboxymethyllysine (CML; a major end-stage AGE). Results At baseline, cases had similar age, body mass index, proportion of family history of prostate cancer, history of benign prostatic hyperplasia, history of hypertension, history of diabetes, smokers and plasma glucose levels as compared to controls. Levels of plasma CML were significantly higher in cases than in controls (182 vs. 152 μg/ml, P < 0.05). In the conditional logistic regression model, an increase in CML equivalent to one standard deviation was associated with increased risk of incident prostate cancer (Relative risk = 1.79, 95% confidence interval = 1.00–3.21), and accounted for ~8% variance of prostate cancer liability. Urine F2-isoprostanes and plasma FlOPs were not associated with prostate cancer incidence. Conclusion Higher levels of plasma CML were associated with increased risk of prostate cancer. This suggests a potential new pathway for prostate cancer prediction and treatment. PMID:25972296

Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people

PubMed Central

2012-01-01

Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people. PMID:23013352

Ghrelin plasma levels in patients with idiopathic short stature.

PubMed

Iñiguez, Germán; Román, Rossana; Youlton, Ronald; Cassorla, Fernando; Mericq, Verónica

2011-02-01

Novel molecular insights have suggested that ghrelin may be involved in the pathogenesis of some forms of short stature. Recently, growth hormone secretagogue receptor (GHSR) mutations that segregate with short stature have been reported. To study plasma ghrelin levels in prepubertal patients with idiopathic short stature (ISS). Fasting total plasma ghrelin levels (radioimmunoassay) in 41 prepubertal patients with ISS (18 females, age 7.9 ± 0.5 years) compared with 42 age- and sex-matched controls (27 females, age 8.0 ± 0.3 years) with normal height. In a subset of 28 patients, the ghrelin receptor was sequenced. ISS patients exhibited a higher level of ghrelin (1,458 ± 137 vs. 935 ± 55 pg/ml, p < 0.01) and similar IGF-I levels (-0.66 ± 1.29 vs. -0.32 ± 0.78 SDS) compared to controls. Ten patients with ISS had ghrelin levels greater than +2 SDS compared to controls. These patients did not differ in height, BMI or IGF-I SDS compared to ISS patients with ghrelin levels within the normal range. Molecular analysis of GHSR did not show any mutations, but showed some polymorphisms. These results suggest that in ISS patients, short stature does not appear to be frequently caused by abnormalities in ghrelin signaling. Copyright © 2010 S. Karger AG, Basel.

Elevated Plasma IL-6 Associates with Increased Risk of Advanced Fibrosis and Cholangiocarcinoma in Individuals Infected by Opisthorchis viverrini

PubMed Central

Sripa, Banchob; Thinkhamrop, Bandit; Mairiang, Eimorn; Laha, Thewarach; Kaewkes, Sasithorn; Sithithaworn, Paiboon; Periago, Maria Victoria; Bhudhisawasdi, Vajarabhongsa; Yonglitthipagon, Ponlapat; Mulvenna, Jason; Brindley, Paul J.; Loukas, Alex; Bethony, Jeffrey M.

2012-01-01

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and increasing risk of advanced fibrosis and bile duct cancer; for example, in age and sex adjusted analyses, individuals with the highest quartiles of plasma IL-6 had a 19 times greater risk of developing advanced periductal fibrosis and a 150 times greater risk of developing of bile duct cancer than individuals with no detectable level of plasma IL-6. Finally, we show that a single plasma IL-6 measurement has excellent positive predictive value for the detection of both advanced bile duct fibrosis and bile duct cancer in regions with high O. viverrini transmission. These data support our hypothesis that common mechanisms drive bile duct fibrosis and bile duct tumorogenesis from chronic O. viverrini infection. Our study also adds a unique aspect to the literature on circulating levels of IL-6 as an immune marker of hepatobiliary pathology by showing that high levels of circulating IL-6 in plasma are not related to infection with O. viverrini, but to the development of the advanced and often lethal pathologies resulting from chronic O. viverrini infection. PMID:22629477

Plasma endothelin-1 and big endothelin-1 levels in women with pre-eclampsia.

PubMed

Sudo, N; Kamoi, K; Ishibashi, M; Yamaji, T

1993-08-01

To examine a possible role for endothelin-1 (ET-1) and conversion of big ET-1 to ET-1 in the pathophysiology of pre-eclampsia, we measured plasma levels of ET-1 and big ET-1 in 16 women with pre-eclampsia in the third trimester and compared them with those in 11 age-matched normotensive pregnant women and in 10 age-matched pregnant women with chronic hypertension in the third trimester. The plasma concentrations of ET-1 and big ET-1 in the normotensive pregnant women were significantly lower than those in 16 non-pregnant women with a higher molar ratio of big ET-1 to ET-1 in the former group. The plasma concentrations of ET-1 and big ET-1 in the women with pre-eclampsia, on the other hand, were significantly higher than those in the normotensive pregnant women and the molar ratio of big ET-1 to ET-1 in the former group was less than that in the latter group. In sharp contrast, plasma ET-1 and big ET-1 levels in the pregnant women with chronic hypertension were not significantly different from those in the normotensive pregnant women. When examined after delivery, elevated plasma ET-1 and big ET-1 in the women with pre-eclampsia declined, with restoration of normal blood pressure, to the levels in the normotensive women after parturition. There were no significant differences of the levels of ET-1 and big ET-1 in umbilical venous plasma and simultaneously drawn maternal plasma at cesarean section between normotensive pregnant women and women with pre-eclampsia, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals.

PubMed

Heng, Eng Chee; Karsani, Saiful Anuar; Abdul Rahman, Mariati; Abdul Hamid, Noor Aini; Hamid, Zalina; Wan Ngah, Wan Zurinah

2013-10-01

Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups. Subjects were divided into two age groups-32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78% tocotrienol and 22% tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting. Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression. TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.

Plasma long-chain omega-3 polyunsaturated fatty acids and macular pigment in subjects with family history of age-related macular degeneration: the Limpia Study.

PubMed

Merle, Bénédicte M J; Buaud, Benjamin; Korobelnik, Jean-François; Bron, Alain; Delyfer, Marie-Noëlle; Rougier, Marie-Bénédicte; Savel, Hélène; Vaysse, Carole; Creuzot-Garcher, Catherine; Delcourt, Cécile

2017-12-01

In numerous epidemiological studies, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age-related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega-3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega-3 PUFAs in subjects with family history of AMD. The Limpia study is a double-blind, placebo-controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40-70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega-3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega-3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high-density lipoprotein (HDL) cholesterol and lutein+zeaxanthin. After multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (β = 0.029, 95% CI: 0.003, 0.055; p = 0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD. In the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega-3 DPA. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Human plasma platelet-derived exosomes: effects of aspirin.

PubMed

Goetzl, Edward J; Goetzl, Laura; Karliner, Joel S; Tang, Norina; Pulliam, Lynn

2016-05-01

Platelet-derived exosomes mediate platelet atherogenic interactions with endothelial cells and monocytes. A new method for isolation of plasma platelet-derived exosomes is described and used to examine effects of aging and aspirin on exosome cargo proteins. Exosome secretion by purified platelets in vitro did not increase after exposure to thrombin or collagen, as assessed by exosome counts and quantification of the CD81 exosome marker. Thrombin and collagen increased exosome content of α-granule chemokines CXCL4 and CXCL7 and cytoplasmic high-mobility group box 1 (HMGB1) protein, but not membrane platelet glycoprotein VI (GPVI), with dependence on extracellular calcium. Aspirin consumption significantly blocked thrombin- and collagen-induced increases in exosome cargo levels of chemokines and HMGB1, without altering total exosome secretion or GPVI cargo. Plasma platelet-derived exosomes, enriched by absorption with mouse antihuman CD42b [platelet glycoprotein Ib (GPIb)] mAb, had sizes and cargo protein contents similar to those of exosomes from purified platelets. The plasma platelet-derived exosome number is lower and its chemokine and HMGB1 levels higher after age 65 yr. Aspirin consumption significantly suppressed cargo protein levels of plasma platelet-derived exosomes without altering total levels of exosomes. Cargo proteins of human plasma platelet-derived exosomes may biomark platelet abnormalities and in vivo effects of drugs.- Goetzl, E. J., Goetzl, L., Karliner, J. S., Tang, N., Pulliam, L. Human plasma platelet-derived exosomes: effects of aspirin. © FASEB.

A preliminary report of increased plasma levels of IL-33 in bipolar disorder: further evidence of pro-inflammatory status.

PubMed

Barbosa, Izabela Guimaraes; Morato, Isabela Boechat; de Miranda, Aline Silva; Bauer, Moisés Evandro; Soares, Jair C; Teixeira, Antônio Lucio

2014-03-01

Recent findings suggest an important role for inflammation in the neurobiology of bipolar disorder (BD). Interleukin 33 (IL-33) is a cytokine with multiple functions and may act as a nuclear factor regulating transcription and as an "alarmin". IL-33 exerts part of its function through the receptor ST2 that also exists in a soluble form (sST2). This study was performed to evaluate IL-33 and sST2 plasma levels in BD patients. We evaluated IL33 and sST2 plasma levels of 46 BD patients (23 in euthymia and 23 in mania) and 23 healthy controls using enzyme-linked immunosorbent assay (ELISA). BD patients were age and gender matched healthy controls. IL-33 levels were higher in BD patients (p=0.02) but there was no difference in sST2 (p=0.55). IL33 and sST2 plasma levels were not correlated with age, neither was influenced by clinical comorbidities nor medications in use. These findings corroborate the view of BD as a multisystem condition with a proinflammatory profile. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans.

PubMed

Carpentier, André C; Frisch, Frédérique; Brassard, Pascal; Lavoie, François; Bourbonnais, Annie; Cyr, Denis; Giguère, Robert; Baillargeon, Jean-Patrice

2007-03-01

Insulin increases plasma nonesterified fatty acid (NEFA) clearance in humans, but whether this is independent of change in plasma NEFA appearance is currently unknown. Nine nondiabetic men (age: 28+/-3 yr, body mass index: 27.2+/-1.7 kg/m2) underwent euglycemic clamps to maintain low (LINS) vs. high (HINS) physiological insulin levels for 6 h. An intravenous infusion of heparin+Intralipid (HI) was performed during 4 of the 6 h of the clamps (in the last 4 h at LINS and in the first 4 h at HINS), whereas saline infusion (SAL) was administered in the remaining 2 h to modulate plasma NEFA levels independently of plasma insulin levels. Four experimental conditions were obtained in each individual: LINS with saline (LINS/SAL) and with HI infusion (LINS/HI) and HINS with saline (HINS/SAL) and with HI infusion (HINS/HI). Plasma palmitate appearance during HINS/SAL was lower than during the three other experimental conditions (P<0.05). In contrast, plasma linoleate appearance, as expected, was increased by HI independently of insulin level (P<0.02). Plasma palmitate clearance during HINS/SAL was higher than LINS/SAL and LINS/HI (P<0.008), and this increase was blunted during HINS/HI. We observed a linear decrease in plasma palmitate clearance with increasing plasma NEFA appearance independent of insulin levels. Plasma NEFA levels increased exponentially with increase in plasma NEFA appearance. We conclude that insulin stimulates plasma NEFA clearance by reducing the endogenous appearance rate of NEFA. The relationship between plasma NEFA level and appearance rate is nonlinear.

Prenatal exposure to selenium may protect against wheezing in children by the age of 3.

PubMed

Baïz, Nour; Chastang, Julie; Ibanez, Gladys; Annesi-Maesano, Isabella

2017-03-01

It has been suggested that human in utero exposure to heavy metals such as selenium can reduce the prevalence of childhood asthma and allergic diseases. However, data on this topic are scarce. The objective of the present study was to assess the putative associations between maternal selenium level during pregnancy and the risk of asthma, wheezing, allergic rhinitis, and atopic dermatitis in children from the EDEN birth cohort by the age of 1 and 3 years. Plasma selenium concentrations were measured in maternal blood during mid-pregnancy (24-28 weeks of gestation) in 861 mothers. Cohort children were followed up from birth to 3 years using health questionnaires filled out by the parents for asthma, wheezing, allergic rhinitis, and atopic dermatitis. Maternal plasma selenium was related to the childhood outcomes by the age of 1 and 3 years. Our results showed a significant negative association between a high maternal plasma selenium level during pregnancy and the risk of wheezing in the child by the age of 1 and 3 years. However, maternal plasma selenium during pregnancy was not associated with the prevalence of asthma, allergic rhinitis or atopic dermatitis. The results of this study suggest that the level of fetal exposure to maternal selenium could have an influence on the risk of wheezing in infancy and potentially on the risk of developing asthma later in life.

Effects of whole-body vibration on plasma sclerostin level in healthy women.

PubMed

Çidem, Muharrem; Karakoç, Yunus; Ekmekçi, Hakan; Küçük, Suat Hayri; Uludağ, Murat; Gün, Kerem; Karamehmetoğlu, Safak Sahir; Karacan, İlhan

2014-01-01

To determine whether plasma sclerostin levels are affected by applying whole-body vibration treatments. Following a pilot study, the pretsent prospective, randomized, controlled single-blind study was performed on 16 healthy volunteer women (ages 20 to 40 years). Subjects were randomly divided into 2 groups, and whole-body vibration was applied to the treatment group but not to the controls. The plasma sclerostin levels were measured before the treatment and at the 10th minute after whole-body vibration on the 1st, 2nd, and 5th days of application. The plasma sclerostin level measured at 10 min after the whole-body vibration treatment increased 91% (P = 0.024) on the 1st day and decreased 31.5% (P = 0.03) on the 5th day in the whole-body vibration group. In the control group, there was no change in the plasma sclerostin level at any time. A progressive increase in baseline plasma sclerostin levels during the 5 days of vibration sessions was also found. Our study demonstrated that whole-body vibration can change plasma sclerostin levels, and that this change is detectable 10 min after whole-body vibration treatments.

Abnormal angiopoietins 1&2, angiopoietin receptor Tie-2 and vascular endothelial growth factor levels in hypertension: relationship to target organ damage [a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)].

PubMed

Nadar, S K; Blann, A; Beevers, D G; Lip, G Y H

2005-10-01

The increased risk of target organ damage (TOD) in hypertension may be related to a prothrombotic or hypercoagulable state, with abnormalities in platelet activation. Altered angiogenesis, possibly related to increased plasma vascular endothelial growth factor (VEGF) is also a feature of hypertension. We hypothesized a link between altered angiogenesis and TOD in hypertension. Accordingly, the angiogenic growth factors VEGF, angiopoietin 1 and 2 (Ang 1 & 2) and soluble angiopoietin receptor Tie-2 in plasma and in platelets were assessed in terms of the presence or absence of hypertensive TOD. We studied 199 patients (75% men; mean age 68 years) with hypertension. Of these, 125 had evidence of hypertensive TOD (stroke, previous myocardial infarction, angina, left ventricular hypertrophy and mild renal failure). Patients were compared with 74 healthy normotensive controls (69% men; mean age 68 years). Plasma VEGF, Ang 1 & 2 and Tie-2, and total platelet levels of VEGF and Ang-1 (obtained by lysing a known number of platelets with 0.5% Tween) were measured by an enzyme-linked immunosorbent assay. Hypertensive patients had higher levels of plasma VEGF, Ang-1, Ang-2, Tie-2 and platelet VEGF (all P

Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice.

PubMed

Kubo, Kin-ya; Yamada, Yukiko; Iinuma, Mitsuo; Iwaku, Fumihiko; Tamura, Yasuo; Watanabe, Kazuko; Nakamura, Hiroyuki; Onozuka, Minoru

2007-03-06

We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8) mice on plasma corticosterone levels, hippocampal neuron number, and spatial performance in the water maze. The bite-raised condition was associated with an accelerated age-related decline in spatial memory, increased plasma corticosterone levels, and a decreased number of neurons in the hippocampal CA3 region. The findings suggest that the bite-raised condition in aged SAMP8 mice induces hippocampal neuron loss, thereby leading to senile memory deficits.

Plasma lipid peroxidation and erythrocyte antioxidant enzymes status in workers exposed to cadmium.

PubMed

Babu, Kalahasthi Ravi; Rajmohan, Hirehal Raghavendra Rao; Rajan, Bagalur Krishna Murthy; Kumar, Karuna M

2006-09-01

Cadmium (Cd) is a corrosion-resistant metal, used extensively for electroplating in the automobile, electronic and aerospace industry. Only a few studies are available regarding Cd-induced oxidative stress in animals, but no reports are available regarding the effects of Cd on oxidative stress during occupational exposure. The present study was carried out to determine the plasma lipid peroxidation and erythrocyte antioxidant enzymes status in workers exposed to Cd during electroplating. 50 subjects exposed to Cd during electroplating formed the study group. An equal number of age-sex matched subjects, working in the administrative section, formed the control group. Urinary Cd levels were determined using the flameless atomic absorption spectrophotometer. Plasma lipid peroxidation and erythrocyte antioxidant enzymes were determined using spectrophotometric methods. A significant increase of plasma lipid peroxidation and a significant decrease of superoxide dismutase and glutathione peroxidase levels were noted in the study group compared with the control group. The level of plasma lipid peroxidation was positively and erythrocyte antioxidant enzymes were negatively and significantly associated with Cd levels in urine. Multiple regression analysis assessed the oxidative stress associated with Cd and other lifestyle confounding factors, such as age, body mass index, the consumption of vegetables, coffee, tea, smoking and alcohol. Analysis showed that the lifestyle confounding factors viz; smoking, body mass index and urinary Cd levels > 5 microg/g of creatinine, were significantly associated with oxidative stress. The results of the present study suggest that increased plasma lipid peroxidation and decreased superoxide dismutase levels could be used as biomarkers of oxidative stress in cadmium-exposed workers.

Aged Garlic Extract Improves Adiponectin Levels in Subjects with Metabolic Syndrome: A Double-Blind, Placebo-Controlled, Randomized, Crossover Study

PubMed Central

Gómez-Arbeláez, Diego; Lahera, Vicente; Oubiña, Pilar; Valero-Muñoz, Maria; de las Heras, Natalia; Rodríguez, Yudy; García, Ronald Gerardo; Camacho, Paul Anthony; López-Jaramillo, Patricio

2013-01-01

Background. Garlic (Allium sativum) has been shown to have important benefits in individuals at high cardiovascular risk. The aim of the present study was to evaluate the effects of the administration of aged garlic extract (AGE) on the risk factors that constitute the cluster of metabolic syndrome (MS). Methods and Design. Double-blind, crossover, randomized, placebo-controlled clinical trial to assess the effect of 1.2 g/day of AGE (Kyolic), for 24 weeks of treatment (12 weeks of AGE and 12 weeks of placebo), on subjects with MS. Results. The administration of AGE increased the plasma levels of adiponectin (P = 0.027). No serious side effects associated with the intervention were reported. Conclusion. The present results have shown for the first time that the administration of AGE for 12 weeks increased plasma adiponectin levels in patients with MS. This suggests that AGE might be a useful, novel, nonpharmacological therapeutic intervention to increase adiponectin and to prevent cardiovascular (CV) complications in individuals with MS. PMID:23533302

Adiponectin: an independent risk factor for coronary heart disease in men in the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

Our aim was to determine whether plasma adiponectin levels were an independent predictor of coronary heart disease (CHD) risk. Plasma adiponectin levels were measured in 3,188 male and female participants from cycle 6 of the Framingham Offspring Study (mean age: 57 years in both men and women; BMI:...

Elevated plasma levels of PAI-1 predict cardiovascular events and cardiovascular mortality in prevalent peritoneal dialysis patients.

PubMed

Arikan, Hakki; Koc, Mehmet; Tuglular, Serhan; Ozener, Cetin; Akoglu, Emel

2009-01-01

Elevated plasminogen activator inhibitor-1 (PAI-1) levels are associated with increased cardiovascular (CV) risk in the general population. It has been shown that peritoneal dialysis (PD) patients have increased plasma levels of PAI-1. The aim of this study was to investigate whether PAI-1 independently predicted CV outcome in PD patients. Seventy-two PD patients (53% females, mean age 49.9 +/- 16.1 years) were studied. Twelve patients who underwent kidney transplantation and 14 patients who transferred to hemodialysis during follow-up were excluded from the analysis. The remaining 46 patients (54% female, mean age 54 +/- 16 years, dialytic age 42 +/- 30 months) were followed a mean time of 45.4 +/- 19.4 months (range 8-71 months). Baseline PAI-1, clinical, and laboratory parameters were assessed in all patients. Survival analyses were made with Kaplan-Meier and Cox regression analysis, with all-cause mortality and CV mortality and CV events (CVEs) as clinical end points. During the follow-up, 29 patients died (17 from CV causes), and 28 fatal and non-fatal CVEs were recorded. The patients were divided according to plasma PAI-1 levels (i.e., 41 ng/mL). The significant independent predictors of all-cause of mortality were age (60 years; p = 0.018), CRP (5 mg/L; p = 0.015), and serum albumin (<3.5 g/L; p = 0.011). Multivariable Cox regression analysis showed that plasma PAI-1 41 ng/mL was independently predictive of higher CV mortality (p = 0.021) and CVEs (p = 0.001). The only other independent predictor of CV mortality was only CRP (5 mg/L; p = 0.008). Plasma levels of PAI-1 41 ng/mL is a significant predictor of CV mortality and CVEs in PD patients.

Relationships between serum brain-derived neurotrophic factor, plasma catecholamine metabolites, cytokines, cognitive function and clinical symptoms in Japanese patients with chronic schizophrenia treated with atypical antipsychotic monotherapy.

PubMed

Hori, Hikaru; Yoshimura, Reiji; Katsuki, Asuka; Atake, Kiyokazu; Igata, Ryohei; Konishi, Yuki; Nakamura, Jun

2017-08-01

Catecholamines, brain-derived neurotrophic factor (BDNF) and cytokines may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations between serum BDNF levels, plasma catecholamine metablolites, cytokines and the cognitive functions of patients with schizophrenia treated with atypical antipsychotic monotherapy. One hundred and forty-six patients with schizophrenia and 51 age- and sex-matched healthy controls were examined for peripheral biological markers and neurocognitive test. There were positive correlations between serum BDNF levels and scores for verbal memory and attention and processing speed as well as between serum BDNF levels and negative symptoms. Furthermore, there was a negative correlation between the plasma homovanillic acid (HVA) level and motor function and a positive correlation between the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level and attention and processing speed. There were no significant correlations between interleukin-6 or tumour necrosis factor alpha and cognitive function. Moreover, there were no significant correlations between the plasma levels of HVA, MHPG, cytokines and clinical symptoms. Serum BDNF levels are positively related to the impairment of verbal memory and attention, plasma HVA levels are positively related to motor function, and plasma MHPG levels are positively related to attention in patients with schizophrenia.

Association of Blood and Seminal Plasma Cadmium and Lead Levels With Semen Quality in Non-Occupationally Exposed Infertile Men in Abakaliki, South East Nigeria

PubMed Central

Famurewa, Ademola C.; Ugwuja, Emmanuel I.

2017-01-01

Objective: To evaluate association of blood and seminal plasma lead and cadmium with sperm quality of non-occupationally exposed male partners of couples with infertility. Materials and methods: A cross-sectional study was conducted on 75 men aged 20-45 years (mean = 37.1 ± 7.0 yrs.) with infertility recruited from the Fertility Clinic of a hospital in Abakaliki. Sperm count done in accordance with the WHO guidelines was used to classify the participants as normospamia, oligospermia and azospermia. Atomic absorption spectrophotometer was used to determine lead and cadmium levels in plasma from blood and semen. Results: There were 15 azospermics, 22 oligospermics and 36 normospermics. Seminal and blood plasma cadmium as well as blood plasma lead were significantly (p < 0.01) higher in azospermic and oligospermic men compared to normospermic men. However, while seminal plasma lead was significantly (p < 0.05) higher in oligospermic and normospernic men than in azospermic men, the seminal plasma lead was comparable between oligospermic and normospermic men. Significant inverse associations (p < 0.01) were found between blood and seminal cadmium levels and sperm count, motility and morphology; blood lead was inversely correlated with sperm count only. Conclusion: The study suggests that environmental exposure to cadmium and lead may contribute to development of poor sperm quality and infertility in men of reproductive age in Nigeria. PMID:29282417

Pomegranate (Punicagranatum) juice decreases lipid peroxidation, but has no effect on plasma advanced glycated end-products in adults with type 2 diabetes: a randomized double-blind clinical trial.

PubMed

Sohrab, Golbon; Angoorani, Pooneh; Tohidi, Maryam; Tabibi, Hadi; Kimiagar, Masoud; Nasrollahzadeh, Javad

2015-01-01

Diabetes mellitus characterized by hyperglycemia could increase oxidative stress and formation of advanced glycated end-products (AGEs), which contribute to diabetic complications. The purpose of this study was to assess the effect of pomegranate juice (PJ) containing natural antioxidant on lipid peroxidation and plasma AGEs in patients with type 2 diabetes (T2D). In a randomized, double-blind, placebo-controlled trial, 44 patients (age range 56±6.8 years), T2D were randomly assigned to one of two groups: group A (PJ, n=22) and group B (Placebo, n=22). At the baseline and the end of 12-week intervention, biochemical markers including fasting plasma glucose, insulin, oxidative stress, and AGE markers including carboxy methyl lysine (CML) and pentosidine were assayed. At baseline, there were no significant differences in plasma total antioxidant capacity (TAC) levels between the two groups, but malondialdehyde (MDA) decreased levels were significantly different (P<0.001). After 12 weeks of intervention, TAC increased (P<0.05) and MDA decreased (P<0.01) in the PJ group when compared with the placebo group. However, no significant differences were observed in plasma concentration of CML and pentosidine between the two groups. The study showed that PJ decreases lipid peroxidation. Therefore, PJ consumption may delay onset of T2D complications related to oxidative stress.

Plasma apolipoprotein E and severity of suicidal behaviour.

PubMed

Asellus, Peter; Nordström, Peter; Nordström, Anna-Lena; Jokinen, Jussi

2016-01-15

There is evidence for association between low cholesterol levels and suicidal behaviour. Since apolipoprotein E (ApoE) is involved in the cholesterol metabolism in both the periphery and in the central nervous system; it may be of particular interest in the neurobiology of suicidal behaviour. Furthermore, hypothalamic-pituitary-adrenal (HPA) axis function, one of the main biological systems implicated in both suicidal behaviour and early-life adversity, affect ApoE levels. Very few studies have assessed plasma ApoE in relation to suicidal behaviour. The purpose of this study was to investigate levels of ApoE in plasma in relation to the severity of suicidal behaviour and life-time adversity in the form of exposure to interpersonal violence in suicide attempters. A total of 100 suicide attempters (67 women and 33 men) were enroled in the study. Information on earlier suicide attempts and age at onset of suicidal behaviour was gathered using the Karolinska Suicide History Interview. The Karolinska Interpersonal Violence Scale was used to assess exposure to interpersonal violence. Plasma ApoE was measured by immunonephelometry according to accredited routines. Patients with at least one earlier suicide attempt had significantly higher ApoE levels compared to suicide attempters debuting with suicidal behaviour at inclusion in the study. A higher number of earlier suicide attempts was significantly correlated with higher plasma ApoE levels. Age at onset was significantly negatively correlated with ApoE after adjusting for age. ApoE showed a significant positive correlation with exposure to interpersonal violence as a child in male suicide attempters. Our findings indicate that ApoE may be related to stress and trauma and the temporal severity of suicidal behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.

Midlife blood pressure, plasma β amyloid and the risk for Alzheimer’s disease: the Honolulu Asia Aging Study

PubMed Central

Shah, Nilay S.; Vidal, Jean-Sébastien; Masaki, Kamal; Petrovitch, Helen; Ross, G. Webster; Tilley, Cathy; DeMattos, Ronald B.; Tracy, Russell P.; White, Lon R.; Launer, Lenore J.

2012-01-01

Beta-amyloid (Aβ), a vasoactive protein, and elevated blood pressure (BP) levels are associated with Alzheimer’s disease (AD) and possibly vascular dementia (VaD). We investigated the joint association of mid-life BP and Aβ peptide levels with the risk for late-life AD and VaD. Subjects were 667 Japanese-American men (including 73 with a brain autopsy), from the prospective Honolulu Heart Program/Honolulu Asia Aging Study (1965 – 2000). Mid-life BP was measured starting in 1971 participants mean age 58 years, Aβ was measured in specimens collected1980/82, and assessment of dementia and autopsy collection started in 1991/93. The outcome measures were prevalent (present in 1991/3) and incident AD (n= 53, including 38 with no contributing cardiovascular disease), and VaD (n=24). Cerebral amyloid angiopathy (CAA), β-amyloid neuritic plaques, and neurofibrillary tangles were evaluated in post-mortem tissue. The risk for AD significantly increased with lower levels of plasma Aβ (Aβ1-40 hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.4 – 3.1; Aβ1-42 HR 1.6, 95% CI 1.1 – 2.3). Evidence of interaction between diastolic BP and plasma Aβ (1-40 pinteraction <0.05; 1-42 pinteraction <0.07) levels, indicated the Aβ-related risk for AD was higher when BP was higher. Low plasma Aβ was associated with the presence of CAA (ptrend<0.05), but not the other neuropathologies. Aβ plasma levels start decreasing at least 15 years before AD is diagnosed, and the association of Aβ to AD is modulated by mid-life diastolic BP. Elevated BP may compromise vascular integrity leading to CAA and impaired Aβ clearance from the brain. PMID:22392902

Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects

PubMed Central

Onishi, Airin; Fujiwara, Yoshinori; Ishiwata, Kiichi; Ishii, Kenji

2017-01-01

Background Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images. Methods Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated. Results Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p < 0.05), and no correlation with plasma insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4–5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24). Conclusion This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images. PMID:28715453

Normal fasting plasma glucose levels and type 2 diabetes in young men.

PubMed

Tirosh, Amir; Shai, Iris; Tekes-Manova, Dorit; Israeli, Eran; Pereg, David; Shochat, Tzippora; Kochba, Ilan; Rudich, Assaf

2005-10-06

The normal fasting plasma glucose level was recently defined as less than 100 mg per deciliter (5.55 mmol per liter). Whether higher fasting plasma glucose levels within this range independently predict type 2 diabetes in young adults is unclear. We obtained blood measurements, data from physical examinations, and medical and lifestyle information from men in the Israel Defense Forces who were 26 to 45 years of age. A total of 208 incident cases of type 2 diabetes occurred during 74,309 person-years of follow-up (from 1992 through 2004) among 13,163 subjects who had baseline fasting plasma glucose levels of less than 100 mg per deciliter. A multivariate model, adjusted for age, family history of diabetes, body-mass index, physical-activity level, smoking status, and serum triglyceride levels, revealed a progressively increased risk of type 2 diabetes in men with fasting plasma glucose levels of 87 mg per deciliter (4.83 mmol per liter) or more, as compared with those whose levels were in the bottom quintile (less than 81 mg per deciliter [4.5 mmol per liter], P for trend <0.001). In multivariate models, men with serum triglyceride levels of 150 mg per deciliter (1.69 mmol per liter) or more, combined with fasting plasma glucose levels of 91 to 99 mg per deciliter (5.05 to 5.50 mmol per liter), had a hazard ratio of 8.23 (95 percent confidence interval, 3.6 to 19.0) for diabetes, as compared with men with a combined triglyceride level of less than 150 mg per deciliter and fasting glucose levels of less than 86 mg per deciliter (4.77 mmol per liter). The joint effect of a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more and a fasting plasma glucose level of 91 to 99 mg per deciliter resulted in a hazard ratio of 8.29 (95 percent confidence interval, 3.8 to 17.8), as compared with a body-mass index of less than 25 and a fasting plasma glucose level of less than 86 mg per deciliter. Higher fasting plasma glucose levels within the normoglycemic range constitute an independent risk factor for type 2 diabetes among young men, and such levels may help, along with body-mass index and triglyceride levels, to identify apparently healthy men at increased risk for diabetes. Copyright 2005 Massachusetts Medical Society.

Elevated pentraxin 3 level at the early stage of exercise training is associated with reduction of arterial stiffness in middle-aged and older adults.

PubMed

Zempo-Miyaki, A; Fujie, S; Sato, K; Hasegawa, N; Sanada, K; Maeda, S; Hamaoka, T; Iemitsu, M

2016-09-01

Regular exercise improves aging-induced deterioration of arterial stiffness, and is associated with elevated production of pentraxin 3 (PTX3) and anti-inflammatory as well as anti-atherosclerotic effects. However, the time-dependent effect of exercise training on arterial stiffness and PTX3 production remains unclear. The purpose of this study was to investigate the time course of the association between the effects of training on the circulating PTX3 level and arterial stiffness in middle-aged and older adults. Thirty-two healthy Japanese subjects (66.2±1.3 year) were randomly divided into two groups: training (exercise intervention) and sedentary controls. Subjects in the training group completed 8 weeks of aerobic exercise training (60-70% peak oxygen uptake (VO2peak) for 45 min, 3 days per week); during the training period, we evaluated plasma PTX3 concentration and carotid-femoral pulse wave velocity (cfPWV) every 2 wk. cfPWV gradually declined over the 8-week training period, and was significantly reduced after 6 and 8 week of exercise intervention (P<0.05). Plasma PTX3 level was significantly increased after 4 weeks of the intervention (P<0.05). In addition, the exercise training-induced reduction in cfPWV was negatively correlated with the percent change in plasma PTX3 level after 6 week (r=-0.54, P<0.05) and 8 weeks (r=-0.51, P<0.05) of the intervention, but not correlated at 4 weeks. Plasma PTX3 level was elevated at the early stage of the exercise training intervention, and was subsequently associated with training-induced alteration of arterial stiffness in middle-aged and older adults.

TMEM106B gene polymorphism is associated with age at onset in granulin mutation carriers and plasma granulin protein levels

PubMed Central

Cruchaga, Carlos; Graff, Caroline; Chiang, Huei-Hsin; Wang, Jun; Hinrichs, Anthony L.; Spiegel, Noah; Bertelsen, Sarah; Mayo, Kevin; Norton, Joanne B.; Morris, John C.; Goate, Alison

2011-01-01

Objective A recent genome-wide association study for frontotemporal lobar degeneration with TAR DNA-binding protein inclusions (FTLD-TDP), identified rs1990622 (TMEM106B) as a risk factor for FTLD-TDP. In this study we tested whether rs1990622 is associated with age at onset (AAO) in granulin (GRN) mutation carriers and with plasma GRN levels in mutation carriers and healthy elderly individuals. Design Rs1990622 was genotyped in GRN mutation carriers and tested for association with AAO using the Kaplan-Meier and a Cox proportional hazards model. Subjects We analyzed 50 affected and unaffected GRN mutation carriers from four previously reported FTLD-TDP families (HDDD1, FD1, HDDD2 and the Karolinska family). GRN plasma levels were also measured in 73 healthy, elderly individuals. Results The risk allele of rs1990622 is associated with a mean decrease of the age at onset of thirteen years (p=9.9×10−7), with lower plasma granulin levels in both healthy older adults (p = 4×10−4) and GRN mutation carriers (p=0.0027). Analysis of the HAPMAP database identified a non-synonymous single nucleotide polymorphism, rs3173615 (T185S) in perfect linkage disequilibrium with rs1990622. Conclusions The association of rs1990622 with AAO explains, in part, the wide range in the age at onset of disease among GRN mutation carriers. We hypothesize that rs1990622 or another variant in linkage disequilibrium could act in a manner similar to APOE in Alzheimer’s disease, increasing risk for disease in the general population and modifying AAO in mutation carriers. Our results also suggest that genetic variation in TMEM106B may influence risk for FTLD-TDP by modulating secreted levels of GRN. PMID:21220649

Effect of 'PC Game Room' use and polycyclic aromatic hydrocarbon exposure on plasma testosterone concentrations in young male Koreans.

PubMed

Kim, Heon; Kang, Jong-Won; Ku, Seung-Yup; Kim, Seok Hyun; Cho, Soo-Hun; Koong, Sung-Soo; Kim, Yong-Dae; Lee, Chul-Ho

2005-03-01

'PC Game Rooms' were first popularized in Korea, although the concept is now becoming popular worldwide. PC Game Rooms provide users with high-performance PC connected to the high-speed internet, and access to computer games. However, PC Game Room users are exposed to various hazardous agents such as cigarette smoke in a confined environment, and thus it is likely that excessive PC Game Room use involves abnormal exposure to polycyclic aromatic hydrocarbons (PAH) as well as being associated with disturbed sleep or circadian rhythm. In this cross-sectional study, the exposure to PAH was evaluated by measuring urinary 1-hydroxypyrene (1-OHP) and 2-naphthol. The correlations between PC Game Room use and PAH exposure and plasma testosterone and LH levels were analysed in 208 young male Koreans. Urinary 1-OHP concentrations increased (P = 0.0001) and plasma testosterone levels decreased (P = 0.0153) significantly with increased duration of PC Game Room use. Correlation analysis showed that plasma testosterone concentrations were significantly negatively correlated with urinary 1-OHP (r = -0.22, P = 0.0012) and 2-naphthol (r = -0.15, P = 0.0308) concentrations. Moreover, these associations persisted after adjusting for other independent variables. However, the duration of PC Game Room use itself was not found to be an independent significant determinant of plasma testosterone level. Rather, PC Game Room use increased PAH exposure, which decreased plasma testosterone level. The younger age group (15-19 years) showed a more prominent decrease in plasma testosterone concentrations with increasing duration of PC Game Room use than the older age group (20-24 years) (r2 = 0.355, P = 0.0301 versus r2 = 0.213, P = 0.0001). These results imply that the excessive use of PC Game Rooms is related to an adverse impact on sex hormonal status in young male Koreans via PAH exposure. This effect was more prominent in the younger age group.

Advanced Glycation End Products in Infant Formulas Do Not Contribute to Insulin Resistance Associated with Their Consumption

PubMed Central

Klenovics, Kristína Simon; Boor, Peter; Somoza, Veronika; Celec, Peter; Fogliano, Vincenzo; Šebeková, Katarína

2013-01-01

Introduction Infant formula-feeding is associated with reduced insulin sensitivity. In rodents and healthy humans, advanced glycation end product (AGE)-rich diets exert diabetogenic effects. In comparison with human breast-milk, infant formulas contain high amounts of AGEs. We assessed the role of AGEs in infant-formula-consumption-associated insulin resistance. Methods Total plasma levels of Nε-(carboxymethyl)lysine (CML), AGEs-associated fluorescence (λex = 370 nm/λem = 445 nm), soluble adhesion molecules, markers of micro- binflammation (hsCRP), oxidative stress (malondialdehyde, 8-isoprostanes) and leptinemia were determined, and correlated with insulin sensitivity in a cross-sectional study in 166 healthy term infants aged 3-to-14 months, subdivided according to feeding regimen (breast-milk- vs. infant formula-fed) and age (3-to-6-month-olds, 7-to-10-month-olds, and 11-to-14-month-old infants). Effects of the consumption of low- vs. high-CML-containing formulas were assessed. 36 infants aged 5.8±0.3 months were followed-up 7.5±0.3 months later. Results Cross-sectional study: 3-to-6-month-olds and 7-to-10-month-old formula-fed infants presented higher total plasma CML levels and AGEs-associated fluorescence (p<0.01, both), while only the 3-to-6-month-olds displayed lower insulin sensitivity (p<0.01) than their breast-milk-fed counterparts. 3-to-6-month-olds fed low-CML-containing formulas presented lower total plasma CML levels (p<0.01), but similar insulin sensitivity compared to those on high-CML-containing formulas. Markers of oxidative stress and inflammation, levels of leptin and adhesion molecules did not differ significantly between the groups. Follow-up study: at initial investigation, the breast-milk-consuming infants displayed lower total plasma CML levels (p<0.01) and AGEs-associated fluorescence (p<0.05), but higher insulin sensitivity (p<0.05) than the formulas-consuming infants. At follow-up, the groups did not differ significantly in either determined parameter. Conclusions In healthy term infants, high dietary load with CML does not play a pathophysiological role in the induction of infant formula-associated insulin resistance. Whether a high load of AGEs in early childhood affects postnatal programming remains to be elucidated. PMID:23301020

[Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) blood levels in patients with acute carbon monoxide poisoning - a preliminary observations].

PubMed

Ciszowski, Krzysztof; Gomółka, Ewa; Gawlikowski, Tomasz; Szpak, Dorota; Potoczek, Anna; Boba, Magdalena

Neurotrophins are the family of proteins which stimulate and regulate the process of neurogenesis. Several factors belong to the family, mainly nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT 3), and neurotrophin-4/5 (NT-4/5). Acute poisoning with carbon monoxide (CO), which usually is accompanied by neurologic symptoms, can potentially change the secretion profile of neurotrophins. Aim of the study. The main goal of the study is to assess the changes of NGF and BDNF plasma levels during an acute phase of CO poisoning as well as immediately after recovery. Additionally, the relationship among neurotrophin levels and selected aspects of clinical course of CO poisoning were studied. The study group consisted of 18 patients (mean age: 31.8±10.3 years) hospitalized in Toxicology Department of University Hospital in Cracow because of acute CO poisoning. There were 10 women (mean age: 30.2±6.9 years) and 8 men (mean age 33.9±13.7 years) in the group. The levels of NGF and BDNF were evaluated using immunoenzymatic method (ELISA) in plasma samples taken thrice in each patient. The sample 1. was taken during hospital admission, the sample 2. about 12-36 hours after admission, and the sample 3. just before the hospital discharging (usually, on the 3rd-4th day). The clinical data were collected from patients’ anamnesis, physical examination and neuropsychological evaluation. The statistical analysis were performed using tools comprised in STATISTICA 12.0 PL (StatSoft Polska, Cracow, Poland) software. The majority of NGF plasma levels were less than 14 pg/mL (values below the limit of quantification), contrary to the sole case of 34.3 pg/mL. BDNF plasma levels ranged from 4.8 ng/mL to above 48 ng/mL, i.e. they were higher than the upper limit of measurement range for the plasma dilution which had been used. The comparison of NGF and BDNF plasma levels in the study group with their analogues in healthy volunteers taken from the literature indicates that NGF level declines and BDNF level rises in patients with CO poisoning. The profile of BDNF concentrations in the majority of patients formed the characteristic pattern: BDNF sample 1. > BDNF sample 2. < BDNF sample 3. Taking all the values of BDNF higher than 48 ng/mL as equal to 48 ng/ mL, the statistically significant difference among 3 sample series was found according to BDNF levels. Maintaining the above mentioned assumption, the statistically significant negative correlation between the number of higher cognitive functions disturbed in one patient at the same time and the BDNF levels in sample series 2 was discovered, as well as the weak correlations between BDNF level in sample series 1 and carboxyhaemoglobin or lactate level. Moreover, weak but statistically significant correlations were present between the duration of CO exposure and BDNF levels in each sample series. The NGF plasma level is probably declined, while the BDNF plasma level is increased in patients with acute CO poisoning. The concentration–time curve for the plasma BDNF may sometimes undergo fluctuations with two peaks on its course. Plasma BDNF level may serve as a biological marker of disturbed higher cognitive functions in acute CO poisoning. Some clinical aspects of CO poisoning (duration of exposure, HbCO and lactate blood levels) may influence BDNF level.

Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient.

PubMed

Miyata, T; van Ypersele de Strihou, C; Imasawa, T; Yoshino, A; Ueda, Y; Ogura, H; Kominami, K; Onogi, H; Inagi, R; Nangaku, M; Kurokawa, K

2001-12-01

Advanced glycation of proteins and their attendant advanced glycation end products (AGEs) contribute to the complications associated with diabetes mellitus or uremia. Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification system of precursor reactive carbonyl compounds (RCOs) in the in vivo AGE formation. Plasma levels of AGEs [pentosidine and Nepsilon-carboxymethyllysine (CML)], their RCO precursors, d-lactate (the final product resulting from the glyoxalase detoxification pathway), as well as of various compounds known to generate AGE precursors and surrogate markers for oxidative stress (antioxidant enzymes and glutathione), were measured in both hemodialysis (HD) patients and normal subjects. The activity and protein expression of glyoxalase I, an enzyme essential for the detoxification of alpha-oxoaldehydes, in red blood cells (RBC) were also examined. In one 69-year-old lady who had been on hemodialysis (HD) for three years and had suffered from recurrent cardiovascular complications despite the absence of significant risk factors, plasma levels of pentosidine (77.3 +/- 2.4 pmol/mg protein) and CML (330.8 +/- 8.2 pmol/mg protein) were markedly elevated as compared to other HD patients (N = 20: 26.6 +/- 11.8 pmol/mg protein for pentosidine and 224.4 +/- 51.7 pmol/mg protein for CML). The plasma level of RCO precursors for pentosidine and CML was also higher in this patient than in other HD patients. Further investigation disclosed a very low activity in RBC of glyoxalase I (1.5 +/- 0.4 mU/106 RBC), as compared to other HD patients (3.9 +/- 0.6 mU/106 RBC) or normal subjects (4.0 +/- 0.6 mU/106 RBC). The glyoxalase I protein level, assessed in RBC by immunoblot analysis with a specific antibody, was markedly lower than that observed in HD patients and normal subjects. The causes of this deficiency remain unknown. Nucleotide sequencing of the products of reverse transcription-polymerase chain reaction from the patient's mononuclear cells revealed no genetic mutation within the coding region of the glyoxalase I gene. Plasma d-lactate level was also in the lower range (0.18 +/- 0.03 mg/dL) of the values measured in the other HD patients (0.27 +/- 0.09 mg/dL) and normal subjects (0.35 +/- 0.12 mg/dL). The plasma levels of various compounds known to generate AGE precursors (glucose, lipids and ascorbic acid) were either normal or low. The surrogate markers for oxidative stress such as antioxidant enzymes (glutathione peroxidases and superoxide dismutase) and glutathione were all within the range observed in the other HD patients. The unusually high levels of AGEs in this patient implicate a deficient glyoxalase detoxification of RCO precursors. The present clinical observation implicates, to our knowledge for the first time, the glyoxalase detoxification system and, in particular, glyoxalase in the actual level of AGEs in a uremic patient.

Electrolyte changes in the blood plasma of broilers as influenced by cooling during summer

NASA Astrophysics Data System (ADS)

Sharma, M. L.; Gangwar, P. C.

1987-09-01

High temperature significantly (P < 0.01) decreased the Na+ and K+ concentrations in the blood plasma of both the sexes of broilers during 4 to 8 weeks of age. Relatively constant levels of these electrolytes were observed during this phase of growth and the sex of the bird had no significant effect on their levels. Greater broiler weights and higher levels of plasma electrolyte were achieved by the use of cooling systems (which were more effective in the hot dry part of the summer than in the hot humid part).

[Human bioaging acceleration as Chernobyl radiation consequence].

PubMed

Neĭfakh, E A; Liuman, G K

2013-01-01

To monitor human bioaging as a health integral index by blood plasma markers as a molar ratio for biochemically coupled monomers of intracellular lipofuscin, an intracellular polymeric aging pigment with free-radical crossed shifts, has been developed. Lipofuscin includes cell debris with catabolites of lipoperoxic cascade and lipid antioxidants. The latter were detected in the plasma samples of normal adults and children, as well as in Chernobyl clean-up workers (24-62 years old by 1990) with external total gamma-doses of 0.9-145 cSv for 4.2 years. Dynamics for bioaging markers as the molar ratio of blood levels of lipoperoxic catabolites to their antioxidants reflected normal physiologic peculiarities for the studied age periods: oxygen stress for newborns, adaptation during childhood, stability for the middle age and an increased lipoperoxidation (mainly for aging men) due to the age weakening of the antioxidant control. The ratio for the fractions of ma- lone dialdehyde (MDA), a lipoperoxic final catabolite, showed the increase of its binding by plasma proteins in proportions to calendar ages for the norm, as it is the case for lipofuscin; The graph of the age normal molar ratio of protein-bound MDA to the free one was pre-set for calibrations into the developed computer Program to calculate Relative Aging Velocities (Wrel) by bioage increments during the period of human exposure to radiation from the CAPS damage. Wrel were increasing logarithmically to the obtained doses if the total radiation exceeded 4 cSv and exceeded their normal velocities at 50 cSv 10 times or more. Slowing down of Wrel in relation to the calendar age increment was found if the sum doses were lower than 4 cSv. Levels of the studied plasma metabolites as their bioage Moles/Moles markers relative to their norms are dynamically stationary in contrast to the lipofuscin intracellular irreversible accumulation. Earlier it was shown that the decreased vitamin E and A levels with the increased lipoperoxic metabolite blood levels that indicate health consequences for the irradiated CAPS personell with related cytogenetic deviations, as well as for the adult population and children from radio-polluted regions, were restored to norms or corrected by adequate peroral therapy with bioantioxidants.

Low plasma progranulin levels in children with autism.

PubMed

Al-Ayadhi, Laila Y; Mostafa, Gehan A

2011-09-05

Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40) of autistic children.On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes.

PubMed

Alkholy, Usama M; Abdalmonem, Nermin; Zaki, Ahmed; Elkoumi, Mohamed A; Hashim, Mustafa I Abu; Basset, Maha A A; Salah, Hossam E

2018-02-07

The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012). Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Selective enrichment of n-3 fatty acids in human plasma lipid motifs following intake of marine fish

USDA-ARS?s Scientific Manuscript database

Plasma levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) are associated with a reduction in risk of cardiovascular disease and other chronic, age-related diseases like Alzheimer’s disease. In this work, we tested the hypothesis that n-3 LCPUFA fatty acids in human plasma are incorporated...

Assessment of nutritional status in noninstitutionalized elderly.

PubMed

Powers, J S; Folk, M C; Burger, C; Wilson, P; Stocking, B J; Collins, J

1989-08-01

Aging may modify both the availability of and needs for certain nutrients. Our study was done to assess the contribution of age alone to micronutrient levels in older volunteers (aged 60 or more). One hundred two healthy elderly white subjects, 63 women and 39 men, carefully screened by history or chart review, were studied in the fasting state. All were noninstitutionalized without serious chronic or acute illness; their diets were nutritionally adequate, containing more than two thirds of the recommended dietary allowance (RDA) for all nutrients, and no subject was taking more than twice the RDA of fat-soluble vitamins. These subjects had higher levels of plasma and red blood cell carnitine, and vitamins A, E, and C. They had lower levels of albumin, transferrin, and zinc than younger laboratory reference subjects. Retinol-binding protein, serum and red blood cell folate, and copper levels were not different. With increasing age, levels of transferrin and vitamins C and E fell; all other measured micronutrient levels were similar. Albumin, vitamin C, and copper values were higher among elderly women, and plasma and red blood cell carnitine values and zinc levels were higher in elderly men. There was great variability in the micronutrient levels despite similar nutrient intakes.

Effects of plasma transfusions on antithrombin levels after paediatric liver transplantation.

PubMed

Arni, D; Wildhaber, B E; McLin, V; Rimensberger, P C; Ansari, M; Fontana, P; Karam, O

2018-05-15

Thrombotic complications affect 3-10% of patients after liver transplantation (LT), leading to potentially life-threatening complications. In the days following LT, antithrombin (AT) is decreased longer than pro-coagulant factors, thus favouring a pro-thrombotic profile. Plasma transfusions are given empirically in some centres to correct AT levels following LT. We assessed the effect of plasma transfusion on AT levels after paediatric LT. Prospective single-centre observational study in 20 consecutive paediatric LT recipients over a 24-month period. Plasma was administered twice daily (10 ml/kg/dose) according to an existing protocol. AT levels were measured once daily, immediately prior to and one hour after the morning plasma transfusion. Sample size was calculated based on a non-inferiority hypothesis. The median age and weight were 11.6 years (IQR 2.8; 14.7) and 40 kg (IQR 12.75; 44.8), respectively. We collected 85-paired blood samples. The median AT level prior to plasma transfusion was 58%. The median difference in AT levels before and after plasma transfusion was 4.2% (P = 0.001). Changes in AT levels after plasma transfusion were not correlated with baseline AT levels (R = 0.19) or patient weight (R = 0.18). Plasma transfusions only marginally increase AT levels in children after LT. Therefore, prophylactic plasma transfusions probably do not seem to confer an advantage in the routine management of paediatric LT patients. Randomized controlled trials are needed to identify the optimal anticoagulation strategy in this specific population. © 2018 International Society of Blood Transfusion.

Circulating microRNA-144-5p is associated with depressive disorders.

PubMed

Wang, Xiao; Sundquist, Kristina; Hedelius, Anna; Palmér, Karolina; Memon, Ashfaque A; Sundquist, Jan

2015-01-01

Depressive/anxiety disorders are the most common types of mental illnesses in the world. The present study was the first to explore the association between plasma microRNAs (miRNAs) and depression/anxiety in primary care patients. In total, 169 patients (aged 20-64 years) from 16 primary health centers were enrolled in the present study. The healthy controls were consisted of 52 individuals. We first performed miRNA screening of plasma samples from 11 patients using a Serum/Plasma Focus microRNA Panel comprising 179 miRNA primer sets. Six miRNAs were differentially expressed and were then validated by quantitative real-time (qRT)-PCR in the entire study cohort. The mean plasma miR-144-5p level in the depression/anxiety patients increased significantly compared to baseline (p < 0.0001) after the 8-week follow-up. No significant associations were found between the differentially expressed miRNAs and a change in the Montgomery-Åsberg Depression Rating Scale (MADRS-S) score after the follow-up. In linear regression analysis, the plasma miR-144-5p expression level was inversely related to the depression score (MADRS-S) (β = -0.02, p < 0.01), after adjustment for sex and age, at baseline. In addition, plasma miR-144-5p levels at baseline in the depression/anxiety patients were significantly lower compared with the healthy controls (p < 0.001). Our findings show that plasma miR-144-5p levels are associated with depressive symptoms. Although confirmatory analyses are required, plasma miRNA-144-5p is a potential peripheral biomarker for pathologic processes related to depression.

High plasma neopterin levels in Chinese children with autism spectrum disorders.

PubMed

Zhao, Hong-xiang; Yin, Sha-sha; Fan, Jin-gang

2015-04-01

Neopterin, a pteridine mainly synthesized by activated macrophages, is a marker of inflammation, immune system activation and an active participant in Autism spectrum disorders (ASD). The aim of this study was to assess the clinical significance of plasma neopterin levels in ASD. Eighty patients diagnosed with ASD and 80 sex and age matched typically developing children were assessed for plasma levels of neopterin at admission. Plasma neopterin levels were measured using a human ELISA kit and severity of ASD were evaluated with the Childhood Autism Rating Scale (CARS) score. We found that the mean plasma neopterin level was significantly (P<0.0001) higher in children with ASD as compared to controls. Plasma neopterin increased with increasing severity of ASD as defined by the CARS score. Based on the ROC curve, the optimal cutoff value of plasma neopterin level as an indicator for auxiliary diagnosis of ASD was projected to be 8.5nmol/L, which yielded a sensitivity of 84.2% and a specificity of 80.1%, with the area under the curve at 0.876 (95% CI, 0.825-0.928). Elevated neopterin (≥8.5nmol/L) was an independent diagnosis indicator of ASD with an adjusted OR of 12.11 (95% CI: 5.48-28.11; P<0.0001). These results indicated that autistic children had higher plasma levels of neopterin, and elevated plasma neopterin levels may be associated with severity of ASD among Chinese children. Copyright © 2015 Elsevier Ltd. All rights reserved.

Skin-autofluorescence, a measure of tissue advanced glycation end-products (AGEs), is related to diastolic function in dialysis patients.

PubMed

Hartog, Jasper W L; Hummel, Yoran M; Voors, Adriaan A; Schalkwijk, Casper G; Miyata, Toshio; Huisman, Roel M; Smit, Andries J; Van Veldhuisen, Dirk J

2008-09-01

Diastolic dysfunction is a frequent cause of heart failure, particularly in dialysis patients. Advanced glycation end-products (AGEs) are increased in dialysis patients and are suggested to play a role in the development of diastolic dysfunction. The aim of our study was to assess whether AGE accumulation in dialysis patients is related to the presence of diastolic dysfunction. Data were analyzed from 43 dialysis patients, age 58 +/- 15 years, of whom 65% were male. Diastolic function was assessed using tissue velocity imaging (TVI) on echocardiography. Tissue AGE accumulation was measured using a validated skin-autofluorescence (skin-AF) reader. Plasma N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) were measured by stable-isotope-dilution tandem mass spectrometry. Plasma pentosidine was measured by high-performance liquid chromatography. Skin-AF correlated with mean E' (r = -0.51, P < .001), E/A ratio (r = -0.39, P = .014), and E/E' (r = 0.38, P = .019). Plasma AGEs were not significantly associated with diastolic function. Multivariable linear regression analysis revealed that 54% of the variance of average E' was explained by age (P = .007), dialysis type (P = 0.016), and skin-AF (P = .013). Tissue AGEs measured as skin-AF, but not plasma AGE levels, were related to diastolic function in dialysis patients. Although this may support the concept that tissue AGEs explain part of the increased prevalence of diastolic dysfunction in these patients, the ambiguous relation between plasma and tissue AGEs needs further exploring.

Effects of methamphetamine exposure on anxiety-like behavior in the open field test, corticosterone, and hippocampal tyrosine hydroxylase in adolescent and adult mice.

PubMed

Struntz, Katelyn H; Siegel, Jessica A

2018-08-01

Methamphetamine (MA) is a psychomotor stimulant drug that can alter behavior, the stress response system, and the dopaminergic system. The effects of MA can be modulated by age, however relatively little research has examined the acute effects of MA in adolescents and how the effects compare to those found in adults. The hippocampal dopamine system is altered by MA exposure and can modulate anxiety-like behavior, but the effects of MA on the hippocampal dopamine system have not been well studied, especially in adolescent animals. In order to assess potential age differences in the effects of MA exposure, this research examined the effects of acute MA exposure on locomotor and anxiety-like behavior in the open field test, plasma corticosterone levels, and hippocampal total tyrosine hydroxylase and phosphorylated tyrosine hydroxylase levels in adolescent and adult male C57BL/6 J mice. Tyrosine hydroxylase is the rate limiting enzyme in the synthesis of dopamine and was used as a marker of the hippocampal dopaminergic system. Mice were exposed to saline or 4 mg/kg MA and locomotor and anxiety-like behavior were measured in the open field test. Serum and brains were collected immediately after testing and plasma corticosterone and hippocampal total tyrosine hydroxylase and phosphorylated tyrosine hydroxylase levels measured. MA-exposed mice showed increased locomotor activity and anxiety-like behavior in the open field test compared with saline controls, regardless of age. There was no effect of MA on plasma corticosterone levels or hippocampal total tyrosine hydroxylase or phosphorylated tyrosine hydroxylase levels in either adolescent or adult mice. These data suggest that acute MA exposure during adolescence and adulthood increases locomotor activity and anxiety-like behavior but does not alter plasma corticosterone levels or hippocampal total tyrosine hydroxylase or phosphorylated tyrosine hydroxylase levels, and that these effects are not modulated by age. Copyright © 2018 Elsevier B.V. All rights reserved.

Increased plasma/serum levels of prolactin in multiple sclerosis: a meta-analysis.

PubMed

Wei, Wei; Liu, Lei; Cheng, Zhong-Le; Hu, Bo

2017-08-01

Prolactin (PRL) is a polypeptide hormone that is known to stimulate humoral and cell mediated immune responses. PRL levels have been investigated in several autoimmune diseases including multiple sclerosis (MS); however, these have yielded different and inconsistent results. This study aims to perform a more precise evaluation on the plasma/serum PRL levels in MS patients, and to explore the available influential factors. Research related to plasma/serum PRL levels in MS patients and healthy controls were gathered using PubMed, EMBASE and The Cochrane Library database (until Mar 31 2016). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I 2 , and publication bias was evaluated using a funnel plot and Egger's linear regression test. 516 articles were obtained after searching databases, and 8 studies with 426 MS patients and 296 controls were finally included. Meta-analysis revealed that, compared with the control group, the MS group had significantly higher plasma/serum PRL levels, with the SMD of 0.55 and 95%CI (0.39, 0.72). Subgroup analyses showed that region, age and disease duration were associated with PRL level in MS patients. In summary, our meta-analysis revealed a significantly higher PRL level in MS patients than healthy controls, and it is influenced by region, age and disease duration.

Identification of vinculin as a potential plasma marker for age-related macular degeneration.

PubMed

Kim, Hye-Jung; Woo, Se Joon; Suh, Eui Jin; Ahn, Jeeyun; Park, Ji Hyun; Hong, Hye Kyoung; Lee, Ji Eun; Ahn, Seong Joon; Hwang, Duck Jin; Kim, Ki Woong; Park, Kyu Hyung; Lee, Cheolju

2014-10-08

To identify plasma protein biomarkers for age-related macular degeneration (AMD) using a large-scale quantitative proteomic discovery procedure. Plasma proteomes from 20 exudative AMD patients and 20 healthy control patients were comparatively profiled by four-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins existing at statistically different levels were validated by enzyme-linked immunosorbent assay (ELISA) and Western blotting in 233 case-controlled samples. Newly discovered plasma biomarkers were further confirmed using in vivo and in vitro experiments. Out of 320 proteins identified, vinculin, protein S100A9, triosephosphate isomerase, protein S100A8, protein Z-dependent protease inhibitor, C-X-C motif chemokine 7, and tenascin X showed significantly differential expression in AMD patient plasma compared to control plasma. Among these, the area under the curve (AUC) for vinculin was 0.871 for discriminating between exudative AMD and controls (n = 201) and 0.879 for discriminating between AMD and controls (n = 233). A proteogenomic combination model using vinculin and two known risk genotypes in ARMS2 and CFH genes additionally provided excellent discrimination of AMD from controls (AUC = 0.916). The plasma level of vinculin was not associated with any confounding clinical variables, such as age, smoking, and other comorbidities. Additionally, vinculin was strongly expressed in retinal pigment epithelial cells of human eyes, and its expression was elevated when exposed to oxidative stress in vitro. Vinculin was identified as a potential plasma biomarker for AMD. The early detection of AMD using novel plasma biomarkers with genetic modeling may enable timely treatment and vision preservation in the elderly. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood.

PubMed

Ebner, Natalie C; Lin, Tian; Muradoglu, Melis; Weir, Devon H; Plasencia, Gabriela M; Lillard, Travis S; Pournajafi-Nazarloo, Hossein; Cohen, Ronald A; Sue Carter, C; Connelly, Jessica J

2018-02-02

The neuropeptide oxytocin (OT) has been implicated in a wide range of affiliative processes. OT exerts its functions via OT receptors, which are encoded by the oxytocin receptor gene (OXTR). Epigenetic modification of OXTR through the process of DNA methylation has been associated with individual differences in behavioral phenotypes. Specifically, lower levels of OXTR methylation have been linked to better social and affective functioning. However, research on epigenetic mechanisms of OXTR is scarce in non-clinical populations, and even less is known about epigenetic variability across adulthood. The present study assessed methylation levels at OXTR CpG site -934 and plasma OT levels in 22 young (20-31 years, M = 23.6) and 34 older (63-80 years, M = 71.4) participants. Lower levels of OXTR methylation and higher plasma OT levels were associated with less self-reported attachment anxiety in young but not older participants, with largely independent contributions of OXTR methylation and plasma OT levels. In contrast, in the overall sample, lower levels of OXTR methylation were associated with higher self-reported attachment avoidance. Age analysis suggested that these results were largely driven by young adults. Plasma OT levels were unrelated to attachment avoidance. Taken together, these findings support the emerging notion in the literature that epigenetic properties of OXTR, in addition to endogenous OT levels, are related to adult attachment. Further, the age effects observed in the associations between OXTR methylation, plasma OT, and adult attachment emphasize the importance of adopting a developmental perspective when studying properties of the OT system and their relation to affiliative processes. Findings contribute to growing evidence suggesting that epigenetic modification of genes regulating OT pathways and endogenous OT levels are associated with the way people form and maintain intimate social relationships. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of Almond- and Olive Oil-Based Docosahexaenoic- and Vitamin E-Enriched Beverage Dietary Supplementation on Inflammation Associated to Exercise and Age

PubMed Central

Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Riera, Joan; Drobnic, Franchek; Tur, Josep Antoni; Pons, Antoni

2016-01-01

n-3-polyunsaturated fatty acids and polyphenols are potential key factors for the treatment and prevention of chronic inflammation associated to ageing and non-communicable diseases. The aim was to analyse effects of an almond and olive oil beverage enriched with α-tocopherol and docosahexaenoic, exercise and age on inflammatory plasma markers, and immune gene expression in peripheral blood mononuclear cells (PBMCs). Five young and five senior athletes who were supplemented for five weeks with a functional beverage performed a stress test under controlled conditions before and after beverage supplementation. Blood samples were taken immediately before and 1 h after each test. Plasma, erythrocytes and PBMCs were isolated. Beverage supplementation increased plasmatic Tumour Necrosis Factor α (TNFα) levels depending on age and exercise. Exercise increased plasma non esterified fatty acids (NEFAs), soluble Intercellular adhesion molecule 3 (sICAM3) and soluble L-selectin (sL-Selectin), and this increase was attenuated by the supplementation. Exercise increased PGE2 plasma levels in supplemented young and in senior placebo athletes. Exercise increased NFkβ-activated levels in PBMCs, which are primed to a pro-inflammatory response increasing pro-inflammatory genes expression after the exercise mainly in the young group after the supplementation. The functional beverage supplementation to young athletes enhances a pro-inflammatory circulating environment in response to the exercise that was less evident in the senior group. PMID:27735833

Effects of Almond- and Olive Oil-Based Docosahexaenoic- and Vitamin E-Enriched Beverage Dietary Supplementation on Inflammation Associated to Exercise and Age.

PubMed

Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Riera, Joan; Drobnic, Franchek; Tur, Josep Antoni; Pons, Antoni

2016-10-09

n -3-polyunsaturated fatty acids and polyphenols are potential key factors for the treatment and prevention of chronic inflammation associated to ageing and non-communicable diseases. The aim was to analyse effects of an almond and olive oil beverage enriched with α-tocopherol and docosahexaenoic, exercise and age on inflammatory plasma markers, and immune gene expression in peripheral blood mononuclear cells (PBMCs). Five young and five senior athletes who were supplemented for five weeks with a functional beverage performed a stress test under controlled conditions before and after beverage supplementation. Blood samples were taken immediately before and 1 h after each test. Plasma, erythrocytes and PBMCs were isolated. Beverage supplementation increased plasmatic Tumour Necrosis Factor α (TNFα) levels depending on age and exercise. Exercise increased plasma non esterified fatty acids (NEFAs), soluble Intercellular adhesion molecule 3 (sICAM3) and soluble L-selectin (sL-Selectin), and this increase was attenuated by the supplementation. Exercise increased PGE2 plasma levels in supplemented young and in senior placebo athletes. Exercise increased NFkβ-activated levels in PBMCs, which are primed to a pro-inflammatory response increasing pro-inflammatory genes expression after the exercise mainly in the young group after the supplementation. The functional beverage supplementation to young athletes enhances a pro-inflammatory circulating environment in response to the exercise that was less evident in the senior group.

Prenatal exposure to selenium may protect against wheezing in children by the age of 3

PubMed Central

Chastang, Julie; Ibanez, Gladys; Annesi‐Maesano, Isabella

2016-01-01

Abstract Introduction It has been suggested that human in utero exposure to heavy metals such as selenium can reduce the prevalence of childhood asthma and allergic diseases. However, data on this topic are scarce. The objective of the present study was to assess the putative associations between maternal selenium level during pregnancy and the risk of asthma, wheezing, allergic rhinitis, and atopic dermatitis in children from the EDEN birth cohort by the age of 1 and 3 years. Methods Plasma selenium concentrations were measured in maternal blood during mid‐pregnancy (24–28 weeks of gestation) in 861 mothers. Cohort children were followed up from birth to 3 years using health questionnaires filled out by the parents for asthma, wheezing, allergic rhinitis, and atopic dermatitis. Maternal plasma selenium was related to the childhood outcomes by the age of 1 and 3 years. Results Our results showed a significant negative association between a high maternal plasma selenium level during pregnancy and the risk of wheezing in the child by the age of 1 and 3 years. However, maternal plasma selenium during pregnancy was not associated with the prevalence of asthma, allergic rhinitis or atopic dermatitis. Conclusions The results of this study suggest that the level of fetal exposure to maternal selenium could have an influence on the risk of wheezing in infancy and potentially on the risk of developing asthma later in life. PMID:28250923

Dietary-induced hyperthyroidism marginally affects neonatal testicular development.

PubMed

Rijntjes, Eddy; Wientjes, Anna T; Swarts, Hans J M; de Rooij, Dirk G; Teerds, Katja J

2008-01-01

The objective of this study was to determine whether dietary-induced mild fetal/neonatal hyperthyroidism influenced the initiation of spermatogenesis and the development of the adult-type Leydig cell population. Previously, the effects of neonatally induced hyperthyroidism have been investigated in rats using rather high doses (5 to 10 microg/100 g body weight) of tri-iodothyronine, which not only influenced testicular development, but also negatively affected the general body condition of the animals. To induce hyperthyroidism the diet of the dams was supplemented with 15 mug thyroxine (T(4))/100 g body weight 2 weeks prior to mating and the dams and their offspring were kept on this diet until sacrifice. Pups were killed between days 7 and 64 after birth. At the age of 12 days plasma thyroid-stimulating hormone (TSH) levels tended to be lower in hyperthyroid pups, and from the age of 15 days onwards plasma TSH levels were significantly lower in hyperthyroid animals. Concomitantly, plasma T(4) levels were significantly elevated. From the age of 12 days onwards, plasma follicle-stimulating hormone levels were lower in hyperthyroid animals compared with age-matched control groups. Sertoli cell differentiation did not seem to be influenced by the mild hyperthyroid condition, as no difference in tubule lumen formation was observed between euthyroid and hyperthyroid animals. Nevertheless, a small effect on the progression of spermatogenesis was observed 15 days after birth, as the most advanced type of germ cells in the control testis were pachytene spermatocytes, whereas in the hyperthyroid testis these were leptotene and zygotene spermatocytes. Leydig cell proliferation was decreased in the hyperthyroid pups at the age of 15 days and slightly elevated at later ages, suggesting a possible slower onset of the proliferative activity of these cells than in the euthyroid control animals. Taken together, the present results suggest that even mild dietary-induced hyperthyroidism transiently affects the development of the adult-type Leydig cell population as well as the initial progression of spermatogenesis.

The potential role of advanced glycation end products (AGEs) and soluble receptors for AGEs (sRAGE) in the pathogenesis of adult-onset still's disease.

PubMed

Chen, Der-Yuan; Chen, Yi-Ming; Lin, Chi-Chen; Hsieh, Chia-Wei; Wu, Yen-Ching; Hung, Wei-Ting; Chen, Hsin-Hua; Lan, Joung-Liang

2015-05-09

Accumulating evidence has demonstrated a pathogenic role of advanced glycation end products (AGEs) and receptors for AGEs (RAGE) in inflammation. Soluble RAGE (sRAGE), with the same ligands-binding capacity as full-length RAGE, acts as a "decoy" receptor. However, there has been scanty data regarding AGEs and sRAGE in adult-onset Still's disease (AOSD). This study aimed to investigate AGEs and sRAGE levels in AOSD patients and examine their association with clinical characteristics. Using ELISA, plasma levels of AGEs and sRAGE were determined in 52 AOSD patients, 36 systemic lupus erythematosus(SLE) patients and 16 healthy controls(HC). Their associations with activity parameters and disease courses were evaluated. Significantly higher median levels of AGEs were observed in active AOSD patients (16.75 pg/ml) and active SLE patients (14.80 pg/ml) than those in HC (9.80 pg/ml, both p < 0.001). AGEs levels were positively correlated with activity scores (r = 0.836, p < 0.001), ferritin levels (r = 0.372, p < 0.05) and CRP levels (r = 0.396, p < 0.005) in AOSD patients. Conversely, significantly lower median levels of sRAGE were observed in active AOSD patients (632.2 pg/ml) and active SLE patients (771.6 pg/ml) compared with HC (1051.7 pg/ml, both p < 0.001). Plasma sRAGE levels were negatively correlated with AOSD activity scores (r = -0.320, p < 0.05). In comparison to AOSD patients with monocyclic pattern, significantly higher AGEs levels were observed in those with polycyclic or chronic articular pattern. With treatment, AGEs levels declined while sRAGE levels increased in parallel with the decrease in disease activity. The elevation of AGEs levels with concomitant decreased sRAGE levels in active AOSD patients, suggests their pathogenic role in AOSD.

Association of Post-Saline Load Plasma Aldosterone Levels With Left Ventricular Hypertrophy in Primary Hypertension.

PubMed

Catena, Cristiana; Verheyen, Nicolas D; Url-Michitsch, Marion; Kraigher-Krainer, Elisabeth; Colussi, GianLuca; Pilz, Stefan; Tomaschitz, Andreas; Pieske, Burkert; Sechi, Leonardo A

2016-03-01

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity in hypertension. Current evidence suggests a contribution to LVH of plasma aldosterone levels that are inappropriately elevated for the salt status. The aim of this study was to investigate whether inappropriate modulation of aldosterone production by a saline load is associated with left ventricular (LV) mass in hypertensive patients. In 90 hypertensive patients free of clinically relevant cardiovascular complications in whom secondary forms of hypertension were ruled out, we performed a standard intravenous saline load (0.9% NaCl, 2 l in 4 hours) with measurement of plasma aldosterone and active renin at baseline and end of infusion. Bi-dimensional echocardiography was performed for the assessment of cardiac morphology and function. LVH was present in 19% of patients who had significantly worse renal function and higher body mass, blood pressure, and plasma aldosterone levels measured both at baseline and after the saline load than patients without LVH. LV mass was directly related to age, body mass, systolic blood pressure, duration of hypertension, baseline, and post-saline load plasma aldosterone levels and inversely to glomerular filtration. Multivariate regression analysis showed independent correlation of LV mass with body mass, systolic blood pressure, and plasma aldosterone levels measured after intravenous saline load, but not at baseline. In patients with hypertension, aldosterone levels measured after intravenous saline load are related to LV mass independent of age, body mass, and blood pressure, suggesting that limited ability of salt to modulate aldosterone production could contribute to LVH. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Plasma and platelet-derived vascular endothelial growth factor and angiopoietin-1 in hypertension: effects of antihypertensive therapy.

PubMed

Nadar, S K; Blann, A D; Lip, G Y H

2004-10-01

Platelets carry angiogenic growth factors vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1). Although platelet-derived growth factors are important in the pathogenesis and metastasis of malignancy, their role in the pathogenesis of complications and the response to treatment in hypertension is less known. To test the hypotheses that there are differences in VEGF and Ang-1 in the plasma and within platelets from patients with hypertension, and that levels change with successful treatment. We recruited 42 previously untreated patients with hypertension (25 male; mean age 53 years) and 30 age- and sex-matched controls. Plasma VEGF, Ang-1 and soluble P-selectin (sPsel, an index of platelet activation), and total platelet [platelet VEGF (pVEGF) and platelet Ang-1 (pAng-1)] were measured by ELISA. The patients were then treated for 6 months with amlodipine-based antihypertensive therapy, achieving a mean blood pressure below 140/80 mmHg. Patients with hypertension had significantly higher levels of plasma sPsel (P =0.01), VEGF (P < 0.001) and Ang-1 (P = 0.01), as well as pVEGF (P < 0.001) and pAng-1 (P =0.02). The levels of plasma and platelet angiogenic growth factors were significantly reduced after antihypertensive treatment (VEGF, P = 0.01; pVEGF, P < 0.001; Ang-1, P < 0.001; pAng-1, P = 0.04). There were no correlations with blood pressure or the levels of sPsel. Levels of plasma and intra-platelet VEGF and Ang-1 are increased in hypertension and are decreased with treatment. Platelet levels of VEGF and Ang-1 may be related to platelet activation but may also involve other mechanisms (for example, the general vascular and haemodynamic changes) that are seen in hypertension.

Alterations in nonenzymatic biochemistry in uremia: origin and significance of "carbonyl stress" in long-term uremic complications.

PubMed

Miyata, T; van Ypersele de Strihou, C; Kurokawa, K; Baynes, J W

1999-02-01

Advanced glycation end products (AGEs), formed during Maillard or browning reactions by nonenzymatic glycation and oxidation (glycoxidation) of proteins, have been implicated in the pathogenesis of several diseases, including diabetes and uremia. AGEs, such as pentosidine and carboxymethyllysine, are markedly elevated in both plasma proteins and skin collagen of uremic patients, irrespective of the presence of diabetes. The increased chemical modification of proteins is not limited to AGEs, because increased levels of advanced lipoxidation end products (ALEs), such as malondialdehydelysine, are also detected in plasma proteins in uremia. The accumulation of AGEs and ALEs in uremic plasma proteins is not correlated with increased blood glucose or triglycerides, nor is it determined by a decreased removal of chemically modified proteins by glomerular filtration. It more likely results from increased plasma concentrations of small, reactive carbonyl precursors of AGEs and ALEs, such as glyoxal, methylglyoxal, 3-deoxyglucosone, dehydroascorbate, and malondialdehyde. Thus, uremia may be described as a state of carbonyl overload or "carbonyl stress" resulting from either increased oxidation of carbohydrates and lipids (oxidative stress) or inadequate detoxification or inactivation of reactive carbonyl compounds derived from both carbohydrates and lipids by oxidative and nonoxidative chemistry. Carbonyl stress in uremia may contribute to the long-term complications associated with chronic renal failure and dialysis, such as dialysis-related amyloidosis and accelerated atherosclerosis. The increased levels of AGEs and ALEs in uremic blood and tissue proteins suggest a broad derangement in the nonenzymatic biochemistry of both carbohydrates and lipids.

Association of faecal elastase 1 with non-fasting triglycerides in type 2 diabetes.

PubMed

Rathmann, Wolfgang; Haastert, Burkhard; Oscarsson, Jan; Berglind, Niklas; Lindkvist, Björn; Wareham, Nicholas J

2016-01-01

Intestinal absorption of esterified fatty acids depends on exocrine pancreatic function and influences plasma triglycerides levels. The aim was to investigate the association of reduced exocrine pancreatic function (low fecal elastase-1; FE1) with plasma triglycerides in type 2 diabetes and controls without diabetes. FE1 (μg/g stool) and non-fasting plasma triglyceride measurements were undertaken in 544 type 2 diabetes patients (age: 63 ± 8 years) randomly selected from diabetes registers in Cambridgeshire (UK), and 544 matched controls (age, sex, practice) without diabetes. Linear regression models were fitted using FE1 as dependent and log-triglycerides as independent variable adjusting for sex, age, body mass index, alcohol consumption, serum lipase, HbA1c, and smoking. FE1 concentrations were lower (mean ± SD: 337 ± 204 vs. 437 ± 216 μg/g, p < 0.05) and plasma triglycerides were higher (geometric mean */: standard deviation factor: 2.2*/:1.9 vs. 1.6*/:1.8 mmol/l, p < 0.05) in type 2 diabetes compared to controls, respectively. Within the category of type 2 diabetes and controls separately, a 10% increase in plasma triglycerides was associated with 4.5 μg/g higher FE1 concentrations (p < 0.01) after adjusting for confounders. In contrast, in diabetes patients and controls with pathological FE1 (<100 μg/g), low FE1 levels were associated with high plasma triglycerides (significant only in controls). Non-fasting triglycerides were positively related to FE1 in both type 2 diabetes and controls suggesting that impairment of exocrine pancreas function is influencing plasma triglycerides. Marked loss of exocrine pancreatic function had the opposite effect, resulting in higher levels of plasma triglycerides. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Levels of plasma selenium and urinary total arsenic interact to affect the risk for prostate cancer.

PubMed

Hsueh, Yu-Mei; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Pu, Yeong-Shiau; Lin, Ying-Chin; Tsai, Cheng-Shiuan; Huang, Chao-Yuan

2017-09-01

This study investigated whether plasma selenium levels modified the risk for prostate cancer (PC) related to arsenic exposure. We conducted a case-control study that included 318 PC patients and 318 age-matched, healthy control subjects. Urinary arsenic profiles were examined using HPLC-HG-AAS and plasma selenium levels were measured by ICP-MS. We found that plasma selenium levels displayed a significant dose-dependent inverse association with PC. The odds ratio (OR) and 95% confidence interval (CI) for PC was 0.07 (0.04-0.13) among participants with a plasma selenium level >28.06 μg/dL vs. ≤19.13 μg/dL. A multivariate analysis showed that participants with a urinary total arsenic concentration >29.28 μg/L had a significantly higher OR (1.75, 1.06-2.89) for PC than participants with ≤29.89 μg/L. The combined presence of a low plasma selenium level and a high urinary total arsenic concentration exponentially increased the OR for PC, and additively interacted with PSA at levels ≥20 ng/mL. This is the first epidemiological study to examine the combined effects of plasma selenium and urinary total arsenic levels on the OR for PC. Our data suggest a low plasma selenium level coupled with a high urinary total arsenic concentration creates a significant risk for aggressive PC. Copyright © 2017 Elsevier Ltd. All rights reserved.

The relationship of endogenous plasma concentrations of β-Hydroxy β-Methyl Butyrate (HMB) to age and total appendicular lean mass in humans.

PubMed

Kuriyan, Rebecca; Lokesh, Deepa P; Selvam, Sumithra; Jayakumar, J; Philip, Mamatha G; Shreeram, Sathyavageeswaran; Kurpad, Anura V

2016-08-01

The maintenance of muscle mass and muscle strength is important for reducing the risk of chronic diseases. The age- related loss of muscle mass and strength is associated with adverse outcomes of physical disability, frailty and death. β-Hydroxy β-Methyl Butyrate (HMB), a metabolite of leucine, has beneficial effects on muscle mass and strength under various catabolic conditions. The objectives of the present study were to determine if age- related differences existed in endogenous plasma HMB levels, and to assess if HMB levels correlated to total appendicular lean mass and forearm grip strength. Anthropometry, dietary and physical activity assessment, and the estimation of fasting plasma HMB concentrations and handgrip strength were performed on the 305 subjects (children, young adults and older adults). Lean mass, which serves as a surrogate for muscle mass was measured using dual energy X-ray absorptiometry (DEXA). Mean plasma HMB concentrations were significantly lower with increasing age groups, with children having highest mean HMB concentration (p<0.01) followed by young adults and older adults. Female subjects (across all ages) had significantly lower plasma HMB concentrations. A significant positive correlation between HMB concentrations and appendicular lean mass normalized for body weight (%), appendicular lean mass (r=0.37; p<0.001) was observed in the young adults and older adults group. Handgrip strength was positively associated with plasma HMB concentrations in young adults (r=0.58; p<0.01) and the older adults group (r=0.28; p<0.01). The findings of the present study suggest that there is an age- related decline in endogenous HMB concentrations in humans and the HMB concentrations were positively correlated with appendicular lean mass and hand grip strength in young adults and older adults group. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The 148 M allele of the PNPLA3 is associated with plasma irisin levels in a population sample of Caucasian children: The PANIC Study.

PubMed

Viitasalo, Anna; Atalay, Mustafa; Pihlajamäki, Jussi; Jääskeläinen, Jarmo; Korkmaz, Ayhan; Kaminska, Dorota; Lindi, Virpi; Lakka, Timo A

2015-07-01

There are no previous data on the association of PNPLA3 I148M polymorphism (rs738409) with circulating adipokines and myokines in children. Subjects were a population sample of 481 Caucasian children aged 6-8 years. We assessed circulating levels of irisin together with IL-6, TNF-α, leptin, high molecular weight (HMW)-adiponectin, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) while the subjects were stratified according to PNPLA3 I148M variants. The PNPLA3 rs738409 polymorphism had a linear relationship with plasma levels of irisin after adjustment for age, sex and body height (p=0.007) but it was not associated with circulating levels of interleukin- 6 (IL-6), tumor-necrosis factor α (TNF-α), leptin or HMW-adiponectin. PNPLA3 148M allele carriers had higher plasma levels of irisin than the non-carriers. This might be due to compensatory mechanism to limit early steatotic and inflammatory changes in the liver. Copyright © 2015 Elsevier Inc. All rights reserved.

Plasma homovanillic acid in schizophrenics: supportive evidence for the two-subtype hypothesis.

PubMed

Chen, T Y; Lee, C F; Lung, F W; Lee, T C; Lin, W L; Hu, W H; Yeh, E K; Chang, W H

1989-06-01

Plasma levels of homovanillic acid (pHVA), a major metabolite of dopamine (DA), were measured in a group of 51 schizophrenic inpatients before and during 6 weeks of neuroleptic treatment. Steady-state plasma drug concentrations were monitored in parallel with pHVA. Good responders (n = 22) had higher pretreatment pHVA levels as compared to poor responders (n = 22). Differential pHVA changes during neuroleptic treatment were also found between each group. The two groups did not differ significantly in terms of age, duration of illness, severity of presenting symptoms, neuroleptic, dose, or plasma drug concentration. Two hypothetical subtypes in the group of schizophrenics were proposed.

Effects of dietary sesame seeds on plasma tocopherol levels.

PubMed

Cooney, R V; Custer, L J; Okinaka, L; Franke, A A

2001-01-01

The tocopherols, the major vitamers of vitamin E, are believed to play a role in the prevention of human aging-related diseases such as cancer and heart disease, yet little is known concerning determinants of their plasma concentrations. Evidence from animal studies suggests that the dietary source of gamma-tocopherol can significantly affect plasma levels of this tocopherol as well as its functional vitamin E activity. To determine whether plasma levels of tocopherols in humans are similarly altered, a study was undertaken in which subjects (n = 9) were fed muffins containing equivalent amounts of gamma-tocopherol from sesame seeds, walnuts, or soy oil. We observed that consumption of as little as 5 mg of gamma-tocopherol per day over a three-day period from sesame seeds, but not from walnuts or soy oil, significantly elevated serum gamma-tocopherol levels (19.1% increase, p = 0.03) and depressed plasma beta-tocopherol (34% decrease, p = 0.01). No significant changes in baseline or postintervention plasma levels of cholesterol, triglycerides, or carotenoids were seen for any of the intervention groups. All subjects consuming sesame seed-containing muffins had detectable levels of the sesame lignan sesamolin in their plasma. Consumption of moderate amounts of sesame seeds appears to significantly increase plasma gamma-tocopherol and alter plasma tocopherol ratios in humans and is consistent with the effects of dietary sesame seeds observed in rats leading to elevated plasma gamma-tocopherol and enhanced vitamin E bioactivity.

Plasma sRAGE and N-(carboxymethyl) lysine in patients with CHF and/or COPD.

PubMed

Boschetto, Piera; Campo, Ilaria; Stendardo, Mariarita; Casimirri, Enrico; Tinelli, Carmine; Gorrini, Marina; Ceconi, Claudio; Fucili, Alessandro; Potena, Alfredo; Papi, Alberto; Ballerin, Licia; Fabbri, Leonardo M; Luisetti, Maurizio

2013-06-01

Knowledge of the role of the receptor for advanced glycation end products (RAGE), particularly its soluble form (sRAGE), and of its advanced glycation end product (AGE) ligand, N-(carboxymethyl)lysine adducts (CML), is limited in chronic heart failure (CHF) and in chronic obstructive pulmonary disease (COPD). We evaluated whether the AGE/RAGE system is activated in stable CHF and COPD, and whether plasma sRAGE and CML levels are affected by clinical and functional parameters. We measured plasma levels of sRAGE and CML using a sandwich enzyme-linked immunosorbent assay (ELISA) in 143 subjects, aged ≥ 65 years, divided into five groups: 58 with CHF, 23 with COPD, 27 with CHF+COPD and 35 controls (17 healthy smokers and 18 healthy nonsmokers). Individuals with diabetes were excluded from the study. Plasma levels of sRAGE and CML were higher in CHF patients than in controls [sRAGE: 0.48 (0.37-0.83) vs. 0.42 (0.29-0.52) ng/mL, P = 0.01; CML: 1.95 (1.58-2.38) vs. 1.68 (1.43-2.00) ng/mL, P = 0.01]. By contrast, sRAGE and CML were not different between both COPD and CHF+COPD patients and controls (P > 0.05). N-terminal pro-brain natriuretic peptide (Nt-pro BNP) correlated with sRAGE, but not with CML, in the patient groups: CHF (r = 0.43, P < 0.001), COPD (r = 0.77, P < 0.0001) and CHF/COPD (r = 0.43, P = 0.003). Plasma levels of sRAGE and CML are increased in CHF, but not in COPD patients. The robust association between NT-pro BNP, a diagnostic and prognostic marker in CHF, and sRAGE concentrations might suggest a possible BNP pathway of amplification of inflammation via the AGE/RAGE system. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

Relationship of salivary and plasma cortisol levels in preterm infants: results of a prospective observational study and systematic review of the literature.

PubMed

Maas, Christoph; Ringwald, Christine; Weber, Karin; Engel, Corinna; Poets, Christian F; Binder, Gerhard; Bassler, Dirk

2014-01-01

(1) To investigate the relationship of salivary and plasma cortisol levels in preterm infants with a focus on the usability of salivary cortisol in diagnostic work-up of infants at risk of adrenal insufficiency. (2) To perform a systematic review addressing this question. Clinical study: We conducted a prospective observational single-center study in preterm infants. We analyzed plasma and saliva cortisol concentrations by enzyme immunoassay. Correlation analysis was used to determine the relation between salivary and plasma cortisol levels and the agreement of the measurement methods was analyzed according to Bland-Altman. Systematic review: A systematic literature search (PubMed and Embase) on the relationship of salivary and plasma cortisol levels in neonates was performed in November 2012. Clinical study: We enrolled 58 preterm infants (median (interquartile range) gestational age at birth was 31.4 (28.1-32.7) weeks, birth weight 1,340 (974-1,745) g, respectively). Correlation analyses revealed a relationship of plasma cortisol and salivary cortisol levels. Rank correlation coefficient was 0.6. Estimating plasma cortisol levels based on measured salivary cortisol levels showed poor agreement of the two methods for determining plasma cortisol levels (direct and via salivary cortisol). Sensitivity and specificity of salivary cortisol for the detection of adrenal insufficiency were 0.66 and 0.62, respectively. Systematic review: Six studies in preterm infants and term neonates depicting the correlation of salivary and plasma cortisol were identified with a range of saliva-plasma correlation coefficients from 0.44 to 0.83. Substitution of plasma cortisol by salivary cortisol determination cannot be recommended in preterm infants because of unsatisfactory agreement between methods.

Racial differences in sensitivity of blood pressure to aldosterone.

PubMed

Tu, Wanzhu; Eckert, George J; Hannon, Tamara S; Liu, Hai; Pratt, Linda M; Wagner, Mary Anne; Dimeglio, Linda A; Jung, Jeesun; Pratt, J Howard

2014-06-01

Blacks in comparison with whites are at risk for a more serious form of hypertension with high rates of complications. Greater sodium retention is thought to underlie the blood pressure (BP)-determining physiology of blacks, but specific mechanisms have not been identified. In a prospective observational study of BP, 226 black children and 314 white children (mean age, 10.6 years) were enrolled initially. Assessments were repeated in 85 blacks and 136 whites after reaching adulthood (mean age, 31 years). The relationship of BP to plasma aldosterone concentration in the context of the prevailing level of plasma renin activity was studied in blacks and whites. In a secondary interventional study, 9-α fludrocortisone was administered for 2 weeks to healthy adult blacks and whites to simulate hyperaldosteronism. BP responses in the 2 race groups were then compared. Although black children had lower levels of plasma renin activity and plasma aldosterone, their BP was positively associated with the plasma aldosterone concentration, an effect that increased as plasma renin activity decreased (P=0.004). Data from black adults yielded similar results. No similar relationship was observed in whites. In the interventional study, 9-α fludrocortisone increased BP in blacks but not in whites. In conclusion, aldosterone sensitivity is a significant determinant of BP in young blacks. Although its role in establishing the risk of hypertension is not known, it could be as relevant as the actual level of aldosterone.

Pomegranate (Punicagranatum) juice decreases lipid peroxidation, but has no effect on plasma advanced glycated end-products in adults with type 2 diabetes: a randomized double-blind clinical trial

PubMed Central

Sohrab, Golbon; Angoorani, Pooneh; Tohidi, Maryam; Tabibi, Hadi; Kimiagar, Masoud; Nasrollahzadeh, Javad

2015-01-01

Introduction Diabetes mellitus characterized by hyperglycemia could increase oxidative stress and formation of advanced glycated end-products (AGEs), which contribute to diabetic complications. The purpose of this study was to assess the effect of pomegranate juice (PJ) containing natural antioxidant on lipid peroxidation and plasma AGEs in patients with type 2 diabetes (T2D). Materials and methods In a randomized, double-blind, placebo-controlled trial, 44 patients (age range 56±6.8 years), T2D were randomly assigned to one of two groups: group A (PJ, n=22) and group B (Placebo, n=22). At the baseline and the end of 12-week intervention, biochemical markers including fasting plasma glucose, insulin, oxidative stress, and AGE markers including carboxy methyl lysine (CML) and pentosidine were assayed. Results At baseline, there were no significant differences in plasma total antioxidant capacity (TAC) levels between the two groups, but malondialdehyde (MDA) decreased levels were significantly different (P<0.001). After 12 weeks of intervention, TAC increased (P<0.05) and MDA decreased (P<0.01) in the PJ group when compared with the placebo group. However, no significant differences were observed in plasma concentration of CML and pentosidine between the two groups. Conclusions The study showed that PJ decreases lipid peroxidation. Therefore, PJ consumption may delay onset of T2D complications related to oxidative stress. PMID:26355954

Anti-Müllerian hormone levels and antral follicle count in women enrolled in in vitro fertilization cycles: relationship to lifestyle factors, chronological age and reproductive history.

PubMed

Nardo, Luciano G; Christodoulou, Dimitra; Gould, Della; Roberts, Steve A; Fitzgerald, Cheryl T; Laing, Ian

2007-01-01

The aims of this prospective study were to investigate the relationship between anti-Müllerian hormone (AMH) and antral follicle count (AFC), and to determine whether these markers of ovarian reserve correlate with lifestyle factors, ethnicity, chronological age and reproductive history. Participants were 136 normo-ovulatory women undergoing infertility work-up within 3 months of their first ovarian stimulation cycle for in vitro fertilization. On day 3 of a spontaneous menstrual cycle, a blood sample for measurement of plasma AMH levels was taken and a transvaginal ultrasound scan to determine the AFC (follicles measuring 2-5 mm in diameter) was performed. Information about smoking, body mass index, alcohol consumption, ethnic origin, chronological age, age at menarche, years since menarche and gravidity were recorded using a case report form. The main outcome measures were plasma AMH concentrations and total number of small antral follicles (AFC). Median plasma levels of AMH were 2.0 ng/ml (interquartile range 1.1-3.6) and AFC was 10 (interquartile range 7-15). A positive correlation between AMH and AFC (r = 0.54, p < 0.0001) was found. AMH and AFC correlated negatively with age (r = -0.30, p < 0.001 and r = -0.27, p = 0.001 respectively) and number of years since menarche (r = -0.23, p = 0.007 and r = -0.21, p = 0.015 respectively), but not with any of the other measures. Circulating AMH levels and AFC correlated with each other and declined significantly with age. There were only weak, non-significant, correlations with lifestyle factors and reproductive history. These putative markers could be used individually or together to assess the age-related decline of ovarian function in normo-ovulatory candidates for IVF.

Association of TMEM106B gene polymorphism with age at onset in granulin mutation carriers and plasma granulin protein levels.

PubMed

Cruchaga, Carlos; Graff, Caroline; Chiang, Huei-Hsin; Wang, Jun; Hinrichs, Anthony L; Spiegel, Noah; Bertelsen, Sarah; Mayo, Kevin; Norton, Joanne B; Morris, John C; Goate, Alison

2011-05-01

To test whether rs1990622 (TMEM106B) is associated with age at onset (AAO) in granulin (GRN) mutation carriers and with plasma GRN levels in mutation carriers and healthy, elderly individuals. Rs1990622 (TMEM106B) was identified as a risk factor for frontotemporal lobar degeneration with TAR DNA-binding protein inclusions (FTLD-TDP) in a recent genome-wide association. Rs1990622 was genotyped in GRN mutation carriers and tested for association with AAO using the Kaplan-Meier method and a Cox proportional hazards model. Alzheimer's Disease Research Center. Subjects  We analyzed 50 affected and unaffected GRN mutation carriers from 4 previously reported FTLD-TDP families (HDDD1, FD1, HDDD2, and the Karolinska family). The GRN plasma levels were also measured in 73 healthy, elderly individuals. Age at onset and GRN plasma levels. The risk allele of rs1990622 was associated with a mean decrease of the AAO of 13 years (P = 9.9 × 10(-7)) and with lower plasma GRN levels in both healthy older adults (P = 4 × 10(-4)) and GRN mutation carriers (P = .0027). Analysis of the HapMap database identified a nonsynonymous single-nucleotide polymorphism rs3173615 (T185S) in perfect linkage disequilibrium with rs1990622. The association of rs1990622 with AAO explains, in part, the wide range in the AAO of disease among GRN mutation carriers. We hypothesize that rs1990622 or another variant in linkage disequilibrium could act in a manner similar to APOE in Alzheimer disease, increasing risk for disease in the general population and modifying AAO in mutation carriers. Our results also suggest that genetic variation in TMEM106B may influence risk for FTLD-TDP by modulating secreted levels of GRN.

Relationship between the effect of dietary fat on swimming endurance and energy metabolism in aged mice.

PubMed

Zhang, Guihua; Shirai, Nobuya; Suzuki, Hiramitsu

2011-10-01

The aim of this study was to investigate the effect of different dietary fats on alterations in endurance, energy metabolism, and plasma levels of interleukin-6 (IL-6) and minerals in mice. Male mice (aged 58 weeks) were fed diets containing 6% safflower oil, fish oil, or lard for 12 weeks. Swimming time to exhaustion, energy metabolism, and plasma IL-6 levels were subsequently determined. Mice fed safflower oil exhibited a marked increase in swimming time compared to the baseline level. Mice fed lard exhibited a significant decrease in swimming time, while mice on a fish oil diet exhibited a small decrease in swimming time. The final swimming time of mice fed safflower oil was significantly longer than that of animals fed lard. This improvement in endurance with dietary safflower oil was accompanied by decreased accumulation of lactate and less glycogen depletion during swimming. In the safflower oil group, muscle carnitine palmitoyltransferase activity increased significantly after swimming, while the plasma non-esterified fatty acid concentration decreased significantly. A trend to increased plasma IL-6 levels was observed in sedentary animals on a safflower oil diet compared to those on a lard diet. These results suggest that dietary safflower oil improves the swimming endurance of aged mice to a greater extent than lard, and that this effect appears to involve glycogen sparing through increased fatty acid utilization. Copyright © 2011 S. Karger AG, Basel.

Homocysteine and Cognitive Performance in Elders with Self-Neglect

NASA Technical Reports Server (NTRS)

Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

2009-01-01

Elevated plasma homocysteine has been associated with altered cognitive performance in older adults. Elders referred to Adult Protective Services (APS) for self-neglect have been reported to have elevated plasma homocysteine levels and to suffer from cognitive impairment. This study assesses the association, if any, between plasma homocysteine and cognitive performance among elders with self-neglect. Methods: Sixty-five community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 matched controls (matched for age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS), the Wolf-Klein Clock Drawing Tests (CDT) and a comprehensive nutritional biochemistry panel, which included plasma homocysteine. Student s t tests and Pearson correlations were conducted to assess for bivariate associations. Results: Elders with self-neglect had significantly higher plasma homocysteine levels (M=12.68umol/L, sd=4.4) compared to the controls (M=10.40umol/L, sd=3.61;t=3.21, df=127, p=.002). There were no statistically significant associations between cognitive performance and plasma homocysteine in the self-neglect group, however there was a significant correlation between plasma homocysteine and the CDT among the controls (r=-.296, p=.022). Conclusion: Mean plasma homocysteine levels were significantly higher in elders with self-neglect, however, they do not appear to be related to cognitive performance, indicating that cognitive impairment in elder self-neglect involve mechanisms other than hyperhomocysteinemia. These findings warrant further investigation

Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome.

PubMed

Klimiec, Elzbieta; Pera, Joanna; Chrzanowska-Wasko, Joanna; Golenia, Aleksandra; Slowik, Agnieszka; Dziedzic, Tomasz

2016-08-15

Activation of Toll-like receptor 4 (TLR4) contributes to brain injury and poor outcome after cerebral ischemia. The expression of this receptor on monocytes is increased in patients with acute ischemic stroke. Endotoxin is an endogenous ligand for TLR4. The aim of our study was to determine if plasma endotoxin activity is increased in stroke patients and correlates with functional outcome. We included 88 patients with ischemic stroke (median age: 71, 56.8% men) and 59 age-matched controls. Plasma endotoxin activity and level of proteins regulating endotoxin interaction with TLR4 (LPS binding protein - LBP and sCD14) were measured in blood samples taken at day 1 (within 24h after stroke symptoms onset), 3 and 6. Short-term functional outcome was assessed at day 14 using modified Rankin Scale. Unfavourable outcome was defined as modified Rankin Scale score>2. Compared to controls, stroke patients had higher plasma endotoxin activity on day 1 (median: 0.39 vs 0.32EU/mL, P=0.03) as well as higher LBP (median: 18.7 vs 11.5μg/mL, P<0.01) and sCD14 level (median: 1330 vs 1070ng/mL, P<0.01). Plasma LPS activity and levels of LBP and sCD14 significantly rose during stroke. Higher LPS activity measured on day 6 was associated with unfavourable outcome (OR: 3.94, 95%CI: 1.03-15.02, P=0.04, adjusted for age and stroke severity). Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Hyperglycemia-related advanced glycation end-products is associated with the altered phosphatidylcholine metabolism in osteoarthritis patients with diabetes

PubMed Central

Zhang, Weidong; Randell, Edward W.; Sun, Guang; Likhodii, Sergei; Liu, Ming; Furey, Andrew

2017-01-01

To test whether type 2 diabetic patients have an elevated level of advanced glycation end-products (AGEs) and responsible for altered phosphatidylcholine metabolism, which we recently found to be associated with osteoarthritis (OA) and diabetes mellitus (DM), synovial fluid (SF) and plasma samples were collected from OA patients with and without DM. Hyperglycemia-related AGEs including methylglyoxal (MG), free methylglyoxal-derived hydroimidazolone (MG-H1), and protein bound N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL) levels were measured in both SF and plasma samples using liquid chromatography coupled tandem mass spectrometry methodology. The correlation between these AGEs and phosphatidylcholine acyl-alkyl C34:3 (PC ae C34:3) and C36:3 (PC ae C36:3) were examined. Eighty four patients with knee OA, including 46 with DM and 38 without DM, were included in the study. There was no significant difference in plasma levels of MG, MG-H1, CML, and CEL between OA patients with and without DM. However, the levels of MG and MG-H1, but not CML and CEL in SF were significantly higher in OA patients with DM than in those without (all p ≤0.04). This association strengthened after adjustment for age, body mass index (BMI), sex and hexose level (p<0.02). Moreover, the levels of MG-H1 in SF was negatively and significantly correlated with PC ae C34:3 (ρ = -0.34; p = 0.02) and PC ae C36:3 (ρ = -0.39; P = 0.03) after the adjustment of age, BMI, sex and hexose level. Our data indicated that the production of non-protein bound AGEs was increased within the OA-affected joint of DM patients. This is associated with changes in phosphatidylcholine metabolism and might be responsible for the observed epidemiological association between OA and DM. PMID:28898260

Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome.

PubMed

Goldstone, A P; Holland, A J; Butler, J V; Whittington, J E

2012-12-01

Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder with several nutritional phases during childhood proceeding from poor feeding, through normal eating without and with obesity, to hyperphagia and life-threatening obesity, with variable ages of onset. We investigated whether differences in appetite hormones may explain the development of abnormal eating behaviour in young children with PWS. In this cross-sectional study, children with PWS (n=42) and controls (n=9) aged 7 months-5 years were recruited. Mothers were interviewed regarding eating behaviour, and body mass index (BMI) was calculated. Fasting plasma samples were assayed for insulin, leptin, glucose, peptide YY (PYY), ghrelin and pancreatic polypeptide (PP). There was no significant relationship between eating behaviour in PWS subjects and the levels of any hormones or insulin resistance, independent of age. Fasting plasma leptin levels were significantly higher (mean ± s.d.: 22.6 ± 12.5 vs 1.97 ± 0.79 ng ml(-1), P=0.005), and PP levels were significantly lower (22.6 ± 12.5 vs 69.8 ± 43.8 pmol l(-1), P<0.001) in the PWS group compared with the controls, and this was independent of age, BMI, insulin resistance or IGF-1 levels. However, there was no significant difference in plasma insulin, insulin resistance or ghrelin levels between groups, though PYY declined more rapidly with age but not BMI in PWS subjects. Even under the age of 5 years, PWS is associated with low levels of anorexigenic PP, as in older children and adults. Hyperghrelinaemia or hypoinsulinaemia was not seen in these young children with PWS. Change in these appetite hormones was not associated with the timing of the transition to the characteristic hyperphagic phase. However, abnormal and/or delayed development or sensitivity of the effector pathways of these appetitive hormones (for example, parasympathetic and central nervous system) may interact with low PP levels, and later hyperghrelinaemia or hypoinsulinaemia, to contribute to hyperphagia in PWS.

[Indices of the antioxidant system and dopamine in blood plasma in the dynamics of microwave resonance therapy in patients with alcoholism].

PubMed

Prokopieva, V D; Yarygina, E G; Krotenko, N M; Boiko, A S; Bokhan, N A; Ivanova, S A

To study effects of microwave resonance therapy (MWRT) on the level of dopamine and some indices of the antioxidant system of blood plasma in patients with alcohol dependence. Dopamine, reduced glutathione, activities of catalase and superoxidismutase (SOD) were measured in blood plasma of alcoholic patients (50 men) before and after therapy. Plasma of 25 physically and mentally healthy men matched for age was used as control. In alcoholic patients in withdrawal state, the significant increase in dopamine (p=0.03), activity of catalase and SOD (p<0.05) as well as a decrease in reduced glutathione (p<0.01) in blood plasma in comparison with controls were found. The level of dopamine decreased significantly as after conventional therapy, as well after the therapy with addition of MWRT. After MWRT, the level of glutathione in blood plasma increased significantly and activities of catalase and SOD decreased practically up to the control level while after conventional therapy (without MWRT), the indices of the antioxidant system did not change significantly. The inclusion of MWRT in complex treatment of patients with alcoholism contributes to the normalization of the activity of catalase and SOD and increases the level of reduced glutathione, but has no significant effect on blood plasma dopamine level.

The Influence of Glycated Hemoglobin on the Cross Susceptibility Between Type 1 Diabetes Mellitus and Periodontal Disease.

PubMed

Lappin, David F; Robertson, Douglas; Hodge, Penny; Treagus, David; Awang, Raja A; Ramage, Gordon; Nile, Christopher J

2015-11-01

Periodontal disease is a major complication of type 1 diabetes mellitus (T1DM). The aim of the present study is to investigate the relationship between glycated hemoglobin and circulating levels of interleukin (IL)-6, IL-8, and C-X-C motif chemokine ligand 5 (CXCL5) in non-smoking patients suffering from T1DM, with and without periodontitis. In addition, to determine the effect of advanced glycation end products (AGE) in the presence and absence of Porphyromonas gingivalis lipopolysaccharide (LPS) on IL-6, IL-8, and CXCL5 expression by THP-1 monocytes and OKF6/TERT-2 cells. There were 104 participants in the study: 19 healthy volunteers, 23 patients with periodontitis, 28 patients with T1DM, and 34 patients with T1DM and periodontitis. Levels of blood glucose/glycated hemoglobin (International Federation of Clinical Chemistry [IFCC]) were determined by high-performance liquid chromatography. Levels of IL-6, IL-8, and CXCL5 in plasma were determined by enzyme-linked immunosorbent assay (ELISA). In vitro stimulation of OKF6/TERT-2 cells and THP-1 monocytes was performed with combinations of AGE and P. gingivalis LPS. Changes in expression of IL-6, IL-8, and CXCL5 were monitored by ELISA and real-time polymerase chain reaction. Patients with diabetes and periodontitis had higher plasma levels of IL-8 than patients with periodontitis alone. Plasma levels of IL-8 correlated significantly with IFCC units, clinical probing depth, and attachment loss. AGE and LPS, alone or in combination, stimulated IL-6, IL-8, and CXCL5 expression in both OKF6/TERT-2 cells and THP-1 monocytes. Elevated plasma levels of IL-8 potentially contribute to the cross-susceptibility between periodontitis and T1DM. P. gingivalis LPS and AGE in combination caused significantly greater expression of IL-6, IL-8, and CXCL5 from THP-1 monocytes and OKF6/TERT-2 cells than LPS alone.

High Protein Intake Does Not Prevent Low Plasma Levels of Conditionally Essential Amino Acids in Very Preterm Infants Receiving Parenteral Nutrition.

PubMed

Morgan, Colin; Burgess, Laura

2017-03-01

We have shown that increasing protein intake using a standardized, concentrated, added macronutrients parenteral (SCAMP) nutrition regimen improves head growth in very preterm infants (VPIs) compared with a control parenteral nutrition (PN) regimen. VPIs are at risk of conditionally essential amino acid (CEAA) deficiencies because of current neonatal PN amino acid (AA) formulations. We hypothesized that the SCAMP regimen would prevent low plasma levels of CEAAs. To compare the plasma AA profiles at approximately day 9 of life in VPIs receiving SCAMP vs a control PN regimen. VPIs (<29 weeks' gestation) were randomized to receive SCAMP (30% more PN AA) or a control regimen. Data were collected to measure parenteral and enteral protein, energy, and individual AA intake and the first plasma AA profile. Plasma profiles of the 20 individual protogenic AA levels were measured using ion exchange chromatography. Plasma AA profiles were obtained at median (interquartile range [IQR]) age of 9 (8-10) days in both SCAMP (n = 59) and control (n = 67) groups after randomizing 150 VPIs. Median (IQR) plasma levels of individual essential AAs were higher than the reference population mean (RPM) in both groups, especially for threonine. SCAMP infants had higher plasma levels of essential AAs than did the controls. Median (IQR) plasma levels of glutamine, arginine, and cysteine (CEAAs) were lower than the RPM in both groups. Plasma AA levels in PN-dependent VPIs indicate there is an imbalance in essential and CEAA provision in neonatal PN AA formulations that is not improved by increasing protein intake.

Low plasma progranulin levels in children with autism

PubMed Central

2011-01-01

Background Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. Methods Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. Results Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40) of autistic children. On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. Conclusions Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism. PMID:21892962

Prediagnostic plasma antibody levels to periodontopathic bacteria and risk of coronary heart disease.

PubMed

Ueno, Masayuki; Izumi, Yuichi; Kawaguchi, Yoko; Ikeda, Ai; Iso, Hiroyasu; Inoue, Manami; Tsugane, Shoichiro

2012-01-01

Many epidemiological studies have indicated that periodontitis is an important risk factor for coronary heart disease (CHD). We examined whether plasma antibody levels to 3 major periodontal pathogens, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia predicted the risk of CHD events. A nested case-control research design (case: n = 191, control: n = 382), by matching gender, age, study area, date of blood collection, and time since last meal at blood collection, was employed in a large cohort of Japanese community residents.Antibody levels of periodontopathic bacteria were associated with risk of CHD after adjusting for BMI, smoking status, alcohol intake, history of hypertension, history of diabetes mellitus, exercise during leisure time, and perceived mental stress. The association was different by age subgroup. For subjects aged 40-55 years, the medium (31.7-184.9 U/mL) or high tertile plasma antibody level (> 184.9 U/mL) of A. actinomycetemcomitans showed higher risk of CHD (medium: OR = 3.72; 95% CI = 1.20-11.56, high: OR = 4.64; 95% CI = 1.52-14.18) than the low tertile level (< 31.7 U/mL). The ORs of CHD incidence became higher with an increase in IgG level of A. actinomycetemcomitans (P for trend = 0.007). For subjects aged 56-69 years, the high tertile level (> 414.1 U/mL) of P. intermedia was associated with higher risk of CHD (OR = 2.65; 95% CI = 1.18-5.94) in a dose-response fashion (P for trend = 0.007). The possible role of periodontopathic bacteria as a risk factor for CHD incidence was suggested by the results of this study by the elevated antibody level to these bacteria with the increased risk of CHD.

Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

PubMed

Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong

2017-10-01

Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Advanced glycation end products affect cholesterol homeostasis by impairing ABCA1 expression on macrophages.

PubMed

Kamtchueng Simo, Olivier; Ikhlef, Souade; Berrougui, Hicham; Khalil, Abdelouahed

2017-08-01

Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly reduced RCT (65.3% reduction in [ 3 H]cholesterol levels in the plasma of D-gal-treated mice after 48 h compared with control mice, P < 0.01). The injection of both D-gal and aminoguanidine hydrochloride increased [ 3 H]cholesterol levels in the plasma, although the levels were lower than those of control mice. The in vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and conjugated diene content of HDLs and significantly reduced PON1 paraoxonase activity (87.4% lower than control HDLs, P < 0.0001). Treating J774A.1 macrophages with glycated fetal bovine serum increased carbonyl formation (39.5% increase, P < 0.003) and reduced ABCA1 protein expression and the capacity of macrophages to liberate cholesterol (69.1% decrease, P < 0.0001). Our results showed, for the first time, that RCT is altered with aging and that AGEs contribute significantly to this alteration.

Dynamic changes in plasma tissue plasminogen activator, plasminogen activator inhibitor-1 and beta-thromboglobulin content in ischemic stroke.

PubMed

Zhuang, Ping; Wo, Da; Xu, Zeng-Guang; Wei, Wei; Mao, Hui-ming

2015-07-01

The aim of this paper is to investigate the corresponding variations of plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities, and beta-thromboglobulin (β-TG) content in patients during different stages of ischemic stroke. Ischemic stroke is a common disease among aging people and its occurrence is associated with abnormalities in the fibrinolytic system and platelet function. However, few reports focus on the dynamic changes in the plasma fibrinolytic system and β-TG content in patients with ischemic stroke. Patients were divided into three groups: acute, convalescent and chronic. Plasma t-PA and PAI-1 activities were determined by chromogenic substrate analysis and plasma β-TG content was detected by radioimmunoassay. Patients in the acute stage of ischemic stroke had significantly increased levels of t-PA activity and β-TG content, but PAI-1 activity was significantly decreased. Negative correlations were found between plasma t-PA and PAI-1 activities and between plasma t-PA activity and β-TG content in patients with acute ischemic stroke. There were significant differences in plasma t-PA and PAI-1 activities in the aged control group, as well as in the acute, convalescent and chronic groups. It can be speculated that the increased activity of t-PA in patients during the acute stage was the result of compensatory function, and that the increase in plasma β-TG level not only implies the presence of ischemic stroke but is likely a cause of ischemic stroke. During the later stages of ischemic stroke, greater attention is required in monitoring levels of PAI-1. Copyright © 2015 Elsevier Ltd. All rights reserved.

Decreased Epidermal Growth Factor (EGF) Associated with HMGB1 and Increased Hyperactivity in Children with Autism

PubMed Central

Russo, Anthony J.

2013-01-01

Background Autism spectrum disorders (ASDs), characterized by impaired social interactions and deficits in verbal and nonverbal communication, are thought to affect 1 in 88 children in the United States. There is much support for the role of growth factors in the etiology of autism. Recent research has shown that epithelial growth factor (EGF) is decreased in young autistic children (2–4 years of age). This study was designed to determine plasma levels of EGF in an older group of autistic children (mean age 10.6 years) and to correlate these EGF levels with putative biomarkers HGF, uPA, uPAR, GAD2, MPO GABA, and HMGB1, as well as symptom severity of 19 different symptoms. Subjects and methods Plasma from 38 autistic children, 11 children with pervasive developmental disorder (PDD-NOS) and 40 neurotypical, age and gender similar controls was assessed for EGF concentration using ELISAs. Severity of 19 symptoms (awareness, expressive language, receptive language, (conversational) pragmatic language, focus/attention, hyperactivity, impulsivity, perseveration, fine motor skills, gross motor skills, hypotonia (low muscle tone), tiptoeing, rocking/pacing, stimming, obsessions/fixations, eye contact, sound sensitivity, light sensitivity, and tactile sensitivity) was assessed and then compared to EGF concentrations. Results In this study, we found EGF levels in autistic children and those with PDD-NOS to be significantly lower when compared with neurotypical controls. EGF levels correlated with HMGB1 levels but not the other tested putative biomarkers, and EGF correlated negatively with hyperactivity, gross motor skills, and tiptoeing but not other symptoms. Conclusions These results suggest an association between decreased plasma EGF levels and selected symptom severity. We also found a strong correlation between plasma EGF and HMGB1, suggesting inflammation is associated with decreased EGF. PMID:23645980

Regulation of plasma factor XIII levels in healthy individuals; a major impact by subunit B intron K c.1952+144 C>G polymorphism.

PubMed

Mezei, Zoltán A; Katona, Éva; Kállai, Judit; Bereczky, Zsuzsanna; Molnár, Éva; Kovács, Bettina; Ajzner, Éva; Bagoly, Zsuzsa; Miklós, Tünde; Muszbek, László

2016-12-01

The regulation of plasma factor XIII (FXIII) levels in healthy individuals has been only partially explored. The identification of major non-genetic and genetic regulatory factors might provide important information on the contribution of FXIII to the risk of cardio/cerebrovascular diseases. To determine the effect of age, smoking, BMI, fibrinogen concentration on plasma FXIII activity, complex FXIII antigen (FXIII-A 2 B 2 ) and total FXIII-B subunit (tFXIII-B) level, to correlate FXIII-B level with the other two FXIII parameters and to assess the variation of FXIII levels in carriers of major FXIII subunit polymorphisms. 268 healthy individuals were enrolled in the study. FXIII activity was measured by the ammonia release assay; FXIII-A 2 B 2 and tFXIII-B were determined by ELISAs. FXIII-A p.Val34Leu, FXIII-B p.His95Arg and FXIII-B intron K c.1952+144 C>G polymorphisms were identified by RT-PCR using melting point analysis with fluorescence resonance energy transfer detection. All investigated FXIII parameters showed significant positive correlation with age and fibrinogen level; gender and BMI influenced only tFXIII-B. A highly significant positive correlation was demonstrated between tFXIII-B and the other FXIII parameters. FXIII-A p.Val34Leu polymorphism had only slight, if any effect on FXIII levels. The FXIII-B Arg95 allele moderately increased all three FXIII parameters, but the effect became statistically significant only after adjustment. The FXIII-B intron K G allele drastically decreased FXIII levels, and it seemed to be in synergism with the FXIII-A Leu34 allele. Plasma FXIII levels are subjected to multifactorial regulation, in which age, fibrinogen level and FXIII-B intron K polymorphism are major determinants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Higher plasma orexin a levels in children with Prader-Willi syndrome compared with healthy unrelated sibling controls.

PubMed

Manzardo, Ann M; Johnson, Lisa; Miller, Jennifer L; Driscoll, Daniel J; Butler, Merlin G

2016-09-01

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder associated with maladaptive social behavior, hyperphagia and morbid obesity. Orexin A is a hypothalamic neuropeptide important as a homeostatic regulator of feeding behavior and in energy metabolism through actions in the lateral hypothalamus. Dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia seen in PWS and we sought to assess orexin A levels in PWS relative to controls children. Morning fasting plasma orexin A levels were analyzed in 23 children (aged 5-11 years) with genetically confirmed PWS and 18 age and gender matched healthy unrelated siblings without PWS. Multiplex immune assays utilized the Milliplex Human Neuropeptide Magnetic panel and the Luminex platform. Natural log-transformed orexin A data were analyzed using general linear model adjusting for diagnosis, gender, age, total body fat, and body mass index (BMI). Plasma orexin A levels were significantly higher (P < 0.006) in children with PWS (average ±SD = 1,028 pg/ml ± 358) compared with unrelated siblings (average ±SD = 609 pg/ml ± 351; P < 0.001). Orexin A levels correlated with age in females and were significantly elevated in PWS even after these effects were controlled. These findings support the hypothesis that dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia in PWS. Further studies are warranted to better understand the complex relationship between orexin A levels and the problematic behaviors consistently found in individuals with PWS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Higher plasma orexin A levels in children with Prader-Willi syndrome compared with healthy unrelated sibling controls.

PubMed

Manzardo, Ann M; Johnson, Lisa; Miller, Jennifer L; Driscoll, Daniel J; Butler, Merlin G

2016-08-01

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder associated with maladaptive social behavior, hyperphagia, and morbid obesity. Orexin A is a hypothalamic neuropeptide important as a homeostatic regulator of feeding behavior and in energy metabolism through actions in the lateral hypothalamus. Dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia seen in PWS and we sought to assess orexin A levels in PWS relative to controls children. Morning fasting plasma orexin A levels were analyzed in 23 children (aged 5-11 years) with genetically confirmed PWS and 18 age and gender matched healthy unrelated siblings without PWS. Multiplex immune assays utilized the Milliplex Human Neuropeptide Magnetic panel and the Luminex platform. Natural log-transformed orexin A data were analyzed using general linear model adjusting for diagnosis, gender, age, total body fat and body mass index (BMI). Plasma orexin A levels were significantly higher (P < 0.006) in children with PWS (average ±SD = 1028 pg/ml ± 358) compared with unrelated siblings (average ±SD = 609 pg/ml ± 351; P < 0.001). Orexin A levels correlated with age in females and were significantly elevated in PWS even after these effects were controlled. These findings support the hypothesis that dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia in PWS. Further studies are warranted to better understand the complex relationship between orexin A levels and the problematic behaviors consistently found in individuals with PWS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Relationship between plasma adropin levels and body composition and lipid characteristics amongst young adolescents in Taiwan.

PubMed

Chang, Jin-Biou; Chu, Nain-Feng; Lin, Fu-Huang; Hsu, Jhu-Ting; Chen, Pi-Yun

Adropin is a 76 amino acid peptide hormone with a molecular weight of 4999.9Da that may be associated with energy homeostasis, insulin resistance and lipid metabolism in mice and human. There is only a few studies that examine plasma adropin levels and body composition in children. This study is to evaluate the relationship between plasma adropin levels, body composition and lipid variables amongst young adolescents in Taiwan. We examined 492 adolescents (269 females and 223 males) ranging from 12 to 15 years old, with a mean age of 13.6 years. Body composition was measured using impedance method by Tanita-BC418. Plasma lipid variables were measured using standard methods and plasma adropin levels were measured using the ELISA method. There was no significant difference in plasma adropin levels between males and females (3.52 vs. 3.58ng/ml). Plasma adropin levels were negatively correlated with fat free mass (r=-0.12, p<0.01). More interestingly, children with higher plasma adropin levels had lower waist-to-hip ratios (WHR) and lower body fat percentage by mass. Furthermore, there is no difference in lipid profiles in high vs. low adropin subjects. Plasma adropin levels are not consistency associated with body composition and no association with lipid variables amongst Taiwanese adolescents. The role of adropin in the development of obesity is still not clear, and further studies are need especially for children. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

20S proteasome in the blood plasma of boys with cryptorchidism.

PubMed

Toliczenko-Bernatowicz, D; Matuszczak, E; Tylicka, M; Sankiewicz, A; Komarowska, M; Gorodkiewicz, E; Debek, W; Hermanowicz, A

2018-02-15

To evaluate the concentration of 20S proteasome in the blood plasma of boys with cryptorchidism. Patients-50 boys aged 1-4 years (median = 2.4 years) with unilateral cryptorchidism. The control group-50 healthy, age-matched boys (aged 1-4 years, median = 2.1 years), admitted for planned herniotomy. In our study, we used a novel technique Surface PLASMON RESONANCE Imaging. The median concentration of 20S proteasome in the blood plasma of boys with cryptorchidism was 2.5-fold higher than in boys with inguinal hernia. We noticed statistically significant difference between 20S proteasome levels in boys with cryptorchidism up to 2 years old and above 2 years old. We believe that the 20S proteasome concentrations in the blood plasma of boys with cryptorchidism reflect the heat-induced apoptosis of germ cells.

Plasma selenium levels and nonalcoholic fatty liver disease in Chinese adults: a cross-sectional analysis

PubMed Central

Yang, Zhen; Yan, Chonghuai; Liu, Gang; Niu, Yixin; Zhang, Weiwei; Lu, Shuai; Li, Xiaoyong; Zhang, Hongmei; Ning, Guang; Fan, Jiangao; Qin, Li; Su, Qing

2016-01-01

Selenium exposure can induce liver insulin resistance and increased liver triglyceride concentrations in animals, which may link to an increased risk of nonalcoholic fatty liver disease (NAFLD). However, epidemiological studies investigating the association between elevated plasma selenium levels and NAFLD were not available. We aimed to investigate the association of selenium levels with the prevalence of NAFLD in Chinese adults. This was a cross-sectional study of 8550 Chinese adults aged 40 yr or older in Shanghai, China. A questionnaire, anthropometric measurements, and laboratory tests were conducted. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Plasma selenium concentration was assessed by inductively coupled plasma mass spectroscopy. The median concentration of plasma selenium was 213.0 μg/L. Elevated plasma selenium levels were associated with higher triglycerides, LDL-cholesterol, fasting plasma glucose, post-loading plasma glucose, A1c, HOMA-IR, as well as ALT, AST and γ-GT (all P < 0.05). The odds ratios were substantially higher for NAFLD (OR = 1.54, 95% CI 1.13–2.18) in the highest selenium quartile compared with those in the lowest quartile, after adjustment for potential cofounder. The results of this study provided epidemiological evidence that increased plasma selenium level is associated with elevated prevalence of NAFLD. PMID:27853246

Relationship of low plasma klotho with poor grip strength in older community-dwelling adults: the InCHIANTI study

PubMed Central

Semba, Richard D.; Cappola, Anne R.; Sun, Kai; Bandinelli, Stefania; Dalal, Mansi; Crasto, Candace; Guralnik, Jack M.; Ferrucci, Luigi

2012-01-01

Handgrip strength is a strong indicator of total body muscle strength and is a predictor of poor outcomes in older adults. The aging suppressor gene klotho encodes a single-pass transmembrane protein that is secreted as a circulating hormone. In mice, disruption of klotho expression results in a syndrome that includes sarcopenia, atherosclerosis, osteoporosis, and shortened lifespan, and conversely, overexpression of klotho leads to a greater longevity. The objective was to determine whether plasma klotho levels are related to skeletal muscle strength in humans. We measured plasma klotho in 804 adults, ≥65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. Grip strength was positively correlated with plasma klotho at threshold <681 pg/mL. After adjusting for age, sex, education, smoking, physical activity, cognition, and chronic diseases, plasma klotho (per 1 standard deviation increase) was associated with grip strength (beta = 1.20, standard error = 0.35, P = 0.0009) in adults with plasma klotho <681 pg/mL. These results suggest that older adults with lower plasma klotho have poor skeletal muscle strength. PMID:21769735

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

PubMed

Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari

2013-10-01

Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly. © 2013 The Anatomical Society and John Wiley & Sons Ltd.

The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age

PubMed Central

Al-Salameh, Abdallah; Croixmarie, Vincent; Masson, Perrine; Corruble, Emmanuelle; Fève, Bruno; Colle, Romain; Ripoll, Laurent; Walther, Bernard; Boursier-Neyret, Claire; Werner, Erwan; Becquemont, Laurent; Chanson, Philippe

2017-01-01

Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the “normal” metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the “normal” metabolome and its main sources of variation. PMID:28278231

The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age.

PubMed

Trabado, Séverine; Al-Salameh, Abdallah; Croixmarie, Vincent; Masson, Perrine; Corruble, Emmanuelle; Fève, Bruno; Colle, Romain; Ripoll, Laurent; Walther, Bernard; Boursier-Neyret, Claire; Werner, Erwan; Becquemont, Laurent; Chanson, Philippe

2017-01-01

Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the "normal" metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the "normal" metabolome and its main sources of variation.

Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.

PubMed

Ioanna, Zygoula; Christian, Schori; Christian, Grimm; Daniel, Barthelmes

2018-02-01

Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.

Selected haematological and plasma chemistry parameters in juvenile and adult degus (Octodon degus).

PubMed

Jekl, V; Hauptman, K; Jeklova, E; Knotek, Z

2011-07-16

Thirty-five juvenile (mean age 6.3 weeks) and 35 adult (mean age 2.0 years) healthy degus (Octodon degus) were studied to investigate selected haematological and plasma biochemistry parameters. Animals were anaesthetised with isoflurane, and blood was withdrawn from the cranial vena cava. Erythrocyte, haematocrit and neutrophil counts (including the percentage of neutrophils) were significantly higher in the adult degus than in the juveniles. In contrast, the reticulocyte count, mean corpuscular volume, mean corpuscular haemoglobin, number of platelets and percentage of lymphocytes were significantly lower in the adult animals. Total protein and globulin levels were significantly higher in the adult degus. The albumin:globulin ratio and plasma levels of urea nitrogen, cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, potassium, total calcium and inorganic phosphorus were significantly lower in adults than in juveniles.

Renal handling of galectin-3 in the general population, chronic heart failure, and hemodialysis.

PubMed

Meijers, Wouter C; van der Velde, A Rogier; Ruifrok, Willem P; Schroten, Nicolas F; Dokter, Martin M; Damman, Kevin; Assa, Solmaz; Franssen, Casper F; Gansevoort, Ron T; van Gilst, Wiek H; Silljé, Herman H; de Boer, Rudolf A

2014-09-18

Galectin-3 is a biomarker for prognostication and risk stratification of patients with heart failure (HF). It has been suggested that renal function strongly relates to galectin-3 levels. We aimed to describe galectin-3 renal handling in HF. In Sprague-Dawley rats, we infused galectin-3 and studied distribution and renal clearance. Furthermore, galectin-3 was measured in urine and plasma of healthy controls, HF patients and hemodialysis patients. To mimic the human situation, we measured galectin-3 before and after the artificial kidney. Infusion in rats resulted in a clear increase in plasma and urine galectin-3. Plasma galectin-3 in HF patients (n=101; mean age 64 years; 93% male) was significantly higher compared to control subjects (n=20; mean age 58 years; 75% male) (16.6 ng/mL versus 9.7 ng/mL, P<0.001), while urinary galectin-3 in HF patients was comparable (28.1 ng/mL versus 35.1 ng/mL, P=0.830). The calculated galectin-3 excretion rate was lower in HF patient (2.3 mL/min [1.5 to 3.4] versus 3.9 mL/min [2.3 to 6.4] in control subjects; P=0.005). This corresponded with a significantly lower fractional excretion of galectin-3 in HF patients (2.4% [1.7 to 3.7] versus 3.0% [1.9 to 5.5]; P=0.018). These differences, however, were no longer significant after correction for age, gender, diabetes, and smoking. HF patients who received diuretics (49%) showed significantly higher aldosterone and galectin-3 levels. Hemodialysis patients (n=105; mean age 63 years; 65% male), without urinary galectin-3 excretion, had strongly increased median plasma galectin-3 levels (70.6 ng/mL). In this small cross-sectional study, we report that urine levels of galectin-3 are not increased in HF patients, despite substantially increased plasma galectin-3 levels. The impaired renal handling of galectin-3 in patients with HF may explain the described relation between renal function and galectin-3 and may account for the elevated plasma galectin-3 in HF. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Age dependence of plasma phospholipid fatty acid levels: potential role of linoleic acid in the age-associated increase in docosahexaenoic acid and eicosapentaenoic acid concentrations.

PubMed

de Groot, Renate H M; van Boxtel, Martin P J; Schiepers, Olga J G; Hornstra, Gerard; Jolles, Jelle

2009-10-01

Limited information is available with respect to the association between age and the plasma phospholipid fatty acid profile. Therefore we investigated the association between plasma phospholipid fatty acid status and age after correction for sex, smoking, alcohol use, BMI and fish intake. Plasma phospholipid fatty acid composition was measured and information on fish intake and other potential covariates was collected in 234 participants of the Maastricht Aging Study. The participants were healthy individuals of both sexes with an age range between 36 and 88 years. Hierarchical linear regression analyses were applied to study the relationship between age and fatty acid concentrations. After correction for fish consumption and other relevant covariates, a significant positive relationship was observed between age of the subjects and their plasma phospholipid concentrations of DHA (22 : 6n-3, P = 0.006) and EPA (20 : 5n-3; P = 0.001). Age contributed 2.3 and 3.9 % to the amount of explained variance, respectively. The higher n-3 long-chain PUFA status at advanced age was confirmed by lower concentrations of their putative 'shortage marker' Osbond acid (ObA, 22 : 5n-6; P = 0.022 for the relationship with age after correction for covariates and fish intake, R2 0.022). Concentrations of linoleic acid (LA; 18 : 2n-6) were negatively associated with age (P < 0.001; R2 0.061). In conclusion, DHA and EPA concentrations appeared to be higher in older age groups, partly because of a higher fish intake and partly because of another age-associated mechanism, possibly involving the well-known competition with LA.

MiOXSYS: a novel method of measuring oxidation reduction potential in semen and seminal plasma.

PubMed

Agarwal, Ashok; Sharma, Rakesh; Roychoudhury, Shubhadeep; Du Plessis, Stefan; Sabanegh, Edmund

2016-09-01

To measure oxidative reduction potential (ORP) in semen and seminal plasma and to establish their reference levels. ORP levels were measured in semen and seminal plasma. Tertiary hospital. Twenty-six controls and 33 infertile men. None. Static ORP (sORP) and capacitance ORP (cORP) were measured in semen and seminal plasma at time 0 and 120 minutes. Correlation of ORP was assessed between [1] semen and seminal plasma and [2] time 0 and 120 minutes. The association with sperm parameters was studied in (a) controls and (b) infertile patients, and a receiver operating characteristic curve was generated to establish the sORP cutoff. Semen sORP and cORP levels were associated with seminal plasma levels at time 0 and time 120 minutes. In controls and infertile patients, an inverse relationship of sORP levels was established with concentration and total sperm count in semen as well as seminal plasma at time 0 and 120 minutes. Classification of subjects based on sperm motility showed that subjects with abnormal motility present with poor concentration, total count, morphology, and elevated levels of semen and seminal plasma sORP at time 120 minutes. The sORP cutoff of 1.48 in semen and 2.09 in seminal plasma based on motility was able to distinguish subjects with normal semen quality from those with abnormal semen quality. The MiOXSYS System can reliably measure ORP levels in semen and seminal plasma. ORP levels are not affected by semen age, making this new technology easy to employ in a clinical setting. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

[The influence of single moderate exercise on the sympathetic nervous system activity in patients with essential hypertension].

PubMed

Gajek, Jacek; Zyśko, Dorota

2002-12-01

Sympathetic nervous system may play an important role in development and maintenance of hypertension. Its activity can be assessed by plasma levels of catecholamines, neuropeptide Y (NPY) and adrenergic receptor density. Hypertensive subjects may be more prone to reveal overactivity of sympathetic nervous system, for instance as a result of physical stress. The aim of the study was to determine the activity of sympathetic nervous system in young patients with newly recognized, untreated mild hypertension. The study was carried out in 22 patients (age 38.5 +/- 10.3 years) and 20 normotensive volunteers (age 38.5 +/- 8.6 years) as a control group, matched for sex. Density of alpha 2- and beta-adrenergic receptors using 3H-yohimbine and 125I-cyanopindolol respectively, total catecholamines and plasma renin activity using radioenzymatic assay, neuropeptide Y and aldosterone using radioimmunoassay were assessed in the blood taken in the supine position and after moderate bicycle ergometer exercise. Plasma concentration of NPY at rest did not differ between the groups, but increased significantly after exercise and was greater in hypertensive patients (p < 0.05). The density of alpha 2- and beta-adrenergic receptors at rest and after exercise in hypertensive subjects was unchanged when comparing to healthy individuals. The plasma concentrations of endogenous catecholamines, plasma renin activity and aldosterone level increase during exercise in both studied groups (p < 0.05). Aldosterone level was higher in hypertensive patients at rest (p < 0.05). There was a negative correlation between baseline aldosterone and NPY levels in hypertensive patients (r = -0.44, p < 0.05). Moderate exercise in hypertensive subjects causes the hyperactivity of sympathetic nervous system expressed as increase of NPY plasma level.

Plasma BDNF Concentration, Val66Met Genetic Variant, and Depression-Related Personality Traits

PubMed Central

Terracciano, Antonio; Martin, Bronwen; Ansari, David; Tanaka, Toshiko; Ferrucci, Luigi; Maudsley, Stuart; Mattson, Mark P.; Costa, Paul T.

2010-01-01

Brain derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurogenesis, and BDNF plasma and serum levels have been associated with depression, Alzheimer's disease, and other psychiatric and neurodegenerative disorders. In a relatively large community sample, drawn from the Baltimore Longitudinal Study of Aging (BLSA), we examine whether BDNF plasma concentration is associated with the Val66Met functional polymorphism of the BDNF gene (n = 335) and with depression-related personality traits assessed with the NEO-PI-R (n = 391). Plasma concentration of BDNF was not associated with the Val66Met variant in either men or women. However, in men, but not in women, BDNF plasma level was associated with personality traits linked to depression. Contrary to the notion that low BDNF is associated with negative outcomes, we found lower plasma levels in men who score lower on depression and vulnerability to stress (two facets of Neuroticism) and higher on Conscientiousness and Extraversion. These findings challenge the prevailing hypothesis that lower peripheral levels of BDNF are a marker of depression. PMID:20345896

Plasma miRNA levels correlate with sensitivity to bone mineral density in postmenopausal osteoporosis patients.

PubMed

Li, Hongqiu; Wang, Zhe; Fu, Qin; Zhang, Jing

2014-11-01

In our study, we detect the levels of three micro-RNAs (miRNAs; miR-21, miR-133a and miR-146a) in the plasma of 120 Chinese postmenopausal women who were divided into three groups (normal, osteopenia and osteoporosis) according to the T-scores. Downregulation of miR-21, as well as upregulation of miR-133a, was validated in the plasma of osteoporosis and osteopenia patients versus the normal group. The difference in expression regarding the miR-146a level in plasma among the three groups was not significant (p > 0.01). The circulating miRNA expression levels and bone mineral density (BMD) were examined during a multiple correlation analysis as a dependent variable after adjusting for age, weight and height. We have demonstrated that specific miRNAs species are significantly changed in the plasma of osteoporosis and osteopenia patients and correlated with the BMD. Our study suggested a potential use of miR-21 and miR-133a as sensitive and plasma biomarkers for postmenopausal osteoporosis.

Chronic aerobic exercise training alleviates myocardial fibrosis in aged rats through restoring bioavailability of hydrogen sulfide.

PubMed

Ma, Ning; Liu, Hong-Mei; Xia, Ting; Liu, Jian-Dong; Wang, Xiao-Ze

2018-06-02

Age-related fibrosis is attenuated by aerobic exercise; however, little is known concerning the underlying molecular mechanism. To address this question, aged rats were given moderate-intensity exercise for 12 weeks. After exercise in aged rats, hydrogen sulfide (H2S) levels in plasma and heart increased 39.8% and 90.9%, respectively. Exercise upregulated expression of cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) in heart of aged rats. Furthermore, aged rats were given moderate-intensity exercise for 12 weeks or treated with NaHS (intraperitoneal injection of 0.1 ml/kg/day of 0.28 mol/l NaHS). After exercise in aged rats, Masson-trichrome staining area decreased 34.8% and myocardial hydroxyproline levels decreased 29.6%. Exercise downregulated expression of collagen-I and α-SMA in heart of aged rats. Exercise in aged rats reduced malondialdehyde levels in plasma and heart and 3-nitrotyrosine in heart. Exercise in aged rats reduced mRNA and protein expression of CHOP, GRP78, and XBP1. Exercise also reduced mRNA and protein expression of IL-6 and MCP-1 and suppressed activation of JNK in aging heart. Similar effects were demonstrated in aged rats treated with NaHS. Collectively, exercise restored bioavailability of hydrogen sulfide in the heart of aged rats, which partly explained the benefits of exercise against myocardial fibrosis of aged population.

Leukocyte telomere length is inversely associated with post-load but not with fasting plasma glucose levels.

PubMed

Khalangot, Mykola; Krasnienkov, Dmytro; Vaiserman, Alexander; Avilov, Ivan; Kovtun, Volodymir; Okhrimenko, Nadia; Koliada, Alexander; Kravchenko, Victor

2017-04-01

Type 2 diabetes mellitus is characterized by shorter leukocyte telomere length, but the relationship between leukocyte telomere length and type 2 diabetes mellitus development is rather questioned. Fasting and post-load glycaemia associated with different types of insulin resistance and their relation with leukocyte telomere length remains unknown. We compared leukocyte telomere length and fasting or post-load glucose levels in persons who do not receive glucose lowering treatment. For 82 randomly selected rural residents of Ukraine, aged 45+, not previously diagnosed with type 2 diabetes mellitus, the WHO oral glucose tolerance test and anthropometric measurements were performed. Leukocyte telomere length was measured by standardized method of quantitative monochrome multiplex polymerase chain reaction in real time. Spearman's or Pearson's rank correlation was used for correlation analysis between fasting plasma glucose or 2-h post-load plasma glucose levels and leukocyte telomere length. Logistical regression models were used to evaluate risks of finding short or long telomeres associated with fasting plasma glucose or 2-h post-load plasma glucose levels. No association of fasting plasma glucose and leukocyte telomere length was revealed, whereas 2-h post-load plasma glucose levels demonstrated a negative correlation ( P < 0.01) with leukocyte telomere length. Waist circumference and systolic blood pressure were negatively related ( P = 0.03) with leukocyte telomere length in men. Oral glucose tolerance test result-based glycemic categories did not show differences between mean leukocyte telomere length in categories of normal fasting plasma glucose and 2-h post-load plasma glucose (NGT, n = 33); diabetes mellitus (DM), n = 18 and impaired fasting glucose/tolerance (IFG/IGT, n = 31) levels. A correlation relationship between leukocyte telomere length and 2-h post-load plasma glucose level in NGT; IFG/IGT and DM groups ( P = 0.027; 0.029 and 0.049, respectively) was revealed; the association between leukocyte telomere length and fasting plasma glucose was confirmed in DM group only ( P = 0.009). Increase of 2-h post-load plasma glucose (but not fasting plasma glucose) level improves the chances of revealing short telomeres: OR 1.52 (95% CI 1.04-2.22), P = 0.03. After the adjustment for age, gender, waist circumference, systolic blood pressure, and fasting plasma glucose, these phenomena remain significant. We conclude that 2-h post-load plasma glucose but not fasting plasma glucose is inversely associated with leukocyte telomere length. Impact statement • Contradictory epidemiologic data have been obtained about the link between the leucocyte telomere length (LTL) and diabetes. Type 2 diabetes (T2D) is likely to be pathophysiologically heterogeneous, but comparison of the association of LTL separately with fasting plasma glucose (FPG) and 2-h post-load plasma glucose (2hPG) levels has not been done before. Thus, the study of LTL changes associated with different types of hyperglycaemia, that largely determine the heterogenity of T2D is important. • In a population-based study of rural Ukrainians, we were the first to demonstrate that the increase of 2hPG (but not FPG) level increases the chances of revealing short telomeres. • The obtained data can help to clarify the relationship between the LTL shortening and different conditions of the insulin resistance (mainly liver resistance in high FPG and mostly muscle and adipose tissue resistance in high 2hPG).

Apolipoprotein E in Temporal Lobe Epilepsy: A Case-Control Study

PubMed Central

Kumar, Amit; Tripathi, Manjari; Pandey, Ravindra M.; Ramakrishnan, Lakshmy; Srinivas, M.; Luthra, Kalpana

2006-01-01

Purpose: To investigate the relationship of apolipoprotein E (apoE) genotype, plasma levels of apoE and lipids in temporal lobe epilepsy (TLE) patients in Asian Indians. Status of plasma levels of Apo E in epilepsy patients has not been reported till date. Methods: ApoE gene polymorphism was analyzed in 58 patients with temporal lobe epilepsy (TLE) and 57 age and sex approximated controls using Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Levels of plasma apoE and lipids were measured using ELISA and enzymatic kits respectively. Results: The distribution of ApoE genotype in epilepsy patients and controls was comparable. Higher levels of plasma ApoE were observed in TLE patients as compared to controls (p = 0.0001). Individuals with plasma levels of apoE > 190 mg/L were at 20 times higher odds (95%CI = 2.46–163.34, p = 0.005), while those with levels of apoE between 150–190 mg/L were at 4.9 times higher odds (95% CI = 1.85–13.9, p = 0.001), to develop TLE. Conclusions: We have observed for the first time, high levels of plasma apoE in epilepsy patients. The findings of this case-control study suggest that apolipoprotein E may play an important role in epilepsy. PMID:17264404

African Ancestry Gradient Is Associated with Lower Systemic F2-Isoprostane Levels

PubMed Central

Annor, Francis; Okosun, Ike; Gower, Barbara A.

2017-01-01

Context. Low levels of systemic F2-isoprostanes (F2-IsoP) increase the risk of diabetes and weight gain and were found in African Americans. Low F2-IsoPs could reflect an unfavorable metabolic characteristic, namely, slow mitochondrial metabolism in individuals with African ancestry. Objective. To examine differences in plasma F2-IsoPs in three groups with a priori different proportion of African ancestry: non-Hispanic Whites (NHWs), US-born African Americans (AAs), and West African immigrants (WAI). Design. Cross-sectional study. Setting. Georgia residents recruited from church communities. Participants. 218 males and females 25–74 years of age, who are self-identified as NHW (n = 83), AA (n = 56), or WAI (n = 79). Main Outcome Measure(s). Plasma F2-IsoPs quantified by gas chromatography-mass spectrometry. Results. After adjustment for age, gender, obesity, and other comorbidities, WAI had lower levels of plasma F2-IsoP than AA (beta-coefficient = −9.8, p < 0.001) and AA had lower levels than NHW (beta-coefficient = −30.3, p < 0.001). Similarly, among healthy nonobese participants, F2-IsoP levels were lowest among WAI, followed by AA, and the highest levels were among NHW. Conclusion. Plasma F2-IsoPs are inversely associated with African ancestry gradient. Additional studies are required to test whether optimization of systemic F2-IsoP levels can serve as means to improve race-specific lifestyle and pharmacological intervention targeted to obesity prevention and treatment. PMID:28250893

African Ancestry Gradient Is Associated with Lower Systemic F2-Isoprostane Levels.

PubMed

Annor, Francis; Goodman, Michael; Thyagarajan, Bharat; Okosun, Ike; Doumatey, Ayo; Gower, Barbara A; Il'yasova, Dora

2017-01-01

Context . Low levels of systemic F 2 -isoprostanes (F 2 -IsoP) increase the risk of diabetes and weight gain and were found in African Americans. Low F 2 -IsoPs could reflect an unfavorable metabolic characteristic, namely, slow mitochondrial metabolism in individuals with African ancestry. Objective . To examine differences in plasma F 2 -IsoPs in three groups with a priori different proportion of African ancestry: non-Hispanic Whites (NHWs), US-born African Americans (AAs), and West African immigrants (WAI). Design . Cross-sectional study. Setting . Georgia residents recruited from church communities. Participants . 218 males and females 25-74 years of age, who are self-identified as NHW ( n = 83), AA ( n = 56), or WAI ( n = 79). Main Outcome Measure(s) . Plasma F 2 -IsoPs quantified by gas chromatography-mass spectrometry. Results . After adjustment for age, gender, obesity, and other comorbidities, WAI had lower levels of plasma F 2 -IsoP than AA (beta-coefficient = -9.8, p < 0.001) and AA had lower levels than NHW (beta-coefficient = -30.3, p < 0.001). Similarly, among healthy nonobese participants, F 2 -IsoP levels were lowest among WAI, followed by AA, and the highest levels were among NHW. Conclusion . Plasma F 2 -IsoPs are inversely associated with African ancestry gradient. Additional studies are required to test whether optimization of systemic F 2 -IsoP levels can serve as means to improve race-specific lifestyle and pharmacological intervention targeted to obesity prevention and treatment.

Copeptin Plasma Levels are Associated With Decline of Renal Function in Patients With Type 2 Diabetes Mellitus.

PubMed

Villela-Torres, Maria De La Luz; Higareda-Mendoza, Ana Edith; Gómez-García, Anel; Alvarez-Paredes, Alfonso Rafael; García-López, Elvia; Stenvikel, Peter; Gu, Harvest F; Rashid-Qureshi, Abbul; Lindholm, Bengt; Alvarez-Aguilar, Cleto

2018-04-14

Chronic kidney disease (CKD) is a leading complication of type 2 diabetes mellitus (T2DM) and is considered as a public health problem. Copeptin is a surrogate marker of arginine vasopressin (AVP) system and is proposed as a biomarker of decline renal function. Evaluate whether plasma copeptin levels may be used as a biomarker of decline renal function in patients with T2DM. A total of 480 patients with T2DM and different stages of CKD were included. Plasma levels of copeptin, cystatin-C, and other biochemical parameters were measured. The correlation between copeptin and glomerular filtration rate (GFR), estimated based on plasma cystatin-C levels, was investigated. Plasma copeptin levels were gradually increased from the stage 1-5 of CKD in the patients with T2DM. In univariate linear regression analysis, high plasma levels of copeptin were associated with lower GFR (Standardized β = -0.535, R 2  = 0.287, p <0.0001). This association remained significant even after being adjusted for glucose levels and years of T2DM diagnosis, mean blood pressure, pharmacological treatment, gender, and age. The results show that high plasma copeptin levels are associated with the decline of renal function in patients with T2DM and, therefore, copeptin may be considered as a biomarker of renal function. Further evaluation of plasma copeptin levels to predict morbidity and mortality of T2DM patients, with or without CKD, has been taken into our consideration. Copyright © 2018. Published by Elsevier Inc.

Regular Exercise and Plasma Lipid Levels Associated with the Risk of Coronary Heart Disease: A 20-Year Longitudinal Study

ERIC Educational Resources Information Center

Teramoto, Masaru; Golding, Lawrence A.

2009-01-01

We investigated the effects of regular exercise on the plasma lipid levels that contribute to coronary heart disease (CHD), of 20 sedentary men who participated in an exercise program over 20 consecutive years. The men, whose initial ages ranged from 30-51 years, participated in the University of Nevada-based exercise program for an average of 45…

Antioxidant defense and oxidative stress in children with acute hepatitis A

PubMed Central

Popovic-Dragonjic, Lidija; Jovanovic, Maja; Vrbic, Miodrag; Konstantinovic, Ljiljana; Kostic, Velimir; Dragonjic, Ivan

2011-01-01

BACKGROUND AND OBJECTIVES: Published data on oxidative stress in children with acute hepatitis A are still very scarce. This study aims to evaluate the oxidant/antioxidant status of these patients. DESIGN AND SETTING: Prospective, case-control study, over 2.5 years in patients under hospitalized and ambulatory care. PATIENTS AND METHODS: The levels of a whole-blood antioxidant, reduced glutathione; and plasma antioxidants, β-carotene, retinol, ascorbic acid, α-tocopherol; and the biomarker of oxidative stress, malondialdehyde, were evaluated in 50 pediatric patients (age range, 5-16 years; 29 males and 21 females) with acute hepatitis A and in 50 healthy children as control subjects (age range, 5-16 years; 25 males and 25 females). RESULTS: Plasma levels of reduced glutathione, β-carotene, retinol, α-tocopherol and ascorbic acid were significantly lower, while malondialdehyde plasma levels were significantly increased in the patient group when compared to the controls (P<.0001 for all parameters). CONCLUSIONS: Our findings show that pediatric patients with acute hepatitis A were influenced by oxidative stress, resulting in significantly lower levels of plasma antioxidants and increased lipid peroxidation. In the absence of other therapeutic options, antioxidant vitamin supplements could be added to the therapy for these patients to help reestablish the oxidant status balance. Further investigations to confirm this suggestion are recommended. PMID:21623054

Serum uric acid is not independently associated with plasma renin activity and plasma aldosterone in hypertensive adults.

PubMed

Mulè, G; Castiglia, A; Morreale, M; Geraci, G; Cusumano, C; Guarino, L; Altieri, D; Panzica, M; Vaccaro, F; Cottone, S

2017-04-01

In experimental investigations conducted in rats, raising serum uric acid (SUA) levels resulted in the stimulation of intrarenal renin expression. Studies in humans exploring the association of SUA with plasma renin activity (PRA) yielded conflicting results. Moreover, little is known about the relationship of SUA with plasma aldosterone concentration (PAC). The study aimed to assess the relationship between SUA levels, PRA, and PAC and the influence of age, gender, body mass index (BMI), and hyperuricemia on these relationships in subjects with essential hypertension (EH). We enrolled 372 hypertensive patients (mean age 45 ± 12 years, men 67%) with uncomplicated EH that was not pharmacologically treated. The study population was divided in tertiles according to SUA levels. While PRA did not differ significantly across the three tertiles, PAC was higher in subjects belonging to the uppermost tertile of SUA than those in the lower ones (p = 0.0429); however, this difference lost statistical significance after adjustment for age, sex, BMI, and serum creatinine. Univariate correlation analyses showed significant associations of SUA with PRA (r = 0.137; p = 0.008) and PAC (r = 0.179; p < 0.001). However, these relationships were not significant after correcting for confounding factors in multiple linear regression analyses. We did not observe statistically significant effect modification by gender, age, BMI, and hyperuricemia. SUA levels are weakly associated with PRA and PAC in adults with untreated EH. These relationships were lost after adjustment for age, sex, BMI, and serum creatinine. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania.

PubMed

Barbosa, Izabela G; Morato, Isabela B; Huguet, Rodrigo B; Rocha, Fabio L; Machado-Vieira, Rodrigo; Teixeira, Antônio L

2014-01-01

To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5, in bipolar disorder (BD). Forty patients with type I BD (18 in remission and 22 in mania) and 25 healthy controls matched for age, gender, and educational attainment were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview; the Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked immunosorbent assay (ELISA). BD patients in mania presented decreased NT-4/5 plasma levels in comparison with controls (p < 0.05). There were no significant differences in NT-3 plasma levels between BD patients and controls. These findings corroborate the view that neurotrophin dysfunction is associated with mood states in patients with BD.

T Cell Activation in South African HIV-Exposed Infants Correlates with Ochratoxin A Exposure

PubMed Central

Wood, Lianna Frances; Wood, Matthew P.; Fisher, Bridget S.; Jaspan, Heather B.; Sodora, Donald L.

2017-01-01

The introduction of non-breastmilk foods to HIV-infected infants is associated with increased levels of immune activation, which can impact the rate of HIV disease progression. This is particularly relevant in countries where mother-to-child transmission of HIV still occurs at unacceptable levels. The goal of this study was to evaluate the levels of the toxic food contaminant ochratoxin A (OTA) in HIV-exposed South African infants that are either breastfed or consuming non-breast milk foods. OTA is a common mycotoxin, found in grains and soil, which is toxic at high doses but has immunomodulatory properties at lower doses. Samples from HIV-exposed and HIV-unexposed infants enrolled in prospective observational cohort studies were collected and analyzed at birth through 14 weeks of age. We observed that infants consuming non-breast milk foods had significantly higher plasma levels of OTA at 6 weeks of age compared to breastfed infants, increasing until 8 weeks of age. The blood levels of OTA detected were comparable to levels observed in OTA-endemic communities. OTA plasma levels correlated with HIV target cell activation (CCR5 and HLADR expression on CD4+ T cells) and plasma levels of the inflammatory cytokine CXCL10. These findings provide evidence that elevated OTA levels in South African infants are associated with the consumption of non-breastmilk foods and activation of the immune system. Reducing infant OTA exposure has the potential to reduce immune activation and provide health benefits, particularly in those infants who are HIV-exposed or HIV-infected. PMID:29312338

Brain-derived neurotrophic factor Val66met polymorphism and plasma levels in road traffic accident survivors.

PubMed

van den Heuvel, Leigh; Suliman, Sharain; Malan-Müller, Stefanie; Hemmings, Sian; Seedat, Soraya

2016-11-01

Alterations in brain-derived neurotrophic factor (BDNF) expression and release may play a role in the pathogenesis of post-traumatic stress disorder (PTSD). This study evaluated road traffic accident (RTA) survivors to determine whether PTSD and trauma-related factors were associated with plasma BDNF levels and BDNF Val66Met carrier status following RTA exposure. One hundred and twenty-three RTA survivors (mean age 33.2 years, SD = 10.6 years; 56.9% male) were assessed 10 (SD = 4.9) days after RTA exposure. Acute stress disorder (ASD), as assessed with the Acute Stress Disorder Scale, was present in 50 (42.0%) of the participants. Plasma BDNF levels were measured with enzyme-linked immunosorbent assay and BDNF Val66Met genotyping was performed. PTSD, as assessed with the Clinician-Administered PTSD Scale, was present in 10 (10.8%) participants at 6 months follow-up. Neither BDNF Val66Met genotype nor plasma BDNF was significantly associated with the presence or severity of ASD or PTSD. Plasma BDNF levels were, however, significantly correlated with the lifetime number of trauma exposures. In RTA survivors, plasma BDNF levels increased with increasing number of prior trauma exposures. Plasma BDNF may, therefore, be a marker of trauma load.

The effect of low and high plasma levels of insulin-like growth factor-1 (IGF-1) on the morphology of major organs: studies of Laron dwarf and bovine growth hormone transgenic (bGHTg) mice

PubMed Central

Piotrowska, Katarzyna; Borkowska, Sylwia J.; Wiszniewska, Barbara; Laszczyńska, Maria; Słuczanowska-Głąbowska, Sylwia; Havens, Aaron M.; Kopchick, John J.; Bartke, Andrzej; Taichman, Russel S.; Kucia, Magda; Ratajczak, Mariusz Z.

2014-01-01

Summary It is well known that somatotrophic/insulin signaling affects lifespan in experimental animals. To study the effects of insulin-like growth factor-1 (IGF-1) plasma level on the morphology of major organs, we analyzed lung, heart, liver, kidney, bone marrow, and spleen isolated from 2-year-old growth hormone receptor knockout (GHR-KO) Laron dwarf mice (with low circulating plasma levels of IGF-1) and 6-month-old bovine growth hormone transgenic (bGHTg) mice (with high circulating plasma levels of IGF-1). The ages of the two mutant strains employed in our studies were selected based on their overall ~50% survival (Laron dwarf mice live up to ~4 years and bGHTg mice up to ~1 year). Morphological analysis of the organs of long-living 2-year-old Laron dwarf mice revealed a lower biological age for their organs compared with normal littermates, with more brown adipose tissue (BAT) surrounding the main body organs, lower levels of steatosis in liver, and a lower incidence of leukocyte infiltration in different organs. By contrast, the organs of 6-month-old, short-living bGHTg mice displayed several abnormalities in liver and kidney and a reduced content of BAT around vital organs. PMID:23613169

Whole exome sequence-based association analyses of plasma amyloid-β in African and European Americans; the Atherosclerosis Risk in Communities-Neurocognitive Study.

PubMed

Simino, Jeannette; Wang, Zhiying; Bressler, Jan; Chouraki, Vincent; Yang, Qiong; Younkin, Steven G; Seshadri, Sudha; Fornage, Myriam; Boerwinkle, Eric; Mosley, Thomas H

2017-01-01

We performed single-variant and gene-based association analyses of plasma amyloid-β (aβ) concentrations using whole exome sequence from 1,414 African and European Americans. Our goal was to identify genes that influence plasma aβ42 concentrations and aβ42:aβ40 ratios in late middle age (mean = 59 years), old age (mean = 77 years), or change over time (mean = 18 years). Plasma aβ measures were linearly regressed onto age, gender, APOE ε4 carrier status, and time elapsed between visits (fold-changes only) separately by race. Following inverse normal transformation of the residuals, seqMeta was used to conduct race-specific single-variant and gene-based association tests while adjusting for population structure. Linear regression models were fit on autosomal variants with minor allele frequencies (MAF)≥1%. T5 burden and Sequence Kernel Association (SKAT) gene-based tests assessed functional variants with MAF≤5%. Cross-race fixed effects meta-analyses were Bonferroni-corrected for the number of variants or genes tested. Seven genes were associated with aβ in late middle age or change over time; no associations were identified in old age. Single variants in KLKB1 (rs3733402; p = 4.33x10-10) and F12 (rs1801020; p = 3.89x10-8) were significantly associated with midlife aβ42 levels through cross-race meta-analysis; the KLKB1 variant replicated internally using 1,014 additional participants with exome chip. ITPRIP, PLIN2, and TSPAN18 were associated with the midlife aβ42:aβ40 ratio via the T5 test; TSPAN18 was significant via the cross-race meta-analysis, whereas ITPRIP and PLIN2 were European American-specific. NCOA1 and NT5C3B were associated with the midlife aβ42:aβ40 ratio and the fold-change in aβ42, respectively, via SKAT in African Americans. No associations replicated externally (N = 725). We discovered age-dependent genetic effects, established associations between vascular-related genes (KLKB1, F12, PLIN2) and midlife plasma aβ levels, and identified a plausible Alzheimer's Disease candidate gene (ITPRIP) influencing cell death. Plasma aβ concentrations may have dynamic biological determinants across the lifespan; plasma aβ study designs or analyses must consider age.

Plasma apelin levels, blood pressure and cardiovascular risk factors in a coastal Chinese population.

PubMed

Zhu, Pengli; Huang, Feng; Lin, Fan; Yuan, Yin; Chen, Falin; Li, Qiaowei

2013-11-01

To describe the relationship of plasma apelin levels with blood pressure in a coastal Chinese population. This cross-sectional study included a total of 1031 subjects from the coastal areas of China. One-way analysis of variance (ANOVA) and linear trend test, Pearson's correlation analysis, as well as multivariate linear regression analysis were used to evaluate the association between plasma apelin levels and blood pressure. Plasma apelin levels dropped with increasing quartiles of systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) (all P<0.001). SBP, DBP, and MABP values decreased as the apelin levels increased within the quartiles. After adjusting for age and gender, the significant differences in SBP, DBP, and MABP between the groups within the apelin quartiles remained (all P<0.05). A significant negative correlation between SBP, DBP, as well as MABP and apelin levels was observed (all P<0.01); even after adjusting for cardiovascular confounding factors, this negative correlation remained (all P<0.001). A negative correlation between plasma apelin levels and blood pressure was found in this 1000-population-based epidemiological study. Apelin may become a potential therapeutic target of anti-hypertensive treatment.

[Plasma cardiac natriuretic peptide as a biological marker of recurrence of atrial fibrillation in elderly people].

PubMed

Mabuchi, N; Tsutamoto, T; Maeda, K; Masahiko, K

2000-07-01

We designed this study to evaluate the relationship between plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels and recurrence of atrial fibrillation (AF) after direct current cardioversion (DC) and the differences with aging. Fifty patients with mild congestive heart failure (CHF) undergoing elective DC of AF were included in this study (New York Heart Association (NYHA) functional class II: n = 42, III = 8). Patients who failed to show restoration of sinus rhythm or those with mitral valve stenosis were excluded. Before successful DC, we measured plasma levels of ANP and BNP and evaluated left atrial dimension (LAD), left ventricular end-diastolic dimension (LVDd), and left ventricular ejection fraction (EF) by echocardiography. Twenty-one patients had recurrence of AF within 2 months after DC (average 9.05 days). We followed up the other 29 patients for 580.5 days. By Cox stepwise multivariate analysis, history of AF (p = 0.007), low plasma levels of ANP (p = 0.003), and high plasma levels of BNP (p = 0.0003) were found to be independent predictors of recurrent AF. High plasma BNP levels indicating ventricular dysfunction and low plasma ANP levels may be due to atrial histological change such as fibrosis. In these patients, plasma ratios of ANP and BNP (ANP/BNP) less than 0.43 were predictive factors for AF recurrence (sensitivity 70%, specificity 62%), especially in patients who were older than 70 years (sensitivity 100%, specificity 80%). Relatively low plasma ANP level compared to BNP is an independent risk factor of AF recurrence in patients with CHF, especially in elderly patients, suggesting that plasma cardiac natriuretic peptides are important biochemical markers of AF recurrence in elderly patients with CHF.

Dynamic changes in plasma total and high molecular weight adiponectin levels in acute heart failure.

PubMed

Ohara, Takahiro; Hashimura, Kazuhiko; Asakura, Masanori; Ogai, Akiko; Amaki, Makoto; Hasegawa, Takuya; Kanzaki, Hideaki; Sonoda, Mina; Nishizawa, Hitoshi; Funahashi, Tohru; Kitakaze, Masafumi

2011-09-01

Elevated levels of total plasma adiponectin (APN) and high molecular weight (HMW)-APN have been observed in chronic heart failure (HF) and are associated with poor prognosis, however, the response of APN levels in acute HF is not known. The purpose of this study was to clarify the dynamic changes of the plasma total APN, HMW-APN levels, and the ratio of HMW-APN to total APN (HMWR) in acute HF. From February 2006 to January 2007, 20 patients with acute HF (non-ischemic and non-valvular origin, 17 men, aged 63±11 years) were enrolled, and blood was sampled before the onset of the treatment and at discharge. Ten patients admitted for the treatment of supraventricular arrhythmia (8 men, aged 45±13 years) were included as controls. The medians and interquartile ranges of the plasma total APN, HMW-APN levels, and HMWR at admission were 20.8 (14.5-38.9) μg/mL, 12.4 (7.7-23.3) μg/mL, and 0.60 (0.50-0.69), respectively. The total APN and HMW-APN values were significantly higher than the values of the control. The plasma total APN, HMW-APN, and HMWR values at discharge decreased to 19.4 (7.2-27.3)μg/mL, 10.5 (3.2-12.8) μg/mL, and 0.52 (0.46-0.57), respectively. An exploratory survival analysis showed that the higher HMWR values at admission and the larger decrease in HMWR were associated with a better prognosis after discharge. Plasma total APN and HMW-APN values are elevated at the admission for acute HF. Plasma total APN, HMW-APN, and HMWR values decrease following treatment. Higher HMWR at admission and its larger decrease may be the signs of favorable treatment responsiveness in acute HF. Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Plasma copeptin as a predictor of intoxication severity and delayed neurological sequelae in acute carbon monoxide poisoning.

PubMed

Pang, Li; Wang, He-Lei; Wang, Zhi-Hao; Wu, Yang; Dong, Ning; Xu, Da-Hai; Wang, Da-Wei; Xu, Hong; Zhang, Nan

2014-09-01

The present study was designed to assess the usefulness of measuring plasma levels of copeptin (a peptide co-released with the hypothalamic stress hormone vasopressin) as a biomarker for the severity of carbon monoxide (CO) poisoning and for predicting delayed neurological sequelae (DNS). Seventy-two patients with CO poisoning and 72 sex and age matched healthy individuals were recruited. Plasma copeptin levels were measured on admission from CO poisoning patients and for healthy individuals at study entry by using a sandwich immunoassay. The CO poisoning patients were divided into two groups according to severity (unconscious and conscious) and occurrence of DNS. The mean plasma copeptin levels (52.5±18.5 pmol/L) in the unconscious group were significantly higher than in the conscious group (26.3±12.7 pmol/L) (P<0.001). Plasma copeptin levels of more than 39.0 pmol/L detected CO poisoning with severe neurological symptoms e.g. unconsciousness (sensitivity 84.6% and specificity 81.4%). The plasma copeptin levels were higher in patients with DNS compared to patients without DNS (52.2±20.6 pmol/L vs. 27.9±14.8 pmol/L, P<0.001). Plasma copeptin levels higher than 40.5 pmol/L predicted the development of DNS (sensitivity 77.8%, specificity 82.1%). Plasma copeptin levels were identified as an independent predictor for intoxication severity [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112-1.638, P=0.002] and DNS (OR 1.313, 95% CI 1.106-1.859, P=0.001). Thus, plasma copeptin levels independently related to intoxication severity and were identified as a novel biomarker for predicting DNS after acute CO poisoning. Copyright © 2014 Elsevier Inc. All rights reserved.

Polymorphisms in genes involved in the triglyceride synthesis pathway and marine omega-3 polyunsaturated fatty acid supplementation modulate plasma triglyceride levels.

PubMed

Ouellette, Catherine; Cormier, Hubert; Rudkowska, Iwona; Guénard, Frédéric; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2013-01-01

Marine omega-3 (n-3) polyunsaturated fatty acids (PUFA) reduce plasma triglyceride (TG) levels. Genetic factors such as single nucleotide polymorphisms (SNPs) could be responsible for the variability of the plasma TG response to n-3 PUFA supplementation. Previous studies have demonstrated that n-3 PUFA supplementation using fish oil modified the expression levels of three genes involved in the TG synthesis pathway (GPAM, AGPAT3 and AGPAT4) in peripheral blood mononuclear cells. A total of 210 subjects consumed 5 g/day of a fish oil supplement for 6 weeks. Plasma lipids were measured before and after the supplementation period. Three SNPs in GPAM, 13 SNPs in AGPAT3 and 35 SNPs in AGPAT4 were genotyped. In an ANOVA for repeated measures adjusted for age, sex and BMI, genotype effects on plasma TG levels were observed for rs1838452 in AGPAT3 as well as for rs746731 and rs2293286 in AGPAT4. Genotype × supplementation interaction effects on plasma TG levels were observed for rs2792751 and rs17129561 in GPAM as well as for rs3798943 and rs9458172 in AGPAT4 (p < 0.05). These results suggest that SNPs in genes involved in the TG synthesis pathway may influence plasma TG levels after n-3 PUFA supplementation. © 2014 S. Karger AG, Basel.

Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes.

PubMed

Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

2016-04-29

Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Plasma catalase activity and malondialdehyde level in patients with cataract.

PubMed

Ateş, N A; Yildirim, O; Tamer, L; Unlü, A; Ercan, B; Muşlu, N; Kanik, A; Hatungil, R; Atik, U

2004-08-01

Oxidative mechanisms play a major role in the aetiology and pathogenesis of cataract, especially in age-related cataract. Our study aims to investigate systemic oxidant and antioxidant markers in cataract patients. The activity of erythrocyte catalase and the level of malondialdehyde in plasma were measured in 40 patients with cataract and 60 healthy control subjects. The malondialdehyde level, as an index of lipid peroxidation, was determined by thiobarbitüric acid reaction according to Yagi. The determination of catalase activity was measured by a method that was defined by Beutler. Catalase enzyme activity and malondialdehyde level were evaluated to find out whether there was a significant difference in these variables. Analysis of variance was used by forming a general linear model that takes age and gender as the covariate. CAT activity was found to be 13 920.2 +/- 847.9 U/l in cataract patients and 16 061.3 +/- 1126.6 U/l in control subjects. CAT activity in cataract patients was significantly lower than the control subjects (P = 0.008). Plasma MDA level is significantly higher in patients with cataract 4.47 +/- 0.35 nmol/ml compared to the control subjects 2.94 +/- 0.26 nmol/ml (P = 0.0001). There was no significant difference between different cataract subgroups when erythrocyte CAT activities and plasma MDA levels were compared (P = 0.322, 0.062). This study shows that oxidant/antioxidant balances alter in the presence of cataract.

Proximity to a Major Road and Plasma Cytokines in School-Aged Children

PubMed Central

Rosser, Franziska; Forno, Erick; Brehm, John; Han, Yueh-Ying; Boutaoui, Nadia; Colón-Semidey, Angel; Alvarez, María; Acosta-Pérez, Edna; Kurland, Kristen S.; Alcorn, John F.; Canino, Glorisa

2016-01-01

Traffic-related air pollution (TRAP) may affect immune responses, including those in the TH2 and TH17 pathways. To examine whether TRAP is associated with plasma level of TH17-, TH1-, and TH2-related cytokines in children with and without asthma, a cross-sectional study of 577 children (ages 6–14 years) with (n = 294) and without (n = 283) asthma in San Juan (Puerto Rico) was performed. Residential distance to a major road was estimated using geocoded home addresses for study participants. A panel of 14 cytokines, enriched for the TH17 pathway, was measured in plasma. Asthma was defined as physician-diagnosed asthma and current wheeze. Multivariable linear regression was used to examine the association of residential distance to a major road (a marker of TRAP), asthma, and cytokine levels. Among all participating children, residential proximity to a major road was significantly associated with increased plasma level of IL-31, even after adjustment for relevant covariates and correction for multiple testing. The presence of asthma modified the estimated effect of the residential distance to a major road on plasma TNF-α (P for interaction = 0.00047). Although living farther from a major road was significantly associated with lower TNF-α level in control subjects, no such decrease was seen in children with asthma. In a direct comparison of cases and control subjects, children with asthma had significantly higher levels of IL-1β, IL-22, and IL-33 than control subjects. TRAP is associated with increased levels of proinflammatory cytokines among Puerto Rican children, who belong to an ethnic group with high risk for asthma. PMID:28265480

Proximity to a Major Road and Plasma Cytokines in School-Aged Children.

PubMed

Rosser, Franziska; Forno, Erick; Brehm, John; Han, Yueh-Ying; Boutaoui, Nadia; Colón-Semidey, Angel; Alvarez, María; Acosta-Pérez, Edna; Kurland, Kristen S; Alcorn, John F; Canino, Glorisa; Celedón, Juan C

2016-09-01

Traffic-related air pollution (TRAP) may affect immune responses, including those in the T H 2 and T H 17 pathways. To examine whether TRAP is associated with plasma level of T H 17-, T H 1-, and T H 2-related cytokines in children with and without asthma, a cross-sectional study of 577 children (ages 6-14 years) with ( n  = 294) and without ( n  = 283) asthma in San Juan (Puerto Rico) was performed. Residential distance to a major road was estimated using geocoded home addresses for study participants. A panel of 14 cytokines, enriched for the T H 17 pathway, was measured in plasma. Asthma was defined as physician-diagnosed asthma and current wheeze. Multivariable linear regression was used to examine the association of residential distance to a major road (a marker of TRAP), asthma, and cytokine levels. Among all participating children, residential proximity to a major road was significantly associated with increased plasma level of IL-31, even after adjustment for relevant covariates and correction for multiple testing. The presence of asthma modified the estimated effect of the residential distance to a major road on plasma TNF-α ( P for interaction = 0.00047). Although living farther from a major road was significantly associated with lower TNF-α level in control subjects, no such decrease was seen in children with asthma. In a direct comparison of cases and control subjects, children with asthma had significantly higher levels of IL-1β, IL-22, and IL-33 than control subjects. TRAP is associated with increased levels of proinflammatory cytokines among Puerto Rican children, who belong to an ethnic group with high risk for asthma.

Age-Dependent Changes in Resting Energy Expenditure (REE): Insights from Detailed Body Composition Analysis in Normal and Overweight Healthy Caucasians

PubMed Central

Geisler, Corinna; Braun, Wiebke; Pourhassan, Maryam; Schweitzer, Lisa; Glüer, Claus-Christian; Bosy-Westphal, Anja; Müller, Manfred J.

2016-01-01

Age-related changes in organ and tissue masses may add to changes in the relationship between resting energy expenditure (REE) and fat free mass (FFM) in normal and overweight healthy Caucasians. Secondary analysis using cross-sectional data of 714 healthy normal and overweight Caucasian subjects (age 18–83 years) with comprehensive information on FFM, organ and tissue masses (as assessed by magnetic resonance imaging (MRI)), body density (as assessed by Air Displacement Plethysmography (ADP)) and hydration (as assessed by deuterium dilution (D2O)) and REE (as assessed by indirect calorimetry). High metabolic rate organs (HMR) summarized brain, heart, liver and kidney masses. Ratios of HMR organs and muscle mass (MM) in relation to FFM were considered. REE was calculated (REEc) using organ and tissue masses times their specific metabolic rates. REE, FFM, specific metabolic rates, the REE-FFM relationship, HOMA, CRP, and thyroid hormone levels change with age. The age-related decrease in FFM explained 59.7% of decreases in REE. Mean residuals of the REE-FFM association were positive in young adults but became negative in older subjects. When compared to young adults, proportions of MM to FFM decreased with age, whereas contributions of liver and heart did not differ between age groups. HOMA, TSH and inflammation (plasma CRP-levels) explained 4.2%, 2.0% and 1.4% of the variance in the REE-FFM residuals, but age and plasma T3-levels had no effects. HMR to FFM and MM to FFM ratios together added 11.8% on to the variance of REE-FFM residuals. Differences between REE and REEc increased with age, suggesting age-related changes in specific metabolic rates of organs and tissues. This bias was partly explained by plasmaT3-levels. Age-related changes in REE are explained by (i) decreases in fat free mass; (ii) a decrease in the contributions of organ and muscle masses to FFM; and (iii) decreases in specific organ and tissue metabolic rates. Age-dependent changes in the REE-FFMassociation are explained by composition of FFM, inflammation and thyroid hormones. PMID:27258302

Age-Dependent Changes in Resting Energy Expenditure (REE): Insights from Detailed Body Composition Analysis in Normal and Overweight Healthy Caucasians.

PubMed

Geisler, Corinna; Braun, Wiebke; Pourhassan, Maryam; Schweitzer, Lisa; Glüer, Claus-Christian; Bosy-Westphal, Anja; Müller, Manfred J

2016-06-01

Age-related changes in organ and tissue masses may add to changes in the relationship between resting energy expenditure (REE) and fat free mass (FFM) in normal and overweight healthy Caucasians. Secondary analysis using cross-sectional data of 714 healthy normal and overweight Caucasian subjects (age 18-83 years) with comprehensive information on FFM, organ and tissue masses (as assessed by magnetic resonance imaging (MRI)), body density (as assessed by Air Displacement Plethysmography (ADP)) and hydration (as assessed by deuterium dilution (D₂O)) and REE (as assessed by indirect calorimetry). High metabolic rate organs (HMR) summarized brain, heart, liver and kidney masses. Ratios of HMR organs and muscle mass (MM) in relation to FFM were considered. REE was calculated (REEc) using organ and tissue masses times their specific metabolic rates. REE, FFM, specific metabolic rates, the REE-FFM relationship, HOMA, CRP, and thyroid hormone levels change with age. The age-related decrease in FFM explained 59.7% of decreases in REE. Mean residuals of the REE-FFM association were positive in young adults but became negative in older subjects. When compared to young adults, proportions of MM to FFM decreased with age, whereas contributions of liver and heart did not differ between age groups. HOMA, TSH and inflammation (plasma CRP-levels) explained 4.2%, 2.0% and 1.4% of the variance in the REE-FFM residuals, but age and plasma T3-levels had no effects. HMR to FFM and MM to FFM ratios together added 11.8% on to the variance of REE-FFM residuals. Differences between REE and REEc increased with age, suggesting age-related changes in specific metabolic rates of organs and tissues. This bias was partly explained by plasmaT3-levels. Age-related changes in REE are explained by (i) decreases in fat free mass; (ii) a decrease in the contributions of organ and muscle masses to FFM; and (iii) decreases in specific organ and tissue metabolic rates. Age-dependent changes in the REE-FFMassociation are explained by composition of FFM, inflammation and thyroid hormones.

The influence of biological and environmental factors on metallothionein concentration in the blood.

PubMed

Kowalska, Katarzyna; Bizoń, Anna; Zalewska, Marta; Milnerowicz, Halina

2015-01-01

The concentration of metallothionein (MT), a low-molecular-weight protein, is regulated by many factors, primarily metals (zinc, cadmium, copper), cytokines, glucocorticoides and free radicals. These factors are determined by such aspects of human biology as gender, pregnancy and age, as well as by environmental factors including the use of oral contraceptives and cigarette smoking, all which may affect MT levels in the body. The aim of this study was to investigate the influence of these biological and environmental factors on MT concentrations in erythrocyte lysate and in plasma. MT concentrations were determined by a two-step direct enzyme-linked immunosorbent assay. Evaluation of exposure to cigarette smoking was performed by checking cotinine levels in the plasma of subjects. The studies showed higher MT concentrations in both the erythrocyte lysate and plasma of women when compared to men. Furthermore, pregnancy causes an increase of MT concentration in plasma, while oral contraceptives cause an elevated concentration of MT in erythrocyte lysate. Age impacts plasma MT concentrations in men, whereas it does not affect concentrations of MT in erythrocyte lysate. Copyright © 2014 Elsevier GmbH. All rights reserved.

Generation of Rabbit Monoclonal Antibody to Amyloid-β38 (Aβ38): Increased Plasma Aβ38 Levels in Down Syndrome.

PubMed

Mehta, Pankaj D; Patrick, Bruce A; Barshatzky, Marc; Mehta, Sangita P; Frackowiak, Janusz; Mazur-Kolecka, Bozena; Miller, David L

2015-01-01

Secreted soluble amyloid-β (Aβ)38 is the second most prominent Aβ form next to Aβ40, and is found in cerebrospinal fluid (CSF) and blood. Recent studies have shown the importance of quantitation of CSF Aβ38 levels in combination with those of Aβ40 and Aβ42 to support the diagnosis of Alzheimer's disease (AD), and other neurodegenerative diseases, and to facilitate drug discovery studies. However, the availability of reliable and specific Aβ38 monoclonal antibody is limited. Our first aim was to generate and partially characterize rabbit monoclonal antibody (RabmAb) to Aβ38. The antibody was specific to Aβ38, since it did not react with Aβ37, Aβ39, Aβ40, or Aβ42 in ELISA or immunoblotting. The antibody was sensitive enough to measure Aβ38 levels in plasma. Our second aim was to quantitate Aβ38 levels in plasma from older Down syndrome (DS) persons and age-matched controls. Persons with DS (35 years and older) have neuropathological changes characteristic of AD. Studies have shown that plasma Aβ40 and Aβ42 levels are higher in older persons with DS than in controls. However, none examined Aβ38 levels in DS. Our quantitation data showed that, like Aβ40 and Aβ42 plasma levels, Aβ38 plasma levels were higher in DS than in controls. Longitudinal studies will determine whether plasma Aβ38 levels in combination with levels of Aβ40 and Aβ42 are useful to predict early signs of AD in DS.

Low Circulating Adropin Concentrations with Obesity and Aging Correlate with Risk Factors for Metabolic Disease and Increase after Gastric Bypass Surgery in Humans

PubMed Central

Tam, Charmaine S.; Stanhope, Kimber L.; Wolfe, Bruce M.; Ali, Mohamed R.; O'Keeffe, Majella; St-Onge, Marie-Pierre; Ravussin, Eric

2012-01-01

Context: Mouse studies suggest that adropin, a peptide hormone, is required for metabolic homeostasis and prevention of obesity-associated insulin resistance. Whether obesity and insulin resistance are associated with low plasma adropin levels in humans is not known. Objectives: Our objective was to investigate the hypothesis that obesity and indicators of insulin resistance are associated with low adropin levels and determine whether weight loss regulates adropin levels. Design and Participants: Plasma was obtained from 85 female [age 21–67 yr, body mass index (BMI) 19.4–71.5 kg/m2] and 45 male (age 18–70 yr, BMI 19.1–62.6 kg/m2) volunteers for other clinical studies. The impact of Roux-en-Y gastric bypass was investigated in 19 obese females (BMI 37–65 kg/m2) using samples collected at baseline and 1–12 months after surgery. Results: Adropin levels correlate negatively with BMI (r = −0.335, P < 0.001) and age (r = −0.263, P=0.003). Age-adjusted adropin levels are higher in males [4.1 ng/ml; 95% confidence interval (CI) = 3.6–4.6 ng/ml] than females (3.0 ng/ml; 95% CI = 2.6–3.4 ng/ml) (P = 0.001). In all subjects, lower age-adjusted adropin levels were observed in overweight (3.3 ng/ml; 95% CI = 2.8–3.8 ng/ml, P = 0.033) and obese (2.7 ng/ml; 95% CI = 2.1–3.3 ng/ml, P = 0.001) compared with healthy-weight subjects (4.1 ng/ml; 95% CI = 3.6–4.5 ng/ml). This effect was gender specific (weight category × gender, P < 0.001) and was observed in males only. Aging and diagnosis with two or more metabolic syndrome risk factors was associated with low adropin levels, irrespective of sex. Adropin concentrations increased after Roux-en-Y gastric bypass, peaking 3 months after surgery (P < 0.01). Conclusions: Although males exhibit higher adropin levels that are reduced by obesity, aging and markers of insulin resistance are associated with low plasma adropin irrespective of sex. PMID:22872690

Predicting normal tissue radiosensitivity

NASA Astrophysics Data System (ADS)

Dickson, Jeanette

Two methods of predicting normal cell radiosensitivity were investigated in different patient groups. Plasma transforming growth factor beta one (TGFbeta1) levels were measured by ELISA, using a commercially available kit. Residual DNA double strand breaks were measured in normal epidermal fibroblasts following 150 Gy. After allowing 24 hours for repair, the DNA damage was assayed using pulsed field gel electrophoresis (PFGE). Pretreatment plasma TGFbeta1 levels were investigated retrospectively in patients with carcinoma of the cervix in relation to tumour control and late morbidity following radiotherapy. Plasma TGFbeta1 levels increased with increasing disease stage. They also correlated with two other known measures of tumour burden i.e. plasma levels of carcinoma antigen 125 (CA125) and tissue polypeptide antigen (TPA). Elevated pretreatment plasma TGFbeta1 levels predicted for a poor outcome both in terms of local control and overall survival. Plasma TGF?l levels did not predict for the development of radiotherapy morbidity of any grade. In conclusion pre-treatment plasma TGFbeta1 levels predict for tumour burden and tumour outcome in patients with carcinoma of the cervix. Changes in plasma TGFbeta1 levels measured prospectively may predict for radiation morbidity and should be investigated. A prospective study was undertaken in patients with carcinoma of the head and neck region. Changes in plasma TGFbeta1 levels between the start and the end of a course of radical radiotherapy were investigated in relation to the development of acute radiation toxicity. Patients were categorised according to the pattern of response of their TGFbeta1 levels over the course of their treatment. Those patients whose TGFbeta1 levels decreased, but did not normalise during radiotherapy were assigned to category 2. Category 2 predicted for a severe acute reaction, as measured using the LENT SOMA score, with a sensitivity of 33% and a specificity of 100%. The positive predictive value of was 100%. As part of the validation of the commercially available TGFbeta1 kit, samples were obtained from sixty-six normal volunteers with a wide age distribution. This large series demonstrated an unexpected age-related rise in TGFbeta1 levels that had not been previously demonstrated in the literature. In breast carcinoma patients, two assays were performed retrospectively. Both pre-treatment plasma TGFbeta1 levels and residual DNA double strand breaks (measured using PFGE) were correlated with clinical outcome. Outcome was in the form of a total LENT SOMA score and late radiation fibrosis score, as measured by clinical palpation. No relationship was demonstrated between either pretreatment TGFbeta1 levels or residual DNA double strand breaks and late radiotherapy outcome. This failed to validate a similar series of patients investigated in the same department using the same technique. This work has shown that measurement of residual DNA double strand breaks using PFGE is not sufficiently robust to be used clinically as a predictor of normal tissue radioresponse. In conclusion, changes in TGFbeta1 plasma levels occurring over time during a course of radical radiotherapy, hold promise for the development of a rapid test of intrinsic radiosensitivity.

Plasma chemistry in booted eagle (Hieraaetus pennatus) during breeding season.

PubMed

Casado, Eva; Balbontin, Javier; Ferrer, Miguel

2002-02-01

Most studies that have examined raptor plasma chemistry have been conducted on birds living in captivity. In this study, we describe typical plasma chemistry values indicators of body condition in free-living Booted Eagles, Hieraaetus pennatus, from Doñana National Park (Spain). Values are compared with those of other raptors. Mean concentrations of creatinine, uric acid and urea were lower in adults than in nestlings, while glucose, DAT and AAT were lower in nestlings than in adults. Interactions of age/sex affected plasma mean levels of creatine kinase, glucose, AAT, uric acid and urea. Adult females showed significantly lower levels of creatine kinase, uric acid and urea than adult males and nestlings. Adult males had significantly higher levels of AAT than the other groups. The lowest levels of glucose and the highest levels of uric acid were found in nestling females. We think the differences in blood parameters can be explained by differences in size of species, of individuals (because of both body condition and sexual dimorphism) and diet.

Estimation of plasma lipids and its significance on histopathological grades in oral cancer: Prognostic significance an original research.

PubMed

Sherubin, Eugenia J; Kannan, Karthiga S; Kumar, Dhineksh N; Joseph, Isaac

2013-01-01

Alterations in the lipid profile have long been associated with various cancers because lipids play a key role in maintenance of cell integrity. This study was to estimate the plasma lipid levels in patients with oral cancer and to correlate the values with the histopathological grades. The study group included 50 patients with oral cancer aged between 20 and 60 years who had visited the Department of Oral Medicine and Radiology during the period of September 2005 to July 2007. After the histotopathological confirmation, their plasma lipid levels were estimated using auto analyzer and the data was statistically analyzed. The study revealed a significant decrease in the total plasma lipid levels in patients with oral cancer in comparison with the standard values. Comparing the plasma lipid levels with the histopathological grades, we observed a significant variation in the levels of total cholesterol, very low density lipoprotein, low-density lipoprotein, high-density lipoprotein and triglycerides. The variation in the levels of plasma cholesterol and other lipid constituents in patients with cancer might be due to their increased utilization by neoplastic cells for new membrane biosynthesis. This study was an attempt to estimate the plasma lipids in oral cancer patients and its significance on histopathological grades. We observed a relationship between lower plasma lipids and oral cancer. The result of our study strongly warrants an in-depth research with larger samples and a longer follow-up to consider the low plasma lipid status in oral cancer patients as a useful indicator to assess the course and prognosis of the disease.

Mining of hospital laboratory information systems: a model study defining age- and gender-specific reference intervals and trajectories for plasma creatinine in a pediatric population.

PubMed

Søeby, Karen; Jensen, Peter Bjødstrup; Werge, Thomas; Sørensen, Steen

2015-09-01

The knowledge of physiological fluctuation and variation of even commonly used biochemical quantities in extreme age groups and during development is sparse. This challenges the clinical interpretation and utility of laboratory tests in these age groups. To explore the utility of hospital laboratory data as a source of information, we analyzed enzymatic plasma creatinine as a model analyte in two large pediatric hospital samples. Plasma creatinine measurements from 9700 children aged 0-18 years were obtained from hospital laboratory databases and partitioned into high-resolution gender- and age-groups. Normal probability plots were used to deduce parameters of the normal distributions from healthy creatinine values in the mixed hospital datasets. Furthermore, temporal trajectories were generated from repeated measurements to examine developmental patterns in periods of changing creatinine levels. Creatinine shows great age dependence from birth throughout childhood. We computed and replicated 95% reference intervals in narrow gender and age bins and showed them to be comparable to those determined in healthy population studies. We identified pronounced transitions in creatinine levels at different time points after birth and around the early teens, which challenges the establishment and usefulness of reference intervals in those age groups. The study documents that hospital laboratory data may inform on the developmental aspects of creatinine, on periods with pronounced heterogeneity and valid reference intervals. Furthermore, part of the heterogeneity in creatinine distribution is likely due to differences in biological and chronological age of children and should be considered when using age-specific reference intervals.

Adiposity-Related Biochemical Phenotype in Senescence-Accelerated Mouse Prone 6 (SAMP6)

PubMed Central

Niimi, Kimie; Takahashi, Eiki; Itakura, Chitoshi

2009-01-01

Senescence-accelerated mouse prone 6 (SAMP6) is a model of senile osteoporosis. From 10 to 22 wk of age, SAMP6 mice were heavier than age-matched AKR/J and SAMR1 mice. Body mass indices of 10- and 25-wk-old SAMP6 mice were higher than those of age-matched AKR/J and SAMR1 mice, indicating obesity in the SAMP6 animals. We compared the blood biochemical values among SAMP6, SAMR1, and AKR/J mice to assess whether the SAMP6 strain has abnormal obesity-related parameters. Plasma glucose, triglyceride, insulin, and leptin levels were higher in 10-wk-old SAMP6 mice than in age-matched SAMR1 and AKR/J mice, whereas plasma glucagon and adiponectin levels in 25-wk-old SAMP6 were lower compared with those in age-matched SAMR1 and AKR/J. Total cholesterol levels in SAMR1 and SAMP6 mice at 10 and 25 wk of age were higher than those in AKR/J mice. Hepatic lipid levels were higher in 10- and 25-wk-old SAMP6 mice compared with age-matched AKR/J and SAMR1 animals. These results indicate that SAMP6 mice exhibit obesity and hyperlipidemia, suggesting that the SAMP6 strain is a potential tool for the study of hyperlipidemia. PMID:19887026

Aerobic exercise training-induced changes in serum adropin level are associated with reduced arterial stiffness in middle-aged and older adults.

PubMed

Fujie, Shumpei; Hasegawa, Natsuki; Sato, Koji; Fujita, Satoshi; Sanada, Kiyoshi; Hamaoka, Takafumi; Iemitsu, Motoyuki

2015-11-15

Aging-induced arterial stiffening is reduced by aerobic exercise training, and elevated production of nitric oxide (NO) participates in this effect. Adropin is a regulator of endothelial NO synthase and NO release, and circulating adropin level decreases with age. However, the effect of habitual aerobic exercise on circulating adropin levels in healthy middle-aged and older adults remains unclear. We sought to determine whether serum adropin level is associated with exercise training-induced changes in arterial stiffness. First, in a cross-sectional study, we investigated the association between serum adropin level and both arterial stiffness and cardiorespiratory fitness in 80 healthy middle-aged and older subjects (65.6 ± 0.9 yr). Second, in an intervention study, we examined the effects of 8-wk aerobic exercise training on serum adropin level and arterial stiffness in 40 healthy middle-aged and older subjects (67.3 ± 1.0 yr) divided into two groups: aerobic exercise training and sedentary controls. In the cross-sectional study, serum adropin level was negatively correlated with carotid β-stiffness (r = -0.437, P < 0.001) and positively correlated with plasma NOx level (r = 0.493, P < 0.001) and cardiorespiratory fitness (r = 0.457, P < 0.001). Serum adropin levels were elevated after the 8-wk aerobic exercise training intervention, and training-induced changes in serum adropin level were correlated with training-induced changes in carotid β-stiffness (r = -0.399, P < 0.05) and plasma NOx level (r = 0.623, P < 0.001). Thus the increase in adropin may participate in the exercise-induced reduction of arterial stiffness. Copyright © 2015 the American Physiological Society.

Vitamin E in cranes: reference ranges and nutrient interactions

USGS Publications Warehouse

Dierenfeld, Ellen S.; Sheppard, C.D.; Langenberg, J.; Mirande, C.; Spratt, J.; Dein, F.J.

1993-01-01

Fat soluble vitamins E and A (quantified as alpha-tocopherol and all-trans retinol, respectively) were measured in plasma samples from 274 captive cranes from four institutions and five free-ranging birds. Ages ranged from 4 mo to 80 yr, and all 15 crane species were represented. Captive cranes had a mean +/- standard error (SE) of 6.57 +/- 0.82 micrograms/ml alpha-tocopherol; migrating greater sandhill cranes (Grus canadenis tabida) had a plasma concentration of 3.71 +/- 0.22 micrograms/ml. Sex and age differences were not significant, but crane species that evolved in temperate habitats had higher circulating levels of alpha-tocopherol than tropical or subtropical species. Mean +/- SE retinol values were 0.69 +/- 0.05 micrograms/ml in captive cranes, and 0.66 +/- 0.08 micrograms/ml in free-ranging cranes; values did not differ significantly by sex, age, or species. Dietary vitamin E concentrations were significantly correlated with plasma alpha-tocopherol levels in a logarithmic relationship. Dietary selenium at 0.5 mg/kg was associated with decreased circulating alpha-tocopherol concentrations.

The Kidney Disease Outcomes Quality Initiative (K/DOQI) Guideline for Bone Metabolism and Disease in CKD: association with mortality in dialysis patients.

PubMed

Noordzij, Marlies; Korevaar, Johanna C; Boeschoten, Elisabeth W; Dekker, Friedo W; Bos, Willem J; Krediet, Raymond T

2005-11-01

In 2003, the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI) published a guideline recommending tight control of serum calcium, phosphorus, calcium-phosphorus product (Ca x P), and intact parathyroid hormone levels in patients with chronic kidney disease. Within the context of this guideline, we explored associations of these plasma concentrations with all-cause mortality risk in incident dialysis patients in The Netherlands. In a large, prospective, multicenter, cohort study (Netherlands Cooperative Study on the Adequacy of Dialysis), we included 1,629 patients new on hemodialysis or peritoneal dialysis therapy between 1997 and 2004. Multivariate Cox regression models containing calcium level, phosphorus level, intact parathyroid hormone level, age, comorbidity, primary kidney disease, nutritional status, albumin level, dialysis dose, and hemoglobin level were used to examine mortality risks. Mean age was 60 +/- 15 (SD) years, 61% were men, and 64% were treated with hemodialysis. In adjusted time-dependent survival analysis, all-cause mortality risk increased in hemodialysis patients by 40% (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1 to 1.7) and in peritoneal dialysis patients by 60% (HR, 1.6; 95% CI, 1.1 to 2.4) for plasma phosphorus levels greater than the target. In addition, having elevated plasma Ca x P product levels increased mortality risk by 40% (HR, 1.4; 95% CI, 1.1 to 1.8) in hemodialysis patients and 50% in peritoneal dialysis patients (HR, 1.5; 95% CI, 1.0 to 2.2). In both patient groups, no significant effects were observed for plasma levels less than the targets. In time-dependent survival analysis, the presence of plasma phosphorus and Ca x P product concentrations greater than K/DOQI targets increased all-cause mortality risk in hemodialysis and peritoneal dialysis patients.

Association between Plasma Ceramides and Phosphatidylcholines and Hippocampal Brain Volume in Late Onset Alzheimer’s Disease

PubMed Central

Kim, Min; Nevado-Holgado, Alejo; Whiley, Luke; Snowden, Stuart G.; Soininen, Hilkka; Kloszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Thambisetty, Madhav; Dobson, Richard J.B.; Powell, John F.; Lupton, Michelle K.; Simmons, Andy; Velayudhan, Latha; Lovestone, Simon; Proitsi, Petroula; Legido-Quigley, Cristina

2016-01-01

Lipids such as ceramides and phosphatidylcholines (PC) have been found altered in the plasma of Alzheimer’s disease (AD) patients in a number of discovery studies. For this reason, the levels of 6 ceramides and 3 PCs, with different fatty acid length and saturation levels, were measured in the plasma from 412 participants (AD n = 205, Control n = 207) using mass spectrometry coupled with ultra-performance liquid chromatography. After this, associations with AD status, brain atrophy, and age-related effects were studied. In the plasma of AD participants, cross-sectional analysis revealed elevated levels of three ceramides (Cer16:0 p < 0.01, Cer18:0 p < 0.01, Cer24:1 p < 0.05). In addition, two PCs in AD plasma (PC36:5 p < 0.05, PC38:6 p < 0.05) were found to be depleted compared to the control group, with PC36:5 also associating with hippocampal atrophy (p < 0.01). Age-specific analysis further revealed that levels of Cer16:0, Cer18:0, and Cer20:0 were associated with hippocampal atrophy only in younger participants (age < 75, p < 0.05), while all 3 PCs did so in the older participants (age > 75, p < 0.05). PC36:5 was associated with AD status in the younger group (p < 0.01), while PC38:6 and 40:6 did so in the older group (p < 0.05). In this study, elevated ceramides and depleted PCs were found in the plasma from 205 AD volunteers. Our findings also suggest that dysregulation in PC and ceramide metabolism could be occurring in different stages of AD progression. PMID:27911300

Exposure to Polybrominated Diphenyl Ethers (PBDEs) and Hypothyroidism in Canadian Women.

PubMed

Oulhote, Youssef; Chevrier, Jonathan; Bouchard, Maryse F

2016-02-01

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in a wide range of products, resulting in widespread human exposure. Epidemiological studies in some populations reported exposure to PBDEs and thyroid hormone levels but little epidemiological data are available among women from the general population. The objective of the study was to examine the association of PBDEs with hypothyroidism. This was a cross-sectional analysis of the 2007-2009 Canadian Health Measures Survey. A total of 745 women representative of Canadian women aged 30-79 years participated in the study. Main Outcome and Methods: We estimated the prevalence ratios (PRs) for hypothyroidism in relation to plasma concentrations of BDE-47, -99, -100, and -153 and their sum (ΣPBDEs). Women were identified as cases if they reported a doctor-diagnosed thyroid condition and underwent thyroid hormone replacement therapy (n = 90). Higher plasma levels of brominated diphenyl ether (BDE)-47 and -100 and ΣPBDEs were associated with an increased prevalence of hypothyroidism. The PR for a 10-fold increase in ΣPBDEs was 1.7 (95% confidence interval [CI] 1.0, 3.0). Associations were consistently higher among women aged 30-50 years than among those 51-79 years for ΣPBDEs and the other PBDE congeners, although the interaction was significant only for BDE-100. For instance, in the younger age group, women with detectable levels of BDE-100 had a PR of 3.8 (95% CI 1.2, 12.3) compared with women with undetectable levels; the corresponding PR in the older age group was 1.2 (95% CI 0.6, 2.3). No association was observed for BDE-99 and -153. Plasma PBDE levels were associated with an increased prevalence of hypothyroidism in Canadian women aged 30-50 years. Although the cross-sectional design of the study limits inferences of causality, these findings have important implications, given the key role of thyroid hormones in several biological mechanisms during reproductive age.

Clinical and metabolic abnormalities associated with occupational exposure to polychlorinated biphenyls (PCBs)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chase, K.H.; Wong, O.; Thomas, D.

1982-02-01

A cross-sectional study of 120 male workers was conducted to determine the prevalence of increased polychlorinated biphenyl (PCB) absorption as well as the presence of potentially related clinical and metabolic abnormalities. Three exposure categories (''exposed'', ''nominally exposed'', ''nonexposed'') were defined. Complete work histories, clinical histories, physical examinations and laboratory tests, including plasma PCB determinations were obtained. In addition, fat PCB levels were determined in randomly selected subjects in each exposed group. Evidence of dermatotoxicity was observed and elevated PCB levels were noted more frequently in the exposed group (p < .00001), correlating well with age and duration of employment. Thesemore » correlations were stronger for fat (p < .001) than for plasma (p < .01) PCB levels. In the exposed group, significant correlations were found between plasma PCB and serum triglyceride (p < .00001) and serum glutamic oxaloacetic transaminase (SGOT) levels (p < .01). These correlations remained significant after controlling for either age or length of employment. No significant correlations were found between PCB levels and levels of cholesterol, high-density lipoprotein cholesterol or levels studied on liver function tests other than SGOT. Further analyses relating frequency of reported direct contact with PCB levels suggested a dermal route of exposure. An analysis by union affiliation demonstrated that those in crafts involving greater direct exposure had correspondingly higher elevations of PCB levels.« less

Clinical and metabolic abnormalities associated with occupational exposure to polychlorinated biphenyls (PCBs)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chase, K.H.; Wong, O.; Thomas, D.

1982-02-01

A cross-sectional study of 120 male workers was conducted to determine the prevalence of increased polychlorinated biphenyl (PCB) absorption as well as the presence of potentially related clinical and metabolic abnormalities. Three exposure categories (''exposed'', ''nominally exposed'', ''nonexposed'') were defined. Complete work histories, clinical histories, physical examinations and laboratory tests, including plasma PCB determinations were obtained. In addition, fat PCB levels were determined in randomly selected subjects in each exposed group. Evidence of dermatotoxicity was observed and elevated PCB levels were noted more frequently in the exposed group (p less than .0001), correlating well with age and duration of employment.more » These correlations were stronger for fat (p less than .001) than for plasma (p less than .01) PCB levels. In the exposed group, significant correlations were found between plasma PCB and serum triglyceride (p less than .0001) and serum glutamic oxaloacetic transaminase (SGOT) levels (p less than .01). These correlations remained significant after controlling for either age or length of employment. No significant correlations were found between PCB levels and levels of cholesterol, high-density lipoprotein cholesterol or levels studied on liver function tests other than SGOT. Further analyses relating frequency of reported direct contact with PCB levels suggested a dermal route of exposure. An analysis by union affiliation demonstrated that those in crafts involving greater direct exposure had correspondingly higher elevations of PCB levels.« less

Influence of triglycerides on other plasma lipids in middle-aged men intended for hypolipidaemic treatment.

PubMed

Kolovou, Genovefa D; Anagnostopoulou, Katherine K; Salpea, Klelia D; Hoursalas, Ioannis S; Petropoulos, Ilias; Bilianou, Helen I; Damaskos, Dimitris S; Giannakopoulou, Vasiliki N; Cokkinos, Dennis V

2006-01-01

The present investigation aimed to evaluate the influence of serum triglycerides (TG) on other plasma lipids in male patients less than 65 years of age intended for hypolipidaemic treatment. Lipid profiles of a cohort of 412 dyslipidaemic male patients aged 53.4 +/- 7.7 years (mean +/- standard deviation) were evaluated. Patients were stratified in accordance with their fasting plasma lipid levels. They were divided into multiple groups on the basis of serum TG (> or = 150 or < 150 mg/dl) and high-density lipoprotein cholesterol (HDL-C > or = 40 or < 40 mg/dl). Patients with TG > or = 150 mg/dl had higher total cholesterol and lower HDL-C levels compared with those with TG < 150 mg/dl (p = 0.005 and p < 0.001, respectively). Patients with HDL-C < 40 mg/dl had similar total cholesterol levels and higher TG levels compared to those with HDL-C > or = 40 mg/dl (p < 0.001). In all patients, an inverse correlation between TG and HDL-C was found (r = -0.286, p < 0.001). Additionally, HDL-C levels were inversely correlated with the TG concentration in patients with TG < 150 mg/dl (r = -0.135, p = 0.042) and TG > or = 150 mg/dl (r = -0.188, p = 0.002). An inverse correlation between TG and HDL-C levels seems to exist in the sampled population, revealing a close link between the metabolic pathways for TG and HDL-C. This inverse correlation appears to persist even in patients with low fasting TG levels.

Reference intervals for orotic acid in urine, plasma and dried blood spot using hydrophilic interaction liquid chromatography-tandem mass spectrometry.

PubMed

D'Apolito, Oceania; Garofalo, Daniela; la Marca, Giancarlo; Dello Russo, Antonio; Corso, Gaetano

2012-02-01

Orotic acid (OA), a marker of hereditary orotic aciduria, is usually used for the differential diagnosis of some hyperammonemic inherited defects of urea cycle and of basic amino acid transporters. This study was aimed to establish age related reference intervals of OA in urine, and for the first time in plasma, and dried blood spot (DBS) from 229 apparently healthy subjects aged from three days to 40 years. The quantification of OA was performed by a previously implemented method, using a stable isotope dilution with 1,3-[(15)N(2)]-orotic acid and hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The method has proved to be sensitive and accurate for a quantitative analysis of OA also in DBS and plasma. According to previous studies, urinary OA levels (mmol/mol of creatinine) decrease significantly with age. The upper limits (as 99th %ile) were of 3.44 and 1.30 in groups aged from three days to 1 year (group 1) and from 1 year to 12 years (group 2), respectively; in teenagers (from 13 to 19 years; group 3) and adults (from 20 to 40 years; group 4) urinary levels became more stable and the upper limits were of 0.64 and 1.21, respectively. Furthermore, OA levels in DBS (μM) also resulted significantly higher in subjects of group 1 (upper limit of 0.89) than in subjects of groups 2, 3 and 4 (upper limits of 0.24, 0.21, and 0.29, respectively). OA levels in plasma (μM) were significantly lower in subjects of group 3 (upper limit of 0.30) than in subjects of groups 1, 2, and 4 (upper limits of 0.59, 0.48, and 0.77, respectively). This method was also employed for OA quantification in plasma and DBS of 17 newborns affected by urea cycle defects, resulting sensitive and specific enough to screen these disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

Male sex and vascular risk factors affect cystatin C-derived renal function in older people without diabetes or overt vascular disease.

PubMed

Werner, Karin Birgitta; Elmståhl, Sölve; Christensson, Anders; Pihlsgård, Mats

2014-05-01

to explore the effect of ageing on renal function with cystatin C as the marker of glomerular filtration rate (GFR) in the general population without vascular disease or diabetes. a cross-sectional analysis of a healthy subset from the Good Aging in Skåne-cohort study representative of the Swedish general population. 1252 participants without vascular disease and diabetes (43.9% men) of whom 203 were over 80 years old were included from the original cohort of 2931. plasma cystatin C and plasma creatinine were used as markers for GFR. Estimated GFR (eGFR) was calculated with three chronic kidney disease epidemiology collaboration (CKD-EPI) formulas involving cystatin C, creatinine or both. the median for plasma cystatin C was 0.93 mg/l (60-69 years old), 1.04 (70-79 years old) and 1.24 (80+ years old). The difference in mg/l between the 5th and 95th percentile was 0.46, 0.62 and 0.90 for these age groups. Male sex increased the age effect on plasma cystatin C levels with 0.004 mg/l/year (P = 0.03), adjusted for vascular risk factors. Smoking, lower HDL and higher diastolic blood pressure were associated with higher cystatin C levels. 54.7% (CKD-EPI creatinine) to 73.9% (CKD-EPI cystatin C) of the 80+ had an eGFR < 60 ml/min/1.73 m2. non-diabetics without overt vascular disease exhibit an age related but heterogeneous decline in renal function. The ageing effect is more pronounced in men. At least half of healthy 80+ years old could be expected to have at least CKD Stage 3 with eGFR < 60 ml/min/1.73 m2.

Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction

PubMed Central

Consitt, Leslie A.; Koves, Timothy R.; Muoio, Deborah M.; Nakazawa, Masato; Newton, Christopher A.; Houmard, Joseph A.

2016-01-01

The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19–29 years) and fifteen middle- to older-aged (57–82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin-stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation. Insulin infusion decreased the majority of plasma short-, medium-, and long-chain (SC, MC, and LC, respectively) AC. However, during the initial 50 min, a number of MC and LC AC species (C10, C10:1, C12:1, C14, C16, C16:1, C18) remained elevated in aged individuals compared to their younger counterparts indicating a lag in responsiveness. Additionally, the insulin-induced decline in skeletal muscle ACC phosphorylation was blunted in the aged compared to young individuals (−24% vs. −56%, P<0.05). These data suggest that a desensitization to insulin during aging, possibly at the level of skeletal muscle ACC phosphorylation, results in a diminished ability to transition to glucose oxidation indicative of metabolic inflexibility. PMID:27693789

Post-translational modifications of eNOS augment nitric oxide availability and facilitates hypoxia adaptation in Ladakhi women.

PubMed

Pooja; Ghosh, Dishari; Bhargava, Kalpana; Sethy, Niroj Kumar

2018-06-09

The lower inhaled oxygen per volume at high altitude poses an intimidating challenge for humans to survive and reproduce. Indigenous populations of the Himalayas reportedly exhibit higher microcirculatory blood flow accompanied by higher orders of magnitude of nitric oxide (NO) products in lung, plasma and red blood cells as a vascular adaptation strategy for hypobaric hypoxia. The precise mechanism of such observed higher NO metabolites for hypoxia adaptation remains elusive. Studying high altitude native Ladakhi women, we observed significant higher eNOS mRNA and protein in blood/plasma as compared to lowland women. We also observed higher level of plasma l-citrulline and NOx (nitrates and nitrites) with concomitant lower levels of arginase mRNA and protein further suggesting higher eNOS activity and NO bioavailability. Interestingly, middle aged postmenopausal Ladakhi women exhibited significantly higher level of eNOS activity, NOx and cGMP as compared to age matched lowland women. Preferential phosphorylation of eNOS on stimulatory Ser1177 and Ser615 as well as dephosphorylation of inhibitory Thr495 site contributed to higher NO availability in Ladakhi women irrespective of age. We also observed higher levels of eNOS activating humoral factors like bradykinin and estrogen in both young and middle-aged Ladakhi women. These results suggest that an altered phosphorylation status, together with an enhanced expression of eNOS and potential humoral endothelial activators, are involved in enhanced activation of the eNOS-NO-cGMP pathway in Ladakhi women irrespective of age, reinforcing the hypothesis that NO metabolites play a major role in Himalayan pattern of hypoxia adaptation. Copyright © 2018 Elsevier Inc. All rights reserved.

Brief Report: Plasma Homocysteine is Not Associated with HIV Serostatus or Antiretroviral Therapy in Women

PubMed Central

Raiszadeh, Farbod; Hoover, Donald R.; Lee, Irene; Shi, Qiuhu; Anastos, Kathryn; Gao, Wei; Kaplan, Robert; Glesby, Marshall J.

2009-01-01

Background The effects of HIV serostatus and combination antiretroviral therapy (cART) on plasma homocysteine (Hcy) are uncertain. Methods Plasma Hcy was assayed in a cross-sectional study of 249 HIV-infected and 127 HIV-uninfected women at the Bronx Women’s Interagency HIV Study site. Results Mean plasma Hcy was 7.42 ± 2.68 in HIV-infected and 7.18 ± 2.66 µmol/L in HIV-uninfected women (P = 0.40). Hyperhomocysteinemia (defined as Hcy > 10 µmol/L) was seen in 16.9% and 13.4 % of HIV-infected and HIV-uninfected women, respectively (P=0.45). Among HIV-infected women, cART use was not associated with Hcy level. Compared to the lowest quartile, women with Hcy in the highest quartile had lower mean serum vitamin B12 and RBC folate levels. In multivariate analysis that did not include micronutrient levels, age, serum creatinine and lower CD4% were significantly associated with plasma Hcy level in HIV-infected women. Conclusions Plasma Hcy was not associated with HIV serostatus or use of cART in this cross-sectional study. Reduced availability of folate cofactors for Hcy remethylation in HIV-infected women with lower folate intake and decreased health status may influence Hcy levels. PMID:19333128

PAI-1 4G/5G polymorphism and plasma levels association in patients with coronary artery disease.

PubMed

Lima, Luciana Moreira; Carvalho, Maria das Graças; Fonseca Neto, Cirilo Pereira; Garcia, José Carlos Faria; Sousa, Marinez Oliveira

2011-12-01

Type-1 plasminogen activator inhibitor (PAI-1) 4G/5G polymorphism may influence the PAI-1 expression. High plasma levels of PAI-1 are associated with coronary artery disease (CAD). This study investigated the influence of PAI-1 4G/5G polymorphism on plasma PAI-1 levels and its association with CAD assessed by coronary angiography. Blood sample of 35 individuals with angiographically normal coronary arteries, 31 individuals presenting mild/moderate atheromatosis, 57 individuals presenting severe atheromatosis and 38 healthy individuals (controls) were evaluated. In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Plasma PAI-1 levels were quantified by ELISA assay (American Diagnostica). No difference was found between groups regarding age, gender and body mass index. Plasma PAI-1 levels and 4G/4G genotype frequency were significantly higher in the severe atheromatosis group compared to the other groups (p<0.001). Furthermore, patients with 4G/4G genotype (r=0.28, p<0.001) had significantly higher plasma PAI-1 levels than those with 5G/5G genotype (r=0.02, p=0.4511). In addition, in a multiple logistic regression model, adjusted for all the other variables, PAI-1 was observed to be independently associated with CAD > 70% (p<0.001). The most important finding of this study was the association between 4G/4G genotype, high plasma PAI-1 levels and coronary stenosis higher than 70% in Brazilian individuals. Whether high plasma PAI-1 levels are a decisive factor for atherosclerosis worsening or it is a consequence remains to be established.

Hyperuricemia Is a Risk Factor for the Onset of Impaired Fasting Glucose in Men with a High Plasma Glucose Level: A Community-Based Study

PubMed Central

Miyake, Teruki; Kumagi, Teru; Furukawa, Shinya; Hirooka, Masashi; Kawasaki, Keitarou; Koizumi, Mitsuhito; Todo, Yasuhiko; Yamamoto, Shin; Abe, Masanori; Kitai, Kohichiro; Matsuura, Bunzo; Hiasa, Yoichi

2014-01-01

Background It is not clear whether elevated uric acid is a risk factor for the onset of impaired fasting glucose after stratifying by baseline fasting plasma glucose levels. We conducted a community-based retrospective longitudinal cohort study to clarify the relationship between uric acid levels and the onset of impaired fasting glucose, according to baseline fasting plasma glucose levels. Methods We enrolled 6,403 persons (3,194 men and 3,209 women), each of whom was 18–80 years old and had >2 annual check-ups during 2003–2010. After excluding persons who had fasting plasma glucose levels ≥6.11 mM and/or were currently taking anti-diabetic agents, the remaining 5,924 subjects were classified into quartiles according to baseline fasting plasma glucose levels. The onset of impaired fasting glucose was defined as fasting plasma glucose ≥6.11 mM during the observation period. Results In the quartile groups, 0.9%, 2.1%, 3.4%, and 20.2% of the men developed impaired fasting glucose, respectively, and 0.1%, 0.3%, 0.5%, and 5.6% of the women developed impaired fasting glucose, respectively (P trend <0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerols, high density lipoprotein-cholesterol, creatinine, fatty liver, family history of diabetes, alcohol consumption, and current smoking, uric acid levels were positively associated with onset of impaired fasting glucose in men with highest-quartile fasting plasma glucose levels (adjusted hazard ratio, 1.003; 95% confidence interval, 1.0001–1.005, P = 0.041). Conclusions Among men with high fasting plasma glucose, hyperuricemia may be independently associated with an elevated risk of developing impaired fasting glucose. PMID:25237894

Plasma CX3CL1 levels and long term outcomes of patients with atrial fibrillation: the West Birmingham Atrial Fibrillation Project.

PubMed

Guo, Yutao; Apostalakis, Stavros; Blann, Andrew D; Lip, Gregory Y H

2014-01-01

There is growing evidence that chemokines are potentially important mediators of the pathogenesis of atherosclerotic disease. Major atherothrombotic complications, such as stroke and myocardial infarction, are common among atrial fibrillation (AF) patients. This increase in risk of adverse events may be predicted by a score based on the presence of certain clinical features of chronic heart failure, hypertension, age 75 years or greater, diabetes and stroke (the CHADS2 score). Our objective was to assess the prognostic value of plasma chemokines CCL2, CXCL4 and CX3CL1, and their relationship with the CHADS2 score, in AF patients. Plasma CCL2, CXCL4 and CX3CL1 were measured in 441 patients (59% male, mean age 75 years, 12% paroxysmal, 99% on warfarin) with AF. Baseline clinical and demographic factors were used to define each subject's CHADS2 score. Patients were followed up for a mean 2.1 years, and major adverse cardiovascular and cerebrovascular events (MACCE) were sought, being the combination of cardiovascular death, acute coronary events, stroke and systemic embolism. Fifty-five of the AF patients suffered a MACCE (6% per year). Those in the lowest CX3CL1 quartile (≤ 0.24 ng/ml) had fewest MACCE (p = 0.02). In the Cox regression analysis, CX3CL1 levels >0.24 ng/ml (Hazard ratio 2.8, 95% CI 1.02-8.2, p = 0.045) and age (p = 0.042) were independently linked with adverse outcomes. The CX3CL1 levels rose directly with the CHADS2 risk score (p = 0.009). The addition of CX3CL1 did not significantly increased the discriminatory ability of the CHADS2 clinical factor-based risk stratification (c-index 0.60 for CHADS2 alone versus 0.67 for CHADS2 plus CX3CL1 >0.24 ng/ml, p = 0.1). Aspirin use was associated with lower levels of CX3CL1 (p = 0.0002) and diabetes with higher levels (p = 0.031). There was no association between CXCL4 and CCL2 plasma levels and outcomes. There is an independent association between low plasma CX3CL1 levels and low risk of major cardiovascular events in AF patients, as well as a linear association between CX3CL1 plasma levels and CHADS2-defined cardiovascular risk. The potential for CX3CL1 in refining risk stratification in AF patients merits consideration. © 2014 S. Karger AG, Basel.

Correlation between plasma pentosidine concentrations and retinal hemodynamics in patients with type 2 diabetes.

PubMed

Sato, Eiichi; Nagaoka, Taiji; Yokota, Harumasa; Takahashi, Atsushi; Yoshida, Akitoshi

2012-05-01

To investigate whether plasma pentosidine, a well-defined advanced glycation end product, is associated with retinal hemodynamic abnormalities in patients with type 2 diabetes. Prospective cross-sectional study. Forty-two eyes with type 2 diabetes mellitus were evaluated. The type 2 diabetic eyes were divided into 2 groups: 22 eyes (22 patients; mean age, 61 years) with nondiabetic retinopathy (NDR) and 20 eyes (20 patients; mean age, 61 years) with mild nonproliferative diabetic retinopathy (NPDR). We used a retinal laser Doppler system to measure the arterial diameter, velocity, and blood flow in the major temporal retinal arteries. The pulsatility ratio, a resistive index expressed as the peak systolic to the end diastolic velocity ratio, was calculated from the blood velocity traces. Plasma pentosidine was measured in 42 patients with diabetes using a commercially available competitive enzyme-linked immunosorbent assay. The pulsatility ratio significantly increased in patients with NPDR (4.8 ± 1.5) compared with patients with NDR (3.7 ± 0.8) (P = .0061). No differences in velocity, diameter, or blood flow were seen between the 2 groups. Plasma pentosidine levels also increased significantly (P = .0085) in patients with NPDR (0.057 ± 0.015) compared to patients with NDR (0.047 ± 0.012). The pulsatility ratio was correlated positively with the plasma pentosidine levels in patients with NPDR (Pearson correlation, r = 0.45, P = .044). Multiple regression analysis showed that the plasma pentosidine level was significantly associated with the pulsatility ratio (standardized coefficient, 0.62; P = .009). The vascular rigidity of the retinal arteries may increase with increasing plasma pentosidine in patients with type 2 diabetes with retinopathy. Copyright © 2012 Elsevier Inc. All rights reserved.

Increased plasma agmatine levels in patients with schizophrenia.

PubMed

Uzbay, Tayfun; Goktalay, Gokhan; Kayir, Hakan; Eker, Salih S; Sarandol, Asli; Oral, Sema; Buyukuysal, Levent; Ulusoy, Gokhan; Kirli, Selcuk

2013-08-01

Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p < 0.0001) compared to those of healthy individuals (control), there were no significant changes in the levels of S100B protein (p = 0.660). An ROC (receiver operating characteristic) curve analysis revealed that measuring plasma agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p < 0.0001). The predictive value of S100B measurements was not statistically significant (p > 0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects

PubMed Central

Al Qarni, Ali Ahmed; Joatar, Faris Elbahi; Das, Nagalla; Awad, Mohamed; Eltayeb, Mona; Al-Zubair, Ahmed Gasim; Ali, Muhalab E.; Al Masaud, Abdulaziz; Shire, Abdirashid M.; Gumaa, Khalid

2017-01-01

Background Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM. Methods Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique. Results Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM. Conclusion The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM. PMID:28555463

Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older.

PubMed

Majerczyk, M; Kocełak, P; Choręza, P; Arabzada, H; Owczarek, A J; Bożentowicz-Wikarek, M; Brzozowska, A; Szybalska, A; Puzianowska-Kuźnicka, M; Grodzicki, T; Więcek, A; Olszanecka-Glinianowicz, M; Chudek, J

2018-03-09

Elevated plasma concentration of retinol binding protein 4 (RBP4) has recently emerged as a potential risk factor as a component of developing metabolic syndrome (MS). Therefore, this study aimed to analyse the relationship between components of MS and concentrations of plasma RBP4 in a population of subjects 65 years and older. The study sample consisted of 3038 (1591 male) participants of the PolSenior study, aged 65 years and older. Serum lipid profile, concentrations of RBP4, glucose, insulin, C-reactive protein, IL-6, and activity of aminotransferases were measured. Nutritional status (BMI/waist circumference) and treatment with statins and fibrates were evaluated. Glomerular filtration rate (eGFR), de Ritis ratio, and fatty liver index (FLI), as well as HOMA-IR were calculated. Our study revealed a strong relationship between components of MS and RBP4 in both sexes: plasma RBP4 levels were increased in men by at least 3×, and in women by at least 4×. Hypertriglyceridemia was most strongly associated with elevated plasma RBP4 levels. Multivariate, sex-adjusted regression analysis demonstrated that chronic kidney disease [OR 1.86 (95% CI 1.78-1.94)], hypertriglyceridemia [OR 1.52 (1.24-1.87)], hypertension [OR 1.15 (1.12-1.19)], low serum HDL cholesterol [OR 0.94 (0.92-0.97)], and age > 80 years [OR 0.86 (0.81-0.90)] were each independently associated with RBP4 concentration (all p < 0.001). In Caucasians 65 years and older, RBP4 serum levels are associated with a number of components of MS, independent of sex and kidney function. Hypertriglyceridemia as a component of MS is most significantly related to RBP4 concentration.

Correlation of Paraoxonase Status with Disease Activity Score and Systemic Inflammation in Rheumatoid Arthritic Patients.

PubMed

Bindal, Usha Dudeja; Saxena, Rahul; Siddiqui, Merajul Haque; Sharma, Dilutpal

2016-03-01

Despite, various preventive efforts on conventional cardiovascular disease (CVD) risk factors, the incidence of CVD in rheumatoid arthritis (RA) patients increases continuously. To solve this conundrum one needs more investigations. The present study was conducted to evaluate the plasma paraoxonase (PON) activity along with the markers of systemic inflammation, oxidative stress and disease activity score-28 (DAS28) in RA patients and clarify their role in determining the probability of RA patients to develop future CVD risk. Plasma PON, total antioxidant activity (TAA), C-reactive protein (CRP), synovial interleukin-6 (IL-6) and erythrocyte malondialdehyde (MDA) levels were estimated in 40 RA patients aged 40-55 years aged and 40 age-matched healthy controls. The data obtained were compared statistically by using Student's t-test and Pearson correlation test. Besides dyslipidaemia, marked reduction in plasma PON and TAA (p< 0.05) were observed in RA patients as compared with that of healthy controls. Erythrocyte MDA, plasma CRP and synovial IL-6 levels were increased significantly (p<0.05) in RA patients. PON was negatively correlated with MDA (r = - 0.672; p < 0.001), CRP (r = -0.458; p<0.05), IL-6 (r = -0.426; p<0.05) and DAS28 (r = -0.598; p < 0.001), and positively correlated with HDL cholesterol (r = 0.648; p<0.001) and TAA (r = 0.608; p< 0.001) levels in RA patients. Alteration in PON activity might contribute to the progression of future CVD risk in RA patients, which may result from interplay of several confounding factors, such as inflammation, oxidative stress and dyslipidaemia. Furthermore, plasma PON activity, CRP and TAA levels could be considered as non-traditional factors to predict CVD risk. Thus, it is suggested that future drugs could be developed to target the non-traditional risk factors in RA patients.

Plasma Protein Pentosidine and Carboxymethyllysine, Biomarkers for Age-related Macular Degeneration*

PubMed Central

Ni, Jiaqian; Yuan, Xianglin; Gu, Jiayin; Yue, Xiuzhen; Gu, Xiaorong; Nagaraj, Ram H.; Crabb, John W.

2009-01-01

Age-related macular degeneration (AMD) causes severe vision loss in the elderly; early identification of AMD risk could help slow or prevent disease progression. Toward the discovery of AMD biomarkers, we quantified plasma protein Nε-carboxymethyllysine (CML) and pentosidine from 58 AMD and 32 control donors. CML and pentosidine are advanced glycation end products that are abundant in Bruch membrane, the extracellular matrix separating the retinal pigment epithelium from the blood-bearing choriocapillaris. We measured CML and pentosidine by LC-MS/MS and LC-fluorometry, respectively, and found higher mean levels of CML (∼54%) and pentosidine (∼64%) in AMD (p < 0.0001) relative to normal controls. Plasma protein fructosyl-lysine, a marker of early glycation, was found by amino acid analysis to be in equal amounts in control and non-diabetic AMD donors, supporting an association between AMD and increased levels of CML and pentosidine independent of other diseases like diabetes. Carboxyethylpyrrole (CEP), an oxidative modification from docosahexaenoate-containing lipids and also abundant in AMD Bruch membrane, was elevated ∼86% in the AMD cohort, but autoantibody titers to CEP, CML, and pentosidine were not significantly increased. Compellingly higher mean levels of CML and pentosidine were present in AMD plasma protein over a broad age range. Receiver operating curves indicate that CML, CEP adducts, and pentosidine alone discriminated between AMD and control subjects with 78, 79, and 88% accuracy, respectively, whereas CML in combination with pentosidine provided ∼89% accuracy, and CEP plus pentosidine provided ∼92% accuracy. Pentosidine levels appeared slightly altered in AMD patients with hypertension and cardiovascular disease, indicating further studies are warranted. Overall this study supports the potential utility of plasma protein CML and pentosidine as biomarkers for assessing AMD risk and susceptibility, particularly in combination with CEP adducts and with concurrent analyses of fructosyl-lysine to detect confounding factors. PMID:19435712

Identification of Neuroprotective Factors Associated with Successful Ageing and Risk of Cognitive Impairment among Malaysia Older Adults

PubMed Central

Rajab, Nor Fadilah; Shahar, Suzana

2017-01-01

The increase of ageing population has raised public attention on the concept of successful ageing. Studies have shown that vitamin D, telomere length, and brain-derived neurotrophic factor (BDNF) have been associated with cognitive function. Therefore, this study aimed to identify neuroprotective factors for cognitive decline in different ageing groups. A total of 300 older adults aged 60 years and above were recruited in this population based cross-sectional study. Participants were categorized into three groups: mild cognitive impairment (MCI) (n = 100), usual ageing (UA) (n = 100), and successful ageing (SA) (n = 100). Dietary vitamin D intake was assessed through Diet History Questionnaire (DHQ). Out of the 300 participants, only 150 were subjected to fasting blood sample collection. These samples were used for serum vitamin D and plasma BDNF measurements. Whole blood telomere length was measured using RT-PCR method. The results show that the reduction of the risk of MCI was achieved by higher serum vitamin D level (OR: 0.96, 95% CI: 0.92–0.99, p < 0.05), higher plasma BDNF level (OR: 0.51, 95% CI: 0.30–0.88,  p < 0.05), and longer telomere (OR: 0.97, 95% CI: 0.95–0.99,  p < 0.001). In conclusion, participants with higher vitamin D level, higher BDNF level, and longer telomere length were more likely to age successfully. PMID:29109736

Effect of aged garlic extract against methotrexate-induced damage to the small intestine in rats.

PubMed

Yüncü, Mehmet; Eralp, Ayhan; Celik, Ahmet

2006-06-01

Methotrexate (MTX) chemotherapy is often accompanied by side effects such as gastrointestinal ulceration and diarrhea. The aim of this study was to examine histologically whether an aged garlic extract (AGE) had a protective effect on the small intestine of rats with MTX-induced damage. Forty male Wistar albino rats were randomized into experimental and control groups and divided into four groups of ten animals. To the first group, MTX was applied as a single dose (20 mg/kg) intraperitoneally. To the second group, in addition to MTX application, AGE (250 mg/kg) was administered orally every day at the same time by intragastric intubation until the rats were killed. To the third group, AGE only was given. The fourth group was the control. All animals were killed 4 days after the intraperitoneal injection of MTX for histopathologic analysis and tissue MDA levels. Before killing, intracardiac blood was obtained from each animal to perform biochemical analysis (plasma lactate level). MTX was found to lead to damage in the jejunal tissues and to increase the MDA and lactate levels in the plasma. Administration of the AGE decreased the severity of jejunal damage, but increased MDA and lactate levels caused by MTX treatment on the other hand. These results suggest that AGE may protect the small intestine of rats from MTX-induced damage. Thus this study substantiated the thought that the protective effect of AGE is derived from the manner in which it interacts with crypt cells.

Increased plasma fibrinopeptide A levels during attacks induced by hyperventilation in patients with coronary vasospastic angina.

PubMed

Oshima, S; Ogawa, H; Yasue, H; Okumura, K; Matsuyama, K; Miyagi, H

1989-07-01

Plasma fibrinopeptide A levels, beta-thromboglobulin levels and platelet factor 4 levels were estimated by enzyme-linked immunosorbent assay before and after hyperventilation in 12 patients with coronary vasospastic angina and in 12 control subjects matched for age and gender. In all 12 study patients, anginal attacks accompanied by electrocardiographic (ECG) changes (ST elevation in 11 patients and ST depression in 1 patient) were induced by hyperventilation. Coronary angiography was performed on 11 of the 12 patients, and coronary artery spasm with the same ECG changes was induced by intracoronary injection of acetylcholine in all 11. The plasma fibrinopeptide A levels increased significantly from 2.0 +/- 0.4 to 10.0 +/- 2.4 ng/ml during the attack (p less than 0.001) in the study patients, but remained unchanged before and after hyperventilation in the control subjects. The plasma levels of beta-thromboglobulin and platelet factor 4 remained unchanged after hyperventilation in both groups. Our data indicate that coronary artery spasm may induce thrombin generation and trigger thrombus formation in the coronary artery.

Plasma Levels of Aβ42 and Tau Identified Probable Alzheimer's Dementia: Findings in Two Cohorts.

PubMed

Lue, Lih-Fen; Sabbagh, Marwan N; Chiu, Ming-Jang; Jing, Naomi; Snyder, Noelle L; Schmitz, Christopher; Guerra, Andre; Belden, Christine M; Chen, Ta-Fu; Yang, Che-Chuan; Yang, Shieh-Yueh; Walker, Douglas G; Chen, Kewei; Reiman, Eric M

2017-01-01

The utility of plasma amyloid beta (Aβ) and tau levels for the clinical diagnosis of Alzheimer's disease (AD) dementia has been controversial. The main objective of this study was to compare Aβ42 and tau levels measured by the ultra-sensitive immunomagnetic reduction (IMR) assays in plasma samples collected at the Banner Sun Health Institute (BSHRI) (United States) with those from the National Taiwan University Hospital (NTUH) (Taiwan). Significant increase in tau levels were detected in AD subjects from both cohorts, while Aβ42 levels were increased only in the NTUH cohort. A regression model incorporating age showed that tau levels identified probable ADs with 81 and 96% accuracy in the BSHRI and NTUH cohorts, respectively, while computed products of Aβ42 and tau increased the accuracy to 84% in the BSHRI cohorts. Using 382.68 (pg/ml) 2 as the cut-off value, the product achieved 92% accuracy in identifying AD in the combined cohorts. Overall findings support that plasma Aβ42 and tau assayed by IMR technology can be used to assist in the clinical diagnosis of AD.

Effects of aspirin on intra-platelet vascular endothelial growth factor, angiopoietin-1, and p-selectin levels in hypertensive patients.

PubMed

Nadar, Sunil; Blann, Andrew D; Lip, Gregory Y H

2006-09-01

Although aspirin is useful in reducing platelet activation and cardiovascular events, its effects on platelet levels of angiogenic factors, such as vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), and markers of platelet activation in hypertension are unknown. The aim of this study was to study the effects of aspirin on the platelet morphology, plasma and platelet levels of VEGF (sVEGF and pVEGF respectively), Ang-1 (sAng-1 and pAng-1 respectively), and P-selectin (sPsel and pPsel respectively) in patients with well controlled hypertension. A total of 35 aspirin-naive, hypertensive patients (29 male and six female; mean age 64 years) were compared with 30 (23 male, seven female, mean age 59 years) normotensive control subjects. Blood was collected for plasma VEGF, P-selectin, and Ang-1 (enzyme-linked immunoassay), intra-platelet levels of VEGF, Ang-1, and P-selectin, and platelet volume and mass. Research indices in hypertensive patients were studied before and after 3 months treatment with aspirin 75 mg daily. Hypertensive patients had significantly higher plasma levels of VEGF (P=.04), Ang-1 (P<.001), as well as pVEGF (P=.008), pAng-1(P=.001), sPsel (P=.02), pPsel (P<.001), and mean platelet mass (P=.01) when compared with control subjects. After treatment with aspirin for 3 months, there were significant reductions in plasma VEGF (P=.01), pAng-1 (P=.04), sPsel (P=.001), and pPsel (P<.001) levels, but not levels of platelet VEGF and plasma Ang-1. Neither pVEGF nor pAng-1 correlated with blood pressure or with their respective plasma levels. The use of aspirin in high-risk hypertensive patients leads to a reduction in intra-platelet angiogenic growth factors and platelet activation. This may have implications for the use of aspirin in conditions (such as vascular disease) that have been associated with an increase in angiogenesis and platelet activation.

Associations of blood homocysteine concentrations in Arab schizophrenic patients.

PubMed

Akanji, A O; Ohaeri, J U; Al-Shammri, S A; Fatania, H R

2007-09-01

This study aimed to evaluate the blood homocysteine concentration in Arab patients with schizophrenia and assess its associations with clinical phenotypes of the disease. Two age-matched groups of subjects were studied: (1) Healthy Controls, HC, n=165; (2) patients with schizophrenia, SZ: n=207. Each subject was evaluated with a standard questionnaire for age at disease onset, family history, disease severity and outcome. Plasma homocysteine levels (Hcys) were measured by immunoassay and serum levels of other biochemical parameters were measured by routine Autoanalyzer techniques. Group HC was heavier (body mass index, BMI) while SZ had greater waist-hip ratio (WHR) and plasma Hcys levels. In SZ, there were significant correlations between Hcys and BMI, triglycerides and HDL. Hcys levels in SZ were highest in the younger male patients. Schizophrenic patients have increased blood Hcys levels which correlate with components of the metabolic syndrome. Hcys levels were highest in the younger male patients and were not influenced by prognostic features of the disease.

Vitamin B-12 status is not associated with plasma homocysteine in parents and their preschool children: lacto-ovo, lacto, and ovo vegetarians and omnivores.

PubMed

Yen, Chin-En; Yen, Chi-Hua; Cheng, Chien-Hsiang; Huang, Yi-Chia

2010-02-01

Vegetarians may be at risk of certain nutrient deficiencies, particularly vitamin B-12. Vitamin B-12 deficiency may increase plasma homocysteine concentration and thus may potentially increase the risk of cardiovascular disease in vegetarians. The purpose of this study was to assess and compare plasma homocysteine and vitamin B-12 status in vegetarian and omnivorous preschool children and their parents. In addition, the association between parents' and children's homocysteine and vitamin B-12 concentration was also examined. Fifty-six omnivores (28 preschool children and one of their parents), 34 lacto-ovo vegetarians (16 parents and 18 children), 5 ovo vegetarians (2 parents and 3 children), 1 lacto vegetarian parent, and 2 vegan parents were enrolled in this study. The mean age of preschool children was 5.1 +/- 1.3 years and that of their parent was 35.4 +/- 4.2 years. Nutrient intakes were recorded using 3-day dietary records. Fasting venous blood samples were obtained to measure serum creatinine, high-sensitivity C-reactive protein, hematological parameters, plasma homocysteine, serum folate, and vitamin B-12 concentrations. There was no significant difference in dietary folate intake between vegetarian and omnivores within parent and child groups. The mean plasma homocysteine level of vegetarian parents and their children was in the physiological range, and they had slightly but not significantly higher plasma homocysteine levels than omnivores. Omnivorous parents and their children had significantly higher vitamin B-12 intake than vegetarian participants but similar serum vitamin B-12 concentrations. Plasma homocysteine concentration was significantly and negatively associated with only serum folate levels (beta = -0.15) and dietary vitamin B-12 intake (beta = -0.05) in the omnivorous parents after adjusting for age, gender, body mass index, and serum creatinine. Vegetarian parents and their preschool children had a lower vitamin B-12 intake than omnivorous parents and their preschool children but similar plasma vitamin B-12 and homocysteine concentrations. Plasma homocysteine was not associated with serum vitamin B-12 levels in the parent, child, or pooled group.

Reduced fasting plasma levels of diazepam-binding inhibitor in adolescents with anorexia nervosa.

PubMed

Conti, Elisa; Tremolizzo, Lucio; Bomba, Monica; Uccellini, Orlando; Rossi, Maria Sara; Raggi, Maria Elisabetta; Neri, Francesca; Ferrarese, Carlo; Nacinovich, Renata

2013-09-01

Altered expression and/or function, both peripherally and centrally, of various neuropeptides is involved in the neurophysiology of anorexia nervosa (AN). Diazepam-binding inhibitor (DBI) is an interesting peptide for understanding this crosstalk. The aim of this work was to assess fasting plasma levels of DBI and leptin in patients with AN. Twenty-four AN adolescents were recruited together with 10 age-comparable healthy controls. Neuropeptide determinations were performed on plasma samples by enzyme-linked immunosorbent assays. Patients with AN were further characterized for the presence of a depressive state or anxiety by using, respectively, the Children's Depression Inventory or the State-Trait Anxiety Inventory form Y. Levels of both plasma DBI and leptin were reduced in patients with AN (∼40 and ∼70%, respectively). DBI levels displayed a tendency to increase in the presence of a depressive state, although not with anxiety, whereas leptin levels correlated exclusively with body mass index. These data further extend our knowledge of neuropeptide dysfunction in AN, and plasma DBI may represent a marker for this disease, in particular considering its correlation with comorbid mood disorders. Copyright © 2013 Wiley Periodicals, Inc.

Relationship between Sustained Reductions in Plasma Lipid and Lipoprotein Concentrations with Apheresis and Plasma Levels and mRNA Expression of PTX3 and Plasma Levels of hsCRP in Patients with HyperLp(a)lipoproteinemia

PubMed Central

Stefanutti, Claudia; Mazza, Fabio; Steiner, Michael; Watts, Gerald F.; De Nève, Joel; Pasqualetti, Daniela; Paal, Juergen

2016-01-01

The effect of lipoprotein apheresis (Direct Adsorption of Lipids, DALI) (LA) on plasma levels of pentraxin 3 (PTX3), an inflammatory marker that reflects coronary plaque vulnerability, and expression of PTX3 mRNA was evaluated in patients with hyperLp(a)lipoproteinemia and angiographically defined atherosclerosis/coronary artery disease. Eleven patients, aged 55 ± 9.3 years (mean ± SD), were enrolled in the study. PTX3 soluble protein levels in plasma were unchanged by 2 sessions of LA; however, a downregulation of mRNA expression for PTX3 was observed, starting with the first session of LA (p < 0.001). The observed reduction was progressively increased in the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session. A statistically significantly greater treatment-effect correlation was observed in patients undergoing weekly treatments, compared with those undergoing treatment every 15 days. A progressive reduction in plasma levels of C-reactive protein was also seen from the first session of LA, with a statistically significant linear correlation for treatment-effect in the change in plasma levels of this established inflammatory marker (R 2 = 0.99; p < 0.001). Our findings suggest that LA has anti-inflammatory and endothelium protective effects beyond its well-established efficacy in lowering apoB100-containing lipoproteins. PMID:26903710

Further evidence for plasma progranulin as a biomarker in bipolar disorder.

PubMed

Kittel-Schneider, Sarah; Weigl, Johannes; Volkert, Julia; Geßner, Alexandra; Schmidt, Brigitte; Hempel, Susanne; Kiel, Tilman; Olmes, David G; Bartl, Jasmin; Weber, Heike; Kopf, Juliane; Reif, Andreas

2014-03-01

A recent study suggested that progranulin (encoded by the fronto-temporal dementia risk gene GRN) plasma levels are decreased in bipolar disorder (BD). Replication of this finding is however lacking. Progranulin plasma levels of bipolar patients (n=104) and healthy controls (n=80) were measured by enzyme-linked immunosorbent assay (ELISA). Participants were also genotyped for three single nucleotide polymorphisms (SNPs) in the GRN gene (rs2879096, rs4792938 and rs5848), and the effect of genetic variation on progranulin levels was examined. Plasma progranulin levels were decreased in BD (ANCOVA, p=0.001). Furthermore, age was significantly and positively correlated with plasma progranulin (Pearson׳s correlation, r=0.269, p<0.001). Also, lithium treatment but no other medication had a significant effect on progranulin plasma levels (ANCOVA, p=0.007). Specifically in BD, the GRN SNP rs5848 was associated with progranulin plasma levels (Kruskal-Wallis test, p<0.005). Subgroup analysis regarding bipolar I vs. bipolar II subtype and polarity of the episode at sampling (manic vs. depressed vs. mixed vs. rapid cycling vs. euthymic) could only be performed with limited validity due to the relatively small sample size. The suitability of peripheral progranulin as a biomarker for BD is limited due to the overlap between patients and controls. The findings strengthen the evidence for progranulin being involved in pathomechanisms of bipolar disorder, and suggest a genetic determinant of progranulin concentrations that is relevant specifically in bipolar patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Elevated plasma oxytocin levels in children with Prader-Willi syndrome compared with healthy unrelated siblings.

PubMed

Johnson, Lisa; Manzardo, Ann M; Miller, Jennifer L; Driscoll, Daniel J; Butler, Merlin G

2016-03-01

Prader-Willi syndrome (PWS) is a rare genetic disorder associated with distinct abnormal behaviors including hyperphagia, profound social deficits, and obsessive-compulsive tendencies. PWS males showed reduced oxytocin receptor (OTR) gene expression and density in the hypothalamic paraventricular nucleus that may play a role in PWS psychopathology. Oxytocin is an anorexigenic neuropeptide similar to vasopressin that is associated with social cognition and obsessive-compulsive behavior. To evaluate oxytocin biology in PWS, we examined overnight fasting plasma oxytocin levels in 23 children with PWS (mean ± SD age: 8.2 ± 2.0 year) having genetic confirmation and 18 age matched healthy unrelated siblings without PWS (mean ± SD age: 8.2 ± 2.3 year) and a similar gender ratio under the same clinical assessments, specimen processing and laboratory conditions. Multiplex immune assays were carried out using the Milliplex Human Neuropeptide Magnetic panel and the Luminex system. Natural log-transformed oxytocin levels were analyzed using general linear model adjusting for diagnosis, gender, age and body mass index (BMI). Oxytocin plasma levels were significantly elevated in children with PWS (168 ± 121 pg/ml) compared with unrelated and unaffected siblings without the diagnosis of PWS (64.8 ± 83.8 pg/ml, F = 8.8, P < 0.01) and the diagnosis of PWS predicted oxytocin level (F = 9.5, P < 0.003) in controlled regression analysis with an overall model fit R(2) = 0.33 (P < 0.01). The symptoms of hyperphagia, anxiety and repetitive behaviors classically seen in PWS may be related to the disruption of oxytocin responsivity or feedback in the hypothalamic paraventricular nucleus possibly influencing vasopressin signaling. Further study is needed to characterize oxytocin function in PWS. © 2015 Wiley Periodicals, Inc.

Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease.

PubMed

Ju, Chun-Rong; Chen, Miao; Zhang, Jian-Heng; Lin, Zhi-Ya; Chen, Rong-Chang

2016-01-01

To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD). The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin. The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 ± 2.95) than in those without (13.56 ± 3.09), and much higher than in controls (8.79±2.79), with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05). Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05. Plasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD.

Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease

PubMed Central

Ju, Chun-rong; Chen, Miao; Zhang, Jian-heng; Lin, Zhi-ya; Chen, Rong-chang

2016-01-01

Objective To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD). Methods The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin. Results The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 ± 2.95) than in those without (13.56 ± 3.09), and much higher than in controls (8.79±2.79), with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05). Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05. Conclusions Plasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD. PMID:26998756

Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma.

PubMed

Stryker, W S; Stampfer, M J; Stein, E A; Kaplan, L; Louis, T A; Sober, A; Willett, W C

1990-04-01

Dietary intake and the plasma levels of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene for 204 cases with malignant melanoma were compared with those of 248 controls. Cases and controls were patients 18 years of age or older making their first visit to a dermatology subspecialty clinic for pigmented lesions from July 1, 1982 to September 1, 1985. Intakes of nutrients were estimated using a semiquantitative food frequency questionnaire. No significant associations with malignant melanoma were observed for higher plasma levels of lycopene, retinol, or alpha-carotene in logistic regression analyses after controlling for age, sex, plasma lipids, and known constitutional risk factors (hair color and ability to tan). In similar models, the odds ratio comparing the highest with the lowest quintile was 0.9 (95% confidence interval (CI) 0.5-1.5) for plasma beta-carotene, 0.7 (95% CI 0.5-1.3) for plasma alpha-tocopherol, 0.7 (95% CI 0.4-1.2) for carotene intake, and 0.7 (95% CI 0.4-1.3) for total vitamin E intake. A trend toward reduced risk of melanoma was observed for increasing intake of iron (not including supplements); this was related to the more frequent consumption of baked goods, such as cake, among controls. Alcohol consumption was positively associated with risk of melanoma (chi for trend = 2.1, p = 0.03); the odds ratio for consumption of over 10 g/day compared with persons with no alcohol intake was 1.8 (95% CI 1.0-3.3).

Plasma levels of advanced glycation endproducts are associated with type 1 diabetes and coronary artery calcification

PubMed Central

2013-01-01

Background Advanced glycation endproducts (AGEs) may play a role in the development of coronary artery calcification (CAC) in type 1 diabetes (T1DM). We studied plasma AGEs in association with T1DM and CAC, and whether or not the latter association could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). Methods We studied 165 individuals with and 169 without T1DM. CAC was quantified in a CAC score based on CT-scanning. Plasma levels of protein-bound pentosidine, Nϵ-(carboxymethyl)lysine (CML) and Nϵ-(carboxyethyl)lysine (CEL) were measured with HPLC/UPLC with fluorescence detection or tandem-mass spectrometry. Tetrahydropyrimidine (THP) was measured with ELISA, as were HsCRP, and sVCAM-1 and vWF, as markers for LGI and ED, respectively. Associations were analyzed with ANCOVA and adjusted for age, sex, BMI, waist-to-hip ratio, smoking, blood pressure, lipid profile, eGFR and T1DM. Results Individuals with T1DM had higher plasma levels of pentosidine, CML and THP compared with controls; means (95% CI) were 0.69 (0.65-0.73) vs. 0.51 (0.48-0.54) nmol/mmol LYS, p < 0.001; 105 (102–107) vs. 93 (90–95) nmol/mmol LYS, p < 0.001; and 126 (118–134) vs. 113 (106–120) U/mL, p = 0.03, respectively. Levels of pentosidine were higher in individuals with T1DM with a moderate to high compared with a low CAC score, means (95% CI) were 0.81 (0.70-0.93) vs. 0.67 (0.63-0.71) nmol/mmol LYS, p = 0.03, respectively. This difference was not attenuated by adjustment for LGI or ED. Conclusions We found a positive association between pentosidine and CAC in T1DM. These results may indicate that AGEs are possibly involved in the development of CAC in individuals with T1DM. PMID:24134530

Early pregnancy fasting plasma glucose and lipid concentrations in pregnancy and association to offspring size: a retrospective cohort study.

PubMed

Liu, Bin; Geng, Huizhen; Yang, Juan; Zhang, Ying; Deng, Langhui; Chen, Weiqing; Wang, Zilian

2016-03-17

Hyperlipidemia and high fasting plasma glucose levels at the first prenatal visit (First Visit FPG) are both related to gestational diabetes mellitus, maternal obesity/overweight and fetal overgrowth. The purpose of the present study is to investigate the correlation between First Visit FPG and lipid concentrations, and their potential association with offspring size at delivery. Pregnant women that received regular prenatal care and delivered in our center in 2013 were recruited for the study. Fasting plasma glucose levels were tested at the first prenatal visit (First Visit FPG) and prior to delivery (Before Delivery FPG). HbA1c and lipid profiles were examined at the time of OGTT test. Maternal and neonatal clinical data were collected for analysis. Data was analyzed by independent sample t test, Pearson correlation, and Chi-square test, followed by partial correlation and multiple linear regression analyses to confirm association. Statistical significance level was α =0.05. Analyses were based on 1546 mother-baby pairs. First Visit FPG was not correlated with any lipid parameters after adjusting for maternal pregravid BMI, maternal age and gestational age at First Visit FPG. HbA1c was positively correlated with triglyceride and Apolipoprotein B in the whole cohort and in the NGT group after adjusting for maternal age and maternal BMI at OGTT test. Multiple linear regression analyses showed neonatal birth weight, head circumference and shoulder circumference were all associated with First Visit FPG and triglyceride levels. Fasting plasma glucose at first prenatal visit is not associated with lipid concentrations in mid-pregnancy, but may influence fetal growth together with triglyceride concentration.

Clinical characteristics of high plasma adiponectin and high plasma leptin as risk factors for arterial stiffness and related end-organ damage.

PubMed

Kohara, Katsuhiko; Ochi, Masayuki; Okada, Yoko; Yamashita, Taiji; Ohara, Maya; Kato, Takeaki; Nagai, Tokihisa; Tabara, Yasuharu; Igase, Michiya; Miki, Tetsuro

2014-08-01

The relationship between plasma levels of adiponectin and cardiovascular events is inconclusive. We evaluated the clinical characteristics of people with high plasma adiponectin and high plasma leptin levels. Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc were divided into four groups by combining the bipartiles of plasma adiponectin and leptin levels in men and women separately: AL, high adiponectin and high leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin; aL, low adiponectin and high leptin. Body composition, including visceral fat area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion, were determined. Twenty percent of the studied population fell within the AL group. This group had a significantly higher visceral fat area than the Al group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain white matter lesions, and albuminuria findings in the AL group were significantly higher than those of the Al group. Multiple and logistic regression analyses with confounding parameters further confirmed that plasma adiponectin was not an independent determinant for brain and renal small vessel-related disease. These findings suggest that the plasma level of adiponectin alone is not enough for the risk stratification of cardiovascular disease. Leptin resistance associated with skeletal muscle loss in addition to obesity may need to be addressed to identify high risk people with high plasma adiponectin levels. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

EVALUATION OF PLASMA SUBSTANCE P AND BETA-ENDORPHIN LEVELS IN CHILDREN WITH PRADER-WILLI SYNDROME.

PubMed

Butler, M G; Nelson, T A; Driscoll, D J; Manzardo, A M

2015-09-01

Prader-Willi syndrome (PWS) is a rare obesity-related genetic disorder often caused by a deletion of the chromosome 15q11-q13 region inherited from the father or by maternal disomy 15. Growth hormone deficiency with short stature, hypogonadism, cognitive and behavioral problems, analgesia, decreased gastric motility and decreased ability to vomit with hyperphagia are common in PWS leading to severe obesity in early childhood, if not controlled. Substance P (SP) and beta-endorphin (BE) are neuropeptides involved with centrally and peripherally mediated pain perception, emotional regulation, and gastric motility impacting nausea, emesis and feeding patterns. The goal of this study was to investigate potential mechanisms for PWS symptom development for pain, emotion and gastric motility and plasma levels of substance P and beta-endorphin between PWS and unrelated unaffected children. Plasma samples were collected from 23 Caucasian children with PWS and 18 unrelated, unaffected siblings with an average age of 8.2 ±2.0 years and age range of 5 to 11 years following an overnight fast and neuropeptide substance p and beta-endorphin levels were assessed using Multiplex sandwich immunoassays using the Luminex magnetic-bead based platform. Linear regression analysis was carried out on log-transformed values adjusted for age, sex, and body mass index (BMI). The mean plasma SP (57 ± 23 pg/ml) and BE (592 ± 200 pg/ml) levels in PWS were significantly higher than SP (35 ± 20 pg/ml, F=10.5, P <0.01) and BE (402 ± 162 pg/ml, F=10.8, P <0.01) levels found in unrelated, unaffected siblings suggesting a previously uncharacterized neuroendocrine pathophysiology in PWS. The increased BE and SP plasma levels relative to unrelated, unaffected siblings may contribute to hyperphagia, abnormal pain sensation and adrenal insufficiency seen in PWS. Increases in SP levels may be modulated by central and/or peripheral actions of BE on opioid, GABA or POMC precursors and may reflect loss of feedback inhibitory control. Further studies are needed to confirm and elucidate the biochemical basis for observed disturbances in neuropeptide levels seen in our study and may impact on the development and persistence of symptoms commonly seen in PWS.

Sample Preparation Report of the Fourth OPCW Confidence Building Exercise on Biomedical Sample Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Udey, R. N.; Corzett, T. H.; Alcaraz, A.

Following the successful completion of the 3rd biomedical confidence building exercise (February 2013 – March 2013), which included the analysis of plasma and urine samples spiked at low ppb levels as part of the exercise scenario, another confidence building exercise was targeted to be conducted in 2014. In this 4th exercise, it was desired to focus specifically on the analysis of plasma samples. The scenario was designed as an investigation of an alleged use of chemical weapons where plasma samples were collected, as plasma has been reported to contain CWA adducts which remain present in the human body for severalmore » weeks (Solano et al. 2008). In the 3rd exercise most participants used the fluoride regeneration method to analyze for the presence of nerve agents in plasma samples. For the 4th biomedical exercise it was decided to evaluate the analysis of human plasma samples for the presence/absence of the VX adducts and aged adducts to blood proteins (e.g., VX-butyrylcholinesterase (BuChE) and aged BuChE adducts using a pepsin digest technique to yield nonapeptides; or equivalent). As the aging of VX-BuChE adducts is relatively slow (t1/2 = 77 hr at 37 °C [Aurbek et al. 2009]), soman (GD), which ages much more quickly (t1/2 = 9 min at 37 °C [Masson et al. 2010]), was used to simulate an aged VX sample. Additional objectives of this exercise included having laboratories assess novel OP-adducted plasma sample preparation techniques and analytical instrumentation methodologies, as well as refining/designating the reporting formats for these new techniques.« less

Effect of castration at 10 months of age on growth physiology and behavior of male feral beef cattle.

PubMed

Álvarez-Rodríguez, Javier; Albertí, Pere; Ripoll, Guillermo; Blasco, Isabel; Sanz, Albina

2017-07-01

This study compared the growth performance, plasma testosterone and cortisol levels around castration at 10 months of age, and plasma insulin-like growth factor (IGF)-I concentration and flight speed, in intact bulls and steers from 10 to 21 months of age in a feral Spanish breed. Fourteen bulls (366.5 ± 48.5 kg live weight) were assigned at random to one of two treatments: surgically castrated (steers) or intact (bulls), and submitted to an identical fattening period. Steers reared until heavy live weights (21 months of age) grew slowly and had lower plasma IGF-I concentrations than intact bulls. These differences were mainly highlighted the month after surgery (11 months of age) and the last part of the fattening period (from 19 to 21 months of age). After surgical castration (11 and 12 months of age), steers showed a tendency to display greater flight speed values than intact bulls but baseline plasma cortisol concentration did not differ between groups at this time. At the end, steers and bulls reached nearly similar temperament, as flight speed did not differ between them. The results confirm the role of IGF-I as a key anabolic hormone in male beef cattle and thus it may reflect growth differences due to altered sex steroids production. © 2016 Japanese Society of Animal Science.

Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Consitt, Leslie A., E-mail: consitt@ohio.edu; Diabetes Institute, Ohio University, Athens, OH, 45701; Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens, OH, 45701

The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19–29 years) and fifteen middle-to older-aged (57–82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin-stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation. Insulin infusion decreased the majority of plasma short-, medium-, and long-chain (SC, MC, and LC, respectively) AC. However, during the initial 50 min, a number ofmore » MC and LC AC species (C10, C10:1, C12:1, C14, C16, C16:1, C18) remained elevated in aged individuals compared to their younger counterparts indicating a lag in responsiveness. Additionally, the insulin-induced decline in skeletal muscle ACC phosphorylation was blunted in the aged compared to young individuals (−24% vs. −56%, P < 0.05). These data suggest that a desensitization to insulin during aging, possibly at the level of skeletal muscle ACC phosphorylation, results in a diminished ability to transition to glucose oxidation indicative of metabolic inflexibility. - Highlights: • Plasma acylcarnitine profiling reveals metabolic inflexibility in aged individuals. • Time course acylcarnitine profiling is critical to identify metabolic dysfunction. • Acetyl-CoA carboxylase phosphorylation status is related to metabolic dysfunction.« less

The effect of cyclodextrin-solubilized curcuminoids on amyloid plaques in Alzheimer transgenic mice: brain uptake and metabolism after intravenous and subcutaneous injection

PubMed Central

2013-01-01

Introduction Curcuminoids may improve pathological conditions associated with Alzheimer's disease. However, their therapeutic potential is limited by their exceedingly low bioavailability after oral administration. A method to deliver solubilized curcuminoids by injection was evaluated in Alzheimer transgenic mice. Methods Amyloid protein precursor (APP)SWE, PS1dE9 mice were intravenously or subcutaneously injected at weekly intervals between the ages of 4 and 12 months with serum- or cyclodextrin-solubilized curcuminoids to assess their potential for plaque prevention. Alternatively, mice between the ages of 11 and 12 months were intravenously injected with cyclodextrin-solubilized curcuminoids at biweekly intervals to evaluate their ability to eliminate existing plaques. Plasma and brain levels of curcuminoids and their metabolites were also determined after subcutaneous and intravenous injection. Results Weekly long-term injections did not result in a significant plaque load reduction. However, intravenous injection of cyclodextrin-solubilized curcuminoids at higher curcuminoid concentrations and at a biweekly frequency between the ages of 11 and 12 months reduced the plaque load to approximately 70% of the control value. After intravenous injection, plasma levels of 100 μM curcuminoids and brain levels of 47 nmol/g could initially be achieved that declined to essentially undetectable levels within 20 minutes. The primary curcuminoid metabolites in plasma were the conjugates of glucuronide or sulfate and hexahydrocurcuminoids as reduction products. In the brain, both hexahydrocurcuminoids and octahydrocurcuminoids were detected as major metabolites. After subcutaneous injection, maximal curcuminoid plasma levels of 23 μM and brain levels of 8 nmol/g were observed at 30 minutes after injection and curcuminoids remained detectable for 2 to 3 h. Conclusion Curcuminoids are rapidly metabolized after injection and their effect on reducing plaque load associated with Alzheimer's disease may be dependent on the frequency of administration. PMID:23537472

Role of elevated plasma soluble ICAM-1 and bronchial lavage fluid IL-8 levels as markers of chronic lung disease in premature infants.

PubMed Central

Little, S.; Dean, T.; Bevin, S.; Hall, M.; Ashton, M.; Church, M.; Warner, J.; Shute, J.

1995-01-01

BACKGROUND--Pulmonary neutrophilia characterises both the relatively transient inflammation associated with infant respiratory distress syndrome (IRDS) and the persistent inflammation of chronic lung disease. The possibility that persistently raised markers of inflammation indicate the development of chronic lung disease in low birth weight (< 1730 g) preterm (< 31 weeks) infants was therefore investigated. METHODS--Soluble ICAM-1 (sICAM-1) levels in plasma, and interleukin (IL)-8 and myeloperoxidase (MPO) levels in bronchial lavage fluid (BLF) obtained from 17 infants on days 1, 5, and 14 following birth were measured and correlations with the number of neutrophils in BLF sought. Peripheral neutrophils were isolated on Polymorphoprep and chemotactic responsiveness to IL-8 was assessed using micro Boyden chambers. RESULTS--Sixteen infants developed IRDS and, of these, 10 infants subsequently developed chronic lung disease. Levels of IL-8 in BLF at 14 days of age correlated with the long term requirement for intermittent positive pressure ventilation (IPPV). Interleukin 8 levels in BLF correlated with neutrophil numbers and MPO concentration, suggesting both recruitment and activation in response to this cytokine. Antibody depletion studies showed that approximately 50% of total neutrophil chemotactic activity in BLF was due to IL-8. No difference in peripheral neutrophil chemotactic responsiveness at any age was observed for infants with IRDS or chronic lung disease. Plasma soluble intercellular adhesion molecule (sICAM-1) was higher at 14 days of age in infants who developed chronic lung disease than in those with resolving IRDS, and correlated with severity of disease, as indicated by duration of IPPV. CONCLUSIONS--The results indicate that high levels of plasma sICAM-1 and IL-8 in BLF at day 14 correlate with the development of chronic lung disease and indicate the severity of disease. PMID:7491556

Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans.

PubMed

Butler, Andrew A; St-Onge, Marie-Pierre; Siebert, Emily A; Medici, Valentina; Stanhope, Kimber L; Havel, Peter J

2015-10-05

Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations.

Calcium Metabolism in Newborn Infants THE INTERRELATIONSHIP OF PARATHYROID FUNCTION AND CALCIUM, MAGNESIUM, AND PHOSPHORUS METABOLISM IN NORMAL, “SICK,” AND HYPOCALCEMIC NEWBORNS

PubMed Central

David, Louis; Anast, Constantine S.

1974-01-01

Serum immunoreactive parathyroid hormone (iPTH) and plasma total calcium, ionized calcium, magnesium, and phosphorus levels were determined during the first 9 days of life in 137 normal term infants, 55 “sick” infants, and 43 hypocalcemic (Ca <7.5 mg/100 ml; Ca++<4.0 mg/100 ml) infants. In the cord blood, elevated levels of plasma Ca++ and Ca were observed, while levels of serum iPTH were either undetectable or low. In normal newborns during the first 48 h of life there was a decrease in plasma Ca and Ca++, while the serum iPTH level in most samples remained undetectable or low; after 48 h there were parallel increases in plasma Ca and Ca++ and serum iPTH levels. Plasma Mg and P levels increased progressively after birth in normal infants. In the sick infants, plasma Ca, Ca++ and P levels were significantly lower than in the normal newborns, while no significant differences were found in the plasma Mg levels. The general pattern of serum iPTH levels in the sick infants was similar to that observed in the normal group, though there was a tendency for the increase in serum iPTH to occur earlier and for the iPTH levels to be higher in the sick infants. In the hypocalcemic infants, plasma Mg levels were consistently lower than in the normal infants after 24 h of age, while no significant differences were found in the plasma P levels. Hyperphosphatemia was uncommon and did not appear to be a contributing factor in the pathogenesis of hypocalcemia in most infants. Most of the hypocalcemic infants, including those older than 48 h, had inappropriately low serum iPTH levels. Evidence obtained from these studies indicates that parathyroid secretion is normally low in the early new born period and impaired parathyroid function, characterized by undetectable or low serum iPTH, is present in most infants with neonatal hypocalcemia. Additional unknown factors appear to contribute to the lowering of plasma Ca in the neonatal period. The net effect of unknown plasma hypocalcemic factor(s) on the one hand and parathyroid activity on the other may account for differences in plasma Ca levels observed between normal, sick, and hypocalcemic infants. Depressed plasma Mg is frequently present in hypocalcemic infants. To what degree the hypomagnesemia reflects parathyroid insufficiency or the converse, to what degree parathyroid insufficiency and hypocalcemia are secondary to hypomagnesemia, is uncertain. PMID:4858778

Plasma markers of inflammation and prediction of cardiovascular disease and mortality in African Americans with type 1 diabetes.

PubMed

Roy, Monique S; Janal, Malvin N; Crosby, Juan; Donnelly, Robert

2016-04-01

To determine whether plasma levels of markers of inflammation are predictive of the incidence of cardiovascular disease (CVD), hypertension, or mortality in African Americans with type 1 diabetes mellitus. A total of 484 African Americans with type 1 diabetes were included. At baseline and 6-year follow-up, a clinical interview and examination were conducted to document CVD and systemic hypertension. Venous blood for glycated hemoglobin and cholesterol was obtained and albumin excretion rate measured. Mortality was assessed annually between baseline and 6-year follow-up by review of the social security death index. Baseline plasma levels of 28 inflammatory biomarkers were measured using multiplex bead analysis system. After adjusting for baseline age and other confounders, African Americans with type 1 diabetes in the highest quartile of plasma interferon-inducible protein 10 (IP-10) were three times more likely to develop CVD than those in the lowest quartile. African Americans with type 1 diabetes in the lowest quartiles of plasma stromal derived factor-1 (SDF-1) had a 75% higher risk of death than patients in the highest quartile, independently of age, low density lipoprotein cholesterol, body mass index, hypertension, and albuminuria. In African Americans with type 1 diabetes, high plasma IP-10 is an independent predictor for incident CVD and low SDF-1 an independent predictor for mortality. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Plasma homovanillic acid and prolactin in Huntington's disease.

PubMed

Markianos, Manolis; Panas, Marios; Kalfakis, Nikos; Vassilopoulos, Dimitrios

2009-05-01

Dopaminergic activity is expected to be altered in patients with Huntington's disease (HD) and be related to factors like duration and severity of illness or patients' specific symptomatology like dementia, depression, or psychotic features. We assessed plasma homovanillic acid (pHVA) and plasma prolactin (pPRL), two correlates of dopaminergic activity, in 116 subjects with CAG repeats expansion in the HD gene, 26 presymptomatic (18 females) and 90 with overt symptomatology (43 females). Patients were evaluated using the Unified HD Rating Scale and the Total Functional Capacity Scale. Presence of dementia, depression, and psychotic features were also assessed. The age range of the patients was 22-83 years, duration of illness from 0.5 to 27 years, and CAG repeat number from 34 to 66. A group of 60 age and sex matched healthy subjects served as control group. Plasma PRL in subjects at risk and in neuroleptic-free patients, evaluated separately for males and females, did not differ from controls. Plasma HVA levels did not differ from controls in the group of presymptomatic subjects, but were significantly higher in the patients group. This increase was positively associated mainly with severity of illness and functional capacity of the patients, and not with presence of depression or dementia. Plasma HVA levels may be proven to be a peripheral index of disease progression. Reducing dopaminergic activity may have not only symptomatic, but also neuroprotective effects in HD.

Progesterone and estradiol plasma levels in neonatally irradiated cycling rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freud, A.; Sod-Moriah, U.A.

1990-01-01

Female rats which were exposed to a single low dose of gamma irradiation (6R or 15R) at the age of 8 days produce smaller litters when mature than untreated controls. The possibility that the impaired fertility resulted from altered ovarian activity as reflected by changes in plasma levels of progesterone or estardiol was investigated. Plasma levels of both steroids were determined throughout the day of proestrus. Progesterone level was also determined in 6R animals on the day of weaning. The maturity of such irradiated rats was assessed by observing the time of vaginal opening. The results indicated that the preovulatorymore » peak of progesterone was delayed in the 6R rats whereas in the 15R group its levels were significantly lower. On the other hand no differences in estradiol plasma levels were noticed between the groups. The higher level of progesterone in the 6R animals was not evident on the day of weaning and was even in both groups, but vaginal opening in the irradiated rats was significantly delayed. The elevated level of progesterone might be responsible, among other endocrine changes, for the lower fertility of neonatally irradiated mature female rats.« less

Visceral predictors of cardiovascular deconditioning in late middle-aged men

NASA Technical Reports Server (NTRS)

Goldwater, D. J.; De Roshia, C.; Natelson, B. H.; Levin, B. E.

1985-01-01

A number of visceral and behavioral factors connected with cardiovascular deconditioning were investigated, in order to identify a method for predicting the degree of orthostatic intolerance to spaceflight in several late-middle-aged men (55-65 years). Preliminary measurements were made of: mean arterial blood pressure plasma cortisol levels; and norepinephrine levels. Measurements of core temperature; plasma epinephrine level and subjective arousal from sleep were also obtained. Pairwise correlations were found for each of the variables and the time-to-blackout due centrifugal acceleration of up to +3 Gz. It is shown that the men with relatively low resting blood pressure were at greater risk of developing the clinical signs of cardiovascular deconditioning than were the men with higher basal blood pressure. Some applications of the experimental results to the development of selection criteria for Shuttle crews are discussed.

Plasma folate levels in early to mid pregnancy after a nation-wide folic acid supplementation program in areas with high and low prevalence of neural tube defects in China.

PubMed

Liu, Jufen; Gao, Lili; Zhang, Yali; Jin, Lei; Li, Zhiwen; Zhang, Le; Meng, Qinqin; Ye, Rongwei; Wang, Linlin; Ren, Aiguo

2015-06-01

Folic acid supplementation is recommended for all women of child-bearing age to prevent neural tube defects (NTDs). A nation-wide folic acid supplementation program was implemented in rural areas of China since 2009; however, changes in plasma folate levels in pregnant women were unknown. A cross-sectional survey was conducted in 2011 to 2012, with 1736 pregnant women enrolled, and results were compared with a previous survey in 2002 to 2004. A microbiological method was used to determine plasma folate levels. Preprogram and postprogram median plasma folate concentrations were compared while stratified by prevalence of NTDs and residence. In the high NTD prevalence population, plasma folate concentration increased to 33.4 (18.7, 58.4) nmol/L in the postprogram sample, which is 2.9 times of the preprogram. In the low NTD prevalence population, plasma folate increased to 67.9 (44.5, 101.9) nmol/L, which is 1.9 times of the preprogram. Gaps remained in plasma folate levels with respect to prevalence of NTDs and residence. Folic acid supplementation has a strong impact on plasma folate concentrations. Earlier supplementation (before the last menstrual period), increased supplementation frequency and more total days of supplementation were associated with a higher plasma folate concentration as demonstrated in both the high- and low-prevalence populations. Plasma folate levels among pregnant Chinese women increased dramatically after the nation-wide folic acid supplementation program in both rural and urban areas, and in populations of high and low NTD prevalence. The nation-wide program should have a component to ensure that supplementation begins before pregnancy. © 2015 Wiley Periodicals, Inc.

Children with cow's milk allergy following an elimination diet had normal growth but relatively low plasma leptin at age two.

PubMed

Dong, Ping; Feng, Jing-Jing; Yan, Dong-Yong; Lyu, Yu-Jing; Xu, Xiu

2018-02-20

To assess nutrient intake, growth and nutritional status of infants with cow's milk allergy (CMA) who follow a therapeutic elimination diet since the first few months of life. Sixty infants younger than four months of age with challenge-proven CMA and 60 healthy age-matched children were investigated. Anthropometric and body composition (BC) were assessed up to 24 months. Dietary intake was recorded by the parents for three consecutive days before visits at 6, 12, 18 and 24 months. Blood albumin, prealbumin, retinol binding protein and metabolic-related hormones were examined at 24 months. The average age at enrolment was 2.9 ± 1.0 months. At the end of the follow-up, there were no differences in daily milk consumption, nutrient intake, weight and height z scores or BC measures between the groups; however, the plasma leptin level was lower in infants with CMA (1.67 ± 1.03 vs 2.05 ± 1.48) (ng/mL) (p < 0.05) compared to healthy children. Children with CMA who followed an elimination diet could achieve a normal nutritional status, except for relatively lower plasma leptin levels, at the age of 2. Further studies with larger cohorts and research on the long-term consequences of these early differences are needed. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Association between body mass index and presence of carotid plaque among low-income adults aged 45 years and older: a population-based cross-sectional study in rural China.

PubMed

Lou, Yongzhong; Li, Bin; Su, Lan; Mu, Zhenhong; Sun, Minghao; Gu, Hongfei; Ni, Jingxian; Wu, Yanan; Tu, Jun; Wang, Jinghua; Ning, Xianjia

2017-10-06

Carotid plaque is a good surrogate endpoint for assessing arterial atherosclerosis, and atherosclerosis is a reliable predictor of cardiovascular diseases. However, the effect of body mass index on carotid plaque is unknown. Therefore, we aimed to explore the association between body mass index and carotid plaque in a low-income Chinese population. Residents aged ≥45 years and free of stroke and cardiovascular diseases were enrolled and divided into four groups based on body mass index. B-mode ultrasonography was performed to measure carotid plaque. The mean age of participants was 59.92 years overall. Significant correlations were observed between the presence of carotid plaque and male sex, older age, systolic blood pressure, fasting plasma glucose, and low-density lipoprotein cholesterol among the different BMI subgroups. Male sex increased the risk of carotid plaque in the overweight and obese groups. Older age and high level of low-density lipoprotein cholesterol were the independent risk factor for carotid plaque in four groups. Increased systolic blood pressure was an independent risk factor in the normal-weight, overweight, and obese groups; however, fasting plasma glucose was only significant in the normal-weight group. Thus, controlling the levels of low-density lipoprotein cholesterol, systolic blood pressure, and fasting plasma glucose is required to reduce carotid plaque risk.

Decreased plasma neuregulin 4 concentration is associated with increased high-sensitivity C-reactive protein in newly diagnosed type 2 diabetes mellitus patients: a cross-sectional study.

PubMed

Yan, Pi-Jun; Xu, Yong; Wan, Qin; Feng, Jian; Li, Hua; Gao, Chen-Lin; Yang, Jun; Zhong, Hai-Hua; Zhang, Zhi-Hong

2017-12-01

Inflammation has been reported to be involved in the pathogenesis of atherosclerosis. This principal objective of this study was to investigate if the secretion of neuregulin 4 (Nrg4), a soluble protein associated with metabolic syndrome and subclinical cardiovascular disease, is correlated with the inflammation marker high-sensitivity C-reactive protein (hs-CRP) in patients with newly diagnosed type 2 diabetes mellitus (nT2DM). A study group of 311 nT2DM patients was divided into three subgroups based on hs-CRP tertiles. Multiple linear regression was conducted to explore the association between plasma Nrg4 and hs-CRP levels. The nT2DM patients with the highest hs-CRP levels (>2.46 mg/L) exhibited higher atherogenic coefficients and atherogenic index of plasma (AIP) levels, but lower levels of plasma Nrg4, as compared to those with the lowest hs-CRP levels (<0.63 mg/L). Plasma Nrg4 levels were inversely associated with white blood cell count, hs-CRP, and AIP and positively associated with high-density lipoprotein cholesterol (HDL-C), before and after adjustment for age, gender, body mass index (BMI), and body fat percentage (P < 0.01 or P < 0.05). hs-CRP was the factor most strongly associated with plasma Nrg4 levels. These results indicate that lower plasma Nrg4 levels may be associated with elevated hs-CRP in nT2DM patients. It generates the hypothesis that decreased levels of Nrg4 may trigger the development of atherosclerosis through its proinflammatory effects. These findings need to be confirmed by further prospective studies.

Plasma carotenoids and the risk of premalignant breast disease in women aged 50 and younger: a nested case-control study.

PubMed

Cohen, Kevin; Liu, Ying; Luo, Jingqin; Appleton, Catherine M; Colditz, Graham A

2017-04-01

To examine the association of plasma carotenoids, micronutrients in fruits, and vegetables, with risk of premalignant breast disease (PBD) in younger women. Blood samples were collected at the Siteman Cancer Center between 2008 and 2012 from 3537 women aged 50 or younger with no history of cancer or PBD. The analysis included 147 participants diagnosed with benign breast disease or breast carcinoma in situ during a 27-month follow-up and 293 controls. Cases and controls were matched on age, race/ethnicity, and date of and fasting status at blood draw. Plasma carotenoids were quantified. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and linear regression to assess racial differences in plasma carotenoids. The risk reduction between the highest and lowest tertiles varied by carotenoid, with β-cryptoxanthin having the greatest reduction (OR 0.62; 95% CI, 0.62-1.09; P trend  = 0.056) and total carotenoids the least (OR 0.83; 95% CI, 0.48-1.44; P trend  = 0.12). We observed an inverse association between plasma carotenoids and risk of PBD in obese women (BMI ≥ 30 kg/m 2 ; 61 cases and 115 controls) but not lean women (BMI < 25 kg/m 2 ; 54 cases and 79 controls), although the interaction was not statistically significant. Compared to white women, black women had lower levels of α and β-carotene and higher levels of β-cryptoxanthin and lutein/zeaxanthin. We observed suggestive inverse associations between plasma carotenoids and risk of PBD in younger women, consistent with inverse associations reported for invasive breast cancer. Carotenoids may play a role early in breast cancer development.

Plasma Carotenoids and the Risk of Premalignant Breast Disease in Women Aged 50 and Younger: A Nested Case-Control Study

PubMed Central

Cohen, Kevin; Liu, Ying; Luo, Jingqin; Appleton, Catherine M.; Colditz, Graham A.

2017-01-01

Purpose To examine the association of plasma carotenoids, micronutrients in fruits and vegetables, with risk of premalignant breast disease (PBD) in younger women. Methods Blood samples were collected at the Siteman Cancer Center between 2008 and 2012 from 3,537 women aged 50 or younger with no history of cancer or PBD. The analysis included 147 participants diagnosed with benign breast disease or breast carcinoma in situ during a 27-month followup and 293 controls. Cases and controls were matched on age, race/ethnicity, and date of and fasting status at blood draw. Plasma carotenoids were quantified. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and linear regression to assess racial differences in plasma carotenoids. Results The risk reduction between the highest and lowest tertiles varied by carotenoid, with β-cryptoxanthin having the greatest reduction (OR 0.62; 95% CI, 0.62–1.09; Ptrend=0.056) and total carotenoids the least (OR 0.83; 95% CI, 0.48–1.44; Ptrend=0.12). We observed an inverse association between plasma carotenoids and risk of PBD in obese women (BMI≥30 kg/m2; 61 cases and 115 controls) but not lean women (BMI<25 kg/m2; 54 cases and 79 controls), although the interaction was not statistically significant. Compared to white women, black women had lower levels of α and β-carotene and higher levels of β-cryptoxanthin and lutein/zeaxanthin. Conclusions We observed suggestive inverse associations between plasma carotenoids and risk of PBD in younger women , consistent with inverse associations reported for invasive breast cancer. Carotenoids may play a role early in breast cancer development. PMID:28190250

Psychosocial job characteristics and plasma fibrinogen in Japanese male and female workers: the Jichi Medical School cohort study.

PubMed

Hirokawa, Kumi; Tsutsumi, Akizumi; Kayaba, Kazunori

2008-06-01

The aim of the study was to explore the association between psychosocial job characteristics and plasma fibrinogen levels among 1588 male and 1677 female Japanese workers aged 65 and younger. Sociodemographic and behavioral variables were obtained by a standardized questionnaire, which included the Japanese version of the demand-control questionnaire. Fibrinogen levels were determined with a one-stage clotting assay kit. Job strain - a ratio of demand to control - was positively associated with plasma fibrinogen (p for trend<0.05) but ANCOVA showed that the main effect was only marginally statistically significant in men. Analyses by individual job characteristics components revealed that men with a high level of job demand (Age-adjusted geometric mean (mg/dl)=234.6, 95% CI: 230.9-238.2) showed a higher fibrinogen level than those with other levels (middle; 227.9, 223.6-232.3, low; 224.8, 220.5-229.1) (F (2, 1584)=6.63, p<0.001). Adjustment for potential confounders including total cholesterol and CRP did not reduce the association. No significant association was found between psychosocial job characteristics and fibrinogen in women. The findings appear to imply a mechanism through which adverse psychosocial job characteristics lead to cardiovascular diseases in men.

Diagnostic Usefulness of Transcutaneous Bilirubinometry in Very Preterm Newborns

PubMed Central

Badiee, Zohreh; Mohammadizadeh, Majid; Shamee, Masih

2012-01-01

Background: This study was performed to find out whether transcutaneous bilirubinometry could be a valid screening method for hyperbilirubinemia in preterm infants, especially for those who needed mechanical ventilation. Methods: We evaluated 63 preterm Iranian newborns who were managed in the neonatal intensive care unit of Shahidbeheshti University Hospital, Isfahan, Iran from April 2009 to April 2010. Transcutaneous bilirubin (TCB) measurements were obtained using BiliCheck™ shortly before or 10 minutes after taking blood for determination of the plasma bilirubin level in premature newborns, who did not receive phototherapy. We assessed the correlation between the transcutaneous bilirubin and plasma bilirubin level by linear regression analysis. We also analyzed the gestational age, birth weight, postnatal age, sex, and hematocrit, for determination of their effect on transcutaneous bilirubin accuracy. Results: The overall bilirubin concentration ranged from 5.4 to 17 mg/dL and from 4.8 to 17.3 mg/dl for total serum bilirubin (TSB) and transcutaneous bilirubin, respectively. The mean values obtained by transcutaneous bilirubinometry were slightly higher than the total TSB values. The correlation coefficient between TSB and TCB was r=0.82, P<0.001, and this was not influenced by gestational age, postnatal age or hematocrit, which were previously considered to be important. The correlation coefficient between TSB and TCB in mechanically ventilated preterm infants was r=0.75, P<0.001. Conclusion: Plasma bilirubin level can be accurately measured by BiliCheck™ in premature newborns, even in newborns who need mechanical ventilation. PMID:22624082

Vitamin E status of Alaskan Eskimos.

PubMed

Wei Wo, C K; Draper, H H

1975-08-01

A survey was conducted during 1971-1973 on the vitamin E status of Alaskan Eskomos. The subjects were 315 residents of the northern coastal villages of Wainwright and Point Hope and the southwestern inland villages of Kasigluk and Nunapitchuk. Plasma vitamin E levels for the 6- to 17-year-old subjects at Wainwright, Point Hope, and Nunapitchuk were 0.81 plus or minus 0.26, 0.90 plus or minus 0.20, and 0.84 plus or minus 0.25 mg/100 ml (mean and standard deviation), respectively. The values for adults at Wainwright, Point Hope, and Kasigluk were 1.23 plus or minus 0.27, 1.23 plus or minus 0.27, and 1.27 plus or minus 0.33 mg/100 ml, respectively. No value less than 0.30 mg/100 ml was observed. Alpha-tocopherol was the only isomer present in significant amounts. Plasma vitamin E levels did not change significantly between 6 and 17 years of age; however, a steady increase with age was observed in the 18- to 69-year-old groups. Plasma alpha-tocopherol concentrations were significantly lower in children than in adults but there were no differences attributable to sex or geographic location. Vitamin E concentration in the blood plasma was linearly correlated with cholesterol concentration. Values are reported for the vitamin E content of some native foods. This study indicates that plasma vitamin E levels in Alaskan Eskimos consuming a high meat or fish diet are comparable to those in adults of the United States consuming a mixed diet.

Diets high in total antioxidant capacity improve risk biomarkers of cardiovascular disease: a 9-month observational study among overweight/obese postmenopausal women.

PubMed

Wang, Ying; Yang, Meng; Lee, Sang-Gil; Davis, Catherine G; Koo, Sung I; Fernandez, Maria Luz; Volek, Jeff S; Chun, Ock K

2014-09-01

Previous studies have shown that total antioxidant capacity (TAC) of typical diets is associated with higher plasma TAC and antioxidant enzyme activities. At present, however, little is known for the association between dietary TAC and inflammatory biomarkers. The present study was designed to examine the association between dietary TAC and inflammatory biomarkers in a group of overweight/obese postmenopausal women, a population with high cardiovascular disease (CVD) risk, during a 9-month period. Thirty-five postmenopausal, overweight or obese, but apparently healthy women aged 40-70 years were recruited for a 9-month observational study. Seven-day food records and 12-h fasting blood samples were collected at baseline and at the end of the study for dietary and plasma biomarker assessments. Dietary TAC was calculated theoretically for taking account of both diet and dietary supplements, and energy-adjusted values were obtained using residual method. At baseline, subjects consuming diets with high dietary TAC had lower levels of plasma C-reactive protein (CRP) and monocyte chemoattractant protein-1 (p < 0.05) compared with those with low dietary TAC. Over the 9-month period, change in dietary TAC had a negative partial correlation with plasma CRP levels (p < 0.01) when age, ethnicity, and changes in BMI, blood total cholesterol and triglyceride were adjusted. Findings suggest that consumption of diets high in TAC are inversely associated with plasma CRP levels cross-sectionally and dynamically and may contribute to CVD protection.

Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals.

PubMed

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A; Sachdev, Perminder S

2012-01-01

Apolipoproteins have recently been implicated in the etiology of Alzheimer's disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

PubMed Central

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A.; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A.; Sachdev, Perminder S.

2012-01-01

Objectives Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. Methods 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. Results At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Conclusions Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals. PMID:22701550

Varying Influences of Aldosterone on the Plasma Potassium Concentration in Blacks and Whites.

PubMed

Tu, Wanzhu; Eckert, George J; Decker, Brian S; Howard Pratt, John

2017-05-01

Aldosterone acts to restrain the extracellular potassium (K+) concentration. Blacks have on average lower plasma aldosterone concentrations (PACs) than Whites. Whether this ethnic difference is associated with similar changes in the concentration of K+ is unclear. Subjects were Blacks and Whites from an observational study of blood pressure regulation. PAC was known to be significantly lower in Blacks than Whites. We sought to test the hypothesis that the concentration of K+ remains constant despite variability in PAC. Initial enrollment took place in childhood in 1986. Some of the original enrollees were studied again in adulthood: 160 healthy Blacks and 271 healthy Whites (ages 5 to 39 years; all were studied as children and as adults). Plasma renin activity [a biomarker of angiotensin II and, more proximally, extracellular fluid volume (ECFV)] and PAC were lower in Blacks (P < 0.0354 and P < 0.001, respectively, for all ages). At the same time no ethnic difference in levels of K+ was observed regardless of age. Plasma K+ concentration and PAC associated differently based on ethnicity: PAC increased in Blacks by 1.5-2.0 and in Whites by 2.3-3.0 ng/dl per mmol/l increase in K+ (P < 0.001). Lower aldosterone levels in Blacks did not translate into higher K+ concentrations. We speculate that reaching the right concentration of K+ was an endpoint of aldosterone production in the presence of varying levels of ECFV and angiotensin II. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Ghrelin and its promoter variant associated with cardiac hypertrophy.

PubMed

Ukkola, O; Pääkkö, T; Kesäniemi, Y A

2012-07-01

The roles of ghrelin, a peptide hormone that has a role in regulating food intake and energy homeostasis, in the cardiovascular system have not yet been unambiguously established. We evaluated the association between plasma ghrelin concentrations and -501A>C single-nucleotide polymorphism (SNP) in the ghrelin gene 5' flanking area and echocardiographic measurements in 1037 middle-aged subjects. Left ventricular mass index (LVMI) was calculated according to Devereux's method. The ambulatory blood pressure (BP) was recorded using the fully automatic SpaceLabs 90207 oscillometric unit. Results suggested that plasma ghrelin was not related to mean ambulatory BP values. However, the highest plasma ghrelin tertile was associated with increased intraventricular septum (P=0.043) and posterior ventricular wall (P=0.002) thicknesses as well as left ventricular mass (P=0.05). After adjustment for age, sex, body mass index and systolic BP, the association persisted between ghrelin tertiles and intraventricular septum (P=0.05) and posterior ventricular wall (P=0.001) thicknesses. The SNP -501A>C polymorphism was associated with LVMI after adjustments for age, sex and systolic BP. In conclusion, ghrelin and its promoter variant are associated with cardiac hypertrophy indexes independent of BP. Positive correlation between ghrelin levels and increased wall thickness parameters may reflect compensatory up-regulation of ghrelin concentrations or direct effects of ghrelin on myocardium. The effects of the SNP seem not to be mediated through its effects on ghrelin plasma levels.

A Pilot Study of Tissue Factor-Tissue Factor Pathway Inhibitor Axis and Other Selected Coagulation Parameters in Broiler Chickens Administered in Ovo with Selected Prebiotics*.

PubMed

Buzala, Mateusz; Ponczek, Michal Blazej; Slomka, Artur; Roslewska, Aleksandra; Janicki, Bogdan; Zekanowska, Ewa; Bednarczyk, Marek

The tissue factor (TF) - tissue factor pathway inhibitor (TFPI) axis plays a major role in hemostasis. Disorders of the coagulation system are commonly diagnosed with the help of screening tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma fibrinogen concentration (PFC). However, the effect of prebiotics on the hemostasis system has not been characterized in poultry yet. This study was designed to determine the effect of in ovo administration ofprebiotics on blood coagulation parameters of broiler chickens depending on their age. The study was conducted with 180 broiler chick embryos, the air cells of which were injected on day 12 of incubation with prebiotics (experimental groups: Bi2tos, DiNovoo and RFO) or physiological saline solution (control group). At 1, 21 and 42 days of rearing, blood was sampled from 15 broiler chickens from each group. An enzyme immunoassay was performed to determine plasma TF and TFPI levels, and PT, aPTT and PFC were determined in the chicken blood. We demonstrated that: 1) total TF levels increased with age in the experimental groups, 2) prebiotics had no significant effect on TF levels between the groups at a particular age, 3) total TFPI levels differed between both the type of in ovo injected substance and the broiler chicken age, 4) in the control group, PT and aPTT were found to increase with age whilst fibrinogen concentration decreased. The main conclusion from this pilot study is that total TF and TFPI levels change with age, however no clear patterns regarding TFPI were detected yet. The levels of PT, aPTT and PFC varied with the prebiotics administered in ovo as well as with the age of broiler chickens.

Myoglobin plasma level related to muscle mass and fiber composition: a clinical marker of muscle wasting?

PubMed

Weber, Marc-André; Kinscherf, Ralf; Krakowski-Roosen, Holger; Aulmann, Michael; Renk, Hanna; Künkele, Annette; Edler, Lutz; Kauczor, Hans-Ulrich; Hildebrandt, Wulf

2007-08-01

Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r = 0.65, p < 0.001) and to the CSA fraction formed by type 1 and 2a fibers (r = 0.80, p < 0.001). However, when adjusted for body height and age by multiple regression, MG yielded a largely improved prediction of total CSA (multiple r = 0.83, p < 0.001) and of fiber type 1 and 2a CSA (multiple r = 0.89, p < 0.001). The correlations between CK and these muscle parameters were weaker, and elevated CK values were observed in 20% of control subjects despite a prior abstinence from exercise for 5 days. In conclusion, plasma MG, when adjusted for anthropometric parameters unaffected by weight, may be considered as a novel marker of muscle mass (CSA) indicating best the mass of MG-rich type 1 and 2a fibers as well as VO(2)max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer-related muscle wasting was not associated with increases in plasma MG or CK in this study.

Role of oxidative stress enzymes in open-angle glaucoma.

PubMed

Yildirim, O; Ateş, N A; Ercan, B; Muşlu, N; Unlü, A; Tamer, L; Atik, U; Kanik, A

2005-05-01

To investigate the role of oxidative stress and lipid peroxidation in the pathogenesis of primary open-angle glaucoma (POAG). The activities of myeloperoxidase (MPO), catalase (CAT), and the levels of plasma malondialdehyde (MDA) were measured in 40 (15 men and 25 women) patients with POAG and 60 (30 men and 30 women) healthy controls. There was no significant difference in the activities of CAT and MPO between the POAG patients and the controls. However, the plasma MDA level was significantly higher in patients than the controls. The results of this preliminary study suggest that the possible alterations of plasma MDA levels may be associated with the pathogenesis of POAG, but further research is needed to understand the role of oxidative damage in this important disorder of aging.

The relationship of plasma catestatin concentrations with metabolic and vascular parameters in untreated hypertensive patients: Influence on high-density lipoprotein cholesterol

PubMed Central

Durakoğlugil, Murtaza Emre; Ayaz, Teslime; Kocaman, Sinan Altan; Kırbaş, Aynur; Durakoğlugil, Tuğba; Erdoğan, Turan; Çetin, Mustafa; Şahin, Osman Zikrullah; Çiçek, Yüksel

2015-01-01

Objective: Catestatin has several cardiovascular actions, in addition to diminished sympatho-adrenal flow. Decreased plasma catestatin levels may reflect a predisposition for the development of hypertension and metabolic disorders. We planned to investigate the possible roles of catestatin in untreated hypertensive patients. As a secondary objective, we compared catestatin concentrations of healthy subjects with those of hypertensive patients in order to understand whether catestatin is increased reactively or diminished at onset. Methods: Our study was cross-sectional and observational. The patient group, comprising 109 consecutive untreated hypertensive patients without additional systemic or coronary heart disease, underwent evaluations of plasma catestatin, waist circumference, lipid parameters, left ventricular mass, carotid intima-media thickness, and flow-mediated dilation of the brachial artery. Additionally, we measured catestatin concentrations of 38 apparently healthy subjects without any disease using a commercial enzyme-linked immunosorbent assay kit. Results: We documented increased catestatin concentrations in previously untreated hypertensive patients compared to healthy controls (2.27±0.83 vs. 1.92±0.49 ng/mL, p=0.004). However, this association became insignificant after adjustments for age, gender, height, and weight. Within the patient group, catestatin levels were significantly higher in females. Among all study parameters, age, high-density lipoprotein cholesterol (HDL-C) correlated positively to plasma catestatin, whereas triglycerides, hemoglobin, and left ventricular mass correlated negatively to plasma catestatin. We could not detect an association between vascular parameters and catestatin. Catestatin levels were significantly elevated with increasing HDL-C (1.91±0.37, 2.26±0.79, and 3.1±1.23 ng/mL in patients with HDL-C <40, 40-60, and >60 mg/dL, respectively). Multiple linear regression analysis revealed age (beta: 0.201, p=0.041) and HDL-C (beta: 0.390, p<0.001) as independent correlates of plasma catestatin concentration. Additionally, male gender (beta:-0.330, p=0.001) and plasma catestatin (beta: 0.299, p=0.002) were significantly associated with HDL-C concentrations. Conclusion: We documented that plasma catestatin is an independent predictor of high-density lipoprotein cholesterol. In addition to antihypertensive effects, catestatin appears to be related to improved lipid and metabolic profiles. Coexistence of low catestatin levels with low HDL-C may provide a probable mechanism for the predictive value of low HDL-C for increased hypertension and cardiovascular events. PMID:25538000

Age and genetic selection affect auto-immune profiles of chickens.

PubMed

Parmentier, Henk K; Harms, Elmer; Lammers, Aart; Nieuwland, Mike G B

2014-12-01

Specificity, antibody isotype distribution and levels, of natural autoantibodies (NAAb) may be potential informative parameters for immune mediated natural disease resistance, immune modulation, and maintenance of physiological homeostasis. In a previous study we detected IgM and IgG antibodies to liver antigens in plasma from 1 year old chickens. Auto-immune profiles directed towards liver antigens differed between chicken lines divergently selected for specific antibody responses to sheep red blood cells. In the present study we measured the presence and typed levels and antibody isotypes (IgG and IgM) of NAAb binding the 'auto-antigen' complex chicken liver cell lysate (CLL) in plasma samples obtained from chickens at 5 weeks and at 1-year of age, respectively, by quantitative western blotting. Extensive staining patterns of plasma antibodies binding CLL were found for both isotypes and at both ages in all birds. At both ages, IgM and IgG bound similar numbers of CLL antigens, which remained almost constant for IgM, whereas the number of IgG stained bands in time was enhanced. Significant differences of binding patterns of NAAb (stained antigen fragments of CLL and staining intensity) were detected between the three different chicken lines at both ages and between both ages, and lines could be clustered on the basis of their auto-antibody profile. The present results indicate that analysis of the plasma NAAb repertoire of poultry like in mammals could provide a way of distinguishing differences of immune competence (as reflected by the selection criterion of antibody responses) between individuals and lines, and could provide tools to select individual birds for health and other traits. The age-dependency of the auto-immune profile suggest that such profiles may also reflect immune maturation, which should be taken into account when relating an auto-immune profile with other traits. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical manifestations and quantitative analysis of virus load in Taiwanese children with Epstein-Barr virus-associated infectious mononucleosis.

PubMed

Cheng, Chia Chi; Chang, Luan Yin; Shao, Pei Lan; Lee, Ping Ing; Chen, Jong Min; Lu, Chun Yi; Lee, Chin Yun; Huang, Li Min

2007-06-01

To delineate the clinical manifestations in different age groups and to define the viral load in patients with Epstein-Barr virus-associated infectious mononucleosis (EBV-associated IM). We reviewed data on 69 children with EBV-associated IM from November 2001 to October 2005. Clinical features were evaluated among four age groups: <3 years, 3 to 5 years, 6 to 9 years and 10 to 18 years. EBV viral load was measured by quantitative real-time polymerase chain reaction (PCR) in 13 patients with 15 specimens. Majority of the children were younger than 7 years of age (76.8%) and the male-to-female ratio was 1.6:1. The symptoms and signs included fever (91.3%), tonsillopharyngitis (88.4%), lymphadenopathy (78.3%) and hepatitis (75.4%). The younger age group had higher monocyte count, lower occurrence of hepatitis, and lower glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels than the older age group. The median (range) EBV viral load of peripheral blood mononuclear cells (PBMCs) and plasma in IM patients was 738 (0-7455) copies/mug DNA and 51 (0-957) copies/mL plasma, respectively. The PBMC detection rate was high in the early (within 10 days after onset) and late phase (>10 days after onset) [90-100%]. The plasma detection rate in the early phase (66.7%) was higher than that in the late phase (40%). The younger age group of EBV-associated IM patients had higher monocyte count, lower occurrence of hepatitis, and lower GOT and GPT levels than the older age group. The PBMC detection rate was almost equally high in both the early and late phases, while the plasma detection rate was higher in the early phase. Quantitative real-time PCR of EBV DNA is useful for diagnosing and monitoring EBV-associated IM, especially in younger children.

Steady state plasma [3H]-noradrenaline kinetics in quadriplegic chronic spinal cord injury patients.

PubMed

Krum, H; Brown, D J; Rowe, P R; Louis, W J; Howes, L G

1990-08-01

1. Steady state plasma noradrenaline kinetics were measured in eight male quadriplegic patients and in eight age and sex matched controls. 2. Plasma noradrenaline levels were significantly lower in quadriplegic patients compared to controls. Noradrenaline spillover rate was markedly reduced in quadriplegics compared to controls while noradrenaline clearance was similar in both groups. 3. Noradrenaline kinetics in quadriplegic patients differ from peripheral autonomic neuropathy patients where reductions in both the spillover and clearance of noradrenaline are present.

Elevated plasma γ-tocopherol and decreased α-tocopherol in men are associated with inflammatory markers and decreased plasma 25-OH vitamin D

PubMed Central

Cooney, Robert V.; Franke, Adrian A; Wilkens, Lynne R.; Gill, Jasmeet; Kolonel, Laurence N.

2010-01-01

Chronic inflammation is a risk factor for many diseases of aging. Endogenous oxidants are thought to mediate the effects of inflammation and γ-Tocopherol (γ-Toc) may mitigate damage from nitrogen-based oxidants, however, no physiological requirement for γ-Toc has been established. Regulation of tocopherols and their functional significance are poorly defined, thereby limiting their application in prevention. Using stored plasma samples from 657 male control subjects in a previous study of prostate cancer we have analyzed associations of the tocopherols, inflammation markers, and 25-OH vitamin D. Plasma α-Toc and γ-Toc were inversely correlated, whereas δ-Toc and α-Toc levels were positively correlated, suggesting a unique regulatory mechanism. γ-Toc levels were positively and α-Toc negatively associated with plasma C-reactive protein (CRP) and urinary isoprostane F2t, which are markers of inflammation and oxidation. Ethnic variability in tocopherols was observed, however, this may be explained by differences in plasma 25-OH vitamin D, as γ-Toc levels varied inversely and α-Toc positively with 25-OH vitamin D. In these data all-cause mortality appeared to be positively associated with CRP and inversely with 25-OH vitamin D. We hypothesize that plasma levels of tocopherols may serve as markers of systemic inflammation, complicating epidemiologic assessment of their role in cancer etiology. PMID:19003577

Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction.

PubMed

Consitt, Leslie A; Koves, Timothy R; Muoio, Deborah M; Nakazawa, Masato; Newton, Christopher A; Houmard, Joseph A

2016-10-28

The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19-29 years) and fifteen middle-to older-aged (57-82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin-stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation. Insulin infusion decreased the majority of plasma short-, medium-, and long-chain (SC, MC, and LC, respectively) AC. However, during the initial 50 min, a number of MC and LC AC species (C10, C10:1, C12:1, C14, C16, C16:1, C18) remained elevated in aged individuals compared to their younger counterparts indicating a lag in responsiveness. Additionally, the insulin-induced decline in skeletal muscle ACC phosphorylation was blunted in the aged compared to young individuals (-24% vs. -56%, P < 0.05). These data suggest that a desensitization to insulin during aging, possibly at the level of skeletal muscle ACC phosphorylation, results in a diminished ability to transition to glucose oxidation indicative of metabolic inflexibility. Copyright © 2016 Elsevier Inc. All rights reserved.

Maternal plasma levels of interleukin-6, C-reactive protein, vitamins C, E and A, 8-isoprostane and oxidative status in women with preterm premature rupture of membranes.

PubMed

Ilhan, Nevin; Celik, Ebru; Kumbak, Banu

2015-02-01

Preterm premature rupture of membranes (PPROM) is associated with significant maternal and perinatal morbidity. This study examined maternal oxidative stress in PPROM. This was a prospective cross-sectional study conducted in a university hospital. A total of 72 pregnant women were recruited into two groups, those with PPROM (38 cases) and those without PPROM (34 controls) matched for gestational age. Plasma interleukin-6, C-reactive protein, vitamins C, E and A, 8-isoprostane, total oxidant status (TOS) and antioxidant status (TAS) were determined for all study participants and the data were compared between the PPROM and control groups. Both case and control groups were comparably matched in age, parity, gestational age and smoking status. There was a significant association between low 8-isoprostane, low vitamin C and high total oxidant status and the occurrence of PPROM (p < 0.001). Plasma vitamin C and 8-isoprostane levels were lower and TOS higher in women with PPROM. Further research is needed to identify robust biological markers for the prevention and also prognosis of PPROM.

Concurrent Aerobic and Resistance Training Has Anti-Inflammatory Effects and Increases Both Plasma and Leukocyte Levels of IGF-1 in Late Middle-Aged Type 2 Diabetic Patients

PubMed Central

Agostini, Deborah; Vallorani, Luciana; Gioacchini, Annamaria; Guescini, Michele; Casadei, Lucia; Passalia, Annunziata; Del Sal, Marta; Piccoli, Giovanni; Andreani, Mauro; Federici, Ario; Stocchi, Vilberto

2017-01-01

Type 2 diabetes (T2D) is an age-related chronic disease associated with metabolic dysregulation, chronic inflammation, and activation of peripheral blood mononuclear cells (PBMC). The aim of this study was to assess the effects of a concurrent exercise training program on inflammatory status and metabolic parameters of T2D patients. Sixteen male patients (age range 55–70) were randomly assigned to an intervention group (n = 8), which underwent a concurrent aerobic and resistance training program (3 times a week; 16 weeks), or to a control group, which followed physicians' usual diabetes care advices. Training intervention significantly improved patients' body composition, blood pressure, total cholesterol, and overall fitness level. After training, plasma levels of adipokines leptin (−33.9%) and RBP4 (−21.3%), and proinflammatory markers IL-6 (−25.3%), TNF-α (−19.8%) and MCP-1 (−15.3%) decreased, whereas anabolic hormone IGF-1 level increased (+16.4%). All improvements were significantly greater than those of control patients. Plasma proteomic profile of exercised patients showed a reduction of immunoglobulin K light chain and fibrinogen as well. Training also induced a modulation of IL-6, IGF-1, and IGFBP-3 mRNAs in the PBMCs. These findings confirm that concurrent aerobic and resistance training improves T2D-related metabolic abnormalities and has the potential to reduce the deleterious health effects of diabetes-related inflammation. PMID:28713486

Long-term administration of pDC-Stimulative Lactococcus lactis strain decelerates senescence and prolongs the lifespan of mice.

PubMed

Sugimura, Tetsu; Jounai, Kenta; Ohshio, Konomi; Suzuki, Hiroaki; Kirisako, Takayoshi; Sugihara, Yoshihiko; Fujiwara, Daisuke

2018-05-01

The decline in immune function caused by aging increases the risk of infectious diseases, tumorigeneses and chronic inflammation, resulting in accelerating senescence. We previously reported a lactic acid bacteria, Lactococcus lactis strain Plasma (synonym of Lactococcus lactis subsp. lactis JCM 5805, Lc-Plasma), that stimulates plasmacytoid dendritic cells (pDCs), which play a crucial role in phylaxis from viral infection. In this study, we investigated the anti-aging effects of long-term oral administration of Lc-Plasma in a senescence-accelerated mouse strain, SAMP6. Mice given Lc-Plasma showed a significant improvement in survival rate at 82 weeks and a decreased senescence score as compared with control mice throughout this study. Anatomic analysis at 82 weeks revealed that the frequency of altered hepatocellular foci was significantly lower, and the incidence of other pathological findings in the liver and lungs tended to be lower in Lc-Plasma mice than in control mice. Transcription level of the IL-1β gene in lungs also tended to be lower in Lc-Plasma mice. Furthermore, the thinning of skin and age-related decrease in muscle mass were also significantly suppressed in the Lc-Plasma group as compared with the control group. Consistent with these phenotypic features, pDCs activity was significantly higher in Lc-Plasma mice than in control mice. In conclusion, long-term administration of Lc-Plasma can decelerate senescence and prolong lifespan via maintenance of the immune system due to activation of pDCs. Copyright © 2018 Elsevier B.V. All rights reserved.

Plasma levels of dioxins, furans, non-ortho-PCBs, and TEQs in the Seveso population 17 years after the accident.

PubMed

Consonni, D; Sindaco, Raffaella; Agnello, L; Caporaso, N E; Landi, Maria Teresa; Pesatori, Angela Cecilia; Bertazzi, P A

2012-01-01

The Seveso accident (Italy) in 1976 caused the contamination of a large population by 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3, 7,8-TCDD). The contaminated territory was divided into three zones: A (very high contamination), B (high contamination), and R (low contamination). We report here the plasma concentrations of seven polychlorinated dibenzo-para-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), four non-ortho-polychlorinated biphenyls PCBs (nPCBs), and Toxic Equivalencies (TEQs) in a sample of residents in the most polluted zones A and B and in a reference non-contaminated zone. From December 1992 to March 1994, 62 individuals were randomly selected from the population living in zone A (No. =7) and B (No. =55). A sample of 59 subjects living in a surrounding non-contaminated area (non-ABR), frequency-matched by gender, age, and smoking history, was used as reference. All subjects were administered a questionnaire surveying demographic, lifestyle, medical history, and accident-related factors. We assayed plasma PCDD, PCDF, and nPCB concentrations by high-resolution gas chromatography/high resolution mass spectrometric (HRGC/HRMS) analysis, with results reported as pg/g of lipid, or parts per trillion (ppt). We calculated TEQs using the WHO 2005 Toxic Equivalency Factors (TEFs). We found elevated median levels of 2,3, 7,8-TCDD in plasma samples of subjects living in zone A (73.3 ppt) and zone B (12.4 ppt), compared with residents in the reference zone (5.5 ppt). In analyses adjusted for gender, age, smoking, and body mass index (BMI), none of the other congeners showed levels higher than reference in the contaminated zones. Compared with men, women showed higher levels (113%) of 2,3, 7,8-TCDD and a slight elevation (17%) of TEQ for the other congeners. Age was strongly positively associated with most congener levels; TEQs for PCDDs, PCDFs, and nPCBs showed respectively 12%, 24%, and 41% increases for every 10 years of age. Current smokers had lower (from -37% to -67%) TEQ levels than subjects who had never smoked. BMI was negatively associated with levels of a few congeners, but with no impact on TEQ values. The Seveso accident caused a severe exposure of the population to 2,3,7,8-TCDD only. None of the other congeners analyzed showed variation across zones. Age showed a strong positive association with TEQs for all classes of compounds (PCDDs, PCDFs, and nPCBs).

Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

PubMed

Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F

1999-04-01

Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P < 0.01] was noted in levels of total cholesterol, and a decrease of 1.70 mmol/l [1.52-2.30 (28%); P < 0.01] in levels of low-density lipoprotein cholesterol. Plasma levels of fibrinogen had increased [from 4.81 g/l (4.26-5.27) to 5.17 g/l (4.81-5.67); P < 0.05], whereas no significant changes had occurred in intraplatelet levels of cGMP [decrease by 0.05 pmol/10(9) platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/10(9) platelets (-0.37 to 0.86); NS], plasma endothelin-1 [decrease by 0.05 pg/ml (-0.60 to 0.70); NS], plasma factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

Trace Element Levels in Congenital Hypogonadotrophic Hypogonadism.

PubMed

Aydogdu, A; Haymana, C; Soykut, B; Erdem, O; Basaran, Y; Baskoy, K; Dinc, M; Taslipinar, A; Sonmez, A; Bolu, E; Azal, O

2016-05-01

Cardiometabolic diseases are prevalent in hypogonadism. The pathophysiologic mechanism of increased cardiometabolic risk in hypogonadal patients is not clear. Recently, trace elements have been linked to the development of chronic disease especially cardiovascular disease. We investigated the trace element levels in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and also searched for the relationship with metabolic risk factors. A total of 89 patients with CHH (mean age 21.8 ± 2.0 years) and 80 healthy control subjects (mean age 21.3 ± 1.1 years) were enrolled. The demographic parameters, homeostatic model assessment of insulin resistance (HOMA-IR) levels and plasma zinc, copper, and selenium levels, were measured in patients and healthy controls. The patients had higher waist circumferences (p = 0.014), triglyceride (p = 0.04), insulin (p = 0.004), HOMA-IR levels (p = 0.001), and lower selenium (p = 0.049), zinc (p = 0.004), and copper (p = 0.012) levels when compared to the healthy controls. There was a significant relationship between zinc levels and HOMA-IR levels (p = 0.015). In the regression analysis, zinc levels were independently associated with the calculated HOMA-IR levels (p = 0.015). The results of the present study show that plasma selenium, zinc, and copper levels are decreased in patients with CHH. Also, plasma zinc levels are independently associated with insulin resistance in patients with hypogonadism. Long-term follow-up studies are warranted to investigate the effect of trace elements on the increased cardiometabolic risk in hypogonadism.

COPD and levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes among coal workers: a case-control study.

PubMed

Cui, Xiuqing; Xing, Jingcai; Liu, Yuewei; Zhou, Yun; Luo, Xin; Zhang, Zhihong; Han, Wenhui; Wu, Tangchun; Chen, Weihong

2015-05-01

This case-control study aimed to investigate whether the levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes were associated with the risk of chronic obstructive pulmonary disease (COPD) among coal workers. A total of 76 COPD cases and 48 age-matched healthy controls from a group of coal workers were included. The case group consisted of 35 COPD patients whose condition was complicated with coal workers' pneumoconiosis (CWP) and 41 COPD patients without CWP. Heat shock proteins (Hsps) in plasma and lymphocytes were detected by ELISA and flow cytometry, respectively. Multiple logistic regression models were applied to estimate the association between Hsp levels and COPD risk. Our results showed that plasma Hsp70 and lymphocyte Hsp27 levels were significantly higher and plasma Hsp27 levels were significantly lower in COPD cases than in controls (p < 0.01). No significant differences in lymphocyte Hsp70 levels were found between COPD cases and the matched subjects. Higher plasma Hsp70 levels (odds ratio (OR) = 13.8, 95 % confidence interval (CI) = 5.7-33.5) and lower plasma Hsp27 levels (OR = 4.6, 95 % CI = 2.0-10.5) were significantly associated with an increased risk of COPD after adjusting for confounders. Higher lymphocyte Hsp27 levels were only associated with an increased risk of COPD with CWP (OR = 6.6, 95 % CI = 2.0-22.1) but not with an increased risk of COPD without CWP (OR = 3.0, 95 % CI = 0.9-8.9). Additionally, there were strong joint effects of different Hsps on COPD risk. These results showed that higher levels of plasma Hsp70 and lower levels of plasma Hsp27 might be associated with an increased risk of COPD among coal workers. They may have the potential to serve as monitoring markers for COPD in coal workers.

Short-term secretory regulation of ghrelin during growth hormone provocative tests in prepubertal children with various growth hormone secretory capacities.

PubMed

Matsuoka, Hisafumi; Hosoda, Hiroshi; Sugawara, Hisae; Iwama, Saika; Kim, Hye Sook; Kangawa, Kenji; Sugihara, Shigetaka

2005-01-01

Ghrelin is a novel gastric peptide which stimulates GH secretion and has been demonstrated to have orexigenic and adipogenic properties. Insulin is a physiological and dynamic modulator of plasma ghrelin, and insulinemia possibly mediates the effect of the nutritional state on the plasma concentrations of ghrelin in adults. No data on the regulation of GH secretion by ghrelin have so far been reported, nor has the possible influence of hypoglycemia on the plasma ghrelin levels in children been reported. Provocative studies were performed using a variety of stimuli, including insulin-induced hypoglycemia, and glucagon, arginine and L-dopa loading. We studied a group of 27 children with short stature being investigated for GH deficiency (10 F, 17 M; age 4-14 years; height SDS -0.92 to -3.27); the subjects were instructed to fast overnight, and the following morning, the relationships among the plasma ghrelin, GH and glucose levels were investigated by determining the plasma ghrelin profiles during those provocative tests. Using a new method for determining the two types of ghrelin, samples were obtained for determination of the plasma ghrelin, serum glucose and serum GH levels after the administration of the aforementioned stimulating agents. All the four stimuli caused a significant decrease in the circulating C- and N-ghrelin levels with a nadir at +30 min, with the exception of the N-ghrelin level following the L-dopa loading. During the same period, the plasma GH level increased following insulin, arginine and L-dopa loading, and the plasma glucose level increased significantly following glucagon loading. In the arginine and L-dopa load connected, a significant correlation was observed between the 30-min change in the serum GH level and the 30-min change in the plasma C-ghrelin level. In the multiple regression analysis to explain the 30-min change in the plasma level of C-ghrelin, the baseline plasma level of C-ghrelin (basal), height and % overweight were the only three significant parameters, accounting for 85.2% of the variance. This study demonstrated that the inverse relation between the circulating GH and ghrelin levels may indicate the existence of a feedback loop, and also lends support to the assumption of a GH-independent relationship between plasma ghrelin and glucose levels. These observations constitute further evidence to suggest that peripheral ghrelin is a direct growth-promoting hormone. Copyright 2005 S. Karger AG, Basel

Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients

PubMed Central

Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

2016-01-01

Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD’s acute inflammatory phase. PMID:27187366

Diurnal intermittent fasting during Ramadan: the effects on leptin and ghrelin levels.

PubMed

Alzoghaibi, Mohammed A; Pandi-Perumal, Seithikurippu R; Sharif, Munir M; BaHammam, Ahmed S

2014-01-01

We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC) at King Saud University on four occasions: 1) adaptation; 2) 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; p<0.05). During Ramadan, there was a significant reduction in plasma leptin levels at 22:00 (194.2±177.2 vs. 132.6±130.4, p<0.05). No significant difference in plasma ghrelin concentrations was detected during the BL, BLF, or Ramadan periods. Cosinor analyses of leptin and ghrelin plasma levels revealed no significant changes in the acrophases of the hormones during the three periods. The nocturnal reduction in plasma leptin levels during fasting may be the result of the changes in meal times during fasting.

Diurnal Intermittent Fasting during Ramadan: The Effects on Leptin and Ghrelin Levels

PubMed Central

Alzoghaibi, Mohammed A.; Pandi-Perumal, Seithikurippu R.; Sharif, Munir M.; BaHammam, Ahmed S.

2014-01-01

We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC) at King Saud University on four occasions: 1) adaptation; 2) 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; p<0.05). During Ramadan, there was a significant reduction in plasma leptin levels at 22:00 (194.2±177.2 vs. 132.6±130.4, p<0.05). No significant difference in plasma ghrelin concentrations was detected during the BL, BLF, or Ramadan periods. Cosinor analyses of leptin and ghrelin plasma levels revealed no significant changes in the acrophases of the hormones during the three periods. The nocturnal reduction in plasma leptin levels during fasting may be the result of the changes in meal times during fasting. PMID:24637892

Reduced plasma levels of coagulation factors in relation to prostate cancer.

PubMed

Beecken, Wolf-Dietrich; Bentas, Wassilios; Engels, Knut; Glienke, Wolfgang; Urbschat, Anja; Jonas, Dietger; Binder, Jochen; Scharrer, Inge

2002-10-01

Prostate cancer has historically been associated with coagulation abnormalities. This study was undertaken to investigate the prevalence of abnormalities of coagulation factors in patients with prostate cancer before and after radical prostatectomy (RP). Because coagulation factors have been shown to be involved in tumor angiogenesis, the vascular density of the prostate tumors was assessed. Plasma of 40 consecutive patients with histologically proven prostate cancer was investigated pre-RP and post-RP. The antigen level for antithrombin, plasminogen activator inhibitor-1, and heparin cofactor-II, and the plasma activity of antithrombin and plasminogen were determined by using immunologic and chromogenic assays. The values of these assays were compared with a group of 28 male, age-matched patients without any evidence of cancer and 18 patients with orthopedic interventions preoperatively and postoperatively. The vascular density of the prostate tumors was assessed by staining paraffin sections with an antibody to CD34. The median plasma antigen levels and/or activities of the investigated factors were below normal in the prostate cancer patients before RP. Furthermore, coagulation factors were significantly lower than in the age-matched control group and patients before and after orthopedic surgery. In prostate cancer patients, the median values of all investigated factors went up to normal levels within 2 weeks after RP, whereas postsurgical levels in orthopedic patients remained stable. No correlations to tumor parameters have been observed. We assume that the reduction of these coagulation factors is a principle concept in prostate cancer that needs further investigation. Copyright 2002 Wiley-Liss, Inc.

Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans.

PubMed

Gonzales, Joaquin U; Thistlethwaite, John R; Thompson, Benjamin C; Scheuermann, Barry W

2009-07-01

Shear stress is the frictional force of blood against the endothelium, a stimulus for endothelial activation and the release of von Willebrand factor (vWF). This study tested the hypothesis that the increase in shear stress associated with exercise correlates with plasma vWF. Young (n = 14, 25.7 +/- 5.4 years) and older (n = 13, 65.6 +/- 10.7 years) individuals participated in 30 min of dynamic handgrip exercise at a moderate intensity. Brachial artery diameter and blood flow were measured using ultrasound Doppler and blood samples were collected before, immediately after, and following 30 min of recovery from exercise with plasma levels of vWF. Plasma levels of vWF increased (P < 0.05) by 6 +/- 2% in young individuals and 4 +/- 1% in older individuals immediately after exercise. The change in plasma vWF was linearly correlated with the increase in shear stress during exercise in older individuals (post-exercise: r = 0.78, 30 min recovery: r = 0.77, P < 0.01), but no association was found in the young individuals. These changes in plasma levels of vWF in humans suggest that aging influences endothelial activation and hemostasis.

Altered metabolites in the plasma of autism spectrum disorder: a capillary electrophoresis time-of-flight mass spectroscopy study.

PubMed

Kuwabara, Hitoshi; Yamasue, Hidenori; Koike, Shinsuke; Inoue, Hideyuki; Kawakubo, Yuki; Kuroda, Miho; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Kano, Yukiko; Kasai, Kiyoto

2013-01-01

Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD.

Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

PubMed Central

Kuwabara, Hitoshi; Yamasue, Hidenori; Koike, Shinsuke; Inoue, Hideyuki; Kawakubo, Yuki; Kuroda, Miho; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Kano, Yukiko; Kasai, Kiyoto

2013-01-01

Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD. PMID:24058493

Plasma Pentraxin 3 as a biomarker of metabolic syndrome.

PubMed

Kardas, Fatih; Akın, Leyla; Kurtoglu, Selim; Kendirci, Mustafa; Kardas, Zehra

2015-01-01

To assess the plasma Pentraxin 3 (PTX3) concentrations in obese children and to investigate the relationship between PTX3 levels and metabolic syndrome (MS) components. Seventy-seven obese patients aged 10-16 y (38 girls, 39 boys) were included in the study. PTX3 levels were compared between the groups with or without MS. In addition, PTX3 was analysed separately by subgroups according to the presence of specific MS components. Plasma PTX3 concentrations were significantly higher in obese children and adolescents with metabolic syndrome than in those without MS (2.1 ± 1.2 ng/ml and 1.4 ± 0.9 ng/ml respectively; P = 0.02). Patients with low HDL levels (<40 mg/dl) had higher plasma PTX3 concentrations than those with normal HDL levels (P = 0.05). Similarly, those who had high triglyceride levels (≥ 150 mg/dl) had higher PTX3 levels (P = 0.01). PTX3 levels were negatively correlated with HDL cholesterol (r = -0.32, P = 0.003) among all patients. PTX3 levels are higher in obese children and adolescents with metabolic syndrome than in those without MS. Thus, PTX3 levels might be a useful biomarker for children and adolescents with metabolic syndrome, dyslipidemia, and cardiovascular risks.

Spider angiomas in patients with liver cirrhosis: Role of vascular endothelial growth factor and basic fibroblast growth factor

PubMed Central

Li, Chung-Pin; Lee, Fa-Yauh; Hwang, Shinn-Jang; Lu, Rei-Hwa; Lee, Wei-Ping; Chao, Yee; Wang, Sung-Sang; Chang, Full-Young; Whang-Peng, Jacqueline; Lee, Shou-Dong

2003-01-01

AIM: To investigate whether vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) are associated with spider angiomas in patients with liver cirrhosis. METHODS: Eighty-six patients with liver cirrhosis were enrolled and the number and size of the spider angiomas were recorded. Fifty-three healthy subjects were selected as controls. Plasma levels of VEGF and bFGF were measured in both the cirrhotics and the controls. RESULTS: Plasma VEGF and bFGF were increased in cirrhotics compared with controls (122 ± 13 vs. 71 ± 11 pg/mL, P = 0.003 for VEGF; 5.1 ± 0.5 vs. 3.4 ± 0.5 pg/mL, P = 0.022 for bFGF). In cirrhotics, plasma VEGF and bFGF were also higher in patients with spider angiomas compared with patients without spider angiomas (185 ± 28 vs. 90 ± 10 pg/mL, P = 0.003 for VEGF; 6.8 ± 1.0 vs. 4.1 ± 0.5 pg/mL, P = 0.017 for bFGF). Multivariate logistic regression showed that young age and increased plasma levels of VEGF and bFGF were the most significant predictors for the presence of spider angiomas in cirrhotic patients (odds ratio [OR] = 6.64, 95% confidence interval [CI] = 2.02-21.79, P = 0.002; OR = 4.35, 95%CI = 1.35-14.01, P = 0.014; OR = 5.66, 95%CI = 1.72-18.63, P = 0.004, respectively). CONCLUSION: Plasma VEGF and bFGF are elevated in patients with liver cirrhosis. Age as well as plasma levels of VEGF and bFGF are significant predictors for spider angiomas in cirrhotic patients. PMID:14669345

Plasma methionine and risk of acute myocardial infarction: Effect modification by established risk factors.

PubMed

Dhar, Indu; Lysne, Vegard; Seifert, Reinhard; Svingen, Gard F T; Ueland, Per M; Nygård, Ottar K

2018-05-01

Methionine (Met) is an essential amino acid involved in methylation reactions and lipid metabolism. A Met-deficient diet may cause hepatic lipid accumulation, which is considered an independent risk factor for atherosclerosis. However, the prospective relationship between circulating Met and incident acute myocardial infarction (AMI) is unknown. We studied the associations of plasma Met and incident AMI in 4156 patients (77% men; median age 62 years) with stable angina pectoris, among whom the majority received lipid lowering therapy with statins. Risk associations were estimated using Cox-regression analyses. Plasma Met was negatively related to age, serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) B at baseline (all p≤0.05). During a median follow-up of 7.5 years, 534 (12.8%) patients experienced an AMI. There was no overall association between plasma Met and incident AMI; however, plasma Met was inversely associated with risk among patients with high as compared to low levels of serum LDL-C or apo B 100 (multivariate adjusted HRs per SD [95% CI] 0.84 [0.73-0.96] and 0.83[0.73-0.95], respectively; p-interaction ≤0.02). Trends towards an inverse risk relationship were also observed among those younger than 62 years and patients without diabetes or hypertension. Low plasma Met was associated with increased risk of AMI in patients with high circulating levels of atherogenic lipids, but also in subgroups with presumably lower cardiovascular risk. The determinants of Met status and their relation with residual cardiovascular risk in patients with coronary heart disease should be further investigated. Copyright © 2018 Elsevier B.V. All rights reserved.

Fructo-oligosaccharide improved brain β-amyloid, β-secretase, cognitive function, and plasma antioxidant levels in D-galactose-treated Balb/cJ mice.

PubMed

Yen, Chi-Hua; Wang, Cheng-Hsin; Wu, Wen-Tzu; Chen, Hsiao-Ling

2017-05-01

Long-term d-galactose injection induces accelerated aging in experimental rodent models. The aim of this study was to determine the effects of dietary fructo-oligosaccharide (FO) on the brain β-amyloid (Aβ), amyloid-associated enzymes, cognitive function, and plasma antioxidant levels in d-galactose-treated Balb/c mice. The subcutaneous (s.c.) injection and the dietary treatment were conducted simultaneously for 49 days. Mice (12 weeks of age) were divided into five groups (n = 14/group): control (s.c. saline, control diet) serving as a young control, DG (s.c. 1.2 g d-galactose/kg body weight, control diet), DG + LFO (2.5% w/w FO, low-dose FO diet), DG + HFO (5% w/w FO, high-dose FO diet), and DG + E (α-tocopherol 0.2% w/w, vitamin E diet) as an antioxidant reference group. Another group of older mice (64 weeks of age) without any injection served as a natural aging (NA) group. The DG and NA groups had greater Aβ levels in the cortex, hippocampus, and the whole brain. High-dose FO, similar to α-tocopherol, attenuated the d-galactose-induced Aβ density in the cortex and hippocampus. In addition, FO attenuated the d-galactose-induced protein expression of Aβ and beta-site amyloid precursor cleaving enzyme of the whole brain in a dose-response manner. Either dose of FO supplementation, similar to α-tocopherol, attenuated the d-galactose-induced cognitive dysfunction. In addition, FO improved the plasma ascorbic acid level in a dose-response manner. Dietary FO (2.5-5% w/w diet) could attenuate the development of Alzheimer's disease, which was likely to be associated with its systematic antioxidant effects.

Different effects of fenofibrate on metabolic and cardiovascular risk factors in mixed dyslipidemic women with normal thyroid function and subclinical hypothyroidism.

PubMed

Krysiak, Robert; Gilowski, Wojciech; Szkrobka, Witold; Okopien, Bogusław

2014-12-01

Subclinical hypothyroidism is suggested to increase cardiovascular risk. No previous study compared the effect of any fibrate on plasma levels of lipids and other cardiovascular risk factors in patients with different thyroid function status. The study included three age-, weight- and lipid-matched groups of women with mixed dyslipidemia in different thyroid function status: patients with untreated subclinical hypothyroidism (group 1, n = 18), women with treated hypothyroidism (group 2, n = 15), and subjects without thyroid disorders (group 3, n = 19). Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were determined before and after 12 weeks of fenofibrate therapy. Despite similar plasma lipid levels, mixed dyslipidemic patients with untreated hypothyroidism had decreased insulin sensitivity, as well as higher circulating levels of uric acid, hsCRP, homocysteine, and fibrinogen in comparison with the other groups. The effect of fenofibrate on plasma lipids and, with the exception of homocysteine, on circulating levels of all investigated risk factors was stronger in patients from groups 2 and 3 than in patients from group 1. The obtained results indicate that the effect of fenofibrate on plasma lipids and circulating levels of cardiovascular risk factors is partially related to thyroid function. They also suggest that to improve the strength of fibrate action in dyslipidemic patients with subclinical hypothyroidism, they should be administered together with L-thyroxine. © 2014 John Wiley & Sons Ltd.

Contribution of nonesterified fatty acids to insulin resistance in the elderly with normal fasting but diabetic 2-hour postchallenge plasma glucose levels: the Baltimore Longitudinal Study of Aging.

PubMed

Carlson, Olga D; David, Jehan D; Schrieder, Jessica M; Muller, Dennis C; Jang, Hyeung-Jin; Kim, Byung-Joon; Egan, Josephine M

2007-10-01

Isolated postchallenge hyperglycemia (IPH) with normal fasting plasma glucose <100 mg/dL and plasma glucose with diabetic 2-hour plasma glucose >or=200 mg/dL after an oral glucose tolerance test (OGTT) is a common occurrence in the elderly. We sought to understand what unique characteristics this population might have that puts it at risk for this particular metabolic finding. We therefore conducted a longitudinal study of volunteers in the Baltimore Longitudinal Study of Aging (BLSA). All volunteers had an OGTT performed (75 g) on 2 or more occasions. We measured plasma levels of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), ghrelin, leptin, adiponectin, resistin, C-reactive protein, cytokines, and their soluble receptors, as well as nonesterified free fatty acids (NEFAs). We determined that 22 subjects in BLSA had IPH, accounting for 2.1% of the BLSA population. All 22 were older than 65 years. They were then matched by age, sex, and body mass index to 12 subjects who had isolated impaired glucose tolerance (IGT) and 15 subjects with normal glucose tolerance (NGT). All subjects had normal fasting glucose levels <100 mg/dL in accordance with the American Diabetes Association Expert Committee on the Classification and Diagnosis of Diabetes Mellitus criteria (2003). We found that subjects with IPH had similar plasma insulin levels to the other 2 groups, except at the 2-hour time when their insulin levels were higher than NGT (P < .05). Although there was a clear trend for differences in the insulinogenic index, the areas under the curves for insulin, systolic blood pressure, adiponectin, and C-reactive protein across the glucose tolerance categories revealed no statistical significance. Cytokines and their soluble receptors, gut hormones, and adipokines were similar in all 3 groups. The NEFA levels were significantly elevated in the fasting state (P < .05) in the IPH compared with NGT, with IGT intermediate between the other 2 groups. The rate of clearance of NEFAs after the OGTT decreased progressively from the NGT to the IPH group (in micromoles per liter per minute: NGT, 11.9 vs IGT, 7.6 vs IPH, 3.0). We conclude that the rate of suppression of lipolysis in the elderly determines the sensitivity of glucose uptake to insulin after OGTT.

Association between cell-bound blood amyloid-β(1-40) levels and hippocampus volume.

PubMed

Sotolongo-Grau, Oscar; Pesini, Pedro; Valero, Sergi; Lafuente, Asunción; Buendía, Mar; Pérez-Grijalba, Virginia; José, Itziar San; Ibarria, Marta; Tejero, Miguel A; Giménez, Joan; Hernández, Isabel; Tárraga, Lluís; Ruiz, Agustín; Boada, Mercé; Sarasa, Manuel

2014-01-01

The identification of early, preferably presymptomatic, biomarkers and true etiologic factors for Alzheimer's disease (AD) is the first step toward establishing effective primary and secondary prevention programs. Consequently, the search for a relatively inexpensive and harmless biomarker for AD continues. Despite intensive research worldwide, to date there is no definitive plasma or blood biomarker indicating high or low risk of conversion to AD. Magnetic resonance imaging and β-amyloid (Aβ) levels in three blood compartments (diluted in plasma, undiluted in plasma and cell-bound) were measured in 96 subjects (33 with mild cognitive impairment, 14 with AD and 49 healthy controls). Pearson correlations were completed between 113 regions of interest (ROIs) (45 subcortical and 68 cortical) and Aβ levels. Pearson correlation analyses adjusted for the covariates age, sex, apolipoprotein E (ApoE), education and creatinine levels showed neuroimaging ROIs were associated with Aβ levels. Two statistical methods were applied to study the major relationships identified: (1) Pearson correlation with phenotype added as a covariate and (2) a meta-analysis stratified by phenotype. Neuroimaging data and plasma Aβ measurements were taken from 630 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects to be compared with our results. The left hippocampus was the brain region most correlated with Aβ(1-40) bound to blood cell pellets (partial correlation (pcor) = -0.37, P = 0.0007) after adjustment for the covariates age, gender and education, ApoE and creatinine levels. The correlation remained almost the same (pcor = -0.35, P = 0.002) if phenotype is also added as a covariate. The association between both measurements was independent of cognitive status. The left hemisphere entorhinal cortex also correlated with Aβ(1-40) cell-bound fraction. AB128 and ADNI plasma Aβ measurements were not related to any brain morphometric measurement. Association of cell-bound Aβ(1-40) in blood with left hippocampal volume was much stronger than previously observed in Aβ plasma fractions. If confirmed, this observation will require careful interpretation and must be taken into account for blood amyloid-based biomarker development.

Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging

PubMed Central

Tuljapurkar, Sonal R; McGuire, Timothy R; Brusnahan, Susan K; Jackson, John D; Garvin, Kevin L; Kessinger, Margaret A; Lane, Judy T; O' Kane, Barbara J; Sharp, John G

2011-01-01

Hematological deficiencies increase with aging, including anemias, reduced responses to hematopoietic stress and myelodysplasias. This investigation tested the hypothesis that increased bone marrow (BM) fat content in humans with age was associated with decreased numbers of side population (SP) hematopoietic stem cells, and this decrease correlated with changes in cytokine levels. BM was obtained from the femoral head and trochanteric region of the femur removed at surgery for total hip replacement (N = 100 subjects). In addition, BM from cadavers (N = 36), with no evidence of hip disease, was evaluated for fat content. Whole trabecular marrow samples were ground in a sterile mortar and pestle, and cellularity and lipid content determined. Marrow cells were stained with Hoechst dye and SP profiles were acquired. Plasma levels of insulin-like growth factor (IGF)-1, stromal-derived factor (SDF)-1 and interleukin (IL)-6 were measured using ELISA. Fat content in the BM of human subjects and cadavers increased with age. The numbers of SP stem cells in BM as well as plasma IGF-1 and SDF-1 levels decreased in correlation with increased BM fat. IL-6 had no relationship to changes in marrow fat. These data suggest that increased BM fat may be associated with a decreased number of SP stem cells and IGF-1 and SDF-1 levels with aging. These data further raise a more general question as to the role of adipose cells in the regulation of tissue stem cells. PMID:21923862

Decreased nitrite levels in erythrocytes of children with β-thalassemia/hemoglobin E.

PubMed

Suvachananonda, Thitiwat; Wankham, Amara; Srihirun, Sirada; Tanratana, Pansakorn; Unchern, Supeenun; Fucharoen, Suthat; Chuansumrit, Ampaiwan; Sirachainan, Nongnuch; Sibmooh, Nathawut

2013-09-01

Nitrite anion is bioactive nitric oxide (NO) species circulating in blood, and represents the NO bioavailability and endothelial function. In this study, we aimed to investigate the nitrite levels and the correlation with hemolysis and severity in β-thalassemia/hemoglobin E (β-thal/HbE). 38 Children (12.0±1.9 years of age) with a diagnosis of mild, moderate and severe β-thalassemia were enrolled in the study. The blood nitrite levels and potential plasma NO consumption were measured by the chemiluminescence method. The nitrite levels in whole blood and erythrocytes of the severe thalassemia subjects were lower than those of the control subjects. At day 7 after transfusion of packed erythrocytes, the nitrite levels in erythrocytes increased. The plasma hemoglobin and NO consumption increased in the severe thalassemia subjects. The nitrite levels in erythrocytes inversely correlated with plasma hemoglobin, lactate dehydrogenase activity, potential NO consumption, and lipid peroxidation. Our studies demonstrate the decreased NO bioavailability in thalassemia, which could result from endothelial dysfunction, the increased potential NO consumption in plasma by cell-free hemoglobin and oxidative stress. Copyright © 2013 Elsevier Inc. All rights reserved.

Assessing salivary C-reactive protein: Longitudinal associations with systemic inflammation and cardiovascular disease risk in women exposed to intimate partner violence

PubMed Central

Out, Dorothée; Hall, Rosalie J.; Granger, Douglas A.; Page, Gayle G.; Woods, Stephanie J.

2012-01-01

This study evaluated individual differences in levels of C-reactive protein (CRP) measured in saliva, cross-sectionally and prospectively, in relation to systemic inflammation and risk for cardiovascular disease (CVD). Plasma and saliva samples, later assayed for CRP, were collected multiple times from an ethnically diverse group of women seeking help from domestic violence crisis shelters-agencies (N = 107; mean age at study start = 34 years). Plasma and saliva CRP levels were moderately associated cross-sectionally and across two years. There were indications that saliva CRP levels were, on average, higher in the morning than evening. Higher levels of saliva and plasma CRP were associated with a higher body mass index, but did not differ between women who did and did not smoke. Salivary CRP reliably discriminated between high and low levels of plasma CRP, using a clinically relevant cutoff point of 3 mg/L, recommended by the American Heart Association. Results build upon an emerging literature suggesting that under specific conditions levels of CRP in saliva may reflect low-grade inflammation and have the potential to serve as a screen for CVD risk status. PMID:22326517

Dietary phytoestrogens and plasma lipids in Dutch postmenopausal women; a cross-sectional study.

PubMed

Kreijkamp-Kaspers, Sanne; Kok, Linda; Bots, Michiel L; Grobbee, Diederick E; van der Schouw, Yvonne T

2005-01-01

Isoflavone supplementation in high doses is associated with plasma lipid, glucose and insulin levels. Little is known about the effects of intake within the range of western diets on these endpoints. We conducted a population-based cross-sectional study in 301 women aged 60-75 years. Dietary isoflavone and lignan intake was assessed with a food frequency questionnaire covering habitual diet during the year preceding enrollment. The outcome measures were total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, Lp(a), fasting glucose and insulin levels. Data were analysed using linear regression and logistic regression models. In the analyses we adjusted for a wide range of potential confounders. High intake of isoflavones was associated with lower Lp(a) levels (tertile three versus tertile one: odds ratio 0.36, 95% CI 0.16; 0.80). No relation was found between blood levels and the other plasma lipids, glucose or insulin was found. The results of this study suggest that an effect of dietary phytoestrogen intake at low levels on plasma lipid levels is of limited magnitude. It is premature to advise postmenopausal women with low phytoestrogen intake to change their diet towards a phytoestrogen rich diet with the sole aim to prevent cardiovascular disease.

Ghrelin plasma levels, gastric ghrelin cell density and bone mineral density in women with rheumatoid arthritis

PubMed Central

Maksud, F.A.N.; Kakehasi, A.M.; Guimarães, M.F.B.R.; Machado, C.J.; Barbosa, A.J.A.

2017-01-01

Generalized bone loss can be considered an extra-articular manifestation of rheumatoid arthritis (RA) that may lead to the occurrence of fractures, resulting in decreased quality of life and increased healthcare costs. The peptide ghrelin has demonstrated to positively affect osteoblasts in vitro and has anti-inflammatory actions, but the studies that correlate ghrelin plasma levels and RA have contradictory results. We aimed to evaluate the correlation between total ghrelin plasma levels, density of ghrelin-immunoreactive cells in the gastric mucosa, and bone mineral density (BMD) in twenty adult women with established RA with 6 months or more of symptoms (mean age of 52.70±11.40 years). Patients with RA presented higher ghrelin-immunoreactive cells density in gastric mucosa (P=0.008) compared with healthy females. There was a positive relationship between femoral neck BMD and gastric ghrelin cell density (P=0.007). However, these same patients presented a negative correlation between plasma ghrelin levels and total femoral BMD (P=0.03). The present results indicate that ghrelin may be involved in bone metabolism of patients with RA. However, the higher density of ghrelin-producing cells in the gastric mucosa of these patients does not seem to induce a corresponding elevation in the plasma levels of this peptide. PMID:28538835

Ghrelin plasma levels, gastric ghrelin cell density and bone mineral density in women with rheumatoid arthritis.

PubMed

Maksud, F A N; Kakehasi, A M; Guimarães, M F B R; Machado, C J; Barbosa, A J A

2017-05-18

Generalized bone loss can be considered an extra-articular manifestation of rheumatoid arthritis (RA) that may lead to the occurrence of fractures, resulting in decreased quality of life and increased healthcare costs. The peptide ghrelin has demonstrated to positively affect osteoblasts in vitro and has anti-inflammatory actions, but the studies that correlate ghrelin plasma levels and RA have contradictory results. We aimed to evaluate the correlation between total ghrelin plasma levels, density of ghrelin-immunoreactive cells in the gastric mucosa, and bone mineral density (BMD) in twenty adult women with established RA with 6 months or more of symptoms (mean age of 52.70±11.40 years). Patients with RA presented higher ghrelin-immunoreactive cells density in gastric mucosa (P=0.008) compared with healthy females. There was a positive relationship between femoral neck BMD and gastric ghrelin cell density (P=0.007). However, these same patients presented a negative correlation between plasma ghrelin levels and total femoral BMD (P=0.03). The present results indicate that ghrelin may be involved in bone metabolism of patients with RA. However, the higher density of ghrelin-producing cells in the gastric mucosa of these patients does not seem to induce a corresponding elevation in the plasma levels of this peptide.

Some amino acids levels: glutamine,glutamate, and homocysteine, in plasma of children with chronic kidney disease.

PubMed

Fadel, Fatina I; Elshamaa, Manal F; Essam, Rascha G; Elghoroury, Eman A; El-Saeed, Gamila S M; El-Toukhy, Safinaz E; Ibrahim, Mona Hamed

2014-03-01

The high prevalence of protein-energy malnutrition is a critical issue for patients with chronic kidney disease (CKD). Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid (AA) profile. Of these, the plasma levels of glutamine, glutamate and homocysteine, correlate well with nutritional status. We measured some plasma AAs in children with different stages CKD to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction. Three amino acids were evaluated along with albumin and high sensitivity C-reactive protein (hs-CRP) in 30 patients with advanced CKD stages 4 and 5. They were divided into two groups undergoing conservative treatment (CT) (n=15) or hemodialysis (HD) (n=15). An additional group of patients with nephrotic syndrome [CKD stage 2] was also studied to assess the alterations of plasma free amino acids with the early stage of CKD. Another 30 age- and sex-matched healthy children served as controls. A significant increase in plasma concentration of amino acid glutamine was observed in children with advanced CKD stages 4 and 5 when compared with controls (P=0.02).Plasma glutamine level was significantly higher in ESRD children on HD than in children with nephrotic syndrome (P=0.02). We did not find a significant difference between HD children and CT children as regard to glutamine level. Notable differences were in the plasma homocysteine level detected in the CKD groups patients, which was greater than that in controls (P=0.0001). Plasma homocysteine level was significantly higher in children on HD than in children with nephrotic syndrome (P=0.01). A significant differences was observed in hs-CRP levels between the CKD groups and the controls (P=0.04). Albumin levels were lower in CKD groups than in controls (p=0.01). Glutamine showed significant positive correlations with blood urea level (r=0.84, P=0.002) and blood ammonia level (r=0.72, P=0.0001). On multiple linear regression, urea was the only variable independently associated with an elevated plasma glutamine level (Beta=0.77, P=0.02). This study indicates that the advanced stages of CKD are associated with increased plasma concentrations of glutamine and homocysteine. Glutamine retained in the plasma of children with CRF, possibly producing higher levels of the waste products (urea and NH3). Dialysis alone is insufficient to redress completely the abnormalities in AA metabolism in ESRD children. Careful consideration of dialysis and dietary measures are necessary.

Dietary Components Affect the Plasma and Tissue Levels of Lutein in Aged Rats with Lutein Deficiency--A Repeated Gavage and Dietary Study.

PubMed

Sheshappa, Mamatha Bangera; Ranganathan, Arunkumar; Bhatiwada, Nidhi; Talahalli, Ramprasad Ravichandra; Vallikannan, Baskaran

2015-10-01

The aim of this study was to find out the influence of selected dietary components on plasma and tissue response of repeated micellar and dietary lutein in aged rats with lutein deficiency. In repeated (16 d) gavage study, micellar lutein was co-ingested with either phosphatidylcholine (PC), lyso-phosphatidylcholine (lysoPC), β-carotene, dietary fiber or vegetable fat (3% soybean oil). In dietary study, rats were fed (4 wk) semi-synthetic diet either with lutein + PC, lutein + dietary fiber or B. alba (lutein source) + PC. The post-prandial plasma and tissue response of lutein was measured by HPLC. Results showed that micellar fat, PC and lysoPC significantly (P ≤ 0.05) increased the lutein levels in plasma (31.1%, 26.8%, and 34.9%), liver (27.4%, 29.5%, and 8.6%), and eyes (63.5%, 90.2%, and 86%) compared to the control group (group gavaged micelles with no dietary components studied). Similarly, dietary study showed an enhanced plasma, liver, and eye lutein levels by 44.8%, 24.1%, and 42.0% (lutein + PC group) and 51.7%, 39.8%, and 31.7% (B.alba + PC group), respectively compared to control. The activity of antioxidant enzymes in plasma and liver of both the studies were also affected compared to control. Result reveals, that PC enhance the intestinal absorption of both micellar and dietary lutein which is either in free or bound form with food matrices in aged rats with lutein deficiency. Hence, PC at a concentration used in this study can be considered to improve the lutein bioavailability in lutein deficiency. Lutein and zeaxanthin are macular pigments acquired mostly from greens, that play an significant role in protecting vision from Age related macular degeneration (AMD). However, their biological availability is poor and affected by dietary components. This study demonstrates the positive influence of dietary PC and lyso PC in improving intestinal uptake of lutein. Our previous and present finding shows there is a possibility of developing functional/supplemental foods with PC and lyso PC targeted to elderly populace thus minimizing or delaying the vision complication associated like AMD. © 2015 Institute of Food Technologists®

Antihypertensive efficacy of the losartan/hydrochlorothiazide combination and its effect on plasma B-type natriuretic peptide in hypertensive patients uncontrolled by angiotensin II type 1 receptor antagonist-based therapy: a multicentre prospective observational study.

PubMed

Meno, Hiroshi; Inou, Tetsuji; Tanaka, Michiko; Tsuchiya, Yoshihiro; Shiga, Yuhei; Kobayashi, Kenji; Nakamura, Yuichiro; Ota, Takeaki; Kubara, Ichiro

2012-03-01

Although strict blood pressure (BP) control is effective in the prevention of cardiovascular events, it is often insufficient in many hypertensive patients. B-type natriuretic peptide (BNP) has been shown to be associated with cardiovascular events. We investigated the effects of the losartan/hydrochlorothiazide combination on BP and plasma BNP in hypertensive patients uncontrolled by an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB])-based therapy. In a multicentre prospective observational study, we enrolled 185 patients aged 36-79 years (mean age 63.8 years) with essential hypertension but without symptoms of heart failure who received an ARB-based therapy for ≥3 months but failed to achieve a target BP recommended by the Japanese Society of Hypertension (JSH). ARBs were switched to losartan (LOS) 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg. The antihypertensive efficacy, safety, and effects of this combination on blood biochemical parameters and plasma BNP were evaluated for 12 months. Mean ± SD systolic and diastolic BP decreased from 152 ± 13/87 ± 10 mmHg to 128 ± 14/74 ± 10 mmHg, respectively, after 12 months (p < 0.001). Mean ± SD plasma BNP levels decreased significantly from 46.0 ± 83.0 pg/mL to 40.8 ± 68.0 pg/mL (p < 0.05). The percentage of patients who achieved the JSH 2004 target BP was 51% after 12 months; the percentage was 63% in elderly patients aged ≥65 years without complications, and 43% in patients with concomitant diabetes mellitus or chronic kidney disease. No association was found between a decrease in plasma BNP levels and BP, age, body mass index or estimated glomerular filtration rate. There was a significant increase in serum uric acid and a decrease in serum potassium, but both were within the range of normal values. Adverse events were observed in 8.6% of the patients. Antihypertensive treatment using two types of drugs (LOS/HCTZ) with different mechanisms yielded potent antihypertensive efficacy with safety and decreased plasma BNP levels.

Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis

PubMed Central

Kondo, Yoshitaka; Masutomi, Hirofumi; Noda, Yoshihiro; Ozawa, Yusuke; Takahashi, Keita; Handa, Setsuko; Maruyama, Naoki; Shimizu, Takahiko; Ishigami, Akihito

2014-01-01

Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that converts superoxide anion radicals into hydrogen peroxide and molecular oxygen. The senescence marker protein-30 (SMP30) is a gluconolactonase that functions as an antioxidant protein in mammals due to its involvement in ascorbic acid (AA) biosynthesis. SMP30 also participates in Ca2+ efflux by activating the calmodulin-dependent Ca2+-pump. To reveal the role of oxidative stress in lipid metabolism defects occurring in non-alcoholic fatty liver disease pathogenesis, we generated SMP30/SOD1-double knockout (SMP30/SOD1-DKO) mice and investigated their survival curves, plasma and hepatic lipid profiles, amounts of hepatic oxidative stress, and hepatic protein levels expressed by genes related to lipid metabolism. While SMP30/SOD1-DKO pups had no growth retardation by 14 days of age, they did have low plasma and hepatic AA levels. Thereafter, 39% and 53% of male and female pups died by 15–24 and 89 days of age, respectively. Compared to wild type, SMP30-KO and SOD1-KO mice, by 14 days SMP30/SOD1-DKO mice exhibited: (1) higher plasma levels of triglyceride and aspartate aminotransferase; (2) severe accumulation of hepatic triglyceride and total cholesterol; (3) higher levels of superoxide anion radicals and thiobarbituric acid reactive substances in livers; and (4) decreased mRNA and protein levels of Apolipoprotein B (ApoB) in livers – ApoB is an essential component of VLDL secretion. These results suggest that high levels of oxidative stress due to concomitant deficiency of SMP30 and/or AA, and SOD1 cause abnormal plasma lipid metabolism, hepatic lipid accumulation and premature death resulting from impaired VLDL secretion. PMID:25003023

Nonlinear Associations between Plasma Cholesterol Levels and Neuropsychological Function

PubMed Central

Wendell, Carrington R.; Zonderman, Alan B.; Katzel, Leslie I.; Rosenberger, William F.; Plamadeala, Victoria V.; Hosey, Megan M.; Waldstein, Shari R.

2016-01-01

Objective Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Method Participants were 190 older adults (53% men, ages 54–83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed/dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier. Results A significant quadratic effect of total cholesterol2 × age was identified for Logical Memory II (b=−.0013, p=.039), such that the 70+ group performed best at high and low levels of total cholesterol than at mid-range total cholesterol (U-shaped), and the <70 group performed worse at high and low levels of total cholesterol than at mid-range total cholesterol (inverted U-shape). Similarly, significant U- and J-shaped effects of LDL cholesterol2 × age were identified for Visual Reproduction II (b=−.0020, p=.026) and log of Trails B (b=.0001, p=.044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Conclusions Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. PMID:27280580

Reduced high-molecular-weight adiponectin and elevated high-sensitivity C-reactive protein are synergistic risk factors for metabolic syndrome in a large-scale middle-aged to elderly population: the Shimanami Health Promoting Program Study.

PubMed

Tabara, Yasuharu; Osawa, Haruhiko; Kawamoto, Ryuichi; Tachibana-Iimori, Rieko; Yamamoto, Miyuki; Nakura, Jun; Miki, Tetsuro; Makino, Hideich; Kohara, Katsuhiko

2008-03-01

In Western countries, one of the most important modifiable targets for the prevention of cardiovascular diseases is metabolic syndrome. Adiponectin is an adipose tissue-specific plasma protein that inversely associates with metabolic syndrome. Among several molecular isoforms, high-molecular-weight (HMW) complex is considered the active form. Increased serum high-sensitivity C-reactive protein (hsCRP) concentration also associates with metabolic syndrome, and adiponectin could modulate plasma C-reactive protein levels. Here, through cross-sectional investigation, we investigated whether reduced HMW adiponectin and increased hsCRP levels in plasma are synergistically associated with metabolic syndrome. Measurement of HMW complex of adiponectin is one of the novelties of this study. We analyzed 1845 community-dwelling middle-aged to elderly subjects (62+/-13 yr). Plasma HMW adiponectin levels were measured by ELISA. Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up. Each component of metabolic syndrome, except for raised blood pressure, showed significantly lower plasma HMW adiponectin concentrations for both men and women (P<0.001). In contrast, plasma hsCRP levels were significantly higher in subjects with metabolic disorders (P<0.001). After adjusting for other confounding factors, HMW adiponectin [log normalized, odds ratio 0.084 (95% confidence interval 0.050-0.142), P<0.001] and hsCRP [3.009 (2.175-4.163), P<0.001] were identified as independent determinants of metabolic syndrome. In addition to the direct associations, we also observed a synergistic effect between these two molecules (F=11.8, P<0.001). Reduced HMW adiponectin and elevated hsCRP are synergistically associated with the accumulation of metabolic disorders. The combination of these markers would be useful for identifying at-risk populations.

Trajectories of plasma IGF-1, IGFBP-3, and their ratio in the Mayo Clinic Study of Aging.

PubMed

Wennberg, Alexandra M V; Hagen, Clinton E; Petersen, Ronald C; Mielke, Michelle M

2018-06-01

Insulin-like growth factor 1 (IGF-1) has been associated with osteoporosis, cardiovascular disease, cancer, neurodegenerative diseases, and mortality in middle and older aged adults. Cross-sectionally, IGF-1 decreases with age and levels of IGF-1 are markedly different between individuals. However, little is known about intra-individual trajectories of IGF-1. We examined baseline and serial measures of plasma total IGF-1, IGF binding protein (IGFBP)-3, and their ratio, which is a proxy for bioavailable IGF-1, among 1618 adults, aged 50-95, enrolled in the Mayo Clinic Study of Aging. At baseline, IGF-1 and IGFBP-3 were strongly correlated (r = 0.62, p < 0.001). Total IGF-1 and IGFBP-3 decreased across age, while the ratio of IGF-1/IGFBP-3 increased across age. This pattern was consistent across ages at baseline and intra-individually over an average 2.3 years follow-up (range = 10 months-5.6 years). In age-adjusted linear regression models, baseline levels of total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 varied by participant characteristics (sex, BMI, gait speed), medical comorbidities (Charlson comorbidity index score, hypertension, diabetes, and cardiovascular disease), and hormone replacement therapy use in women. High interclass correlation coefficients (ICCs) suggest little intra-individual variability in levels of total IGF-1 (ICC = 0.84), IGFBP-3 (ICC = 0.88), and IGF-1/IGFBP-3 (ICC = 0.81) over time. In mixed effects models that specified age as a time scale, men showed greater decreases in total IGF-1 and IGFBP-3 with age, while more comorbidities and decreasing gait speed were associated with increasing IGFBP-3. In sex-stratified models, trajectories of total IGF-1, IGFBP-3, and IGF-1/IGFBP-3, as a function of participant demographics, health characteristics, and medical conditions, differed between men and women. These results suggest that change in levels of plasma total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 are associated with demographics, health characteristics, and medical conditions, and that the trajectories of change differ by sex. Future research should consider how IGF-1 and IGFBP-3 might be useful in research or clinic, paying particular attention to how sex may impact levels as a function of demographics, health characteristics, and medical conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

Paternal behavior and testosterone plasma levels in the Volcano Mouse Neotomodon alstoni (Rodentia: Muridae).

PubMed

Luis, Juana; Ramírez, Lorena; Carmona, Agustín; Ortiz, Guadalupe; Delgado, Jesús; Cárdenas, René

2009-01-01

Paternal behavior and testosterone plasma levels in the Volcano Mouse Neotomodon alstoni (Rodentia: Muridae). Although initially it was thought that testosterone inhibited the display of paternal behavior in males of rodents, it has been shown that in some species high testosterone levels are needed for exhibition of paternal care. In captivity, males of Volcano Mouse (Neotomodon alstoni) provide pups the same care provided by the mother, with the exception of suckling. Here we measured plasmatic testosterone concentrations 10 days after mating, five and 20 days postpartum, and 10 days after males were isolated from their families in order to determine possible changes in this hormone, associated to the presence and age of pups. Males of Volcano Mouse exhibited paternal behavior when their testosterone levels were relatively high. Although levels of this hormone did not change with the presence or pups age, males that invested more time in huddling showed higher testosterone levels. It is possible that in the Volcano Mouse testosterone modulates paternal behavior indirectly, as in the California mouse.

Long-term effects of telmisartan on blood pressure, the renin-angiotensin-aldosterone system, and lipids in hypertensive patients.

PubMed

Aoki, Akiko; Ogawa, Tetsuya; Sumino, Hiroyuki; Kumakura, Hisao; Takayama, Yoshiaki; Ichikawa, Shuichi; Nitta, Kosaku

2010-05-01

We prospectively evaluated long-term (12 months) effects of telmisartan on blood pressure (BP), circulating renin-angiotensin-aldosterone levels, and lipids in hypertensive patients. There were 13 men and 11 women, 59 +/- 8.7 years of age (mean +/- SEM), with untreated essential hypertension. The 20-60 mg doses of telmisartan were administered once daily in the morning until BP130/85 was obtained. Blood pressure and plasma renin activity, plasma angiotensin (Ang) I and Ang II, serum angiotensin-converting enzyme (ACE) activity, plasma aldosterone concentration, plasma human atrial natriuretic peptide (hANP) concentration, and serum lipids were obtained 6 and 12 months after starting telmisartan administration. Systolic and diastolic BP were significantly (P < 0.001, P < 0.001) decreased from 162 +/- 3.3 and 97.7 +/- 2.1 mmHg to 128 +/- 3.8 and 79.6 +/- 2.0 mmHg after 12 months of treatment, respectively. Plasma Ang I and Ang II were unchanged at 12 months. Plasma renin activity and serum ACE activity were significantly (P < 0.001, P < 0.05) increased and plasma aldosterone concentration was unchanged during the study period. Total cholesterol levels were unchanged, but serum triglycerides levels were significantly decreased at 12 months (P < 0.01). Plasma hANP showed no significant alteration throughout the 12-month period. In hypertensive patients, telmisartan is a beneficial antihypertensive drug that also lowers serum triglycerides.

Circulating D-dimer level correlates with disease characteristics in hepatoblastoma patients

PubMed Central

Zhang, BinBin; Liu, GongBao; Liu, XiangQi; Zheng, Shan; Dong, Kuiran; Dong, Rui

2017-01-01

Abstract Objectives: Hepatoblastoma (HB) is the most common pediatric liver malignancy, typically affecting children within the first 4 years of life. However, only a few validated blood biomarkers are used in clinical evaluation. The current study explored the clinical application and significance of D-dimer levels in patients with HB. Method: Forty-four patients with HB were included in this retrospective study. D-dimer and plasma fibrinogen levels were examined, and their correlation with other clinical features was analyzed. D-dimer and plasma fibrinogen levels were examined between HB and other benign hepatic tumors. Results: D-dimer levels were significantly associated with high-risk HB features, such as advanced stage and high α-fetoprotein (AFP) levels. Higher D-dimer levels were observed in stage 4 patients compared with stage 1/2/3 patients (P = .028). Higher D-dimer levels were also observed in patients with higher AFP levels before chemotherapy compared with patients with lower AFP levels after chemotherapy (P< 0.001). In addition, higher D-dimer levels were observed in HB compared with other benign hepatic tumors such as hepatic hemangioma and hepatocellular adenoma (P = .012). No significant difference in D-dimer levels was found between sex (P = .503) and age (≥12 vs <12 months, P = .424). There was no significant difference in plasma fibrinogen levels between sex or age and high-risk HB features, such as advanced stage and high AFP levels. Conclusions: Elevated D-dimer levels could be a useful determinant biomarker for high-risk features in patients with HB. This finding also supports the clinical application of D-dimer in HB. PMID:29381980

Changes in visceral adipose tissue plasma membrane lipid composition in old rats are associated with adipocyte hypertrophy with aging.

PubMed

Bonzón-Kulichenko, Elena; Moltó, Eduardo; Pintado, Cristina; Fernández, Alejandro; Arribas, Carmen; Schwudke, Dominik; Gallardo, Nilda; Shevchenko, Andrej; Andrés, Antonio

2018-04-16

Increased adiposity, through adipocyte hypertrophy and/or hyperplasia, characterizes aging and obesity. Both are leptin-resistant states, associated to disturbed lipid metabolism, reduced insulin sensitivity and inflammation. Nevertheless, fat tissue dysfunction appears earlier in obesity than in normal aging. In contrast, lipodystrophy is accompanied by diabetes, and improving the fat cell capacity to expand rescues the diabetic phenotype. Fat tissue dysfunction is extensively studied in the diet-induced obesity, but remains relatively neglected in the aging-associated obesity. In the Wistar rat, as occurs in humans, early or middle aging is accompanied by an increase in adiposity. Using this experimental model, we describe the molecular mechanisms contributing to the white adipose tissue (WAT) hypertrophy. WAT from middle-old age rats is characterized by decreased basal lipogenesis and lipolysis, increased esterification, as demonstrated by the higher TAG and cholesterol content in visceral WAT, and the maintenance of total ceramide levels within normal values. In addition, we describe alterations in the adipose tissue plasma membrane lipid composition, as increased total ether-phosphatidylcholine, sphingomyelin and free cholesterol levels that favor an enlarged fat cell size with aging. All these metabolic changes may be regarded as a survival advantage that prevents the aged rats from becoming overtly diabetic.

New compounds able to control hepatic cholesterol metabolism: Is it possible to avoid statin treatment in aged people?

PubMed Central

Trapani, Laura; Segatto, Marco; Pallottini, Valentina

2013-01-01

Aging is characterized by the loss of homeostasis that leads to changes in the biochemical composition of tissues, reduced ability to respond adaptively to environmental stimuli, and increased susceptibility and vulnerability to diseases including coronary artery diseases, carotid artery disease and brain vessel disease. Hypercholesterolemia is one of the primary risk factors for these pathologies, whose incidence is highly related to aging. Almost 25% of men and 42% of women older than 65 years have a serum total cholesterol level greater than 240 mg/dL. The mechanisms behind this age-related increase in plasma cholesterol are still incompletely understood, thus, the control of plasma cholesterol content in aged people is more challenging than in adults. In this review the different pharmacological approaches to reduce plasma cholesterol levels, particularly in aged people, will be discussed. In brief, current therapies are mostly based on the prescription of statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) that are pretty effective but that exert several side effects. More attention should be given to potential drug interactions, potential age-related changes in drug pharmacokinetics, adverse effects such as myopathy and competing risks when statins are prescribed to old patients. In combination or in alternative to statin therapy, other agents might be required to reduce low density lipoprotein (LDL) cholesterol levels. Among the available drugs, the most commonly prescribed are those addressed to reduce cholesterol absorption, to modulate lipoprotein lipase activity and bile acid sequestrants: even these pharmacological interventions are not exempt from side effects. The use of antioxidants or organoselenium compounds and the discovery of new proteins able to modulate exclusively LDL receptor recycling such as Proprotein convertase subtilisin kexin 9 and SEC24 offer new pharmacological approaches to selectively reduce the main causes of dyslipidemia. PMID:24432184

Creatinine plasma at uncontrolled type 2 diabetes mellitus and controlled type 2 diabetes mellitus patients at primary health care in Binjai city, Indonesia

NASA Astrophysics Data System (ADS)

Rusdiana; Savira, M.; Syahputra, M.; Santoso, A.

2018-03-01

The aim of the study knowing the comparison creatinine plasma levels at uncontrolled type 2 diabetes mellitus and controlled type 2 diabetes mellitus patients at Primary Health Care in Binjai city of North Sumatera in Indonesia. This cross-sectional study was conductedon 40 type 2 Diabetes Mellitus patients who attended Primary Health Care in Binjai. Patients with age > 40 years old, (both sexes) were included in the study. We recorded different demographic parameter as age, Body Mass Index, Blood Pressure, and personal history status. And we examined the biochemicalparameters including Hba1c, Fasting Blood Sugar Levels (FBL) and creatinine serum. We separated into two groups base on HbA1c test, controlled type 2 diabetes mellitus and uncontrolled type 2 diabetes mellitus. We measured FBL by using the portable measuring instrument, and Thamrin clinical laboratory measured Hba1c, andwe measured creatinine plasmaby spectrophotometry in Biochemistry laboratory. With statistical analysis using T-test found that there was asignificant differencein creatinine plasma levels between uncontrolled type 2 diabetes mellitus with controlled type 2 diabetes mellitus (p<0.005).

Effects of vitamin D3 supplementation and UVb exposure on the growth and plasma concentration of vitamin D3 metabolites in juvenile bearded dragons (Pogona vitticeps).

PubMed

Oonincx, D G A B; Stevens, Y; van den Borne, J J G C; van Leeuwen, J P T M; Hendriks, W H

2010-06-01

The effectiveness of dietary vitamin D3 and UVb exposure on plasma vitamin D metabolites in growing bearded dragons (Pogona vitticeps) was studied. A total of 84 (40 males and 44 females) newly hatched bearded dragons were allocated to six levels of oral vitamin D3 supplementation (0 to 400%) or six UVb exposure times (2 to 12 h). At 3 and 6 months of age, blood samples were obtained from each animal and analysed for 25(OH)D3 and 1,25(OH)2D3. At 3 months of age, plasma concentrations of 25(OH)D3 did not increase with increasing vitamin D3 supplementation unlike the 1,25(OH)2D3. At 6 months of age, plasma concentrations of both 25(OH)D(3) and 1,25(OH)2D3 increased with increasing vitamin D(3) supplementation. Plasma concentrations in UVb-exposed animals were 18 times higher for 25(OH)D3 (178.4+/-9.0 vs. 9.9+/-1.3 nmol/L) and 5.3 times higher for 1,25(OH)2D3 (1.205+/-0.100 vs. 0.229+/-0.025 nmol/L) than in vitamin D(3) supplemented animals at 6 months of age. This study shows that 2h of UVb exposure enables adequate physiological concentrations of plasma vitamin D metabolites to be maintained in growing bearded dragons. Oral supplementation of vitamin D(3) is ineffective in raising plasma concentrations of 25(OH)D3 and 1,25(OH)2D3 to concentrations observed in UVb-exposed animals. 2010 Elsevier Inc. All rights reserved.

Partitioning the variability of fasting plasma glucose levels in pedigrees. Genetic and environmental factors.

PubMed

Boehnke, M; Moll, P P; Kottke, B A; Weidman, W H

1987-04-01

Fasting plasma glucose measurements made in 1972-1977 on normoglycemic individuals in three-generation Caucasian pedigrees from Rochester, Minnesota were analyzed. The authors determined the contributions of polygenic loci and environmental factors to fasting plasma glucose variability in these pedigrees. To that end, fasting plasma glucose measurements were normalized by an inverse normal scores transformation and then regressed separately for males and females on measured concomitants including age, body mass index (weight/height2), season of measurement, sex hormone use, and diuretic use. The authors found that 27.7% of the variability in normalized fasting plasma glucose in these pedigrees is explained by these measured concomitants. Subsequent variance components analysis suggested that unmeasured polygenic loci and unmeasured shared environmental factors together account for at least an additional 36.7% of the variability in normalized fasting plasma glucose, with genes alone accounting for at least 27.3%. These results are consistent with the known familiality of diabetes, for which fasting plasma glucose level is an important predictor. Further, these familial factors provide an explanation for at least half the variability in normalized fasting plasma glucose which remains after regression on known concomitants.

Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain.

PubMed

Liu, Cui-Cui; Zhang, Xin-Sheng; Ruan, Yu-Ting; Huang, Zhu-Xi; Zhang, Su-Bo; Liu, Meng; Luo, Hai-Jie; Wu, Shao-Ling; Ma, Chao

2017-08-01

Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 μm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain. NEW & NOTEWORTHY Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain. Copyright © 2017 the American Physiological Society.

Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes.

PubMed

Wewer Albrechtsen, Nicolai J; Junker, Anders E; Christensen, Mette; Hædersdal, Sofie; Wibrand, Flemming; Lund, Allan M; Galsgaard, Katrine D; Holst, Jens J; Knop, Filip K; Vilsbøll, Tina

2018-01-01

Patients with type 2 diabetes (T2D) and patients with nonalcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and α-cell hyperplasia may result from elevated levels of plasma amino acids when glucagon's action on hepatic amino acid metabolism is disrupted. We therefore measured plasma levels of glucagon and individual amino acids in patients with and without biopsy-verified NAFLD and with and without type T2D. Fasting levels of amino acids and glucagon in plasma were measured, using validated ELISAs and high-performance liquid chromatography, in obese, middle-aged individuals with I) normal glucose tolerance (NGT) and NAFLD, II) T2D and NAFLD, III) T2D without liver disease, and IV) NGT and no liver disease. Elevated levels of total amino acids were observed in participants with NAFLD and NGT compared with NGT controls (1,310 ± 235 µM vs. 937 ± 281 µM, P = 0.03) and in T2D and NAFLD compared with T2D without liver disease (1,354 ± 329 µM vs. 511 ± 235 µM, P < 0.0001). Particularly amino acids with known glucagonotropic effects (e.g., glutamine) were increased. Plasma levels of total amino acids correlated to plasma levels of glucagon also when adjusting for body mass index (BMI), glycated hemoglobin (Hb A1c ), and cholesterol levels (β = 0.013 ± 0.007, P = 0.024). Elevated plasma levels of total amino acids associate with hyperglucagonemia in NAFLD patients independently of glycemic control, BMI or cholesterol - supporting the potential importance of a "liver-α-cell axis" in which glucagon regulates hepatic amino acid metabolism. Fasting hyperglucagonemia as seen in T2D may therefore represent impaired hepatic glucagon action with increasing amino acids levels. NEW & NOTEWORTHY Hypersecretion of glucagon (hyperglucagonemia) has been suggested to be linked to type 2 diabetes. Here, we show that levels of amino acids correlate with levels of glucagon. Hyperglucagonemia may depend on hepatic steatosis rather than type 2 diabetes.

Selenium status and fungi in the protein-losing enteropathy of persistent diarrhea.

PubMed

Dwipoerwantoro, Pramita G; Lukito, Widjaja; Aulia, Diana; Arnaud, Josiane; Roussel, Anne-Marie

2017-06-01

A vicious cycle of infection, malabsorption, and malnutrition has been implicated in the perpetuation of diarrheal disease. This study examined whether persistent diarrhea is associated with changes in selenium status and stool alpha-1 antitrypsin (AAT) concentration. This cross-sectional study included 30 children aged 1-12 years with persistent diarrhea who were hospitalized in Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta, and 30 apparently healthy children who were matched by age and sex and lived in a rural area of Jakarta. Clinical examinations, blood routine tests, erythrocyte glutathione peroxidase (GPX) activity and plasma selenium levels as well as AAT in fresh stool samples were performed in all the subjects. Of 30 children with persistent diarrhea, 17 had moderate malnutrition and 13 had severe malnutrition. The mean plasma selenium was significantly lower in children with persistent diarrhea than in children without diarrhea (86.0 μg/L [95% CI: 76.1-95.9] vs 110 μg/L [95% CI: 104-116, p<0.0001). The mean stool AAT concentration was significantly higher in children with persistent diarrhea than in those without diarrhea (115 mg/dL [95% CI: 38.5-191] vs 16 mg/dL [95% CI: 4.0-13.5, p<0.0001]). Selenium correlated with AAT (p=0.05). Fecal fungi were persistently present. Although selenium status in both groups was optimal for the obtained plasma GPX activity, children with persistent diarrhea exhibited lower plasma selenium levels. This study suggests that the decrease in the plasma selenium level may be the consequence of protein loss and that fungi may be involved.

Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity.

PubMed

Bozaoglu, Kiymet; Attard, Chantal; Kulkarni, Hemant; Cummings, Nik; Diego, Vincent P; Carless, Melanie A; Shields, Katherine A; Johnson, Matthew P; Kowlessur, Sudhir; Dyer, Thomas D; Comuzzie, Anthony G; Almasy, Laura; Zimmet, Paul; Moses, Eric K; Göring, Harald H H; Curran, Joanne E; Blangero, John; Jowett, Jeremy B M

2014-09-01

Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity. The pathogenetic and clinical influences of sIL1RAP are unknown. The objective of the study was to elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts. The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230). Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study. A significant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM_134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 × 10(-23)) within the IL1RAP gene. Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity.

A Novel Tool for the Assessment Oxidative Stress in Age-Related Macular Degeneration: Thiol/Disulfide Homeostasis Revisited.

PubMed

Arıkan Yorgun, Mücella; Toklu, Yasin; Altınkaynak, Hasan; Tanrıverdi, Burak; Ergin, Merve; Biçer, Cemile

2016-12-01

To investigate thiol/disulfide status using a novel automated assay in patients with age-related macular degeneration (AMD) compared to age-matched healthy controls. A total of 64 AMD patients [51 (79%) non-exudative, 13 (21%) exudative AMD] and 21 age-matched healthy control subjects were enrolled in this study. Plasma total thiol, native thiol, disulfide levels were measured and native thiol/disulfide ratio (TDR) was calculated using a novel spectrophotometric assay. Patients with AMD had significantly lower levels of total thiol (434.8 ± 7.0 μmol/L vs. 472.2 ± 7.9 μmol/L, p < 0.001), native thiol (393.6 ± 6.5 μmol/L vs. 437.5 ± 7.1 μmol/L, p = 0.004) compared to healthy controls. However, plasma disulfide levels were higher in AMD patients (20.6 ± 0.9 μmol/L vs. 17.3 ± 1.3 μmol/L, p = 0.113) compared to healthy controls. The TDR was not statistically different between the early AMD group and healthy controls (24.2 ± 2.3 vs. 29.5 ± 3.1, p = 0.345). However, intermediate and advanced stage AMD groups had significantly lower levels of TDR compared to healthy controls (21.6 ± 2.6 vs. 29.5 ± 3.1, p = 0.023 and 20.3 ± 1.2 vs. 29.5 ± 3.1, p = 0.005, respectively). Native TDR was significantly lower in patients with exudative and non-exudative AMD (19.9 ± 2.3 vs. 29.5 ± 3.1, p = 0.024 and 21.8 ± 1.14 vs. 29.47 ± 3.1 respectively, p = 0.011). A greater extent of thiol consumption occurred in AMD patients compared to age-matched healthy controls. However, despite the similar levels of total thiol levels between several grades of AMD, the plasma native TDR value was decreased in accordance with the severity of the disease, which reflected the disease grade better.

Glyoxylate, a New Marker Metabolite of Type 2 Diabetes

PubMed Central

Nikiforova, Victoria J.; Giesbertz, Pieter; Wiemer, Jan; Bethan, Bianca; Looser, Ralf; Liebenberg, Volker; Ruiz Noppinger, Patricia; Daniel, Hannelore; Rein, Dietrich

2014-01-01

Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs). Reactive aldehydes derived from sugars play an important role in the generation of AGEs. Using metabolite profiling to characterize human plasma from diabetic versus nondiabetic subjects we observed in a recent study that the reactive aldehyde glyoxylate was increased before high levels of plasma glucose, typical for a diabetic condition, could be measured. Following this observation, we explored the relevance of increased glyoxylate in diabetic subjects and in diabetic C57BLKS/J-Leprdb/db−/− mice in the pathophysiology of diabetes. A retrospective study using samples of long-term blood donors revealed that glyoxylate levels unlike glucose levels became significantly elevated up to 3 years prior to diabetes diagnosis (difference to control P = 0.034). Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy. Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies. PMID:25525609

Trace element status and fatty acids metabolism during healthy ageing: an example of a population from the Tunisian eastern coast.

PubMed

Sfar, Sonia; El Heni, Jihen; Laporte, François; Braham, Hamadi; Jawed, Abdelhafidh; Amor, Salah; Sfar, Mohamed Tahar; Kerkeni, Abdelhamid

2012-03-01

Micronutrients as well as essential fatty acids are indispensable for the correct functioning of the organism. The risk of disturbance in the associated nutrition and metabolism is expected to increase during ageing. In addition, it seems that trace elements are involved in the fatty acids metabolism. The aim of the present study was then to assess age-related changes in trace elements status and in plasma essential fatty acids composition with an emphasis on the desaturase activity estimation. Two hundred healthy Tunisian subjects (30-85 years old) were recruited and separated into two subgroups: elderly (65-85 years old) and middle-aged (30-60 years old). The findings revealed that plasma zinc and calcium concentrations significantly decreased according to age. The prevalence of zinc deficiency was therefore shown to increase in old age (over 60% of elderly subjects were deficient or at risk of deficiency). No age-related changes were obtained for copper or magnesium status. The Δ6 desaturase, involved in the EFAs conversion, was shown to decrease according to age and to be associated with the plasma zinc level. Since elderly subjects were at risk of nutritional imbalance, it would be interesting to set optimal dietary proportion. This will help to prevent age-associated alterations and diseases for a better and healthy ageing. Copyright © 2011 Elsevier Inc. All rights reserved.

Aging and sleep deprivation induce the unfolded protein response in the pancreas: implications for metabolism

PubMed Central

Naidoo, Nirinjini; Davis, James G; Zhu, Jingxu; Yabumoto, Maya; Singletary, Kristan; Brown, Marishka; Galante, Raymond; Agarwal, Beamon; Baur, Joseph A

2014-01-01

Sleep disruption has detrimental effects on glucose metabolism through pathways that remain poorly defined. Although numerous studies have examined the consequences of sleep deprivation (SD) in the brain, few have directly tested its effects on peripheral organs. We examined several tissues in mice for induction of the unfolded protein response (UPR) following acute SD. In young animals, we found a robust induction of BiP in the pancreas, indicating an active UPR. At baseline, pancreata from aged animals exhibited a marked increase in a pro-apoptotic transcription factor, CHOP, that was amplified by SD, whereas BiP induction was not observed, suggesting a maladaptive response to cellular stress with age. Acute SD increased plasma glucose levels in both young and old animals. However, this change was not overtly related to stress in the pancreatic beta cells, as plasma insulin levels were not lower following acute SD. Accordingly, animals subjected to acute SD remained tolerant to a glucose challenge. In a chronic SD experiment, young mice were found to be sensitized to insulin and have improved glycemic control, whereas aged animals became hyperglycemic and failed to maintain appropriate plasma insulin concentrations. Our results show that both age and SD cooperate to induce the UPR in pancreatic tissue. While changes in insulin secretion are unlikely to play a major role in the acute effects of SD, CHOP induction in pancreatic tissues suggests that chronic SD may contribute to the loss or dysfunction of endocrine cells and that these effects may be exacerbated by normal aging. PMID:24102714

Obstructive sleep apnea and obesity are associated with reduced GPR 120 plasma levels in children.

PubMed

Gozal, David; Kheirandish-Gozal, Leila; Carreras, Alba; Khalyfa, Abdelnaby; Peris, Eduard

2014-05-01

Obstructive sleep apnea (OSA) is a common health problem, particularly in obese children, in whom a vicious cycle of obesity and OSA interdependencies promotes increased food intake. G protein-coupled receptor 120 (GPR 120) is a long-chain free fatty acid (FFA) receptor that plays an important role in energy homeostasis, and protects against insulin resistance and systemic inflammation. We hypothesized that GPR 120 levels would be reduced in children with OSA, particularly among obese children. Cross-sectional prospectively recruited cohort. Academic pediatric sleep program. Two hundred twenty-six children (mean age: 7.0 ± 2.1 y) underwent overnight polysomnographic evaluation and a fasting blood draw the morning after the sleep study. In addition to lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hsCRP) assays, monocyte GPR 120 expression, and plasma GPR 120 levels were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay kits. Obese children and those with OSA had significantly lower GPR 120 monocyte expression and plasma GPR 120 levels. Furthermore, when both obesity and OSA were present, GPR 120 levels were lowest. Linear associations emerged between GPR 120 plasma levels and body mass index (BMI) z score, as well as with apnea-hypopnea index (AHI), saturation of peripheral oxygen (SpO2) nadir, and respiratory arousal index (RAI), with RAI remaining statistically significant when controlling for age, ethnicity, sex, and BMI z score (P < 0.001). Similarly, HOMA-IR was significantly associated with GPR 120 levels, but neither low density lipoprotein nor high density lipoprotein cholesterol or hsCRP levels exhibited significant correlations. G protein-coupled receptor 120 (GPR 120) levels are reduced in pediatric OSA and obesity (particularly when both are present) and may play a role in modulating the degree of insulin resistance. The short- and long-term significance of reduced GPR 120 relative to food intake and glycemic deregulation remains undefined.

Prolonged Caloric Restriction in Obese Patients With Type 2 Diabetes Mellitus Decreases Plasma CETP and Increases Apolipoprotein AI Levels Without Improving the Cholesterol Efflux Properties of HDL

PubMed Central

Wang, Yanan; Snel, Marieke; Jonker, Jacqueline T.; Hammer, Sebastiaan; Lamb, Hildo J.; de Roos, Albert; Meinders, A. Edo; Pijl, Hanno; Romijn, Johannes A.; Smit, Johannes W.A.; Jazet, Ingrid M.; Rensen, Patrick C.N.

2011-01-01

OBJECTIVE Using a mouse model for human-like lipoprotein metabolism, we observed previously that reduction of the hepatic triglyceride (TG) content resulted in a decrease in plasma cholesteryl ester transfer protein (CETP) and an increase in HDL levels. The aim of the current study was to investigate the effects of prolonged caloric restriction in obese patients with type 2 diabetes mellitus, resulting in a major reduction in hepatic TG content, on plasma CETP and HDL levels. RESEARCH DESIGN AND METHODS We studied 27 obese (BMI: 37.2 ± 0.9 kg/m2) insulin-dependent patients with type 2 diabetes mellitus (14 men and 13 women, aged 55 ± 2 years) who received a 16-week very low calorie diet (VLCD). At baseline and after a 16-week VLCD, plasma lipids, lipoproteins, and CETP were measured. Furthermore, functionality of HDL with respect to inducing cholesterol efflux from human monocyte cells (THP-1) was determined. RESULTS A 16-week VLCD markedly decreased plasma CETP concentration (−18%; P < 0.01) and increased plasma apolipoprotein (apo)AI levels (+16%; P < 0.05), without significantly affecting plasma HDL-cholesterol and HDL-phospholipids. Although a VLCD results in HDL that is less lipidated, the functionality of HDL with respect to inducing cholesterol efflux in vitro was unchanged. CONCLUSIONS The marked decrease in hepatic TG content induced by a 16-week VLCD is accompanied by a decrease in plasma CETP concentration and an increase in apoAI levels, without improving the cholesterol efflux properties of HDL in vitro. PMID:21994427

Blood cholinesterase levels in a group of Malaysian blood donors.

PubMed

Chan, L; Balabaskaran, S; Delilkan, A E; Ong, L H

1994-12-01

Data on blood cholinesterase levels in the Malaysian population is lacking. The spectrophotometric method of Ellman was used to determine the red cell, plasma and whole blood cholinesterase (ChE) levels in 407 Malaysian blood donors. The mean+1SD for plasma ChE in females (n = 48) was 2.37 + 0.70 umol/min/ml and 2.76 + 0.75 umol/min/ml in males (n = 359). The mean plasma ChE in males was higher than in females (p < 0.001). The mean+1SD for red cell ChE in females was 9.01 + 1.20 umol/min/ml whereas in males it was 7.69 +1.30 umol/min/ml (the mean red cell ChE in females was higher than in males, p < 0.0001). The mean+1SD for whole blood ChE for females was 4.31+ 0.58 umol/min/ml and for males it was 4.95 + 0.71 umol/min/ml. The mean whole blood ChE in males was higher than in females (p < 0.0001). Sex influenced the plasma, red cell and whole blood ChE. In males the plasma ChE was affected by the race factor. The mean+1SD plasma ChE for the Malay, Chinese and Indian were 2.92 + 0.80, 2.73 + 0.71 and 2.61+ 0.73 respectively (p < 0.002). The age factor in males affected the red cell ChE with 7.88 + 1.32 in the (30-69) age group and 7.47 + 1.23 in the (15-29) age group (p < 0.005). The whole blood ChE in females was affected by blood groups. The mean+1SD whole blood ChE for blood groups A,B and O were 4.19 + 0.42, 3.93 + 0.46 and 4.49 + 0.62 respectively (p < 0.03). The significant difference is between the ChE of group B and O, but the ChE of group A could not be determined to be different from group B or O. These results serve as guidelines for our local population in the evaluation of cholinesterase levels with regard to pesticide poisoning, liver biosynthetic capacity and unusual sensitivity to succinylcholine.

Effect of omega 3 and omega 6 fatty acid intakes from diet and supplements on plasma fatty acid levels in the first 3 years of life.

PubMed

Hoyos, Camilla; Almqvist, Catarina; Garden, Frances; Xuan, Wei; Oddy, Wendy H; Marks, Guy B; Webb, Karen L

2008-01-01

The optimal method for conducting omega (n-)3 polyunsaturated fatty acid (PUFA) supplementation trials in children is unknown. To assess the impact of n-3 and n-6 PUFA intake from the background diet on plasma levels of n-3 and n-6 PUFA in children aged 0-3 years, with and without n-3 supplementation. Subjects were randomised antenatally to receive either n-3 PUFA supplements and low n-6 PUFA cooking oils and spreads or a control intervention, designed to maintain usual fatty acid intake. Dietary intake was assessed at 18 months by 3-day weighed food record and at 3 years by food frequency questionnaire. Plasma phospholipids were measured at both time points. Associations were tested by regression. N-3 PUFA intake from background diet did not significantly affect plasma n-3 levels. In contrast, n-6 PUFA intake in background diet was positively related to plasma n-6 levels in both study groups. In addition, n-6 PUFA intake from diet was negatively associated with plasma n-3 levels at 18 months and 3 years (-0.16%/g n-6 intake, 95%CI -0.29 to -0.03 and -0.05%/g n-6 intake, 95%CI -0.09 to -0.01, respectively) in the active group, but not in the control group. Interventions intending to increase plasma n-3 PUFA in children by n-3 supplementation should also minimise n-6 PUFA intake in the background diet.

Plasma melatonin and insulin-like growth factor-1 responses to dim light at night in dairy heifers.

PubMed

Muthuramalingam, P; Kennedy, A D; Berry, R J

2006-04-01

The effect of dim (5, 10 and 50 1x) light at night on night plasma melatonin level (NML) and night plasma insulin-like growth factor-1 (IGF-1) level was determined in 12 prepubertal Holstein heifers (245 +/- 16 days age) using a 4 x 4 Latin Square design with 14-day treatment and 14-day recovery periods. Blood samples were collected at 23:00 hr (prior to the 8 hr night treatment which commenced at mid-night) on days 0, 3 and 13, and throughout the night at 01:00, 02:00, 03:00, 04:00, 06:00 and 08:00 hr on days 1, 4 and 14 of treatment. Plasma was analysed by radioimmunoassay for melatonin (all samples) and IGF-1 (samples for day 14, 04:00 hr only). Treatment (P = 0.03) and treatment x time (P = 0.02) were significant for NML. Exposure to 50 lx suppressed NML by 50% during the initial 2 hr of the night, but not thereafter. Exposure to 5 and 10 lx had no effect on NML. The NML response to 50 lx was found on all treatment days studied (treatment x time x day; P = 0.99). There was no treatment effect on plasma IGF-1 level (P = 0.89), but plasma IGF-1 level was higher (P = 0.001) during period 4. Plasma IGF-1 level and NML tended (P = 0.10) to be negatively correlated. Light intensities of 10 lx or less appear safe for use at night in dairy barns where darkness is recommended.

Decreased Circulating mtDNA Levels in Professional Male Volleyball Players.

PubMed

Nasi, Milena; Cristani, Alessandro; Pinti, Marcello; Lamberti, Igor; Gibellini, Lara; De Biasi, Sara; Guazzaloca, Alessandro; Trenti, Tommaso; Cossarizza, Andrea

2016-01-01

Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance. Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed. The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters. Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.

Reassessment of ABO blood group, sex, and age on laboratory parameters used to diagnose von Willebrand disorder: potential influence on the diagnosis vs the potential association with risk of thrombosis.

PubMed

Favaloro, Emmanuel J; Soltani, Soma; McDonald, Jane; Grezchnik, Ella; Easton, Leanne; Favaloro, James W C

2005-12-01

We reassessed the influence of ABO blood group, sex, and age on plasma levels of von Willebrand factor (vWF) antigen, vWF:ristocetin cofactor, vWF:collagen binding assay, and factor VIII coagulant (FVIII:C). Data show that levels of vWF and FVIII:C increase with increasing age (P < .001 for all parameters) and that the ABO blood group influences plasma levels such that O group levels are significantly less than non-O group levels. There was no significant association with sex and Rh status. The selection of normal ranges based on ABO blood groups may influence the clinical diagnosis of von Willebrand disease (vWD) but might not be clinically relevant or help identify people at increased risk of bleeding. Differences in ABO-related ranges were more extensive at the high end of the ranges. This is of particular interest because high levels of vWF and FVIII are associated with thrombosis risk, and an ABO relationship also has been described. O group individuals may or may not be at greater risk for bleeding (they have lower levels of vWF and FVIII:C) and are more likely to be diagnosed with vWD. It also is possible that O group status may be protective for thrombosis.

Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population - results from the PolSenior substudy.

PubMed

Olszanecka-Glinianowicz, Magdalena; Owczarek, Aleksander; Bożentowicz-Wikarek, Maria; Brzozowska, Aniceta; Mossakowska, Małgorzata; Zdrojewski, Tomasz; Grodzicki, Tomasz; Więcek, Andrzej; Chudek, Jerzy

2014-11-01

Circulating visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) levels according to some studies are related to nutritional status and insulin resistance. These associations have not been studied in large elderly populations. Therefore, the aim of our study was to assess the relationships between circulating visfatin/NAMPT levels, nutritional status, and insulin resistance in a large population of the elderly. Concentrations of glucose, albumin, creatinine, CRP, interleukin-6, insulin, and visfatin/NAMPT (by ELISA) were assessed, and HOMA-IR calculated in 3050 elderly participants of the PolSenior study. The highest plasma visfatin/NAMPT levels were observed in obese, as well as in non-diabetic insulin resistant subjects; however there were only significant differences found in women. The regression models showed that plasma visfatin/NAMPT levels decline with age and increased with waist circumference, BMI, and hs-CRP. Waist circumference was better correlated than BMI for visfatin/NAMPT levels in statistical models not adjusted by sex, and just the opposite in models which were. We demonstrated a 0.023ng/mL increase of Visfatin/NAMPT levels for 1mg/L increase of hs-CRP, and a 0.007ng/mL decline for each year of age. Our study revealed that in elderly subjects, circulating visfatin/NAMPT levels are related to age, nutritional status, especially visceral obesity, and inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessment of erythrocyte acetylcholine esterase activities in painters.

PubMed

Khan, Mohd Imran; Mahdi, Abbas Ali; Islam, Najmul; Rastogi, Subodh Kumar; Negi, M P S

2009-04-01

Thirty-five male painters in the age group of 20-50 years occupationally engaged in domestic and commercial painting for 5-12 years having blood lead levels (BLL)

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study

PubMed Central

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-01-01

Kale (Brassica oleracea var. acephala), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21–64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140–187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30–120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (Cmax; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0–2 h (AUC0–2 h) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe. PMID:27882216

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

PubMed

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-11-01

Kale ( Brassica oleracea var. acephala ), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (C max ; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0-2 h (AUC 0-2 h ) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.

The association between insulin-like growth factor 1 (IGF-1), IGF-binding proteins (IGFBPs), and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis.

PubMed

Szeremeta, A; Jura-Półtorak, A; Komosińska-Vassev, K; Zoń-Giebel, A; Kapołka, D; Olczyk, K

2017-05-01

To assess the association between plasma levels of the insulin-like growth factor (IGF) system including IGF-1, IGF-binding proteins (IGFBPs) including IGFBP-1, total (t-)IGFBP-3 and functional (f-)IGFBP-3, and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis (RA). Plasma concentrations of IGF-1, IGFBP-1, t-IGFBP-3, f-IGFBP-3, and PICP were measured by immunoassay. No significant difference was observed in plasma IGF-1 levels between pre- and postmenopausal subjects. Plasma levels of IGFBP-1 were elevated in RA. PICP and f-IGFBP-3 were greatly affected by menopausal status. Of the three IGFBPs tested, only f-IGFBP-3 plasma levels in RA women correlated negatively with age and disease duration. A positive correlation was demonstrated between PICP and erythrocyte sedimentation rate (ESR) in RA. Moreover, there was no correlation between PICP and IGF-1 and any of the IGFBPs in RA women. Considerable disruption of the IGF system in RA was found to be related to disease activity and duration. Changes in the IGF-IGFBP axis and PICP levels were different in pre- and postmenopausal women with RA. Elevated plasma PICP concentrations may indicate an increased rate of bone formation in postmenopausal RA women. Additionally, the observed changes in the IGF/IGFBP system did not affect bone formation during RA.

Plasma adiponectin levels and incident glucose intolerance in Japanese-Brazilians: a seven-year follow-up study.

PubMed

Vendramini, Marcio F; Ferreira, Sandra R G; Gimeno, Suely G A; Kasamatsu, Teresa S; Miranda, Walkiria L; Moisés, Regina S

2006-09-01

The objective of this study was to investigate whether decreased baseline adiponectin levels are an independent risk factor for development of glucose intolerance in a population-based study of Japanese-Brazilians, a group with one of the highest prevalence rates of diabetes worldwide. We examined 210 Japanese-Brazilians (97 male and 113 female, aged 56.7+/-10.1 years) with normal glucose tolerance (NGT). Plasma adiponectin, insulin, fasting and 2-h plasma glucose and lipid profile were evaluated at baseline and also at 7-year follow-up. Plasma adiponectin levels were significantly lower in glucose intolerance progressors compared with subjects who remained NGT. By increasing tertiles of adiponectin, the frequencies of subjects who progressed to glucose intolerance were 40%, 33% and 27% and the frequencies of subjects who remained NGT were 13%, 35% and 52% (chi2=15.8, p=0.001). Logistic regression analyses showed that adiponectin levels (OR for the highest versus lowest tertile: 0.31; 95% CI: 0.12-0.84, p=0.021), male sex (OR: 2.61, 95% CI: 1.21-5.65, p=0.015), fasting plasma glucose (0R: 3.05, 95% CI: 1.35-6.91, p=0.008) and waist circumference (OR: 1.04, 95% CI: 1.00-1.08, p=0.046) were independent risk factors for the progression to glucose intolerance. In conclusion, low plasma levels of adiponectin is one of several independent predictors of glucose intolerance in a Japanese-Brazilian population.

The Effect of Flax Seed (Linum Usitatissimum) Hydroalcoholic Extract on Brain, Weight and Plasma Sexual Hormone Levels in Aged and Young Mice.

PubMed

Bahmanpour, Soghra; Kamali, Mahsa

2016-05-01

Flax is a food and fiber crop that is grown in some regions of the world. Its value will account for its great popularity as a food, medical and cosmetic applications. Flax fibers are taken from the stem of the plant and are two to three times as strong as cotton. In this study, we compared brain weight and plasma sex hormone levels in young and aged mice after the administration of Linum usitatissimum (flax seed) hydro alcoholic extract. In this study, 32 aged and 32 young mice were divided into 4 groups. Controls remained untreated and experimental groups were fed with flax seed hydroalcoholic extract by oral gavages during 3 weeks. After 3 weeks, the brain was removed and blood samples were collected to measure sex hormone levels by ELISA. Data analysis was done by statistical ANOVA test using SPSS version 18 (P<0.05). The results of this study shows that the brain weight of mice did not change significantly, but the sex hormone levels in the experimental groups in comparison with the control groups increased significantly (P<0.05). The hydroalcoholic extract of flax seed had no effect on the brain weight, but this extract improved the sexual hormone levels.

Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer--Norfolk prospective study.

PubMed

Harding, Anne-Helen; Wareham, Nicholas J; Bingham, Sheila A; Khaw, KayTee; Luben, Robert; Welch, Ailsa; Forouhi, Nita G

2008-07-28

Epidemiologic studies suggest that greater consumption of fruit and vegetables may decrease the risk of diabetes mellitus, but the evidence is limited and inconclusive. Plasma vitamin C level is a good biomarker of fruit and vegetable intake, but, to our knowledge, no prospective studies have examined its association with diabetes risk. This study aims to examine whether fruit and vegetable intake and plasma vitamin C level are associated with the risk of incident type 2 diabetes. We administered a semiquantitative food frequency questionnaire to men and women from a population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk) study who were aged 40 to 75 years at baseline (1993-1997) when plasma vitamin C level was determined and habitual intake of fruit and vegetables was assessed. During 12 years of follow-up between February 1993 and the end of December 2005, 735 clinically incident cases of diabetes were identified among 21 831 healthy individuals. We report the odds ratios of diabetes associated with sex-specific quintiles of fruit and vegetable intake and of plasma vitamin C levels. A strong inverse association was found between plasma vitamin C level and diabetes risk. The odds ratio of diabetes in the top quintile of plasma vitamin C was 0.38 (95% confidence interval, 0.28-0.52) in a model adjusted for demographic, lifestyle, and anthropometric variables. In a similarly adjusted model, the odds ratio of diabetes in the top quintile of fruit and vegetable consumption was 0.78 (95% confidence interval, 0.60-1.00). Higher plasma vitamin C level and, to a lesser degree, fruit and vegetable intake were associated with a substantially decreased risk of diabetes. Our findings highlight a potentially important public health message on the benefits of a diet rich in fruit and vegetables for the prevention of diabetes.

The effect of testosterone on cardiometabolic risk factors in atorvastatin-treated men with late-onset hypogonadism.

PubMed

Krysiak, Robert; Gilowski, Wojciech; Okopień, Bogusław

2016-02-01

By reducing LDL cholesterol levels, statins may decrease androgen production. This study was aimed at investigating whether testosterone treatment has an impact on cardiometabolic risk factors in statin-treated men with late-onset hypogonadism (LOH). The study included 31 men with LOH who had been treated for at least 6 months with atorvastatin (20-40mg daily). On the basis of patient preference, atorvastatin-treated patients were divided into two matched groups of patients: receiving intramuscular testosterone enanthate (100mg weekly, n=16) and not treated with this hormone (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 4 months of therapy. Compared with the control age-, weight, and lipid-matched statin-naïve subjects with LOH (n=12), atorvastatin-treated patients were characterized by decreased levels of testosterone, hsCRP, and homocysteine. In patients not receiving testosterone therapy, plasma lipids, glucose homeostasis markers, as well as plasma levels of the investigated risk factors remained at the similar levels throughout the whole period of atorvastatin treatment. In atorvastatin-naïve patients, testosterone increased its plasma levels and decreased HDL cholesterol. Apart from an increase in testosterone levels, if administered to atorvastatin-treated subjects with LOH, testosterone reduced plasma levels of LDL cholesterol, uric acid, hsCRP, homocysteine, and fibrinogen, as well as improved insulin sensitivity. Our study may suggest the clinical benefits associated with combination therapy with a statin and testosterone in elderly men with LOH. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

PubMed

Martin, Genevieve E; Gouillou, Maelenn; Hearps, Anna C; Angelovich, Thomas A; Cheng, Allen C; Lynch, Fiona; Cheng, Wan-Jung; Paukovics, Geza; Palmer, Clovis S; Novak, Richard M; Jaworowski, Anthony; Landay, Alan L; Crowe, Suzanne M

2013-01-01

Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

PubMed

Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

2015-10-01

Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without BM invasion showing high level of bone marrow plasma vascular endothelial growth factor per platelet count had significantly shorter progression-free survival and overall survival. Bone marrow plasma vascular endothelial growth factor level per platelet count might be associated with bone marrow invasion by diffuse large B-cell lymphoma and is correlated with clinical outcomes after treatment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Combined association of maternal and paternal family history of diabetes with plasma leptin and adiponectin in overweight Hispanic children.

PubMed

Koebnick, C; Kelly, L A; Lane, C J; Roberts, C K; Shaibi, G Q; Toledo-Corral, C M; Davis, J N; Weigensberg, M J; Goran, M I

2008-09-01

To investigate the importance of a maternal and paternal family history of Type 2 diabetes and their combined association with plasma leptin and adiponectin levels in overweight Latino children with a family history of Type 2 diabetes (T2DM). This cross-sectional study investigated the combined association of a maternal and paternal family history of T2DM with leptin and adiponectin in 175 overweight Latino children (age 11.1 +/- 1.7 years). All subjects had a family history of T2DM. Plasma adiponectin and leptin levels, body fat measured by dual-energy X-ray absorptiometry, Tanner stage, age and insulin sensitivity were assessed. After adjustment for age, gestational diabetes, insulin sensitivity and body fat, a combined maternal and paternal family history of T2DM was associated with higher leptin concentrations (P = 0.004) compared with a maternal or paternal family history alone. This association was most pronounced at Tanner stage 1 (P for interaction family history x tanner stage = 0.022). The presence of a combined maternal and paternal family history of T2DM accounted for 4% (P = 0.003) of the variation in leptin concentrations. No such combined association was observed for adiponectin levels. Maternal and paternal family history of T2DM may have an additive impact on leptin, but not on adiponectin levels independent of adiposity and insulin sensitivity in overweight Latino children. This may contribute to a further clinically relevant deterioration of metabolic health in this population.

Increased plasma levels of big-endothelin-2 and big-endothelin-3 in patients with end-stage renal disease.

PubMed

Miyauchi, Yumi; Sakai, Satoshi; Maeda, Seiji; Shimojo, Nobutake; Watanabe, Shigeyuki; Honma, Satoshi; Kuga, Keisuke; Aonuma, Kazutaka; Miyauchi, Takashi

2012-10-15

Big endothelins (pro-endothelin; inactive-precursor) are converted to biologically active endothelins (ETs). Mammals and humans produce three ET family members: ET-1, ET-2 and ET-3, from three different genes. Although ET-1 is produced by vascular endothelial cells, these cells do not produce ET-3, which is produced by neuronal cells and organs such as the thyroid, salivary gland and the kidney. In patients with end-stage renal disease, abnormal vascular endothelial cell function and elevated plasma ET-1 and big ET-1 levels have been reported. It is unknown whether big ET-2 and big ET-3 plasma levels are altered in these patients. The purpose of the present study was to determine whether endogenous ET-1, ET-2, and ET-3 systems including big ETs are altered in patients with end-stage renal disease. We measured plasma levels of ET-1, ET-3 and big ET-1, big ET-2, and big ET-3 in patients on chronic hemodialysis (n=23) and age-matched healthy subjects (n=17). In patients on hemodialysis, plasma levels (measured just before hemodialysis) of both ET-1 and ET-3 and big ET-1, big ET-2, and big ET-3 were markedly elevated, and the increase was higher for big ETs (Big ET-1, 4-fold; big ET-2, 6-fold; big ET-3: 5-fold) than for ETs (ET-1, 1.7-fold; ET-3, 2-fold). In hemodialysis patients, plasma levels of the inactive precursors big ET-1, big ET-2, and big ET-3 levels are markedly increased, yet there is only a moderate increase in plasma levels of the active products, ET-1 and ET-3. This suggests that the activity of endothelin converting enzyme contributing to circulating levels of ET-1 and ET-3 may be decreased in patients on chronic hemodialysis. Copyright © 2012 Elsevier Inc. All rights reserved.

Maternal blood, plasma, and breast milk lead: lactational transfer and contribution to infant exposure.

PubMed

Ettinger, Adrienne S; Roy, Ananya; Amarasiriwardena, Chitra J; Smith, Donald; Lupoli, Nicola; Mercado-García, Adriana; Lamadrid-Figueroa, Hector; Tellez-Rojo, Martha Maria; Hu, Howard; Hernández-Avila, Mauricio

2014-01-01

Human milk is a potential source of lead exposure. Yet lactational transfer of lead from maternal blood into breast milk and its contribution to infant lead burden remains poorly understood. We explored the dose-response relationships between maternal blood, plasma, and breast milk to better understand lactational transfer of lead from blood and plasma into milk and, ultimately, to the breastfeeding infant. We measured lead in 81 maternal blood, plasma, and breast milk samples at 1 month postpartum and in 60 infant blood samples at 3 months of age. Milk-to-plasma (M/P) lead ratios were calculated. Multivariate linear, piecewise, and generalized additive models were used to examine dose-response relationships between blood, plasma, and milk lead levels. Maternal lead levels (mean±SD) were as follows: blood: 7.7±4.0 μg/dL; plasma: 0.1±0.1 μg/L; milk: 0.8±0.7 μg/L. The average M/P lead ratio was 7.7 (range, 0.6-39.8) with 97% of the ratios being >1. The dose-response relationship between plasma lead and M/P ratio was nonlinear (empirical distribution function=6.5, p=0.0006) with the M/P ratio decreasing by 16.6 and 0.6 per 0.1 μg/L of plasma lead, respectively, below and above 0.1 μg/L plasma lead. Infant blood lead level (3.4±2.2 μg/dL) increased by 1.8 μg/dL per 1 μg/L milk lead (p<0.0001, R2=0.3). The M/P ratio for lead in humans is substantially higher than previously reported, and transfer of lead from plasma to milk may be higher at lower levels of plasma lead. Breast milk is an important determinant of lead burden among breastfeeding infants.

Increased production of active ghrelin is relevant to hyperphagia in nonobese spontaneously diabetic Torii rats.

PubMed

Mifune, Hiroharu; Nishi, Yoshihiro; Tajiri, Yuji; Masuyama, Taku; Hosoda, Hiroshi; Kangawa, Kenji; Kojima, Masayasu

2012-04-01

An abnormal eating behavior is often associated with diabetes mellitus in individuals. In the present study, we investigated the mechanisms underlying the relationship among uncontrolled diabetes, food intake, and the production of ghrelin, an orexigenic hormone, in spontaneous diabetic Torii (SDT) rats. Male SDT rats and age-matched control Sprague-Dawley (SD) rats were housed from 8 to 38 weeks of age. Body weight and daily food intake were measured weekly, whereas blood and whole stomach samples were obtained at the age of 8, 25, and 38 weeks in both SDT and SD rats. The SDT rats at both 25 and 38 weeks of age demonstrated significantly lower body weights despite almost doubled food consumption compared with the SD rats of the same age. The SDT rats showed overt hyperglycemia at 25 and 38 weeks of age with concomitant hypoinsulinemia. The plasma active ghrelin levels and the ratio to total ghrelin levels of SDT rats at 38 weeks of age were significantly higher than those of SD rats of the same age. Stomach ghrelin and ghrelin O-acyltransferase messenger RNA expression levels were higher in SDT rats than in SD rats after the induction of diabetes, with a concomitant decrease of stomach ghrelin-immunopositive cell numbers in SDT rats at 38 weeks of age. The SDT rats with uncontrolled hyperglycemia show hyperphagia with a concomitant increase of plasma active ghrelin concentration. This report is the first to clarify the relevance of ghrelin to hyperphagia in diabetic state over an extended period. Copyright © 2012 Elsevier Inc. All rights reserved.

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

PubMed

Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

2008-05-01

Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans

PubMed Central

Butler, Andrew A.; St-Onge, Marie-Pierre; Siebert, Emily A.; Medici, Valentina; Stanhope, Kimber L.; Havel, Peter J.

2015-01-01

Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations. PMID:26435060

Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.

PubMed

Yorbik, Ozgur; Mutlu, Caner; Ozilhan, Selma; Eryilmaz, Gul; Isiten, Nuket; Alparslan, Serdar; Saglam, Esra

2015-06-01

There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma. The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay. Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects. Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate dose formulations such as 45-mg tablets for OROS-MPH may contribute to the optimization.

MicroRNAs as Biomarkers for Acute Atrial Remodeling in Marathon Runners (The miRathon Study – A Sub-Study of the Munich Marathon Study)

PubMed Central

Hildebrand, Bianca; Kääb, Stefan; Hoster, Eva; Klier, Ina; Martens, Eimo; Hanley, Alan; Hanssen, Henner; Halle, Martin; Nickel, Thomas

2016-01-01

Introduction Physical activity is beneficial for individual health, but endurance sport is associated with the development of arrhythmias like atrial fibrillation. The underlying mechanisms leading to this increased risk are still not fully understood. MicroRNAs are important mediators of proarrhythmogenic remodeling and have potential value as biomarkers in cardiovascular diseases. Therefore, the objective of our study was to determine the value of circulating microRNAs as potential biomarkers for atrial remodeling in marathon runners (miRathon study). Methods 30 marathon runners were recruited into our study and were divided into two age-matched groups depending on the training status: elite (ER, ≥55 km/week, n = 15) and non-elite runners (NER, ≤40 km/week, n = 15). All runners participated in a 10 week training program before the marathon. MiRNA plasma levels were measured at 4 time points: at baseline (V1), after a 10 week training period (V2), immediately after the marathon (V3) and 24h later (V4). Additionally, we obtained clinical data including serum chemistry and echocardiography at each time point. Results MiRNA plasma levels were similar in both groups over time with more pronounced changes in ER. After the marathon miR-30a plasma levels increased significantly in both groups. MiR-1 and miR-133a plasma levels also increased but showed significant changes in ER only. 24h after the marathon plasma levels returned to baseline. MiR-26a decreased significantly after the marathon in elite runners only and miR-29b showed a non-significant decrease over time in both groups. In ER miRNA plasma levels showed a significant correlation with LA diameter, in NER miRNA plasma levels did not correlate with echocardiographic parameters. Conclusion MiRNAs were differentially expressed in the plasma of marathon runners with more pronounced changes in ER. Plasma levels in ER correlate with left atrial diameter suggesting that circulating miRNAs could potentially serve as biomarkers of atrial remodeling in athletes. PMID:26859843

Cytophilic antibodies to Plasmodium falciparum glutamate rich protein are associated with malaria protection in an area of holoendemic transmission.

PubMed

Lusingu, John P A; Vestergaard, Lasse S; Alifrangis, Michael; Mmbando, Bruno P; Theisen, Michael; Kitua, Andrew Y; Lemnge, Martha M; Theander, Thor G

2005-09-29

Several studies conducted in areas of medium or low malaria transmission intensity have found associations between malaria immunity and plasma antibody levels to glutamate rich protein (GLURP). This study was conducted to analyse if a similar relationship could be documented in an area of intense malaria transmission. A six month longitudinal study was conducted in an area of holoendemic malaria transmission in north-eastern Tanzania, where the incidence of febrile malaria decreased sharply by the age of three years, and anaemia constituted a significant part of the malaria disease burden. Plasma antibodies to glutamate rich protein (GLURP) were analysed and related with protection against malaria morbidity in models correcting for the effect of age. The risk of febrile malaria episodes was reduced significantly in children with measurable anti-GLURP IgG1 antibodies at enrollment [adjusted odds ratio: 0.39 (95% CI: 0.15, 0.99); P = 0.047]. Interestingly, there was an inverse relationship between the plasma anti-GLURP IgG1 and IgG3 levels and the levels of parasitaemia at enrollment. However, anti-GLURP IgG2 and IgG4 levels were not associated with reduction in parasite density. Similarly, antibody levels were not associated with haemoglobin levels or anaemia risk. Cytophilic IgG1 and IgG3 antibodies against R0-GLURP may contribute to the control of parasite multiplication and reduction in febrile malaria incidence in children living in an area of intense malaria transmission.

Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors

PubMed Central

Castley, Alison; Williams, Leah; James, Ian; Guelfi, George; Berry, Cassandra; Nolan, David

2016-01-01

We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p<0.001), sCD163 was significantly reduced among ‘aviraemic’ patients only (p = 0.02), while sCD14 was unaffected by virological status under 10,000 copies/mL (p>0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation. PMID:27355513

Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

PubMed

Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

2014-12-01

Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

Levels of plasma and fecal glucocorticoid metabolites following an ACTH challenge in male and female coyotes (Canis latrans).

PubMed

Stevenson, Erika T; Gese, Eric M; Neuman-Lee, Lorin A; French, Susannah S

2018-03-01

Knowledge of endocrine stress responses can be advantageous for understanding how animals respond to their environment. One tool in wildlife endocrinology is to measure the adrenocortical activity as a parameter of disturbance of animals. Fecal glucocorticoid metabolites (GCMs) provide a noninvasive assessment of adrenocortical activity. Using an adrenocorticotropic hormone (ACTH) challenge administered to 28 captive coyotes (Canis latrans), we measured the levels of plasma cortisol, and fecal cortisol and corticosterone metabolites (i.e., GCMs). Our goal was to determine the dose-response in the plasma and fecal samples following the injection and determine if there were effects of sex, age, and time of day. Specifically, animals were anesthetized for ~ 90 min with treatment animals intravenously injected with exogenous ACTH and control animals receiving saline. We collected blood samples prior to injection and at 4 different time points post-injection. We also collected fecal samples 2 days pre- and 2 days post-injection to measure fecal GCMs and determine if an endocrine stress response could be detected in fecal samples. We found a definite response in cortisol levels in the plasma for coyotes to the ACTH challenge. There was a response in fecal corticosterone 1 day post-injection, but the control males showed a similar response indicating a handling effect. Fecal cortisol levels did not indicate a response to the ACTH challenge, and were significantly lower than corticosterone concentrations. We also found significant sex, but not age or diurnal, differences in fecal GCMs. Radioimmunoassays for fecal corticosterone levels appeared to be a reliable indicator of physiological stress in coyotes.

Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

PubMed

Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

2014-09-05

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=-0.51, P<0.001, respectively). On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels. Copyright © 2014 by the American Society of Nephrology.

Changes in plasma steroids and cytokines levels in betel chewing patients in Taiwan.

PubMed

Hu, Sindy; Chen, Wen-Chyuan; Hwang, Guey-Shyang; Chen, Szu-Tah; Kuo, Song-Bor; Chen, Yifen; Idova, Galina; Wang, Shyi-Wu

2016-07-01

Betel nut is the second largest economic food product in Taiwan. In Southeast Asia, the habit of chewing betel nut seems to be highly correlated with oral submucous fibrosis and oral squamous cell carcinoma. Oral submucous fibrosis is characterized by abnormal accumulation of oral submucous collagen fibers and limitation of mouth opening. Although the mechanism responsible for tissue damage is still unknown, prolonged irritation caused by betel nut and tobacco is considered to be a major factor contributing to the pathogenesis of oral submucous fibrosis. The effect of betel nut chewing on immune system remains unknown. Present study aims to investigate the change of plasma hormones including cortisol, testosterone, and inflammatory cytokine concentrations in male chewing betel nut compared with normal subjects. Heparinized blood was obtained from control group (normal young+mid-aged individuals), betel nut-chewing, and oral cancer male subjects. The study was approved by the Ethics Committee of the Chang-Gung Memorial Hospital. Written informed consent was granted by the patients. Plasma cortisol and testosterone concentrations were detected by commercial enzyme-linked immunosorbent assay (ELISA). The inflammatory cytokines, including interleukin-1β (IL-1β), IL-15, tumor necrosis factor-α (TNF-α), were analyzed by ELISA with commercial monoclonal capture antibodies and polyclonal detection antibodies. The median concentrations of plasma IL-1β, IL-15, and TNF-α were 3.14pg/ml, 3.14pg/ml, and 6.85pg/ml, respectively, in patients with oral cancer, compared with median plasma IL-1β, IL-15, and TNF-α concentration of 2.64pg/ml, 5.86pg/ml, and 5.38pg/ml, respectively, in patients with betel nut-chewing habit. In contrast, the median concentrations of plasma IL-1β, IL-15, and TNF-α in mid-aged males (aged 30-50) were 7.00pg/ml, 10.64pg/ml, and 31.73pg/ml, respectively, compared with median plasma concentration of IL-1β, IL-15, and TNF-α of 4.48pg/ml, 33.36pg/ml, and 97.77pg/ml in young males (aged 20-22), respectively. Also, significantly elevated plasma cortisol concentration was noted in betel nut-chewing (median 727.2ng/ml) and oral cancer patients (561.9ng/ml) compared to the mid-aged (176.8ng/ml) and young males (173.4ng/ml), respectively. In addition, lower plasma testosterone concentrations were found in betel nut-chewing subjects compared with young males (2.6±3.3ng/ml vs 6.2±2.9ng/ml). To summarize, the inflammatory cytokines and steroid hormones may reflect the degree of inflammation in betel nut-chewing males and the oral cancer subjects. The above findings suggest that betel nut-chewing or oral cancer inhibits plasma cytokines and regulates steroid hormones concentrations compared to mid-aged or young normal subjects. It is also indicated that betel nut-chewing causes decreased inflammatory cytokines as the same levels as in oral cancer subjects. Copyright © 2016 Elsevier Inc. All rights reserved.

Marine n-3 polyunsaturated fatty acids in patients with end-stage renal failure and in subjects without kidney disease: a comparative study.

PubMed

Madsen, Trine; Christensen, Jeppe H; Svensson, My; Witt, Petra M; Toft, Egon; Schmidt, Erik B

2011-03-01

Patients with end-stage renal disease treated with chronic hemodialysis (HD) are reported to have low levels of marine n-3 polyunsaturated fatty acids (PUFA) in plasma and cell membranes compared with healthy subjects. The aim of this study was to investigate whether n-3 PUFA levels in plasma and cells are lower in HD patients as compared with subjects without kidney disease. A comparative study was carried out. This study was carried out at the Departments of Nephrology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Denmark. This study consisted of 2 study populations comprising HD patients and 5 study populations comprising subjects without kidney disease. The fatty acid distribution in plasma phospholipids and platelet phospholipids was measured using gas chromatography. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) levels in plasma or serum phospholipids and platelet phospholipids in HD patients were compared with n-3 PUFA levels in subjects without kidney disease. EPA and DHA were lower and AA/EPA was higher in plasma/serum phospholipids in HD patients than in subjects without kidney disease. Similarly, higher AA and AA/EPA and lower EPA and DHA levels were found in platelet phospholipids of HD patients. Adjustment for gender, age, and habitual intake of fish and fish oil supplements did not change these results. HD patients have lower n-3 PUFA levels in plasma and cells compared with subjects without kidney disease. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Early and advanced glycosylation end products. Kinetics of formation and clearance in peritoneal dialysis.

PubMed Central

Friedlander, M A; Wu, Y C; Elgawish, A; Monnier, V M

1996-01-01

The chronic contact of glucose-containing dialysate and proteins results in the deposition of advanced glycation end products (AGEs) on peritoneal tissues in patients treated by peritoneal dialysis (PD), yet plasma levels of the AGE pentosidine are significantly lower in PD than in hemodialysis (HD). We measured glycation of peritoneal proteins in patients on PD over the time course of intraperitoneal equilibration of fresh peritoneal dialysate. The glycated content of peritoneal proteins (furosine method) was initially identical to plasma but increased 200% within 4 h due to in situ glycation as also demonstrated in vitro. In contrast, peritoneal proteins contained a 2-4 x greater content of the AGE pentosidine at all equilibrium time points. Plasma protein furosine content was identical in patients on PD and on HD. Fractionation by gel filtration of serum from patients on PD and HD revealed that > 95% of the pentosidine was linked to proteins > 10,000 mol wt; < 1% to proteins < 10,000 mol wt; and < 1%, free. Neither HD nor PD affected protein-bound pentosidine. The HD treatment decreased free and < 10,000 mol wt bound pentosidine. However clearance of protein-associated pentosidine by the peritoneal membrane may explain lower steady state levels in patients treated by PD. PMID:8609229

Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging.

PubMed

Tuljapurkar, Sonal R; McGuire, Timothy R; Brusnahan, Susan K; Jackson, John D; Garvin, Kevin L; Kessinger, Margaret A; Lane, Judy T; O' Kane, Barbara J; Sharp, John G

2011-11-01

Hematological deficiencies increase with aging, including anemias, reduced responses to hematopoietic stress and myelodysplasias. This investigation tested the hypothesis that increased bone marrow (BM) fat content in humans with age was associated with decreased numbers of side population (SP) hematopoietic stem cells, and this decrease correlated with changes in cytokine levels. BM was obtained from the femoral head and trochanteric region of the femur removed at surgery for total hip replacement (N = 100 subjects). In addition, BM from cadavers (N = 36), with no evidence of hip disease, was evaluated for fat content. Whole trabecular marrow samples were ground in a sterile mortar and pestle, and cellularity and lipid content determined. Marrow cells were stained with Hoechst dye and SP profiles were acquired. Plasma levels of insulin-like growth factor (IGF)-1, stromal-derived factor (SDF)-1 and interleukin (IL)-6 were measured using ELISA. Fat content in the BM of human subjects and cadavers increased with age. The numbers of SP stem cells in BM as well as plasma IGF-1 and SDF-1 levels decreased in correlation with increased BM fat. IL-6 had no relationship to changes in marrow fat. These data suggest that increased BM fat may be associated with a decreased number of SP stem cells and IGF-1 and SDF-1 levels with aging. These data further raise a more general question as to the role of adipose cells in the regulation of tissue stem cells. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

PubMed

Lamon-Fava, S; Fisher, E C; Nelson, M E; Evans, W J; Millar, J S; Ordovas, J M; Schaefer, E J

1989-01-01

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

Inverse association of plasma vanadium levels with newly diagnosed type 2 diabetes in a Chinese population.

PubMed

Wang, Xia; Sun, Taoping; Liu, Jun; Shan, Zhilei; Jin, Yilin; Chen, Sijing; Bao, Wei; Hu, Frank B; Liu, Liegang

2014-08-15

Vanadium compounds have been proposed to have beneficial effects on the pathogenesis and complications of type 2 diabetes. Our objective was to evaluate the association between plasma vanadium levels and type 2 diabetes. We performed a case-control study involving 1,598 Chinese subjects with or without newly diagnosed type 2 diabetes (December 2004-December 2007). Cases and controls were frequency-matched by age and sex. Plasma vanadium concentrations were measured and compared between groups. Analyses showed that plasma vanadium concentrations were significantly lower in cases with newly diagnosed type 2 diabetes than in controls (P = 0.001). Mean plasma vanadium levels in participants with and without diabetes were 1.0 μg/L and 1.2 μg/L, respectively. Participants in the highest quartile of plasma vanadium concentration had a notably lower risk of newly diagnosed type 2 diabetes (odds ratio = 0.26, 95% confidence interval: 0.19, 0.35; P < 0.001), compared with persons in the lowest quartile. The trend remained significant after adjustment for known risk factors and in further stratification analyses. Our results suggested that plasma vanadium concentrations were inversely associated with newly diagnosed type 2 diabetes in this Chinese population. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Plasma visfatin, associated with a genetic polymorphism -1535C>T, is correlated with C-reactive protein in Chinese Han patients with traumatic brain injury.

PubMed

Weng, Jian-Feng; Chen, Jun; Hong, Wei-Cong; Luo, Li-Feng; Yu, Wei; Luo, Shi-Da

2013-02-01

Visfatin is a newly identified pro-inflammatory adipokine and a genetic polymorphism -1535 C>T located in the visfatin gene promoter has been suggested to be associated with the regulation of visfatin expression in some inflammatory illness. However, there were some conflicting results regarding whether this variant is functional or not. This study aimed to examine the relations of the -1535 C>T single nucleotide polymorphism (SNP) of visfatin gene to the plasma visfatin and C-reactive protein concentrations in traumatic brain injury (TBI). 318 Chinese Han patients with TBI were recruited in this study. Plasma visfatin and C-reactive protein levels were significantly different between the genotypes in the SNP-1535 C>T even after adjustment for age, sex and body mass index. The genotype C-C had the highest plasma visfatin and C-reactive protein concentrations. The plasma visfatin and C-reactive protein concentrations between the variant genotypes C-T and T-T did not differ significantly. Plasma visfatin level was significantly associated with plasma C-reactive protein level using multivariate linear regression. Thus, the SNP-1535 C>T of visfatin gene seemed to be potentially involved in the inflammatory component of TBI through a decreased production of visfatin. Copyright © 2012 Elsevier Inc. All rights reserved.

Plasma adiponectin concentrations are associated with dietary glycemic index in Malaysian patients with type 2 diabetes.

PubMed

Loh, Beng-In; Sathyasuryan, Daniel Robert; Mohamed, Hamid Jan Jan

2013-01-01

Adiponectin, an adipocyte-derived hormone has been implicated in the control of blood glucose and chronic inflammation in type 2 diabetes. However, limited studies have evaluated dietary factors on plasma adiponectin levels, especially among type 2 diabetic patients in Malaysia. The aim of this study was to investigate the influence of dietary glycemic index on plasma adiponectin concentrations in patients with type 2 diabetes. A cross-sectional study was conducted in 305 type 2 diabetic patients aged 19-75 years from the Penang General Hospital, Malaysia. Socio-demographic information was collected using a standard questionnaire while dietary details were determined by using a pre-validated semi-quantitative food frequency questionnaire. Anthropometry measurement included weight, height, BMI and waist circumference. Plasma adiponectin concentrations were measured using a commercial ELISA kit. Data were analyzed using multiple linear regression. After multivariate adjustment, dietary glycemic index was inversely associated with plasma adiponectin concentrations (β =-0.272, 95% CI -0.262, - 0.094; p<0.001). It was found that in individuals who consumed 1 unit of foods containing high dietary glycemic index that plasma adiponectin level reduced by 0.3 μg/mL. Thirty two percent (31.9%) of the variation in adiponectin concentrations was explained by age, sex, race, smoking status, BMI, waist circumference, HDL-C, triglycerides, magnesium, fiber and dietary glycemic index according to the multiple linear regression model (R2=0.319). These results support the hypothesis that dietary glycemic index influences plasma adiponectin concentrations in patients with type 2 diabetes. Controlled clinical trials are required to confirm our findings and to elucidate the underlying mechanism.

Intra-individual variation of plasma trimethylamine-N-oxide (TMAO), betaine and choline over 1 year.

PubMed

Kühn, Tilman; Rohrmann, Sabine; Sookthai, Disorn; Johnson, Theron; Katzke, Verena; Kaaks, Rudolf; von Eckardstein, Arnold; Müller, Daniel

2017-02-01

Circulating trimethylamine-N-oxide (TMAO) has been implicated in the development of cardiovascular and chronic kidney diseases (CKD). However, while higher TMAO levels have been associated with increased risks of cardiovascular or renal events in first prospective studies, it remained unclear how much plasma TMAO concentrations vary over time. We measured fasting plasma levels of TMAO and two of its precursors, betaine and choline by LC-MS, in two samples of 100 participants of the European Investigation into Cancer and Nutrition (EPIC)-Heidelberg study (age range: 47-80 years, 50% female) that were collected 1 year apart, and assessed their intra-individual variation by Spearman's correlation coefficients (ρ). Correlations of metabolite concentrations over 1 year were at ρ=0.29 (p=0.003) for TMAO, ρ=0.81 (p<0.001) for betaine, and ρ=0.61 (p<0.001) for choline. Plasma levels of TMAO were not significantly associated with food intake, lifestyle factors, or routine biochemistry parameters such as C-reactive protein (CRP), low-density lipoprotein (LDL)-cholesterol, or creatinine. In contrast to fasting plasma concentrations of betaine and choline, concentrations of TMAO were more strongly affected by intra-individual variation over 1 year in adults from the general population. The modest correlation of TMAO levels over time should be considered when interpreting associations between TMAO levels and disease endpoints.

Nonlinear associations between plasma cholesterol levels and neuropsychological function.

PubMed

Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

2016-11-01

Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier. A significant quadratic effect of Total Cholesterol² × Age was identified for Logical Memory II ( b = -.0013, p = .039), such that the 70+ group performed best at high and low levels of total cholesterol than at midrange total cholesterol (U-shaped) and the <70 group performed worse at high and low levels of total cholesterol than at midrange total cholesterol (inverted U shape). Similarly, significant U- and J-shaped effects of LDL Cholesterol² × Age were identified for Visual Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage/dysfunction and activation in pregnancy induced hypertension.

PubMed

Nadar, Sunil K; Al Yemeni, Eman; Blann, Andrew D; Lip, Gregory Y H

2004-01-01

Endothelial disturbance (whether activation, dysfunction or damage) is a likely pathogenic mechanism in pre-eclampsia and pregnancy-induced hypertension (PIH). We set out to determine which of three plasma markers of endothelial disturbance, indicating endothelial activation (E-selectin) or damage/dysfunction (von Willebrand factor (vWf), soluble thrombomodulin), would provide the best discriminator of PIH compared to normotensive pregnancy. Cross-sectional study of 36 consecutive women with PIH (age 31+/-6 years) and 36 consecutive women with normotensive pregnancies (age 29+/-5 years) of similar parity. Plasma levels of vWf, E-selectin and thrombomodulin were measured using ELISA. As expected, women with PIH had significantly higher levels of plasma vWf (by 19%, p=0.003), E-selectin (by 40%, p<0.001) and thrombomodulin (by 61%, p=0.01) than normotensive women. However, on stepwise multiple regression analysis, only thrombomodulin was an independent significant predictor of the presence of PIH (p=0.023). We conclude that although vWf, E-selectin and thrombomodulin are all raised in PIH, only thrombomodulin was independently associated with PIH. This molecule could potentially be useful in monitoring and in providing clues in aetiology and pathophysiology, and may have implications for the clinical complications associated with PIH.

Reduced levels of S-nitrosothiols in plasma of patients with systemic sclerosis and Raynaud's phenomenon.

PubMed

Kundu, Devi; Abraham, David; Black, Carol M; Denton, Christopher P; Bruckdorfer, K Richard

2014-12-01

S-Nitrosothiols (RSNOs) are bioactive forms of nitric oxide which are involved in cell signalling and redox regulation of vascular function. Circulating S-nitrosothiols are predominantly in the form of S-nitrosoalbumin. In this study plasma concentrations of S-nitrosothiols were measured in patients with systemic sclerosis (SSc) where NO metabolism is known to be abnormal. Venous blood was collected from 16 patients with Raynaud's phenomenon (RP), 45 with systemic sclerosis (SSc) (34 patients had limited SSc (IcSSc) and 11 diffuse cutaneous disease (dcSSc)). Twenty six healthy subjects were used as controls. Plasma S-nitrosothiol concentrations were measured by chemiluminescence. The measurements were related to the extent of biological age, capillary/skin scores and disease duration. Plasma RSNO levels in patients with Raynaud's phenomenon (RP) and in those with SSc was significantly lower compared to the concentrations in control subjects. In SSc, plasma S-nitrosothiols were often below the level of detection (1nM). Low S-nitrosothiol concentrations were observed in the blood of patients with SSc and patients with RP indicating a profound disturbance of nitric oxide metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Endothelin-1 and big endothelin-1 in NIDDM patients with and without microangiopathy.

PubMed

Kamoi, K; Ishibashi, M; Yamaji, T

1994-07-01

To examine a possible role for endothelin-1 in the pathophysiology of diabetic microangiopathy, we measured plasma levels of endothelin-1 and big endothelin-1, a precursor peptide of endothelin-1, in 33 untreated patients with non-insulin-dependent diabetes mellitus. There was no significant difference among the mean plasma endothelin-1 concentrations in 18 patients with microangiopathy, in 15 patients without microangiopathy and in 33 age-matched normal subjects. In contrast, the mean plasma big endothelin-1 concentration in patients with microangiopathy was significantly higher than in those without microangiopathy or in normal subjects. As a consequence, the mean big endothelin-1 to endothelin-1 ratio in patients with microangiopathy was significantly higher than in the other two groups. There was no significant correlation between plasma levels of endothelin-1 or big endothelin-1 and fasting blood glucose, HbA1c, mean blood pressure, or period of duration of diabetes mellitus in the patient groups. The results indicate that elevation of plasma big endothelin-1 levels with diminished conversion of big endothelin-1 to endothelin-1 is associated with diabetic microangiopathy, which may be the effect rather than the cause of endothelial dysfunction.

The Differences in Homocysteine Level between Obstructive Sleep Apnea Patients and Controls: A Meta-Analysis

PubMed Central

Dong, Jiaqi; Zhang, Rui; Lu, Meixia; Kong, Weijia

2014-01-01

Background Studies have reported inconsistent findings regarding the relationship between obstructive sleep apnea (OSA) and homocysteine (HCY) level. This study aimed to assess the difference in plasma HCY level between OSA patients and controls by conducting a meta-analysis of published studies. Methods Database of PubMed, SCI, and China National Knowledge Internet (CNKI) were comprehensively searched. Eligible studies regarding plasma HCY level in OSA patients were identified by two independent reviewers. RevMan (version 5.2) and STATA (version 12.0) were employed for data synthesis. Results A total of 10 studies involving 432 subjects were included. Meta-analysis showed that plasma HCY levels in OSA group were 3.11 µmol/l higher than that in control group (95% confidence interval: 2.08 to 4.15, P<0.01). Subgroup analysis revealed a more significant differences between OSA patients and controls when average body mass index ≥30 (the total weighted mean difference (WMD) was 3.64), average age<50 (the total WMD was 3.96) and average apnea hypopnea index ≥35 (the total WMD was 4.54). Conclusions In this meta-analysis, plasma HCY levels were found to be higher in OSA patients compared to control subjects. PMID:24769854

Dyslipidemia and reference values for fasting plasma lipid concentrations in Danish/North-European White children and adolescents.

PubMed

Nielsen, Tenna Ruest Haarmark; Lausten-Thomsen, Ulrik; Fonvig, Cilius Esmann; Bøjsøe, Christine; Pedersen, Lise; Bratholm, Palle Skov; Hansen, Torben; Pedersen, Oluf; Holm, Jens-Christian

2017-04-28

Dyslipidemia is reported in 27 - 43% of children and adolescents with overweight/obesity and tracks into adulthood, increasing the risk of cardiovascular morbidity. Cut-off values for fasting plasma lipid concentrations are typically set at fixed levels throughout childhood. The objective of this cross-sectional study was to generate fasting plasma lipid references for a Danish/North-European White population-based cohort of children and adolescents, and investigate the prevalence of dyslipidemia in this cohort as well as in a cohort with overweight/obesity. A population-based cohort of 2141 (1275 girls) children and adolescents aged 6 - 19 (median 11.5) years was recruited from 11 municipalities in Denmark. Additionally, a cohort of children and adolescents of 1421 (774 girls) with overweight/obesity aged 6 - 19 years (median 11.8) was recruited for the study. Height, weight, and fasting plasma lipid concentrations were measured on all participants. Smoothed reference curves and percentiles were generated using the Generalized Additive Models for Location Scale and Shape package in the statistical software R. In the population-based cohort, plasma concentrations of total cholesterol (TC) (P < 0.05), low-density lipoprotein cholesterol (LDL) (P < 0.005), and high-density lipoprotein cholesterol (HDL) (P < 0.005) were higher in the youngest compared to the oldest tertile. Fasting plasma levels of triglycerides (TG) (P < 0.005) increased with age in both sexes. In boys, non-HDL was lower in the oldest compared to the youngest tertile (P < 0.0005). Concentrations of TC, LDL, non-HDL, and TG were higher (P < 0.05), and HDL lower (P < 0.05) in the cohort with overweight/obesity in both sexes and for all ages except for TC in the youngest girls. The overall prevalence of dyslipidemia was 6.4% in the population-based cohort and 28.0% in the cohort with overweight/obesity. The odds ratio for exhibiting dyslipidemia in the cohort with overweight/obesity compared with the population-based cohort was 6.2 (95% CI: 4.9 - 8.1, P < 2*10 -16 ). Fasting plasma lipid concentrations change during childhood and adolescence and differ with sex and age. Children and adolescents with obesity have increased concentrations of circulating lipids and exhibit an increased prevalence of dyslipidemia. The study is part of The Danish Childhood Obesity Biobank; ClinicalTrials.gov ID-no.: NCT00928473 retrospectively registered on June 25th 2009.

Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants

PubMed Central

Mupfudze, Tatenda G.; Stoltzfus, Rebecca J.; Rukobo, Sandra; Moulton, Lawrence H.; Humphrey, Jean H.; Prendergast, Andrew J.

2015-01-01

Objective Anemia in infancy is a global public health problem. We evaluated the relative contributions of iron deficiency and inflammation to infant anemia. Methods We measured plasma hepcidin, ferritin, soluble transferrin receptor (sTfR), alpha-1-acid glycoprotein and C-reactive protein (CRP) by ELISA on archived plasma from 289 HIV-unexposed anemic or non-anemic Zimbabwean infants at ages 3mo, 6mo and 12mo. Among anemic infants, we determined the proportion with iron-deficiency anemia (IDA) and anemia of inflammation (AI). We undertook regression analyses of plasma hepcidin and anemia status, adjusting for sex, age and birthweight. Results Anemic infants at 3mo were more stunted and had higher CRP (median 0.45 vs 0.21mg/L; P = 0.037) and hepcidin (median 14.7 vs 9.7ng/mL; P = 0.022) than non-anemic infants, but similar levels of ferritin and sTfR; 11% infants had IDA and 15% had AI. Anemic infants at 6mo had higher hepcidin (median 7.9 vs 4.5ng/mL; P = 0.016) and CRP (median 2.33 vs 0.32mg/L; P<0.001), but lower ferritin (median 13.2 vs 25.1μg/L; P<0.001) than non-anemic infants; 56% infants had IDA and 12% had AI. Anemic infants at 12mo had lower ferritin (median 3.2 vs 22.2μg/L; P<0.001) and hepcidin (median 0.9 vs 1.9ng/mL; P = 0.019), but similar CRP levels; 48% infants had IDA and 8% had AI. Comparing anemic with non-anemic infants, plasma hepcidin was 568% higher, 405% higher and 64% lower at 3mo, 6mo and 12mo, respectively, after adjusting for sex and birthweight (all p<0.01). Plasma hepcidin declined significantly with age among anemic but not non-anemic infants. Girls had 61% higher hepcidin than boys, after adjusting for age, anemia and birthweight (p<0.001). Conclusion Anemia is driven partly by inflammation early in infancy, and by iron deficiency later in infancy, with plasma hepcidin concentrations reflecting the relative contribution of each. However, there is need to better characterize the drivers of hepcidin during infancy in developing countries. PMID:26252205

Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants.

PubMed

Mupfudze, Tatenda G; Stoltzfus, Rebecca J; Rukobo, Sandra; Moulton, Lawrence H; Humphrey, Jean H; Prendergast, Andrew J; Jones, Andrew D; Manges, Amee; Mangwadu, Goldberg; Maluccio, John A; Mbuya, Mduduzi N N; Ntozini, Robert; Tielsch, James M

2015-01-01

Anemia in infancy is a global public health problem. We evaluated the relative contributions of iron deficiency and inflammation to infant anemia. We measured plasma hepcidin, ferritin, soluble transferrin receptor (sTfR), alpha-1-acid glycoprotein and C-reactive protein (CRP) by ELISA on archived plasma from 289 HIV-unexposed anemic or non-anemic Zimbabwean infants at ages 3 mo, 6 mo and 12 mo. Among anemic infants, we determined the proportion with iron-deficiency anemia (IDA) and anemia of inflammation (AI). We undertook regression analyses of plasma hepcidin and anemia status, adjusting for sex, age and birthweight. Anemic infants at 3 mo were more stunted and had higher CRP (median 0.45 vs 0.21 mg/L; P = 0.037) and hepcidin (median 14.7 vs 9.7 ng/mL; P = 0.022) than non-anemic infants, but similar levels of ferritin and sTfR; 11% infants had IDA and 15% had AI. Anemic infants at 6 mo had higher hepcidin (median 7.9 vs 4.5 ng/mL; P = 0.016) and CRP (median 2.33 vs 0.32 mg/L; P<0.001), but lower ferritin (median 13.2 vs 25.1 μg/L; P<0.001) than non-anemic infants; 56% infants had IDA and 12% had AI. Anemic infants at 12 mo had lower ferritin (median 3.2 vs 22.2 μg/L; P<0.001) and hepcidin (median 0.9 vs 1.9 ng/mL; P = 0.019), but similar CRP levels; 48% infants had IDA and 8% had AI. Comparing anemic with non-anemic infants, plasma hepcidin was 568% higher, 405% higher and 64% lower at 3 mo, 6 mo and 12 mo, respectively, after adjusting for sex and birthweight (all p<0.01). Plasma hepcidin declined significantly with age among anemic but not non-anemic infants. Girls had 61% higher hepcidin than boys, after adjusting for age, anemia and birthweight (p<0.001). Anemia is driven partly by inflammation early in infancy, and by iron deficiency later in infancy, with plasma hepcidin concentrations reflecting the relative contribution of each. However, there is need to better characterize the drivers of hepcidin during infancy in developing countries.

Predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among reproductive-aged men.

PubMed

Wang, Yi-Xin; Liu, Chong; Chen, Ying-Jun; Chen, Heng-Gui; Yang, Pan; Wang, Peng; Huang, Li-Li; Ai, Song-Hua; Duan, Peng; Pan, An; Zeng, Qiang; Lu, Wen-Qing

2018-02-01

Certain phthalates are suspected to be endocrine disruptors that are adversely associated with male reproductive health. However, the predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among reproductive-aged men have not been thoroughly studied. To investigate the predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among adult Chinese males. We measured mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-octyl phthalate (MOP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) concentrations in seminal plasma and repeated spot-urine samples from 687 men who visited a reproductive center. Mixed-effect models were used to examine the associations of sociodemographic, lifestyle and medical factors with urinary metabolite concentrations. Linear regression models were used to identify predictors of metabolite concentrations in seminal plasma and correlations between metabolite concentrations in spot urine samples and seminal plasma. Measurements taken from spot urine samples poorly predicted same-day seminal plasma concentrations (all R 2 <0.10). Inverse associations were observed between education level and urinary MBP and MEOHP and between household income and urinary MMP; receiving intravenous infusion therapy was associated with increased urinary MBP, MEHHP and MEOHP, use of facial cleanser/cream was associated with increased MEP, and smoking was associated with increased MEHP. The predictors of metabolite concentrations in seminal plasma differed from those in urine, except for the association of intravenous infusion therapy with MBP. BMI was associated with increased seminal plasma MBP, MEHP and MEOHP, smoking was associated with increased MEP, and contact with plastics was associated with increased MEOHP. Phthalate metabolite concentrations in adult men varied in accordance with sociodemographic variables, lifestyle factors and intravenous therapy. Measures of metabolite levels in urine may not directly reflect the exposure status of the male reproductive system. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiorespiratory fitness modifies the association between dietary fat intake and plasma fatty acids.

PubMed

König, D; Väisänen, S B; Bouchard, C; Halle, M; Lakka, T A; Baumstark, M W; Alen, M; Berg, A; Rauramaa, R

2003-07-01

To investigate the relation between (1) cardiorespiratory fitness and plasma saturated, monounsaturated and polyunsaturated fatty acids and (2) the interactions between cardiorespiratory fitness, dietary fat intake and plasma fatty acid composition. Cross-sectional analysis. The subjects were randomly selected, 127 middle-aged Finnish men participating in the DNASCO exercise intervention study. Cardiorespiratory fitness was determined spiroergometrically, dietary intake of macro- and micronutrients by 4-day food records and plasma fatty acids by gas chromatography. The subjects were divided into tertiles of aerobic fitness. Differences between fitness tertiles were not observed for dietary intake of total fat, and saturated, monounsaturated or polyunsaturated fatty acids (percent of total energy). In contrast, plasma saturated fatty acids were significantly lower (P <0.01) and polyunsaturated fatty acids significantly higher (P <0.05) in the highest fitness tertile compared to the lowest tertile. Dietary saturated fat intake was positively associated with plasma saturated fatty acids (r=0.342; P <0.05) and inversely with plasma polyunsaturated fatty acids (r=-0.453; P <0.01) only in the lowest fitness tertile. In addition, a positive correlation between body mass index and plasma saturated fatty acids (r=0.516; P <0.01) as well as a negative correlation between body mass index and plasma polyunsaturated fatty acids (r=-0.516; P <0.01) was observed in the lowest tertile solely. Different levels in cardiorespiratory fitness are associated with different levels in plasma saturated and polyunsaturated fatty acids and lead to modifications in the association between dietary and plasma fatty acids. These findings can perhaps be explained by a reduced hepatic fatty acid and lipoprotein synthesis as well as by an enhanced muscular lipid utilization, which are commonly seen in those who are physically active and who exhibit a higher level of fitness.

The dynamics of post-operative plasma ACTH values following transsphenoidal surgery for Cushing's disease.

PubMed

Srinivasan, Lakshmi; Laws, Edward R; Dodd, Robert L; Monita, Monique M; Tannenbaum, Christyn E; Kirkeby, Kjersti M; Chu, Olivia S; Harsh, Griffith R; Katznelson, Laurence

2011-12-01

Rapid assessment of adrenal function is critical following transsphenoidal surgery (TSS) for Cushing's disease (CD) in order to determine surgical efficacy. We hypothesize that there may be a role for ACTH measurement as a rapid indicator of adrenal function. Following surgery for CD, glucocorticoids were withheld and paired plasma ACTH and serum cortisol levels were measured every 6 h. Post-operative hypocortisolemia was defined as serum cortisol <2 mcg/dl or a serum cortisol <5 mcg/dl with the onset of symptoms of adrenal insufficiency within 72 h. We studied 12 subjects, all female, mean age 44.6 years (range 25-55), including 13 surgeries: nine subjects attained hypocortisolemia. Plasma ACTH levels decreased more in subjects with hypocortisolemia (0.9 pg/ml/hr, P = 0.0028) versus those with persistent disease (0 0.2 pg/ml/hr, P = 0.26) within the first 48 h after surgery. In contrast to subjects with persistent disease, all subjects with hypocortisolemia achieved a plasma ACTH <20 pg/ml by 19 h (range 1-19 h). Four of the nine subjects with hypocortisolemia achieved plasma ACTH <20 pg/ml by 13 h and the remaining five subjects by 19 h. Hypocortisolemia occurred between 3-36 h following achievement of a plasma ACTH <20 pg/ml. In CD, a reduction in postoperative plasma ACTH levels differentiates subjects with surgical remission versus subjects with persistent disease. The utility of plasma ACTH measurements in the postoperative management of CD remains to be determined.

Relationship between microRNA-146a expression and plasma renalase levels in hemodialyzed patients

PubMed Central

Koch, Wojciech; Kukula-Koch, Wirginia; Gaweł, Kinga; Bednarek-Skublewska, Anna; Małecka-Massalska, Teresa; Milanowski, Janusz; Petkowicz, Beata; Solski, Janusz

2017-01-01

Background microRNA (miRNA) belongs to the non-coding RNAs family responsible for the regulation of gene expression. Renalase is a protein composed of 342 amino acids, secreted by the kidneys and possibly plays an important role in the regulation of sympathetic tone and blood pressure. The aim of the present study was to investigate plasma renalase concentration, and explore the relationship between miRNA-146a-5p expression and plasma renalase levels in hemodialyzed patients. Methods The study population comprised 55 subjects who succumbed to various cardiac events, 27 women and 28 men, aged 65–70 years. The total RNA including miRNA fraction was isolated using QiagenmiRNEasy Serum/Plasma kit according to the manufacturer’s protocol. The isolated miRNAs were analyzed using a quantitative polymerase chain reaction (qRT-PCR) technique. The plasma renalase levels were measured using a commercial ELISA kit. Results In the group of patients with high levels of renalase, higher miRNA-146a expression was found, compared with those with low concentration of renalase. Patients with simultaneous low miRNA-146a expression and high level of renalase were confirmed to deliver a significantly longer survival time compared with other patients. Conclusions miRNA-146a and plasma renalase levels were estimated as independent prognostic factors of hemodialyzed patients’ survival time. Patients with low miRNA-146a expression demonstrated a significantly longer survival time in contrast to the patients with a high expression level of miRNA-146a. Moreover, a significantly longer survival time was found in patients with high renalase activity compared with patients with low activity of the enzyme. PMID:28614373

Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.

PubMed

Tiwari, Priya; Thomas, M K; Pathania, Subha; Dhawan, Deepa; Gupta, Y K; Vishnubhatla, Sreenivas; Bakhshi, Sameer

2015-01-01

Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.

Posaconazole plasma concentrations in pediatric patients receiving antifungal prophylaxis during neutropenia.

PubMed

Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Klinker, Hartwig; Eikemeier, Melinda; Feucht, Judith; Blaeschke, Franziska; Schwarze, Carl-Philipp; Ebinger, Martin; Feuchtinger, Tobias; Handgretinger, Rupert; Heinz, Werner J

2017-06-01

Invasive fungal infections are one of the major complications in pediatric patients during prolonged neutropenia after chemotherapy. Evaluation of the efficacy and safety of the triazole posaconazole in these patients is missing. This multicenter survey analyzed trough concentrations of 33 pediatric patients with a median age of 8 years during 108 neutropenic episodes who received prophylactic posaconazole oral suspension. A total of 172 posaconazole trough levels were determined to median 438 ng/ml (range 111-2011 ng/ml; mean 468 ± 244 ng/ml). Age and gender had no influence on posaconazole plasma levels. Posaconazole was not discontinued due to adverse events in any of the patients. Only hepatic parameters significantly increased beyond the upper normal limit to median values of ALT of 87 U/l (P < .0001), and AST of 67 U/l (P < .0001). One patient with a median posaconazole trough concentration of 306 ng/ml experienced an invasive fungal infection. In conclusion, posaconazole was effective, safe and feasible in 33 pediatric patients with neutropenia ≥5 days after chemotherapy. Median posaconazole plasma concentrations were approximately 1.6-fold lower than the recommended plasma level of 700 ng/ml. Larger patient cohorts are needed to evaluate these findings. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmacokinetics and bactericidal activity of cefuroxime axetil.

PubMed Central

Ginsburg, C M; McCracken, G H; Petruska, M; Olson, K

1985-01-01

The pharmacokinetics of cefuroxime axetil were studied in 10 adult volunteers aged 24 to 31 years (mean age, 27), 22 infants and children aged 11 to 68 months (mean age, 33 months), and 11 children aged 7 years, 7 months to 12 years, 3 months (mean age, 11 years, 1 month). Mean peak plasma concentrations of cefuroxime occurred between 90 and 120 min in all study patients and were independent of the fasting or feeding status. The areas under the concentration-time curves were significantly higher in adult volunteers who received cefuroxime axetil with milk than in those who received the drug while fasting or with applesauce. The bioavailability of cefuroxime axetil was significantly enhanced in children by the concomitant ingestion of cefuroxime axetil and infant formula or whole milk. The areas under the concentration-time curves were 25 to 88% higher when cefuroxime axetil and milk were administered simultaneously than when the same dose was given to all fasting patients. The plasma bactericidal activities of cefuroxime against beta-lactamase-positive and -negative strains of Haemophilus influenzae and Staphylococcus aureus at the time of peak plasma concentrations were independent of feeding status and were similar in adults and in children. Against these strains, 52% of the children and 38% of the adults had peak bactericidal levels of 1:8 or greater. PMID:3878129

Risk factors for Type 2 Diabetes Mellitus in college students: association with sociodemographic variables1

PubMed Central

Lima, Adman Câmara Soares; Araújo, Márcio Flávio Moura; de Freitas, Roberto Wagner Júnior Freire; Zanetti, Maria Lúcia; de Almeida, Paulo César; Damasceno, Marta Maria Coelho

2014-01-01

Objective identify the modifiable risk factors for type 2 diabetes mellitus in college students and associate these factors with their sociodemographic variables. Method cross-sectional study, involving 702 college students from Fortaleza-CE, Brazil. Sociodemographic, anthropometric, physical exercise data and blood pressure and fasting plasma glucose levels were collected. Results the most prevalent risk factor was sedentariness, followed by overweight, central obesity, high fasting plasma glucose and arterial hypertension. A statistically significant association was found between overweight and sex (p=0.000), age (p=0.004) and marital status (p=0.012), as well as between central obesity and age (p=0.018) and marital status (p=0.007) and between high fasting plasma glucose and sex (p=0.033). Conclusion distinct risk factors were present in the study population, particularly sedentariness and overweight. PMID:25029061

The M16 mouse: an outbred animal model of early onset polygenic obesity and diabesity.

PubMed

Allan, Mark F; Eisen, Eugene J; Pomp, Daniel

2004-09-01

To characterize the phenotypic consequences of long-term selective breeding for rapid weight gain, with an emphasis on obesity and obesity-induced diabetes (diabesity). M16 is the result of long-term selection for 3- to 6-week weight gain from an ICR base population. Experiment 1 characterized males from both lines for body weights (3, 6, and 8 weeks), feed (4 to 8 weeks) and H(2)O (6 to 8 weeks) consumption, and heat loss, body composition, and levels of several plasma proteins at 8 weeks of age. Experiment 2 characterized differences between lines for both sexes at three ages (6, 8, and 16 weeks) and fed two diets (high and normal fat). Body weight, composition, blood glucose, and plasma insulin and leptin levels were evaluated after an 8-hour fast. At all ages measured, M16 mice were heavier, fatter, hyperphagic, hyperinsulinemic, and hyperleptinemic relative to ICR. M16 males and females were hyperglycemic relative to ICR, with 56% and 22% higher fasted blood glucose levels at 8 weeks of age. M16 mice represent an outbred animal model to facilitate gene discovery and pathway regulation controlling early onset polygenic obesity and type 2 diabetic phenotypes. Phenotypes prevalent in the M16 model, with obesity and diabesity exhibited at a young age, closely mirror current trends in human populations.

A cross-sectional study measuring vanadium and chromium levels in paediatric patients with CKD

PubMed Central

Filler, Guido; Kobrzynski, Marta; Sidhu, Hargun Kaur; Belostotsky, Vladimir; Huang, Shih-Han S; McIntyre, Chris; Yang, Liju

2017-01-01

Objectives Although many secondary effects of high levels of vanadium (V) and chromium (Cr) overlap with symptoms seen in paediatric patients with chronic kidney disease (CKD), their plasma V and Cr levels are understudied. Design Ancillary cross-sectional study to a prospective, longitudinal, randomised controlled trial. Setting Children’s Hospital of Western Ontario, London Health Sciences Centre, London, Ontario, Canada. Participants 36 children and adolescents 4–18 years of age with CKD. Interventions 1–6 trace element measurements per patient. Cystatin C (CysC) estimated glomerular filtration rate (eGFR) was calculated using the Filler formula. Plasma V and Cr levels were measured using high-resolution sector field inductively coupled mass spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart programme. Water Cr and V data were obtained from the Ontario Water (Stream) Quality Monitoring Network. Primary and secondary outcome measures Primary outcomes: plasma Cr and V. Secondary outcomes: age, season, CysC, CysC eGFR, and Cr and V levels in environmental water. Results The median (IQR) eGFR was 51 mL/min/1.73 m2 (35, 75). The median V level was 0.12 µg/L (0.09, 0.18), which was significantly greater than the 97.5th percentile of the reference interval of 0.088 µg/L; 32 patients had at least one set of V levels above the published reference interval. The median Cr level was 0.43 µg/L (0.36, 0.54), which was also significantly greater than the established reference interval; 34 had at least one set of Cr levels above the published reference interval. V and Cr levels were moderately correlated. Only some patients had high environmental exposure. Conclusions Our study suggests that paediatric patients with CKD have elevated plasma levels of V and Cr. This may be the result of both environmental exposure and a low eGFR. It may be necessary to monitor V and Cr levels in patients with an eGFR <30 mL/min/1.73 m2. Trial registration number NCT02126293; HC#172241. PMID:28592575

Levels of persistent organic pollutants (POPs) in a coastal northern Norwegian population with high fish-liver intake.

PubMed

Sandanger, T M; Brustad, M; Sandau, C D; Lund, E

2006-05-01

Recent research has again raised the issue regarding the potential health effects of long term exposure to persistent organic pollutants (POPs) in the context of a risk-benefit analysis. There remains clear evidence of the beneficial effects of fish consumption on public health and in particular fatty fish with its essential fatty acids. In addition to providing fatty acids, fish fat constitutes an essential source to vitamin D for the northern Norwegian population. Norwegian Food Control Authorities have recommended that children and women of childbearing age should not consume fish liver due to the risk associated with high intake of POPs. The aim of this study was to assess the influence of fish liver intake on the levels of PCBs and chlorinated pesticides in a rural coastal community (n = 31) in northern Norway, applying a cross-sectional design. The geometric mean plasma levels of sum of PCBs (14 congeners) and p,p'-DDE was found to be 558 microg kg(-1) lipids and 179 microg kg(-1) lipids, respectively. These levels were not significantly affected by the reported intake of fish liver, when age and gender were considered. Age in particular, but also gender were significant predictors for most compounds. When merging the dataset with an urban population with considerable lower intake of fish liver, the intake of cod liver still did not significantly affect the levels of PCBs and p,p'-DDE when adjusted for age and gender. Age and gender remain the strongest predictors of plasma levels of POPs in this study whereas fish liver intake was not significantly associated with the POPs.

Plasma Carotenoids, Tocopherols, and Retinol in the Age-Stratified (35-74 Years) General Population: A Cross-Sectional Study in Six European Countries.

PubMed

Stuetz, Wolfgang; Weber, Daniela; Dollé, Martijn E T; Jansen, Eugène; Grubeck-Loebenstein, Beatrix; Fiegl, Simone; Toussaint, Olivier; Bernhardt, Juergen; Gonos, Efstathios S; Franceschi, Claudio; Sikora, Ewa; Moreno-Villanueva, María; Breusing, Nicolle; Grune, Tilman; Bürkle, Alexander

2016-09-30

Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/β-carotene and higher β-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene ( r = -0.248), α-tocopherol ( r = 0.208), α-carotene ( r = -0.112), and β-cryptoxanthin ( r = 0.125; all p < 0.001). Age was inversely associated with lycopene (-6.5% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m²)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7% vs. 2.4% per five-year age increase). The association of higher β-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (-4.8% vs. -3.8% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene.

Prognostic utility of plasma S100A12 levels to establish a novel scoring system for predicting mortality in maintenance hemodialysis patients: a two-year prospective observational study in Japan

PubMed Central

2013-01-01

Background S100A12 protein is an endogenous receptor ligand for advanced glycation end products. In this study, the plasma S100A12 level was assessed as an independent predictor of mortality, and its utility in clinical settings was examined. Methods In a previous cross-sectional study, plasma S100A12 levels were measured in 550 maintenance hemodialysis patients to determine the association between S100A12 and the prevalence of cardiovascular diseases (CVD). In this prospective study, the risk of mortality within a two-year period was determined. An integer scoring system was developed to predict mortality on the basis of the plasma S100A12 levels. Results Higher plasma S100A12 levels (≥18.79 ng/mL) were more closely associated with higher all-cause mortality than lower plasma S100A12 levels (<18.79 ng/mL; P = 0.001). Multivariate Cox proportional hazards analysis revealed higher plasma S100A12 levels [hazard ratio (HR), 2.267; 95% confidence interval (CI), 1.195–4.302; P = 0.012], age ≥65 years (HR, 1.961; 95%CI, 1.017–3.781; P = 0.044), serum albumin levels <3.5 g/dL (HR, 2.198; 95%CI, 1.218–3.968; P = 0.012), and history of CVD (HR, 2.068; 95%CI, 1.146–3.732; P = 0.016) to be independent predictors of two-year all-cause mortality. The integer score was derived by assigning points to these factors and determining total scores. The scoring system revealed trends across increasing scores for predicting the all-cause mortality [c-statistic = 0.730 (0.656–0.804)]. The resulting model demonstrated good discriminative power for distinguishing the validation population of 303 hemodialysis patients [c-statistic = 0.721 (0.627–0.815)]. Conclusion The results indicate that plasma S100A12 level is an independent predictor for two-year all-cause mortality. A simple integer scoring system was therefore established for predicting mortality on the basis of plasma S100A12 levels. PMID:23324110

Association between polymorphisms in phospholipase A2 genes and the plasma triglyceride response to an n-3 PUFA supplementation: a clinical trial.

PubMed

Tremblay, Bénédicte L; Cormier, Hubert; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2015-02-21

Fish oil-derived long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma triglyceride (TG) levels. Genetic factors such as single-nucleotide polymorphisms (SNPs) found in genes involved in metabolic pathways of n-3 PUFA could be responsible for well-recognized heterogeneity in plasma TG response to n-3 PUFA supplementation. Previous studies have shown that genes in the glycerophospholipid metabolism such as phospholipase A2 (PLA2) group II, IV, and VI, demonstrate changes in their expression levels in peripheral blood mononuclear cells (PBMCs) after n-3 PUFA supplementation. A total of 208 subjects consumed 3 g/day of n-3 PUFA for 6 weeks. Plasma lipids were measured before and after the supplementation period. Five SNPs in PLA2G2A, six in PLA2G2C, eight in PLA2G2D, six in PLA2G2F, 22 in PLA2G4A, five in PLA2G6, and nine in PLA2G7 were genotyped. The MIXED Procedure for repeated measures adjusted for age, sex, BMI, and energy intake was used in order to test whether the genotype, supplementation or interaction (genotype by supplementation) were associated with plasma TG levels. The n-3 PUFA supplementation had an independent effect on plasma TG levels. Genotype effects on plasma TG levels were observed for rs2301475 in PLA2G2C, rs818571 in PLA2G2F, and rs1569480 in PLA2G4A. Genotype x supplementation interaction effects on plasma TG levels were observed for rs1805018 in PLA2G7 as well as for rs10752979, rs10737277, rs7540602, and rs3820185 in PLA2G4A. These results suggest that, SNPs in PLA2 genes may influence plasma TG levels during a supplementation with n-3 PUFA. This trial was registered at clinicaltrials.gov as NCT01343342.

CXCL4 Plasma Levels Are Not Associated with the Extent of Coronary Artery Disease or with Coronary Plaque Morphology

PubMed Central

Erbel, Christian; Korosoglou, Grigorios; Ler, Pearlyn; Akhavanpoor, Mohammadreza; Domschke, Gabriele; Linden, Fabian; Doesch, Andreas O.; Buss, Sebastian J.; Giannitsis, Evangelos; Katus, Hugo A.; Gleissner, Christian A.

2015-01-01

Background CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling. Methods and Results CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD. Conclusions While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis. PMID:26524462

CXCL4 Plasma Levels Are Not Associated with the Extent of Coronary Artery Disease or with Coronary Plaque Morphology.

PubMed

Erbel, Christian; Korosoglou, Grigorios; Ler, Pearlyn; Akhavanpoor, Mohammadreza; Domschke, Gabriele; Linden, Fabian; Doesch, Andreas O; Buss, Sebastian J; Giannitsis, Evangelos; Katus, Hugo A; Gleissner, Christian A

2015-01-01

CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling. CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD. While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis.

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

PubMed

Choi, Woo Suk; Heo, Nam Ju; Paick, Jae-Seung; Son, Hwancheol

2016-04-01

To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 μg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume. © 2016 The Japanese Urological Association.

Regional Hippocampal Atrophy and Higher Levels of Plasma Amyloid-Beta Are Associated With Subjective Memory Complaints in Nondemented Elderly Subjects.

PubMed

Cantero, Jose L; Iglesias, Juan E; Van Leemput, Koen; Atienza, Mercedes

2016-09-01

Evidence suggests a link between the presence of subjective memory complaints (SMC) and lower volume of the hippocampus, one of the first regions to show neuropathological lesions in Alzheimer's disease. However, it remains unknown whether this pattern of hippocampal atrophy is regionally specific and whether SMC are also paralleled by changes in peripheral levels of amyloid-beta (Aβ). The volume of hippocampal subregions and plasma Aβ levels were cross-sectionally compared between elderly individuals with (SMC(+); N = 47) and without SMC (SMC(-); N = 48). Significant volume differences in hippocampal subregions were further correlated with plasma Aβ levels and with objective memory performance. Individuals with SMC exhibited significantly higher Aβ1-42 concentrations and lower volumes of CA1, CA4, dentate gyrus, and molecular layer compared with SMC(-) participants. Regression analyses further showed significant associations between lower volume of the dentate gyrus and both poorer memory performance and higher plasma Aβ1-42 levels in SMC(+) participants. The presence of SMC, lower volumes of specific hippocampal regions, and higher plasma Aβ1-42 levels could be conditions associated with aging vulnerability. If such associations are confirmed in longitudinal studies, the combination may be markers recommending clinical follow-up in nondemented older adults. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Substance P, mean apnoea duration and the sudden infant death syndrome (SIDS).

PubMed

Scholle, S; Zwacka, G; Glaser, S; Knöfel, B; Scheidt, B; Oehme, P; Rathsack, R

1990-01-01

In order to evaluate disturbances of the respiratory control in the first year of life in children with a statistically enhanced risk of SIDS, substance P-like immunoreactivity (SPLI) in plasma and mean apnoea duration (MA) were examined. 4 groups of infants were investigated: Controls, full-term infants with anamnestic SIDS-risk factors, preterm infants with additional risk factors and preterm infants without such factors. Infants aged from -4(corrected age) to 63 weeks. SPLI in plasma was determined by a specific, homologous radioimmunoassay. The SPLI-level was significantly higher in controls (n = 41; means +/- SE = 36.37 +/- 4.86 pg/ml) than in preterm infants without (n = 21; 25.41 +/- 5.54 pg/ml) or with additional anamnestic risk factors (n = 111; 25.89 +/- 3.09 pg/ml). SPLI was higher in full-term SIDS-risk infants (n = 150; 30.73 +/- 2.35 pg/ml) than in the preterm groups. There is a significant age dependence in the groups full-term SIDS-risk infants and preterm infants with additional risk factors. During maturation the SPLI-level in plasma rises in these groups from lower values. The MA-values were determined by means of a daytime polygraphy. There is an age dependence of the MA-values during active sleep in full-term SIDS-risk infants and in preterm infants with additional anamnestic risk factors. In the age group 4-17 weeks (peak of SIDS frequency) in active sleep the MA-values were significantly higher in all 3 risk groups than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between diet and plasma long-chain n-3 PUFAs in older people: impact of apolipoprotein E genotype

PubMed Central

Samieri, Cécilia; Lorrain, Simon; Buaud, Benjamin; Vaysse, Carole; Berr, Claudine; Peuchant, Evelyne; Cunnane, Stephen C.; Barberger-Gateau, Pascale

2013-01-01

The main risk factors for Alzheimer's disease, age and the ϵ4 allele of the APOE gene (APOE4), might modify the metabolism of n-3 PUFAs and in turn, their impact on cognition. The aim of this study was to investigate the association between dietary fat and plasma concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in elderly persons, taking the APOE4 genotype into account. The sample was composed of 1,135 participants from the Three-City study aged 65 years and over, of whom 19% were APOE4 carriers. Mean plasma proportions of EPA [1.01%, standard deviation (SD) 0.60] and DHA (2.41%, SD 0.81) did not differ according to APOE4. In multivariate models, plasma EPA increased with frequency of fish consumption (P < 0.0001), alcohol intake (P = 0.0006), and female gender (P = 0.02), and decreased with intensive consumption of n-6 oils (P = 0.02). The positive association between fish consumption and plasma DHA was highly significant whatever the APOE genotype (P < 0.0001) but stronger in APOE4 noncarriers than in carriers (P = 0.06 for interaction). Plasma DHA increased significantly with age (P = 0.009) in APOE4 noncarriers only. These findings suggest that dietary habits, gender, and APOE4 genotype should be considered when designing interventions to increase n-3 PUFA blood levels in older people. PMID:23801662

Biological ageing and frailty markers in breast cancer patients.

PubMed

Brouwers, Barbara; Dalmasso, Bruna; Hatse, Sigrid; Laenen, Annouschka; Kenis, Cindy; Swerts, Evalien; Neven, Patrick; Smeets, Ann; Schöffski, Patrick; Wildiers, Hans

2015-05-01

Older cancer patients are a highly heterogeneous population in terms of global health and physiological reserves, and it is often difficult to determine the best treatment. Moreover, clinical tools currently used to assess global health require dedicated time and lack a standardized end score. Circulating markers of biological age and/or fitness could complement or partially substitute the existing screening tools. In this study we explored the relationship of potential ageing/frailty biomarkers with age and clinical frailty. On a population of 82 young and 162 older non-metastatic breast cancer patients, we measured mean leukocyte telomere length and plasma levels of interleukin-6 (IL-6), regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein 1 (MCP-1), insulin-like growth factor 1 (IGF-1). We also developed a new tool to summarize clinical frailty, designated Leuven Oncogeriatric Frailty Score (LOFS), by integrating GA results in a single, semi-continuous score. LOFS' median score was 8, on a scale from 0=frail to 10=fit. IL-6 levels were associated with chronological age in both groups and with clinical frailty in older breast cancer patients, whereas telomere length, IGF-1 and MCP-1 only correlated with age. Plasma IL-6 should be further explored as frailty biomarker in cancer patients.

Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer's mice.

PubMed

Cao, Chuanhai; Wang, Li; Lin, Xiaoyang; Mamcarz, Malgorzata; Zhang, Chi; Bai, Ge; Nong, Jasson; Sussman, Sam; Arendash, Gary

2011-01-01

Retrospective and prospective epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer's disease (AD). Underscoring this premise, our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase. Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD, we examined effects of caffeinated and decaffeinated coffee on plasma cytokines, comparing their effects to caffeine alone. In both AβPPsw+PS1 transgenic mice and non-transgenic littermates, acute i.p. treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines. The increase in GCSF is particularly important because long-term treatment with coffee (but not decaffeinated coffee) enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines. Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms (e.g., recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis), the same mechanisms could be complimentary to caffeine's established ability to suppress Aβ production. We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD.

Vitamin E supplementation protects erythrocyte membranes from oxidative stress in healthy Chinese middle-aged and elderly people.

PubMed

Sun, Yongye; Ma, Aiguo; Li, Yong; Han, Xiuxia; Wang, Qiuzhen; Liang, Hui

2012-05-01

Elderly people are subject to higher levels of oxidative stress than are young people. Vitamin E, as a powerful antioxidant residing mainly in biomembranes, may provide effective protection against oxidative membrane damage and resultant age-related deterioration, especially in the elderly. We hypothesized that appropriate levels of vitamin E supplementation would protect erythrocyte membranes from oxidative stress and thus improve membrane fluidity in healthy middle-aged and elderly people. To test this, we conducted a 4-month double-blind, randomized trial in which 180 healthy subjects (55-70 years old) were randomly divided into 4 groups: group C (control), and 3 treatment groups in which daily doses of 100 mg (VE1), 200 mg (VE2), and 300 mg (VE3) dl-α-tocopheryl acetate were administered. We measured plasma α-tocopherol concentration, malondialdehyde, and superoxide dismutase levels, erythrocyte hemolysis, and erythrocyte membrane fluidity at the beginning and end of the trial. After 4 months supplementation, plasma α-tocopherol concentrations in the 3 treatment groups had increased by 71%, 78%, and 95%, respectively (all P < .01), and significant decreases in plasma malondialdehyde concentrations were observed in these groups (all P < .05). Erythrocyte hemolysis was decreased by 20% to 38% after vitamin E supplementation (all P < .05), and in addition, groups VE2 and VE3 showed dramatic improvements in erythrocyte membrane fluidity (P < .01). Surprisingly, superoxide dismutase activity also decreased significantly in the treatment groups (all P < .05). In summary, vitamin E supplementation apparently alleviates oxidative stress in healthy middle-aged to elderly people, at least in part by improving erythrocyte membrane fluidity and reducing erythrocyte hemolysis. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function

PubMed Central

Kanias, Tamir; Triulzi, Darrel; Donadee, Chenell; Barge, Suchitra; Badlam, Jessica; Jain, Shilpa; Belanger, Andrea M.; Kim-Shapiro, Daniel B.

2015-01-01

Rationale: A major abnormality that characterizes the red cell “storage lesion” is increased hemolysis and reduced red cell lifespan after infusion. Low levels of intravascular hemolysis after transfusion of aged stored red cells disrupt nitric oxide (NO) bioavailabity, via accelerated NO scavenging reaction with cell-free plasma hemoglobin. The degree of intravascular hemolysis post-transfusion and effects on endothelial-dependent vasodilation responses to acetylcholine have not been fully characterized in humans. Objectives: To evaluate the effects of blood aged to the limits of Food and Drug Administration–approved storage time on the human microcirculation and endothelial function. Methods: Eighteen healthy individuals donated 1 U of leukopheresed red cells, divided and autologously transfused into the forearm brachial artery 5 and 42 days after blood donation. Blood samples were obtained from stored blood bag supernatants and the antecubital vein of the infusion arm. Forearm blood flow measurements were performed using strain-gauge plethysmography during transfusion, followed by testing of endothelium-dependent blood flow with increasing doses of intraarterial acetylcholine. Measurements and Main Results: We demonstrate that aged stored blood has higher levels of arginase-1 and cell-free plasma hemoglobin. Compared with 5-day blood, the transfusion of 42-day packed red cells decreases acetylcholine-dependent forearm blood flows. Intravascular venous levels of arginase-1 and cell-free plasma hemoglobin increase immediately after red cell transfusion, with more significant increases observed after infusion of 42-day-old blood. Conclusions: We demonstrate that the transfusion of blood at the limits of Food and Drug Administration–approved storage has a significant effect on the forearm circulation and impairs endothelial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01137656) PMID:26222884

Tocotrienol rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: A randomized controlled study

PubMed Central

2011-01-01

Background Vitamin E supplements containing tocotrienols are now being recommended for optimum health but its effects are scarcely known. The objective was to determine the effects of Tocotrienol Rich Fraction (TRF) supplementation on lipid profile and oxidative status in healthy older individuals at a dose of 160 mg/day for 6 months. Methods Sixty-two subjects were recruited from two age groups: 35-49 years (n = 31) and above 50 years (n = 31), and randomly assigned to receive either TRF or placebo capsules for six months. Blood samples were obtained at 0, 3rd and 6th months. Results HDL-cholesterol in the TRF-supplemented group was elevated after 6 months (p < 0.01). Protein carbonyl contents were markedly decreased (p < 0.001), whereas AGE levels were lowered in the > 50 year-old group (p < 0.05). Plasma levels of total vitamin E particularly tocopherols were significantly increased in the TRF-supplemented group after 3 months (p < 0.01). Plasma total tocotrienols were only increased in the > 50 year-old group after receiving 6 months of TRF supplementation. Changes in enzyme activities were only observed in the > 50 year-old group. SOD activity was decreased after 3 (p < 0.05) and 6 (p < 0.05) months of TRF supplementation whereas CAT activity was decreased after 3 (p < 0.01) and 6 (p < 0.05) months in the placebo group. GPx activity was increased at 6 months for both treatment and placebo groups (p < 0.05). Conclusion The observed improvement of plasma cholesterol, AGE and antioxidant vitamin levels as well as the reduced protein damage may indicate a restoration of redox balance after TRF supplementation, particularly in individuals over 50 years of age. PMID:21702918

Current data on the background burden to the persistent organochlorine pollutants HCB, p,p'-DDE as well as PCB 138, PCB 153 and PCB 180 in plasma of the general population in Germany.

PubMed

Schettgen, Thomas; Alt, Anne; Esser, Andre; Kraus, Thomas

2015-06-01

Despite their long-term ban, persistent organochlorine compounds like hexachlorobenzene (HCB), p,p'-dichlorodiphenylethylene (DDE) as well as polychlorinated biphenyls (PCBs) are still of environmental concern. For the evaluation of potential occupational or environmental exposures to these substances, it is essential to know the current background burden of the general population. As representative and up-to-date information is missing for Germany, we have analysed a large dataset generated in studies on potential exposure to lower chlorinated PCBs to fill this gap for the levels of HCB, DDE as well as PCB 138, PCB 153 and PCB 180. We have investigated n=2750 plasma samples of persons of the general population living in North Rhine-Westfalia and Hesse aged 6-65 years and sampled between September 2010 and March 2014. For evaluation of the age-dependent accumulation in the general population we have generated seven age groups in the collective. Our laboratory used a validated and quality controlled procedure using GC/MS for quantification of the organochlorine compounds in plasma (LOQ: 0.01μg/L). The median (95th percentile) levels for ∑ PCB 138+PCB 153+PCB 180 were 0.14 (0.73); 0.30 (0.82); 0.38 (0.88); 0.50 (1.14); 0.92; 1.58 (3.54) and 2.41 (4.82)μg/L plasma in the age groups 6-10 years (n=102), 11-17 years (n=499), 18-25 years (n=157), 26-35 years (n=710), 36-45 years (n=400), 46-55 years (n=525) and 56-65 years (n=357), respectively. Similarly, the median (95th percentile) levels of p,p'-DDE were 0.18 (1.24); 0.18 (0.74); 0.24 (0.85); 0.30 (1.20); 0.45 (1.74); 0.64 (3.25) and 0.94 (4.7)μg/L plasma. Finally, the median (95th percentile) of HCB in plasma in these age groups was 0.05 (0.10); 0.06 (0.11); 0.08 (0.15); 0.08 (0.15); 0.11 (0.22); 0.14 (0.42) and 0.20 (0.68)μg/L plasma. Our results prove an overall substantial reduction in the body burden to organochlorine compounds in Germany compared to earlier studies. However, 15% and 3.6% of the examined collective exceeded the HBM-I- and HBM-II-values for PCBs established by the German Human Biomonitoring Commission. Due to a large sample size and a collection period from 2010 to 2014, our data might be suitable for the evaluation of additional exposures to these POPs and may serve as reference values. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

Effects of a chronic l-arginine supplementation on the arginase pathway in aged rats.

PubMed

Moretto, Johnny; Guglielmetti, Anne-Sophie; Tournier-Nappey, Maude; Martin, Hélène; Prigent-Tessier, Anne; Marie, Christine; Demougeot, Céline

2017-04-01

While ageing is frequently associated with l-arginine deficiency, clinical and experimental studies provided controversial data on the interest of a chronic l-arginine supplementation with beneficial, no or even deleterious effects. It was hypothesized that these discrepancies might relate to a deviation of l-arginine metabolism towards production of l-ornithine rather than nitric oxide as a result of age-induced increase in arginase activity. This study investigated the effect of ageing on arginase activity/expression in target tissues and determined whether l-arginine supplementation modulated the effect of ageing on arginase activity. Arginase activity and expression were measured in the heart, vessel, brain, lung, kidney and liver in young rats (3-months old) and aged Wistar rats (22-24-months-old) with or without l-arginine supplementation (2.25% in drinking water for 6weeks). Plasma levels of l-arginine and l-ornithine were quantified in order to calculate the plasma l-arginine/l-ornithine ratio, considered as a reflection of arginase activity. Cardiovascular parameters (blood pressure, heart rate) and aortic vascular reactivity were also studied. Ageing dramatically reduced plasma l-arginine and l-arginine/l-ornithine ratio, decreased liver and kidney arginase activities but did not change activities in other tissues. l-Arginine supplementation normalized plasma l-arginine and l-arginine/l-ornithine ratio, improved endothelial function and decreased systolic blood pressure. These effects were associated with decreased arginase activity in aorta along with no change in the other tissues except in the lung in which activity was increased. A strong mismatch was therefore observed between arginase activity and expression in analyzed tissues. The present study reveals that ageing selectively changes arginase activity in clearance tissues, but does not support a role of the arginase pathway in the potential deleterious effect of the l-arginine supplementation in aged patients. Moreover, our data argue against the use of the measurement of plasma l-arginine/l-ornithine ratio to estimate arginase activity in aged patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Ghrelin level negatively predicts quality of life in obese women.

PubMed

Lu, P H; Song, Y L; Hsu, C H

2017-02-01

A cross-sectional cohort study was conducted to investigate whether ghrelin level in obese women predicts the quality of life (QOL). A total of 307 subjects fulfilled the criteria: (1) age between 20 and 65 years old, (2) body mass index ≥27 kg/m 2 (3) waist circumference ≥80 cm were enrolled in the study. All subjects were assigned to one of the plasma ghrelin level categories according to the quartiles. The median of age and BMI of the 307 obese women were 45 ± 18 years and 29.9 ± 4.1 kg/m 2 , respectively. The main outcome evaluated is the associations of plasma ghrelin level and QOL, which were evaluated using multiple linear regression analysis. Results of linear trend test show significant statistical difference in plasma lipoproteins (triglyceride, cholesterol, HDL-cholestero and LDL-cholesterol = and levels of obesity-related hormone peptides, including leptin, adiponectin, insulin among quartiles of ghrelin. Multiple liner regression analysis of serum obesity-related hormone peptide level and QOL using stepwise method shows ghrelin concentration was the only predictor of QOL, including PCS-12 level (β = -0.18, p = 0.001), MCS-12 level (β = -0.14, p = 0.009), WHOQOL-BREF scores: physical (β = -0.13, p = 0.03), psychological (β = -0.16, p = 0.007), social (β = -0.21, p =  < 0.001), and environmental (β = -0.22, p =  <0.001), after adjusting other factors for obese female subjects. This study demonstrated that ghrelin concentration is strongly associated with QOL level among obese women. Hence, ghrelin concentration might be a valuable marker to be monitored in obese women.

Evaluating the efficacy of osteopontin expression as a prognostic marker in oral squamous cell carcinoma in the Indian subpopulation.

PubMed

Ingale, Yashwant; Routray, Samapika; Kheur, Supriya M; Kheur, Mohit; Mohanty, Neeta

2014-09-01

This study aimed to correlate the prognostic value of osteopontin (OPN) expression using both tissue and plasma samples from patients with clinically and histologically confirmed oral squamous cell carcinoma (OSCC). The study group comprised of sixty patients (n = 60), which were clinically and histologically diagnosed for oral squamous cell carcinoma (OSCC). The Control group comprised of ten (n = 10) healthy volunteers. Plasma OPN levels were assayed using a quantitative enzyme-linked immunosorbent assay (OPN ELISA). Expression of OPN was also identified and evaluated by immunohistochemistry in tissue sections. These OPN expressions were then correlated with different parameters like age, sex, site, clinical presentation, tumor node metastasis (TNM) staging, histopathological grading and lymph node metastasis. One-way analysis of variance (ANOVA) was used to evaluate the difference in tissue intensity and plasma OPN levels between the OSCC and the normal control groups. The distribution of the plasma OPN levels and tissue OPN intensity in OSCC cohorts were compared to histopathological grades and analyzed. When evaluated OPN expression in tissue had higher intensity observed in OSCC (95% +ve) cases. And the mean plasma OPN concentration in OSCC cohort was more in comparison to the normal cohort. The results clearly showed that the plasma OPN levels and intensity grading in tissue correlated with tumor grades. The study highlights OPN as a biomarker for prognosis in OSCC in both plasma and tissue samples. We would like to emphasize on the evaluation of plasma OPN as a protocol of blood examination for all cancer patient, as it may serve as an indicator for tumor progression and potential risk of metastasis.

The potential of pigeon pea (Cajanus cajan) beverage as an anti-diabetic functional drink

NASA Astrophysics Data System (ADS)

Ariviani, S.; Affandi, D. R.; Listyaningsih, E.; Handajani, S.

2018-01-01

The number of patients with diabetes continues to increase. Diabetes complications might induce serious diseases such as kidney, nervous, cardiovascular diseases and stroke. Diabetic complications can be prevented by keeping blood glucose and cholesterol at normal levels. This study aims to determine the potential of pigeon pea beverage for lowering glucose and total cholesterol plasma levels and increasing the antioxidant status of diabetic-hypercholesterolemia rats. The research was conducted using 18 Sprague Dawley male rats aged 3 months old with an average body weight of 154 g. The rats were divided into three groups: normal group, D-H group (diabetic-hypercholesterolemia group), and pigeon pea beverage group. The results showed that pigeon pea beverage diet showed hypoglycemic and hypocholesterolemic activities, and could improve the antioxidant status of diabetic-hypercholesterolemia rats. Plasma glucose and total cholesterol levels of diabetic-hypercholesterolemia rats decreased 33.86% and 19.78% respectively. The improvement of the plasma antioxidant status was indicated by the decrease of plasma MDA (malondialdehyde) level, reaching 37.16%. The research result provides an alternative to diabetes management by using the local bean as an anti-diabetic functional drink.

Glucose Intolerance, Plasma Insulin Levels, and Colon Adenomas in Japanese Men

PubMed Central

Kono, Suminori; Abe, Hiroshi; Eguchi, Hiroyuki; Shimazaki, Kae; Hatano, Ben; Hamada, Hiroaki

2001-01-01

Hyperinsulinemia may be related to colon carcinogenesis. Several studies have suggested that diabetes mellitus is related to increased risk of colon cancer. We examined cross‐sectionally the relation of fasting plasma insulin levels and glucose tolerance status to colon adenomas. In a consecutive series of 951 men undergoing total colonoscopy for a health examination at the Japan Self Defense Forces Fukuoka Hospital from April 1998 to August 1999, we identified 233 cases of colon adenomas and 497 controls with normal colonoscopy. Glucose tolerance status was determined by a 75‐g oral glucose tolerance test, and subjects were classified as normal, unpaired glucose tolerance (IGT) or non‐insulin dependent diabetes mellitus (NIDDM). Plasma insulin levels were measured after subjects had fasted overnight. Logistic regression analysis and analysis of covariance was used to control for age and obesity. While plasma insulin levels were unrelated to colon adenomas, NIDDM was associated with a significantly increased risk of colon adenomas. There was no association between IGT and colon adenomas. NIDDM was more strongly associated with proximal colon adenomas. The findings suggest that long‐term hyperinsulinemic status associated with NIDDM may increase the risk of colon adenomas, and subsequently of colon cancer. PMID:11509114

Detection of Free Advanced Glycation End Products in Vivo during Hemodialysis.

PubMed

Hohmann, Christoph; Liehr, Kristin; Henning, Christian; Fiedler, Roman; Girndt, Matthias; Gebert, Michael; Hulko, Michael; Storr, Markus; Glomb, Marcus A

2017-02-01

Advanced glycation end products (AGEs) are often regarded as glycotoxins, which are normally removed by the kidney. Patients with end-stage renal failure rely on hemodialysis (HD) treatment to eliminate these compounds. In the present work, a highly selective LC-MS/MS method was used for quantitation of AGE levels in plasma and in dialysis fluids of HD patients, with a focus on AGE-free adducts. A broad range of 19 amino acid modifications was identified and quantitated. It was expected that the AGE-free adducts are successfully eliminated by dialysis treatment. Indeed, with a mean elimination rate of 71%, this assumption proved to be valid for all target analytes with the exception of pyrraline, which showed an opposite behavior. Here, plasma and dialysate levels increased during the treatment by about 59%. The notions that pyrraline was formed in high amounts in the patient's bloodstream (I) after intake of the corresponding precursor compound 3-deoxyglucosone with the dialysis fluid or (II) by catalytic effects on the formation by the dialysis membrane were ruled out. In contrast, in a dietary study, the comparison of pyrraline concentrations in plasma before and after food consumption confirmed that the increase in pyrraline originates solely from digestion of glycated food proteins. Additionally, by detailed analyses of the food consumed during dialysis sessions, bread rolls with a pyrraline content of about 21.7 μmol per serving were identified as the main source.

Cardiovascular risk factors in the normoglycaemic Asian-Indian population--influence of urbanisation.

PubMed

Snehalatha, C; Ramachandran, A

2009-04-01

The aim of this study was to investigate the prevalence of cardiovascular risk factors in normoglycaemic Asian-Indians and its association with urbanisation and plasma glucose. Data on 5,517 normoglycaemic individuals aged >/=20 years (1,521, 1,851 and 2,145 inhabitants of a city, a town and villages, respectively), from a 2006 diabetes survey, were used. The presence of single and multiple abnormalities, including obesity, abdominal obesity, hypertension and dyslipidaemia, was analysed. Risk associations for hypertension and dyslipidaemia were analysed using multivariate analysis after adjusting for confounding variables. Both the prevalence and clustering of cardiovascular risk variables were higher in urban areas than in villages, and were higher in the city than in the town. Nearly half (47%) of the normoglycaemic individuals from villages had at least one risk factor. Age, male sex, BMI, waist circumference, lack of physical activity and living in an urban environment were associated with hypertension and dyslipidaemia; postprandial glucose level showed no association with hypertension or dyslipidaemia after adjusting for these risk factors. Fasting plasma glucose level showed an independent association with dyslipidaemia. There is a high prevalence of cardiovascular risk factors even among normoglycaemic individuals, and this is highest in urban areas. Fasting plasma glucose level showed an association with dyslipidaemia but not hypertension.

No effect of cigarette smoking dose on oxidized plasma proteins

PubMed Central

Yeh, Chih-Ching; Barr, R. Graham; Powell, Charles A.; Mesia-Vela, Sonia; Wang, Yuanjia; Hamade, Nada K.; Austin, John H.M.; Santella, Regina M.

2008-01-01

Cigarette smoking is a major source of oxidative stress. Protein carbonyls have been used as a biomarker of oxidative stress because of the relative stability of carbonylated proteins and the high protein concentration in blood. Increased levels of carbonyl groups have been found in serum proteins of smokers compared to nonsmokers. However, neither the dose effect of current cigarette smoke nor other predictors of oxidative stress have been studied. Hence, we used an ELISA (Enzyme-Linked Immunosorbent Assay) to evaluate plasma protein carbonyls in smokers recruited in the Early Lung Cancer Action Project (ELCAP) program. The lung cancer screening program enrolled current and former smokers age 60 years and over without a prior cancer diagnosis. A total of 542 participants (282 men and 260 women) completed a baseline questionnaire and provided blood samples for the biomarker study. Protein oxidation was measured by derivatization of the carbonyl groups with 2,4-dinitrophenylhydrazine (DNPH) and ELISA quantitation of the DNPH group. Current smoking status was confirmed with urinary cotinine. The mean (± SD) protein carbonyl level was 17.9 ± 2.9 nmol carbonyls/ml plasma. Protein carbonyls did not differ significantly by gender. Carbonyl levels were higher among current than former smokers, but these differences did not attain statistical significance, nor did differences by urine cotinine levels, pack-years, pack/day among current smokers, and smoking duration. In a multiple regression analysis, higher protein carbonyl levels were independently associated with increasing age (0.59 nmol/ml increase per 10 years, 95% CI 0.14, 1.05, p = 0.01), African-American vs. white race/ethnicity, (1.30 nmol/ml, 95% CI 0.4, 2.19, p =0.008), and lower educational attainment (0.75 nmol/ml, 95% CI 0.12, 1.38, p = 0.02). Although we found no significant difference between current versus past cigarette smoking and protein carbonyls in this older group of smokers, associations were found for age, ethnicity and educational attainment. Our results indicate that the measurement of plasma carbonyls by this ELISA technique is still an easy and suitable method for studies of diseases related to oxidative stress. PMID:17996865

Overweight is associated with lower serum leptin in Peruvian Indian than in Caucasian women: A dissociation contributing to low blood pressure?

PubMed

Lindgärde, F; Söderberg, S; Olsson, T; Ercilla, M B; Correa, L R; Ahrén, B

2001-03-01

We tested whether plasma levels of leptin and insulin are associated with the lower blood pressure in women of Peruvian Indian heritage compared with Caucasian women. A total of 181 women from Peru and 85 from Sweden, aged 20 to 60 years, with normal plasma glucose levels participated in the study. Measurements of anthropometry, blood pressure, and blood tests were performed after overnight fasting. Compared with women from Umeå in Sweden, women from Lima, Peru had higher body mass index (BMI) (26.2 +/- 4.9 v 24.4 +/- 3.8 kg/m(2)), waist circumference (85 +/- 11 v 79 +/- 10 cm), lower systolic blood pressure (99 +/- 15 v 114 +/- 14 mm; P <.001) and diastolic blood pressure (67 +/- 7 v 74 +/- 10 mm; P <.001). In addition, they had a reduction of the ratio of plasma leptin to BMI (0.52 +/- 0.22 v 0.61 +/- 0.36; P <.001), greater plasma insulin (80 +/- 42 v 41 +/- 21 pmol/L), but lower plasma glucose (4.2 +/- 0.5 v 5.1 +/- 0.5 mmol/L; P <.001). Furthermore, the 181 women from Lima had higher plasma triglyceride levels (1.5 +/- 0.8 v 1.3 +/- 0.7; P =.039), but lower plasma high-density lipoprotein (HDL)-cholesterol (1.0 +/- 0.2 v 1.5 +/- 0.4 mmol/L; P <.001) and total plasma cholesterol (5.0 +/- 1.1 v 5.9 +/- 1.3 mmol/L; P <.001) levels. Plasma leptin correlated with blood pressure and BMI in both populations (P <.001). In multiple regression analysis, BMI, but not log leptin, emerged as the determinant for systolic blood pressure. We concluded that women living in Lima have significant lower blood pressure levels in association with elevated plasma insulin concentrations, but lower plasma leptin values adjusted for BMI in comparison with women from northern Sweden. This may suggest that the concept of metabolic syndrome is different among women with Peruvian Indian heritage in comparison to a Caucasian population. Copyright 2001 by W.B. Saunders Company

Lipid profile in oral submucous fibrosis.

PubMed

Mehrotra, Ravi; Pandya, Shruti; Chaudhary, Ajay Kumar; Singh, Himanshu Pratap; Jaiswal, Ritesh Kumar; Singh, Mangal; Gupta, S C; Singh, Mamta

2009-07-24

Changes in lipid profile have long been associated with malignancies as lipids play a key role in maintenance of cell integrity. This study evaluated the alterations in extended lipid profile in untreated patients of oral submucous fibrosis (OSMF) and studied the correlation between lipid levels with tobacco consumption. In this hospital-based study, 65 clinically diagnosed and histopathologically proven patients of OSMF and 42 age and sex matched controls were studied. In these samples serum lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) (v) triglycerides (vi) Apo-A1 (viii) Apo-B and (viii) LPa were analyzed. A significant decrease in plasma total cholesterol, HDLC and Apo-A1 was observed in patients with OSMF as compared to the controls. Thus an inverse relationship between plasma lipid levels and patients was found in OSMF. The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in patients with oral precancerous conditions.

The association of oxidant-antioxidant status in patients with chronic renal failure.

PubMed

Aziz, Manal A; Majeed, Ghanim H; Diab, Kareem S; Al-Tamimi, Raid J

2016-01-01

Oxidative stress has been linked to disease progression, including chronic renal failure (CRF). The aim of the present study was to determine malondialdehyde (MDA) as a sign of lipid peroxidation, and to investigate the association between antioxidant activities and three trace elements, in 49 patients with CRF. The erythrocyte and plasma trace elements [selenium (Se), zinc (Zn), and copper (Cu)] and antioxidant defense levels were determined: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), vitamins E and C. The obtained values were compared with 42 age- and sex-matched healthy controls. There were significantly lower mean values of plasma Se, GPx, vitamins E and C, erythrocyte Se, SOD and CAT levels in the patient group compared to the control group (p < 0.001). Plasma MDA showed a significant increase in all CRF patients in comparison with controls. No significant difference was found in plasma Cu, Zn, and erythrocyte GPx, Cu and Zn levels between patient and control groups. These findings indicate oxidative stress is present in patients of CRF, and may serve to establish a simple protocol for evaluation of renal function.

Plasma apolipoproteins and physical and cognitive health in very old individuals.

PubMed

Muenchhoff, Julia; Song, Fei; Poljak, Anne; Crawford, John D; Mather, Karen A; Kochan, Nicole A; Yang, Zixuan; Trollor, Julian N; Reppermund, Simone; Maston, Kate; Theobald, Adam; Kirchner-Adelhardt, Susanne; Kwok, John B; Richmond, Robyn L; McEvoy, Mark; Attia, John; Schofield, Peter W; Brodaty, Henry; Sachdev, Perminder S

2017-07-01

Apolipoproteins play a crucial role in lipid metabolism with implications in cardiovascular disease, obesity, diabetes, Alzheimer's disease, and longevity. We quantified 7 apolipoproteins in plasma in 1067 individuals aged 56-105 using immunoassays and explored relationships with APOE polymorphism ε2/3/4, vascular health, frailty, and cognition. ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH, and ApoJ decreased from mid-life, although ApoE and ApoJ had U-shaped trends. Centenarians had the highest ApoE levels and the lowest frequency of APOE ε4 allele relative to younger groups. Apolipoprotein levels trended lower in APOE ε4 homozygotes and heterozygotes compared with noncarriers, with ApoE and ApoJ being significantly lower. Levels of all apolipoproteins except ApoH were higher in females. Sex- and age-related differences were apparent in the association of apolipoproteins with cognitive performance, as only women had significant negative associations of ApoB, ApoE, ApoH, and ApoJ in mid-life, whereas associations at older age were nonsignificant or positive. Our findings suggest levels of some apolipoproteins, especially ApoE, are associated with lifespan and cognitive function in exceptionally long-lived individuals. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of mild aerobic exercise and a mild hypocaloric diet on plasma leptin in sedentary women.

PubMed

Okazaki, T; Himeno, E; Nanri, H; Ogata, H; Ikeda, M

1999-01-01

1. The present study was conducted to investigate whether mild aerobic exercise and a mild hypocaloric diet, instead of severe restrictions on caloric intake, would affect weight reduction and plasma leptin concentrations. 2. Forty-one middle-aged sedentary women (15 obese and 26 non-obese) participated in a 12 week lifestyle-modification programme to reduce cardiovascular risk factors. Bodyweight, body composition, plasma leptin concentrations, serum lipid profiles, fasting plasma glucose and fasting plasma insulin were measured before and after the 12 week intervention. The intervention consisted of aerobic exercise, corresponding to approximately 50% of maximal oxygen consumption, and personal diet counselling. 3. Bodyweight decreased by (mean +/- SD) 3.9 +/- 3.4 kg in the obese group (P < 0.05) and by 1.7 +/- 1.8 kg in the non-obese group (P < 0.05). The plasma leptin concentration decreased significantly from 14.7 +/- 5.3 to 8.9 +/- 3.6 ng/mL in the obese group (P < 0.001) and from 7.6 +/- 3.9 to 5.6 +/- 2.2 ng/mL in the non-obese group (P < 0.01). 4. Overall, for all subjects, both pre- and postintervention, the plasma leptin concentration was significantly correlated with body mass index (BMI; pre-intervention: r = 0.73, P < 0.0001; postintervention: r = 0.67, P < 0.0001), fat mass (FM; pre-intervention: r = 0.74, P < 0.0001; postintervention: r = 0.63, P < 0.0001) and fasting plasma insulin (pre-intervention: r = 0.66, P < 0.001; postintervention: r = 0.45, P < 0.01). The change in plasma leptin concentration was significantly correlated with the respective changes in BMI (r = 0.64, P < 0.0001), FM (r = 0.48, P < 0.01) and fasting plasma insulin (r = 0.58, P < 0.0001). Interestingly, the ratio of plasma leptin concentration to BMI or FM diminished significantly after intervention. In addition, we found that the plasma leptin concentration decreased in participants whose FM did not decrease. These results suggest that the production of leptin per unit FM decreased after intervention. 5. Mild aerobic exercise and a mild hypocaloric intake decreased body mass and the plasma leptin level in Japanese middle-aged sedentary women. This decrease in plasma leptin levels was likely to be associated with weight reduction plus some unknown factor(s).

Changes in the level and activation state of the plasma membrane H(+)-ATPase during aging of red beet slices.

PubMed

Papini, R; De Michelis, M I

1997-07-01

The effect of aging on the plasma membrane (PM) H(+)-ATPase of red beet (Beta vulgaris L.) parenchyma discs was analyzed in PM purified by aqueous two-phase partitioning. Aging increased both the activity in the amount of immunodetectable H(+)-ATPase in the PM. The activity assayed at slightly alkaline pH values increased earlier and more strongly than that assayed at acidic pH values, so that the pH curve of the enzyme from aged beet discs was shifted toward more alkaline values. Aging decreased the stimulation of the PM H(+)-ATPase activity by controlled trypsin treatments or by lysophosphatidylcholine. After trypsin treatment the pH dependence of H(+)-ATPase from dormant or aged beet discs became equal. These results indicate that aging not only increases the level of H(+)-ATPase in the PM, but also determines its activation, most likely by modifying the interaction between the autoinhibitory carboxyl-terminal domain and the catalytic site. When the PM H(+)-ATPase activity was assayed at a slightly alkaline pH, the tyrosine modifier N-acetylimidazole inhibited the H(+)-ATPase in the PM from dormant beet discs much less than in the PM from aged discs, suggesting that modification of a tyrosine residue may be involved in the activation of the PM H(+)-ATPase induced by aging. The results are discussed with regard to aging-induced development of transmembrane transport activities.

Relation between plasma antioxidant vitamin levels, adiposity and cardio-metabolic profile in adolescents: Effects of a multidisciplinary obesity programme.

PubMed

Guerendiain, Marcela; Mayneris-Perxachs, Jordi; Montes, Rosa; López-Belmonte, Gemma; Martín-Matillas, Miguel; Castellote, Ana I; Martín-Bautista, Elena; Martí, Amelia; Martínez, J Alfredo; Moreno, Luis; Garagorri, Jesús Mª; Wärnberg, Julia; Caballero, Javier; Marcos, Ascensión; López-Sabater, M Carmen; Campoy, Cristina

2017-02-01

In vivo and in vitro evidence suggests that antioxidant vitamins and carotenoids may be key factors in the treatment and prevention of obesity and obesity-associated disorders. Hence, the objective of the present study was to determine the relationship between plasma lipid-soluble antioxidant vitamin and carotenoid levels and adiposity and cardio-metabolic risk markers in overweight and obese adolescents participating in a multidisciplinary weight loss programme. A therapeutic programme was conducted with 103 adolescents aged 12-17 years old and diagnosed with overweight or obesity. Plasma concentrations of α-tocopherol, retinol, β-carotene and lycopene, anthropometric indicators of general and central adiposity, blood pressure and biochemical parameters were analysed at baseline and at 2 and 6 months of treatment. Lipid-corrected retinol (P < 0.05), β-carotene (P = 0.001) and α-tocopherol (P < 0.001) plasma levels increased significantly, whereas lipid-corrected lycopene levels remained unaltered during the treatment. Anthropometric indicators of adiposity (P < 0.001), blood pressure (P < 0.01) and biochemical parameters (P < 0.05) decreased significantly, whereas fat free mass increased significantly (P < 0.001). These clinical and biochemical improvements were related to changes in plasma lipid-corrected antioxidant vitamin and carotenoid levels. The adolescents who experienced the greatest weight loss also showed the largest decrease in anthropometric indicators of adiposity and biochemical parameters and the highest increase in fat free mass. Weight loss in these adolescents was related to an increase in plasma levels of lipid-corrected α-tocopherol (P = 0.001), β-carotene (P = 0.034) and lycopene (P = 0.019). Plasma lipid-soluble antioxidant vitamin and carotenoid levels are associated with reduced adiposity, greater weight loss and an improved cardio-metabolic profile in overweight and obese adolescents. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Sex differences in plasma homovanillic acid levels in schizophrenia and normal controls: relation to neuroleptic resistance.

PubMed

Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

1997-03-01

Plasma homovanillic acid (pHVA) levels were compared in a large number of neuroleptic-resistant and -responsive schizophrenic patients (male/female = 161/46) and normal controls (67/27), and correlated with various measures of psychopathology. Psychopathology was evaluated with the brief psychiatric rating scale, the Schedule for Affective Disorders and Schizophrenia-Change version (SADS-C) and SADS-C Global Assessment Scale, the Scale for Assessment of Negative Symptoms, the Scale for Assessment of Positive Symptoms (SAPS), and the Quality of Life Scale. No significant differences in pHVA levels between neuroleptic-resistant (n = 104) or -responsive (n = 103) schizophrenic patients, and normal controls, were found; however, there was a main effect for sex, due to higher pHVA levels in women than men. There were no diagnosis x gender or age effects on pHVA levels. No significant correlations were observed between psychopathology ratings and baseline pHVA levels, except with the Hallucinations subscale of SAPS in neuroleptic-responsive patients. Neither duration of neuroleptic washout nor plasma prolactin levels correlated with pHVA levels. Further studies on the origin and significance of the gender difference in pHVA are indicated.

Oral choline supplementation in children with intestinal failure.

PubMed

Guerrerio, Anthony L; Mattis, Lynn; Conner, Kim G; Hampsey, Jenifer; Stasinopoulos, D Mikis; DeJong, Robert; Boctor, Emad M; Sheth, Shelia; Hamper, Ulrike M; Scheimann, Ann O

2011-07-01

Choline deficiency leads to steatohepatitis, elevated transaminases, susceptibility to septic shock, and an increased risk of central catheter thrombosis. Children with intestinal failure (IF) are at risk for choline deficiency. In an unblinded, open-label study, we studied 7 children with IF on parenteral nutrition, measured their plasma free choline level, and, if low, supplemented enterally with adequate intake (AI) doses of choline. Four to 6 weeks later we remeasured their plasma free choline. Unlike adults, infants did not respond to oral choline supplementation at AI doses. Additionally, we have calculated plasma free choline percentiles versus age for normal children.

CSF and plasma testosterone in attempted suicide.

PubMed

Stefansson, Jon; Chatzittofis, Andreas; Nordström, Peter; Arver, Stefan; Åsberg, Marie; Jokinen, Jussi

2016-12-01

Very few studies have assessed testosterone levels in the cerebrospinal fluid in suicide attempters. Aggressiveness and impulsivity are common behavioural traits in suicide attempters. Dual-hormone serotonergic theory on human impulsive aggression implies high testosterone/cortisol ratio acting on the amygdala and low serotonin in the prefrontal cortex. Our aim was to examine the CSF and plasma testosterone levels in suicide attempters and in healthy volunteers. We also assessed the relationship between the testosterone/cortisol ratio, aggressiveness and impulsivity in suicide attempters. 28 medication-free suicide attempters and 19 healthy volunteers participated in the study. CSF and plasma testosterone sulfate and cortisol levels were assessed with specific radio-immunoassays. The Karolinska Scales of Personality was used to assess impulsivity and aggressiveness. All patients were followed up for cause of death. The mean follow-up period was 21 years. Male suicide attempters had higher CSF and plasma testosterone levels than age- matched male healthy volunteers. There were no significant differences in CSF testosterone levels in female suicide attempters and healthy female volunteers. Testosterone levels did not differ significantly in suicide victims compared to survivors. In male suicide attempters, the CSF testosterone/cortisol ratio showed a significant positive correlation with both impulsivity and aggressiveness. Higher CSF testosterone levels may be associated with attempted suicide in young men through association with both aggressiveness and impulsivity, a key endophenotype in young male suicide attempters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Employment status and heart disease risk factors in middle-aged women: the Rancho Bernardo Study.

PubMed Central

Kritz-Silverstein, D; Wingard, D L; Barrett-Connor, E

1992-01-01

BACKGROUND. In recent years, an increasing number of women have been entering the labor force. It is known that in men, employment is related to heart disease risk, but there are few studies examining this association among women. METHODS. The relation between employment status and heart disease risk factors including lipid and lipoprotein levels, systolic and diastolic blood pressure, fasting and postchallenge plasma glucose and insulin levels, was examined in 242 women aged 40 to 59 years, who were participants in the Rancho Bernardo Heart and Chronic Disease Survey. At the time of a follow-up clinic visit between 1984 and 1987, 46.7% were employed, primarily in managerial positions. RESULTS. Employed women smoked fewer cigarettes, drank less alcohol, and exercised more than unemployed women, but these differences were not statistically significant. After adjustment for covariates, employed women had significantly lower total cholesterol and fasting plasma glucose levels than unemployed women. Differences on other biological variables, although not statistically significant, also favored the employed women. CONCLUSIONS. Results of this study suggest that middle-aged women employed in managerial positions are healthier than unemployed women. PMID:1739150

Cerebral Folate Deficiency

ERIC Educational Resources Information Center

Gordon, Neil

2009-01-01

Cerebral folate deficiency (CFD) is associated with low levels of 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) with normal folate levels in the plasma and red blood cells. The onset of symptoms caused by the deficiency of folates in the brain is at around 4 to 6 months of age. This is followed by delayed development, with deceleration…

[Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol].

PubMed

Robaczyk, Maciej G

2002-01-01

The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk when compared to OTY subjects. Absolute LEP levels were correlated with trunk BF in CUS patients whereas in KON and AD groups these levels were correlated only with limb fat. Absolute LEP levels in CUS and OTY groups were comparable, whereas LEP/BFM and LEP/%BF indices were higher in the CUS group (Table 1) reflecting upregulation of LEP levels (Figs. 1, 2). BFM-corrected LEP levels were comparable in groups with normal cortisolemia, i.e. in OTY and KON groups, whereas in the AD group both absolute and BFM-corrected LEP levels were lower than in controls. No correlation was found between plasma levels of F and LEP in CUS and AD groups. This correlation was negative in KON (Fig. 3) and positive in OTY groups (Fig. 4). Moreover, KON and AD groups demonstrated a negative correlation between plasma ACTH and LEP levels. CUS patients showed positive, BFM-independent correlations between LEP levels, FIRI and G values, and a positive, BFM-dependent correlation between IRI and LEP levels. OTY patients exhibited a BFM-dependent positive correlation between FIRI and LEP levels. In these and in AD patients, a positive, BFM-independent correlation between IRI and LEP levels was found. Moreover, a negative, BFM-dependent correlation between GH and LEP levels was found in OTY patients. In this group, B-EP levels were positively correlated with LEP/BFM and LEP/%BF indices (Fig. 5). A negative correlation between LEP levels, LEP/BFM and LEP/%BF indices was ascertained in the AD group. In CUS, OTY, and KON groups, but not in the AD group, a midnight increase in leptin levels was observed. In conclusion, upregulation of leptin levels in relation to body fat in Cushing's syndrome is independent of the source of hypercortisolism. Apparently, it results from insulin resistance and hyperglycaemia and contributes to coexisting metabolic abnormalities. In Addison's disease, downregulation of leptin may reflect an adaptation mechanism to cortisol deficiency and result from low insulin and extremely high adrenocorticotrophin levels. In women with normal cortisol levels, irrespectively of nutritional status; leptin levels reflect body fat content. In obese subjects, leptin levels may be influenced by cortisol levels, high levels of insulin, IGF-1, and beta-endorphin as well as low levels of growth hormone. Disturbed function of hypothalamic-pituitary-adrenal axis (CUS, AD) does not directly influence diurnal variation in plasma leptin levels. In Cushing's syndrome, visceral fat may be a predominant source of leptin, whereas in women with normal or low cortisol levels peripherally accumulated fat may determine leptin secretion.

Pertinent plasma indicators of the ability of chickens to synthesize and store lipids.

PubMed

Baéza, E; Jégou, M; Gondret, F; Lalande-Martin, J; Tea, I; Le Bihan-Duval, E; Berri, C; Collin, A; Métayer-Coustard, S; Louveau, I; Lagarrigue, S; Duclos, M J

2015-01-01

Excessive deposition of body fat is detrimental to production efficiency. The aim of this study was to provide plasma indicators of chickens' ability to store fat. From 3 to 9 wk of age, chickens from 2 experimental lines exhibiting a 2.5-fold difference in abdominal fat content and fed experimental diets with contrasted feed energy sources were compared. The diets contained 80 vs. 20 g of lipids and 379 vs. 514 g of starch per kg of feed, respectively, but had the same ME and total protein contents. Cellulose was used to dilute energy in the high-fat diet. At 9 wk of age, the body composition was analyzed and blood samples were collected. A metabolome-wide approach based on proton nuclear magnetic resonance spectroscopy was associated with conventional measurements of plasma parameters. A metabolomics approach showed that betaine, glutamine, and histidine were the most discriminating metabolites between groups. Betaine, uric acid, triglycerides, and phospholipids were positively correlated (r > 0.3; P < 0.05) and glutamine, histidine, triiodothyronine, homocysteine, and β-hydroxybutyrate were negatively correlated (r < -0.3; P < 0.05) with relative weight of abdominal fat and/or fat situated at the top of external face of the thigh. The combination of plasma free fatty acids, total cholesterol, phospholipid, β-hydroxybutyrate, glutamine, and methionine levels accounted for 74% of the variability of the relative weight of abdominal fat. On the other hand, the combination of plasma triglyceride and homocysteine levels accounted for 37% of the variability of fat situated at the top of external face of the thigh. The variations in plasma levels of betaine, homocysteine, uric acid, glutamine, and histidine suggest the implication of methyl donors in the control of hepatic lipid synthesis and illustrate the interplay between AA, glucose, and lipid metabolisms in growing chickens.

Interaction of SNP in the CRP gene and plasma fatty acid profile in inflammatory pattern: A cross-sectional population-based study.

PubMed

Oki, Erica; Norde, Marina M; Carioca, Antônio A F; Ikeda, Renata E; Souza, José M P; Castro, Inar A; Marchioni, Dirce M L; Fisberg, Regina M; Rogero, Marcelo M

2016-01-01

To assess the interaction of three single nucleotide polymorphisms in the C-reactive protein (CRP) gene and plasma fatty acid (FA) levels in modulating inflammatory profile. A total of 262 subjects, aged >19 y and <60 y, participated in a cross-sectional, population-based study performed in Brazil. Three single nucleotide polymorphisms (rs1205, rs1417938, and rs2808630) spanning the CRP gene were genotyped. Eleven plasma inflammatory biomarkers and plasma FA profile were determined. Cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups: an inflammatory (INF) and a noninflammatory group. The INF cluster had higher age, waist circumference, systolic blood pressure, and diastolic blood pressure; higher levels of triacylglycerol, high-sensitivity CRP, tumor necrosis factor-α, interleukin (IL)-8, IL-6, IL-1β, IL-12, IL-10, soluble monocyte chemoattractant protein-1, soluble intercellular adhesion molecule-1, C16:0, polyunsaturated fatty acid, and omega (n)-6 polyunsaturated fatty acid; and greater C20:4n-6, C18:1/18:0, and C20:4/20:3 ratios than the noninflammatory group. Statistically significant gene-plasma C16:1n-7 interaction was detected for rs1417938 (P = 0.047). Those with a dominant homozygous rs2808630 had a lower risk of belonging to the INF group with the upper 50th percentile of C20:4n-6, n-3 highly unsaturated FA, and C20:4/20:3 ratio. Regarding rs1205, A allele carriers had lower risk of being in the INF group when C20:5n-3 and n-3 highly unsaturated FA levels were greater than the median. The INF group exhibited changes in metabolic parameters that predispose this group to chronic disease, where polymorphisms in the CRP gene modulated the risk of being in the INF group depending on individual plasma fatty acid and lipid profile. Copyright © 2016 Elsevier Inc. All rights reserved.

Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution.

PubMed

Calderón-Garcidueñas, Lilian; Vincent, Renaud; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Garrido-García, Luis; Camacho-Reyes, Laura; Valencia-Salazar, Gildardo; Paredes, Rogelio; Romero, Lina; Osnaya, Hector; Villarreal-Calderón, Rafael; Torres-Jardón, Ricardo; Hazucha, Milan J; Reed, William

2007-08-01

Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O(3) that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. We conducted a study of 81 children, 7.9 +/- 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O(3) levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 mum in aerodynamic diameter (PM(2.5)) before endothelin-1 measurement (p = 0.03). Chronic exposure of children to PM(2.5) is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure.

Elevated cytokine and chemokine levels in the placenta are associated with in-utero HIV-1 mother-to-child transmission.

PubMed

Kumar, Surender B; Rice, Cara E; Milner, Danny A; Ramirez, Nilsa C; Ackerman, William E; Mwapasa, Victor; Turner, Abigail Norris; Kwiek, Jesse J

2012-03-27

To determine whether there is an association between cytokine and chemokine levels in plasma isolated from the placenta and HIV-1 mother-to-child transmission (MTCT). We designed a case-control study of HIV-infected, pregnant women enrolled in the Malaria and HIV in Pregnancy cohort. Participants were recruited in Blantyre, Malawi, from 2000 to 2004. Patients were women whose children were HIV-1 DNA-positive at birth (in-utero MTCT) or HIV-1 DNA-negative at birth and HIV-1 DNA-positive at 6 weeks postpartum (intrapartum MTCT); controls were women whose children were HIV-1 DNA-negative both at birth and 6 weeks postpartum. After delivery, blood was isolated from an incision on the basal plate of the placenta. We used a Bio-Plex human cytokine assay (Bio-Rad, Hercules, California USA) to simultaneously quantify 27 cytokines, chemokines and growth factors in placental plasma. HIV-1 RNA copies were quantified with the Roche Amplicor kit. Levels of interleukin (IL) 4, IL-5, IL-6, IL-7, IL-9, eotaxin, IL-1Ra and interferon gamma-induced protein 10 (IP-10) were significantly elevated in placental plasma isolated from cases of in-utero HIV-1 MTCT. In contrast, only granulocyte colony-stimulating factor was elevated in placental plasma isolated from cases of intrapartum MTCT. After adjusting for maternal age, gestational age and peripheral CD4(+) T-cell count, every log(10) increase in placental IP-10 was associated with a three-fold increase in the prevalence of in-utero HIV-1 MTCT. Elevated cytokine and chemokine levels in placental plasma were associated with in-utero and not intrapartum MTCT. IP-10, which is both a T-cell chemokine and potentiator of HIV-replication, was robustly and independently associated with prevalent, in-utero MTCT.

Childhood Chronic Physical Aggression Associates with Adult Cytokine Levels in Plasma

PubMed Central

Provençal, Nadine; Suderman, Matthew J.; Vitaro, Frank; Szyf, Moshe; Tremblay, Richard E.

2013-01-01

Background An increasing number of animal and human studies are indicating that inflammation is associated with behavioral disorders including aggression. This study investigates the association between chronic physical aggression during childhood and plasma cytokine levels in early adulthood. Methodology/Principal Findings Two longitudinal studies were used to select males on a chronic physical aggression trajectory from childhood to adolescence (n = 7) and a control group from the same background (n = 25). Physical aggression was assessed yearly by teachers from childhood to adolescence and plasma levels of 10 inflammatory cytokines were assessed at age 26 and 28 years. Compared to the control group, males on a chronic physical aggression trajectory from childhood to adolescence had consistently lower plasma levels of five cytokines: lower pro-inflammatory interleukins IL-1α (T(28.7) = 3.48, P = 0.002) and IL-6 (T(26.9) = 3.76, P = 0.001), lower anti-inflammatory interleukin IL-4 (T(27.1) = 4.91, P = 0.00004) and IL-10 (T(29.8) = 2.84, P = 0.008) and lower chemokine IL-8 (T(26) = 3.69, P = 0.001). The plasma levels of four cytokines accurately predicted aggressive and control group membership for all subjects. Conclusions/Significance Physical aggression of boys during childhood is a strong predictor of reduced plasma levels of cytokines in early adulthood. The causal and physiological relations underlying this association should be further investigated since animal data suggest that some cytokines such as IL-6 and IL-1β play a causal role in aggression. PMID:23922720

No effect of pinealectomy on the parallel shift in circadain rhythms of adrenocortical activity and food intake in blinded rats.

PubMed

Takahashi, K; Inoue, K; Takahashi, Y

1976-10-01

Twenty-four-hr patterns of plasma corticosterone levels were determined at 4-hr intervals every 3-4 weeks in sighted and blinded pinealectomized rats of adult age. Through the whole period of the experiment, 24-hr patterns of food intake were also measured weekly. The sighted rats manifested the same 24-hr patterns of plasma corticosterone levels and food intake for 15 weeks after pinealectomy as those observed in the intact control rats. The magnitude of peak levels of plasma corticosterone and the amount of food intake did not differ between the two groups. A phase shift in circadian rhythms of plasma corticosterone levels and food intake was observed in both groups of blinded rats, with and without pinealectomy. Between the two groups, the patterns of phase shift were essentially similar for 10 weeks examined after optic enucleation. The peak elevation of plasma levels took place at 11 p.m. at the end of the 4th week after optic enucleation. Thereafter, 4- to 8-hr delay of peak appearance was observed every 3 weeks. No significant differences were found in peak values between the two groups of blinded rats. Furthermore, the circadian rhythm of food intake shifted in parallel with that of plasma corticosterone levels. A phase reversal of these two activities was observed between the 8th and 10th week after the operation. These results indicate that the pineal gland does not play any important role either in the maintenance of normal circadian periodicities of adrenocortical activity and food intake or in the shift in circadian rhythms of the two activities in the blinded rats.

Effects of climatic factors on plasma lipid levels: A 5-year longitudinal study in a large Chinese population.

PubMed

Zhou, Xiaoming; Lin, Haiyan; Zhang, Shigang; Ren, Jianwei; Wang, Zhe; Zhang, Yun; Wang, Mansen; Zhang, Qunye

2016-01-01

The rules and mechanisms of seasonal changes in plasma lipid levels, which may be related to annual rhythmicity of incidence and mortality of cardiovascular diseases, are still controversial. The objectives of this study were to study the effects of climatic factors on plasma lipid levels and to preliminarily reveal mechanisms of annual rhythmicity of plasma lipid levels. A longitudinal study was performed using health examination data of 5 consecutive years (47,270 subjects) in Jinan, China. The climate in Jinan is typical temperate continental monsoon climate with huge temperature difference between winter and summer (>30°C). After considering and adjusting those classical lipid-associated risk factors, such as age, gender, diet, exercise, blood pressure, body weight, change of body weight, body mass index, glycemia, alanine aminotransferase, and creatinine, only air temperature could still significantly affect plasma lipid levels among the main climatic factors (humidity, precipitation, and so forth). For men, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was decreased significantly 0.35, 0.18, and 0.06 mmol/L, respectively, whereas triglyceride was increased significantly 0.12 mmol/L for every 10°C increase in air temperature. For women, total cholesterol and high-density lipoprotein cholesterol were decreased notably 0.73 and 0.32 mmol/L, and low-density lipoprotein cholesterol was increased significantly 0.26 mmol/L for every 10°C increase in air temperature, whereas triglyceride was not significantly affected by air temperature. Air temperature is an independent risk factor for plasma lipid levels besides those classical lipid-associated risk factors. The annual air temperature fluctuations might be an important mechanism of the seasonal changes of lipids. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Effect of intermittent glutamine supplementation on skeletal muscle is not long-lasting in very old rats.

PubMed

Meynial-Denis, D; Beaufrère, A-M; Mignon, M; Patureau Mirand, P

2013-01-01

Muscle is the major site for glutamine synthesis via glutamine synthetase (GS). This enzyme is increased 1.5-2 fold in 25-27-mo rats and may be a consequence of aging-induced stress. This stimulation is similar to the induction observed following a catabolic state such as glucocorticoid treatment (6 to 24 months). Although oral glutamine supply regulates the plasma glutamine level, nothing is known if this supplementation is interrupted before the experiment. Adult (8-mo) and very old (27-mo) female rats were exposed to intermittent glutamine supplementation for 50 % of their age lifetime. Treated rats received glutamine added to their drinking water and control rats water alone but the effect of glutamine supplementation was only studied 15 days after the last supplementation. Glutamine pretreatment discontinued 15 days before the experiment increased plasma glutamine to ~ 0.6 mM, a normal value in very old rats. However, it failed to decrease the up-regulated GS activity in skeletal muscle from very old rats. Our results suggest that long-term treatment with glutamine started before advanced age but discontinued 15 days before rat sacrifice is effective in increasing plasma glutamine to recover basal adult value and in maintaining plasma glutamine in very old rats, but has no long-lasting effect on the GS activity of skeletal muscle with advanced age.

Plasma amyloid levels within the Alzheimer's process and correlations with central biomarkers.

PubMed

Hanon, Olivier; Vidal, Jean-Sébastien; Lehmann, Sylvain; Bombois, Stéphanie; Allinquant, Bernadette; Tréluyer, Jean-Marc; Gelé, Patrick; Delmaire, Christine; Blanc, Fredéric; Mangin, Jean-François; Buée, Luc; Touchon, Jacques; Hugon, Jacques; Vellas, Bruno; Galbrun, Evelyne; Benetos, Athanase; Berrut, Gilles; Paillaud, Elèna; Wallon, David; Castelnovo, Giovanni; Volpe-Gillot, Lisette; Paccalin, Marc; Robert, Philippe-Henri; Godefroy, Olivier; Dantoine, Thierry; Camus, Vincent; Belmin, Joël; Vandel, Pierre; Novella, Jean-Luc; Duron, Emmanuelle; Rigaud, Anne-Sophie; Schraen-Maschke, Suzanna; Gabelle, Audrey

2018-02-17

Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aβ 42 and Aβ 40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers. One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included. Plasma Aβ 1-42 and Aβ 1-40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aβ 1-42 and P = .04 for Aβ 1-40 ). Globally, plasma Aβ 1-42 correlated with age, Mini-Mental State Examination, and APOE ε4 allele. Plasma Aβ 1-42 correlated with all CSF biomarkers in MCI but only with CSF Aβ 42 in AD. Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of early adolescent methamphetamine exposure on anxiety-like behavior and corticosterone levels in mice.

PubMed

Rud, Micaela A; Do, Thao N; Siegel, Jessica A

2016-10-28

Methamphetamine (MA) is an addictive psychomotor stimulant that affects the central nervous system and alters behavior. The effects of MA are modulated by age, and while much research has examined the effects of MA use in adults, relatively little research has examined the effects in adolescents. As the brain is developing during adolescence, it is important that we understand the effects of MA exposure in adolescence. This research examined the effects of acute MA exposure on locomotor and anxiety-like behavior in the open field test and plasma corticosterone levels in adolescent male C57BL/6J mice. Baseline locomotor and anxiety-like behaviors were assessed in the open field test. Immediately following baseline measurements, mice were exposed to saline or 4mg/kg MA and locomotor and anxiety-like behavior were measured. Serum was collected immediately after testing and plasma corticosterone levels measured. There were no group differences in baseline behavioral measurements. MA-exposed adolescent mice showed increased locomotor activity and anxiety-like behavior in the open field compared with saline controls. There was no effect of MA on plasma corticosterone levels. These data suggest that acute MA exposure during adolescence increases locomotor activity and anxiety-like behavior, but does not alter plasma corticosterone levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Study of telomere length and different markers of oxidative stress in patients with Parkinson's disease.

PubMed

Watfa, G; Dragonas, C; Brosche, T; Dittrich, R; Sieber, C C; Alecu, C; Benetos, A; Nzietchueng, R

2011-04-01

Many studies have shown that short telomere length (TL) is associated with high oxidative stress and various age-related diseases. Parkinson's disease (PD) is an age-related disease, and although its pathogenic mechanism is uncertain, oxidative stress is believed to be implicated in this pathology. The aim of this case-control study was to assess both TL and the different markers of oxidative stress in elderly patients with PD compared to age control subjects. 20 PD patients and 15 age-matched controls, >65 years were studied. TL was measured by Southern blotting from DNA samples extracted from white blood cells. Superoxide dismutase (SOD) activity and plasma levels of total glutathione and protein carbonyls were determined. There was a trend for lower TL in PD patients: 6.06 ± 0.81 kb in PD versus 6.45 ± 0.73 kb in controls (p = 0.08). No significant difference was found between the two groups in terms of oxidative stress markers. In controls, age was the main determinant of telomere shortening (r = -0.547; p = 0.03) whereas, in PD patients, telomere shortening was mainly dependent on plasmatic concentrations of carbonyl proteins (r= -0.544; p=0.044). In PD patients, a negative association was observed between plasma carbonyl protein levels and SOD activity (r= -0.622, p=0.004). In PD, TL is shorter in presence of high oxidative stress as measured by carbonyl protein levels. The absence of telomere attrition with age among patients with PD could reflect a telomere regulation by mechanisms other than age.

Plasma glycoprotein V levels in the general population: normal distribution, associated parameters and implications for clinical studies.

PubMed

Aleil, Boris; Meyer, Nicolas; Wolff, Valérie; Kientz, Daniel; Wiesel, Marie-Louise; Gachet, Christian; Cazenave, Jean-Pierre; Lanza, François

2006-10-01

Soluble glycoprotein V (sGPV) is a new plasma marker of thrombosis released from the platelet surface by thrombin. sGPV levels are increased in patients with atherothrombotic diseases, but the determinants of sGPV levels are unknown in the general population. Identification of these potential confounding factors is needed for correct design and analysis of clinical studies on cardiovascular diseases. The aim of this study was to determine the normal range of plasma values and the factors controlling sGPV levels in a population of normal individuals. Three hundred blood donors were recruited at the Etablissement Français du Sang-Alsace for the measurement of plasma levels of sGPV, platelet factor 4 (PF4), thrombin-antithrombin complexes (TAT) and D-dimers. The plasma level of sGPV was (median [interquartile range]) 27.5 [23.5-34.4] microg/l and displayed a Gaussian distribution. sGPV had a lower interindividual coefficient of variation (33%) than PF4 (176%), TAT (87%) or D-dimers (82%). sGPV levels were independent of age and sex but sensitive to red cell (r = 0.412; p < 0.0001) and platelet counts (r = 0.267; p = 0.001), total cholesterol (r = -0.313; p < 0.0001), food intake (r = 0.184; p = 0.0014) and smoking (r = -0.154; p = 0.039). Contrary to PF4 and TAT, sGPV did not differ between venous and arterial blood samples of 12 healthy individuals. Red cell and platelet counts, total cholesterol, current smoking and recent food intake are important determinants of sGPV levels and must be taken into account in clinical studies using sGPV as a thrombosis marker. Normal distribution of sGPV levels in the general population supports its use in clinical applications.

Soluble Suppression of Tumorigenicity-2 Predicts Hospital Mortality in Burn Patients: An Observational Prospective Cohort Pilot Study.

PubMed

Ruiz-Castilla, Mireia; Bosacoma, Pau; Dos Santos, Bruce; Baena, Jacinto; Guilabert, Patricia; Marin-Corral, Judith; Masclans, Joan R; Roca, Oriol; Barret, Juan P

2018-04-10

The IL33/ST2 pathway has been implicated in the pathogenesis of different inflammatory diseases. Our aim was to analyze whether plasma levels of biomarkers involved in the IL33/ST2 axis might help to predict mortality in burn patients. Single-center prospective observational cohort pilot study performed at the Burns Unit of the Plastic and Reconstructive Surgery Department of the Vall d'Hebron University Hospital (Barcelona). All patients aged ≥18 years old with second or third-degree burns requiring admission to the Burns Unit were considered for inclusion. Blood samples were taken to measure levels of interleukins (IL)6, IL8, IL33, and soluble suppression of tumorigenicity-2 (sST2) within 24 h of admission to the Burns Unit and at day 3. Results are expressed as medians and interquartile ranges or as frequencies and percentages. Sixty-nine patients (58 [84.1%] male, mean age 52 [35-63] years, total body surface area burned 21% [13%-30%], Abbreviated Burn Severity Index 6 [4-8]) were included. Thirteen (18.8%) finally died in the Burns Unit. Plasma levels of sST2 measured at day 3 after admission demonstrated the best prediction accuracy for survival (area under the ROC curve 0.85 [0.71-0.99]; P < 0.001). The best cutoff point for the AUROC index was estimated to be 2,561. In the Cox proportional hazards model, after adjusting for potential confounding, a plasma sST2 level ≥2,561 measured at day 3 was significantly associated with mortality (HR 6.94 [1.73-27.74]; P = 0.006). Plasma sST2 at day 3 predicts hospital mortality in burn patients.

Effects on the immune system associated with living near a pesticide dump site.

PubMed Central

Vine, M F; Stein, L; Weigle, K; Schroeder, J; Degnan, D; Tse, C K; Hanchette, C; Backer, L

2000-01-01

In this paper, we report results of the second phase of a larger study designed to evaluate the effects on the immune system of living near a Superfund site containing organochlorine pesticides, volatile organic compounds, and metals. Phase II was conducted to determine whether living near the site, consisting of six locations in Aberdeen, North Carolina, is associated with higher plasma organochlorine levels, immune suppression, or DNA damage. Each of 302 residents of Aberdeen and neighboring communities provided a blood specimen, underwent a skin test, and answered a questionnaire. Blood specimens were analyzed for organochlorine pesticides, immune markers, and micronuclei. Of 20 organochlorines tested, only DDE was detected in the blood of participants (except for one individual). Age-adjusted mean plasma DDE levels were 4.05 ppb for Aberdeen residents and 2.95 ppb (p = 0.01) for residents of neighboring communities. Residents of 40-59 years of age who lived within a mile of any site, but particularly the Farm Chemicals site, had higher plasma DDE levels than residents who lived farther away. Residents who lived near the Farm Chemicals site before versus after 1985 also had higher plasma DDE levels. Overall, there were few differences in immune markers between residents of Aberdeen and the neighboring communities. However, residents who lived closer to the dump sites had statistically significantly lower mitogen-induced lymphoproliferative activity than residents who lived farther away (p < 0.05). Residential location was not consistently associated with frequency of micronuclei or skin test responses. Although some statistically significant differences in immune markers were noted in association with residential location, the magnitude of effects are of uncertain clinical importance. PMID:11133390

Interaction of dietary vitamin E with Eimeria maxima infections in chickens.

PubMed

Allen, P C; Fetterer, R H

2002-01-01

In two trials, broiler chickens, processed similarly to those placed in commercial operation, were fed, from 1 d of age, a range (13 to 200 ppm) of DL-alpha-tocopheryl acetate (VE-AC) levels, and the effects on the pathology of Eimeria maxima infections were assessed at 6 d postinoculation (PI). In Trial 1, dietary levels of VE-AC had little significant effect on variables characterizing pathology except for the number of oocysts shed, which was significantly increased in chicks treated with higher VE-AC levels. The infection was judged to be mild based on moderate lesion scores (2.2+/-0.2), lack of significant effects on weight gain (7+/-1.6% decrease), moderate reduction in plasma carotenoids (21+/-2%) and small increases in plasma NO2-+NO3- (141+/-12%). In uninfected and infected chickens, plasma alpha-tocopherol (AT) increased with dietary levels of VE-AC; however, E. maxima infection caused a fairly constant decrease in AT of 35.3+/-3.2% across these levels. Plasma gamma-tocopherol (GT) levels were unaffected by dietary VE-AC or E. maxima infection. In Trial 2, pathology, again, was relatively unaffected by dietary VE-AC level. The infection was judged to be severe based on lesion scores (3.5+/-0.1), reduction in weight gain (30.7+/-3%), plasma carotenoids (72.4+/-1.5%), uric acid (16.3+/-3.4), albumin (37.8+/-2.8%), large increases (261+/-8%) in plasma NO2-+NO3-, and high numbers of oocysts shed per chick (4.12+/-0.4 x 10(7)). Plasma AT again increased with increasing dietary VE-AC levels in uninfected and infected chicks, but the mean decrease across VE-AC levels caused by E. maxima infection was 73.14+/-3.3%. GT levels were erratic and unrelated to dietary VEAC or infection. Thus, in processed broiler chickens, high dietary VE-AC did not prevent or lessen the pathology caused by mild or severe infections with E. maxima. The main effect of E. maxima infection appeared to be reduction in plasma AT levels. We postulate that this reduction may be due to malabsorption of AT, which results from physical damage to the absorptive mucosa, reduction in esterases required to hydrolyze the VE-AC, and a generalized lipid malabsorption, preventing movement of the free AT to circulating blood and infected tissues.

Vascular endothelial growth factor levels and rheumatic diseases of the elderly.

PubMed

Smets, Perrine; Devauchelle-Pensec, Valérie; Rouzaire, Paul-Olivier; Pereira, Bruno; Andre, Marc; Soubrier, Martin

2016-12-01

Increasing vascular endothelial growth factor (VEGF) has been reported in remitting symmetrical seronegative synovitis with pitting edema (RS3PE) syndrome, rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). The aim of this study was to compare VEGF levels in patients over 60 years of age who have RS3PE, RA, PMR or GCA so as to determine whether elevated VEGF is specific for a rheumatic disease, the inflammation or edema that occurs with these pathological conditions. In this retrospective, multicentric study we assessed serum and plasma levels of VEGF in patients over 60 years of age with rheumatic diseases that were either de novo or of recent onset according to the initial clinical presentation, and we compared these patients with a control group. Serum and plasma VEGF levels were determined in 80 patients (5 with RS3PE, 13 with RA, 44 with PMR, and 18 with GCA) and 37 controls. Edema occurred in five patients with RS3PE, four with RA, and one with PMR, but not patients with GCA. Serum VEGF levels were significantly higher in individuals with rheumatic diseases (849 (405.5-1235.5) pg/ml) relative to the controls (484 (302-555) pg/ml) (p < 0.001). There were no significant differences between patients with RS3PE, RA, PMR, or GCA in terms of the VEGF serum levels (p = 0.60) or plasma levels (p = 0.57). Similarly, the occurrence of edema did not correlate with VEGF levels. VEGF increases in rheumatic diseases compared to a control group. This was not associated with specific rheumatic diseases or with edematous rheumatic diseases.

Smoking habits and plasma lipid peroxide and vitamin E levels in never-treated first-episode patients with schizophrenia.

PubMed

2000-03-01

Lipid peroxidation may be increased in schizophrenia, due to the illness, lifestyle or medication. To determine plasma lipid peroxide levels and serum vitamin E and A levels in first-episode never-treated people with schizophrenia and in controls. Thirty in-patients with a first episode of schizophrenia or schizophreniform psychosis were recruited, as were controls matched for gender, age, smoking and dietary status. Blood samples were taken, smoking status was recorded and body mass index measured. There were no significant differences between patients and controls in plasma peroxide levels. Seventy-three per cent of the patients smoked. Patients who smoked had a higher mean lipid peroxide level than non-smokers. Seventy-seven per cent of patients and 70% of controls had a ratio of vitamin E to cholesterol of less than 5. Body mass index was lower in patients than in controls. As a result of the high prevalence of smoking this group shows increased lipid peroxidation. Low serum ratios of vitamin E to cholesterol in both patients and controls suggest an unsatisfactory diet.

Plasma Chemerin Levels Are Increased in ST Elevation Myocardial Infarction Patients with High Thrombus Burden.

PubMed

Ateş, Ahmet Hakan; Arslan, Uğur; Aksakal, Aytekin; Yanık, Ahmet; Özdemir, Metin; Kul, Selim

2018-01-01

To investigate plasma chemerin levels in ST elevation myocardial infarction (STEMI) patients and find out possible relationships between plasma chemerin levels and angiographic characteristics. Ninety-seven consecutive patients who presented with STEMI and underwent primary percutaneous coronary intervention (PCI) with coronary stents were enrolled, and 30 age- and sex-matched patients with stable angina pectoris who underwent coronary angiography formed the control group. Angiographic characteristics of the patients including thrombolysis in myocardial infarction (TIMI) thrombus and Gensini scores were noted. Blood samples were taken to detect several biochemical markers including plasma chemerin levels at the admission to hospital. Serum chemerin and C-reactive protein (CRP) levels were significantly increased in patients with STEMI. Among STEMI patients, serum chemerin levels were significantly higher in patients with high thrombus burden (581.5 ± 173.7 versus 451.3 ± 101.2 mg/dL, p < 0.001). CRP levels and peak creatine kinase-MB (CK-MB) levels were higher, and left ventricular ejection fraction and post-PCI TIMI flow were lower in patients with high thrombus burden. After multivariate analysis, serum chemerin levels were also higher in patients with high thrombus grade (odds ratio: 1.009 (1.005-1.014), p < 0.001). Besides, serum chemerin levels were also found to be significantly correlated with CRP ( r =0.47, p < 0.001) and peak CK-MB ( r =0.376, p < 0.001) levels. Results from our study have demonstrated for the first time that chemerin levels were higher in STEMI patients with greater thrombus burden and higher level of inflammation.

Unexpected lower testosterone in faster growing farmed saltwater crocodile (Crocodylus porosus) hatchlings.

PubMed

Finger, John W; Thomson, Peter C; Isberg, Sally R

2016-01-15

Agricultural production of the saltwater crocodile (Crocodylus porosus) is an emergent industry in northern Australia with many of the factors affecting production remaining unknown. In this study, we sought to expand upon our previous findings of reference corticosterone and immune function by reporting baseline sex hormone levels [testosterone (TEST) and estradiol (ESTR)] and their association with growth. This was achieved by sampling 253 hatchling crocodiles repeatedly at 3, 6, and 9months of age. Sampling age had a significant effect on both TEST (p<0.001) and ESTR (p<0.001) suggesting climatic/abiotic factors have an influence even in prepubescent crocodiles. Stress, as measured by plasma corticosterone, had no detectable effect on plasma ESTR or TEST levels. Unexpectedly however, TEST was higher in slower-growing crocodiles, which is contrary to what has been reported for the American alligator. ESTR was not associated with growth. Copyright © 2015 Elsevier Inc. All rights reserved.

Plasma Levels of Soluble Interleukin 1 Receptor Accessory Protein Are Reduced in Obesity

PubMed Central

Attard, Chantal; Kulkarni, Hemant; Cummings, Nik; Diego, Vincent P.; Carless, Melanie A.; Shields, Katherine A.; Johnson, Matthew P.; Kowlessur, Sudhir; Dyer, Thomas D.; Comuzzie, Anthony G.; Almasy, Laura; Zimmet, Paul; Moses, Eric K.; Göring, Harald H. H.; Curran, Joanne E.; Blangero, John; Jowett, Jeremy B. M.

2014-01-01

Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity. The pathogenetic and clinical influences of sIL1RAP are unknown. Objective: The objective of the study was to elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts. Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230). Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study. Results: A significant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM_134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 × 10−23) within the IL1RAP gene. Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity. PMID:24915116

Association Between Plasma Level of Galectin-9 and Survival of Patients With Drug-Induced Acute Liver Failure.

PubMed

Rosen, Hugo R; Biggins, Scott W; Niki, Toshiro; Gralla, Jane; Hillman, Holly; Hirashima, Mitsuomi; Schilsky, Michael; Lee, William M

2016-04-01

Fewer than 50% of patients with acute liver failure (ALF) recover spontaneously, and ALF has high mortality without liver transplantation. Kupffer cells have been reported to mediate liver inflammation during drug-induced injury. Galectin-9 is produced by Kupffer cells and has diverse roles in regulating immunity. We investigated whether plasma levels of galectin-9 are associated with outcomes of patients with ALF. We analyzed plasma samples (collected at time of hospital admission) and clinical data from 149 patients included in the Acute Liver Failure Study Group from July 2006 through November 2010 (110 had acetaminophen-induced hepatotoxicity and 39 had nonacetaminophen drug-induced liver injury). We compared data with those from all patients enrolled in the study (from July 1, 2006 through October 30, 2013), and from healthy individuals of similar ages with no evidence of liver disease (control subjects). Plasma levels of galectin-9 were measured using a polyclonal antibody and colorimetric assay. Patients with ALF had statistically higher plasma levels of galectin-9 than control subjects, but levels did not differ significantly between patients with acetaminophen-induced liver injury and drug-induced liver injury. A level of galectin-9 above 690 pg/mL was associated with a statistically significant increase in risk for mortality or liver transplantation caused by ALF. Competing risk analyses associated level of galectin-9 with transplant-free survival, independently of Model For End-Stage Liver Disease score or systemic inflammatory response syndrome. A one-time measurement of plasma galectin-9 level can be used to assign patients with ALF to high-, intermediate-, and low-risk groups. The combination of galectin-9 level and Model For End-Stage Liver Disease score was more closely associated with patient outcome than either value alone. These data might be used to determine patient prognoses and prioritize patients for liver transplantation. ClinicalTrials.gov ID NCT00518440. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Adipocyte Triglyceride Turnover Is Independently Associated With Atherogenic Dyslipidemia

PubMed Central

Frayn, Keith; Bernard, Samuel; Spalding, Kirsty; Arner, Peter

2012-01-01

Background Inappropriate storage of fatty acids as triglycerides in adipocytes and their removal from adipocytes through lipolysis and subsequent oxidation may cause the atherogenic dyslipidemia phenotype of elevated apolipoprotein B levels and subsequent hypertriglyceridemia. We tested whether turnover of triglycerides in fat cells was related to dyslipidemia. Methods and Results The age of triglycerides (reflecting removal) and triglyceride storage in adipocytes was determined under free living conditions by measuring incorporation of atmospheric 14C into these lipids within the adipocytes in 47 women and 26 men with a large interindividual variability in body mass index. Because limited 14C data were available, triglyceride age was also determined in 97 men and 233 women by using an algorithm based on adipocyte lipolysis, body fat content, waist‐to‐hip ratio, and insulin sensitivity. This cohort consisted of nonobese subjects since obesity per se is related to all components in the algorithm. Triglyceride turnover (age and storage) was compared with plasma levels of apolipoproteins and lipids. Plasma levels of apolipoprotein B and triglycerides were positively related to triglyceride age in adipocytes, when measured directly using radiocarbon analyses (r=0.45 to 0.47; P<0.0001). This effect was independent of subject age, waist circumference measures, and insulin sensitivity (partial r=0.29 to 0.45; P from 0.03 to <0.0001). Triglyceride storage showed no independent correlation (partial r=0.02 to 0.11; P=0.42 to 0.91). Algorithm‐based values for adipocyte removal of triglycerides were positively associated with plasma triglycerides and apolipoprotein B (r=0.44 to 0.45; P<0.0001) and (also positively) with the inflammation status of adipose tissue (r=0.39 to 0.47; P<0.05). These correlations were statistically independent of subject age and observed in men and women as well as in lean and overweight subjects when subgroups were examined separately. Conclusions Decreased removal of adipocyte triglycerides (as indicated by a high triglyceride age in fat cells) is independently associated with circulating apolipoprotein B and triglycerides. This suggests a hitherto unknown role of triglyceride turnover in adipocytes for the development and/or maintenance of atherogenic dyslipidemia. PMID:23316323

Higher Plasma Pyridoxal Phosphate Is Associated with Increased Antioxidant Enzyme Activities in Critically Ill Surgical Patients

PubMed Central

Cheng, Chien-Hsiang; Huang, Shih-Chien; Chiang, Ting-Yu; Wong, Yueching

2013-01-01

Critically ill patients experience severe stress, inflammation and clinical conditions which may increase the utilization and metabolic turnover of vitamin B-6 and may further increase their oxidative stress and compromise their antioxidant capacity. This study was conducted to examine the relationship between vitamin B-6 status (plasma and erythrocyte PLP) oxidative stress, and antioxidant capacities in critically ill surgical patients. Thirty-seven patients in surgical intensive care unit of Taichung Veterans General Hospital, Taiwan, were enrolled. The levels of plasma and erythrocyte PLP, serum malondialdehyde, total antioxidant capacity, and antioxidant enzyme activities (i.e., superoxide dismutase (SOD), glutathione S-transferase, and glutathione peroxidase) were determined on the 1st and 7th days of admission. Plasma PLP was positively associated with the mean SOD activity level on day 1 (r = 0.42, P < 0.05), day 7 (r = 0.37, P < 0.05), and on changes (Δ (day 7 − day 1)) (r = 0.56, P < 0.01) after adjusting for age, gender, and plasma C-reactive protein concentration. Higher plasma PLP could be an important contributing factor in the elevation of antioxidant enzyme activity in critically ill surgical patients. PMID:23819116

MicroRNA-134 plasma levels before and after treatment with valproic acid for epilepsy patients

PubMed Central

Wang, Xiaofeng; Luo, Yifeng; Liu, Shuangxi; Tan, Liming; Wang, Sanhu; Man, Rongyong

2017-01-01

Background Temporal lobe epilepsy is the second most common neurological disorders characterized by recurrent spontaneous seizures. MicroRNAs play a vital role in regulating synaptic plasticity, brain development and post-transcriptional expression of proteins. In both animal models of epilepsy and human patients, miR-134, a brain-specific microRNA has recently been identified as a potential regulator of epileptogenesis. Methods microRNA identified as targets for the actions of valproic acid (VPA) are known to have important effects in brain function. In this study, 59 new-onset epilepsy patients and 20 controls matched by sex and age were enrolled. Patients with a score < 3 were allocated into the mild group, 3-5 into the moderate group and >5 into the severe group. The plasma miRNA-134 level was quantitatively measured using real-time PCR. Results Plasma miRNA-134 level in new-onset epilepsy patients was significantly up-regulated when compared with that in healthy controls, and then considerably down-regulated after oral intake of valproic acid medication. The up-regulated plasma miRNA-134 levels may be directly associated with the pathophysiology and severity of epilepsy. Conclusion Plasma miRNA-134 in epilepsy may be considered as a potential peripheral biomarker that responds to the incidence of epilepsy and associates with use of anti-epilepsy drugs. PMID:29069823

Endothelial dysfunction in patients with coronary atherosclerosis.

PubMed

Chapidze, L; Kapanadze, S; Dolidze, N; Bakhutashvili, Z; Latsabidze, N

2007-01-01

It is well known that endothelial dysfunction as a nontraditional risk factor is an important early event in the pathogenesis of coronary atherosclerosis, contributing to plaque initiation and progression. In order to assess endothelial function plasma nitric oxide (NO) concentrations were determined. A total of 157 patients (119 men and 38 women, mean age 57+/-5,4 years) with coronary atherosclerosis were enrolled in the research. The study was cross-sectional in design. Most of the patients (n=127) had undergone myocardial revascularization procedures. There was statistically significant difference in mean values of plasma nitric oxide levels between patients with coronary atherosclerosis and healthy subjects (11,1+/-2,52 mkmol/L and 22,3+/-3,27 mkmol/L, respectively. p<0,01). Among all 157 patients only 17% had normal NO concentrations. In 59% cases low and in 24% cases high nitric oxide levels were found. Extent of coronary artery disease was associated with severity of endothelial dysfunction. The patients with three-vessel disease had the lowest mean plasma NO concentration. There was statistically significant negative correlation between mean plasma NO level and extent of coronary artery disease. Measurement of plasma nitric oxide concentration will give useful information for cardiologists, modification of abnormal levels of this parameter may delay progression of aggressive atherosclerotic process and thus, may prevent recurrent coronary events in patients with coronary atherosclerosis.

Dynamics of L-Carnitine in Plasma and Urine in Patients Undergoing Cisplatin Chemotherapy.

PubMed

Gomi, Daisuke; Tanaka, Aika; Fukushima, Toshirou; Kobayashi, Takashi; Matsushita, Hirohide; Sekiguchi, Nodoka; Sakamoto, Akiyuki; Sasaki, Shigeru; Mamiya, Keiko; Koizumi, Tomonobu

2017-01-01

Several studies have indicated that cisplatin (cis-diamminedichloroplatinum II; CDDP) causes urinary excretion of L-carnitine (LC). However, the underlying cofactors affecting the increased urinary excretion remain unclear. The present study was performed to evaluate the dynamics of LC in plasma and urine after CDDP chemotherapy and to examine the relations with clinical parameters, such as gender, body mass index (BMI), and renal function. Twenty-two patients treated with CDDP therapy were selected. Blood and urine samples were taken from patients before starting CDDP treatment (day 0), on the next day (day 1), and on the seventh day (day 7). We measured plasma and urine concentrations of total, free, and acyl-LC, and examined the relationships with gender, age, treatment cycle, skeletal muscle mass, BMI, glomerular filtration rate, and change in creatinine concentration after CDDP administration. Both urinary and plasma concentrations of 3 types of LC increased markedly on day 1 and subsequently reverted to the pre-CDDP level on day 7. There was a positive correlation between the % changes in plasma and urine LC (correlation coefficient 0.59, p = 0.003) on day 1, but no significant relations were seen in other clinical parameters. CDDP transiently increased plasma LC levels. The mechanism seemed to involve recruitment for marked urinary loss of LC. However, these changes in plasma and urinary LC levels were not related to clinical factors, suggesting that the dynamics of LC were independent of preexisting physical parameters. © 2017 S. Karger AG, Basel.

[Experimental and clinical evaluation of latamoxef in newborn and premature infants].

PubMed

Motohiro, T; Tanaka, K; Koga, T; Shimada, Y; Tomita, N; Sakata, Y; Fujimoto, T; Nishiyama, T; Ishimoto, K; Tominaga, K

1983-09-01

Latamoxef (LMOX) was administered as a one-shot intravenous injection of 10 mg/kg or 20 mg/kg to 28 newborn and immature infants of 1 to 28 days of age. For 6 hours following the administration, the concentrations of the drug in the plasma and in the urine were monitored and the urinary recovery rate was determined. In addition, 17 patients, consisting of newborns, immature infants and suckling infants, aged 0 days to 2 months and diagnosed as having various bacterial infections, were also treated with LMOX; the mean daily dosage was 103 mg/kg, administered in 2 to 6 divided doses as one-shot intravenous injections for an average duration of 11 days. These patients were subjected to the analysis for the clinical efficacy and bacteriological efficacy of the therapy. Furthermore, with the inclusion of 35 drop-out cases, a total of 52 patients was investigated for the occurrence of side effects by the LMOX therapy. The findings of these studies are summarized below. The patients were divided into 5 groups on the basis of age: 3 days old or less, 4--7 days, 8--14 days, 15--21 days and 22--28 days. Only in the 8--14 day-old group administered LMOX at 20 mg/kg, the maximum mean plasma concentration of the drug occurred at the time of 15 minutes postadministration, although some individuals showed peaks at 5 minutes. In all of the other age groups, for both the 10 and 20 mg/kg dosages, the maximum plasma concentration of LMOX occurred 5 minutes postinjection. In each of the age groups, a dose response was seen between the 2 dosage levels. However, a comparison of each group and control infants in terms of the LMOX plasma concentration at 30 minutes after injection revealed that the concentrations in the patients in this study were low. In terms of the half-life of the drug at the 2 dosage levels, both the mean and individual values in each of the age groups were longer than the half-lives in control infants. This tendency was especially marked in the case of infants 7 days of age or less. The values for the AUC also tended to be larger in the younger patient groups. A good level of LMOX was detected in the urine during each of the 0--2, 2--4 and 4--6 hour periods following administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Related factors to disparity of diabetes care in Iran.

PubMed

Mirzazadeh, Ali; Baradaran, Hamid R; Haghdoost, Ali A; Salari, Pooria

2009-05-01

We determined, in Iranian patients with diabetes mellitus, the prevalence of inadequate glycemic control and its predictors. The data from a national population-based survey that included a random sample of 89 404 Iranian individuals in 2005 were analyzed. In that sample, 2923 diabetic subjects (age range, 25-64 years) were identified. We linked the results of their fasting plasma glucose levels with demographic and behavioral variables to determine predictors of poor glycemic control. About 57% of the subjects had a fasting plasma glucose level of > or =130 mg/dL. That percentage was comparable in male and female subjects and in literate and illiterate subjects. However, inhabitants in rural areas controlled their fasting plasma glucose level about 11% better than did subjects who lived in an urban area. We also found that control of the fasting plasma glucose level was much better in relatively younger diabetic patients. Diabetic subjects with a family history of type 2 diabetes mellitus exhibited a higher uncontrolled fasting plasma glucose level than those without positive family history of diabetes. The percentage of uncontrolled type 2 diabetes found in our study suggests that the Iranian healthcare system should devote more attention to that disorder, particularly in elderly individuals, who are more vulnerable to the complications of diabetes and control their disorder less well than do younger diabetic patients. The recent integration of diabetic care in primary healthcare systems in Iranian rural areas was found to have a promising effect on community health.

Effects of cadmium, calcium, age and parity on bone mineral, density and strength in female rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammond, B.F.

Weanling female rats were fed diets containing one of three levels of calcium and one of four levels of cadmium in the drinking water. Approximately 10 animals from each group were sacrificed after the first pregnancy and the remaining animals after the fourth pregnancy. Reproductive performance, plasma and bone Ca and P and bone density and strength were measured. After the first pregnancy, offspring of dams treated with 5 or 10 ppM Cd were smaller at birth than offspring of dams treated with 0 or 1 ppM Cd. Offspring of dams fed 5 or 10 ppM Cd or the 0.3%more » Ca diet had decreased weaning weight regardless of parity. Cadmium treatment had no effect on the plasma Ca or the Ca-P ratio. At Cd levels of 5 or 10 ppM the plasma P was increased. The 0.3% Ca diet depressed the plasma Ca and the 0.9% Ca diet elevated the plasma Ca and depressed the plasma P when compared to the 0.6% diet. Parity did not affect plasma Ca but, after four pregnancies, plasma P was decreased. Plasma Ca of mature dams was higher than that of adolescent dams but plasma P was unaffected. Bone mineral, density and strength were decreased by the 0.3% Ca diet especially when Cd levels reached 10 ppM. Increasing dietary Ca above normal increased femur Ca of dams fed 1 ppM Cd but did not increase the Ca of the femur of dams given higher levels of Cd. After the first pregnancy, femur Ca of mature dams was greater than that of adolescent dams. After the fourth pregnancy, femurs of mature dams were less strong than those of adolescent dams; however, the density was the same. Increasing dietary Ca above 0.6% lessened the detrimental effects of 5 ppM Cd ingestion on bone density. Mature dams were less affected by the 0.3% Ca 10 ppM Cd treatment than were adolescent dams. 60 refs., 3 figs., 26 tabs.« less

α-Synuclein Aggregated with Tau and β-Amyloid in Human Platelets from Healthy Subjects: Correlation with Physical Exercise

PubMed Central

Daniele, Simona; Pietrobono, Deborah; Fusi, Jonathan; Lo Gerfo, Annalisa; Cerri, Eugenio; Chico, Lucia; Iofrida, Caterina; Petrozzi, Lucia; Baldacci, Filippo; Giacomelli, Chiara; Galetta, Fabio; Siciliano, Gabriele; Bonuccelli, Ubaldo; Trincavelli, Maria L.; Franzoni, Ferdinando; Martini, Claudia

2018-01-01

The loss of protein homeostasis that has been associated with aging leads to altered levels and conformational instability of proteins, which tend to form toxic aggregates. In particular, brain aging presents characteristic patterns of misfolded oligomers, primarily constituted of β-amyloid (Aβ), tau, and α-synuclein (α-syn), which can accumulate in neuronal membranes or extracellular compartments. Such aging-related proteins can also reach peripheral compartments, thus suggesting the possibility to monitor their accumulation in more accessible fluids. In this respect, we have demonstrated that α-syn forms detectable hetero-aggregates with Aβ or tau in red blood cells (RBCs) of healthy subjects. In particular, α-syn levels and its heteromeric interactions are modulated by plasma antioxidant capability (AOC), which increases in turn with physical activity. In order to understand if a specific distribution of misfolded proteins can occur in other blood cells, a cohort of human subjects was enrolled to establish a correlation among AOC, the level of physical exercise and the concentrations of aging-related proteins in platelets. The healthy subjects were divided depending on their level of physical exercise (i.e., athletes and sedentary subjects) and their age (young and older subjects). Herein, aging-related proteins (i.e., α-syn, tau and Aβ) were confirmed to be present in human platelets. Among such proteins, platelet tau concentration was demonstrated to decrease in athletes, while α-syn and Aβ did not correlate with physical exercise. For the first time, α-syn was shown to directly interact with Aβ and tau in platelets, forming detectable hetero-complexes. Interestingly, α-syn interaction with tau was inversely related to plasma AOC and to the level of physical activity. These results suggested that α-syn heterocomplexes, particularly with tau, could represent novel indicators to monitor aging-related proteins in platelets. PMID:29441013

Risk of type 2 diabetes mellitus associated with plasma lipid levels: The rural Chinese cohort study.

PubMed

Zhang, Ming; Zhou, Junmei; Liu, Yu; Sun, Xizhuo; Luo, Xinping; Han, Chengyi; Zhang, Lu; Wang, Bingyuan; Ren, Yongcheng; Zhao, Yang; Zhang, Dongdong; Liu, Xuejiao; Hu, Dongsheng

2018-01-01

To investigate the association of type 2 diabetes mellitus (T2DM) risk and plasma lipid levels in rural Chinese. Each lipid variable was divided into quartiles and dichotomized by clinical cutoff points. Cox proportional-hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of T2DM risk and plasma lipid levels and explore the interaction between plasma lipid levels and other risk factors. 11,929 participants were included in the analysis. We documented 720 incident cases of T2DM over 70,720.84 person-years of follow-up, for an incidence of 10.18/1,000 person-years. In the multivariable-adjusted model, risk of T2DM was increased with the highest versus lowest quartiles of total cholesterol (TC) and triglycerides (TG) levels and TC/high-density lipoprotein-cholesterol (HDL-C) and TG/HDL-C ratios. The HRs (95% CIs) for the fourth quartiles, for example, were 1.34 (1.03-1.74), 2.32 (1.73-3.13), 1.66 (1.23-2.25), and 1.84 (1.38-2.45), respectively. In addition, risk of T2DM was increased with high TG level and TC/HDL-C and TG/HDL-C ratios by clinical cutoffs. The HRs (95% CIs) were 1.50 (1.25-1.80), 1.24 (1.03-1.48), and 1.44 (1.18-1.75), respectively. Risk of T2DM was associated with interactions between all lipid variables and age and BMI. TG level and TG/HDL-C ratio additionally interacted with gender (all P interaction  < 0.0001). Risk of T2DM was increased with elevated serum levels of TC and TG and TC/HDL-C and TG/HDL-C ratios and also with interactions between high TC and TG levels and TC/HDL-C and TG/HDL-C ratios and age and BMI in a rural Chinese population. Copyright © 2017 Elsevier B.V. All rights reserved.

S-1-Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Study.

PubMed

Kim, Namju; Kim, Jin Won; Baek, Je-Hyun; Kim, Jin-Soo; Choung, Ho-Kyung; Kim, Tae-Yong; Lee, Kyung-Hun; Bang, Yung-Jue; Khwarg, Sang In; Ahn, Sang-Hoon; Park, Do Joong; Kim, Hyung-Ho; Chung, Jae-Yong; Ahn, Soyeon; Lee, Keun-Wook

2018-01-01

This prospective study was conducted to determine the incidence of lacrimal drainage obstruction (LDO) during S-1 chemotherapy and evaluate the association between the development of LDO and the concentrations of ingredients/metabolites of S-1 in tears and plasma. A total of 145 patients with gastric cancer who received adjuvant S-1 therapy were enrolled. Ophthalmologic examinations were performed regularly during S-1 chemotherapy. Concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and 5-fluorouracil at steady-state trough level were measured in both tears and plasma. Fifty-three patients (37%) developed LDO. The median time to the onset of LDO was 10.9 weeks, and LDO developed most frequently in the nasolacrimal duct. Univariable analyses revealed that an older age (≥ 70 years), creatinine clearance rate (Ccr) < 80 mL/min, 5-fluorouracil concentration in plasma ≥ 22.3 ng/mL (median), CDHP concentration in plasma ≥ 42.0 ng/mL (median), and tegafur concentration in tears ≥ 479.2 ng/mL (median) were related to increased development of LDO. Multivariable analysis indicated that a high plasma 5-fluorouracil concentration was predictive of increased development of LDO (hazard ratio, 2.02; p=0.040), along with older age and decreased Ccr. Patients with LDO also developed S-1-related non-hematologic toxicity more frequently than those without LDO (p=0.016). LDO is a frequent adverse event during S-1 chemotherapy. An older age, decreased Ccr, and high plasma 5-fluorouracil concentration were found to be independent risk factors for LDO. The high incidence of LDO warrants regular ophthalmologic examination and early intervention in patients receiving S-1 therapy.

A 3 years follow-up of a Mediterranean diet rich in virgin olive oil is associated with high plasma antioxidant capacity and reduced body weight gain.

PubMed

Razquin, C; Martinez, J A; Martinez-Gonzalez, M A; Mitjavila, M T; Estruch, R; Marti, A

2009-12-01

The aim of this study was to analyze the influence of a Mediterranean dietary pattern on plasma total antioxidant capacity (TAC) after 3 years of intervention and the associations with adiposity indexes in a randomized dietary trial (PREDIMED trial) with high cardiovascular risk patients. 187 subjects were randomly selected from the PREDIMED-UNAV center after they completed 3-year intervention program. Participants were following a Mediterranean-style diet with high intake of virgin olive oil or high intake of nuts, or a conventional low-fat diet. Adiposity indexes were measured at baseline and at year 3. Plasma TAC was evaluated using a commercially available colorimetric assay kit. Plasma TAC in the control, olive oil and nuts groups was 2.01+/-0.15, 3.51+/-0.14 and 3.02+/-0.14 mM Trolox, respectively after adjusting for age and sex. The differences between the Mediterranean diet and control groups were statistically significant (P<0.001). Moreover higher levels of TAC were significantly associated with a reduction in body weight after 3 years of intervention among subjects allocated to the virgin olive oil group (B=-1.306; 95% CI=-2.439 to -0.173; P=0.025, after adjusting for age, sex and baseline body mass index). Mediterranean diet, especially rich in virgin olive oil, is associated with higher levels of plasma antioxidant capacity. Plasma TAC is related to a reduction in body weight after 3 years of intervention in a high cardiovascular risk population with a Mediterranean-style diet rich in virgin olive oil.

Plasma Carotenoids, Tocopherols, and Retinol in the Age-Stratified (35–74 Years) General Population: A Cross-Sectional Study in Six European Countries

PubMed Central

Stuetz, Wolfgang; Weber, Daniela; Dollé, Martijn E. T.; Jansen, Eugène; Grubeck-Loebenstein, Beatrix; Fiegl, Simone; Toussaint, Olivier; Bernhardt, Juergen; Gonos, Efstathios S.; Franceschi, Claudio; Sikora, Ewa; Moreno-Villanueva, María; Breusing, Nicolle; Grune, Tilman; Bürkle, Alexander

2016-01-01

Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/β-carotene and higher β-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene (r = −0.248), α-tocopherol (r = 0.208), α-carotene (r = −0.112), and β-cryptoxanthin (r = 0.125; all p < 0.001). Age was inversely associated with lycopene (−6.5% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m2)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7% vs. 2.4% per five-year age increase). The association of higher β-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (−4.8% vs. −3.8% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene. PMID:27706032

Plasma selenium levels and oxidative stress biomarkers: a gene-environment interaction population-based study.

PubMed

Galan-Chilet, Inmaculada; Tellez-Plaza, Maria; Guallar, Eliseo; De Marco, Griselda; Lopez-Izquierdo, Raul; Gonzalez-Manzano, Isabel; Carmen Tormos, M; Martin-Nuñez, Gracia M; Rojo-Martinez, Gemma; Saez, Guillermo T; Martín-Escudero, Juan C; Redon, Josep; Javier Chaves, F

2014-09-01

The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 µg/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above ~110 μg/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of Aflatoxin B1 and Fumonisin B1 on Blood Biochemical Parameters in Broilers

PubMed Central

Tessari, Eliana N. C.; Kobashigawa, Estela; Cardoso, Ana Lúcia S. P.; Ledoux, David R.; Rottinghaus, George E.; Oliveira, Carlos A. F.

2010-01-01

The individual and combined effects of dietary aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days of age. Dietary treatments included a 3 × 3 factorial arrangement with three levels of AFB1 (0, 50 and 200 μg AFB1/kg), and three levels of FB1 (0, 50 and 200 mg FB1/kg). At 33 days post feeding, with the exception of birds fed 50 mg FB1 only, concentrations of AST were higher (p < 0.05) in all other treatment groups when compared with controls. Plasma TP was lower (p < 0.05) at six days post feeding in groups fed 200 μg AFB1/kg alone or in combination with FB1. At day 33 days post feeding, with the exception of birds fed the highest combination of AFB1 and FB1 which had higher plasma TP than control birds, plasma TP of birds fed other dietary treatments were similar to controls. Broilers receiving the highest levels of AFB1 and FB1 had bile duct proliferation and trabecular disorder in liver samples. AFB1 singly or in combination with FB at the levels studied, caused liver damage and an increase in serum levels of AST. PMID:22069595

Age dependency for coagulation parameters in paediatric populations. Results of a multicentre study aimed at defining the age-specific reference ranges.

PubMed

Toulon, Pierre; Berruyer, Micheline; Brionne-François, Marie; Grand, François; Lasne, Dominique; Telion, Caroline; Arcizet, Julien; Giacomello, Roberta; De Pooter, Neila

2016-07-04

Understanding of developmental haemostasis is critical to ensure optimal prevention, diagnosis, and treatment of haemorrhagic and thrombotic diseases in children. As coagulation test results are known to be dependent on the reagents/analysers used, it is recommended for each laboratory to define the age-dependent reference ranges by using its own technical condition. That study was carried out in seven centers to establish age-specific reference ranges using the same reagents and analyser. Plasma samples were obtained from 1437 paediatric patients from the following age groups: 15 days-4 weeks (n=36), 1-5 months (n=320), 6-12 months (n=176), 1-5 years (n=507), 6-10 years (n=132) and 11-17 years (n=262). Indication of coagulation testing was pre-operative screening for non-acute diseases in most cases. PT values were similar in the different age groups to those in adults, whereas longer aPTTs were demonstrated in the younger children. Plasma levels of all clotting factors, except for FV, were significantly decreased (p<0.0001) in the youngest children, adult values being usually reached before the end of the first year. The same applied to antithrombin, protein C/S, and plasminogen. In contrast, FVIII and VWF levels were elevated in the youngest children and returned to adult values within six months. The same applied to D-dimer levels, which were found elevated, particularly until six months of life, until puberty. These data suggest that most coagulation test results are highly dependent on age, mainly during the first year of life, and that age-specific reference ranges must be used to ensure proper evaluation of coagulation in children.

Contrasting effects of age on the plasma/whole blood lead ratio in men and women with a history of lead exposure.

PubMed

Barbosa, Fernando; Ramires, Irene; Rodrigues, Maria Heloísa C; Saint' Pierre, Tatiana D; Curtius, Adilson J; Buzalaf, Marilia R; Gerlach, Raquel F; Tanus-Santos, José E

2006-09-01

We examined the effect of age and sex on the relationship between the concentrations of Pb in blood (Pb-B) and in plasma (Pb-P) in an adult population with a history of lead exposure. Pb-P was determined by inductively coupled plasma mass spectrometry (ICP-MS) and Pb-B by graphite furnace atomic absorption spectrometry (GF AAS). We studied 154 adults (56 men and 98 women) from 18 to 60-year old. Pb-B levels varied from 10.0 to 428.0 microg/L, with a mean of 76 microg/L. Blood lead levels varied from 10.0 to 428.0 microg/L in men (mean, 98.3 microg/L) and from 10.0 to 263.0 microg/L (mean, 62.8 microg/L) in women. Corresponding Pb-Ps were 0.02-2.9 microg/L (mean, 0.66 microg/L) and 0.02-1.5 microg/L (mean, 0.42 microg/L) in men and women, respectively. The relationship between Pb-B and Pb-P was found to be curvilinear (r = 0.757, P < 0.001 Spearman's correlation). The two quantities are related by the line y = 0.0006x(1492) (y = Pb-P, and x = Pb-B). The %Pb-P/Pb-B ratio ranged from 0.03% to 1.85%. A positive association was found between %Pb-P/Pb-B ratio and Pb-B levels. When data were separated by sex, this association was also relevant for men (y = 0.0184x(0.702)) and women (y = 0.0534x(0.5209)) (y = %Pb-P/Pb-B and x = Pb-B). Moreover, we found an interesting positive correlation between Log (Pb-P/Pb-B) and age for women (r = 0.31, P < 0.0001) and a negative correlation for men (r = -0.164, P = 0.07). Taken together, these results suggest contrasting effects of age on the plasma/whole blood lead ratio in men and women with a history of lead exposure. Moreover, sex might play an important role in the metabolism of lead, implying further consideration on the kinetic models constructed of lead toxicity.

Antioxidant Defence, Oxidative Stress and Oxidative Damage in Saliva, Plasma and Erythrocytes of Dementia Patients. Can Salivary AGE be a Marker of Dementia?

PubMed Central

Choromańska, Magdalena; Klimiuk, Anna; Kostecka-Sochoń, Paula; Wilczyńska, Karolina; Kwiatkowski, Mikołaj; Okuniewska, Natalia; Waszkiewicz, Napoleon; Zalewska, Anna

2017-01-01

Oxidative stress plays a crucial role in dementia pathogenesis; however, its impact on salivary secretion and salivary qualities is still unknown. This study included 80 patients with moderate dementia and 80 healthy age- and sex-matched individuals. Salivary flow, antioxidants (salivary peroxidase, catalase, superoxide dismutase, uric acid and total antioxidant capacity), and oxidative damage products (advanced oxidation protein products, advanced glycation end products (AGE), 8-isoprostanes, 8-hydroxy-2’-deoxyguanosine and total oxidant status) were estimated in non-stimulated and stimulated saliva, as well as in plasma and erythrocytes. We show that in dementia patients the concentration/activity of major salivary antioxidants changes, and the level of oxidative damage to DNA, proteins and lipids is increased compared to healthy controls. Non-stimulated and stimulated salivary secretions were significantly reduced in dementia patients. The deterioration in mini mental state examination (MMSE) score correlated with salivary AGE levels, which when considered with receiver operating characteristic (ROC) analysis, suggests their potential role in the non-invasive diagnosis of dementia. In conclusion, dementia is associated with disturbed salivary redox homeostasis and impaired secretory function of the salivary glands. Salivary AGE may be useful in the diagnosis of dementia. PMID:29053628

Elevated Prostaglandin E Metabolites and Abnormal Plasma Fatty Acids at Baseline in Pediatric Cystic Fibrosis Patients: A Pilot Study

PubMed Central

O’Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F.; Laposata, Michael; Seegmiller, Adam

2016-01-01

Background Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). Methods This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6 to 18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Results Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Conclusions Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. PMID:27720040

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.

PubMed

O'Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F; Laposata, Michael; Seegmiller, Adam

2016-10-01

Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum dehydroepiandrosterone sulphate, total antioxidant capacity, and total oxidant status in central serous chorioretinopathy.

PubMed

Türkcü, Fatih Mehmet; Yüksel, Harun; Yüksel, Hatice; Sahin, Alparslan; Cinar, Yasin; Cingü, Abdullah Kürşat; Sahin, Muhammed; Caça, Ihsan

2014-01-01

The objective of this work is to evaluate plasma total antioxidant capacity (TAC), total oxidant status (TOS), and dehydroepiandrosterone sulphate (DHEA-S) levels in patients diagnosed with acute central serous chorioretinopathy (CSCR) and control samples. The TAC, TOS, and DHEA-S levels were assessed in the plasma of 46 CSCR patients and compared with 40 control samples. The TAC level was 1.16 ± 0.08 and 1.20 ± 0.09 mmol Trolox eq./l; TOS level was 28.77 ± 33.33 and 19.95 ± 10.42 μmol H202/l; DHEA-S level was 203.79 ± 84.75 μg/dl and 249.36 ± 122.93 μg/dl in the CSCR group and in the control group, respectively. The plasma TAC and DHEA-S values were significantly lower in the CSCR group than in the control group (p = 0.027 and p = 0.046, respectively). There was no significant difference between the CSCR and the control groups in terms of age, gender, and TOS levels (p > 0.05). We demonstrated that the levels of plasma DHEA-S and antioxidative parameters were reduced in CSCR. Our results suggest that the antioxidant defense system may be inadequate or corrupted in CSCR. Reduced DHEA-S level is one of the factors that trigger this insufficiency.

Effect of 14 days of bed rest on urine metabolite excretion and plasma enzyme levels

NASA Technical Reports Server (NTRS)

Pace, N.; Grunbaum, B. W.; Kodama, A. M.; Rahlmann, D. F.; Newsom, B. D.

1974-01-01

After 1 week of ambulatory base-line measurement, a group of 8 men 19-26 years of age remained continuously recumbent for 14 days. Studies were continued for 1 week following the prolonged recumbency. Urine excretion rates for a number of constituents were determined 2 days before bed rest, on day 14 of bed rest, and day 6 after bed rest. Blood plasma samples were also obtained at these times, and analyzed for several enzymes. On day 14 of bed rest significant increases were observed in urine excretion of total osmotically-active substances, magnesium, calcium, phosphate, creatinine, hydroxyproline, and 17-OH corticosteroids. A decrease occurred in urinary glucose excretion. Plasma levels of alkaline phosphatase and LDH-3 were depressed, while plasma GPT was elevated. Many of these changes persisted on day 6 after bed rest, and are interpreted as concomitants of the disuse atrophy of the musculoskeletal system that characterizes prolonged bed rest and weightlessness.

Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

PubMed

Takahashi, L K; Kalin, N H

1991-08-30

Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

Comparison of point-of-care methods for preparation of platelet concentrate (platelet-rich plasma).

PubMed

Weibrich, Gernot; Kleis, Wilfried K G; Streckbein, Philipp; Moergel, Maximilian; Hitzler, Walter E; Hafner, Gerd

2012-01-01

This study analyzed the concentrations of platelets and growth factors in platelet-rich plasma (PRP), which are likely to depend on the method used for its production. The cellular composition and growth factor content of platelet concentrates (platelet-rich plasma) produced by six different procedures were quantitatively analyzed and compared. Platelet and leukocyte counts were determined on an automatic cell counter, and analysis of growth factors was performed using enzyme-linked immunosorbent assay. The principal differences between the analyzed PRP production methods (blood bank method of intermittent flow centrifuge system/platelet apheresis and by the five point-of-care methods) and the resulting platelet concentrates were evaluated with regard to resulting platelet, leukocyte, and growth factor levels. The platelet counts in both whole blood and PRP were generally higher in women than in men; no differences were observed with regard to age. Statistical analysis of platelet-derived growth factor AB (PDGF-AB) and transforming growth factor β1 (TGF-β1) showed no differences with regard to age or gender. Platelet counts and TGF-β1 concentration correlated closely, as did platelet counts and PDGF-AB levels. There were only rare correlations between leukocyte counts and PDGF-AB levels, but comparison of leukocyte counts and PDGF-AB levels demonstrated certain parallel tendencies. TGF-β1 levels derive in substantial part from platelets and emphasize the role of leukocytes, in addition to that of platelets, as a source of growth factors in PRP. All methods of producing PRP showed high variability in platelet counts and growth factor levels. The highest growth factor levels were found in the PRP prepared using the Platelet Concentrate Collection System manufactured by Biomet 3i.

Role of adipocytokines and its correlation with endocrine pancreatic function in patients with pancreatic cancer.

PubMed

Gąsiorowska, Anita; Talar-Wojnarowska, Renata; Kaczka, Aleksandra; Borkowska, Anna; Czupryniak, Leszek; Małecka-Panas, Ewa

2013-01-01

Some authors suggest that adipocytokines contribute to the induction of pancreatic carcinogenesis as well as the development of endocrine insufficiency. We evaluate the circulating concentrations of leptin, resistin and visfatin in patients with newly diagnosed pancreatic cancer (PC) and relationship between serum adipocytokines level and clinicopathological features of PC. Moreover the usefulness of those adipocytokines as possible biomarkers of endocrine pancreatic function in PC has been assessed. The pilot study group consisted of 45 individuals (mean age 65.6 ± 11.5 years, BMI 21.8 ± 3.4 kg/m(2)) with newly diagnosed PC (within last 1-3 months) and 13 healthy individuals with age, gender and BMI matched to the study group. Among PC patients 18 (40%) had recently diagnosed diabetes. Fasting plasma leptin, resistin, visfatin concentrations were determined with ELISA (R&D Systems, Phoenix Pharmaceuticals) and insulin by RIA (DakoCytomation). Patients with PC as compared to controls had significantly lower plasma leptin (40.6 ± 21.3 vs 63.2 ± 16.3 pg/mL; p < 0,0008). In contrast PC patients showed more than six fold higher level of resistin (126.2 ± 143.2 vs 18.9 ± 7.2 ng/mL; p < 0.009) than controls. The median plasma visfatin was 2.8 ± 1.8 ng/mL, which was not significantly different from the controls (3.8 ± 1.1 ng/mL). When PC patients with and without diabetes were considered separately, plasma leptin concentrations among nondiabetic patients were slightly, but not significantly higher (44.6 ± 21.0) as compared to diabetics (34.5 ± 20.7). Moreover there was no difference between visfatin and resistin level in PC, among patients with and without diabetes. No significant differences between serum level of leptin, visfatin and resistin and age, gender, BMI, smoking status, tumor localization, distant metastases and pain has been found. The results of this study confirm previous findings that patients with newly diagnosed pancreatic cancer are characterized with lower level of leptin. This pilot study showed significantly higher resistin concentrations in patients with PC in comparison to healthy controls, which may be helpful in PC early diagnosis. Changes in leptin and resistin level in PC are not likely related to endocrine disorders. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Relationship of Area of Soft Drusen in Retina with Cerebral Amyloid-β Accumulation and Blood Amyloid-β Level in the Elderly.

PubMed

Shoda, Chiho; Kitagawa, Yorihisa; Shimada, Hiroyuki; Yuzawa, Mitsuko; Tateno, Amane; Okubo, Yoshiro

2018-01-01

Histopathological studies have confirmed that soft drusen contains amyloid-β (Aβ). To examine the relationship between the area of soft drusen in the macular area and cerebral Aβ accumulation or plasma Aβ level in elderly persons without dementia. Fourteen consecutive patients (18 eyes) aged ≥50 years with macular soft drusen were studied prospectively. From color fundus photographs, the area of soft drusen (pixel) within a 6,000 μm diameter with the macula as center was measured. Standard uptake value ratio (SUVR) was obtained from positron emission tomography using florbetapir, which indicates the ratio of cerebral cortical-to-cerebellar Aβ accumulation. Ratio of plasma Aβ1-42 to Aβ1-40 level was calculated. Mean age was 73.3±7.6 years. The soft drusen area was 4.32±2.42 mm2. The SUVR was 1.08±0.15. Plasma Aβ1-42/Aβ1-40 ratio was 0.17±0.08. When SUVR ≥1.10 was defined as positive and <1.10 as negative, the soft drusen area in SUVR-positive patients (6.19±1.14 mm2) was significantly (p = 0.0043) larger than that in SUVR-negative patients (3.13±2.27 mm2). Multivariate regression analysis showed that SUVR positivity correlated with soft drusen area (p = 0.0484) and with Voxel-based Specific Regional Analysis System for Alzheimer's Disease score (p = 0.0360). However, there was no correlation with gender (p = 0.1921), age (p = 0.2361), Alzheimer's Disease Assessment Scale score (p = 0.6310), Mini-Mental State Examination score (p = 0.4246), or plasma Aβ1-42/Aβ1-40 ratio (p = 0.8398). Among elderly persons without dementia, the area of soft drusen was larger in those with more extensive cerebral Aβ accumulation. The area of soft drusen may be a biomarker of cerebral Aβ accumulation.

Cardiovascular disease markers in women with polycystic ovary syndrome with emphasis on asymmetric dimethylarginine and homocysteine.

PubMed

Mohamadin, Ahmed M; Habib, Fawzia A; Al-Saggaf, Abdulrahman A

2010-01-01

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Little is known about cardiovascular risk factors in patients with PCOS. We investigated plasma markers of cardiovascular disease in Saudi women with PCOS, with an emphasis on asymmetric dimethylarginine (ADMA) and total homocysteine (tHcy). Fifty Saudi women with PCOS diagnosed by the Rotterdam criteria (mean age [SD] 30.2 [3.0] years) and 40 controls without PCOS (mean age 29.3 [2.5] years) had measyrements taken of clinical, metabolic, and hormonal parameters, including plasma ADMA, tHcy, lipoprotein (a) ([Lp(a)], and serum high sensitivity C-reactive protein (hs-CRP), nitric oxid, and fibrinogen. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). Women with PCOS had significantly higher fasting insulin, HOMA-IR, and luteinizing hormone (LH) levels than healthy controls (P P P CONCLUSION: Our study revealed that Saudi women with PCOS had a significantly different levels of plasma markers of cardiovascular disease compared with normal controls. Therefore, clinicians who manage women with PCOS should follow up on these markers to reduce the risk of cardiovascular disease.

Effects of coffee consumption on glucose tolerance, serum glucose and insulin levels--a cross-sectional analysis.

PubMed

Bidel, S; Hu, G; Sundvall, J; Kaprio, J; Tuomilehto, J

2006-01-01

Coffee has several metabolic effects that could reduce the risk of type 2 diabetes. Our objective was to examine the effects of coffee consumption on glucose tolerance, glucose and insulin levels. A subsample of subjects aged 45 to 64 years in 1987 and in 1992 from the population-based FINRISK study (12,287 individuals) was invited to receive the standard oral glucose tolerance test at baseline. Plasma samples were taken after an overnight fast, and a two-hour oral glucose tolerance test was administered. Fasting and two-hour plasma glucose and insulin were measured in 2434 subjects with data on coffee use and potential confounders. After adjustment for potential confounding factors (age, body mass index, systolic blood pressure, occupational, commuting and leisure time physical activity, alcohol and tea drinking, smoking), coffee consumption was significantly and inversely associated with fasting glucose, two-hour plasma glucose, and fasting insulin in both men and women. Coffee consumption was significantly and inversely associated with impaired fasting glucose, impaired glucose regulation, and hyperinsulinemia among both men and women and with isolated impaired glucose tolerance among women. In this cross-sectional analysis, coffee showed positive effects on several glycemia markers.

Assessment of perfluorinated compounds (PFCs) in plasma of bottlenose dolphins from two southeast US estuarine areas: relationship with age, sex and geographic locations.

PubMed

Fair, Patricia A; Houde, Magali; Hulsey, Thomas C; Bossart, Gregory D; Adams, Jeff; Balthis, Len; Muir, Derek C G

2012-01-01

Plasma PFCs were measured in 157 bottlenose dolphins (Tursiops truncatus) sampled from two US southeast Atlantic sites (Charleston (CHS), SC and Indian River Lagoon (IRL), FL) during 2003-2005. ∑PFCs, perfluoroalkyl carboxylates (∑PFCAs), perfluoroalkyl sulfonates (∑PFSAs) and individual compounds were significantly higher in CHS dolphins for all age/sex categories compared to IRL dolphins. Highest ∑PFCs concentrations occurred in CHS juvenile dolphins (2340 ng/g w.w.); significantly higher than found in adults (1570 ng/g w.w. males; 1330 ng/g w.w. females). ∑PFCAs were much greater in CHS dolphins (≈ 21%) compared to IRL dolphins (≈ 7%); ∑PFSAs were 79% in CHS dolphins versus 93% in IRL dolphins. PFOS, the dominant compound, averaged 72% and 84%, respectively, in CHS and IRL dolphins. Decreasing PFC levels occurred with age on the bioaccumulation of PFCs in both sites. These observations suggest PFC accumulation in these two dolphin populations are influenced by site-specific exposures with significantly higher levels in CHS dolphins. Published by Elsevier Ltd.