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  1. Residual mitochondrial transmembrane potential decreases unsaturated fatty acid level in sake yeast during alcoholic fermentation

    PubMed Central

    Sawada, Kazutaka

    2016-01-01

    Oxygen, a key nutrient in alcoholic fermentation, is rapidly depleted during this process. Several pathways of oxygen utilization have been reported in the yeast Saccharomyces cerevisiae during alcoholic fermentation, namely synthesis of unsaturated fatty acid, sterols and heme, and the mitochondrial electron transport chain. However, the interaction between these pathways has not been investigated. In this study, we showed that the major proportion of unsaturated fatty acids of ester-linked lipids in sake fermentation mash is derived from the sake yeast rather than from rice or koji (rice fermented with Aspergillus). Additionally, during alcoholic fermentation, inhibition of the residual mitochondrial activity of sake yeast increases the levels of unsaturated fatty acids of ester-linked lipids. These findings indicate that the residual activity of the mitochondrial electron transport chain reduces molecular oxygen levels and decreases the synthesis of unsaturated fatty acids, thereby increasing the synthesis of estery flavors by sake yeast. This is the first report of a novel link between residual mitochondrial transmembrane potential and the synthesis of unsaturated fatty acids by the brewery yeast during alcoholic fermentation. PMID:26839744

  2. Residual mitochondrial transmembrane potential decreases unsaturated fatty acid level in sake yeast during alcoholic fermentation.

    PubMed

    Sawada, Kazutaka; Kitagaki, Hiroshi

    2016-01-01

    Oxygen, a key nutrient in alcoholic fermentation, is rapidly depleted during this process. Several pathways of oxygen utilization have been reported in the yeast Saccharomyces cerevisiae during alcoholic fermentation, namely synthesis of unsaturated fatty acid, sterols and heme, and the mitochondrial electron transport chain. However, the interaction between these pathways has not been investigated. In this study, we showed that the major proportion of unsaturated fatty acids of ester-linked lipids in sake fermentation mash is derived from the sake yeast rather than from rice or koji (rice fermented with Aspergillus). Additionally, during alcoholic fermentation, inhibition of the residual mitochondrial activity of sake yeast increases the levels of unsaturated fatty acids of ester-linked lipids. These findings indicate that the residual activity of the mitochondrial electron transport chain reduces molecular oxygen levels and decreases the synthesis of unsaturated fatty acids, thereby increasing the synthesis of estery flavors by sake yeast. This is the first report of a novel link between residual mitochondrial transmembrane potential and the synthesis of unsaturated fatty acids by the brewery yeast during alcoholic fermentation. PMID:26839744

  3. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    SciTech Connect

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  4. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    EPA Science Inventory

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

  5. Increased glutamate and homocysteine and decreased glutamine levels in autism: a review and strategies for future studies of amino acids in autism.

    PubMed

    Ghanizadeh, Ahmad

    2013-01-01

    There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids. PMID:24167375

  6. Fish oil N-3 fatty acids increase adiponectin and decrease leptin levels in patients with systemic lupus erythematosus.

    PubMed

    Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Morimoto, Helena Kaminami; Scavuzzi, Bruna Miglioranza; Iriyoda, Tathiana Veiga Mayumi; Reiche, Edna Maria Vissoci; Cecchini, Rubens; Dichi, Isaias

    2015-02-01

    Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE. PMID:25690094

  7. Fish Oil N-3 Fatty Acids Increase Adiponectin and Decrease Leptin Levels in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Lozovoy, Marcell Alysson Batisti; Colado Simão, Andréa Name; Morimoto, Helena Kaminami; Scavuzzi, Bruna Miglioranza; Iriyoda, Tathiana Veiga Mayumi; Reiche, Edna Maria Vissoci; Cecchini, Rubens; Dichi, Isaias

    2015-01-01

    Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE. PMID:25690094

  8. Potato chip intake increases ascorbic acid levels and decreases reactive oxygen species in SMP30/GNL knockout mouse tissues.

    PubMed

    Kondo, Yoshitaka; Sakuma, Rui; Ichisawa, Megumi; Ishihara, Katsuyuki; Kubo, Misako; Handa, Setsuko; Mugita, Hiroyuki; Maruyama, Naoki; Koga, Hidenori; Ishigami, Akihito

    2014-09-24

    Potato chips (PC) contain abundant amounts of the free radical scavenger ascorbic acid (AA) due to the rapid dehydration of potato tubers (Solanum tuberosum) that occurs during frying. To evaluate the antioxidant activity of PC, this study examined reactive oxygen species (ROS) levels in tissues from SMP30/GNL knockout (KO) mice that cannot synthesize AA and determined AA and ROS levels after the animals were fed 20 and 10% PC diets for 7 weeks. Compared with AA-sufficient mice, AA-depleted SMP30/GNL KO mice showed high ROS levels in tissues. SMP30/GNL KO mice fed a PC diet showed high AA and low ROS levels in the brain, heart, lung, testis, soleus muscle, plantaris muscle, stomach, small intestine, large intestine, eyeball, and epididymal fat compared with AA-depleted mice. The data suggest that PC intake increases AA levels and enhances ROS scavenging activity in tissues of SMP30/GNL KO mice, which are a promising model for evaluating the antioxidant activity of foods. PMID:25180784

  9. Bisphenol A Alters n-6 Fatty Acid Composition and Decreases Antioxidant Enzyme Levels in Rat Testes: A LC-QTOF-Based Metabolomics Study

    PubMed Central

    Qiao, Shanlei; Hu, Nan; Hu, Yanhui; Wu, Wei; Qiu, Lianglin; Zhang, Ruyang; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

    2012-01-01

    Background Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. Methodology/Principal Findings Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group. Conclusions/Significance BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity. PMID:23024759

  10. Temperature Shift Experiments Suggest That Metabolic Impairment and Enhanced Rates of Photorespiration Decrease Organic Acid Levels in Soybean Leaflets Exposed to Supra-Optimal Growth Temperatures.

    PubMed

    Sicher, Richard C

    2015-01-01

    Elevated growth temperatures are known to affect foliar organic acid concentrations in various plant species. In the current study, citrate, malate, malonate, fumarate and succinate decreased 40 to 80% in soybean leaflets when plants were grown continuously in controlled environment chambers at 36/28 compared to 28/20 °C. Temperature effects on the above mentioned organic acids were partially reversed three days after plants were transferred among optimal and supra-optimal growth temperatures. In addition, CO2 enrichment increased foliar malate, malonate and fumarate concentrations in the supra-optimal temperature treatment, thereby mitigating effects of high temperature on respiratory metabolism. Glycerate, which functions in the photorespiratory pathway, decreased in response to CO2 enrichment at both growth temperatures. The above findings suggested that diminished levels of organic acids in soybean leaflets upon exposure to high growth temperatures were attributable to metabolic impairment and to changes of photorespiratory flux. Leaf development rates differed among temperature and CO2 treatments, which affected foliar organic acid levels. Additionally, we report that large decreases of foliar organic acids in response to elevated growth temperatures were observed in legume species. PMID:26251925

  11. Temperature Shift Experiments Suggest That Metabolic Impairment and Enhanced Rates of Photorespiration Decrease Organic Acid Levels in Soybean Leaflets Exposed to Supra-Optimal Growth Temperatures

    PubMed Central

    Sicher, Richard C.

    2015-01-01

    Elevated growth temperatures are known to affect foliar organic acid concentrations in various plant species. In the current study, citrate, malate, malonate, fumarate and succinate decreased 40 to 80% in soybean leaflets when plants were grown continuously in controlled environment chambers at 36/28 compared to 28/20 °C. Temperature effects on the above mentioned organic acids were partially reversed three days after plants were transferred among optimal and supra-optimal growth temperatures. In addition, CO2 enrichment increased foliar malate, malonate and fumarate concentrations in the supra-optimal temperature treatment, thereby mitigating effects of high temperature on respiratory metabolism. Glycerate, which functions in the photorespiratory pathway, decreased in response to CO2 enrichment at both growth temperatures. The above findings suggested that diminished levels of organic acids in soybean leaflets upon exposure to high growth temperatures were attributable to metabolic impairment and to changes of photorespiratory flux. Leaf development rates differed among temperature and CO2 treatments, which affected foliar organic acid levels. Additionally, we report that large decreases of foliar organic acids in response to elevated growth temperatures were observed in legume species. PMID:26251925

  12. Low level of trans-10, cis-12 conjugated linoleic acid decreases adiposity and increases browning independent of inflammatory signaling in overweight Sv129 mice

    PubMed Central

    Shen, Wan; Baldwin, Jessie; Collins, Brian; Hixson, Lindsay; Lee, Kuan-Ting; Herberg, Timothy; Starnes, Joseph; Cooney, Paula; Chuang, Chia-Chi; Hopkins, Robin; Reid, Tanya; Gupta, Sat; McIntosh, Michael

    2015-01-01

    The objective of this study was to determine the extent to which a low level of trans-10, cis-12 (10,12) conjugated linoleic acid (CLA) decreases adiposity and increases browning in overweight mice, its dependence on inflammatory signaling, and potential synergistic effects of daily exercise. Young, Sv129 male mice were fed a high fat diet for 5 wk to make them fat and glucose intolerant, and then switch them to a low fat diet with or without 0.1% 10,12 CLA, sodium salicylate, or exercise for another 7 wk. 10,12 CLA decreased white adipose tissue (WAT) and brown adipose tissue mass, and increased the mRNA and protein levels, and activities of enzymes associated with thermogenesis or fatty acid oxidation in WAT. Mice fed 10,12 CLA had lower body temperatures compared to controls during cold exposure, which coincided with decreased adiposity. Although sodium salicylate decreased 10,12 CLA-mediated increases in markers of inflammation in WAT, it did not affect other outcomes. Exercise had no further effect on the outcomes measured. Collectively, these data indicate that 10,12 CLA-mediated reduction of adiposity is independent of inflammatory signaling, and possibly due to up-regulation of fatty acid oxidation and heat production in order to regulate body temperature. Although this low level of 10,12 CLA reduced adiposity in overweight mice, hepatomegaly and inflammation are major health concerns. PMID:25801353

  13. Intracerebroventricular administration of α-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats.

    PubMed

    Wisniewski, Miriam S W; Carvalho-Silva, Milena; Gomes, Lara M; Zapelini, Hugo G; Schuck, Patrícia F; Ferreira, Gustavo C; Scaini, Giselli; Streck, Emilio L

    2016-04-01

    Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine as well as their corresponding transaminated branched-chain α-ketoacids. This disorder is clinically characterized by ketoacidosis, seizures, coma, psychomotor delay and mental retardation whose pathophysiology is not completely understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. However, the effect of accumulating α-ketoacids in MSUD on neurotrophic factors has not been investigated. Thus, the objective of the present study was to evaluate the effects of acute intracerebroventricular administration of α-ketoisocaproic acid (KIC) on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the brains of young male rats. Ours results showed that intracerebroventricular administration of KIC decreased BDNF levels in hippocampus, striatum and cerebral cortex, without induce a detectable change in pro-BDNF levels. Moreover, NGF levels in the hippocampus were reduced after intracerebroventricular administration of KIC. In conclusion, these data suggest that the effects of KIC on demyelination and memory processes may be mediated by reduced trophic support of BDNF and NGF. Moreover, lower levels of BDNF and NGF are consistent with the hypothesis that a deficit in this neurotrophic factor may contribute to the structural and functional alterations of brain underlying the psychopathology of MSUD, supporting the hypothesis of a neurodegenerative process in MSUD. PMID:26586008

  14. Arabidopsis serotonin N-acetyltransferase knockout mutant plants exhibit decreased melatonin and salicylic acid levels resulting in susceptibility to an avirulent pathogen.

    PubMed

    Lee, Hyoung Yool; Byeon, Yeong; Tan, Dun-Xian; Reiter, Russel J; Back, Kyoungwhan

    2015-04-01

    Serotonin N-acetyltransferase (SNAT) is the penultimate enzyme in the melatonin biosynthesis pathway in plants. We examined the effects of SNAT gene inactivation in two Arabidopsis T-DNA insertion mutant lines. After inoculation with the avirulent pathogen Pseudomonas syringe pv. tomato DC3000 harboring the elicitor avrRpt2 (Pst-avrRpt2), melatonin levels in the snat knockout mutant lines were 50% less than in wild-type Arabidopsis Col-0 plants. The snat knockout mutant lines exhibited susceptibility to pathogen infection that coincided with decreased induction of defense genes including PR1, ICS1, and PDF1.2. Because melatonin acts upstream of salicylic acid (SA) synthesis, the reduced melatonin levels in the snat mutant lines led to decreased SA levels compared to wild-type, suggesting that the increased pathogen susceptibility of the snat mutant lines could be attributed to decreased SA levels and subsequent attenuation of defense gene induction. Exogenous melatonin treatment failed to induce defense gene expression in nahG Arabidopsis plants, but restored the induction of defense gene expression in the snat mutant lines. In addition, melatonin caused translocation of NPR1 (nonexpressor of PR1) protein from the cytoplasm into the nucleus indicating that melatonin-elicited pathogen resistance in response to avirulent pathogen attack is SA-dependent in Arabidopsis. PMID:25652756

  15. Increasing serum Pre-adipocyte factor-1 (Pref-1) correlates with decreased body fat, increased free fatty acids, and level of recent alcohol consumption in excessive alcohol drinkers

    PubMed Central

    Liangpunsakul, Suthat; Bennett, Rachel; Westerhold, Chi; Ross, Ruth A.; Crabb, David W.; Lai, Xianyin; Witzmann, Frank A.

    2014-01-01

    Background Patients with alcoholic liver disease have been reported to have a significantly lower percentage of body fat (%BF) than controls. The mechanism for the reduction in %BF in heavy alcohol users has not been elucidated. In adipose tissue, Pref-1 is specifically expressed in pre-adipocytes but not in adipocytes. Pref-1 inhibits adipogenesis and elevated levels are associated with reduced adipose tissue mass. We investigated the association between serum Pref-1 and %BF, alcohol consumption, and serum free fatty acids (FFA) in a well-characterized cohort of heavy alcohol users compared to controls. Methods One hundred forty-eight subjects were prospectively recruited. The Time Line Follow-Back (TLFB) questionnaire was used to quantify the amount of alcohol consumed over the 30-day period before their enrollment. Anthropometric measurements were performed to calculate %BF. Serum Pref-1 and FFA were measured. Results Fifty-one subjects (mean age 32 ± 9 years, 88% men) were non-excessive drinkers whereas 97 were excessive drinkers (mean age 41 ± 18 years, 69% men). Compared to non-excessive drinkers, individuals with excessive drinking had significantly higher levels of Pref-1 (p < 0.01), FFA (p < 0.001), and lower %BF (p = 0.03). Serum levels of Pref-1 were associated with the amount of alcohol consumed during the previous 30 days. Serum Pref-1 was negatively correlated with %BF, but positively associated with serum FFA. Conclusions Our data suggest that elevated Pref-1 levels in excessive drinkers might inhibit the expansion of adipose tissue, decreasing %BF in alcoholics. Further work is needed to validate these findings and to better understand the role of Pref-1 and its clinical significance in subjects with heavy alcohol use. PMID:25449367

  16. Increasing serum pre-adipocyte factor-1 (Pref-1) correlates with decreased body fat, increased free fatty acids, and level of recent alcohol consumption in excessive alcohol drinkers.

    PubMed

    Liangpunsakul, Suthat; Bennett, Rachel; Westerhold, Chi; Ross, Ruth A; Crabb, David W; Lai, Xianyin; Witzmann, Frank A

    2014-12-01

    Patients with alcoholic liver disease have been reported to have a significantly lower percentage of body fat (%BF) than controls. The mechanism for the reduction in %BF in heavy alcohol users has not been elucidated. In adipose tissue, Pref-1 is specifically expressed in pre-adipocytes but not in adipocytes. Pref-1 inhibits adipogenesis and elevated levels are associated with reduced adipose tissue mass. We investigated the association between serum Pref-1 and %BF, alcohol consumption, and serum free fatty acids (FFA) in a well-characterized cohort of heavy alcohol users compared to controls. One hundred forty-eight subjects were prospectively recruited. The Time Line Follow-Back (TLFB) questionnaire was used to quantify the amount of alcohol consumed over the 30-day period before their enrollment. Anthropometric measurements were performed to calculate %BF. Serum Pref-1 and FFA were measured. Fifty-one subjects (mean age 32 ± 9 years, 88% men) were non-excessive drinkers whereas 97 were excessive drinkers (mean age 41 ± 18 years, 69% men). Compared to non-excessive drinkers, individuals with excessive drinking had significantly higher levels of Pref-1 (p<0.01), FFA (p < 0.001), and lower %BF (p = 0.03). Serum levels of Pref-1 were associated with the amount of alcohol consumed during the previous 30 days. Serum Pref-1 was negatively correlated with %BF, but positively associated with serum FFA. Our data suggest that elevated Pref-1 levels in excessive drinkers might inhibit the expansion of adipose tissue, decreasing %BF in alcoholics. Further work is needed to validate these findings and to better understand the role of Pref-1 and its clinical significance in subjects with heavy alcohol use. PMID:25449367

  17. Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria.

    PubMed

    Laschi, Marcella; Bernardini, Giulia; Dreassi, Elena; Millucci, Lia; Geminiani, Michela; Braconi, Daniela; Marzocchi, Barbara; Botta, Maurizio; Manetti, Fabrizio; Santucci, Annalisa

    2016-04-01

    Alkaptonuria (AKU) is a rare multisystem metabolic disease caused by deficient activity of homogentisate 1,2-dioxygenase (HGD), which leads to the accumulation of homogentisic acid (HGA). Currently, there is no treatment for AKU. The sole drug with some beneficial effects is the herbicide nitisinone (1), an inhibitor of p-hydroxyphenylpyruvate dioxygenase (4-HPPD). 1 has been used as a life-saving drug in infants with type I tyrosinemia despite severe side effects due to the buildup of tyrosine. Four clinical trials of nitisinone to treat AKU have shown that 1 consistently decreases HGA levels, but also caused the accumulation of tyrosine in blood serum. Moreover, the human preclinical toxicological data for 1 are incomplete. In this work, we performed pharmacodynamics and toxicological evaluations of 1, providing the first report of LD50 values in human cells. Intracellular tyrosinemia was also evaluated. Three additional 4-HPPD inhibitors with a more favorable profile than that of 1 in terms of IC50, LD50, and tyrosine accumulation were also identified among commercially available compounds. These may be promising starting points for the development of new therapeutic strategies for the treatment of AKU. PMID:26947423

  18. Malate-aspartate shuttle inhibitor aminooxyacetic acid leads to decreased intracellular ATP levels and altered cell cycle of C6 glioma cells by inhibiting glycolysis.

    PubMed

    Wang, Caixia; Chen, Heyu; Zhang, Mingchao; Zhang, Jie; Wei, Xunbin; Ying, Weihai

    2016-08-01

    NADH shuttles, including malate-aspartate shuttle (MAS) and glycerol-3-phosphate shuttle, can shuttle the reducing equivalents of cytosolic NADH into mitochondria. It is widely accepted that the major function of NADH shuttles is to increase mitochondrial energy production. Our study tested the hypothesis that the novel major function of NADH shuttles in cancer cells is to maintain glycolysis by decreasing cytosolic NADH/NAD(+) ratios. We found that AOAA, a widely used MAS inhibitor, led to decreased intracellular ATP levels, altered cell cycle and increased apoptosis and necrosis of C6 glioma cells, without affecting the survival of primary astrocyte cultures. AOAA also decreased the glycolytic rate and the levels of extracellular lactate and pyruvate, without affecting the mitochondrial membrane potential of C6 cells. Moreover, the toxic effects of AOAA were completely prevented by pyruvate treatment. Collectively, our study has suggested that AOAA may be used to selectively decrease glioma cell survival, and the major function of MAS in cancer cells may be profoundly different from its major function in normal cells: The major function of MAS in cancer cells is to maintain glycolysis, instead of increasing mitochondrial energy metabolism. PMID:27157912

  19. Are urban noise pollution levels decreasing?

    PubMed

    Arana, M

    2010-04-01

    The majority of acoustic impact studies developed over the last 50 years have used a similar acoustic parameter (L(eq), L(dn)) but the noise mapping methodology has been very uneven. The selection of the measurement points, the measurement periods, or the evaluation indices have not followed a unique criterion. Therefore, it is not possible to compare the sound pollution levels between different cities from those studies, at least in a rigorous sense. Even more, different studies carried out in the same city by different researchers during different years and using different methodologies are not conclusive whether the acoustic pollution increases or decreases. The present paper shows results, with statistical significance, about the evolution of the acoustic pollution obtained for two Spanish cities, Pamplona and Madrid. In both cases, it can be concluded that noise pollution decreases over time (P<0.01). PMID:20369990

  20. ASCORBID ACID IS DECREASED IN INDUCED SPUTUM OF MILD ASTHMATICS

    EPA Science Inventory

    ABSTRACT
    Evidence suggests that the antioxidant ascorbic acid (AA), plays an essential role in defending against oxidant attack in the airways. Decreased levels of AA have been reported in asthmatics but not at the site directly proximal to asthma pathology, i.e. the bronchial...

  1. Betulinic acid decreases specificity protein 1 (Sp1) level via increasing the sumoylation of sp1 to inhibit lung cancer growth.

    PubMed

    Hsu, Tsung-I; Wang, Mei-Chun; Chen, Szu-Yu; Huang, Shih-Ting; Yeh, Yu-Min; Su, Wu-Chou; Chang, Wen-Chang; Hung, Jan-Jong

    2012-12-01

    Previous studies have shown that the inhibitory effect of betulinic acid (BA) on specificity protein 1 (Sp1) expression is involved in the prevention of cancer progression, but the mechanism of this effect remains to be delineated. In this study, we determined that BA treatment in HeLa cells increased the sumoylation of Sp1 by inhibiting sentrin-specific protease 1 expression. The subsequent recruitment of E3 ubiquitin-protein ligase RING finger protein 4 resulted in ubiquitin-mediated degradation in a 26S-proteosome-dependent pathway. In addition, both BA treatment and mithramycin A (MMA) treatment inhibited lung tumor growth and down-regulated Sp1 protein expression in Kras(G12D)-induced lung cancers of bitransgenic mice. In gene expression profiles of Kras(G12D)-induced lung cancers in bitransgenic mice with and without Sp1 inhibition, 542 genes were affected by MMA treatment. One of the gene products, cyclin A2, which was involved in the S and G(2)/M phase transition during cell cycle progression, was investigated in detail because its expression was regulated by Sp1. The down-regulation of cyclin A2 by BA treatment resulted in decreased retinoblastoma protein phosphorylation and cell cycle G(2)/M arrest. The BA-mediated cellular Sp1 degradation and antitumor effect were also confirmed in a xenograft mouse model by using H1299 cells. The knockdown of Sp1 in lung cancer cells attenuated the tumor-suppressive effect of BA. Taken together, the results of this study clarify the mechanism of BA-mediated Sp1 degradation and identify a pivotal role for Sp1 in the BA-induced repression of lung cancer growth. PMID:22956772

  2. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels.

    PubMed

    Reddy, I A; Pino, J A; Weikop, P; Osses, N; Sørensen, G; Bering, T; Valle, C; Bluett, R J; Erreger, K; Wortwein, G; Reyes, J G; Graham, D; Stanwood, G D; Hackett, T A; Patel, S; Fink-Jensen, A; Torres, G E; Galli, A

    2016-01-01

    Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from the ventral tegmental area to the LS and express the DA transporter (DAT). Cocaine acts by altering DA bioavailability by targeting the DAT. Therefore, GLP-1R signaling might exert effects on DAT to account for its regulation of cocaine-induced behaviors. We show that the GLP-1R is highly expressed within the LS. GLP-1, in LS slices, significantly enhances DAT surface expression and DAT function. Exenatide (Ex-4), a long-lasting synthetic analog of GLP-1 abolished cocaine-induced elevation of DA. Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA). Notably, AA reduces septal DAT function pointing to AA as a novel regulator of central DA homeostasis. We further show that AA oxidation product γ-ketoaldehyde (γ-KA) forms adducts with the DAT and reduces DAT plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA. PMID:27187231

  3. Temperature shift experiments suggest that metabolic impairment and enhanced rates of photorespiration decrease organic acid levels in soybean leaflets exposed to supra-optimal growth temperatures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrate, malate, malonate, fumarate and succinate in soybean leaflets decreased 40 to 80% when plants were grown continuously in controlled environment chambers at 36/28 compared to 28/20 °C. Glycerate was not temperature responsive in this study. Temperature effects on the above mentioned organi...

  4. Decreased selenium levels in acute myocardial infarction

    SciTech Connect

    Kok, F.J.; Hofman, A.; Witteman, J.C.M.; de Bruijn, A.M.; Kruyssen, D.H.C.M.; de Bruin, M.; Valkenburg, H.A. )

    1989-02-24

    To study the association between selenium status and the risk of myocardial infarction, the authors compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls. Because toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event.

  5. Cadmium level of metro sludge steadily decreases

    SciTech Connect

    Not Available

    1989-04-01

    According to a preliminary review of 1988 cadmium levels, sludge from Seattle Metro's West Point and Renton treatment plants averaged under 25 ppm per year. Data will be officially analyzed and published this spring. The sludge Metro recycles as fertilizer is high-quality for all metals. Federal guidelines require cadmium levels in sludge to be below 25 ppm for sludge to be applied to food-chain crops. As a policy, Metro does not apply the sludge to food chain crops. Instead, the agency recycles its sludge in forestry, soil improvement and composting projects. The metal reduction is attributed to a municipal control project to reduce corrosion of water pipes and to Metro's industrial waste pretreatment program.

  6. Huggable communication medium decreases cortisol levels

    PubMed Central

    Sumioka, Hidenobu; Nakae, Aya; Kanai, Ryota; Ishiguro, Hiroshi

    2013-01-01

    Interpersonal touch is a fundamental component of social interactions because it can mitigate physical and psychological distress. To reproduce the psychological and physiological effects associated with interpersonal touch, interest is growing in introducing tactile sensations to communication devices. However, it remains unknown whether physical contact with such devices can produce objectively measurable endocrine effects like real interpersonal touching can. We directly tested this possibility by examining changes in stress hormone cortisol before and after a conversation with a huggable communication device. Participants had 15-minute conversations with a remote partner that was carried out either with a huggable human-shaped device or with a mobile phone. Our experiment revealed significant reduction in the cortisol levels for those who had conversations with the huggable device. Our approach to evaluate communication media with biological markers suggests new design directions for interpersonal communication media to improve social support systems in modern highly networked societies. PMID:24150186

  7. Rosuvastatin Decreases Intestinal Fatty Acid Binding Protein (I-FABP), but Does Not Alter Zonulin or Lipopolysaccharide Binding Protein (LBP) Levels, in HIV-Infected Subjects on Antiretroviral Therapy

    PubMed Central

    Funderburg, Nicholas T.; Boucher, Morgan; Sattar, Abdus; Kulkarni, Manjusha; Labbato, Danielle; Kinley, Bruce I.; McComsey, Grace A.

    2016-01-01

    Introduction Altered gastrointestinal (GI) barrier integrity and subsequent microbial translocation may contribute to immune activation in HIV infection. We have reported that rosuvastatin improved several markers of immune activation in HIV+ participants, but the effect of statin treatment on markers of GI barrier dysfunction is unknown. Methods SATURN-HIV is a randomized, double-blind, placebo-controlled trial assessing the effect of rosuvastatin (10mg/daily) on markers of cardiovascular disease, inflammation, and immune activation in ART-treated patients. Gut-barrier integrity was assessed by the surrogate markers intestinal fatty acid binding protein (I-FABP), a marker of enterocyte death, and zonulin-1, a marker of gut epithelial cell function. Levels of lipopolysaccharide binding protein (LBP) were measured as a marker of microbial translocation. Results Rosuvastatin significantly reduced levels of I-FABP during the treatment period compared to the placebo. There was no effect of rosuvastatin treatment on levels of zonulin or LBP. Baseline levels of LBP were directly related to several markers of immune activation in samples from all participants, including soluble CD163, IP-10, VCAM-1, TNFR-II, and the proportion of CD4+ and CD8+ T cells expressing CD38 and HLA-DR. Many of these relationships, however, were not seen in the statin arm alone at baseline or over time, as inflammatory markers often decreased and LBP levels were unchanged. Conclusions Forty-eight weeks of rosuvastatin treatment reduced levels of I-FABP, but did not affect levels of zonulin or LBP. The reduction in levels of inflammatory markers that we have reported with rosuvastatin treatment is likely mediated through other mechanisms not related to gut integrity or microbial translocation.

  8. Recovery of Neonatal Head Turning to Decreased Sound Pressure Level.

    ERIC Educational Resources Information Center

    Tarquinio, Nancy; And Others

    1990-01-01

    Investigated newborns' responses to decreased sound pressure level (SPL) by means of a localized head turning habituation procedure. Findings, which demonstrated recovery of neonatal head turning to decreased SPL, were inconsistent with the selective receptor adaptation model. (RH)

  9. Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats

    PubMed Central

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

    2015-01-01

    Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

  10. Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

    PubMed

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

    2015-01-01

    Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography-tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

  11. Tigecycline Treatment Causes a Decrease in Fibrinogen Levels

    PubMed Central

    Zhang, Qian; Zhou, Suming

    2014-01-01

    The objective of this study was to assess the impact of tigecycline treatment on coagulation parameters, specifically fibrinogen, in patients with severe infections. We examined 20 cases of tigecycline-treated patients with severe infections, including hospital-acquired pneumonia, complicated intra-abdominal infections, complicated skin and soft tissue infections, and bloodstream infections. We monitored the relative markers of coagulation and renal and liver function before, during, and after treatment. Fibrinogen (FIB) levels decreased significantly after the use of tigecycline and normalized after the cessation of treatment. FIB levels significantly decreased in the patients treated with the recommended dose or a higher treatment dose. The FIB levels decreased more in the higher-treatment-dose group. There was no difference in the decrease in FIB levels or the FIB level recovery by age. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged after tigecycline use. The TT decreased after the cessation of treatment, and the PT and APTT also decreased but not to a significant level. There was no change in platelet, alanine aminotransferase (ALT), or creatinine (Cr) levels associated with treatment. The use of tigecycline was associated with decreased FIB levels, which returned to normal after the cessation of treatment. A high-dose treatment group showed greater decreases in FIB levels than did patients treated with the recommended dose. The decline in FIB was not related to patient age. The use of tigecycline was associated with prolonged PT, APTT, and TT. PMID:25547356

  12. ASCORBIC ACID IS DECREASED IN INDUCED SPUTUM OF MILD ASTHMATICS

    EPA Science Inventory

    Asthma is primarily an airways inflammatory disease, and the bronchial airways have been shown to be particularly susceptible to oxidant-induced tissue damage. The antioxidant ascorbic acid (AA) plays an essential role in defending against oxidant attack in the airways. Decreased...

  13. Using nonesterified fatty acids and β-hydroxybutyrate concentrations during the transition period for herd-level monitoring of increased risk of disease and decreased reproductive and milking performance.

    PubMed

    Ospina, Paula A; McArt, Jessica A; Overton, Thomas R; Stokol, Tracy; Nydam, Daryl V

    2013-07-01

    Dairy cows visit a state of negative energy balance (NEB) as they transition from late gestation to early lactation. At the individual level, there are several metabolic adaptations to manage NEB, including mobilization of nonesterified fatty acids (NEFA) from body fat reserves and glucose sparing for lactogenesis. Based on current pen-level feeding and management practices, strategies to minimize excessive NEB in both the individual and herd should focus on herd-level testing and management. This article reviews strategies for testing and monitoring of excessive NEB at the herd level through individual testing of 2 energy markers: NEFA and β-hydroxybutyrate. PMID:23809897

  14. Intravenous Tranexamic Acid Decreases Allogeneic Transfusion Requirements in Periacetabular Osteotomy.

    PubMed

    Bryan, Andrew J; Sanders, Thomas L; Trousdale, Robert T; Sierra, Rafael J

    2016-01-01

    Bernese (Ganz) periacetabular osteotomy is associated with significant blood loss and the need for perioperative transfusion. Tranexamic acid decreases blood loss and minimizes transfusion rates in total joint arthroplasty. However, no reports have described its use in patients undergoing Bernese periacetabular osteotomy. This study reports the use of intravenous tranexamic acid in these patients. The study included 137 patients (150 hips) who underwent isolated periacetabular osteotomy at a single institution between 2003 and 2014. Of these, 68 patients (75 hips) received intravenous tranexamic acid 1 g at the time of incision and 1 g at the time of closure. A group of 69 patients (75 hips) served as control subjects who underwent periacetabular osteotomy without administration of intravenous tranexamic acid. Thromboembolic disease was defined as deep venous thrombosis or pulmonary embolism occurring within 6 weeks of surgery. Outcomes measured included transfusion requirements, pre- and postoperative hemoglobin values, operative times, and thromboembolic disease rates. Aspirin was used as the thromboembolic prophylactic regimen in 95% of patients. The rate of allogeneic transfusion was 0 in the tranexamic acid group compared with 21% in the control group (P=.0001). No significant difference was found in the autologous cell salvage requirement (.96 vs 1.01; P=.43) or the thromboembolic disease rate between the tranexamic acid group and the control group (2.67% vs 1.33%; P=.31). The use of intravenous tranexamic acid led to a decreased transfusion requirement with no increased risk of thromboembolic disease in this contemporary cohort of patients undergoing periacetabular osteotomy. PMID:26726988

  15. Can Delignification Decrease Cellulose Digestibility in Acid Pretreated Corn Stover?

    SciTech Connect

    Ishizawa, C. I.; Jeoh, T.; Adney, W. S.; Himmel, M. E.; Johnson, D. K.; Davis, M. F.

    2009-01-01

    It has previously been shown that the improved digestibility of dilute acid pretreated corn stover is at least partially due to the removal of xylan and the consequent increase in accessibility of the cellulose to cellobiohydrolase enzymes. We now report on the impact that lignin removal has on the accessibility and digestibility of dilute acid pretreated corn stover. Samples of corn stover were subjected to dilute sulfuric acid pretreatment with and without simultaneous (partial) lignin removal. In addition, some samples were completely delignified after the pretreatment step using acidified sodium chlorite. The accessibility and digestibility of the samples were tested using a fluorescence-labeled cellobiohydrolase (Trichoderma reesei Cel7A) purified from a commercial cellulase preparation. Partial delignification of corn stover during dilute acid pretreatment was shown to improve cellulose digestibility by T. reesei Cel7A; however, decreasing the lignin content below 5% (g g{sup -1}) by treatment with acidified sodium chlorite resulted in a dramatic reduction in cellulose digestibility. Importantly, this effect was found to be enhanced in samples with lower xylan contents suggesting that the near complete removal of xylan and lignin may cause aggregation of the cellulose microfibrils resulting in decreased cellulase accessibility.

  16. [Is it possible to decrease cholesterol levels with dietary supplements?].

    PubMed

    Rodondi, Pierre-Yves; Degoumois, Florence; Marques-Vidal, Pedro; Rodondi, Nicolas

    2016-03-01

    Patients often use dietary supplements for cardiovascular prevention. An US study showed that 75% of patients with cardiovascular disease used dietary supplements. Red yeast rice, phytosterols and fibers can significantly decrease LDL. The level of monacolin in red yeast rice can vary between products and toxins can sometimes be found. Prospective studies showed that fibers could decrease cardiovascular risk. Others substances, like guggul, soy and artichoke leaf extracts, did not show a clear benefit for cardiovascular prevention. Measurements of cholesterol levels can help the physician to discuss with his patient about the effects of some dietary supplements. PMID:27089602

  17. Psychiatric considerations in patients with decreased levels of consciousness.

    PubMed

    Young, James L; Rund, Douglas

    2010-08-01

    When patients present to the emergency department with changes in behavior and levels of consciousness, psychiatric causes often move to the top of the list of diagnostic considerations. It is important to thoroughly assess such patients for medical causes. Although it is not common for primary psychiatric conditions to present with altered levels of consciousness, severe cases may present in this fashion. Altered mental states may also be caused by adverse reactions to psychiatric medications. In this article, the authors review some of the psychiatric causes of decreased levels of consciousness, as well as certain adverse drug reactions to psychotropic medications. PMID:20709245

  18. Decreased Circulating Levels of APRIL: Questioning Its Role in Diabetes

    PubMed Central

    Carvalho-Santos, Adriana; Ribeiro-Alves, Marcelo; Cardoso-Weide, Luciene Carvalho; Nunes, Joyce; Kuhnert, Lia Rafaella Ballard; Xavier, Analucia Rampazzo; Cunha, Samuel; Hahne, Michael; Villa-Verde, Déa Maria Serra; Carvalho-Pinto, Carla Eponina

    2015-01-01

    Diabetes mellitus is a chronic disease that affects over 382 million people worldwide. Type-1 Diabetes (T1D) is classified as an autoimmune disease that results from pancreatic β-cell destruction and insulin deficiency. Type-2 Diabetes (T2D) is characterized principally by insulin resistance in target tissues followed by decreased insulin production due to β-cell failure. It is challenging to identify immunological markers such as inflammatory molecules that are triggered in response to changes during the pathogenesis of diabetes. APRIL is an important member of the TNF family and has been linked to chronic inflammatory processes of various diseases since its discovery in 1998. Therefore, this study aimed to evaluate APRIL serum levels in T1D and T2D. For this, we used the ELISA assay to measure serum APRIL levels of 33 T1D and 30 T2D patients, and non-diabetic subjects as control group. Our data showed a decrease in serum APRIL levels in T1D patients when compared with healthy individuals. The same pattern was observed in the group of T2D patients when compared with the control. The decrease of serum APRIL levels in diabetic patients suggests that this cytokine has a role in T1D and T2D. Diabetes is already considered as an inflammatory condition with different cytokines being implicated in its physiopathology. Our data suggest that APRIL can be considered as a potential modulating cytokine in the inflammatory process of diabetes. PMID:26469782

  19. Decreased Circulating Levels of APRIL: Questioning Its Role in Diabetes.

    PubMed

    Carvalho-Santos, Adriana; Ribeiro-Alves, Marcelo; Cardoso-Weide, Luciene Carvalho; Nunes, Joyce; Kuhnert, Lia Rafaella Ballard; Xavier, Analucia Rampazzo; Cunha, Samuel; Hahne, Michael; Villa-Verde, Déa Maria Serra; Carvalho-Pinto, Carla Eponina

    2015-01-01

    Diabetes mellitus is a chronic disease that affects over 382 million people worldwide. Type-1 Diabetes (T1D) is classified as an autoimmune disease that results from pancreatic β-cell destruction and insulin deficiency. Type-2 Diabetes (T2D) is characterized principally by insulin resistance in target tissues followed by decreased insulin production due to β-cell failure. It is challenging to identify immunological markers such as inflammatory molecules that are triggered in response to changes during the pathogenesis of diabetes. APRIL is an important member of the TNF family and has been linked to chronic inflammatory processes of various diseases since its discovery in 1998. Therefore, this study aimed to evaluate APRIL serum levels in T1D and T2D. For this, we used the ELISA assay to measure serum APRIL levels of 33 T1D and 30 T2D patients, and non-diabetic subjects as control group. Our data showed a decrease in serum APRIL levels in T1D patients when compared with healthy individuals. The same pattern was observed in the group of T2D patients when compared with the control. The decrease of serum APRIL levels in diabetic patients suggests that this cytokine has a role in T1D and T2D. Diabetes is already considered as an inflammatory condition with different cytokines being implicated in its physiopathology. Our data suggest that APRIL can be considered as a potential modulating cytokine in the inflammatory process of diabetes. PMID:26469782

  20. Decreased frontal lobe phosphocreatine levels in methamphetamine users

    PubMed Central

    Sung, Young-Hoon; Yurgelun-Todd, Deborah A.; Shi, Xian-Feng; Kondo, Douglas G.; Lundberg, Kelly J.; McGlade, Erin C.; Hellem, Tracy L.; Huber, Rebekah S.; Fiedler, Kristen K.; Harrell, Renee E.; Nickerson, Bethany R.; Kim, Seong-Eun; Jeong, Eun-Kee; Renshaw, Perry F.

    2012-01-01

    BACKGROUND Mitochondria-related mechanisms have been suggested to mediate methamphetamine (METH) toxicity. However, changes in brain energetics associated with highenergy phosphate metabolism have not been investigated in METH users. Phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) was used to evaluate changes in mitochondrial high energy phosphates, including phosphocreatine (PCr) and β-nucleoside triphosphate (β-NTP, primarily ATP in brain) levels. We hypothesized that METH users would have decreased high-energy PCr levels in the frontal gray matter. METHODS Study participants consisted of 51 METH (age=32.8±6.7) and 23 healthy comparison (age=31.1±7.5) subjects. High-energy phosphate metabolite levels were compared between the groups and potential gender differences were explored. RESULTS METH users had lower ratios of PCr to total pool of exchangeable phosphate (PCr/TPP) in the frontal lobe as compared to the healthy subjects (p=0.001). The lower PCr levels in METH subjects were significantly associated with lifetime amount of METH use (p=0.003). A sub-analysis for gender differences revealed that female METH users, who had lower daily amounts (1.1±1.0 gram) of METH use than males (1.4±1.7 gram), had significantly lower PCr/TPP ratios than male METH users, controlling for the amount of METH use (p=0.02). CONCLUSIONS The present findings suggest that METH compromises frontal lobe high-energy phosphate metabolism in a dose-responsive manner. Our findings also suggest that the abnormality in frontal lobe high-energy phosphate metabolism might be more prominent in female than in male METH users. This is significant as decreased PCr levels have been associated with depressive symptoms, and poor responses to antidepressant treatment have been reported in those with decreased PCr levels. PMID:23084413

  1. Decreased consumption of branched chain amino acids improves metabolic health

    PubMed Central

    Arriola Apelo, Sebastian I.; Neuman, Joshua C.; Kasza, Ildiko; Schmidt, Brian A.; Cava, Edda; Spelta, Francesco; Tosti, Valeria; Syed, Faizan A.; Baar, Emma L.; Veronese, Nicola; Cottrell, Sara E.; Fenske, Rachel J.; Bertozzi, Beatrice; Brar, Harpreet K.; Pietka, Terri; Bullock, Arnold D.; Figenshau, Robert S.; Andriole, Gerald L.; Merrins, Matthew J.; Alexander, Caroline M.; Kimple, Michelle E.; Lamming, Dudley W.

    2016-01-01

    Protein restricted, high carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Further, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderately protein restricted (PR) diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet, via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health, and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet. PMID:27346343

  2. Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis

    PubMed Central

    Oliveira, Flora Magno de Jesus; Burth, Patrícia; Bozza, Patrícia Torres; Castro Faria, Mauro Velho; Silva, Adriana Ribeiro; de Castro-Faria-Neto, Hugo Caire

    2016-01-01

    Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA) are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA), a monounsaturated fatty acid (MUFA). We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP). OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS) production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A) mRNA levels were increased, while uncoupling protein 2 (UCP2) liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK) expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA). PMID:27078880

  3. Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis.

    PubMed

    Gonçalves-de-Albuquerque, Cassiano Felippe; Medeiros-de-Moraes, Isabel Matos; Oliveira, Flora Magno de Jesus; Burth, Patrícia; Bozza, Patrícia Torres; Castro Faria, Mauro Velho; Silva, Adriana Ribeiro; Castro-Faria-Neto, Hugo Caire de

    2016-01-01

    Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA) are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA), a monounsaturated fatty acid (MUFA). We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP). OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS) production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A) mRNA levels were increased, while uncoupling protein 2 (UCP2) liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK) expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA). PMID:27078880

  4. Forearm muscle oxygenation decreases with low levels of voluntary contraction

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Kahan, N. J.; Hargens, A. R.; Rempel, D. M.

    1997-01-01

    The purpose of our investigation was to determine if the near infrared spectroscopy technique was sensitive to changes in tissue oxygenation at low levels of isometric contraction in the extensor carpi radialis brevis muscle. Nine subjects were seated with the right arm abducted to 45 degrees, elbow flexed to 85 degrees, forearm pronated 45 degrees, and wrist and forearm supported on an armrest throughout the protocol. Altered tissue oxygenation was measured noninvasively with near infrared spectroscopy. The near infrared spectroscopy probe was placed over the extensor carpi radialis brevis of the subject's right forearm and secured with an elastic wrap. After 1 minute of baseline measurements taken with the muscle relaxed, four different loads were applied just proximal to the metacarpophalangeal joint such that the subjects isometrically contracted the extensor carpi radialis brevis at 5, 10, 15, and 50% of the maximum voluntary contraction for 1 minute each. A 3-minute recovery period followed each level of contraction. At the end of the protocol, with the probe still in place, a value for ischemic tissue oxygenation was obtained for each subject. This value was considered the physiological zero and hence 0% tissue oxygenation. Mean tissue oxygenation (+/-SE) decreased from resting baseline (100% tissue oxygenation) to 89 +/- 4, 81 +/- 8, 78 +/- 8, and 47 +/- 8% at 5, 10, 15, and 50% of the maximum voluntary contraction, respectively. Tissue oxygenation levels at 10, 15, and 50% of the maximum voluntary contraction were significantly lower (p < 0.05) than the baseline value. Our results indicate that tissue oxygenation significantly decreases during brief, low levels of static muscle contraction and that near infrared spectroscopy is a sensitive technique for detecting deoxygenation noninvasively at low levels of forearm muscle contraction. Our findings have important implications in occupational medicine because oxygen depletion induced by low levels of muscle

  5. Pentoxifylline Decreases Serum Level of Adhesion Molecules in Atherosclerosis Patients

    PubMed Central

    Mohammadpour, Amir Hooshang; Falsoleiman, Homa; Shamsara, Jamal; Abadi, Ghazaleh Allah; Rasooli, Ramin; Ramezani, Mohammad

    2014-01-01

    Background: Inflammation is involved in development, progression, and complications of atherosclerotic disease. Clinical studies have indicated that the level of monocyte chemoattractant protein 1 (MCP-1), IL-18, and adhesion molecules correlates with the severity of atherosclerosis and can predict future cardiovascular events. Experimental studies have shown pentoxifylline (PTX) reduces these factors in animal models. The purpose of the present pilot study was to evaluate effect of PTX on a group of inflammatory biomarkers in patients with coronary artery disease (CAD). Methods: Forty patients with angiographically documented CAD, who fulfilled inclusion and exclusion criteria, were entered in the double-blind, randomized, pilot clinical study. The patients were randomly given PTX (400 mg three times daily) or placebo (3 tab/day) for 2 months. Serum concentrations of MCP-1, IL-18, intercellular adhesion Molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured before and at the end of intervention by enzyme-linked immunosorbant assay. Results: Our study showed that the serum levels of ICAM-1 and VCAM-1 was decreased in the study population after two-month treatment (P<0.05). Conclusion: Based on the results of our pilot study, administration of PTX in CAD patients significantly decreases adhesion molecules levels. PMID:24375159

  6. From aquatic to terrestrial food webs: decrease of the docosahexaenoic acid/linoleic acid ratio.

    PubMed

    Koussoroplis, Apostolos-Manuel; Lemarchand, Charles; Bec, Alexandre; Desvilettes, Christian; Amblard, Christian; Fournier, Christine; Berny, Philippe; Bourdier, Gilles

    2008-05-01

    Fatty acid composition of the adipose tissue of six carnivorous mammalian species (European otter Lutra lutra, American mink Mustela vison, European Mink Mustela lutreola, European polecat Mustela putorius, stone marten Martes foina and European wild cat Felis silvestris) was studied. These species forage to differing degrees in aquatic and terrestrial food webs. Fatty acid analysis revealed significant differences in polyunsaturated fatty acid composition between species. More specifically, our results underline a gradual significant decrease in the docosahexaenoic acid (DHA)/linoleic acid (LNA) ratio of carnivore species as their dependence on aquatic food webs decreases. In conclusion, the use of the DHA/LNA ratio in long-term studies is proposed as a potential proxy of changes in foraging behaviour of semi-aquatic mammals. PMID:18335265

  7. PBDE levels in breast milk are decreasing in California.

    PubMed

    Guo, Weihong; Holden, Arthur; Smith, Sabrina Crispo; Gephart, Rosanne; Petreas, Myrto; Park, June-Soo

    2016-05-01

    To assess the efficacy of the bans in reducing PBDE levels, we recruited 67 California first time mothers (sampled during 2009-2012) and collected cord blood at birth (n = 31), breast milk (n = 66) and maternal blood (n = 65) at 3-8 weeks postpartum. Using the same sample extraction procedures and analytical instrumentation method (GC-HRMS), we compared PBDE as well as PCB levels in these breast milk samples to those from our previous study (n = 82, sampled during 2003-2005) and found that the sum of PBDEs over the ∼7 year course declined by 39% (GeoMean = 67.8 ng/g lipid in 2003-2005; 41.5 ng/g lipid in 2009-2012) and that the sum of PCBs declined by 36% (GeoMean = 71.6 ng/g lipid in 2003-2005; 45.7 ng/g lipid in 2009-2012). This supports our earlier finding of a PBDE decline (39%) in blood. We also found that the PBDE concentrations and congener profiles were similar in breast milk and their matched maternal/cord blood: BDE-47 was the dominant congener, followed by BDE-153, -99, and -100. Similar levels and congener profiles of PBDEs in these matrices suggest that they are at equilibrium. Therefore, we propose that maternal serum levels may be used to predict an infant's daily dose of PBDE exposure from breastfeeding when breast milk levels are not available. In addition, our study confirmed that breastfeeding babies are still exposed to high levels of PBDEs, even though PBDE levels are decreasing. PMID:26693645

  8. Increased kinin levels and decreased responsiveness to kinins during aging.

    PubMed

    Pérez, Viviana; Velarde, Victoria; Acuña-Castillo, Claudio; Gómez, Christian; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe

    2005-08-01

    Kinins are vasoactive peptides released from precursors called kininogens, and serum levels of both T- and K-kininogens increase dramatically as rats age. Kinin release is tightly regulated, and here we show that serum kinin levels also increase with age, from 63 +/- 16 nmol/L in young Fisher 344 rats to 398 +/- 102 nmol/L in old animals. Both K- and T-kininogens contribute sequentially to this increase, with the increase in middle-aged animals being driven primarily by K-kininogen, whereas the further augmentation in older rats occurs by increasing T-kininogen. By measuring ERK activation, we show that aorta endothelial cells from old animals are hyporesponsive to exogenous bradykinin. However, if serum kinin levels are experimentally decreased by lipopolysaccharide treatment, then the endothelial response to bradykinin is re-established. These results indicate that serum levels of kinins increase with age, whereas the responsiveness of target cells to kinins is reduced in these same animals. PMID:16127100

  9. Activation of the Nrf2 pathway, but decreased {gamma}-glutamylcysteine synthetase heavy subunit chain levels and caspase-3-dependent apoptosis during exposure of primary mouse hepatocytes to diphenylarsinic acid

    SciTech Connect

    Sumi, Daigo; Manji, Aiko; Shinkai, Yasuhiro; Toyama, Takashi; Kumagai, Yoshito

    2007-09-15

    Diphenylarsinic acid (DPAsV) is a degradation product of chemical warfare agents, over which there has been a public outcry in the Kamisu Area of Ibaraki Prefecture in Japan. In this study, we investigated the cytotoxicity of and cellular response to DPAsV in primary mouse hepatocytes. Exposure of the hepatocytes to DPAsV resulted in cell damage accompanied by cellular accumulation of DPAsV in a time-dependent manner. The cell death caused by DPAsV was attributable to apoptosis. DPAsV activated a basic leucine-zipper transcription factor Nrf2 as determined by the nuclear translocation of Nrf2, anti-oxidant response element (ARE)-dependent luciferase activity, and upregulation of downstream gene products. However, {gamma}-glutamylcysteine synthetase heavy subunit chain ({gamma}-GCS{sub H}), which is regulated by Nrf2, underwent cleavage by activated caspase-3 to a 17 kDa fragment, leading to a minimal level of constitutive {gamma}-GCS{sub H} expression 72 h following the exposure (25 {mu}M). Experiments with cycloheximide revealed that the DPAsV-mediated reduction in {gamma}-GCS{sub H} was due to a post-translational modification. The results suggest that DPAsV causes caspase-3-dependent cleavage of {gamma}-GCS{sub H} regardless of Nrf2 activation in primary mouse hepatocytes.

  10. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    PubMed

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. PMID:25616451

  11. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    SciTech Connect

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  12. Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells

    PubMed Central

    Natarelli, Lucia; Ranaldi, Giulia; Leoni, Guido; Roselli, Marianna; Guantario, Barbara; Comitato, Raffaella; Ambra, Roberto; Cimino, Francesco; Speciale, Antonio; Virgili, Fabio; Canali, Raffaella

    2015-01-01

    Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG). In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9) and effector caspases (caspase 7 and 3) and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins. PMID:26544184

  13. New discovery of cryptorchidism: Decreased retinoic acid in testicle.

    PubMed

    Peng, Jinpu; Shen, Lianju; Chen, Jinjun; Cao, Xining; Zhou, Yue; Weng, Huali; Long, Chunlan; Zhang, Deying; Tu, Shengfen; Zhang, Yan; He, Dawei; Lin, Tao; Wei, Guanghui

    2016-05-01

    This study focuses on investigation of cryptorchidism induced by flutamide (Flu) and its histopathological damage, and detects retinoic acid concentration in testicle tissue, in order to find a new method for clinical treatment to infertility caused by cryptorchidism. Twenty SD (Sprague Dawley) pregnant rats were randomly divided into Flu cryptorchidism group (n = 10) and normal control group (n = 10). HE stained for observing morphological difference. Transmission electron microscope (TEM) was used for observing the tight junction structure between Sertoli cells. Epididymal caudal sperms were counted and observed in morphology. The expression of stimulated by retinoic acid gene 8 (Stra8) was detected using immunohistochemistry, western blot, and Q-PCR. High performance liquid chromatography (HPLC) analysis was made on retinoic acid content. Sperm count and morphology observation confirmed cryptorchidism group was lower than normal group in sperm quantity and quality. The observation by TEM showed a loose structure of tight junctions between Sertoli cells. Immunohistochemistry, western blot, and Q-PCR showed that cryptorchidism group was significantly lower than normal group in the expression of Stra8. HPLC showed that retinoic acid content was significantly lower in cryptorchid testis than in normal testis. In the cryptorchidism model, retinoic acid content in testicular tissue has a significant reduction; testicles have significant pathological changes; damage exists in the structure of tight junctions between Sertoli cells; Stra8 expression has a significant reduction, perhaps mainly contributing to spermatogenesis disorder. PMID:27275115

  14. Krill oil significantly decreases 2-arachidonoylglycerol plasma levels in obese subjects.

    PubMed

    Banni, Sebastiano; Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Giordano, Elena; Sirigu, Anna Rita; Berge, Kjetil; Vik, Hogne; Maki, Kevin C; Di Marzo, Vincenzo; Griinari, Mikko

    2011-01-01

    We have previously shown that krill oil (KO), more efficiently than fish oil, was able to downregulate the endocannabinoid system in different tissues of obese zucker rats.We therefore aimed at investigating whether an intake of 2 g/d of either KO or menhaden oil (MO), which provides 309 mg/d of EPA/DHA 2:1 and 390 mg/d of EPA/DHA 1:1 respectively, or olive oil (OO) for four weeks, is able to modify plasma endocannabinoids in overweight and obese subjects.The results confirmed data in the literature describing increased levels of endocannabinoids in overweight and obese with respect to normo-weight subjects. KO, but not MO or OO, was able to significantly decrease 2-arachidonoylglycerol (2-AG), although only in obese subjects. In addition, the decrease of 2-AG was correlated to the plasma n-6/n-3 phospholipid long chain polyunsaturated fatty acid (LCPUFA) ratio. These data show for the first time in humans that relatively low doses of LCPUFA n-3 as KO can significantly decrease plasma 2-AG levels in obese subjects in relation to decrease of plasma phospholipid n-6/n-3 LCPUFA ratio. This effect is not linked to changes of metabolic syndrome parameters but is most likely due to a decrease of 2-AG biosynthesis caused by the replacement of 2-AG ultimate precursor, arachidonic acid, with n-3 PUFAs, as previously described in obese Zucker rats. PMID:21276269

  15. Decreased valproate level caused by VPA-glucuronidase inhibition by carbapenem antibiotics.

    PubMed

    Nakamura, Yutaka; Nakahira, Keiko; Mizutani, Takaharu

    2008-12-01

    The serum concentration of valproic acid (VPA) in epilepsy patients decreased in the administration of carbapenem antibiotics (CP), such as meropenem, panipenem, biapenem or imipenem, to a sub-therapeutic level. The liver is the key organ for the decrease of VPA concentration by CP, because it has been reported that no decrease of the VPA level by CP was found in hepatectomized rats. This effect was also shown with monkey and rat liver slices. In this report, we show the results of in vitro inhibition of VPA-glucuronidase in human liver microsomes and cytosol by CP. We found the highest metabolic activity of VPA-glucuronide in human liver cytosol. The level in liver cytosol was 149 pmol/min/mg protein. The level in human liver microsomes (HLM) was one-fifth of that in cytosol and the level in serum was negligible. We found that this hydrolysis depends on VPA-glucuronidase in cytosol, because digestion was inhibited by D-saccharic acid 1,4-lactonemonohydrate of a specific inhibitor of beta-glucuronidase, but not by phenylmethylsulfonylfluoride of an esterase inhibitor. We also found the inhibition of VPA-glucuronidase in cytosol by CP, and the maximum inhibition was found with panipenem (IC(50) = 3 microM). We also found inhibition of VPA-glucuronidase in HLM by meropenem. These results showed that the inhibition in liver slices depended on the inhibition of VPA-glucuronidase by CP. We considered that the inhibition of VPA-glucuronidase by CP in cytosol is a key factor to decrease the plasma VPA level. PMID:19356106

  16. Decreased Coenzyme Q10 Levels in Multiple System Atrophy Cerebellum.

    PubMed

    Barca, Emanuele; Kleiner, Giulio; Tang, Guomei; Ziosi, Marcello; Tadesse, Saba; Masliah, Eliezer; Louis, Elan D; Faust, Phyllis; Kang, Un J; Torres, Jose; Cortes, Etty P; Vonsattel, Jean-Paul G; Kuo, Sheng-Han; Quinzii, Catarina M

    2016-07-01

    In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q10 (CoQ10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ10 biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ10 deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ10 To investigate whether CoQ10 deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ10 levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, and 12 controls. We also assessed mitochondrial respiratory chain enzyme activities, oxidative stress, mitochondrial mass, and levels of enzymes involved in CoQ biosynthesis. Our studies revealed CoQ10 deficiency in MSA cerebellum, which was associated with impaired CoQ biosynthesis and increased oxidative stress in the absence of COQ2 mutations. The levels of CoQ10 in the cerebella of ET and PD patients were comparable or higher than in controls. These findings suggest that CoQ10 deficiency may contribute to the pathogenesis of MSA. Because no disease modifying therapies are currently available, increasing CoQ10 levels by supplementation or upregulation of its biosynthesis may represent a novel treatment strategy for MSA patients. PMID:27235405

  17. Decrease in erythrocyte glycophorin sialic acid content is associated with increased erythrocyte aggregation in human diabetes.

    PubMed

    Rogers, M E; Williams, D T; Niththyananthan, R; Rampling, M W; Heslop, K E; Johnston, D G

    1992-03-01

    1. Sialic acid moieties of erythrocyte membrane glycoproteins are the principal determinants of the negative charge on the cell surface. The resultant electrostatic repulsion between the cells reduces erythrocyte aggregation and hence the low shear rate viscosity and yield stress of blood. 2. Using g.c.-m.s., a decrease in sialic acid content has been observed in the major erythrocyte membrane glycoprotein, glycophorin A, obtained from nine diabetic patients compared with that from seven normal control subjects [median (range): 3.30 (0.01-11.90) versus 18.60 (3.20-32.60) micrograms/100 micrograms of protein, P less than 0.02]. 3. Erythrocyte aggregation, measured by viscometry as the ratio of suspension viscosity to supernatant viscosity (LS/S) in fibrinogen solution, was increased in ten diabetic patients compared with ten normal control subjects (mean +/- SEM, 37.6 +/- 1.3 versus 33.8 +/- 0.6, P less than 0.02). 4. In the patients in whom both viscometry and carbohydrate analysis were performed, the decrease in erythrocyte glycophorin sialylation and the increase in erythrocyte aggregation in fibrinogen solution were related statistically (LS/S correlated negatively with glycophorin sialic acid content, r = 0.73, P less than 0.05). 5. Decreased glycophorin sialylation provides an explanation at the molecular level for increased erythrocyte aggregation and it may be important in the pathogenesis of vascular disease in diabetes. PMID:1312416

  18. Lysobisphosphatidic acid controls endosomal cholesterol levels.

    PubMed

    Chevallier, Julien; Chamoun, Zeina; Jiang, Guowei; Prestwich, Glenn; Sakai, Naomi; Matile, Stefan; Parton, Robert G; Gruenberg, Jean

    2008-10-10

    Most cell types acquire cholesterol by endocytosis of circulating low density lipoprotein, but little is known about the mechanisms of intra-endosomal cholesterol transport and about the primary cause of its aberrant accumulation in the cholesterol storage disorder Niemann-Pick type C (NPC). Here we report that lysobisphosphatidic acid (LBPA), an unconventional phospholipid that is only detected in late endosomes, regulates endosomal cholesterol levels under the control of Alix/AlP1, which is an LBPA-interacting protein involved in sorting into multivesicular endosomes. We find that Alix down-expression decreases both LBPA levels and the lumenal vesicle content of late endosomes. Cellular cholesterol levels are also decreased, presumably because the storage capacity of endosomes is affected and thus cholesterol clearance accelerated. Both lumenal membranes and cholesterol can be restored in Alix knockdown cells by exogenously added LBPA. Conversely, we also find that LBPA becomes limiting upon pathological cholesterol accumulation in NPC cells, because the addition of exogenous LBPA, but not of LBPA isoforms or analogues, partially reverts the NPC phenotype. We conclude that LBPA controls the cholesterol capacity of endosomes. PMID:18644787

  19. A strong decrease in Saturn's equatorial jet at cloud level.

    PubMed

    Sánchez-Lavega, A; Pérez-Hoyos, S; Rojas, J F; Hueso, R; French, R G

    2003-06-01

    The atmospheres of the giant planets Jupiter and Saturn have a puzzling system of zonal (east-west) winds alternating in latitude, with the broad and intense equatorial jets on Saturn having been observed previously to reach a velocity of about 470 m x s(-1) at cloud level. Globally, the location and intensity of Jupiter's jets are stable in time to within about ten per cent, but little is known about the stability of Saturn's jet system. The long-term behaviour of these winds is an important discriminator between models for giant-planet circulations. Here we report that Saturn's winds show a large drop in the velocity of the equatorial jet of about 200 m x s(-1) from 1996 to 2002. By contrast, the other measured jets (primarily in the southern hemisphere) appear stable when compared to the Voyager wind profile of 1980-81. PMID:12789333

  20. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease.

    PubMed

    Lake, April D; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D; Lu, Zhenqiang; Lehman-McKeeman, Lois D; Cherrington, Nathan J

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the 'classical' (neutral) and 'alternative' (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. PMID:23391614

  1. Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.

    PubMed

    Burrage, Lindsay C; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H; Nagamani, Sandesh C S

    2014-01-01

    Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. PMID:25042691

  2. Getting on with persistent pollutants: Decreasing trends of perfluoroalkyl acids (PFAAs) in sewage sludge.

    PubMed

    Ulrich, Hanna; Freier, Korbinian P; Gierig, Michael

    2016-10-01

    Sewage sludge can be a relevant source of perfluoroalkyl acids (PFAAs) for the environment. In order to reduce emissions from this source, Bavarian authorities enforced in 2008 an analysis of PFAAs from sewage sludge derived from municipal wastewater treatment plants (WWTPs). 4981 sludge samples from 1165 different WWTPs were analyzed between 2008 and 2013 for 11 PFAAs compounds. During this period, 71 WWTPs exceeded the precautionary limit of 125 μg kg(-1) dm of total PFAAs in sludge samples at least once with a decreasing tendency. The yearly exceedances of the investigated WWTPs decreased from 6% in 2008 to 0.8% in 2013. At the same time, the percentage of uncontaminated WWTPs increased from 33% to 65%. Perfluorooctane sulfonic acid (PFOS) was the predominant compound found in 41% of all sludge samples. Perfluorodecanoic acid (PFDA) was detected in 19% and Perfluorooctanoic acid (PFOA) in 7%. Very high PFAAs concentrations (>500 μg kg(-1) dm) in sewage sludge were generally caused by firefighting foams containing PFAAs or emissions from PFAAs-using industries including metal plating, textile, leather or paper industries. Trend analyses of the six year period show that PFAAs contamination in sewage sludge clearly decreased for 47% of the WWTPs. However, for 16% of the WWTPs an increasing trend was detected, even though the concentration levels were below the precautionary limit. During the six years of investigation the load of total PFAAs in sewage sludge was reduced by more than 90%, from 17 t a(-1) in 2008 to 1.5 t a(-1) in 2013. PMID:27472434

  3. Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential role in chemoprevention.

    PubMed

    Ai, Guoqiang; Dachineni, Rakesh; Muley, Pratik; Tummala, Hemachand; Bhat, G Jayarama

    2016-02-01

    Epidemiological studies have demonstrated a significant correlation between regular aspirin use and reduced colon cancer incidence and mortality; however, the pathways by which it exerts its anti-cancer effects are still not fully explored. We hypothesized that aspirin's anti-cancer effect may occur through downregulation of c-Myc gene expression. Here, we demonstrate that aspirin and its primary metabolite, salicylic acid, decrease the c-Myc protein levels in human HCT-116 colon and in few other cancer cell lines. In total cell lysates, both drugs decreased the levels of c-Myc in a concentration-dependent fashion. Greater inhibition was observed in the nucleus than the cytoplasm, and immunofluorescence studies confirmed these observations. Pretreatment of cells with lactacystin, a proteasome inhibitor, partially prevented the downregulatory effect of both aspirin and salicylic acid, suggesting that 26S proteasomal pathway is involved. Both drugs failed to decrease exogenously expressed DDK-tagged c-Myc protein levels; however, under the same conditions, the endogenous c-Myc protein levels were downregulated. Northern blot analysis showed that both drugs caused a decrease in c-Myc mRNA levels in a concentration-dependent fashion. High-performance liquid chromatography (HPLC) analysis showed that aspirin taken up by cells was rapidly metabolized to salicylic acid, suggesting that aspirin's inhibitory effect on c-Myc may occur through formation of salicylic acid. Our result suggests that salicylic acid regulates c-Myc level at both transcriptional and post-transcription levels. Inhibition of c-Myc may represent an important pathway by which aspirin exerts its anti-cancer effect and decrease the occurrence of cancer in epithelial tissues. PMID:26314861

  4. Long chain n-3 polyunsaturated fatty acids decrease feelings of anger in substance abusers

    PubMed Central

    Buydens-Branchey, Laure; Branchey, Marc

    2008-01-01

    It has been suggested that low levels of n-3 polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of some psychiatric disorders. In light of the existence of strong associations between high-frequency and high-severity aggressive behaviors and substance use disorders and of our observation that substance abusers have poor dietary habits, the possibility that the administration of supplements of n-3 PUFAs would decrease their anger levels was explored. A life long history of aggressive behaviors and problems with the law was obtained in 24 patients. Thirteen patients received on a daily basis capsules containing 3 g of n-3 PUFAs (EPA+DHA). Eleven patients received placebo capsules. The trial was double-blind, randomized, and lasted 3 months. An anger scale was administered at baseline and every month thereafter. Six PUFA group patients and eight placebo group patients were followed for an additional 3 months after treatment discontinuation. Four patients in each group had a history of assaultive behavior. The baseline fish and n-3 PUFA intakes of these 8 patients were significantly lower than those of the non-aggressive patients. When given for 3 months, n-3 PUFAs were superior to placebo in diminishing anger scores. These scores remained decreased for 3 months following treatment discontinuation. These data provide further support to emerging evidence indicating that supplementation with long-chain n-3 PUFAs could be beneficial in the treatment of some individuals with aggressive tendencies. PMID:17900705

  5. Amino acid repletion does not decrease muscle protein catabolism during hemodialysis.

    PubMed

    Raj, Dominic S C; Adeniyi, Oladipo; Dominic, Elizabeth A; Boivin, Michel A; McClelland, Sandra; Tzamaloukas, Antonios H; Morgan, Nancy; Gonzales, Lawrence; Wolfe, Robert; Ferrando, Arny

    2007-06-01

    Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol.min(-1).100 ml (-1)) was more negative during HD-O compared with pre-HD (-33.7 +/- 1.5 vs. -6.0 +/- 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (-16.9 +/- 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively (P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown. PMID:17264222

  6. Response of DOC in acid-sensitive Maine lakes to decreasing sulfur deposition (1993 - 2009)

    EPA Science Inventory

    In response to the Clean Air Act Amendments of 1990, sulfur deposition has decreased across the northeastern United States. As a result, sulfate concentrations in lakes and streams have also decreased and many surface waters have become less acidic. Over the same time period, th...

  7. Decreased homovanilic acid in cerebrospinal fluid correlates with impaired neuropsychologic function in HIV-1-infected patients.

    PubMed

    di Rocco, A; Bottiglieri, T; Dorfman, D; Werner, P; Morrison, C; Simpson, D

    2000-01-01

    To determine whether dopamine metabolism is abnormal in HIV infected patients and whether dopamine metabolism abnormalities are related to specific neuropsychologic characteristics in HIV-infected patients, we measured cerebrospinal fluid (CSF) levels of homovanilic acid (HVA), the primary dopamine metabolite, in 10 HIV-infected patients and compared it to HVA levels in CSF in a group of 13 healthy control subjects. HIV-infected patients were also assessed with a battery of neuropsychologic tests and HVA levels were then correlated with performance on specific neuropsychologic tests. The mean (+/-SD) HVA level in CSF was 100.9 +/- 29.3 nmol/L in the HIV-infected study group and 230.5 +/- 50.0 nmol/L in the non-HIV-infected control group (p < 0.0001). The decrease in concentrations of HVA in CSF correlated with impairment on performance on neuropsychologic testing (Spearman r = 0.67; p = 0.03). When the relationship between HVA levels and specific cognitive domains was evaluated, we observed trends for positive correlation between HVA levels and tests that measure motor speed (r = 0.59; p = 0.074) and those testing attention, concentration, and executive control (r = 0.54; p = 0.108). There was no relationship between performance on memory tests and CSF HVA levels (r = -0.0061; p = 0.987). These results further support the hypothesis that dopaminergic dysfunction plays an important role in the pathogenesis of AIDS dementia complex (ADC) and suggest that specific motor and cognitive abnormalities may be related to depressed dopaminergic activity. This may have important implications for the development of treatments or preventive strategies for ADC. PMID:11020122

  8. Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: decreased CIMT, reduced plasma lipid levels, and decreased blood pressure

    PubMed Central

    Fogelman, Yacov; Gaitini, Diana; Carmeli, Eli

    2016-01-01

    Background Ethanolic extract of licorice root has been shown to reduce low-density lipoprotein (LDL) oxidation in atherosclerotic mice and in both hypercholesterolemic and normal lipidemic humans. Objective This study examined the effect of licorice-root extract on carotid intima-media thickness (CIMT) in individuals with hypercholesterolemia. Design Individuals with hypercholesterolemia (total cholesterol ≥6.18 mmol/L [240 mg/dL]) and without significant stenosis were randomly allocated to two groups: an experimental group that consumed 0.2 g/day of ethanolic extract of licorice root for 12 months, and a control group that received a placebo. Results Of 110 eligible participants, 94 (41–80 years old) completed the study. A significant CIMT decrease from 0.92±0.25 mm to 0.84±0.21 mm was observed in the experimental group compared with an increase from 0.85±0.17 mm to 0.88±0.19 mm in the control group. Mean plasma total cholesterol levels and LDL cholesterol decreased, at the range baseline to 1 year, from 284±32 mg/dl to 262±25 mg/dl and from 183±8.5 mg/dl to 174±9.1 mg/dl, respectively, for the experimental group (p<0.001) and from 291±35 to 289±31 mg/dl and from 177.6±10.7 to 179.3±9.6 (p=0.08), respectively, for the control group. Mean high-density lipoprotein (HDL) did not change significantly in either group. In the experimental group, systolic blood pressure decreased from 138±12 mmHg to 125±13 mmHg after 1 year (p=0.01) and increased from 136±15 mmHg to 137±13 mmHg in the control group. Diastolic blood pressure decreased from 92±9 mmHg to 84±10 mmHg (p=0.01) in the experimental group and increased from 89±11 mmHg to 90±8 mmHg in the control group. Conclusion Following 1 year of licorice consumption, mean CIMT, total cholesterol, LDL levels, and blood pressure were decreased. This suggests that licorice may attenuate the development of atherosclerosis and of related cardiovascular diseases. PMID:27113136

  9. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

    PubMed

    Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

    2009-03-01

    Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII. PMID:19358933

  10. Phospholipase D1 decreases type I collagen levels in hepatic stellate cells via induction of autophagy.

    PubMed

    Seo, H-Y; Jang, B-K; Jung, Y-A; Lee, E-J; Kim, H-S; Jeon, J-H; Kim, J-G; Lee, I-K; Kim, M-K; Park, K-G

    2014-06-20

    Hepatic stellate cells (HSCs) are major players in liver fibrogenesis. Accumulating evidence shows that suppression of autophagy plays an important role in the development and progression of liver disease. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA) and choline, was recently shown to modulate autophagy. However, little is known about the effects of PLD1 on the production of type I collagen that characterizes liver fibrosis. Here, we examined whether PLD1 regulates type I collagen levels in HSCs through induction of autophagy. Adenovirus-mediated overexpression of PLD-1 (Ad-PLD1) reduced type I collagen levels in the activated human HSC lines, hTERT and LX2. Overexpression of PLD1 in HSCs led to induction of autophagy as demonstrated by increased LC3-II conversion and formation of LC3 puncta, and decreased p62 abundance. Moreover, inhibiting the induction of autophagy by treating cells with bafilomycin or a small interfering (si)RNA for ATG7 rescued Ad-PLD1-induced suppression of type I collagen accumulation in HSCs. The effects of PLD on type I collagen levels were not related to TGF-β/Smad signaling. Furthermore, treatment of cells with PA induced autophagy and inhibited type I collagen accumulation. The present study indicates that PLD1 plays a role in regulating type I collagen accumulation through induction of autophagy. PMID:24802400

  11. Decreased plasma and tissue isoleucine levels after simulated gastrointestinal bleeding by blood gavages in chronic portacaval shunted rats.

    PubMed Central

    Olde Damink, S W; Dejong, C H; Deutz, N E; Soeters, P B

    1997-01-01

    BACKGROUND: Previously, arterial concentrations of the essential branched chain amino acid isoleucine (Ile) were found to have decreased by more than 50% after gastrointestinal haemorrhage in patients and after intragastric blood administration in healthy humans and pigs. Hypothetically, this induced hypoisoleucinaemia could deplete tissue Ile pools. AIMS: To study the effect of repeated blood gavages on arterial and tissue Ile levels during normal and impaired liver function. SUBJECTS: Male Wistar rats. METHODS: 14 days after portacaval shunting or sham surgery, rats received 3 ml bovine erythrocytes or saline at 0, 1, 2, and 3 hours via a gastrostomy catheter in the duodenum. At 0, 2, 4, 6 and 8 hours arterial blood and at 8 hours intestine, liver, muscle, and cerebral cortex were sampled for determination of ammonia and amino acid concentrations. RESULTS: In both groups repeated blood administration resulted in a marked decrease in plasma Ile (40-60%). This was accompanied by decreased tissue Ile concentrations in liver (50%), muscle (40-60%), and cerebral cortex (40-50%), but unaltered intestinal Ile levels. In contrast, the arterial and tissue concentrations of ammonia, urea, and of most amino acids increased, most strikingly of the other two branched chain amino acids, valine and leucine. CONCLUSIONS: Simulated gastrointestinal bleeding by blood gavages in rats with and without impaired liver function leads to hypoisoleucinaemia and decreased tissue Ile pools. PMID:9135535

  12. Decreased Vitamin B12 and Folic Acid Concentrations in Acne Patients After Isotretinoin Therapy: A Controlled Study

    PubMed Central

    Gökalp, Hilal; Bulur, I; Gürer, MA

    2014-01-01

    Background: Oral isotretinoin treatment might influence the levels of vitamin B12 and folic acid. Aims and Objectives: The aim of this study is to compare vitamin B12 and folic acid levels in patients with moderate and severe acne vulgaris with those of the healthy control group and to investigate the effect of isotretinoin treatment on these vitamins. Materials and Methods: Patients who completed 6 months of isotretinoin therapy for moderate and severe forms of acne vulgaris and a control group consisting of healthy individuals between February 2011 and March 2012 were included in the study. Before isotretinoin therapy and at 6.- months of the therapy, serum vitamin B12 and folic acid levels were measured. In the healthy control group, vitamin B12 and folic acid levels were assessed only once. Results: In total, 120 patients with moderate and severe acne vulgaris who completed 6 months isotretinoin therapy and 100 healthy individuals who constituted the control group were included in the study. Pre-treatment vitamin B12 values of the patient group were found to be statistically significantly higher (P = 0.002), but any statistically significant difference was not detected in folic acid measurements (P = 0.566). A statistically significant decrease was detected in post-treatment vitamin B12 and folic acid levels (P < 0.05). Conclusion: Vitamin B12/folic acid treatment should be given under medical surveillance before and during isotretinoin therapy. Supplementation of these vitamins should be recommended in cases of their deficiency, so as to decrease the risks of neuropsychiatric and occlusive vascular diseases. PMID:25484410

  13. Boric acid-dependent decrease in regulatory histone H3 acetylation is not mutagenic in yeast.

    PubMed

    Pointer, Benjamin R; Schmidt, Martin

    2016-07-01

    Candida albicans is a dimorphic yeast commonly found on human mucosal membranes that switches from yeast to hyphal morphology in response to environmental factors. The change to hyphal growth requires histone H3 modifications by the yeast-specific histone acetyltransferase Rtt109. In addition to its role in morphogenesis, Rtt109-dependent acetylation of histone H3 lysine residues 9 and 56 has regulatory functions during DNA replication and repair. Boric acid (BA) is a broad-spectrum agent that specifically inhibits C. albicans hyphal growth, locking the fungus in its harmless commensal yeast state. The present study characterizes the effect of BA on C. albicans histone acetylation in respect to specificity, time-course and significance. We demonstrate that sublethal concentrations of BA reduce H3K9/H3K56 acetylation, both on a basal level and in response to genotoxic stress. Acetylation at other selected histone sites were not affected by BA. qRT-PCR expression analysis of the DNA repair gene Rad51 indicated no elevated level of genotoxic stress during BA exposure. A forward-mutation analysis demonstrated the BA does not increase spontaneous or induced mutations. The findings suggest that DNA repair remains effective even when histone H3 acetylation decreases and dispels the notion that BA treatment impairs genome integrity in yeast. PMID:27190149

  14. Synergism of α-linolenic acid, conjugated linoleic acid and calcium in decreasing adipocyte and increasing osteoblast cell growth.

    PubMed

    Kim, Youjin; Kelly, Owen J; Ilich, Jasminka Z

    2013-08-01

    Whole fat milk and dairy products (although providing more energy compared to low- or non-fat products), are good sources of α-linolenic acid (ALA), conjugated linoleic acid (CLA) and calcium, which may be favorable in modulating bone and adipose tissue metabolism. We examined individual and/or synergistic effects of ALA, CLA and calcium (at levels similar to those in whole milk/dairy products) in regulating bone and adipose cell growth. ST2 stromal, MC3T3-L1 adipocyte-like and MC3T3-E1 osteoblast-like cells were treated with: (a) linoleic acid (LNA):ALA ratios = 1-5:1; (b) individual/combined 80-90 % c9, t11 (9,11) and 5-10 % t10, c12 (10,12) CLA isomers; (c) 0.5-3.0 mM calcium; (d) combinations of (a), (b), (c); and (e) control. Local mediators, including eicosanoids and growth factors, were measured. (a) The optimal effect was found at the 4:1 LNA:ALA ratio where insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) production was the lowest in MC3T3-L1 cells. (b) All CLA isomer blends decreased MC3T3-L1 and increased MC3T3-E1 cell differentiation. (c) 1.5-2.5 mM calcium increased ST2 and MC3T3-E1, and decreased MC3T3-L1 cell proliferation. (d) Combination of 4:1 LNA:ALA + 90:10 % CLA + 2.0 mM calcium lowered MC3T3-L1 and increased MC3T3-E1 cell differentiation. Overall, the optimal LNA:ALA ratio to enhance osteoblastogenesis and inhibit adipogenesis was 4:1. This effect was enhanced by 90:10 % CLA + 2.0 mM calcium, indicating possible synergism of these dietary factors in promoting osteoblast and inhibiting adipocyte differentiation in cell cultures. PMID:23757205

  15. Determining and surveying the role of carnitine and folic acid to decrease fatigue in β-thalassemia minor subjects.

    PubMed

    Tabei, Seyed Mohammad Bagher; Mazloom, Maryam; Shahriari, Mahdi; Zareifar, Soheila; Azimi, Ali; Hadaegh, Amirhossein; Karimi, Mehran

    2013-11-01

    Beta-thalassemia minor (BTM) patients usually experience fatigue, bone pain complaint, and muscle weakness. Carnitine is an essential protein for transportation of long-chain fatty acids to the matrix for beta-oxidation. BTM patients have abnormally low plasma carnitine concentrations, which results in deficient ATP production. Carnitine and folic acid together may have a role in preventing bone pain complaint and fatigue in these patients. The aim of this study is to determine the effect of carnitine and folic acid supplementation in subjects with BTM. Seventy three BTM (mean age 11.06 ± 5.46 years) and 23 healthy controls (mean age 8.48 ± 3.78 years) were enrolled in the study. Fasting blood was drawn to determine baseline free and total carnitine levels, red blood cell folate concentration, and hemoglobin level. BTM were divided into three groups and received different types of supplementation for 3 months: Group 1, 50 mg/kg/day carnitine; Group 2, 50 mg/kg/day carnitine plus 1 mg/day folic acid; and Group 3, 1 mg/day folic acid. Controls did not receive supplementation. Laboratory parameters were again evaluated after 3 months' supplementation. A detailed quality of life questionnaire was designed to investigate muscle symptoms before and after supplementation. Free and total plasma carnitine concentration and hemoglobin levels in BTM subjects increased significantly after carnitine supplementation (P < .0001). Bone pain complaint and muscle weakness decreased with carnitine. Red blood cell folate level increased after folic acid supplementation. Carnitine and folic acid supplementation resulted in a decrease in bone pain complaint and muscle weakness in cases with β-thalassemia minor. PMID:23458634

  16. Maternal High Fat Diet Is Associated with Decreased Plasma n–3 Fatty Acids and Fetal Hepatic Apoptosis in Nonhuman Primates

    PubMed Central

    Grant, Wilmon F.; Gillingham, Melanie B.; Batra, Ayesha K.; Fewkes, Natasha M.; Comstock, Sarah M.; Takahashi, Diana; Braun, Theodore P.; Grove, Kevin L.; Friedman, Jacob E.; Marks, Daniel L.

    2011-01-01

    To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6∶n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6∶n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate. PMID:21364873

  17. Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming.

    PubMed

    Nüsken, Eva; Gellhaus, Alexandra; Kühnel, Elisabeth; Swoboda, Isabelle; Wohlfarth, Maria; Vohlen, Christina; Schneider, Holm; Dötsch, Jörg; Nüsken, Kai-Dietrich

    2016-07-01

    Regulation of placental nutrient transport significantly affects fetal development and may modify intrauterine growth restriction (IUGR) and fetal programming. We hypothesized that placental nutrient transporters are differentially affected both by utero-placental insufficiency and prenatal surgical stress. Pregnant rats underwent bilateral uterine artery and vein ligation (LIG), sham operation (SOP) or no operation (controls, C) on gestational day E19. Placentas were obtained by caesarean section 4 h (LIG, n=20 placentas; SOP, n=24; C, n=12), 24 h (LIG, n=28; SOP, n=20; C, n=12) and 72 h (LIG, n=20; SOP, n=20; C, n=24) after surgery. Gene and protein expression of placental nutrient transporters for fatty acids (h-FABP, CD36), amino acids (SNAT1, SNAT2) and glucose (GLUT-1, Connexin 26) were examined by qRT-PCR, western blot and immunohistochemistry. Interestingly, the mean protein expression of h-FABP was doubled in placentas of LIG and SOP animals 4, 24 (SOP significant) and 72 h (SOP significant) after surgery. CD36 protein was significantly increased in LIG after 72 h. SNAT1 and SNAT2 protein and gene expressions were significantly reduced in LIG and SOP after 24 h. Further significantly reduced proteins were GLUT-1 in LIG (4 h, 72 h) and SOP (24 h), and Connexin 26 in LIG (72 h). In conclusion, placental nutrient transporters are differentially affected both by reduced blood flow and stress, probably modifying the already disturbed intrauterine milieu and contributing to IUGR and fetal programming. Increased fatty acid transport capacity may affect energy metabolism and could be a compensatory reaction with positive effects on brain development. J. Cell. Biochem. 117: 1594-1603, 2016. © 2015 Wiley Periodicals, Inc. PMID:26590355

  18. Acute and chronic administration of the branched-chain amino acids decreases nerve growth factor in rat hippocampus.

    PubMed

    Scaini, Giselli; Mello-Santos, Lis Mairá; Furlanetto, Camila B; Jeremias, Isabela C; Mina, Francielle; Schuck, Patrícia F; Ferreira, Gustavo C; Kist, Luiza W; Pereira, Talita C B; Bogo, Maurício R; Streck, Emilio L

    2013-12-01

    Maple syrup urine disease (MSUD) is a neurometabolic disorder caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain α-keto acid dehydrogenase leading to accumulation of the branched-chain amino acids (BCAA) and their corresponding branched-chain α-keto acids. In this study, we examined the effects of acute and chronic administration of BCAA on protein levels and mRNA expression of nerve growth factor (NGF) considering that patients with MSUD present neurological dysfunction and cognitive impairment. Considering previous observations, it is suggested that oxidative stress may be involved in the pathophysiology of the neurological dysfunction of MSUD. We also investigated the influence of antioxidant treatment (N-acetylcysteine and deferoxamine) in order to verify the influence of oxidative stress in the modulation of NGF levels. Our results demonstrated decreased protein levels of NGF in the hippocampus after acute and chronic administration of BCAA. In addition, we showed a significant decrease in the expression of ngf in the hippocampus only following acute administration in 10-day-old rats. Interestingly, antioxidant treatment was able to prevent the decrease in NGF levels by increasing ngf expression. In conclusion, the results suggest that BCAA is involved in the regulation of NGF in the developing rat. Thus, it is possible that alteration of neurotrophin levels during brain maturation could be of pivotal importance in the impairment of cognition provoked by BCAA. Moreover, the decrease in NGF levels was prevented by antioxidant treatment, reinforcing that the hypothesis of oxidative stress can be an important pathophysiological mechanism underlying the brain damage observed in MSUD. PMID:23559405

  19. Gallic acid decreases hepatitis C virus expression through its antioxidant capacity

    PubMed Central

    GOVEA-SALAS, MAYELA; RIVAS-ESTILLA, ANA MARIA; RODRÍGUEZ-HERRERA, RAUL; LOZANO-SEPÚLVEDA, SONIA A.; AGUILAR-GONZALEZ, CRISTOBAL N.; ZUGASTI-CRUZ, ALEJANDRO; SALAS-VILLALOBOS, TANYA B.; MORLETT-CHÁVEZ, JESUS ANTONIO

    2016-01-01

    Gallic acid (GA) is a natural phenolic compound that possesses various biological effects, including antioxidant, anti-inflammatory, antibiotic, anticancer, antiviral and cardiovascular protection activities. In addition, numerous studies have reported that antioxidants possess antiviral activities. Hepatitis C virus (HCV) is one of the most important causes of chronic liver diseases worldwide, but until recently, only a small number of antiviral agents had been developed against HCV. Therefore, the present study investigated whether GA exhibits an anti-HCV activity. The effects of GA on HCV expression were examined using a subgenomic HCV replicon cell culture system that expressed HCV nonstructural proteins (NSs). In addition, GA cytotoxicity was evaluated at concentrations between 100–600 mg/ml using an MTT assay. Huh-7 replicon cells were incubated with 300 mg/ml GA for different times, and the HCV-RNA and protein levels were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Pyrrolidine dithiocarbamate (PDTC) was used as an antioxidant control and reactive oxygen species (ROS) production was measured during the exposure. The results indicated that GA did not produce a statistically significant cytotoxicity in parental and HCV replicon cells. Furthermore, GA downregulated the expression levels of NS5A-HCV protein (~55%) and HCV-RNA (~50%) in a time-dependent manner compared with the levels in untreated cells. Notably, GA treatment decreased ROS production at the early time points of exposure in cells expressing HCV proteins. Similar results were obtained upon PDTC exposure. These findings suggest that the antioxidant capacity of GA may be involved in the downregulation of HCV replication in hepatoma cells. PMID:26893656

  20. Alginic acid decreases postprandial upright gastroesophageal reflux. Comparison with equal-strength antacid.

    PubMed

    Castell, D O; Dalton, C B; Becker, D; Sinclair, J; Castell, J A

    1992-04-01

    This study tested the hypothesis that (alginic) acid may have a preferential effect on reflux in the upright position. We evaluated the effect of a compound containing alginic acid plus antacid (extra-strength Gaviscon) versus active control antacid with equal acid-neutralizing capacity on intraesophageal acid exposure following a high-fat meal (61% fat: sausage, egg, and biscuit). In random sequence, each of the 10 volunteers received either alginic acid-antacid or control antacid immediately following and 1, 2, and 3 hr after the meal. The sequence was repeated for both test drugs in the supine and upright positions with constant pH monitoring. Alginic acid-antacid significantly decreased postprandial reflux in the upright position compared to an equal amount of antacid. This effect did not occur in the supine position. These findings support the hypothesis that alginic acid is primarily effective in the upright position and the clinical observations of the effectiveness of alginic acid on daytime reflux symptoms. PMID:1551350

  1. Puget Sound acidity levels drop after ASARCO shutdown

    SciTech Connect

    Not Available

    1987-07-01

    The levels of acidity in Puget Sound region rainfall have decreased significantly since the shutdown of the ASARCO copper smelter in Tacoma, Washington, according to a study funded by the US Environmental Protection Agency. Results indicate that sulfate and hydrogen ion concentrations obtained from samples taken before the closure were significantly different than those collected after the shutdown. Rainwater samples collected downwind during smelter operation were also significantly different from those collected upwind. Sulfur dioxide is considered to be one of the principal contributors to acid rain. The smelter was a major source of sulfur dioxide emissions in the Puget Sound region before it shut down in March 1985.

  2. Increased isoprostane levels in oleic acid-induced lung injury

    SciTech Connect

    Ono, Koichi; Koizumi, Tomonobu; Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki; Nakagawa, Rikimaru; Obata, Toru

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  3. Response of DOC in Acid-Sensitive Maine Lakes to Decreasing Sulfur Deposition (1993 - 2009)

    NASA Astrophysics Data System (ADS)

    Oelsner, G. P.; Sanclements, M.; McKnight, D. M.; Stoddard, J. L.

    2010-12-01

    In response to the Clean Air Act Amendments of 1990, sulfur deposition has decreased across the northeastern United States. As a result, sulfate concentrations in lakes and streams have also decreased and many surface waters have become less acidic. Over the same time period, there has been a concurrent increase in dissolved organic carbon (DOC) concentrations in many lakes and streams which has been difficult to interpret. To assess the biogeochemical processes driving increasing DOC concentrations we analyzed archived samples from 9 acid-sensitive lakes in Maine collected between 1993 and 2009 using UV-Vis and fluorescence spectroscopy. The fluorescence index (FI) was calculated for all samples. The FI represents the ratio of the emission intensity at 450 nm to 550 nm at an excitation wavelength of 370 nm and provides information regarding the source of dissolved organic matter (DOM). This index has a value of approximately 1.9 for microbially derived fluvic acids and a value of approximately 1.4 for terrestrially (higher-plant) derived fluvic acids. All four lakes with increasing DOC trends had concomitant decreases in the FI index. Two of five lakes with no significant DOC trend also demonstrated no trend in FI values over time, while three lakes revealed a decrease in FI values. To confirm that the FI measured in whole water was primarily reflective of fulvic acids (FA), XAD-resin was used to isolate FA from a subset of samples. Analysis of the FA indicates that the FI values for the humic substances are slightly higher, yet well correlated with whole water samples. This suggests that despite prolonged storage in plastic, the FI trends are meaningful. The FI trends suggest a terrestrial source for the increasing DOC and may be driven by increased DOM production from soils experiencing decreased acid loading. Decreases in sulfate deposition can increase soil pH and soil organic matter solubility, as well as decrease the ionic strength of the soil solution, and

  4. Nanocellulose coated with various free fatty acids can adsorb fumonisin B1, and decrease its toxicity.

    PubMed

    Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

    2015-10-01

    The aim of this study was to evaluate the adsorption and biological properties of nanocellulose coated with free fatty acids (NCCFFAs). At first, nanocellulose was synthesized by acid hydrolysis, and then separately coated with different free fatty acids (FFAs), including lauric acid, alpha linoleic acid, oleic acid, and palmitic acid. Next, the serial concentrations of NCCFFAs (1, 10, 100, and 1000 μg/mL) was separately added to fumonisin B1 (FB1) at 1000 μg/mL, and separately incubated at 37 °C for 1, 2, and 3h. Then, the percentage of adsorption was calculated. In the next experiment, the viability of mouse liver cells was measured when they exposed to serial concentrations of NCCFFAs, FFAs, and FB1. This study showed that the increase of incubation time and concentration of NCCFFAs led to increase of FB1 adsorption. Although FFAs and NCCFFAs had no remarkable toxicity, the high toxicity was observed for FB1. Importantly, the toxicity of FB1 was highly decreased, when incubated together with FFAs or NCCFFAs. These novel adsorbents, NCCFFAs, can be used together with different foodstuffs to remove FB1. PMID:26142625

  5. Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin.

    PubMed

    Arsenijevic, Denis; Gallmann, Eva; Moses, William; Lutz, Thomas; Erlanson-Albertsson, Charlotte; Langhans, Wolfgang

    2005-07-01

    This study investigated the chronic effect of enterostatin on body weight and some of the associated changes in postprandial metabolism. Rats were adapted to 6 h of food access/day and a choice of low-fat and high-fat (HF) food and then given enterostatin or vehicle by an intraperitoneally implanted minipump delivering 160 nmol enterostatin/h continuously over a 5-day infusion period. Enterostatin resulted in a slight but significant reduction of HF intake and body weight. After the last 6-h food access period, enterostatin-treated animals had lower plasma triglyceride and free fatty acid but higher plasma glucose and lactate levels than control animals. Enterostatin infusion resulted in increased uncoupling protein-2 (UCP2) expression in various tissues, including epididymal fat and liver. UCP2 was reduced in the pancreas of enterostatin-treated animals, and this was associated with increased plasma levels of insulin and amylin. Whether these two hormones are involved in the observed decreased food intake due to enterostatin remains to be determined. As lipid metabolism appeared to be altered by enterostatin, we measured peroxisome proliferator-activated receptor (PPAR) expression in tissues and observed that PPARalpha, -beta, -gamma1, and -gamma2 expression were modified by enterostatin in epididymal fat, pancreas, and liver. This further links altered lipid metabolism with body weight loss. Our data suggest that alterations in UCP2 and PPARgamma2 play a role in the control of insulin and amylin release from the pancreas. This implies that enterostatin changes lipid and carbohydrate metabolic pathways in addition to its effects on food intake and energy expenditure. PMID:15713687

  6. Heavy metals influence on ascorbic acid level

    NASA Astrophysics Data System (ADS)

    Kamaldinov, E. V.; Patrashkov, S. A.; Batenyeva, E. V.; Korotkevich, O. S.

    2003-05-01

    It is well known that heavy metals (HM) are extremely dangerous pollutants influencing to metabolism in animals' organisms. The vitamin C is one of the most important metabolites taking part in many biochemical processes. We studied the influence of main essential HM-Zn and Cu as well as the based supertoxical elements - Cd and Pd on ascorbic acid level in serum. The studies were carried out in Tulinskoe farm of Novosibirsk region. The objects of investigations were piglets (2 month after weaning) and 6-month pigs of Early Ripe Meat breed. The levels of HM in bristle were found by stripping voltammetric analysis using the TA-2 analyzer. Vitamin C content was determined by I.P. Kondrakhin (1985) method using 2,2-dipyridyl. The significant negative correlations between Pb, Cd content and vitamin C (-0.46 ± 0.18, -0.47 ± 0.19) in 6-month pigs were determined. The tendencies of negative correlation between all HM levels in hair and ascorbic acid level in plasma of piglets were revealed. Thus, the obtained correlations let us to suppose that all studied HM influence on 1-gulono-gamma-lactone oxidase and other vitamin C metabolism enzymes activity.

  7. Verruculogen: a new substance for decreasing of GABA levels in CNS.

    PubMed

    Hotujac, L; Muftić, R H; Filipović, N

    1976-01-01

    In our previous work we examined the mechanism of action of the new tremorogenic substance verruculogen isolated by Cole and coworkers. Examining the effect of various substances with known mechanisms of action on verruculogen-induced tremor, we concluded that this tremor was probably related to decrease of GABA levels in CNS. In order to further define the mechanisms of action of verruculogen, we determined brain GABA levels in animals in which tremor was produced by verruculogen administration. Verruculogen administration produced a decrease in GABA levels in mouse CNS. This finding substantiates our earlier suggestion that verruculogen-induced tremor is mediated by a loss of inhibitory GABA function. PMID:935244

  8. Humic acid decreases acute toxicity and ventilation frequency in eastern rainbowfish (Melanotaenia splendida splendida) exposed to acid mine drainage.

    PubMed

    Holland, Aleicia; Duivenvoorden, Leo J; Kinnear, Susan H W

    2014-12-01

    Acid mine drainage (AMD) is a global problem leading to the acidification of freshwaters, as well as contamination by heavy metals. The ability of humic substances (HS) such as humic acid (HA) to decrease toxicity of heavy metals is widely known, whereas limited studies have examined the ability of HS to decrease toxicity linked with multiple stressors such as those associated with AMD. This study investigated the ability of HA to decrease acute toxicity defined as morbidity and ventilation frequency (measured via the time elapsed for ten operculum movements) in eastern rainbowfish (Melanotaenia splendida splendida) exposed to the multiple stressors of AMD-driven heavy metal concentrations, together with low pH. Water from the Mount Morgan open pit (a now closed gold and copper mine site), located at Mount Morgan, Central Queensland, Australia, was used as the AMD source. Fish were exposed to zero per cent (pH 7.3), two per cent (pH 6.7), three per cent (pH 5.7) and four per cent (pH 4.6) AMD in the presence of 0, 10 and 20mg/L Aldrich Humic Acid (AHA) over 96h. HA was shown to significantly decrease the acute toxicity of AMD and its adverse effects on ventilation frequency. These results are important in showing that HA can influence toxicity of metal mixtures and low pH, thus indicating a potential role for HA in decreasing toxicity of multiple environmental stressors more widely, and possible value as a rehabilitation aid. PMID:25173849

  9. Incremental amounts of ground flaxseed decrease milk yield but increase n-3 fatty acids and conjugated linoleic acids in dairy cows fed high-forage diets(1).

    PubMed

    Resende, T L; Kraft, J; Soder, K J; Pereira, A B D; Woitschach, D E; Reis, R B; Brito, A F

    2015-07-01

    The objective of this study was to investigate the effect of incremental amounts of ground flaxseed (GFX) on milk yield and concentrations and yields of milk components, milk fatty acids (FA) profile, ruminal metabolism, and nutrient digestibility in dairy cows fed high-forage diets. Twelve multiparous Jersey cows averaging (mean ± SD) 112±68d in milk and 441±21kg of body weight and 8 primiparous Jersey cows averaging 98±43d in milk and 401±43kg of body weight were randomly assigned to treatment sequences in a replicated 4×4 Latin square design. Each period lasted 21d with 14d for diet adaptation and 7d for data and sample collection. Treatments were fed as a total mixed ration (63:37 forage-to-concentrate ratio) with corn meal and soybean meal replaced by incremental levels (i.e., 0, 5, 10, or 15% diet dry matter) of GFX. The ruminal molar proportions of acetate and butyrate decreased linearly with GFX supplementation, whereas the ruminal molar proportion of propionate increased linearly resulting in decreased acetate-to-propionate ratio. Apparent total-tract digestibilities of nutrients either decreased (dry matter) or tended to decrease (organic matter, neutral detergent fiber, acid detergent fiber) linearly in cows fed GFX. Milk yield decreased linearly in cows fed increasing amounts of GFX, which is explained by the linear reduction in dry matter intake. Except for the concentrations of milk protein and urea N, which decreased linearly with GFX supplementation, no other changes in the concentration of milk components were observed. However, yields of milk protein and fat decreased linearly with GFX supplementation. The linear decrease in the yields of milk fat and protein are explained by reduced milk yield, whereas that in milk urea N is explained by decreased crude protein intake. No treatment effects were observed for plasma urea N and nonesterified fatty acids, serum cortisol, and body weight change. Milk odd- and branched-chain FA and saturated FA

  10. Inhibition of arachidonic acid metabolism decreases tumor cell invasion and matrix metalloproteinase expression.

    PubMed

    Koontongkaew, Sittichai; Monthanapisut, Paopanga; Saensuk, Theeranuch

    2010-11-01

    Head and neck cancers are known to synthesize arachidonic acid metabolites. Interfering with arachidonic acid metabolism may inhibit growth and invasiveness of cancer cells. In this study we investigate effects of sulindac (the non-selective COX inhibitor), aspirin (the irreversible, preferential COX-1 inhibitor), NS-398 (the selective COX-2 inhibitor), NDGA (nordihydroguaiaretic acid, the selective LOX inhibitor) and ETYA (5,8,11,14-eicosatetraynoic acid, the COX and LOX inhibitor) on cell viability, MMP-2 and MMP-9 activities, and in vitro invasion of cancer cells derived from primary and metastatic head and neck, and colon cancers. The inhibitors of COX and/or LOX could inhibit cell proliferation, MMP activity and invasion in head and neck and colon cancer cells. However, the inhibitory effect was obviously observed in colon cancer cells. Inhibition of arachidonic acid metabolism caused a decrease in cancer cell motility, which partially explained by the inhibition of MMPs. Therefore, COX and LOX pathways play important roles in head and neck cancer cell growth. PMID:20654727

  11. CONJUGATED LINOLEIC ACIDS (CLA) DECREASE THE BREAST CANCER RISK IN DMBA-TREATED RATS.

    PubMed

    Białek, Agnieszka; Tokarz, Andrzej; Zagrodzki, Paweł

    2016-01-01

    The aim of this study was to investigate how supplementation of diet of female Sprague-Dawley rats with different doses of conjugated linoleic acids and for a varied period of time influences breast cancer risk, fatty acids profile and lipids peroxidation in chemically induced mammary tumors. Animals were divided into nine groups with different modifications of diet (vegetable oil, 1.0 or 2.0% of CLA) and period of supplementation, which lasted after (A), before (B) and before and after (BA) carcinogenic agent--7,12-dimethylbenz[a]anthracene administration at 50th day of life. Mammary adenocarcinomas occurred in all groups, but CLA supplementation decreased the cancer morbidity. Two percent CLA seems to be excessive because of the coexisting cachexia. Two CLA isomers (9-cis, 11-trans and 10-trans, 12-cis) were detected in tumors but content of rumenic acid was higher. Dietary supplementation significantly influenced some unsaturated fatty acids content (C18:2 n-6 trans, C20:1, C20:5 n-3, C22:2), but the anti- or prooxidant properties of CLA were not confirmed. CLA can inhibit chemically induced mammary tumors development in female rats, but their cytotoxic action seems not to be connected with lipids peroxidation. CLA isomers differ with their incorporation into cancerous tissues and they influence the content of some other fatty acids. PMID:27180424

  12. Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration.

    PubMed

    Douglas, Gavin M; Wilson, Michael D; Moses, Alan M

    2016-06-01

    Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions.We find evidence for decreased TF binding levels nearby two primate pseudogenes compared with functional liver genes. However, the majority of TF-bound sequences nearby pseudogenes do not show evidence for lineage-specific accelerated rates of evolution. We conclude that decreases in TF binding level could be a marker for regulatory degeneration, while sequence degeneration in primate cis-regulatory modules may be obscured by background rates of TF binding site turnover. PMID:26882985

  13. Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration

    PubMed Central

    Douglas, Gavin M.; Wilson, Michael D.; Moses, Alan M.

    2016-01-01

    Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions. We find evidence for decreased TF binding levels nearby two primate pseudogenes compared with functional liver genes. However, the majority of TF-bound sequences nearby pseudogenes do not show evidence for lineage-specific accelerated rates of evolution. We conclude that decreases in TF binding level could be a marker for regulatory degeneration, while sequence degeneration in primate cis-regulatory modules may be obscured by background rates of TF binding site turnover. PMID:26882985

  14. Experimental Warming Decreases the Average Size and Nucleic Acid Content of Marine Bacterial Communities.

    PubMed

    Huete-Stauffer, Tamara M; Arandia-Gorostidi, Nestor; Alonso-Sáez, Laura; Morán, Xosé Anxelu G

    2016-01-01

    Organism size reduction with increasing temperature has been suggested as a universal response to global warming. Since genome size is usually correlated to cell size, reduction of genome size in unicells could be a parallel outcome of warming at ecological and evolutionary time scales. In this study, the short-term response of cell size and nucleic acid content of coastal marine prokaryotic communities to temperature was studied over a full annual cycle at a NE Atlantic temperate site. We used flow cytometry and experimental warming incubations, spanning a 6°C range, to analyze the hypothesized reduction with temperature in the size of the widespread flow cytometric bacterial groups of high and low nucleic acid content (HNA and LNA bacteria, respectively). Our results showed decreases in size in response to experimental warming, which were more marked in 0.8 μm pre-filtered treatment rather than in the whole community treatment, thus excluding the role of protistan grazers in our findings. Interestingly, a significant effect of temperature on reducing the average nucleic acid content (NAC) of prokaryotic cells in the communities was also observed. Cell size and nucleic acid decrease with temperature were correlated, showing a common mean decrease of 0.4% per °C. The usually larger HNA bacteria consistently showed a greater reduction in cell and NAC compared with their LNA counterparts, especially during the spring phytoplankton bloom period associated to maximum bacterial growth rates in response to nutrient availability. Our results show that the already smallest planktonic microbes, yet with key roles in global biogeochemical cycling, are likely undergoing important structural shrinkage in response to rising temperatures. PMID:27242747

  15. Experimental Warming Decreases the Average Size and Nucleic Acid Content of Marine Bacterial Communities

    PubMed Central

    Huete-Stauffer, Tamara M.; Arandia-Gorostidi, Nestor; Alonso-Sáez, Laura; Morán, Xosé Anxelu G.

    2016-01-01

    Organism size reduction with increasing temperature has been suggested as a universal response to global warming. Since genome size is usually correlated to cell size, reduction of genome size in unicells could be a parallel outcome of warming at ecological and evolutionary time scales. In this study, the short-term response of cell size and nucleic acid content of coastal marine prokaryotic communities to temperature was studied over a full annual cycle at a NE Atlantic temperate site. We used flow cytometry and experimental warming incubations, spanning a 6°C range, to analyze the hypothesized reduction with temperature in the size of the widespread flow cytometric bacterial groups of high and low nucleic acid content (HNA and LNA bacteria, respectively). Our results showed decreases in size in response to experimental warming, which were more marked in 0.8 μm pre-filtered treatment rather than in the whole community treatment, thus excluding the role of protistan grazers in our findings. Interestingly, a significant effect of temperature on reducing the average nucleic acid content (NAC) of prokaryotic cells in the communities was also observed. Cell size and nucleic acid decrease with temperature were correlated, showing a common mean decrease of 0.4% per °C. The usually larger HNA bacteria consistently showed a greater reduction in cell and NAC compared with their LNA counterparts, especially during the spring phytoplankton bloom period associated to maximum bacterial growth rates in response to nutrient availability. Our results show that the already smallest planktonic microbes, yet with key roles in global biogeochemical cycling, are likely undergoing important structural shrinkage in response to rising temperatures. PMID:27242747

  16. Inhibition of Fatty Acid Synthase Decreases Expression of Stemness Markers in Glioma Stem Cells

    PubMed Central

    Yasumoto, Yuki; Miyazaki, Hirofumi; Vaidyan, Linda Koshy; Kagawa, Yoshiteru; Ebrahimi, Majid; Yamamoto, Yui; Ogata, Masaki; Katsuyama, Yu; Sadahiro, Hirokazu; Suzuki, Michiyasu; Owada, Yuji

    2016-01-01

    Cellular metabolic changes, especially to lipid metabolism, have recently been recognized as a hallmark of various cancer cells. However, little is known about the significance of cellular lipid metabolism in the regulation of biological activity of glioma stem cells (GSCs). In this study, we examined the expression and role of fatty acid synthase (FASN), a key lipogenic enzyme, in GSCs. In the de novo lipid synthesis assay, GSCs exhibited higher lipogenesis than differentiated non-GSCs. Western blot and immunocytochemical analyses revealed that FASN is strongly expressed in multiple lines of patient-derived GSCs (G144 and Y10), but its expression was markedly reduced upon differentiation. When GSCs were treated with 20 μM cerulenin, a pharmacological inhibitor of FASN, their proliferation and migration were significantly suppressed and de novo lipogenesis decreased. Furthermore, following cerulenin treatment, expression of the GSC markers nestin, Sox2 and fatty acid binding protein (FABP7), markers of GCSs, decreased while that of glial fibrillary acidic protein (GFAP) expression increased. Taken together, our results indicate that FASN plays a pivotal role in the maintenance of GSC stemness, and FASN-mediated de novo lipid biosynthesis is closely associated with tumor growth and invasion in glioblastoma. PMID:26808816

  17. OKN-007 decreases VEGFR-2 levels in a preclinical GL261 mouse glioma model

    PubMed Central

    de Souza, Patricia Coutinho; Smith, Nataliya; Pody, Richard; He, Ting; Njoku, Charity; Silasi-Mansat, Robert; Lupu, Florea; Meek, Bill; Chen, Hong; Dong, Yunzhou; Saunders, Debra; Orock, Albert; Hodges, Erik; Colijn, Sarah; Mamedova, Nadezda; Towner, Rheal A

    2015-01-01

    Angiogenesis is essential to tumor progression, and the precise imaging of the angiogenic marker vascular endothelial growth factor receptor 2 (VEGFR-2) may provide an accurate evaluation for angiogenesis during a therapeutic response. With the use of molecular magnetic resonance imaging (mMRI), an in vitro cell assay indicated significantly decreased T1 relaxation values when tumor endothelial cells (TEC), which positively expressed VEGFR-2 (Western blot), were in the presence of the VEGFR-2 probe compared to TEC alone (P < 0.001). For in vivo mMRI evaluations, we assessed VEGFR-2 levels in untreated and OKN-007-treated GL261 mouse gliomas. Regarding treatment response, OKN-007 was also able to significantly decrease tumor volumes (P < 0.01) and increase survival (P < 0.001) in treated animals. Regarding in vivo detection of VEGFR-2, OKN-007 was found to significantly decrease the amount of VEGFR-2 probe (P < 0.05) compared to an untreated control group. Fluorescence imaging for the VEGFR-2 probe indicated that there was colocalization with the endothelial marker CD31 in an untreated tumor bearing mouse and decreased levels for an OKN-007-treated animal. Immuno-fluorescence imaging for VEGFR-2 indicated that OKN-007 treatment significantly decreased VEGFR-2 levels (P < 0.0001) when compared to untreated tumors. Immuno-electron microscopy was used with gold-labeled anti-biotin to detect the anti-VEGFR-2 probe within the plasma membrane of GL261 tumor endothelial cells. This is the first attempt at detecting in vivo levels of VEGFR-2 in a mouse GL261 glioma model and assessing the anti-angiogenic capability of an anticancer nitrone. The results indicate that OKN-007 treatment substantially decreased VEGFR-2 levels in a GL261 glioma model, and can be considered as an anti-angiogenic therapy in human gliomas. PMID:26269774

  18. Retinoic acid treatment of fibroblasts causes a rapid decrease in ( sup 3 H)inositol uptake

    SciTech Connect

    Sinha, R.; Creek, K.E.; Silverman-Jones, C.; de Luca, L.M. )

    1989-04-01

    NIH 3T3 fibroblasts treated with all-trans-retinoic acid (RA) showed a dramatic decrease in the uptake of ({sup 3}H)inositol compared to solvent-treated controls. The onset of RA-induced inhibition of ({sup 3}H)inositol uptake was rapid with a 10-15% decrease occurring after 2-3 h of RA exposure and 60-70% reduction after 16 h of RA treatment. A progressive dose-dependent decrease in inositol uptake was found as the concentration of RA increased from 10{sup {minus}8} to 10{sup {minus}5} M and the effect was fully reversible within 48 h after RA removal. RA inhibition of inositol uptake was also observed in 3T3-Swiss and Balb/3T3 cells but not in two virally transformed 3T3 cell lines. Phlorizin, amiloride, and monensin inhibited inositol uptake by 66, 74, and 58%, respectively, and this inhibition was additive when the cells were treated with RA as well as these inhibitors. A decreased incorporation of ({sup 3}H)inositol into polyphosphoinositides was also observed in RA-treated cells but not to the same extent as for ({sup 3}H)inositol uptake. In conclusion, RA treatment of 3T3 fibroblasts decreases the uptake of ({sup 3}H)inositol by up to 70% within 8 to 10 h at near physiological concentrations in a reversible and specific manner.

  19. In situ clinical evidence that zinc levels are decreased in breast invasive ductal carcinoma

    PubMed Central

    Zou, Jing; Franklin, Renty B.

    2016-01-01

    Purpose Altered zinc levels in malignant cells versus their normal cells have important implications in the development and progression of several cancers. Prostate, pancreatic, and hepatocellular carcinomas exhibit consistent marked zinc decrease in situ in the malignant cells, and other cancers (such as kidney, lung, and thyroid) also exhibit decreased tissue zinc levels. However, zinc levels are increased in breast cancer tissue compared to breast normal tissue, and the contemporary dominant view is that zinc is increased in invasive ductal carcinoma. This has important implications regarding the role and effects of zinc in breast malignancy compared to other cancers, which caused us to initiate this study to either confirm or challenge the contemporary view of an increased zinc level in the invasive ductal malignant cells. Methods We employed dithizone staining of breast tissue sections and tissue cores to determine the relative in situ cellular zinc levels specifically in the invasive ductal malignant cells as compared to normal ductal epithelium. This approach had not been employed in any of the reported breast studies. Results The results revealed that the zinc levels are consistently and markedly decreased in the ductal malignant cells as compared with higher prominent zinc levels in the normal ductal epithelium. Decreased zinc is evident in Grade 1 well-differentiated malignancy and in Grade 2 and Grade 3 carcinomas. Among the twenty-five cancer cases in this study, none exhibited increased zinc in the invasive ductal carcinoma compared to the zinc level in the normal ductal epithelium. Conclusions The decreased zinc levels in breast invasive ductal carcinoma is consistent with prostate, pancreatic, and liver carcinomas in which the decrease in zinc is a required event in the development of malignancy to prevent cytotoxicity that would result from the higher zinc levels in the normal cells. This new understanding requires a redirection in elucidating the

  20. Hexabromocyclododecane Decreases the Lytic Function and ATP Levels of Human Natural Killer Cells

    PubMed Central

    Hinkson, Natasha C.; Whalen, Margaret M.

    2009-01-01

    This study investigates the effect of Hexabromocyclododecane (HBCD) on the lytic function of human natural killer (NK) cells and on ATP levels in NK cells. NK cells are capable of lysing tumor cells, virally infected cells, and antibody-coated cells. HBCD is a, brominated cyclic alkane used primarily as an additive flame retardant. If HBCD interferes with NK cell function, this could increase risk of tumor development and/or viral infection. NK cells were exposed to various concentrations of HBCD for 24 h, 48 h, and 6 days before determining lytic function and ATP levels. ATP levels and lytic function were also determined in NK cells that were exposed to HBCD for 1 h followed by 24 h, 48 h, and 6 days in HBCD-free media. The results indicated that exposure of NK cells to 10 μM HBCD for 24 h causes a very significant decrease in both NK cell lytic function and ATP levels (93.5% and 90.5%, respectively). Exposure of NK cells to 10 μM HBCD for 1 h followed by 24 h in HBCD-free media showed a progressive and persistent loss of lytic function (89.3%) as well as a decrease in ATP levels (46.1%). The results indicate that HBCD exposures decreased lytic function as well as ATP levels. However, a decrease in lytic function was not necessarily accompanied by a similar decrease in ATP. Importantly, these results also indicate that a brief (1 h) exposure to HBCD causes a progressive loss of lytic function over a 6 d period. PMID:19551757

  1. Aspartame decreases evoked extracellular dopamine levels in the rat brain: an in vivo voltammetry study.

    PubMed

    Bergstrom, Brian P; Cummings, Deirdre R; Skaggs, Tricia A

    2007-12-01

    Conflicting reports exist concerning the effect aspartame (APM, l-aspartyl-l-phenylalanine methyl ester) has upon brain biogenic amines. In the following study, in vivo voltammetry was utilized to measure evoked extracellular dopamine (DA) levels in the striatum of rats in order to assess APM's effect. Time-course experiments revealed a significant decline in evoked extracellular DA levels within 1h of a single systemic dose (500mg/kg i.p.) when compared to vehicle-injected controls. The effect was frequency dependent and showed a significant decrease utilizing high frequency stimulation parameters (50 and 60Hz). In order to further determine APM's potential to alter evoked extracellular DA levels, extended stimulation periods were employed to deplete releasable stores both before and after APM administration in intact and 6-OHDA partially lesioned animals. The extended stimulation periods were applied at 60Hz for 2,5,10 and 20s durations. APM decreased DA levels under these conditions in both intact and 6-OHDA partially lesioned animals by an average of 34% and 51%, respectively. Kinetic analysis performed on frequency series indicated that the diminished DA levels corresponded to a significant reduction in DA release. These findings suggest that APM has a relatively potent effect of decreasing evoked extracellular DA levels when administered systemically under the conditions specified. PMID:17976663

  2. Changes in soil pH across England and Wales in response to decreased acid deposition

    NASA Astrophysics Data System (ADS)

    Kirk, G. J. D.; Bellamy, P. H.

    2009-04-01

    In our recent analysis of data from the National Soil Inventory of England and Wales, we found widespread changes in soil pH across both countries between the two samplings of the Inventory. In general, soil pH increased - i.e. soils became less acid - under all land uses. The Inventory was first sampled in 1978-83 on a 5-km grid over the whole area. This yielded about 6,000 sites of which 5,662 could be sampled for soil. Roughly 40% of the sites were re-sampled at intervals from 12 to 25 years after the original sampling - in 1994/96 for agricultural land and in 2002/03 for non-agricultural. Exactly the same sampling and analytical protocols were used in the two samplings. In arable soils, the increase in pH was right across the range, whereas in grassland soils the main increase was at the acid end of the scale (pH < 5.5) with a small increase above pH 7. Some part of the change is likely to have been due to changes in land management. This includes better targeting of agricultural lime on acid soils; changes in nitrogen fertilizer use; deeper ploughing bringing up more calcareous subsoil on soils on calcareous materials; and so forth. However a major driver appears to have been decreased acid deposition to land. The total amounts of nitrogen compounds deposited were relatively unchanged over the survey period, but the amounts of acidifying sulphur compounds decreased by approximately 50%. We constructed a linear regression model to assess the relation between the rate of change in pH (normalised to an annual basis) and the rate of change in acid deposition, as modified by soil properties (pH, clay content, organic matter content), rainfall and past acid deposition. We used data on rainfall and acid deposition over the survey period on the same 5-km grid as the NSI data. We fitted the model separately for each land use category. The results for arable land showed a significant effect of the change in rate of acid deposition, though a significant part of the

  3. Decreased exposure of simvastatin and simvastatin acid in a rat model of type 2 diabetes

    PubMed Central

    Xu, Dan; Li, Feng; Zhang, Mian; Zhang, Ji; Liu, Can; Hu, Meng-yue; Zhong, Ze-yu; Jia, Ling-ling; Wang, Da-wei; Wu, Jie; Liu, Li; Liu, Xiao-dong

    2014-01-01

    Aim: Simvastatin is frequently administered to diabetic patients with hypercholesterolemia. The aim of the study was to investigate the pharmacokinetics of simvastatin and its hydrolysate simvastatin acid in a rat model of type 2 diabetes. Methods: Diabetes was induced in 4-week-old rats by a treatment of high-fat diet combined with streptozotocin. After the rats received a single dose of simvastatin (20 mg/kg, po, or 2 mg/kg, iv), the plasma concentrations of simvastatin and simvastatin acid were determined. Simvastatin metabolism and cytochrome P4503A (Cyp3a) activity were assessed in hepatic microsomes, and its uptake was studied in freshly isolated hepatocytes. The expression of Cyp3a1, organic anion transporting polypeptide 2 (Oatp2), multidrug resistance-associated protein 2 (Mrp2) and breast cancer resistance protein (Bcrp) in livers was measured using qRT-PCR. Results: After oral or intravenous administration, the plasma concentrations and areas under concentrations of simvastatin and simvastatin acid were markedly decreased in diabetic rats. Both simvastatin metabolism and Cyp3a activity were markedly increased in hepatocytes of diabetic rats, accompanied by increased expression of hepatic Cyp3a1 mRNA. Furthermore, the uptake of simvastatin by hepatocytes of diabetic rats was markedly increased, which was associated with increased expression of the influx transporter Oatp2, and decreased expression of the efflux transporters Mrp2 and Bcrp. Conclusion: Diabetes enhances the metabolism of simvastatin and simvastatin acid in rats via up-regulating hepatic Cyp3a activity and expression and increasing hepatic uptake. PMID:25152023

  4. A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents

    SciTech Connect

    Kato, Yoshihisa; Suzuki, Hiroshi; Haraguchi, Koichi; Ikushiro, Shinichi; Ito, Yoshihiko; Uchida, Shinya; Yamada, Shizuo; Degawa, Masakuni

    2010-12-15

    Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T{sub 4}) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. One day after the final administration of PB (80 mg/kg, intraperitoneal, once daily for 4 days), significant decreases in the levels of the serum total T{sub 4} and free T{sub 4} occurred in mice, hamsters, and rats, while a significant decrease in the level of serum triiodothyronine was observed in hamsters and rats among the animals examined. In addition, a significant decrease in the level of serum thyroid-stimulating hormone was observed in only hamsters among the rodents examined. Significant increases in the level and activity of hepatic T{sub 4}-UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice, hamsters, and rats, while the increase in the amount of biliary [{sup 125}I]T{sub 4}-glucuronide after an intravenous injection of [{sup 125}I]T{sub 4} to the PB-pretreated animals occurred only in rats. In mice, rats, and hamsters, but not guinea pigs, PB pretreatment promoted the clearance of [{sup 125}I]T{sub 4} from the serum, led to a significant increase in the steady-state distribution volumes of [{sup 125}I]T{sub 4}, and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [{sup 125}I]T{sub 4}. The present findings indicate that the PB-mediated decreases in the serum T{sub 4} level in mice, hamsters, and rats, but not guinea pigs, occur mainly through an increase in the accumulation level of T{sub 4} in the liver.

  5. Decreased plasma cholesterol levels during aging in transgenic mouse models of Alzheimer's disease.

    PubMed

    Wirths, Oliver; Thelen, Karin; Breyhan, Henning; Luzón-Toro, Berta; Hoffmann, Karl-Heinz; Falkai, Peter; Lütjohann, Dieter; Bayer, Thomas A

    2006-02-01

    A large number of studies deals with the association of cholesterol and Abeta levels, however, the results are so far controversial. Whereas some studies report on increased cholesterol levels, other authors refer to an association of decreased peripheral cholesterol and the incidence of Alzheimer's disease. It is also questionable whether plasma cholesterol levels could be used as a predictive biomarker for the incidence of Alzheimer's disease. In the present report, we studied the relationship between these two parameters during aging in different transgenic mouse models of Alzheimer's disease, expressing both mutant human amyloid precursor protein and mutant human presenilin-1. Measurements of plasma cholesterol levels revealed a significant reduction in aged APP/PS1 and APP/PS1ki mice, whereas plasma levels in young and aged control mice remained almost unchanged. Furthermore, statistical analysis revealed a significant negative correlation between plasma cholesterol and brain Abeta42 levels during aging in the mice expressing both APP and PS1. PMID:16307858

  6. Ethanol Effects On Physiological Retinoic Acid Levels

    PubMed Central

    Napoli, Joseph L.

    2011-01-01

    Summary All-trans-retinoic acid (atRA) serves essential functions during embryogenesis and throughout post-natal vertebrate life. Insufficient or excess atRA causes teratogenic and/or toxic effects in the developing embryo: interference with atRA biosynthesis or signaling likely underlies some forms of cancer. Many symptoms of vitamin A (atRA precursor) deficiency and/or toxicity overlap with those of another pleiotropic agent—ethanol. These overlapping symptoms have prompted research to understand whether interference with atRA biosynthesis and/or action may explain (in part) pathology associated with excess ethanol consumption. Ethanol affects many aspects of retinoid metabolism and mechanisms of action site-specifically, but no robust data support inhibition of vitamin A metabolism, resulting in decreased atRA in vivo during normal vitamin A nutriture. Actually, ethanol either has no effect on or increases atRA at select sites. Despite this realization, insight into whether interactions between ethanol and retinoids represent cause vs. effect requires additional research. PMID:21766417

  7. Chlorogenic Acid Decreases Intestinal Permeability and Increases Expression of Intestinal Tight Junction Proteins in Weaned Rats Challenged with LPS

    PubMed Central

    Ruan, Zheng; Liu, Shiqiang; Zhou, Yan; Mi, Shumei; Liu, Gang; Wu, Xin; Yao, Kang; Assaad, Houssein; Deng, Zeyuan; Hou, Yongqing; Wu, Guoyao; Yin, Yulong

    2014-01-01

    Chlorogenic acid, a natural phenolic acid present in fruits and plants, provides beneficial effects for human health. The objectives of this study were to investigate whether chlorogenic acid (CHA) could improve the intestinal barrier integrity for weaned rats with lipopolysaccharide (LPS) challenge. Thirty-two weaned male Sprague Dawley rats (21±1 d of age; 62.26±2.73 g) were selected and randomly allotted to four treatments, including weaned rat control, LPS-challenged and chlorogenic acid (CHA) supplemented group (orally 20 mg/kg and 50 mg/kg body). Dietary supplementation with CHA decreased (P<0.05) the concentrations of urea and albumin in the serum, compared to the LPS-challenged group. The levels of IFN-γ and TNF-α were lower (P<0.05) in the jejunal and colon of weaned rats receiving CHA supplementation, in comparison with the control group. CHA supplementation increased (P<0.05) villus height and the ratio of villus height to crypt depth in the jejunal and ileal mucosae under condictions of LPS challenge. CHA supplementation decreased (P<0.05) intestinal permeability, which was indicated by the ratio of lactulose to mannitol and serum DAO activity, when compared to weaned rats with LPS challenge. Immunohistochemical analysis of tight junction proteins revealed that ZO-1 and occludin protein abundances in the jejunum and colon were increased (P<0.05) by CHA supplementation. Additionally, results of immunoblot analysis revealed that the amount of occludin in the colon was also increased (P<0.05) in CHA-supplemented rats. In conclusion, CHA decreases intestinal permeability and increases intestinal expression of tight junction proteins in weaned rats challenged with LPS. PMID:24887396

  8. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

    PubMed

    Zhang, Yiting; Hodgson, Nathaniel W; Trivedi, Malav S; Abdolmaleky, Hamid M; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders. PMID:26799654

  9. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia

    PubMed Central

    Zhang, Yiting; Hodgson, Nathaniel W.; Trivedi, Malav S.; Abdolmaleky, Hamid M.; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C.

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders. PMID:26799654

  10. Involvement of decreased neuroglobin protein level in cognitive dysfunction induced by 1-bromopropane in rats.

    PubMed

    Guo, Ying; Yuan, Hua; Jiang, Lulu; Yang, Junlin; Zeng, Tao; Xie, Keqin; Zhang, Cuili; Zhao, Xiulan

    2015-03-10

    1-Bromopropane (1-BP) is used as a substitute for ozone-depleting solvents (ODS) in industrial applications. 1-BP could display central nervous system (CNS) neurotoxicity manifested by cognitive dysfunction. Neuroglobin (Ngb) is an endogenous neuroprotectant and is predominantly expressed in the nervous system. The present study aimed to investigate Ngb involvement in CNS neurotoxicity induced by 1-BP in rats. Male Wistar rats were randomly divided into 5 groups (n=14) and treated with 0, 100, 200, 400 and 800 mg/kg bw 1-BP, respectively, by gavage for consecutive 12 days. Rats displayed cognitive dysfunction dose-dependently through Morris water maze (MWM) test. Significant neuron loss in layer 5 of the prelimbic cortex (PL) was observed. Moreover, 1-BP decreased Ngb protein level in cerebral cortex and Ngb decrease was significantly positively correlated with cognitive dysfunction. Glutathione (GSH) content, GSH/oxidized glutathione (GSSG) ratio and glutamate cysteine ligase (GCL) activity decreased in cerebral cortex, coupled with the increase in GSSG content. GSH and GSH/GSSG ratio decrease were significantly positively correlated with cortical Ngb decrease. Additionally, levels of N-epsilon-hexanoyl-lysine (HEL) and 4-hydroxy-2-nonenal (4-HNE) modified proteins in cerebral cortex of 1-BP-treated rats increased significantly. In conclusion, it was suggested that 1-BP resulted in decreased endogenous neuroprotectant Ngb in cerebral cortex, which might play an important role in CNS neurotoxicity induced by 1-BP and that 1-BP-induced oxidative stress in cerebral cortex might partly be responsible for Ngb decrease. PMID:25557405

  11. Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid.

    PubMed

    Liu, Xudong; Zhang, Yuchao; Li, Jinquan; Wang, Dong; Wu, Yang; Li, Yan; Lu, Zhisong; Yu, Samuel C T; Li, Rui; Yang, Xu

    2014-01-01

    Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects. PMID:24596461

  12. Retinoic acid decreases the severity of Salmonella enterica serovar Typhimurium mediated gastroenteritis in a mouse model.

    PubMed

    Sinha, Ritam; Howlader, Debaki Ranjan; Mukherjee, Priyadarshini; Rai, Sulabh; Nag, Dhrubajyoti; Koley, Hemanta

    2016-07-01

    Gastroenteritis is a global burden; it's the major cause of morbidity and mortality both in adults and children of developing countries. Salmonella is one of the leading causes of bacteria-mediated gastroenteritis and due to its increasing multidrug antibiotic resistance; Salmonella-mediated gastroenteritis is difficult to control. Retinoic acid, the biologically active agent of vitamin A has an anti-inflammatory effect on experimental colitis. In this study we have shown All trans retinoic acid (ATRA) treatment down regulates Salmonella-mediated colitis in a murine model. Macroscopic signs of inflammation such as decrease in body weight and cecum weight, shorter length of proximal colon and pathological score of colitis were observed less in ATRA treated mice than in a vehicle control group. ATRA treatment not only reduced pro-inflammatory cytokine responses, such as TNF-α, IL-6, IL-1β, IFN-γ and IL-17 production but also increased IL-10 response in the supernatant of intestinal tissue. Results also suggested that ATRA treatment enhances the number of FoxP3-expressing T regulatory cells in MLN and also decreases bacterial load in systemic organs. We concluded that ATRA treatment indeed reduces Salmonella Typhimurium-mediated gastroenteritis in mice, suggesting it could be an important part of an alternative therapeutic approach to combat the disease. PMID:26858186

  13. Chronic inflammation contributes to the development of hepatocellular carcinoma by decreasing miR-122 levels

    PubMed Central

    Li, Changfei; Deng, Mengmeng; Hu, Jun; Li, Xin; Chen, Lizhao; Ju, Ying; Hao, Junli; Meng, Songdong

    2016-01-01

    Persistent inflammation in chronic hepatitis plays a major role in the development of hepatocellular carcinoma (HCC). In this study, the major inflammatory cytokines expressed in chronic hepatitis, IL-6 and TNF-α, induced a marked decrease in microRNA-122 (miR-122) levels, and miR-122 expression was downregulated in the livers of chronic hepatitis B (CHB) patients. The decrease of miR-122 caused upregulation of the proinflammatory chemokine CCL2. IL-6 and TNF-α suppressed miR-122 both by directly downregulating the transcription factor C/EBPα and indirectly upregulating c-myc, which blocks C/EBPα-mediated miR-122 transcription. In addition, IL-6 and TNF-α levels were elevated and miR-122 levels were decreased in mouse and rat models of diethylnitrosamine (DEN)-induced HCC. Restoration of miR-122 levels through delivery of agomir-122 suppressed DEN-induced hepatocarcinogenesis in mice. Our results show that inflammation-induced miR-122 downregulation in hepatitis contributes to carcinogenesis and suggest that increasing miR-122 may be an effective strategy for preventing HCC development in CHB patients. PMID:26933995

  14. Increasing dietary palmitic acid decreases fat oxidation and daily energy expenditure123

    PubMed Central

    Bunn, Janice Y; Ugrasbul, Figen

    2005-01-01

    Background Oleic acid (OA) is oxidized more rapidly than is palmitic acid (PA). Objective We hypothesized that changing the dietary intakes of PA and OA would affect fatty acid oxidation and energy expenditure. Design A double-masked trial was conducted in 43 healthy young adults, who, after a 28-d, baseline, solid-food diet (41% of energy as fat, 8.4% as PA, and 13.1% as OA), were randomly assigned to one of two 28-d formula diets: high PA (40% of energy as fat, 16.8% as PA, and 16.4% as OA; n = 21) or high OA (40% of energy as fat, 1.7% as PA, and 31.4% as OA; n = 22). Differences in the change from baseline were evaluated by analysis of covariance. Results In the fed state, the respiratory quotient was lower (P = 0.01) with the high OA (0.86 ± 0.01) than with the high-PA (0.89 ± 0.01) diet, and the rate of fat oxidation was higher (P = 0.03) with the high-OA (0.0008 ± 0.0001) than with the high-PA (0.0005 ± 0.0001 mg · kg fat-free mass−1 · min−1) diet. Resting energy expenditure in the fed and fasting states was not significantly different between groups. Change in daily energy expenditure in the high-OA group (9 ± 60 kcal/d) was significantly different from that in the high-PA group (−214 ±69 kcal/d; P = 0.02 or 0.04 when expressed per fat-free mass). Conclusions Increases in dietary PA decrease fat oxidation and daily energy expenditure, whereas decreases in PA and increases in OA had the opposite effect. Increases in dietary PA may increase the risk of obesity and insulin resistance. PMID:16087974

  15. Poly-lactic-glycolic-acid surface nanotopographies selectively decrease breast adenocarcinoma cell functions

    NASA Astrophysics Data System (ADS)

    Zhang, Lijuan; Webster, Thomas J.

    2012-04-01

    The ability of poly(lactic-co-glycolic acid) (PLGA, 50:50 PLG/PGA, wt%) nanotopographies to decrease lung epithelial carcinoma cell functions (including adhesion, proliferation, apoptosis and vascular endothelial growth factor (VEGF) secretion) has been previously reported. Specifically, results demonstrated decreased lung epithelial carcinoma cell VEGF synthesis on 23 nm surface-featured PLGA compared to traditional nanosmooth PLGA. However, clearly, different cell lines could have different behaviors on similar biomaterials. Thus, to investigate the universality of nanopatterned PLGA substrates to inhibit numerous cancer cell functions, here, breast epithelial adenocarcinoma cell (MCF-7) adhesion, proliferation, apoptosis and VEGF secretion were determined on different PLGA nanometer surface topographies. To isolate surface nanotopographical effects from all other surface properties, PLGA surfaces with various nanotopographies but similar chemistry and hydrophobicity were fabricated here. Atomic force microscopy (AFM) verified the varied nanotopographies on the PLGA surfaces prepared in this study. Importantly, results demonstrated for the first time significantly decreased breast adenocarcinoma cell functions (including decreased proliferation rate, increased apoptosis and decreased VEGF synthesis) on 23 nm featured PLGA surfaces compared to all other PLGA surface topographies fabricated (specifically, nanosmooth, 300 and 400 nm surface-featured PLGA surfaces). In contrast, healthy breast epithelial cells proliferated more (24%) on the 23 nm featured PLGA surfaces compared to all other PLGA samples. In summary, these results provided further insights into understanding the role PLGA surface nanotopographies can have on cancer cell functions and, more importantly, open the possibility of using polymer nanotopographies for a wide range of anticancer regenerative medicine applications (without resorting to the use of chemotherapeutics).

  16. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health.

    PubMed

    Fontana, Luigi; Cummings, Nicole E; Arriola Apelo, Sebastian I; Neuman, Joshua C; Kasza, Ildiko; Schmidt, Brian A; Cava, Edda; Spelta, Francesco; Tosti, Valeria; Syed, Faizan A; Baar, Emma L; Veronese, Nicola; Cottrell, Sara E; Fenske, Rachel J; Bertozzi, Beatrice; Brar, Harpreet K; Pietka, Terri; Bullock, Arnold D; Figenshau, Robert S; Andriole, Gerald L; Merrins, Matthew J; Alexander, Caroline M; Kimple, Michelle E; Lamming, Dudley W

    2016-07-12

    Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet. PMID:27346343

  17. Serum level of vascular endothelial growth factor decreased in chronic ketamine abusers

    PubMed Central

    Fan, Ni; Zhang, Minling; Xu, Ke; Ke, Xiaoyin; Ding, Yi; Wang, Daping; Liu, Yuping; Ning, Yuping; Deng, Xuefeng; He, Hongbo

    2016-01-01

    Aims To evaluate the serum level of vascular endothelial growth factor (VEGF) in a group of chronic ketamine abusers in comparison to healthy controls. Methods Eighty-one ketamine abusers who were hospitalized for the treatment of ketamine dependence and 39 healthy controls were recruited. Serum VEGF level was measured by enzyme linked immunosorbent assay (ELISA). Psychopathological symptoms were assessed using Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Results Serum level of VEGF was significantly lower in chronic ketamine abusers compared to healthy controls (64.6 ± 42.1 vs. 92.4 ± 59.4 pg/ml, F = 7.243, p = 0.008). Conclusions Serum level of VEGF decreased in chronic ketamine abusers compared to healthy controls. PMID:26003336

  18. Forearm Muscle Oxygenation Decreases During Low Levels of Brief, Isometric Contraction

    NASA Technical Reports Server (NTRS)

    Murthy Gita; Kahan, N. J.; Hargens, Alan R.; Rempel, D. M.; Hargens, Murthy G. (Technical Monitor)

    1997-01-01

    Regional muscle pain syndromes can be caused by repeated and sustained exertion of a specific muscle. Such exertion may elevate local tissue fluid pressure, reduce blood flow and tissue oxygenation (TO2), and cause fatigue, pain and functional deficits of the Involved muscle. Low levels (less than 20% maximum voluntary contraction (MVC)) of prolonged static contraction of the upper extremity are common In many occupational settings and May cause fatigue. The purpose of our Investigation was to determine whether TO2 decreases significantly at low levels of static contraction of the extensor carpi radialis brevis (ECRB).

  19. Elevated plasma leptin levels of fasted rainbow trout decrease rapidly in response to feed intake.

    PubMed

    Johansson, Marcus; Björnsson, Björn Thrandur

    2015-04-01

    Leptin has an anorexigenic effect in fish, indicating a role in regulation of growth and energy homeostasis. The study aimed to further clarify the physiological role of leptin in rainbow trout, specifically its short-term response to feed intake after a period of fasting. Utilizing a salmonid leptin radioimmunoassay, the study demonstrates differences in plasma leptin levels in fishes with different nutritional status and at the onset of feeding. Some of the fasted fish were clearly in a state of anorexia, and did not initiate feeding during the 72h refeeding period. For those fish that did initiate feeding, both previously fed and fasted, plasma leptin levels rapidly decreased during the first 24h in correlation with increased amount of food reaching the gastrointestinal tract, while non-feeding individuals retained a high plasma leptin levels. The data indicate that the leptin-induced anorexic state is broken after onset of feeding and that the regulatory mechanisms leading to decreased plasma leptin levels are linked to nutrient levels. PMID:25745812

  20. Investigating the Causes for Decreased Levels of Glutathione in Individuals with Type II Diabetes

    PubMed Central

    Lagman, Minette; Ly, Judy; Saing, Tommy; Morris, Devin; Chi, Po-Ting; Ochoa, Cesar; Sathananthan, Airani; Venketaraman, Vishwanath

    2015-01-01

    Tuberculosis (TB) remains an eminent global burden with one third of the world’s population latently infected with Mycobacterium tuberculosis (M. tb). Individuals with compromised immune systems are especially vulnerable to M. tb infection. In fact, individuals with Type 2 Diabetes Mellitus (T2DM) are two to three times more susceptible to TB than those without T2DM. In this study, we report that individuals with T2DM have lower levels of glutathione (GSH) due to compromised levels of GSH synthesis and metabolism enzymes. Transforming growth factor beta (TGF-β), a cytokine that is known to decrease the expression of the catalytic subunit of glutamine-cysteine ligase (GCLC) was found in increased levels in the plasma samples from individuals with T2DM, explaining the possible underlying mechanism that is responsible for decreased levels of GSH in individuals with T2DM. Moreover, increased levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-17 (IL-17) were observed in plasma samples isolated from individuals with T2DM. Increased levels of IL-6 and IL-17 was accompanied by enhanced production of free radicals further indicating an alternative mechanism for the decreased levels of GSH in individuals with T2DM. Augmenting the levels of GSH in macrophages isolated from individuals with T2DM resulted in improved control of M. tb infection. Furthermore, cytokines that are responsible for controlling M. tb infection at the cellular and granuloma level such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), were found to be compromised in plasma samples isolated from individuals with T2DM. On the other hand, interleukin-10 (IL-10), an immunosuppressive cytokine was increased in plasma samples isolated from individuals with T2DM. Overall, these findings suggest that lower levels of GSH in individuals with T2DM lead to their increased susceptibility to

  1. Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure

    PubMed Central

    Huang, Ying; Lin, Yingzhong; Zhang, Shumin; Wang, Zhijian; Zhang, Jianwei; Chang, Chao; Liu, Ling; Ji, Qingwei; Liu, Xiaofei

    2016-01-01

    Background. Recent evidence demonstrated that the circulating levels of omentin-1 are related to the presence of ischemic heart disease and heart failure. However, omentin-1 plasma levels in patients with nonischemic dilated cardiomyopathy (DCM), which is the most common etiology of heart failure, have yet to be investigated. Methods. Plasma levels of omentin-1 and adiponectin were measured in 100 patients with DCM and 45 healthy controls. Results. Plasma omentin-1 levels significantly decreased in DCM patients compared with the control group, whereas adiponectin levels significantly increased in DCM patients compared with the control group. Plasma omentin-1 levels were negatively correlated with adiponectin (R = −0.376, P = 0.005), C-reactive protein (CRP) (R = −0.320, P = 0.001), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (R = −0.365, P = 0.000) levels as well as left ventricular end-diastolic diameter (LVEDD) (R = −0.200, P = 0.046) but were positively correlated with left ventricular ejection fraction (LVEF) (R = 0.496, P = 0.000). Plasma adiponectin levels were positively correlated with CRP (R = 0.273, P = 0.006) and NT-proBNP (R = 0.329, P = 0.001) levels but were negatively correlated with fasting glucose (R = −0.218, P = 0.029) and LVEF (R = −0.615, P = 0.000) levels. Furthermore, omentin-1 (OR 0.983, 95% CI 0.970 to 0.996; P = 0.008) levels were independently associated with the presence of DCM before NT-proBNP was added. Conclusions. Omentin-1 is a novel biomarker of DCM. PMID:27313334

  2. Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure.

    PubMed

    Huang, Ying; Lin, Yingzhong; Zhang, Shumin; Wang, Zhijian; Zhang, Jianwei; Chang, Chao; Liu, Ling; Ji, Qingwei; Liu, Xiaofei

    2016-01-01

    Background. Recent evidence demonstrated that the circulating levels of omentin-1 are related to the presence of ischemic heart disease and heart failure. However, omentin-1 plasma levels in patients with nonischemic dilated cardiomyopathy (DCM), which is the most common etiology of heart failure, have yet to be investigated. Methods. Plasma levels of omentin-1 and adiponectin were measured in 100 patients with DCM and 45 healthy controls. Results. Plasma omentin-1 levels significantly decreased in DCM patients compared with the control group, whereas adiponectin levels significantly increased in DCM patients compared with the control group. Plasma omentin-1 levels were negatively correlated with adiponectin (R = -0.376, P = 0.005), C-reactive protein (CRP) (R = -0.320, P = 0.001), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (R = -0.365, P = 0.000) levels as well as left ventricular end-diastolic diameter (LVEDD) (R = -0.200, P = 0.046) but were positively correlated with left ventricular ejection fraction (LVEF) (R = 0.496, P = 0.000). Plasma adiponectin levels were positively correlated with CRP (R = 0.273, P = 0.006) and NT-proBNP (R = 0.329, P = 0.001) levels but were negatively correlated with fasting glucose (R = -0.218, P = 0.029) and LVEF (R = -0.615, P = 0.000) levels. Furthermore, omentin-1 (OR 0.983, 95% CI 0.970 to 0.996; P = 0.008) levels were independently associated with the presence of DCM before NT-proBNP was added. Conclusions. Omentin-1 is a novel biomarker of DCM. PMID:27313334

  3. OKN-007 decreases free radical levels in a preclinical F98 rat glioma model.

    PubMed

    Coutinho de Souza, Patricia; Smith, Nataliya; Atolagbe, Oluwatomisin; Ziegler, Jadith; Njoku, Charity; Lerner, Megan; Ehrenshaft, Marilyn; Mason, Ronald P; Meek, Bill; Plafker, Scott M; Saunders, Debra; Mamedova, Nadezda; Towner, Rheal A

    2015-10-01

    Free radicals are associated with glioma tumors. Here, we report on the ability of an anticancer nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)] to decrease free radical levels in F98 rat gliomas using combined molecular magnetic resonance imaging (mMRI) and immunospin-trapping (IST) methodologies. Free radicals are trapped with the spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), to form DMPO macromolecule radical adducts, and then further tagged by immunospin trapping by an antibody against DMPO adducts. In this study, we combined mMRI with a biotin-Gd-DTPA-albumin-based contrast agent for signal detection with the specificity of an antibody for DMPO nitrone adducts (anti-DMPO probe), to detect in vivo free radicals in OKN-007-treated rat F98 gliomas. OKN-007 was found to significantly decrease (P < 0.05) free radical levels detected with an anti-DMPO probe in treated animals compared to untreated rats. Immunoelectron microscopy was used with gold-labeled antibiotin to detect the anti-DMPO probe within the plasma membrane of F98 tumor cells from rats administered anti-DMPO in vivo. OKN-007 was also found to decrease nuclear factor erythroid 2-related factor 2, inducible nitric oxide synthase, 3-nitrotyrosine, and malondialdehyde in ex vivo F98 glioma tissues via immunohistochemistry, as well as decrease 3-nitrotyrosine and malondialdehyde adducts in vitro in F98 cells via ELISA. The results indicate that OKN-007 effectively decreases free radicals associated with glioma tumor growth. Furthermore, this method can potentially be applied toward other types of cancers for the in vivo detection of macromolecular free radicals and the assessment of antioxidants. PMID:26119786

  4. Pregnant rats show enhanced spatial memory, decreased anxiety, and altered levels of monoaminergic neurotransmitters

    PubMed Central

    Macbeth, A.H.; Gautreaux, C.; Luine, V.N.

    2008-01-01

    Spatial memory, anxiety and central monoaminergic activities were measured in non-pregnant (NP) and pregnant females during two time periods of pregnancy: gestational day 7–9 (GD7, GD9) & gestation day 16–18 (GD16, GD18). Pregnant females discriminated between object locations on both test days on an object placement task, whereas NP females were unable to discriminate between locations. Pregnant females displayed decreased anxiety on the elevated plus maze on GD9 compared to NP females, followed by increased anxiety-like behavior on the elevated plus maze on GD18. Monoamine levels and activity (as indexed by turnover ratio) were measured in prefrontal cortex (PFC), CA1 and CA3 regions of the hippocampus (areas important for memory), and medial preoptic area (mPOA, an area important in display of maternal behaviors). In the PFC, NP females generally had higher monoamine levels and turnover ratios; however, norepinephrine (NE) turnover was higher in pregnant females at GD18. In the CA1 and CA3 regions of the hippocampus, monoamine levels and turnover ratios were generally higher during pregnancy, particularly on GD9. In the mPOA, pregnancy was associated with increases in NE activity, a previously unreported finding. The present study expands upon existing research indicating that pregnancy is beneficial to spatial memory and may decrease anxiety. Changes in monoamine levels and activity in specific brain regions indicate that the dopamine, norepinephrine and serotonin systems may contribute to the observed behavioral differences. PMID:18823955

  5. Decrease in TSH levels after lactose restriction in Hashimoto's thyroiditis patients with lactose intolerance.

    PubMed

    Asik, Mehmet; Gunes, Fahri; Binnetoglu, Emine; Eroglu, Mustafa; Bozkurt, Neslihan; Sen, Hacer; Akbal, Erdem; Bakar, Coskum; Beyazit, Yavuz; Ukinc, Kubilay

    2014-06-01

    We aimed to evaluate the prevalence of lactose intolerance (LI) in patients with Hashimoto's thyroiditis(HT) and the effects of lactose restriction on thyroid function in these patients. Eighty-three HT patients taking L-thyroxine (LT4) were enrolled, and lactose tolerance tests were performed on all patients. Lactose intolerance was diagnosed in 75.9 % of the patients with HT. Thirty-eight patients with LI were started on a lactose-restricted diet for 8 weeks. Thirty-eight patients with LI (30 euthyroid and 8 with subclinical hypothyroidism), and 12 patients without LI were included in the final analysis. The level of TSH significantly decreased in the euthyroid and subclinical hypothyroid patients with LI [from 2.06 ± 1.02 to 1.51 ±1.1 IU/mL and from 5.45 ± 0.74 to 2.25 ± 1.88 IU/mL,respectively (both P<0.05)]. However, the level of TSH in patients without LI did not change significantly over the 8 weeks (P>0.05). Lactose intolerance occurs at a high frequency in HT patients. Lactose restriction leads to decreased levels of TSH, and LI should be considered in hypothyroid patients who require increasing LT4 doses,have irregular TSH levels and are resistant to LT4 treatment. PMID:24078411

  6. Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis.

    PubMed

    Fernandes, Luis G V; Filho, Antonio F S; Souza, Gisele O; Vasconcellos, Silvio A; Romero, Eliete C; Nascimento, Ana L T O

    2016-08-01

    Pathogenic bacteria of the genus Leptospira are the causative agent of leptospirosis, an emergent infectious disease that affects humans and animals worldwide. Severe forms of the disease in humans include jaundice, multiple organ failure and intense haemorrhage. Up to now, mechanisms associated with the haemorrhage foci are poorly understood. We report in this work that, despite the low levels of antithrombin III in convalescent human serum samples, virulent, culture-attenuated and saprophyte strains of Leptospira are unable to bind and/or degrade this thrombin inhibitor, suggesting an indirect mechanism of pathogenesis. Lower levels of prothrombin were found in serum samples at the onset and convalescent phase of the disease when compared to normal human sera. The concomitant decreased levels of antithrombin III and prothrombin suggest a process of stimulated coagulation, which is corroborated by the increase of prothrombin fragment F1+2 in the serum samples. Data obtained with hamsters experimentally infected with virulent Leptospira interrogans serovars Kennewicki and Canicola strongly point out that haemorrhage is correlated with decreased levels of thrombin inhibitors and prothrombin. Activated coagulation might lead to an overconsumption of coagulation factors ultimately leading to bleeding and organ failure. PMID:27260249

  7. Fatty acid amide supplementation decreases impulsivity in young adult heavy drinkers.

    PubMed

    van Kooten, Maria J; Veldhuizen, Maria G; de Araujo, Ivan E; O'Malley, Stephanie S; Small, Dana M

    2016-03-01

    Compromised dopamine signaling in the striatum has been associated with the expression of impulsive behaviors in addiction, obesity and alcoholism. In rodents, intragastric infusion of the fatty acid amide oleoylethanolamide increases striatal extracellular dopamine levels via vagal afferent signaling. Here we tested whether supplementation with PhosphoLean™, a dietary supplement that contains the precursor of the fatty acid amide oleoylethanolamide (N-oleyl-phosphatidylethanolamine), would reduce impulsive responding and alcohol use in heavy drinking young adults. Twenty-two individuals were assigned to a three-week supplementation regimen with PhosphoLean™ or placebo. Impulsivity was assessed with self-report questionnaires and behavioral tasks pre- and post-supplementation. Although self-report measures of impulsivity did not change, supplementation with PhosphoLean™, but not placebo, significantly reduced false alarm rate on a Go/No-Go task. In addition, an association was found between improved sensitivity on the Go/No-Go task and reduced alcohol intake. These findings provide preliminary evidence that promoting fatty acid derived gut-brain dopamine communication may have therapeutic potential for reducing impulsivity in heavy drinkers. PMID:26656766

  8. Selective decrease of bis(monoacylglycero)phosphate content in macrophages by high supplementation with docosahexaenoic acid.

    PubMed

    Bouvier, Jérôme; Zemski Berry, Karin A; Hullin-Matsuda, Françoise; Makino, Asami; Michaud, Sabine; Geloën, Alain; Murphy, Robert C; Kobayashi, Toshihide; Lagarde, Michel; Delton-Vandenbroucke, Isabelle

    2009-02-01

    Bis(monoacylglycero)phosphate (BMP) is a unique phospholipid (PL) preferentially found in late endosomal membranes, where it forms specialized lipid domains. Recently, using cultured macrophages treated with anti-BMP antibody, we showed that BMP-rich domains are involved in cholesterol homeostasis. We had previously stressed the high propensity of BMP to accumulate docosahexaenoic acid (DHA), compared with other PUFAs. Because phosphatidylglycerol (PG) was reported as a precursor for BMP synthesis in RAW macrophages, we examined the effects of PG supplementation on both FA composition and amount of BMP in this cell line. Supplementation with dioleoyl-PG (18:1/18:1-PG) induced BMP accumulation, together with an increase of oleate proportion. Supplementation with high concentrations of didocosahexaenoyl-PG (22:6/22:6-PG) led to a marked enrichment of DHA in BMP, resulting in the formation of diDHA molecular species. However, the amount of BMP was selectively decreased. Similar effects were observed after supplementation with high concentrations of nonesterified DHA. Addition of vitamin E prevented the decrease of BMP and further increased its DHA content. Supplementation with 22:6/22:6-PG promoted BMP accumulation with an enhanced proportion of 22:6/22:6-BMP. DHA-rich BMP was significantly degraded after cell exposure to oxidant conditions, in contrast to oleic acid-rich BMP, which was not affected. Using a cell-free system, we showed that 22:6/22:6-BMP is highly oxidizable and partially protects cholesterol oxidation, compared with 18:1/18:1-BMP. Our data suggest that high DHA content in BMP led to specific degradation of this PL, possibly through the diDHA molecular species, which is very prone to peroxidation and, as such, a potential antioxidant in its immediate vicinity. PMID:18809971

  9. Dependence of intestinal amino acid uptake on dietary protein or amino acid levels

    SciTech Connect

    Karasov, W.H.; Solberg, D.H.; Diamond, J.M.

    1987-05-01

    To understand how intestinal amino acid (AA) transport is regulated by dietary substrate levels, the authors measured uptake of seven radioactively-labelled AAs and glucose across the jejunal brush-border membrane of mice kept on one of three isocaloric rations differing in nitrogen content. In the high-protein ration, uptake increased by 77-81% for the nonessential, less toxic AAs, proline, and aspartate but only by 32-61% for the more toxic essential AAs tested. In the nitrogen-deficient ration, uptake decreased for the nonessential aspartate and proline but stayed constant or increased for essential AAs and for the nonessential alanine. These patterns imply independent regulation of the intestine's various AA transporters. With decreasing dietary AA (or protein), the imino acid and acidic AA private transporters are repressed, while activities of the basic AA transporter and the neutral AA public transporter decrease to an asymptote or else go through a minimum. These regulatory patterns can be understood as a compromise among conflicting constraints imposed by protein's multiple roles as a source of calories, nitrogen, and essential AAs and by the toxicity of essential AAs at high concentrations.

  10. Oxidative stress and decreased thiol level in patients with migraine: cross-sectional study.

    PubMed

    Eren, Yasemin; Dirik, Ebru; Neşelioğlu, Salim; Erel, Özcan

    2015-12-01

    Although migraine is a neurological disorder known since long, its physiopathology remains unclear. Recent studies suggest that migraine is associated with oxidative stress; however, they report divergent results. The aim of the present study was to evaluate total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and serum thiol level in migraine patients with or without aura. The study group consisted of 141 migraine patients. The control group included 70 healthy subjects. TAS, TOS, OSI were evaluated using a method developed by Erel. Serum thiol level was measured using the Hu method. No difference was found in TAS, TOS, OSI between the patients and controls. The level of thiol was significantly lower in patients than in controls. Negative correlations were detected between thiol level and Migraine Disability Assessment score in patients. Although TAS, TOS, and OSI were similar to those of the control group, serum thiol level, an important marker of antioxidant capacity, was significantly lower in migraines compared with controls, and caused more serious disability. Novel treatment approaches may be developed based on these data, and compounds containing thiol, such as alpha lipoic acid and N-acetyl cysteine, may be used in prophylaxis. PMID:25595415

  11. A decrease in phytic acid content substantially affects the distribution of mineral elements within rice seeds.

    PubMed

    Sakai, Hiroaki; Iwai, Toru; Matsubara, Chie; Usui, Yuto; Okamura, Masaki; Yatou, Osamu; Terada, Yasuko; Aoki, Naohiro; Nishida, Sho; Yoshida, Kaoru T

    2015-09-01

    Phytic acid (myo-inositol hexakisphosphate; InsP6) is the storage compound of phosphorus and many mineral elements in seeds. To determine the role of InsP6 in the accumulation and distribution of mineral elements in seeds, we performed fine mappings of mineral elements through synchrotron-based X-ray microfluorescence analysis using developing seeds from two independent low phytic acid (lpa) mutants of rice (Oryza sativa L.). The reduced InsP6 in lpa seeds did not affect the translocation of mineral elements from vegetative organs into seeds, because the total amounts of phosphorus and the other mineral elements in lpa seeds were identical to those in the wild type (WT). However, the reduced InsP6 caused large changes in mineral localization within lpa seeds. Phosphorus and potassium in the aleurone layer of lpa greatly decreased and diffused into the endosperm. Zinc and copper, which were broadly distributed from the aleurone layer to the inner endosperm in the WT, were localized in the narrower space around the aleurone layer in lpa mutants. We also confirmed that similar distribution changes occurred in transgenic rice with the lpa phenotype. Using these results, we discussed the role of InsP6 in the dynamic accumulation and distribution patterns of mineral elements during seed development. PMID:26259185

  12. Pyrrole-hyaluronic acid conjugates for decreasing cell binding to metals and conducting polymers

    PubMed Central

    Lee, Jae Young; Schmidt, Christine E.

    2010-01-01

    Surface modification of electrically conductive biomaterials has been studied to improve biocompatibility for a number of applications, such as implantable sensors and microelectrode arrays. In this study, we electrochemically coated electrodes with biocompatible and non-cell adhesive hyaluronic acid (HA) to reduce cellular adhesion for potential use in neural prostheses. To this end, pyrrole-conjugated hyaluronic acid (PyHA) was synthesized and employed for electrochemical coating of platinum, indium-tin-oxide, and polystyrene sulfonate-doped polypyrrole electrodes. This PyHA conjugate consists of (1) a pyrrole moiety that allows the compound to be electrochemically deposited onto a conductive substrate and (2) non-adhesive HA to minimize cell adhesion and to potentially decrease inflammatory tissue responses. Our characterization results showed the presence of a hydrophilic p(PyHA) layer on the modified electrode, and impedance measurements revealed impedance that was statistically the same as the unmodified electrode. We found that the p(PyHA)-coated electrodes minimized adhesion and migration of fibroblasts and astrocytes for a minimum of up to 3 months. Also, the coating was stable in physiological solution for 3 months and also stable against enzymatic degradation by hyaluronidase. These studies suggest that this p(PyHA)-coating has the potential to be used to mask conducting electrodes from adverse glial responses that occur upon implantation. In addition, electrochemical coating with PyHA can be potentially extended for the surface modification of other metallic and conducting substances such as stents and biosensors. PMID:20558330

  13. Amino acid loss during volume regulatory decrease in cultured chick heart cells.

    PubMed

    Rasmusson, R L; Davis, D G; Lieberman, M

    1993-01-01

    Mechanisms of volume regulation in hyposomotically treated cultured chick heart cell preparations were studied using optical, biochemical, and nuclear magnetic resonance methods. This approach afforded the resolution of time-dependent responses that might ordinarily be obscured by the complex morphology of intact cardiac muscle preparations. In hyposmotic solutions, cells swelled to a peak volume within 3 min and slowly regulated toward original volume (regulatory volume decrease, RVD). Upon return of the cells to isosmotic solution following hyposmotic treatment, the cells shrank to a steady-state volume that was substantially less than the initial volume in control solution. A vigorous RVD could also be elicited by hyposmotic swelling under Cl(-)-free conditions. Measurement of both inorganic cation loss via atomic absorption spectroscopy and organic solute loss via 1H-nuclear magnetic resonance and high-pressure liquid chromatographic techniques revealed that the RVD observed following exposure to hyposomotic solutions was mediated in part by a substantial loss of taurine, glutamate, aspartate, and glycine as well as loss of inorganic ions (Na+,K+). The hyposmotically activated transport of amino acids was also associated with the production of glutamate and aspartate. The volume regulatory release and production of amino acids have significant implications for the metabolic and functional integrity of cardiac cells. PMID:8430762

  14. Decreased apoptosis during CAR-mediated hepatoprotection against lithocholic acid-induced liver injury in mice.

    PubMed

    Beilke, Lisa D; Aleksunes, Lauren M; Olson, Erik R; Besselsen, David G; Klaassen, Curtis D; Dvorak, Katerina; Cherrington, Nathan J

    2009-07-10

    Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR). Activation of CAR can protect the liver against bile acid-induced toxicity and it may have a role in cell death via apoptosis by altering expression of Bcl-2 family proteins such as myeloid cell leukemia-1 (Mcl-1). Our aim was to determine if activation of CAR reduces hepatocellular apoptosis during cholestasis as a mechanism of hepatoprotection. CAR(+/+) (WT) and CAR(-/-) (CAR-null) mice were pre-treated with compounds known to activate CAR prior to induction of intrahepatic cholestasis using the secondary bile acid lithocholic acid (LCA). Pre-treatment with the CAR activators phenobarbital (PB) and TCPOBOP (TC), as well as the non-CAR activator pregnenolone 16alpha-carbontrile (PCN), protected against LCA-induced liver injury in WT mice, whereas liver injury was more extensive without CAR (CAR-null). Unexpectedly, expression of anti-apoptotic Mcl-1 and Bcl-x(L) was not increased in hepatoprotected mice. Compared to unprotected groups, apoptosis was decreased in hepatoprotected mice as evidenced by the absence of cleaved caspase 3 (cCasp3). In contrast to the cytoplasmic localization in the injured livers (LCA and oltipraz), Mcl-1 protein was localized in the nucleus of hepatoprotected livers to potentially promote cell survival. This study demonstrates that although apoptosis is reduced in hepatoprotected mice pre-treated with CAR and non-CAR activators; hepatoprotection is not directly a result of CAR-induced Mcl-1 expression. PMID:19433268

  15. R-ETODOLAC DECREASES BETA-CATENIN LEVELS ALONG WITH SURVIVAL AND PROLIFERATION OF HEPATOMA CELLS

    PubMed Central

    Behari, Jaideep; Zeng, Gang; Otruba, Wade; Thompson, Michael; Muller, Peggy; Micsenyi, Amanda; Sekhon, Sandeep S.; Leoni, Lorenzo; Monga, Satdarshan P. S.

    2007-01-01

    Background Inhibition of hepatoma cells by cyclooxygenase (COX)-2 dependent and independent mechanisms has been shown previously. Here, we examine the effect of Celecoxib, a COX-2-inhibitor and R-Etodolac, an enantiomer of the nonsteroidal anti-inflammatory drug Etodolac, which lacks COX-inhibitory activity, on the Wnt/β-catenin pathway and human hepatoma cells. Methods Hep3B and HepG2 cell lines were treated with Celecoxib or R-Etodolac, and examined for viability, DNA synthesis, Wnt/β-catenin pathway components, and downstream target gene expression. Results Celecoxib at high doses affected β-catenin protein by inducing its degradation via GSK3β and APC along with diminished tumor cell proliferation and survival. R-Etodolac at physiological doses caused decrease in total and activated β-catenin protein secondary to decrease in its gene expression and post-translationally through GSK3β activation. In addition, increased β-catenin-E-cadherin was also observed at the membrane. An associated inhibition of β-catenin-dependent Tcf reporter activity, decreased levels of downstream target gene products glutamine synthetase and cyclin-D1, and decreased proliferation and survival of hepatoma cells was evident. Conclusion The antitumor effects of Celecoxib (at high concentrations) and R-Etodolac (at physiological doses) on HCC cells were accompanied by the down-regulation of β-catenin demonstrating a useful therapeutic strategy in hepatocellular cancer. PMID:17275129

  16. Optimal intravenous infusion to decrease the haematocrit level in patient of DHF infection

    NASA Astrophysics Data System (ADS)

    Handayani, D.; Nuraini, N.; Saragih, R.; Wijaya, K. P.; Naiborhu, J.

    2014-02-01

    The optimal control of infusion model for Dengue Hemorrhagic Fever (DHF) infection is formulated here. The infusion model will be presented in form of haematocrit level. The input control aim to normalize the haematocrit level and is expressed as infusion volume on mL/day. The stability near the equilibrium points will be analyzed. Numerical simulation shows the dynamic of each infection compartments which gives a description of within-host dynamic of dengue virus. These results show particularly that infected compartments tend to be vanished in ±15days after the onset of the virus. In fact, without any control added, the haematocrit level will decrease but not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control. Control treatment for a fixed time using a control input can bring haematocrit level to normal range 42-47%. The optimal control in this paper is divided into three cases, i.e. fixed end point, constrained input, and tracking haematocrit state. Each case shows different infection condition in human body. However, all cases require that the haematocrit level to be in normal range in fixed final time.

  17. THE BISPHOSPHONATE ZOLEDRONIC ACID DECREASES TUMOR GROWTH IN BONE IN MICE WITH DEFECTIVE OSTEOCLASTS*

    PubMed Central

    Hirbe, Angela C.; Roelofs, Anke J.; Floyd, Desiree H.; Deng, Hongju; Becker, Stephanie N.; Lanigan, Lisa G.; Apicelli, Anthony J.; Xu, Zhiqiang; Prior, Julie L.; Eagleton, Mark C.; Piwnica-Worms, David; Rogers, Michael J.; Weilbaecher, Katherine

    2009-01-01

    Bisphosphonates (BPs), bone targeted drugs that disrupt osteoclast function, are routinely used to treat complications of bone metastasis. Studies in preclinical models of cancer have shown that BPs reduce skeletal tumor burden and increase survival. Similarly, we observed in the present study that administration of the Nitrogen-containing BP (N-BP), zoledronic acid (ZA) to osteolytic tumor-bearing Tax+ mice beginning at 6 months of age led to resolution of radiographic skeletal lesions. N-BPs inhibit farnesyl diphosphate (FPP) synthase, thereby inhibiting protein prenylation and causing cellular toxicity. We found that ZA decreased Tax+ tumor and B16 melanoma viability and caused the accumulation of unprenylated Rap1a proteins in vitro. However, it is presently unclear whether N-BPs exert anti-tumor effects in bone independent of inhibition of osteoclast (OC) function in vivo. Therefore, we evaluated the impact of treatment with ZA on B16 melanoma bone tumor burden in irradiated mice transplanted with splenic cells from src-/- mice, which have non-functioning OCs. OC-defective mice treated with ZA demonstrated a significant 88% decrease in tumor growth in bone compared to vehicle-treated OC-defective mice. These data support an osteoclast-independent role for N-BP therapy in bone metastasis. PMID:19442620

  18. Pharmacologic Resuscitation Decreases Circulating CINC-1 Levels and Attenuates hemorrhage-Induced Acute Lung Injury

    PubMed Central

    Fukudome, Eugene Y.; Li, Yongqing; Kochanek, Ashley R.; Lu, Jennifer; Smith, Eleanor J.; Liu, Baoling; Kim, Kyuseok; Velmahos, George C.; deMoya, Marc A.; Alam, Hasan B.

    2016-01-01

    Background Acute lung injury (ALI) is a complication of hemorrhagic shock (HS). Histone deacetylase inhibitors (HDACI) such as valproic acid (VPA) can improve survival following HS, however, their effects on late organ injury are unknown. Here, we have investigated the effects of HS and VPA treatment on ALI as well as circulating cytokines that may serve as biomarkers for the development of organ injury. Materials and Methods Anesthetized Wistar-Kyoto rats (250-300g) underwent 40% blood volume hemorrhage over 10 minutes followed by 30 minutes of un-resuscitated shock and were treated with 1) VPA 300mg/kg or 2) vehicle control. Blood samples were obtained at baseline, following shock, and prior to sacrifice (1h, 4h, and 20h; n=3-4/timepoint/group). Serum samples were screened for possible biomarkers using a multiplex electrochemiluminescence detection assay, and results were confirmed using ELISA. Additionally, lung tissue lysate was examined for chemokine and myeloperoxidase (MPO) levels as a marker for neutrophil infiltration and ALI. Additionally, lung CINC-1 (a chemokine belonging to the IL-8 family that promotes neutrophil chemotaxis) mRNA levels were measured by real-time PCR. Results Serum screening revealed that hemorrhage rapidly altered levels of circulating CINC-1. ELISA confirmed that CINC-1 protein was significantly elevated in the serum as early as 4h, and in the lung at 20h following hemorrhage, without any significant changes in the CINC-1 mRNA expression. Lung MPO levels were also elevated 4h and 20h after hemorrhage. VPA treatment attenuated these changes Conclusions Hemorrhage resulted in development of ALI, which was prevented with VPA treatment. Circulating CINC-1 levels rose rapidly after hemorrhage, and serum CINC-1 levels correlated with lung CINC-1 and MPO levels. This suggests that circulating CINC-1 could be used as an early marker for the subsequent development of organ inflammation and injury. PMID:22657731

  19. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins.

    PubMed

    Hannukainen, Jarna C; Nuutila, Pirjo; Borra, Ronald; Ronald, Borra; Kaprio, Jaakko; Kujala, Urho M; Janatuinen, Tuula; Heinonen, Olli J; Kapanen, Jukka; Viljanen, Tapio; Haaparanta, Merja; Rönnemaa, Tapani; Parkkola, Riitta; Knuuti, Juhani; Kalliokoski, Kari K

    2007-01-01

    Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 +/- 10% higher (P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 +/- 4.3 versus 9.0 +/- 6.1 micromol (100 ml)(-1) min(-1), P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake. PMID:17053033

  20. Decreased Endothelin-1 Plasma Levels in Multiple Sclerosis Patients: A Possible Factor of Vascular Dysregulation?

    PubMed Central

    Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona; Palasik, Witold; Bik, Wojciech; Wolińska-Witort, Ewa

    2015-01-01

    Background Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system with possible involvement of vascular dysregulation secondary to endothelial dysfunction caused by destruction of the vessel wall. Vascular dysregulation leads to excessive vasoconstriction or insufficient vasodilatation, resulting in vasospasm mediated by endothelin-1 (ET-1), the most potent and long-lasting mediator. Vascular dysregulation can play an important role in the pathogenesis of some eye disorders and it has been hypothesized that it is a vascular risk factor for glaucomatous optic neuropathy. The aim of this study was to estimate endothelin-1 (ET-1) plasma levels in patients with MS. Material/Methods The MS group consisted of 39 patients (9 males, 30 females), mean age: 38.8±10.02 years, range: 22–62. The control group consisted of 27 healthy volunteers (3 males and 24 females), mean age: 37.4±10.88 years, range: 20–62; clinically, in a non-active stage of the disease. ET-1 plasma levels were measured using the Endothelin-1 ELISA Kit (Immuno-Biological Laboratories Co., Japan). Statistical analysis was performed with the nonparametric Mann-Whitney U test for independent groups. Results Endothelin-1 (ET-1) plasma levels were significantly lower in MS patients compared to healthy controls: mean value 0.55±0.44 pg/ml (146.05±118.27 fmol/ml) vs. 0.95±0.48 pg/ml (252.83±127.16 fmol/ml); P=0.012. Conclusions Significantly decreased ET-1 plasma levels in the MS patients could reflect the non-active disease at the time of ET-1 measurements or the effects of immunomodulatory treatment, but it cannot be excluded that decreased ET-1 plasma levels in these patients might result from vascular dysregulation. PMID:25864450

  1. Decreased glycogen synthase kinase-3 levels and activity contribute to Huntington's disease.

    PubMed

    Fernández-Nogales, Marta; Hernández, Félix; Miguez, Andrés; Alberch, Jordi; Ginés, Silvia; Pérez-Navarro, Esther; Lucas, José J

    2015-09-01

    Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by brain atrophy particularly in striatum leading to personality changes, chorea and dementia. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase in the crossroad of many signaling pathways that is highly pleiotropic as it phosphorylates more than hundred substrates including structural, metabolic, and signaling proteins. Increased GSK-3 activity is believed to contribute to the pathogenesis of neurodegenerative diseases like Alzheimer's disease and GSK-3 inhibitors have been postulated as therapeutic agents for neurodegeneration. Regarding HD, GSK-3 inhibitors have shown beneficial effects in cell and invertebrate animal models but no evident efficacy in mouse models. Intriguingly, those studies were performed without interrogating GSK-3 level and activity in HD brain. Here we aim to explore the level and also the enzymatic activity of GSK-3 in the striatum and other less affected brain regions of HD patients and of the R6/1 mouse model to then elucidate the possible contribution of its alteration to HD pathogenesis by genetic manipulation in mice. We report a dramatic decrease in GSK-3 levels and activity in striatum and cortex of HD patients with similar results in the mouse model. Correction of the GSK-3 deficit in HD mice, by combining with transgenic mice with conditional GSK-3 expression, resulted in amelioration of their brain atrophy and behavioral motor and learning deficits. Thus, our results demonstrate that decreased brain GSK-3 contributes to HD neurological phenotype and open new therapeutic opportunities based on increasing GSK-3 activity or attenuating the harmful consequences of its decrease. PMID:26082469

  2. Decreased blood riboflavin levels are correlated with defective expression of RFT2 gene in gastric cancer

    PubMed Central

    Eli, Maynur; Li, De-Sheng; Zhang, Wei-Wei; Kong, Bing; Du, Chen-Song; Wumar, Maimaitiaili; Mamtimin, Batur; Sheyhidin, Ilyar; Hasim, Ayshamgul

    2012-01-01

    AIM: To investigate the relationship between blood riboflavin levels and riboflavin transporter 2 (RFT2) gene expression in gastric carcinoma (GC) development. METHODS: High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC. Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue. RESULTS: A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane (0.398 ± 0.149 vs 1.479 ± 0.587; P = 0.040). Tumors exhibited low RFT2 protein expression (75%, 16.7%, 8.3% and 0% for no RFT2 staining, weak staining, medium staining and strong staining, respectively), which was significantly lower than that in the normal mucous membrane (10%, 16.7%, 26.7% and 46.7% for no RFT2 staining, weak staining, medium staining and strong staining, respectively; P < 0.05). Tumors with low RFT2 expression were significantly associated with tumor stage and histological grade. Moreover, a significantly decrease in Uyghur patients was observed compared with Han patients. However, other parameters-gender, tumor location and lymph node metastasis-showed no significant relationship with RFT2 expression. Blood riboflavin levels were reverse correlated with development of GC (1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients; P < 0.05). A positive correlation of plasma riboflavin levels with defective expression of RFT2 protein was found in GC patients (χ2 = 2.619; P = 0.019). CONCLUSION: Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC. PMID:22791947

  3. Decreased melatonin levels and increased levels of advanced oxidation protein products in the seminal plasma are related to male infertility.

    PubMed

    Kratz, Ewa Maria; Piwowar, Agnieszka; Zeman, Michal; Stebelová, Katarína; Thalhammer, Theresia

    2016-03-01

    Melatonin, an indolamine secreted by the pineal gland, is known as a powerful free-radical scavenger and wide-spectrum antioxidant. Therefore, the aim of this study was to correlate markers of oxidative protein damage (advanced oxidation protein products, AOPPs) and the total antioxidant capacity (TAC) with melatonin levels in the seminal plasma of men with azoospermia (n=37), theratozoospermia (n=29) and fertile controls (normozoospermia, n=37). Melatonin concentration was measured by radioimmunoassay. The levels of AOPP as well as TAC efficiency (determined by the ferric reducing antioxidant power, FRAP) were estimated by spectrophotometric methods. The concentration of melatonin and AOPP significantly differed in azoospermic (P<0.0001) and theratozoospermic (P<0.0001) patients versus fertile men, and correlated negatively (r=-0.33, P=0.0016). The TAC levels were significantly higher in azoospermia than in theratozoospermia (P=0.0022) and the control group (P=0.00016). In azoospermia, the AOPP concentration was also significantly higher than that observed in theratozoospermia (P=0.00029). Decreased levels of melatonin together with elevated AOPP altered the oxidative-antioxidative balance in the ejaculate, thereby reducing fertility. Therefore, melatonin and AOPP levels may serve as additional diagnostic markers of semen quality and male reproductive potential. PMID:25218686

  4. Decrease in plasma levels of vasoactive intestinal polypeptide in short bowel syndrome: experimental study.

    PubMed

    Martin Del Olmo, J C; Carbajo Caballero, M A; Blanco Alvarez, J I; Audivert Mena, L; Vaquero Puerta, C

    1998-01-01

    To investigate the behaviour of the vasoactive intestinal polypeptide (VIP) in short bowel syndrome (SBS), an experimental model of massive intestinal resection (MIR) was developed. For this purpose, 20 'minipigs' were divided into two experimental groups: A (control) and B (MIR). The parameters determined were the mean plasma levels of VIP and the degree of steatorrhea at four different times: T1 (basal), T2 (one week after surgery), T3 (two weeks after surgery), and T4 (24 weeks after surgery). The results indicated that, after MIR, a progressive decrease in the mean plasma levels of VIP takes place, with statistical significance in T3 (p < 0.05) and T4 (p < 0.01). This situation seems to be a direct result of the massive loss of intestinal tissue, and could lead to the use of this peptide to mark the evolution of the intestinal adaptation process. PMID:9851334

  5. Cerebellar Soluble Mutant Ataxin-3 Level Decreases during Disease Progression in Spinocerebellar Ataxia Type 3 Mice

    PubMed Central

    Weber, Jonasz Jeremiasz; Grueninger, Stephan; Riess, Olaf; Weiss, Andreas

    2013-01-01

    Spinocerebellar Ataxia Type 3 (SCA3), also known as Machado-Joseph disease, is an autosomal dominantly inherited neurodegenerative disease caused by an expanded polyglutamine stretch in the ataxin-3 protein. A pathological hallmark of the disease is cerebellar and brainstem atrophy, which correlates with the formation of intranuclear aggregates in a specific subset of neurons. Several studies have demonstrated that the formation of aggregates depends on the generation of aggregation-prone and toxic intracellular ataxin-3 fragments after proteolytic cleavage of the full-length protein. Despite this observed increase in aggregated mutant ataxin-3, information on soluble mutant ataxin-3 levels in brain tissue is lacking. A quantitative method to analyze soluble levels will be a useful tool to characterize disease progression or to screen and identify therapeutic compounds modulating the level of toxic soluble ataxin-3. In the present study we describe the development and application of a quantitative and easily applicable immunoassay for quantification of soluble mutant ataxin-3 in human cell lines and brain samples of transgenic SCA3 mice. Consistent with observations in Huntington disease, transgenic SCA3 mice reveal a tendency for decrease of soluble mutant ataxin-3 during disease progression in fractions of the cerebellum, which is inversely correlated with aggregate formation and phenotypic aggravation. Our analyses demonstrate that the time-resolved Förster resonance energy transfer immunoassay is a highly sensitive and easy method to measure the level of soluble mutant ataxin-3 in biological samples. Of interest, we observed a tendency for decrease of soluble mutant ataxin-3 only in the cerebellum of transgenic SCA3 mice, one of the most affected brain regions in Spinocerebellar Ataxia Type 3 but not in whole brain tissue, indicative of a brain region selective change in mutant ataxin-3 protein homeostasis. PMID:23626768

  6. Cerebellar soluble mutant ataxin-3 level decreases during disease progression in Spinocerebellar Ataxia Type 3 mice.

    PubMed

    Nguyen, Huu Phuc; Hübener, Jeannette; Weber, Jonasz Jeremiasz; Grueninger, Stephan; Riess, Olaf; Weiss, Andreas

    2013-01-01

    Spinocerebellar Ataxia Type 3 (SCA3), also known as Machado-Joseph disease, is an autosomal dominantly inherited neurodegenerative disease caused by an expanded polyglutamine stretch in the ataxin-3 protein. A pathological hallmark of the disease is cerebellar and brainstem atrophy, which correlates with the formation of intranuclear aggregates in a specific subset of neurons. Several studies have demonstrated that the formation of aggregates depends on the generation of aggregation-prone and toxic intracellular ataxin-3 fragments after proteolytic cleavage of the full-length protein. Despite this observed increase in aggregated mutant ataxin-3, information on soluble mutant ataxin-3 levels in brain tissue is lacking. A quantitative method to analyze soluble levels will be a useful tool to characterize disease progression or to screen and identify therapeutic compounds modulating the level of toxic soluble ataxin-3. In the present study we describe the development and application of a quantitative and easily applicable immunoassay for quantification of soluble mutant ataxin-3 in human cell lines and brain samples of transgenic SCA3 mice. Consistent with observations in Huntington disease, transgenic SCA3 mice reveal a tendency for decrease of soluble mutant ataxin-3 during disease progression in fractions of the cerebellum, which is inversely correlated with aggregate formation and phenotypic aggravation. Our analyses demonstrate that the time-resolved Förster resonance energy transfer immunoassay is a highly sensitive and easy method to measure the level of soluble mutant ataxin-3 in biological samples. Of interest, we observed a tendency for decrease of soluble mutant ataxin-3 only in the cerebellum of transgenic SCA3 mice, one of the most affected brain regions in Spinocerebellar Ataxia Type 3 but not in whole brain tissue, indicative of a brain region selective change in mutant ataxin-3 protein homeostasis. PMID:23626768

  7. Smelling lavender and rosemary increases free radical scavenging activity and decreases cortisol level in saliva.

    PubMed

    Atsumi, Toshiko; Tonosaki, Keiichi

    2007-02-28

    Free radicals/reactive oxygen species are related to many biological phenomena such as inflammation, aging, and carcinogenesis. The body possesses various antioxidative systems (free radical scavenging activity, FRSA) for preventing oxidative stress, and saliva contains such activity. In the present study, we measured the total salivary FRSA induced after the smelling of lavender and rosemary essential oils that are widely used in aromatherapy. Various physiologically active substances in saliva such as cortisol, secretory IgA, and alpha-amylase activity were found to be correlated with aroma-induced FRSA. The subjects (22 healthy volunteers) sniffed aroma for 5 min, and each subject's saliva was collected immediately. FRSA was measured using 1,1-diphenyl-2-picrylhydrazyl. The FRSA values were increased by stimulation with low concentrations (1000 times dilution) of lavender or by high-concentrations (10 times dilution) of rosemary. In contrast, both lavender and rosemary stimulations decreased cortisol levels. A significant inverse correlation was observed between the FRSA values and the cortisol levels with each concentration of rosemary stimulation. No significant changes were noted in sIgA or alpha-amylase. These findings clarify that lavender and rosemary enhance FRSA and decrease the stress hormone, cortisol, which protects the body from oxidative stress. PMID:17291597

  8. Restored expression levels of TET1 decrease the proliferation and migration of renal carcinoma cells

    PubMed Central

    FAN, MIN; HE, XIAOZHOU; XU, XIANLIN

    2015-01-01

    Renal carcinoma is the most common type of kidney cancer in adults and is responsible for ~90–95% of the cases of kidney cancer. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is a member of the TET family of enzymes, and is expressed at low levels in multiple malignancies. In the present study, a series of experiments were designed and performed to investigate whether the expression of TET1 is clinically correlated with clinical outcomes in renal carcinoma, and to examine the associations between TET1 expression level and the proliferation and migration in renal carcinoma cells. As a result, TET1 was observed to exhibit markedly low expression levels in 54 tumor tissue samples from 54 patients with renal carcinoma. Furthermore, statistical analysis revealed a clinical correlation between low expression levels of TET1 and the prognosis of patients with renal carcinoma. When TET1 was overexpressed in renal carcinoma cells, the viability and invasive abilities of the cells were decreased, and the rate of apoptosis was increased. In conclusion, the results demonstrated that TET1 is involved in tumor inhibition in renal carcinoma by promoting cell apoptosis and inhibiting cell proliferation and invasion, which may be exploited as a novel therapeutic target in the treatment of renal carcinoma. PMID:26165803

  9. Neurons detect increases and decreases in oxygen levels using distinct guanylate cyclases.

    PubMed

    Zimmer, Manuel; Gray, Jesse M; Pokala, Navin; Chang, Andy J; Karow, David S; Marletta, Michael A; Hudson, Martin L; Morton, David B; Chronis, Nikos; Bargmann, Cornelia I

    2009-03-26

    Homeostatic sensory systems detect small deviations in temperature, water balance, pH, and energy needs to regulate adaptive behavior and physiology. In C. elegans, a homeostatic preference for intermediate oxygen (O2) levels requires cGMP signaling through soluble guanylate cyclases (sGCs), proteins that bind gases through an associated heme group. Here we use behavioral analysis, functional imaging, and genetics to show that reciprocal changes in O2 levels are encoded by sensory neurons that express alternative sets of sGCs. URX sensory neurons are activated by increases in O2 levels, and require the sGCs gcy-35 and gcy-36. BAG sensory neurons are activated by decreases in O2 levels, and require the sGCs gcy-31 and gcy-33. The sGCs are instructive O2 sensors, as forced expression of URX sGC genes causes BAG neurons to detect O2 increases. Both sGC expression and cell-intrinsic dynamics contribute to the differential roles of URX and BAG in O2-dependent behaviors. PMID:19323996

  10. Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells.

    PubMed

    Lamparter, Christina L; Winn, Louise M

    2016-09-01

    The teratogenicity of the antiepileptic drug valproic acid (VPA) is well established and its inhibition of histone deacetylases (HDAC) is proposed as an initiating factor. Recently, VPA-mediated HDAC inhibition was demonstrated to involve transcriptional downregulation of histone acetyltransferases (HATs), which was proposed to compensate for the increased acetylation resulting from HDAC inhibition. Cbp and p300 are HATs required for embryonic development and deficiencies in either are associated with congenital malformations and embryolethality. The objective of the present study was to characterize Cbp/p300 following VPA exposure in P19 cells. Consistent with previous studies, exposure to 5mM VPA over 24h induced a moderate decrease in Cbp/p300 mRNA, which preceded a strong decrease in total cellular protein mediated by ubiquitin-proteasome degradation. Nuclear Cbp/p300 protein was also decreased following VPA exposure, although to a lesser extent. Total cellular and nuclear p300 HAT activity was reduced proportionately to p300 protein levels, however while total cellular HAT activity also decreased, nuclear HAT activity was unaffected. Using the Cbp/p300 HAT inhibitor C646, we demonstrated that HAT inhibition similarly affected many of the same endpoints as VPA, including increased reactive oxygen species and caspase-3 cleavage, the latter of which could be attenuated by pre-treatment with the antioxidant catalase. C646 exposure also decreased NF-κB/p65 protein, which was not due to reduced mRNA and was not attenuated with catalase pre-treatment. This study provides support for an adaptive HAT response following VPA exposure and suggests that reduced Cbp/p300 HAT activity could contribute to VPA-mediated alterations. PMID:27381264

  11. Low Temperature Development Induces a Specific Decrease in trans-Δ3-Hexadecenoic Acid Content which Influences LHCII Organization 1

    PubMed Central

    Huner, Norman P. A.; Krol, Marianna; Williams, John P.; Maissan, Ellen; Low, Phillip S.; Roberts, Dane; Thompson, John E.

    1987-01-01

    Lipid and fatty acid analyses were performed on whole leaf extracts and isolated thylakoids from winter rye (Secale cereale L. cv Puma) grown at 5°C cold-hardened rye (RH) and 20°C nonhardened rye (RNH). Although no significant change in total lipid content was observed, growth at low, cold-hardening temperature resulted in a specific 67% (thylakoids) to 74% (whole leaves) decrease in the trans-Δ3-hexadecenoic acid (trans-16:1) level associated with phosphatidyldiacylglycerol (PG). Electron spin resonance and differential scanning calorimetry (DSC) indicated no significant difference in the fluidity of RH and RNH thylakoids. Separation of chlorophyll-protein complexes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the ratio of oligomeric light harvesting complex:monomeric light harvesting complex (LHCII1:LHCII3) was 2-fold higher in RNH than RH thylakoids. The ratio of CP1a:CP1 was also 1.5-fold higher in RNH than RH thylakoids. Analyses of winter rye grown at 20, 15, 10, and 5°C indicated that both, the trans-16:1 acid levels in PG and the LHCII1:LHCII3 decreased concomitantly with a decrease in growth temperature. Above 40°C, differential scanning calorimetry of RNH thylakoids indicated the presence of five major endotherms (47, 60, 67, 73, and 86°C). Although the general features of the temperature transitions observed above 40°C in RH thylakoids were similar to those observed for RNH thylakoids, the transitions at 60 and 73°C were resolved as inflections only and RH thylakoids exhibited transitions at 45 and 84°C which were 2°C lower than those observed in RNH thylakoids. Since polypeptide and lipid compositions of RH and RNH thylakoids were very similar, we suggest that these differences reflect alterations in thylakoid membrane organization. Specifically, it is suggested that low developmental temperature modulates LHCII organization such that oligomeric LHCII predominates in RNH thylakoids whereas a monomeric or an

  12. Zinc fortification decreases ZIP1 gene expression of some adolescent females with appropriate plasma zinc levels.

    PubMed

    Méndez, Rosa O; Santiago, Alejandra; Yepiz-Plascencia, Gloria; Peregrino-Uriarte, Alma B; de la Barca, Ana M Calderón; García, Hugo S

    2014-06-01

    Zinc homeostasis is achieved after intake variation by changes in the expression levels of zinc transporters. The aim of this study was to evaluate dietary intake (by 24-h recall), absorption, plasma zinc (by absorption spectrophotometry) and the expression levels (by quantitative PCR), of the transporters ZIP1 (zinc importer) and ZnT1 (zinc exporter) in peripheral white blood cells from 24 adolescent girls before and after drinking zinc-fortified milk for 27 day. Zinc intake increased (p < 0.001) from 10.5 ± 3.9 mg/day to 17.6 ± 4.4 mg/day, and its estimated absorption from 3.1 ± 1.2 to 5.3 ± 1.3 mg/day. Mean plasma zinc concentration remained unchanged (p > 0.05) near 150 µg/dL, but increased by 31 µg/dL (p < 0.05) for 6/24 adolescents (group A) and decreased by 25 µg/dL (p < 0.05) for other 6/24 adolescents (group B). Expression of ZIP1 in blood leukocytes was reduced 1.4-fold (p < 0.006) in group A, while for the expression of ZnT1 there was no difference after intervention (p = 0.39). An increase of dietary zinc after 27-days consumption of fortified-milk did not increase (p > 0.05) the plasma level of adolescent girls but for 6/24 participants from group A in spite of the formerly appropriation, which cellular zinc uptake decreased as assessed by reduction of the expression of ZIP1. PMID:24922175

  13. Zinc Fortification Decreases ZIP1 Gene Expression of Some Adolescent Females with Appropriate Plasma Zinc Levels

    PubMed Central

    Méndez, Rosa O.; Santiago, Alejandra; Yepiz-Plascencia, Gloria; Peregrino-Uriarte, Alma B.; de la Barca, Ana M. Calderón; García, Hugo S.

    2014-01-01

    Zinc homeostasis is achieved after intake variation by changes in the expression levels of zinc transporters. The aim of this study was to evaluate dietary intake (by 24-h recall), absorption, plasma zinc (by absorption spectrophotometry) and the expression levels (by quantitative PCR), of the transporters ZIP1 (zinc importer) and ZnT1 (zinc exporter) in peripheral white blood cells from 24 adolescent girls before and after drinking zinc-fortified milk for 27 day. Zinc intake increased (p < 0.001) from 10.5 ± 3.9 mg/day to 17.6 ± 4.4 mg/day, and its estimated absorption from 3.1 ± 1.2 to 5.3 ± 1.3 mg/day. Mean plasma zinc concentration remained unchanged (p > 0.05) near 150 µg/dL, but increased by 31 µg/dL (p < 0.05) for 6/24 adolescents (group A) and decreased by 25 µg/dL (p < 0.05) for other 6/24 adolescents (group B). Expression of ZIP1 in blood leukocytes was reduced 1.4-fold (p < 0.006) in group A, while for the expression of ZnT1 there was no difference after intervention (p = 0.39). An increase of dietary zinc after 27-days consumption of fortified-milk did not increase (p > 0.05) the plasma level of adolescent girls but for 6/24 participants from group A in spite of the formerly appropriation, which cellular zinc uptake decreased as assessed by reduction of the expression of ZIP1. PMID:24922175

  14. PPAR-α Agonist Fenofibrate Decreased RANTES Levels in Type 2 Diabetes Patients with Hypertriglyceridemia.

    PubMed

    Feng, Xiaomeng; Gao, Xia; Jia, Yumei; Zhang, Heng; Xu, Yuan; Wang, Guang

    2016-01-01

    BACKGROUND Regulated upon activation, normal T cells expressed and secreted (RANTES) is associated with inflammation and atherosclerosis. We investigated the effect of fenofibrate, a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, on RANTES in type 2 diabetes mellitus (T2DM) patients with hypertriglyceridemia. MATERIAL AND METHODS This study evaluated cross-sectional and interventional studies of 25 T2DM patients with hypertriglyceridemia (group A) and 32 controls (group B). Group A was treated with fenofibrate (200 mg/day) for 8 weeks. Serum RANTES and clinical characteristics were examined. RESULTS Serum RANTES was significantly higher in group A compared with group B (59.04±16.74 vs. 38.57±12.98 ng/ml, P<0.001) and correlated with triglycerides (TG) (r=0.535, P<0.001), fasting blood glucose (FBG) (r=0.485, P<0.001), glycosylated hemoglobin (HbA1c) (r=0.485, P<0.001), homocysteine (Hcy) (r=0.520, P<0.001), and high-sensitivity C-reactive protein (hsCRP) (r=0.701, P<0.001). In multiple regression analysis after controlling for confounders, increased hsCRP levels (β=7.430, P<0.001) and T2DM with hypertriglyceridemia (β=11.496, P=0.002) were independently related to high serum RANTES levels. After 8 weeks of fenofibrate treatment, serum RANTES significantly decreased in group A compared with baseline (52.75±17.41 vs. 59.04±16.74 ng/ml, P=0.018). CONCLUSIONS Fenofibrate decreased serum RANTES levels in T2DM patients with hypertriglyceridemia, indicating that PPAR-a agonists may play an important role in inhibiting inflammatory responses. PMID:26944934

  15. PPAR-α Agonist Fenofibrate Decreased RANTES Levels in Type 2 Diabetes Patients with Hypertriglyceridemia

    PubMed Central

    Feng, Xiaomeng; Gao, Xia; Jia, Yumei; Zhang, Heng; Xu, Yuan; Wang, Guang

    2016-01-01

    Background Regulated upon activation, normal T cells expressed and secreted (RANTES) is associated with inflammation and atherosclerosis. We investigated the effect of fenofibrate, a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, on RANTES in type 2 diabetes mellitus (T2DM) patients with hypertriglyceridemia. Material/Methods This study evaluated cross-sectional and interventional studies of 25 T2DM patients with hypertriglyceridemia (group A) and 32 controls (group B). Group A was treated with fenofibrate (200 mg/day) for 8 weeks. Serum RANTES and clinical characteristics were examined. Results Serum RANTES was significantly higher in group A compared with group B (59.04±16.74 vs. 38.57±12.98 ng/ml, P<0.001) and correlated with triglycerides (TG) (r=0.535, P<0.001), fasting blood glucose (FBG) (r=0.485, P<0.001), glycosylated hemoglobin (HbA1c) (r=0.485, P<0.001), homocysteine (Hcy) (r=0.520, P<0.001), and high-sensitivity C-reactive protein (hsCRP) (r=0.701, P<0.001). In multiple regression analysis after controlling for confounders, increased hsCRP levels (β=7.430, P<0.001) and T2DM with hypertriglyceridemia (β=11.496, P=0.002) were independently related to high serum RANTES levels. After 8 weeks of fenofibrate treatment, serum RANTES significantly decreased in group A compared with baseline (52.75±17.41 vs. 59.04±16.74 ng/ml, P=0.018). Conclusions Fenofibrate decreased serum RANTES levels in T2DM patients with hypertriglyceridemia, indicating that PPAR-α agonists may play an important role in inhibiting inflammatory responses. PMID:26944934

  16. Autophagy Alleviates Melamine-Induced Cell Death in PC12 Cells Via Decreasing ROS Level.

    PubMed

    Wang, Hui; Gao, Na; Li, Zhigui; Yang, Zhuo; Zhang, Tao

    2016-04-01

    Since melamine was illegally added to raw milk for increasing the apparent protein content, such a scandal has not been quite blown out. Previous studies showed that melamine induced apoptosis and oxidative damage in both in vivo and in vitro experiments. It is well known that autophagy is closely related to oxidative stress. In the present study, we examined whether autophagy played an important role in protecting PC12 cells, which were damaged by melamine. Immunofluorescence assay showed that melamine enhanced the number of punctuate dot, indicating the increase of autophagosomes. Western blot assay presented that melamine significantly elevated the expression level of autophagy markers including LC3-II/LC3-I ratio, beclin-1, and Atg 7. Rapamycin further enhanced the effect, whereas 3-methyadenine (3-MA) inhibited it. MTT assay exhibited that rapamycin significantly enhanced the cell viability (P < 0.01), while 3-MA considerably reduced it in melamine-treated PC12 cells (P < 0.01). Furthermore, flow cytometry assay showed that rapamycin considerably reduced the reactive oxygen species (ROS) level of the cells (P < 0.01), but 3-MA increased the generation of ROS (P < 0.01). Additionally, the superoxide dismutase (SOD) activity was notably increased by rapamycin in melamine-treated PC12 cells (P < 0.01), while the activity of which was prominently decreased by 3-MA (P < 0.01). Malondialdehyde (MDA) assay showed that rapamycin remarkably decreased the MDA level of the cells (P < 0.05), while 3-MA increased it (P < 0.01). Consequently, this study demonstrated that autophagy protected PC12 cells from melamine-induced cell death via inhibiting the excessive generation of ROS. Regulating autophagy may become a new targeted therapy to relieve the damage induced by melamine. PMID:25724280

  17. MicroRNA‐210 Decreases heme Levels by Targeting Ferrochelatase in Cardiomyocytes

    PubMed Central

    Qiao, Aijun; Khechaduri, Arineh; Kannan Mutharasan, R.; Wu, Rongxue; Nagpal, Varun; Ardehali, Hossein

    2013-01-01

    Background MicroRNA‐210 (miR‐210) increases in hypoxia and regulates mitochondrial respiration through modulation of iron‐sulfur cluster assembly proteins (ISCU1/2), a protein that is involved in Fe/S cluster synthesis. However, it is not known how miR‐210 affects cellular iron levels or production of heme, another iron containing molecule that is also needed for cellular and mitochondrial function. Methods and Results To screen for micro‐ribonucleic acids (miRNAs) regulated by iron, we performed a miRNA gene array in neonatal rat cardiomyocytes treated with iron chelators. Levels of miR‐210 are significantly increased with iron chelation, however, this response was mediated entirely through the hypoxia‐inducible factor (HIF) pathway. Furthermore, miR‐210 reduced cellular heme levels and the activity of mitochondrial and cytosolic heme‐containing proteins by modulating ferrochelatase (FECH), the last enzyme in heme biosynthesis. Mutation of the 2 miR‐210 binding sites in the 3′ untranslated region (UTR) of FECH reversed the miR‐210 response, while mutation of either binding site in isolation did not exert any effects. Changes mediated by miR‐210 in heme and FECH were independent of ISCU, as overexpression of an ISCU construct lacking the 3′ UTR does not alter miR‐210 regulation of heme and FECH. Finally, FECH levels increased in hypoxia, and this effect was not reversed by miR‐210 knockdown, suggesting that the effects of miR‐210 on heme are restricted to normoxic conditions, and that the pathway is overriden in hypoxia. Conclusions Our results identify a role for miR‐210 in the regulation of heme production by targeting and inhibiting FECH under normoxic conditions. PMID:23608607

  18. Hydrogen sulfide decreases adenosine triphosphate levels in aortic rings and leads to vasorelaxation via metabolic inhibition

    PubMed Central

    Kiss, Levente; Deitch, Edwin A; Szabó, Csaba

    2014-01-01

    Aims Hydrogen sulfide (H2S) at low concentrations serves as a physiological endogenous vasodilator molecule, while at higher concentrations it can trigger cytotoxic effects. The aim of our study was to elucidate the potential mechanisms responsible for the effects of H2S on vascular tone. Main methods We measured the vascular tone in vitro in precontracted rat thoracic aortic rings and we have tested the effect of different oxygen levels and a variety of inhibitors affecting known vasodilatory pathways. We have also compared the vascular effect of high concentrations of H2S to those of pharmacological inhibitors of oxidative phosphorylation. Furthermore, we measured adenosine triphosphate (ATP)-levels in the same vascular tissues. Key findings We have found that in rat aortic rings: (1) H2S decreases ATP levels; (2) relaxations to H2S depend on the ambient oxygen concentration; (3) prostaglandins do not take part in the H2S induced relaxations; (4) the 3':5'-cyclic guanosine monophosphate (cGMP) – nitric oxide (NO) pathway does not have a role in the relaxations (5) the role of KATP channels is limited, while Cl−/HCO3− channels have a role in the relaxations. (6): We have observed that high concentrations of H2S relax the aortic rings in a fashion similar to sodium cyanide, and both agents reduce cellular ATP levels to a comparable degree. Significance H2S, a new gasotransmitter of emerging importance, leads to relaxation via Cl−/HCO3− channels and metabolic inhibition and the interactions of these two factors depend on the oxygen levels of the tissue. PMID:18790700

  19. Elevated triglyceride and decreased high density lipoprotein level in carbon disulfide workers in Taiwan.

    PubMed

    Luo, Jiin-Chyuan John; Chang, Ho-Yuan; Chang, Shu-Ju; Chou, Tzu-Chieh; Chen, Chiou-Jong; Shih, Tung-Sheng; Huang, Chin-Chang

    2003-01-01

    Carbon disulfide (CS2) is a man-made product utilized primarily in the manufacture of viscose rayon. Overexposure to CS2 has been associated with an increase in coronary heart disease. The aims of this study were to examine the dose-response relationship of CS2 exposure and elevated lipid profile tests among CS2-exposed workers in Taiwan. A total of 132 workers were recruited from two viscose rayon plants. Air sampling was performed to determine the CS2 exposure of workers. Demographic data and work history were gathered by a standard self-administered questionnaire. Lipid profile tests were also performed by routine methods. The average CS2 exposure concentration was 50.6 +/- 25.6 ppm (range: 24-127 ppm) in the high-exposure group, 12.9 +/- 5 ppm (range: 5.2-22.3 ppm) in the mid-exposure group, and 3.5 +/- 1.2 ppm (range 0.97-5.2 ppm) in the low-exposure group. There were 21 out of 33 (63.7%) elevated triglyceride levels among high-CS2-exposure workers, 27 out of 64 (42.2%) among the middle-CS2-exposure, and 14 out of 35 (40%) among low-CS2-exposure workers, respectively. Compared to the low-CS2-exposure workers, the age- and weight-adjusted odds ratios (and 95% confidence intervals) of the prevalence of elevated triglyceride value were 1.12 (0.5, 2.7) for middle-CS2-exposure workers, and 2.81 (1.02, 7.8) for high-CS2-exposure workers. There was a significant linear trend between CS2 exposure and the prevalence of elevated triglyceride value (P = 0.046) after adjusting for other factors. There was also a lower prevalence of elevated HDL level in high-CS2-exposure workers than low-CS2-exposure workers (15.2% versus 31.4%). Compared to the low-CS2-exposure workers, the age- and weight-adjusted odds ratio (and 95% confidence intervals) of elevated HDL level were 0.34 (0.1, 1.18) for high-CS2-exposure workers, which was borderline significant. In conclusion, this study suggests that elevated triglyceride level and decreased HDL level are associated with CS2 exposure

  20. Decrease of intracellular pH as possible mechanism of embryotoxicity of glycol ether alkoxyacetic acid metabolites

    SciTech Connect

    Louisse, Jochem; Verwei, Miriam; Sandt, Johannes J.M. van de; Rietjens, Ivonne M.C.M.

    2010-06-01

    Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabolites using the methoxyacetic acid (MAA) metabolite of ethylene glycol monomethyl ether as the model compound. The results obtained demonstrate an MAA-induced decrease of the intracellular pH (pH{sub i}) of embryonic BALB/c-3T3 cells as well as of embryonic stem (ES)-D3 cells, at concentrations that affect ES-D3 cell differentiation. These results suggest a mechanism for MAA-mediated embryotoxicity similar to the mechanism of embryotoxicity of the drugs valproic acid and acetazolamide (ACZ), known to decrease the pH{sub i}in vivo, and therefore used as positive controls. The embryotoxic alkoxyacetic acid metabolites ethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid also caused an intracellular acidification of BALB/c-3T3 cells at concentrations that are known to inhibit ES-D3 cell differentiation. Two other embryotoxic compounds, all-trans-retinoic acid and 5-fluorouracil, did not decrease the pH{sub i} of embryonic cells at concentrations that affect ES-D3 cell differentiation, pointing at a different mechanism of embryotoxicity of these compounds. MAA and ACZ induced a concentration-dependent inhibition of ES-D3 cell differentiation, which was enhanced by amiloride, an inhibitor of the Na{sup +}/H{sup +}-antiporter, corroborating an important role of the pH{sub i} in the embryotoxic mechanism of both compounds. Together, the results presented indicate that a decrease of the pH{sub i} may be the mechanism of embryotoxicity of the alkoxyacetic acid metabolites of the glycol ethers.

  1. Accumulation of metals in GOLD4 COPD lungs is associated with decreased CFTR levels

    PubMed Central

    2014-01-01

    Background The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that primarily resides in airway epithelial cells. Decreased CFTR expression and/or function lead to impaired airway surface liquid (ASL) volume homeostasis, resulting in accumulation of mucus, reduced clearance of bacteria, and chronic infection and inflammation. Methods Expression of CFTR and the cigarette smoke metal content were assessed in lung samples of controls and COPD patients with established GOLD stage 4. CFTR protein and mRNA were quantified by immunohistochemistry and quantitative RT-PCR, respectively. Metals present in lung samples were quantified by ICP-AES. The effect of cigarette smoke on down-regulation of CFTR expression and function was assessed using primary human airway epithelial cells. The role of leading metal(s) found in lung samples of GOLD 4 COPD patients involved in the alteration of CFTR was confirmed by exposing human bronchial epithelial cells 16HBE14o- to metal-depleted cigarette smoke extracts. Results We found that CFTR expression is reduced in the lungs of GOLD 4 COPD patients, especially in bronchial epithelial cells. Assessment of metals present in lung samples revealed that cadmium and manganese were significantly higher in GOLD 4 COPD patients when compared to control smokers (GOLD 0). Primary human airway epithelial cells exposed to cigarette smoke resulted in decreased expression of CFTR protein and reduced airway surface liquid height. 16HBE14o-cells exposed to cigarette smoke also exhibited reduced levels of CFTR protein and mRNA. Removal and/or addition of metals to cigarette smoke extracts before exposure established their role in decrease of CFTR in airway epithelial cells. Conclusions CFTR expression is reduced in the lungs of patients with severe COPD. This effect is associated with the accumulation of cadmium and manganese suggesting a role for these metals in the pathogenesis of COPD. PMID:24957904

  2. Novel beta-spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA.

    PubMed

    Maciag, Monika; Płochocka, Danuta; Adamowicz-Salach, Anna; Burzyńska, Beata

    2009-08-01

    Hereditary spherocytosis (HS) is one of the most frequent and heterogeneous inherited haemolytic anaemias. It is associated with abnormalities of several erythrocyte membrane proteins. We investigated relative mRNA quantification of red blood cell membrane protein genes using real-time quantitative polymerase chain reaction (qPCR) in order to better characterize HS cases and to select genes to search for mutations in patients with spherocytosis. qPCR experiments indicated that the spectrin beta gene (SPTB) could be involved in anaemia pathogenesis. DNA analysis of SPTB in the HS subjects with decreased SPTB mRNA levels revealed the presence of five previously undescribed mutations: R1756X, 781delT and IVS22nt-4G>A, 1502insA and IVS20nt-2A>G. PMID:19538529

  3. Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge?

    PubMed

    AbdElgawad, Hamada; Zinta, Gaurav; Beemster, Gerrit T S; Janssens, Ivan A; Asard, Han

    2016-01-01

    Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including "all" papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity. PMID:27200030

  4. Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge?

    PubMed Central

    AbdElgawad, Hamada; Zinta, Gaurav; Beemster, Gerrit T. S.; Janssens, Ivan A.; Asard, Han

    2016-01-01

    Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including “all” papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity. PMID:27200030

  5. Nutrient Starvation Decreases Cx43 Levels and Limits Intercellular Communication in Primary Bovine Corneal Endothelial Cells.

    PubMed

    D'hondt, Catheleyne; Iyyathurai, Jegan; Welkenhuyzen, Kirsten; Himpens, Bernard; Leybaert, Luc; Bultynck, Geert

    2016-06-01

    Connexin (Cx) proteins form large conductance channels which function as regulators of communication between neighboring cells via gap junctions and/or hemichannels. Intercellular communication is essential to coordinate cellular responses in tissues and organs, thereby fulfilling an essential role in the spreading of signaling, survival and death processes. Connexin 43 (Cx43), a major connexin isoform in brain and heart, is rapidly turned over. Recent studies implicated that autophagy, a lysosomal degradation pathway induced upon nutrient starvation, mediates connexins, including Cx43, degradation. Here, we examined the impact of nutrient starvation on endogenous Cx43-protein levels and endogenous Cx43-driven intercellular communication in primary bovine corneal endothelial cells (BCECs). Hank's Balanced Salt Solution (HBSS) was used as a starvation condition that induces autophagic flux without impacting the survival of the BCECs. Nutrient starvation of BCECs caused a rapid decline in Cx43-protein levels, both as gap junctions and as hemichannels. The time course of the decline in Cx43-protein levels coincided with the time course of the decline in intercellular communication, assessed as intercellular Ca(2+)-wave propagation in BCECs exposed to a single-cell mechanical stimulus. The decline in Cx43-protein levels, both as gap junctions and as hemichannels, could be prevented by the addition of bafilomycin A1, a lysosomal inhibitor, during the complete nutrient starvation period. Consistent with this, bafilomycin A1 significantly alleviated the decrease in intercellular Ca(2+)-wave propagation. This study further underpins the importance of autophagy as an important degradation pathway for Cx43 proteins during periods of nutrient deprivation, thereby impacting the ability of cells to perform intercellular communication. PMID:26873723

  6. Modulation of sialic acid levels among some organs during insulin resistance or hyperglycemic states.

    PubMed

    Ibrahim, Mohammed Auwal; Abdulkadir, Aisha; Onojah, Alice; Sani, Lawal; Adamu, Auwal; Abdullahi, Hadiza

    2016-01-01

    Previous studies have suggested a possible connection between insulin resistance and chronic hyperglycemia with membrane sialic acid content. In this study, the effects of high (20% ad libitum) fructose and glucose feeding on the sialic acid levels of some organs were investigated in rats. The blood glucose levels of the high fructose- and glucose-fed rats were consistently and significantly (P < 0.05) higher than the normal control throughout the experiment. Free serum sialic acid and total hepatic sialic acid levels were elevated in the high fructose- and glucose-fed rats compared to normal control, but only the data for the high glucose-fed group were significantly (P < 0.05) different from the normal control. Conversely, a significant (P < 0.05) decrease in the pancreatic sialic acid level was observed in high glucose-fed group compared to normal control. Also, the high fructose-fed rats had lower, but insignificant (P > 0.05), pancreatic sialic acid level than the normal control. On the other hand, high fructose and glucose feeding did not significantly (P > 0.05) affect the sialic acid levels of the skeletal muscle and heart, though a tendency to increase the sialic acid level was evident in the heart. In the kidney, the sialic acid level was significantly (P < 0.05) increased in both high fructose- and glucose-fed groups. It was concluded that the liver and kidney tend to stimulate sialic acid synthesis, while the pancreas downregulate sialic acids synthesis and/or promote sialic acid release from glycoconjugates. Also, these organs may contribute to high-serum sialic acid level observed during diabetes. PMID:26468092

  7. Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial.

    PubMed

    Biemann, Ronald; Penner, Marina; Borucki, Katrin; Westphal, Sabine; Luley, Claus; Rönicke, Raik; Biemann, Kathleen; Weikert, Cornelia; Lux, Anke; Goncharenko, Nikolai; Marschall, Hanns-Ulrich; Schneider, Jochen G; Isermann, Berend

    2016-01-01

    Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45-55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control arm. Before and after a 6 months intervention period clinical and laboratory parameters, body composition, serum BA profile, FGF-19, and GLP-1 concentrations were determined in fasting blood samples. 30 participants in the control and 33 participants in the treatment arm completed the study and were included in the data analysis. In participants of the treatment arm lifestyle-induced weight loss resulted in markedly improved insulin sensitivity. Serum levels of BA species and total GLP-1 decreased, while FGF-19 remained stable. Serum BA composition changed towards an increased 12α-hydroxylated/non-12α-hydroxylated ratio. None of these parameters changed in participants of the control arm. Our results demonstrate that improved metabolic control by lifestyle modifications lowers serum levels of BAs and GLP-1 and changes serum BA composition towards an increased 12α/non-12α ratio (ICTRP Trial Number: U1111-1158-3672). PMID:27452603

  8. Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial

    PubMed Central

    Biemann, Ronald; Penner, Marina; Borucki, Katrin; Westphal, Sabine; Luley, Claus; Rönicke, Raik; Biemann, Kathleen; Weikert, Cornelia; Lux, Anke; Goncharenko, Nikolai; Marschall, Hanns-Ulrich; Schneider, Jochen G.; Isermann, Berend

    2016-01-01

    Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45–55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control arm. Before and after a 6 months intervention period clinical and laboratory parameters, body composition, serum BA profile, FGF-19, and GLP-1 concentrations were determined in fasting blood samples. 30 participants in the control and 33 participants in the treatment arm completed the study and were included in the data analysis. In participants of the treatment arm lifestyle-induced weight loss resulted in markedly improved insulin sensitivity. Serum levels of BA species and total GLP-1 decreased, while FGF-19 remained stable. Serum BA composition changed towards an increased 12α-hydroxylated/non-12α-hydroxylated ratio. None of these parameters changed in participants of the control arm. Our results demonstrate that improved metabolic control by lifestyle modifications lowers serum levels of BAs and GLP-1 and changes serum BA composition towards an increased 12α/non-12α ratio (ICTRP Trial Number: U1111-1158-3672). PMID:27452603

  9. Hydroxytyrosol in functional hydroxytyrosol-enriched biscuits is highly bioavailable and decreases oxidised low density lipoprotein levels in humans.

    PubMed

    Mateos, Raquel; Martínez-López, Sara; Baeza Arévalo, Gema; Amigo-Benavent, Miryam; Sarriá, Beatriz; Bravo-Clemente, Laura

    2016-08-15

    Hydroxytyrosol (HT) and its derivatives in olive oil protect low-density lipoproteins (LDL) against oxidation. Biscuits could be a convenient alternative to broaden consumers' choice of HT-rich foods, although the biscuit matrix could affect HT bioavailability. We performed a crossover, randomized, double-blind study to evaluate HT bioavailability in HT-enriched biscuits (HT-B) versus non-enriched biscuits (C-B), and the effects on oxidative postprandial status. On two separate days, 13 subjects consumed 30 g of C-B or HT-B (5.25mg HT) after overnight-fasting. Blood and urine were collected at different intervals and analysed by LC-MS-QToF. After HT-B consumption, plasma metabolites peaked between 0.5 and 1h and were extensively excreted in urine. HT-sulphate and 3,4-dihydroxyphenylacetic acid (DOPAC)-sulphate were the main metabolites, followed by DOPAC and homovanillic acid (HVA). HT-glucuronide, DOPAC-glucuronide, HVA-glucuronide and HVA-sulphate were also detected. Postprandial oxidised-LDL concentrations decreased with HT-B. HT is a promising functional ingredient and, in biscuits, it is highly bioavailable and lowers postprandial oxidised-LDL levels. PMID:27006237

  10. Endurance training associated with slightly lowered serum estradiol levels decreases mineral density of canine skeleton.

    PubMed

    Puustjärvi, K; Karjalainen, P; Nieminen, J; Arokoski, J; Parviainen, M; Helminen, H J; Soimakallio, S

    1992-06-01

    The effects of long-term running exercise were studied in 20 beagle dogs. A total of 10 dogs ran from the age of 15 weeks to the age of 70 weeks in a progressive program for up to 40 km/day. A total of 10 sister dogs spent the study period in individual cages. When the dogs were 70 weeks old, bone mineral density of the vertebrae, hip, and radius was analyzed by dual-energy x-ray absorptiometry (DEXA; Lunar) and the vertebrae were also assessed by quantitative computed tomography (QCT; Siemens DR 1). Mineral density was lower in the running dogs than in the controls. The difference was greatest in the spine in the QCT analysis. Blood chemistry analyses revealed that the metabolism of the bone was significantly accelerated. The estradiol levels showed the trend to be reduced in the running group. The beneficial effect of exercise on mineral density has been shown in many earlier studies. However, in this study we demonstrate the possibility of adverse effects of long-term exercise on bone tissue. The change was associated with a decrease of serum estradiol level. PMID:1414479

  11. HSP90 inhibitors decrease AID levels and activity in mice and in human cells

    PubMed Central

    Montamat-Sicotte, Damien; Liztler, Ludivine C; Abreu, Cecilia; Safavi, Shiva; Zahn, Astrid; Orthwein, Alexandre; Muschen, Markus; Oppezzo, Pablo; Muñoz, Denise P; Di Noia, Javier M

    2015-01-01

    Activation induced deaminase (AID) initiates somatic hypermutation and class switch recombination of the Ig genes in antigen-activated B cells, underpinning antibody affinity maturation and isotype switching. AID can also be pathogenic by contributing to autoimmune diseases and oncogenic mutations. Moreover, AID can exert non-canonical functions when aberrantly expressed in epithelial cells. The lack of specific inhibitors prevents therapeutic applications to modulate AID functions. Here, we have exploited our previous finding that the HSP90 molecular chaperoning pathway stabilizes AID in B cells, to test whether HSP90 inhibitors could target AID in vivo. We demonstrate that chronic administration of HSP90 inhibitors decreases AID protein levels and isotype switching in immunized mice. HSP90 inhibitors also reduce disease severity in a mouse model of acute B-cell lymphoblastic leukemia in which AID accelerates disease progression. We further show that human AID protein levels are sensitive to HSP90 inhibition in normal and leukemic B cells, and that HSP90 inhibition prevents AID-dependent epithelial to mesenchymal transition in a human breast cancer cell line in vitro. Thus, we provide proof-of-concept that HSP90 inhibitors indirectly target AID in vivo and that endogenous human AID is widely sensitive to them, which could have therapeutic applications. PMID:25912253

  12. Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients

    PubMed Central

    Schottlaender, Lucia V.; Bettencourt, Conceição; Kiely, Aoife P.; Chalasani, Annapurna; Neergheen, Viruna; Holton, Janice L.; Hargreaves, Iain; Houlden, Henry

    2016-01-01

    Background The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases. Methods Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as well as idiopathic Parkinson's disease (n = 7), dementia with Lewy bodies (n = 20), corticobasal degeneration (n = 15) and cerebellar ataxia (n = 18) patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography. Results We detected a statistically significant decrease (by 3–5%) in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001), specifically in OPCA (P = 0.001) and mixed cases (P = 0.005), when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001), idiopathic Parkinson's disease (P<0.001), corticobasal degeneration (P<0.001), and cerebellar ataxia (P = 0.001)]. Conclusion Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated. PMID:26894433

  13. HSP90 inhibitors decrease AID levels and activity in mice and in human cells.

    PubMed

    Montamat-Sicotte, Damien; Litzler, Ludivine C; Abreu, Cecilia; Safavi, Shiva; Zahn, Astrid; Orthwein, Alexandre; Müschen, Markus; Oppezzo, Pablo; Muñoz, Denise P; Di Noia, Javier M

    2015-08-01

    Activation induced deaminase (AID) initiates somatic hypermutation and class switch recombination of the Ig genes in antigen-activated B cells, underpinning antibody affinity maturation and isotype switching. AID can also be pathogenic by contributing to autoimmune diseases and oncogenic mutations. Moreover, AID can exert noncanonical functions when aberrantly expressed in epithelial cells. The lack of specific inhibitors prevents therapeutic applications to modulate AID functions. Here, we have exploited our previous finding that the HSP90 molecular chaperoning pathway stabilizes AID in B cells, to test whether HSP90 inhibitors could target AID in vivo. We demonstrate that chronic administration of HSP90 inhibitors decreases AID protein levels and isotype switching in immunized mice. HSP90 inhibitors also reduce disease severity in a mouse model of acute B-cell lymphoblastic leukemia in which AID accelerates disease progression. We further show that human AID protein levels are sensitive to HSP90 inhibition in normal and leukemic B cells, and that HSP90 inhibition prevents AID-dependent epithelial to mesenchymal transition in a human breast cancer cell line in vitro. Thus, we provide proof-of-concept that HSP90 inhibitors indirectly target AID in vivo and that endogenous human AID is widely sensitive to them, which could have therapeutic applications. PMID:25912253

  14. Decreased bile-acid synthesis in livers of hepatocyte-conditional NADPH-cytochrome P450 reductase-null mice results in increased bile acids in serum.

    PubMed

    Cheng, Xingguo; Zhang, Youcai; Klaassen, Curtis D

    2014-10-01

    NADPH-cytochrome P450 reductase (Cpr) is essential for the function of microsomal cytochrome P450 monooxygenases (P450), including those P450s involved in bile acid (BA) synthesis. Mice with hepatocyte-specific deletion of NADPH-cytochrome P450 reductase (H-Cpr-null) have been engineered to understand the in vivo function of hepatic P450s in the metabolism of xenobiotics and endogenous compounds. However, the impact of hepatic Cpr on BA homeostasis is not clear. The present study revealed that H-Cpr-null mice had a 60% decrease in total BA concentration in liver, whereas the total BA concentration in serum was almost doubled. The decreased level of cholic acid (CA) in both serum and livers of H-Cpr-null mice is likely due to diminished enzyme activity of Cyp8b1 that is essential for CA biosynthesis. Feedback mechanisms responsible for the reduced liver BA concentrations and/or increased serum BA concentrations in H-Cpr-null mice included the following: 1) enhanced alternative BA synthesis pathway, as evidenced by the fact that classic BA synthesis is diminished but chenodeoxycholic acid still increases in both serum and livers of H-Cpr-null mice; 2) inhibition of farnesoid X receptor activation, which increased the mRNA of Cyp7a1 and 8b1; 3) induction of intestinal BA transporters to facilitate BA absorption from the intestine to the circulation; 4) induction of hepatic multidrug resistance-associated protein transporters to increase BA efflux from the liver to blood; and 5) increased generation of secondary BAs. In summary, the present study reveals an important contribution of the alternative BA synthesis pathway and BA transporters in regulating BA concentrations in H-Cpr-null mice. PMID:25034404

  15. Degradation of Malaysian peatlands decreases levels of phenolics in soil and in leaves of Macaranga pruinosa

    NASA Astrophysics Data System (ADS)

    Yule, Catherine; Lim, Yau; Lim, Tse

    2016-04-01

    Indo-Malaysian tropical peat swamp forests (PSF) sequester enormous stores of carbon in the form of phenolic compounds, particularly lignin as well as tannins. These phenolic compounds are crucial for ecosystem functioning in PSF through their inter-related roles in peat formation and plant defenses. Disturbance of PSF causes destruction of the peat substrate, but the specific impact of disturbance on phenolic compounds in peat and its associated vegetation has not previously been examined. A scale was developed to score peatland degradation based on the three major human impacts that affect tropical PSF – logging, drainage and fire. The objectives of this study were to compare the amount of phenolic compounds in Macaranga pruinosa, a common PSF tree, and in the peat substrate along a gradient of peatland degradation from pristine peat swamp forest to cleared, drained and burnt peatlands. We examined phenolic compounds in M. pruinosa and in peat and found that levels of total phenolic compounds and total tannins decrease in the leaves of M.pruinosa and also in the surface peat layers with an increase in peatland degradation. We conclude that waterlogged conditions preserve the concentration of phenolic compounds in peat, and that even PSF that has been previously logged but which has recovered a full canopy cover will have high levels of total phenolic content (TPC) in peat. High levels of TPC in peat and in the flora are vital for the inhibition of decomposition of organic matter and this is crucial for the accretion of peat and the sequestration of carbon. Thus regional PSF flourish despite the phenolic rich, toxic, waterlogged, nutrient poor, conditions, and reversal of such conditions is a sign of degradation.

  16. Two Levels of Caffeine Ingestion on Blood Lactate and Free Fatty Acid Responses during Incremental Exercise.

    ERIC Educational Resources Information Center

    McNaughton, Lars

    1987-01-01

    Research was conducted to determine the effects of two doses of caffeine on the lactate threshold and also to examine the effects on substrate utilization during incremental cycle ergometry. Results found that caffeine increased heart rates and free fatty acid levels for all workloads and decreased blood lactate levels at some of the workloads.…

  17. Angiotensin II receptor blockers decrease serum concentration of fatty acid-binding protein 4 in patients with hypertension.

    PubMed

    Furuhashi, Masato; Mita, Tomohiro; Moniwa, Norihito; Hoshina, Kyoko; Ishimura, Shutaro; Fuseya, Takahiro; Watanabe, Yuki; Yoshida, Hideaki; Shimamoto, Kazuaki; Miura, Tetsuji

    2015-04-01

    Elevated circulating fatty acid-binding protein 4 (FABP4/A-FABP/aP2), an adipokine, is associated with obesity, insulin resistance, hypertension and cardiovascular events. However, how circulating FABP4 level is modified by pharmacological agents remains unclear. We here examined the effects of angiotensin II receptor blockers (ARBs) on serum FABP4 level. First, essential hypertensives were treated with ARBs: candesartan (8 mg day(-1); n=7) for 2 weeks, olmesartan (20 mg day(-1); n=9) for 12 weeks, and valsartan (80 mg day(-1); n=94) or telmisartan (40 mg day(-1); n=91) for 8 weeks added to amlodipine (5 mg day(-1)). Treatment with ARBs significantly decreased blood pressure and serum FABP4 concentrations by 8-20% without significant changes in adiposity or lipid variables, though the M value determined by hyperinsulinemic-euglycemic glucose clamp, a sensitive index of insulin sensitivity, was significantly increased by candesartan. Next, alterations in FABP4 secretion from 3T3-L1 adipocytes were examined under several agents. Lipolytic stimulation of the β-adrenoceptor in 3T3-L1 adipocytes by isoproterenol increased FABP4 secretion, and conversely, insulin suppressed FABP4 secretion. However, treatment of 3T3-L1 adipocytes with angiotensin II or ARBs for 2 h had no effect on gene expression or secretion of FABP4 regardless of β-adrenoceptor stimulation. In conclusion, treatment with structurally different ARBs similarly decreases circulating FABP4 concentrations in hypertensive patients as a class effect of ARBs, which is not attributable to blockade of the angiotensin II receptor in adipocytes. Reduction of FABP4 levels by ARBs might be involved in suppression of cardiovascular events. PMID:25672659

  18. Fatty acid desaturase 1 knockout mice are lean with improved glycemic control and decreased development of atheromatous plaque

    PubMed Central

    Powell, David R; Gay, Jason P; Smith, Melinda; Wilganowski, Nathaniel; Harris, Angela; Holland, Autumn; Reyes, Maricela; Kirkham, Laura; Kirkpatrick, Laura L; Zambrowicz, Brian; Hansen, Gwenn; Platt, Kenneth A; van Sligtenhorst, Isaac; Ding, Zhi-Ming; Desai, Urvi

    2016-01-01

    Delta-5 desaturase (D5D) and delta-6 desaturase (D6D), encoded by fatty acid desaturase 1 (FADS1) and FADS2 genes, respectively, are enzymes in the synthetic pathways for ω3, ω6, and ω9 polyunsaturated fatty acids (PUFAs). Although PUFAs appear to be involved in mammalian metabolic pathways, the physiologic effect of isolated D5D deficiency on these pathways is unclear. After generating >4,650 knockouts (KOs) of independent mouse genes and analyzing them in our high-throughput phenotypic screen, we found that Fads1 KO mice were among the leanest of 3,651 chow-fed KO lines analyzed for body composition and were among the most glucose tolerant of 2,489 high-fat-diet-fed KO lines analyzed by oral glucose tolerance test. In confirmatory studies, chow- or high-fat-diet-fed Fads1 KO mice were leaner than wild-type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 38% and 31% lower in Fads1 male and female KO mice, respectively. Fads1 KO mice also had lower glucose and insulin excursions during oral glucose tolerance tests along with lower fasting glucose, insulin, triglyceride, and total cholesterol levels. In additional studies using a vascular injury model, Fads1 KO mice had significantly decreased femoral artery intima/media ratios consistent with a decreased inflammatory response in their arterial wall. Based on this result, we bred Fads1 KO and WT mice onto an ApoE KO background and fed them a Western diet for 14 weeks; in this atherogenic environment, aortic trees of Fads1 KO mice had 40% less atheromatous plaque compared to WT littermates. Importantly, PUFA levels measured in brain and liver phospholipid fractions of Fads1 KO mice were consistent with decreased D5D activity and normal D6D activity. The beneficial metabolic phenotype demonstrated in Fads1 KO mice suggests that selective D5D inhibitors may be useful in the treatment of human obesity, diabetes, and atherosclerotic cardiovascular disease. PMID:27382320

  19. Blockade of P-Glycoprotein Decreased the Disposition of Phenformin and Increased Plasma Lactate Level

    PubMed Central

    Choi, Min-Koo; Song, Im-Sook

    2016-01-01

    This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal transport and became saturated with increasing phenformin concentration (2–75 μM) in LLC-PK1-Pgp, suggesting the involvement of P-gp in phenformin transport. Intrinsic clearance mediated by P-gp was 1.9 μL/min while passive diffusion clearance was 0.31 μL/min. Thus, P-gp contributed more to phenformin transport than passive diffusion. To investigate the contribution of P-gp on the pharmacokinetics and adverse effect of phenformin, the effects of verapamil, a P-gp inhibitor, on the pharmacokinetics of phenformin were also examined in rats. The plasma concentrations of phenformin were increased following oral administration of phenformin and intravenous verapamil infusion compared with those administerd phenformin alone. Pharmacokinetic parameters such as Cmax and AUC of phenformin increased and CL/F and Vss/F decreased as a consequence of verapamil treatment. These results suggested that P-gp blockade by verapamil may decrease the phenformin disposition and increase plasma phenformin concentrations. P-gp inhibition by verapamil treatment also increased plasma lactate concentration, which is a crucial adverse event of phenformin. In conclusion, P-gp may play an important role in phenformin transport process and, therefore, contribute to the modulation of pharmacokinetics of phenformin and onset of plasma lactate level. PMID:26797108

  20. Blockade of P-Glycoprotein Decreased the Disposition of Phenformin and Increased Plasma Lactate Level.

    PubMed

    Choi, Min-Koo; Song, Im-Sook

    2016-03-01

    This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal transport and became saturated with increasing phenformin concentration (2-75 μM) in LLC-PK1-Pgp, suggesting the involvement of P-gp in phenformin transport. Intrinsic clearance mediated by P-gp was 1.9 μL/min while passive diffusion clearance was 0.31 μL/min. Thus, P-gp contributed more to phenformin transport than passive diffusion. To investigate the contribution of P-gp on the pharmacokinetics and adverse effect of phenformin, the effects of verapamil, a P-gp inhibitor, on the pharmacokinetics of phenformin were also examined in rats. The plasma concentrations of phenformin were increased following oral administration of phenformin and intravenous verapamil infusion compared with those administerd phenformin alone. Pharmacokinetic parameters such as Cmax and AUC of phenformin increased and CL/F and Vss/F decreased as a consequence of verapamil treatment. These results suggested that P-gp blockade by verapamil may decrease the phenformin disposition and increase plasma phenformin concentrations. P-gp inhibition by verapamil treatment also increased plasma lactate concentration, which is a crucial adverse event of phenformin. In conclusion, P-gp may play an important role in phenformin transport process and, therefore, contribute to the modulation of pharmacokinetics of phenformin and onset of plasma lactate level. PMID:26797108

  1. Isolation and characterization of Bacillus megaterium mutants containing decreased levels of spore protease.

    PubMed Central

    Postemsky, C J; Dignam, S S; Setlow, P

    1978-01-01

    A proteolytic activity present in spores of Bacillus megaterium has previously been implicated in the initiation of hydrolysis of the A, B, and C proteins which are degraded during spore germination. Four mutants of B. megaterium containing 20 to 30% of the normal level of spore proteolytic activity have been isolated. Partial purification of the protease from wild-type spores by a reviewed procedure resulted in the resolution of spore protease activity on the A, B, and C proteins into two peaks--a major one (protease II) and a minor one (protease I). The protease mutants tested lacked active protease II. All of the mutants exhibited a decreased rate of degradation of the A, B, and C proteins during spore germination at 30 degrees C, but degradation of the proteins did occur. Degradation of the A, B, and C proteins during germination of the mutant spores was decreased neither by blockade of ATP production nor by germination at 44 degrees C. Initiation of spore germination was normal in all four mutants, and all four mutants went through outgrowth, grew, and sporulated normally in rich medium. Similarly, outgrowth of spores of two of the four mutants was normal in minimal medium at 30 degrees C. In the two mutants studied, the kinetics of loss of spore heat resistance and spore UV light resistance during germination were identical to those of wild-type spores. This indicates that the A, B, and C proteins alone are not sufficient to account for the heat or UV light resistance of the dormant spore. PMID:99436

  2. Decreased level of antibodies against Helicobacter pylori in patients with rheumatoid arthritis receiving intramuscular gold.

    PubMed Central

    Janssen, M; Dijkmans, B A; Vandenbroucke, J P; van Duijn, W; Peña, A S; Lamers, C B

    1992-01-01

    BACKGROUND: Sodium aurothiomalate has been reported to have in vitro activity against Helicobacter pylori. Intramuscular gold, as given to patients with rheumatoid arthritis (RA), may therefore influence the colonisation of the gastric mucosa with H pylori. METHODS: Two groups were compared. One group of 42 patients was treated with intramuscular gold; the other group of 58 patients was treated with antimalarial drugs. Antibodies to H pylori (IgA and IgG) were assessed by an enzyme linked immunosorbent assay (ELISA) and total IgA and IgG were measured by nephelometry. RESULTS: IgA and IgG antibody titres against H pylori and total IgA and IgG levels were lower in the patients treated with gold than in the group treated with antimalarial drugs. The ratio of IgA antibodies to H pylori to total IgA antibodies and the ratio of IgG antibodies to H pylori to total IgG antibodies were lower in the group treated with gold. The percentage of seropositivity to H pylori was significantly lower in the group treated with gold than in the group treated with antimalarial drugs for the two IgA antibodies (35 and 55% respectively) and IgG antibodies to H pylori (40 and 65% respectively). CONCLUSIONS: Although this study cannot completely exclude the possibility that a suppressive effect of intramuscular gold on total immunoglobulin production plays a part in the decrease in the titres of IgA antibodies to H pylori and IgG antibodies to H pylori, the lower ratios of antibodies to H pylori to total immunoglobulin antibodies and the lower percentages of seropositivity to H pylori in the group treated with gold suggests that treatment with intramuscular gold decreases H pylori colonisation. PMID:1417132

  3. Plasma and cerebrosponal fluid amino acid levels in diabetic ketoacidosis before and after corrective therapy.

    PubMed

    Aoki, T T; Assal J-P; Manzano, F M; Kozak, G P; Cahill, G F

    1975-05-01

    To evaluate the effect of insulin-saline-bicarbonate therapy on amino acid metabolism in diabetic ketoacidosis, arterial and venous blood samples as well as cerebrospinal fluid (CSF) were obtained from six patients before and after initiation of corrective therapy. Levels of CSF glutamine were decreased while alanine alpha-amino-n-butyrate, valine, isoleucine and leucine were increased significantly compared to a control group composed of six normal, postabsorptive adults free of any neurologic disease. Following therapy, CSF levels of alanine, alpha-amino-n-butyrate, valine, isoleucine, and leucine declined while glutamine levels did not change. Admission arterial plasma levels of the glycogenic amino acids were lower than normal while the branched-chain amino acids were elevated. Plasma alanine and glutamine arterio-venous (A-V) differences across forearm tissue were larger. After four hours of corrective therapy, arterial plasma levels of most of the amino acids had declined sharply and A-V differences for glutamine and alanine were markedly reduced (p smaller than.025 and p smaller than.01, paired t, respectively). Coincident with the decrease in A-V amino acid differences, plasma glucagon and free fatty acid levels declined significantly. These data suggest that the effect exerted by insulin-saline-bicarbonate therapy on amino acid metabolism is manifested by diminished A-V plasma alanine and glutamine differences across forearm tissue. Thus, the role played by the splanchnic bed both before and following corrective measures may be secondary to substrate availability. PMID:805076

  4. Hemodiafiltration Decreases Serum Levels of Inflammatory Mediators in Severe Leptospirosis: A Prospective Study

    PubMed Central

    Cleto, Sérgio Aparecido; Rodrigues, Camila Eleutério; Malaque, Ceila Maria; Sztajnbok, Jaques; Seguro, Antônio Carlos; Andrade, Lúcia

    2016-01-01

    Background Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with convective clearance, via hemodiafiltration (SLEDf), in patients with severe leptospirosis. Methods In this prospective study, conducted in the intensive care unit (ICU) from 2009 through 2012, we compared two groups—SLED (n = 19) and SLEDf (n = 20)—evaluating demographic, clinical, and biochemical parameters, as well as serum levels of interleukins, up to the third day after admission. All patients received dialysis early and daily thereafter. Results During the study period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis; 39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on mechanical ventilation and were comparable in terms of respiratory parameters. Mortality did not differ between the SLEDf and SLED groups. However, post-admission decreases in the serum levels of interleukin (IL)-17, IL-7, and monocyte chemoattractant protein-1 were significantly greater in the SLEDf group. Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen ratio were significantly higher in the SLED group. We identified the following risk factors (sensitivities/specificities) for mortality in severe leptospirosis: age ≥ 55 years (67%/91%); serum urea ≥ 204 mg/dl (100%/70%); creatinine ≥ 5.2 mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score ≥ 39.5 (67%/88%); Sequential

  5. The significance of plasma phytanic acid levels in adults.

    PubMed Central

    Britton, T C; Gibberd, F B; Clemens, M E; Billimoria, J D; Sidey, M C

    1989-01-01

    The presence of phytanic acid in tissues and plasma has been considered diagnostic of heredopathia atactica polyneuritiformis (Refsum's disease), but recently slightly raised plasma phytanic acid levels have been reported in other conditions. Forty two normal people were found to have a phytanic acid level of 0-33 mumol/l. Fourteen patients with heredopathia atactica polyneuritiformis had a plasma phytanic acid level before treatment of 992-6400 mumol/l. Five patients with retinitis pigmentosa but not heredopathia atactica polyneuritiformis had plasma levels of 38-192 mumol/l. It was concluded that some patients with retinitis pigmentosa without heredopathia atactica polyneuritiformis but a raised plasma phytanic acid may represent a group of patients with a disease or diseases as yet uncharacterised apart from the retinal condition. PMID:2475586

  6. Fragrance chemicals lyral and lilial decrease viability of HaCat cells' by increasing free radical production and lowering intracellular ATP level: protection by antioxidants.

    PubMed

    Usta, Julnar; Hachem, Yassmine; El-Rifai, Omar; Bou-Moughlabey, Yolla; Echtay, Karim; Griffiths, David; Nakkash-Chmaisse, Hania; Makki, Rajaa Fakhoury

    2013-02-01

    We investigate in this study the biochemical effects on cells in culture of two commonly used fragrance chemicals: lyral and lilial. Whereas both chemicals exerted a significant effect on primary keratinocyte(s), HaCat cells, no effect was obtained with any of HepG2, Hek293, Caco2, NIH3T3, and MCF7 cells. Lyral and lilial: (a) decreased the viability of HaCat cells with a 50% cell death at 100 and 60 nM respectively; (b) decreased significantly in a dose dependant manner the intracellular ATP level following 12-h of treatment; (c) inhibited complexes I and II of electron transport chain in liver sub-mitochondrial particles; and (d) increased reactive oxygen species generation that was reversed by N-acetyl cysteine and trolox and the natural antioxidant lipoic acid, without influencing the level of free and/or oxidized glutathione. Lipoic acid protected HaCat cells against the decrease in viability induced by either compound. Dehydrogenation of lyral and lilial produce α,β-unsaturated aldehydes, that reacts with lipoic acid requiring proteins resulting in their inhibition. We propose lyral and lilial as toxic to mitochondria that have a direct effect on electron transport chain, increase ROS production, derange mitochondrial membrane potential, and decrease cellular ATP level, leading thus to cell death. PMID:22940465

  7. SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane

    PubMed Central

    Morrissey, Meghan A.; Jayadev, Ranjay; Miley, Ginger R.; Blebea, Catherine A.; Chi, Qiuyi; Ihara, Shinji; Sherwood, David R.

    2016-01-01

    Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments. Using the model of anchor cell invasion through the basement membrane (BM) extracellular matrix in Caenorhabditis elegans, we find that SPARC overexpression is highly pro-invasive and rescues BM transmigration in mutants with defects in diverse aspects of invasion, including cell polarity, invadopodia formation, and matrix metalloproteinase expression. By examining BM assembly, we find that overexpression of SPARC specifically decreases levels of BM type IV collagen, a crucial structural BM component. Reduction of type IV collagen mimicked SPARC overexpression and was sufficient to promote invasion. Tissue-specific overexpression and photobleaching experiments revealed that SPARC acts extracellularly to inhibit collagen incorporation into BM. By reducing endogenous SPARC, we also found that SPARC functions normally to traffic collagen from its site of synthesis to tissues that do not express collagen. We propose that a surplus of SPARC disrupts extracellular collagen trafficking and reduces BM collagen incorporation, thus weakening the BM barrier and dramatically enhancing its ability to be breached by invasive cells. PMID:26926673

  8. SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane.

    PubMed

    Morrissey, Meghan A; Jayadev, Ranjay; Miley, Ginger R; Blebea, Catherine A; Chi, Qiuyi; Ihara, Shinji; Sherwood, David R

    2016-02-01

    Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments. Using the model of anchor cell invasion through the basement membrane (BM) extracellular matrix in Caenorhabditis elegans, we find that SPARC overexpression is highly pro-invasive and rescues BM transmigration in mutants with defects in diverse aspects of invasion, including cell polarity, invadopodia formation, and matrix metalloproteinase expression. By examining BM assembly, we find that overexpression of SPARC specifically decreases levels of BM type IV collagen, a crucial structural BM component. Reduction of type IV collagen mimicked SPARC overexpression and was sufficient to promote invasion. Tissue-specific overexpression and photobleaching experiments revealed that SPARC acts extracellularly to inhibit collagen incorporation into BM. By reducing endogenous SPARC, we also found that SPARC functions normally to traffic collagen from its site of synthesis to tissues that do not express collagen. We propose that a surplus of SPARC disrupts extracellular collagen trafficking and reduces BM collagen incorporation, thus weakening the BM barrier and dramatically enhancing its ability to be breached by invasive cells. PMID:26926673

  9. Climate change affects low trophic level marine consumers: warming decreases copepod size and abundance.

    PubMed

    Garzke, Jessica; Ismar, Stefanie M H; Sommer, Ulrich

    2015-03-01

    Concern about climate change has re-ignited interest in universal ecological responses to temperature variations: (1) biogeographical shifts, (2) phenology changes, and (3) size shifts. In this study we used copepods as model organisms to study size responses to temperature because of their central role in the pelagic food web and because of the ontogenetic length constancy between molts, which facilitates the definition of size of distinct developmental stages. In order to test the expected temperature-induced shifts towards smaller body size and lower abundances under warming conditions, a mesocosm experiment using plankton from the Baltic Sea at three temperature levels (ambient, ambient +4 °C, ambient -4 °C) was performed in summer 2010. Overall copepod and copepodit abundances, copepod size at all life stages, and adult copepod size in particular, showed significant temperature effects. As expected, zooplankton peak abundance was lower in warm than in ambient treatments. Copepod size-at-immature stage significantly increased in cold treatments, while adult size significantly decreased in warm treatments. PMID:25413864

  10. Transient postnatal fluoxetine leads to decreased brain arachidonic acid metabolism and cytochrome P450 4A in adult mice

    PubMed Central

    Ramadan, Epolia; Blanchard, Helene; Cheon, Yewon; Fox, Meredith A.; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.; Basselin, Mireille

    2014-01-01

    Fetal and perinatal exposure to selective serotonin (5-HT) reuptake inhibitors (SSRIs) has been reported to alter childhood behavior, while transient early exposure in rodents is reported to alter their behavior and decrease brain extracellular 5-HT in adulthood. Since 5-HT2A/2C receptor-mediated neurotransmission can involve G-protein coupled activation of cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (ARA) from synaptic membrane phospholipid, we hypothesized that transient postnatal exposure to fluoxetine would decrease brain ARA metabolism in adult mice. Brain ARA incorporation coefficients k* and rates Jin were quantitatively imaged following intravenous [1-14C]ARA infusion of unanesthetized adult mice that had been injected daily with fluoxetine (10 mg/kg i.p.) or saline during postnatal days P4–P21. Expression of brain ARA metabolic enzymes and other relevant markers also was measured. On neuroimaging, k* and Jin was decreased widely in early fluoxetine- compared to saline-treated adult mice. Of the enzymes measured, cPLA2 activity was unchanged, while Ca2+-independent iPLA2 activity was increased. There was a significant 74% reduced protein level of cytochrome P450 (CYP) 4A, which can convert ARA to 20-HETE. Reduced brain ARA metabolism in adult mice transiently exposed to postnatal fluoxetine, and a 74% reduction in CYP4A protein, suggest long-term effects independent of drug presence in brain ARA metabolism, and in CYP4A metabolites. Comparable changes in humans might contribute to reported altered behavior following early SSRI. PMID:24529827

  11. Genetic decrease in fatty acid unsaturation of phosphatidylglycerol increased photoinhibition of photosystem I at low temperature in tobacco leaves.

    PubMed

    Ivanov, A G; Allakhverdiev, S I; Huner, N P A; Murata, N

    2012-08-01

    Leaves of transgenic tobacco plants with decreased levels of fatty acid unsaturation in phosphatidylglycerol (PG) exhibited a slightly lower level of the steady state oxidation of the photosystem I (PSI) reaction center P700 (P700(+)) than wild-type plants. The PSI photochemistry of wild-type plants was only marginally affected by high light treatments. Surprisingly, all plants of transgenic lines exhibited much higher susceptibility to photoinhibition of PSI than wild-type plants. This was accompanied by a 2.5-fold faster re-reduction rate of P700(+) in the dark, indicating a higher capacity for cyclic electron flow around PSI in high light treated transgenic leaves. This was associated with a much higher intersystem electron pool size suggesting over-reduction of the PQ pool in tobacco transgenic lines with altered PG unsaturation compared to wild-type plants. The physiological role of PG unsaturation in PSI down-regulation and modulation of the capacity of PSI-dependent cyclic electron flows and distribution of excitation light energy in tobacco plants under photoinhibitory conditions at low temperatures is discussed. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial. PMID:22445720

  12. Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0) Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins.

    PubMed

    Venn-Watson, Stephanie K; Parry, Celeste; Baird, Mark; Stevenson, Sacha; Carlin, Kevin; Daniels, Risa; Smith, Cynthia R; Jones, Richard; Wells, Randall S; Ridgway, Sam; Jensen, Eric D

    2015-01-01

    Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A) and lower (n = 19, Group B) mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P < 0.0001) and their dietary fish. In addition to higher insulin, triglycerides, and ferritin, Group A had lower percent serum heptadecanoic acid (C17:0) compared to Group B (0.3 ± 0.1 and 1.3 ± 0.4%, respectively; P < 0.0001). Using multivariate stepwise regression, higher percent serum C17:0, a saturated fat found in dairy fat, rye, and some fish, was an independent predictor of lower insulin in dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B's diet, had C17:0 (41 and 67 mg/100g, respectively). When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg), C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g); nonfat dairy products had no detectable C17:0. We hypothesize that humans' movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome. PMID:26200116

  13. Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0) Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins

    PubMed Central

    Venn-Watson, Stephanie K.; Parry, Celeste; Baird, Mark; Stevenson, Sacha; Carlin, Kevin; Daniels, Risa; Smith, Cynthia R.; Jones, Richard; Wells, Randall S.; Ridgway, Sam; Jensen, Eric D.

    2015-01-01

    Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A) and lower (n = 19, Group B) mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P < 0.0001) and their dietary fish. In addition to higher insulin, triglycerides, and ferritin, Group A had lower percent serum heptadecanoic acid (C17:0) compared to Group B (0.3 ± 0.1 and 1.3 ± 0.4%, respectively; P < 0.0001). Using multivariate stepwise regression, higher percent serum C17:0, a saturated fat found in dairy fat, rye, and some fish, was an independent predictor of lower insulin in dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B’s diet, had C17:0 (41 and 67 mg/100g, respectively). When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg), C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g); nonfat dairy products had no detectable C17:0. We hypothesize that humans’ movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome. PMID:26200116

  14. [Serum uric acid levels and risk of developing preeclampsia].

    PubMed

    Corominas, Ana I; Balconi, Silvia M; Palermo, Mario; Maskin, Bernardo; Damiano, Alicia E

    2014-01-01

    It is well known that preeclampsia is associated to high uric acid levels, but the clinical assessment of this relationship is still under consideration. Our research was to evaluate if periodic doses of uric acid during pregnancy might help to identify a high risk group prior to the onset of preeclampsia. We conducted a retrospective investigation in 79 primary gestates with normal blood pressure and 79 women with preeclampsia who were assisted at Hospital Nacional Posadas during 2010. Serum uric acid levels, creatininemia, uremia, and proteinuria data from the clinical records of the pregnant women were considered. Uric acid levels were similar in both groups during the first half of gestation. However, as of the 20th week, uric acid increased 1.5-times in preeclamptic women with no changes in creatinine and urea, confirming that these patients had no renal complications. Furthermore, we noted that higher levels of uric acid correlated with low birth weight. We also observed that pregnant women with a family history of hypertension were more likely to develop this condition. Moreover, we did not find a direct relationship with the fetal sex or the appearance of clinical symptoms. The analytical evidence suggests that changes in uric acid concentrations may be due to metabolic alterations at the initial stages of preeclampsia. Therefore, we propose that monitoring levels of uric acid during pregnancy might contribute to the early control of this condition. PMID:25555007

  15. Oral branched-chain amino acids decrease whole-body proteolysis

    NASA Technical Reports Server (NTRS)

    Ferrando, A. A.; Williams, B. D.; Stuart, C. A.; Lane, H. W.; Wolfe, R. R.

    1995-01-01

    BACKGROUND: This study reports the effects of ingesting branched-chain amino acids (leucine, valine, and isoleucine) on protein metabolism in four men. METHODS: To calculate leg protein synthesis and breakdown, we used a new model that utilized the infusion of L-[ring-13C6]phenylalanine and the sampling of the leg arterial-venous difference and muscle biopsies. In addition, protein-bound enrichments provided for the direct calculation of muscle fractional synthetic rate. Four control subjects ingested an equivalent amount of essential amino acids (threonine, methionine, and histidine) to discern the effects of branched-chain amino acid nitrogen vs the effects of essential amino acid nitrogen. Each drink also included 50 g of carbohydrate. RESULTS: Consumption of the branched-chain and the essential amino acid solutions produced significant threefold and fourfold elevations in their respective arterial concentrations. Protein synthesis and breakdown were unaffected by branched-chain amino acids, but they increased by 43% (p < .05) and 36% (p < .03), respectively, in the group consuming the essential amino acids. However, net leg balance of phenylalanine was unchanged by either drink. Direct measurement of protein synthesis by tracer incorporation into muscle protein (fractional synthetic rate) revealed no changes within or between drinks. Whole-body phenylalanine flux was significantly suppressed by each solution but to a greater extent by the branched-chain amino acids (15% and 20%, respectively) (p < .001). CONCLUSIONS: These results suggest that branched-chain amino acid ingestion suppresses whole-body proteolysis in tissues other than skeletal muscle in normal men.

  16. Biochemical and Molecular Characterization of a Mutation That Confers a Decreased Raffinosaccharide and Phytic Acid Phenotype on Soybean Seeds

    PubMed Central

    Hitz, William D.; Carlson, Thomas J.; Kerr, Phil S.; Sebastian, Scott A.

    2002-01-01

    A single, recessive mutation in soybean (Glycine max L. Merr.), which confers a seed phenotype of increased inorganic phosphate, decreased phytic acid, and a decrease in total raffinosaccharides, has been previously disclosed (S.A. Sebastian, P.S. Kerr, R.W. Pearlstein, W.D. Hitz [2000] Soy in Animal Nutrition, pp 56–74). The genetic lesion causing the multiple changes in seed phenotype is a single base change in the third base of the codon for what is amino acid residue 396 of the mature peptide encoding a seed-expressed myo-inositol 1-phospate synthase gene. The base change causes residue 396 to change from lysine to asparagine. That amino acid change decreases the specific activity of the seed-expressed myo-inositol 1-phosphate synthase by about 90%. Radio tracer experiments indicate that the supply of myo-inositol to the reaction, which converts UDP-galactose and myo-inositol to galactinol is a controlling factor in the conversion of total carbohydrate into the raffinosaccharides in both wild-type and mutant lines. That same decrease in myo-inositol 1-phosphate synthetic capacity leads to a decreased capacity for the synthesis of myo-inositol hexaphosphate (phytic acid) and a concomitant increase in inorganic phosphate. PMID:11842168

  17. Longitudinal decrease in blood oxygenation level dependent response in cerebral amyloid angiopathy

    PubMed Central

    Switzer, Aaron R.; McCreary, Cheryl; Batool, Saima; Stafford, Randall B.; Frayne, Richard; Goodyear, Bradley G.; Smith, Eric E.

    2016-01-01

    Lower blood oxygenation level dependent (BOLD) signal changes in response to a visual stimulus in functional magnetic resonance imaging (fMRI) have been observed in cross-sectional studies of cerebral amyloid angiopathy (CAA), and are presumed to reflect impaired vascular reactivity. We used fMRI to detect a longitudinal change in BOLD responses to a visual stimulus in CAA, and to determine any correlations between these changes and other established biomarkers of CAA progression. Data were acquired from 22 patients diagnosed with probable CAA (using the Boston Criteria) and 16 healthy controls at baseline and one year. BOLD data were generated from the 200 most active voxels of the primary visual cortex during the fMRI visual stimulus (passively viewing an alternating checkerboard pattern). In general, BOLD amplitudes were lower at one year compared to baseline in patients with CAA (p = 0.01) but were unchanged in controls (p = 0.18). The longitudinal difference in BOLD amplitudes was significantly lower in CAA compared to controls (p < 0.001). White matter hyperintensity (WMH) volumes and number of cerebral microbleeds, both presumed to reflect CAA-mediated vascular injury, increased over time in CAA (p = 0.007 and p = 0.001, respectively). Longitudinal increases in WMH (rs = 0.04, p = 0.86) or cerebral microbleeds (rs = − 0.18, p = 0.45) were not associated with the longitudinal decrease in BOLD amplitudes. PMID:27104140

  18. Uric Acid Levels in Normotensive Children of Hypertensive Parents

    PubMed Central

    Yildirim, Ali; Keles, Fatma; Kosger, Pelin; Ozdemir, Gokmen; Ucar, Birsen; Kilic, Zubeyir

    2015-01-01

    This study evaluated uric acid concentrations in normotensive children of parents with hypertension. Eighty normotensive children from families with and without a history of essential hypertension were included. Concentrations of lipid parameters and uric acid were compared. Demographic and anthropometric characteristics were similar in the groups. Systolic and diastolic blood pressure were higher in the normotensive children of parents with hypertension without statistically significant difference (P > 0.05). Uric acid concentrations were higher in the normotensive children of parents with hypertension (4.61 versus 3.57 mg/dL, P < 0.01). Total cholesterol and triglyceride concentrations were similar in the two groups. Systolic and diastolic blood pressure were significantly higher in control children aged >10 years (P < 0.01). Uric acid levels were significantly higher in all children with more pronounced difference after age 10 of years (P < 0.001). Positive correlations were found between the level of serum uric acid and age, body weight, body mass index, and systolic and diastolic blood pressure in the normotensive children of parents. The higher uric acid levels in the normotensive children of hypertensive parents suggest that uric acid may be a predeterminant of hypertension. Monitoring of uric acid levels in these children may allow for prevention or earlier treatment of future hypertension. PMID:26464873

  19. Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARγ.

    PubMed

    Kim, Dong Hyun; Vanella, Luca; Inoue, Kazuyoshi; Burgess, Angela; Gotlinger, Katherine; Manthati, Vijaya Lingam; Koduru, Sreenivasulu Reddy; Zeldin, Darryl C; Falck, John R; Schwartzman, Michal L; Abraham, Nader G

    2010-12-01

    Human mesenchymal stem cells (MSCs) expressed substantial levels of CYP2J2, a major CYP450 involved in epoxyeicosatrienoic acid (EET) formation. MSCs synthesized significant levels of EETs (65.8 ± 5.8 pg/mg protein) and dihydroxyeicosatrienoic acids (DHETs) (15.83 ± 1.62 pg/mg protein), suggesting the presence of soluble epoxide hydrolase (sEH). The addition of an sEH inhibitor to MSC culture decreased adipogenesis. EETs decreased MSC-derived adipocytes in a concentration-dependent manner, 8,9- and 14,15-EET having the maximum reductive effect on adipogenesis. We examined the effect of 12-(3-hexylureido)dodec-8(Z)-enoic acid, an EET agonist, on MSC-derived adipocytes and demonstrated an increased number of healthy small adipocytes, attenuated fatty acid synthase (FAS) levels (P < 0.01), and reduced PPARγ, C/EBPα, FAS, and lipid accumulation (P < 0.05). These effects were accompanied by increased levels of heme oxygenase (HO)-1 and adiponectin (P < 0.05), and increased glucose uptake (P < 0.05). Inhibition of HO activity or AKT by tin mesoporphyrin (SnMP) and LY2940002, respectively, reversed EET-induced inhibition of adipogenesis, suggesting that activation of the HO-1-adiponectin axis underlies EET effect in MSCs. These findings indicate that EETs decrease MSC-derived adipocyte stem cell differentiation by upregulation of HO-1-adiponectin-AKT signaling and play essential roles in the regulation of adipocyte differentiation by inhibiting PPARγ, C/EBPα, and FAS and in stem cell development. These novel observations highlight the seminal role of arachidonic acid metabolism in MSCs and suggest that an EET agonist may have potential therapeutic use in the treatment of dyslipidemia, diabetes, and the metabolic syndrome. PMID:20412023

  20. Epoxyeicosatrienoic Acid Agonist Regulates Human Mesenchymal Stem Cell–Derived Adipocytes Through Activation of HO-1-pAKT Signaling and a Decrease in PPARγ

    PubMed Central

    Kim, Dong Hyun; Vanella, Luca; Inoue, Kazuyoshi; Burgess, Angela; Gotlinger, Katherine; Manthati, Vijaya Lingam; Koduru, Sreenivasulu Reddy; Zeldin, Darryl C.; Falck, John R.; Schwartzman, Michal L.

    2010-01-01

    Human mesenchymal stem cells (MSCs) expressed substantial levels of CYP2J2, a major CYP450 involved in epoxyeicosatrienoic acid (EET) formation. MSCs synthesized significant levels of EETs (65.8 ± 5.8 pg/mg protein) and dihydroxyeicosatrienoic acids (DHETs) (15.83 ± 1.62 pg/mg protein), suggesting the presence of soluble epoxide hydrolase (sEH). The addition of an sEH inhibitor to MSC culture decreased adipogenesis. EETs decreased MSC-derived adipocytes in a concentration-dependent manner, 8,9- and 14,15-EET having the maximum reductive effect on adipogenesis. We examined the effect of 12-(3-hexylureido)dodec-8(Z)-enoic acid, an EET agonist, on MSC-derived adipocytes and demonstrated an increased number of healthy small adipocytes, attenuated fatty acid synthase (FAS) levels (P < 0.01), and reduced PPARγ, C/EBPα, FAS, and lipid accumulation (P < 0.05). These effects were accompanied by increased levels of heme oxygenase (HO)-1 and adiponectin (P < 0.05), and increased glucose uptake (P < 0.05). Inhibition of HO activity or AKT by tin mesoporphyrin (SnMP) and LY2940002, respectively, reversed EET-induced inhibition of adipogenesis, suggesting that activation of the HO-1-adiponectin axis underlies EET effect in MSCs. These findings indicate that EETs decrease MSC-derived adipocyte stem cell differentiation by upregulation of HO-1-adiponectin-AKT signaling and play essential roles in the regulation of adipocyte differentiation by inhibiting PPARγ, C/EBPα, and FAS and in stem cell development. These novel observations highlight the seminal role of arachidonic acid metabolism in MSCs and suggest that an EET agonist may have potential therapeutic use in the treatment of dyslipidemia, diabetes, and the metabolic syndrome. PMID:20412023

  1. [Hydroxycinnamic acid levels of various batches from mugwort flowering tops].

    PubMed

    Fraisse, D; Carnat, A; Carnat, A-P; Guédon, D; Lamaison, J-L

    2003-07-01

    Dried flowering tops of 24 harvested batches (Artemisia vulgaris: 13; Artemisia verlotiorum: 11) and 12 batches of mugwort from commercial origin were examined. The levels of principal compounds averaged respectively: total hydroxycinnamic acids 6.09; 10.29 and 9.13%, chlorogenic acid 0.79; 2.05 and 1.35%, 1,5-dicaffeoylquinic acid 0.51; 4.01 and 1.25%, 3,5-dicaffeoylquinic acid 2.21; 1.25 and 2.60%. Specifications were discussed for an European Pharmacopoeial monography. PMID:12843960

  2. Flavonoid metabolite 3-(3-hydroxyphenyl)propionic acid formed by human microflora decreases arterial blood pressure in rats.

    PubMed

    Najmanová, Iveta; Pourová, Jana; Vopršalová, Marie; Pilařová, Veronika; Semecký, Vladimír; Nováková, Lucie; Mladěnka, Přemysl

    2016-05-01

    There are reports of positive effects of quercetin on cardiovascular pathologies, however, mainly due to its low biovailability, the mechanism remains elusive. Here, we report that one metabolite formed by human microflora (3-(3-hydroxyphenyl)propionic acid)relaxed isolated rat aorta and decreased arterial blood pressure in rats. PMID:26790841

  3. Long-term recovery of lakes in the Adirondack region of New York to decreases in acidic deposition

    NASA Astrophysics Data System (ADS)

    Waller, Kristin; Driscoll, Charles; Lynch, Jason; Newcomb, Dani; Roy, Karen

    2012-01-01

    After years of adverse impacts to the acid-sensitive ecosystems of the eastern United States, the Acid Rain Program and Nitrogen Budget Program were developed to control sulfur dioxide (SO 2) and nitrogen oxide (NO x) emissions through market-based cap and trade systems. We used data from the National Atmospheric Deposition Program's National Trends Network (NTN) and the U.S. EPA Temporally Integrated Monitoring of Ecosystems (TIME) program to evaluate the response of lake-watersheds in the Adirondack region of New York to changes in emissions of sulfur dioxide and nitrogen oxides resulting from the Acid Rain Program and the Nitrogen Budget Program. TIME is a long-term monitoring program designed to sample statistically selected subpopulations of lakes and streams across the eastern U.S. to quantify regional trends in surface water chemistry due to changes in atmospheric deposition. Decreases in wet sulfate deposition for the TIME lake-watersheds from 1991 to 2007 (-1.04 meq m -2-yr) generally corresponded with decreases in estimated lake sulfate flux (-1.46 ± 0.72 meq m -2-yr), suggesting declines in lake sulfate were largely driven by decreases in atmospheric deposition. Decreases in lake sulfate and to a lesser extent nitrate have generally coincided with increases in acid neutralizing capacity (ANC) resulting in shifts in lakes among ANC sensitivity classes. The percentage of acidic Adirondack lakes (ANC <0 μeq L -1) decreased from 15.5% (284 lakes) to 8.3% (152 lakes) since the implementation of the Acid Rain Program and the Nitrogen Budget Program. Two measures of ANC were considered in our analysis: ANC determined directly by Gran plot analysis (ANC G) and ANC calculated by major ion chemistry (ANC calc = CB - CA). While these two metrics should theoretically show similar responses, ANC calc (+2.03 μeq L -1-yr) increased at more than twice the rate as ANC G (+0.76 μeq L -1-yr). This discrepancy has important implications for assessments of lake recovery

  4. Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes.

    PubMed

    Nanthirudjanar, Tharnath; Furumoto, Hidehiro; Zheng, Jiawen; Kim, Young-Il; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kawada, Teruo; Park, Si-Bum; Hirata, Akiko; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2015-11-01

    Hydroxy and oxo fatty acids were recently found to be produced as intermediates during gut microbial fatty acid metabolism. Lactobacillus plantarum produces these fatty acids from unsaturated fatty acids such as linoleic acid. In this study, we investigated the effects of these gut microbial fatty acid metabolites on the lipogenesis in liver cells. We screened their effect on sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells treated with a synthetic liver X receptor α (LXRα) agonist (T0901317). The results showed that 10-hydroxy-12(Z)-octadecenoic acid (18:1) (HYA), 10-hydroxy-6(Z),12(Z)-octadecadienoic acid (18:2) (γHYA), 10-oxo-12(Z)-18:1 (KetoA), and 10-oxo-6(Z),12(Z)-18:2 (γKetoA) significantly decreased SREBP-1c mRNA expression induced by T0901317. These fatty acids also downregulated the mRNA expression of lipogenic genes by suppressing LXRα activity and inhibiting SREBP-1 maturation. Oral administration of KetoA, which effectively reduced triacylglycerol accumulation and acetyl-CoA carboxylase 2 (ACC2) expression in HepG2 cells, for 2 weeks significantly decreased Srebp-1c, Scd-1, and Acc2 expression in the liver of mice fed a high-sucrose diet. Our findings suggest that the hypolipidemic effect of the fatty acid metabolites produced by L. plantarum can be exploited in the treatment of cardiovascular diseases or dyslipidemia. PMID:26399511

  5. Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation.

    PubMed

    Song, No-Joon; Yun, Ui Jeong; Yang, Sunghee; Wu, Chunyan; Seo, Cho-Rong; Gwon, A-Ryeong; Baik, Sang-Ha; Choi, Yuri; Choi, Bo Youn; Bahn, Gahee; Kim, Suji; Kwon, So-Mi; Park, Jin Su; Baek, Seung Hyun; Park, Tae Joo; Yoon, Keejung; Kim, Byung-Joon; Mattson, Mark P; Lee, Sung-Joon; Jo, Dong-Gyu; Park, Kye Won

    2016-01-01

    Notch signaling pathways modulate various cellular processes, including cell proliferation, differentiation, adhesion, and communication. Recent studies have demonstrated that Notch1 signaling also regulates hepatic glucose production and lipid synthesis. However, the effect of Notch1 signaling on hepatic lipid oxidation has not yet been directly investigated. To define the function of Notch1 signaling in hepatic lipid metabolism, wild type mice and Notch1 deficient antisense transgenic (NAS) mice were fed a high-fat diet. High-fat diet -fed NAS mice exhibited a marked reduction in hepatic triacylglycerol accumulation compared with wild type obese mice. The improved fatty liver was associated with an increased expression of hepatic genes involved in fatty acid oxidation. However, lipogenic genes were not differentially expressed in the NAS liver, suggesting lipolytic-specific regulatory effects by Notch1 signaling. Expression of fatty acid oxidative genes and the rate of fatty acid oxidation were also increased by inhibition of Notch1 signaling in HepG2 cells. In addition, similar regulatory effects on lipid accumulation were observed in adipocytes. Taken together, these data show that inhibition of Notch1 signaling can regulate the expression of fatty acid oxidation genes and may provide therapeutic strategies in obesity-induced hepatic steatosis. PMID:26786165

  6. Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation

    PubMed Central

    Song, No-Joon; Yun, Ui Jeong; Yang, Sunghee; Wu, Chunyan; Seo, Cho-Rong; Gwon, A-Ryeong; Baik, Sang-Ha; Choi, Yuri; Choi, Bo Youn; Bahn, Gahee; Kim, Suji; Kwon, So-Mi; Park, Jin Su; Baek, Seung Hyun; Park, Tae Joo; Yoon, Keejung; Kim, Byung-Joon; Mattson, Mark P.; Lee, Sung-Joon; Jo, Dong-Gyu; Park, Kye Won

    2016-01-01

    Notch signaling pathways modulate various cellular processes, including cell proliferation, differentiation, adhesion, and communication. Recent studies have demonstrated that Notch1 signaling also regulates hepatic glucose production and lipid synthesis. However, the effect of Notch1 signaling on hepatic lipid oxidation has not yet been directly investigated. To define the function of Notch1 signaling in hepatic lipid metabolism, wild type mice and Notch1 deficient antisense transgenic (NAS) mice were fed a high-fat diet. High-fat diet -fed NAS mice exhibited a marked reduction in hepatic triacylglycerol accumulation compared with wild type obese mice. The improved fatty liver was associated with an increased expression of hepatic genes involved in fatty acid oxidation. However, lipogenic genes were not differentially expressed in the NAS liver, suggesting lipolytic-specific regulatory effects by Notch1 signaling. Expression of fatty acid oxidative genes and the rate of fatty acid oxidation were also increased by inhibition of Notch1 signaling in HepG2 cells. In addition, similar regulatory effects on lipid accumulation were observed in adipocytes. Taken together, these data show that inhibition of Notch1 signaling can regulate the expression of fatty acid oxidation genes and may provide therapeutic strategies in obesity-induced hepatic steatosis. PMID:26786165

  7. Cutaneous retinoic acid levels determine hair follicle development and downgrowth.

    PubMed

    Okano, Junko; Levy, Clara; Lichti, Ulrike; Sun, Hong-Wei; Yuspa, Stuart H; Sakai, Yasuo; Morasso, Maria I

    2012-11-16

    Retinoic acid (RA) is essential during embryogenesis and for tissue homeostasis, whereas excess RA is well known as a teratogen. In humans, excess RA is associated with hair loss. In the present study, we demonstrate that specific levels of RA, regulated by Cyp26b1, one of the RA-degrading enzymes, are required for hair follicle (hf) morphogenesis. Mice with embryonic ablation of Cyp26b1 (Cyp26b1(-/-)) have excessive endogenous RA, resulting in arrest of hf growth at the hair germ stage. The altered hf development is rescued by grafting the mutant skin on immunodeficient mice. Our results show that normalization of RA levels is associated with reinitiation of hf development. Conditional deficiency of Cyp26b1 in the dermis (En1Cre;Cyp26b1f/-) results in decreased hair follicle density and specific effect on hair type, indicating that RA levels also influence regulators of hair bending. Our results support the model of RA-dependent dermal signals regulating hf downgrowth and bending. To elucidate target gene pathways of RA, we performed microarray and RNA-Seq profiling of genes differentially expressed in Cyp26b1(-/-) skin and En1Cre;Cyp26b1f/- tissues. We show specific effects on the Wnt-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families, indicating that RA modulates pathways and factors implicated in hf downgrowth and bending. Our results establish that proper RA distribution is essential for morphogenesis, development, and differentiation of hfs. PMID:23007396

  8. Cutaneous Retinoic Acid Levels Determine Hair Follicle Development and Downgrowth*

    PubMed Central

    Okano, Junko; Levy, Clara; Lichti, Ulrike; Sun, Hong-Wei; Yuspa, Stuart H.; Sakai, Yasuo; Morasso, Maria I.

    2012-01-01

    Retinoic acid (RA) is essential during embryogenesis and for tissue homeostasis, whereas excess RA is well known as a teratogen. In humans, excess RA is associated with hair loss. In the present study, we demonstrate that specific levels of RA, regulated by Cyp26b1, one of the RA-degrading enzymes, are required for hair follicle (hf) morphogenesis. Mice with embryonic ablation of Cyp26b1 (Cyp26b1−/−) have excessive endogenous RA, resulting in arrest of hf growth at the hair germ stage. The altered hf development is rescued by grafting the mutant skin on immunodeficient mice. Our results show that normalization of RA levels is associated with reinitiation of hf development. Conditional deficiency of Cyp26b1 in the dermis (En1Cre;Cyp26b1f/−) results in decreased hair follicle density and specific effect on hair type, indicating that RA levels also influence regulators of hair bending. Our results support the model of RA-dependent dermal signals regulating hf downgrowth and bending. To elucidate target gene pathways of RA, we performed microarray and RNA-Seq profiling of genes differentially expressed in Cyp26b1−/− skin and En1Cre;Cyp26b1f/− tissues. We show specific effects on the Wnt-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families, indicating that RA modulates pathways and factors implicated in hf downgrowth and bending. Our results establish that proper RA distribution is essential for morphogenesis, development, and differentiation of hfs. PMID:23007396

  9. Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels

    PubMed Central

    Kloiber, Stefan; Ripke, Stephan; Kohli, Martin A.; Reppermund, Simone; Salyakina, Daria; Uher, Rudolf; McGuffin, Peter; Perlis, Roy H.; Hamilton, Steven P.; Pütz, Benno; Hennings, Johannes; Brückl, Tanja; Klengel, Torsten; Bettecken, Thomas; Ising, Marcus; Uhr, Manfred; Dose, Tatjana; Unschuld, Paul G.; Zihl, Josef; Binder, Elisabeth; Müller-Myhsok, Bertram; Holsboer, Florian; Lucae, Susanne

    2013-01-01

    Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9 × 10−5) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant

  10. Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels.

    PubMed

    Kloiber, Stefan; Ripke, Stephan; Kohli, Martin A; Reppermund, Simone; Salyakina, Daria; Uher, Rudolf; McGuffin, Peter; Perlis, Roy H; Hamilton, Steven P; Pütz, Benno; Hennings, Johannes; Brückl, Tanja; Klengel, Torsten; Bettecken, Thomas; Ising, Marcus; Uhr, Manfred; Dose, Tatjana; Unschuld, Paul G; Zihl, Josef; Binder, Elisabeth; Müller-Myhsok, Bertram; Holsboer, Florian; Lucae, Susanne

    2013-07-01

    Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9×10(-5)) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR(⁎)D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant

  11. Inhibitions of several antineoplastic drugs on serum sialic Acid levels in mice bearing tumors.

    PubMed

    Lu, Da-Yong; Xu, Jing; Lu, Ting-Ren; Wu, Hong-Ying; Xu, Bin

    2013-03-01

    Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, thiotepa, adriamycin, probimane, cisplatin, oxalysine, cortisone, nitrogen mustard, lycobetaine, Ara-C, harringtonine, and cyclophosphamide) on the content of sialic acids in mice blood bearing solid tumors of either S180 or Lewis lung carcinoma was observed. Different inhibitions of antineoplastic drugs on both tumor growth and serum sialic acid levels in mice bearing tumors were found. Among these antineoplastic drugs, probimane, cisplatin, nitrogen mustard, and lycobetaine were able to decrease the serum sialic acid levels in mice bearing tumors. Since these four antineoplastic drugs are all DNA chelating agents, it was proposed that the inhibition of tumor sialic acids by these drugs might be through the DNA template via two ways. Since we have found no effect of antineoplastic drugs on serum sialic acid levels in normal mice, this suggests that the inhibition of antineoplastic drugs on sialic acids is by tumor involvement. PMID:23641340

  12. Serum uric acid levels during leprosy reaction episodes

    PubMed Central

    Alves-Junior, Eduardo R.; Arruda, Talita A.; Lopes, Jose C.; Fontes, Cor J.F.

    2016-01-01

    Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18–69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with

  13. Serum uric acid levels during leprosy reaction episodes.

    PubMed

    Morato-Conceicao, Yvelise T; Alves-Junior, Eduardo R; Arruda, Talita A; Lopes, Jose C; Fontes, Cor J F

    2016-01-01

    Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18-69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with type

  14. PHOSPHATED, ACID-ETCHED IMPLANTS DECREASE MINERAL APPOSITION RATES NEAR IMPLANTS IN CANINES

    PubMed Central

    Foley, Christine Hyon; Kerns, David G.; Hallmon, William W.; Rivera-Hidalgo, Francisco; Nelson, Carl J.; Spears, Robert; Dechow, Paul C.; Opperman, Lynne A.

    2010-01-01

    Purpose: This study evaluated the effects of phosphate-coated titanium on mineral apposition rate (MAR) and new bone-to-implant contact (BIC) in canines. Materials and Methods: 2.2 mm × 4 mm electrolytically phosphated or non-phosphated titanium implants with acid-etched surfaces were placed in 48 mandibular sites in 6 foxhounds. Tetracycline and calcein dyes were administered 1 week after implant placement and 1 week before sacrifice. At twelve weeks following implant healing, animals were sacrificed. MAR and BIC were evaluated using fluorescence microscopy. Light microscopic and histological evaluation was performed on undecalcified sections. Results: Microscopic evaluation showed the presence of healthy osteoblasts lining bone surfaces near implants. Similar bone-to-implant contact was observed in phosphated and non-phosphated titanium implant sites. MAR was significantly higher near non-phosphated titanium implant surfaces than the phosphated titanium samples. No significant differences were found between dogs or implant sites. Discussion and Conclusion: Acid-etched only implants showed significantly higher mineral apposition rates compared to acid-etched, phosphate-coated implants. PMID:20369085

  15. Can Email Prompting Minimize the Decrease in Wintertime Physical Activity Levels?

    ERIC Educational Resources Information Center

    Liguori, Gary; Mozumdar, Arupendra

    2007-01-01

    The primary purpose of this study is to evaluate the effectiveness of using email prompts to attenuate the decrease of physical activity in adults during a winter season. In addition, the secondary purposes were (1) to evaluate the effectiveness of email prompts at increasing motivation towards physical activity and (2) to evaluate the awareness…

  16. Evaluation of serum sialic acid, fucose levels and their ratio in oral squamous cell carcinoma

    PubMed Central

    Chinnannavar, Sangamesh Ningappa; Ashok, Lingappa; Vidya, Kodige Chandrashekhar; Setty, Sunil Mysore Kantharaja; Narasimha, Guru Eraiah; Garg, Ranjana

    2015-01-01

    Background: Detection of cancer at the early stage is of utmost importance to decrease the morbidity and mortality of the disease. Apart from the conventional biopsy, minimally invasive methods like serum evaluation are used for screening large populations. Thus, this study aimed to estimate serum levels of sialic acid and fucose and their ratio in oral cancer patients and in healthy control group to evaluate their role in diagnosis. Materials and Methods: Serum samples were collected from 52 healthy controls (group I) and 52 squamous cell carcinoma patients (group II). Estimation of serum levels of sialic acid and fucose and their ratio was performed. This was correlated histopathologically with the grades of carcinoma. Statistical analysis was done by using analysis of variance (ANOVA) test and unpaired “t” test. Results: Results showed that serum levels of sialic acid and fucose were significantly higher in oral cancer patients compared to normal healthy controls (P < 0.001). The sialic acid to fucose ratio was significantly lower in cancer patients than in normal controls (P < 0.01). However, comparison with histological grading, habits, gender, and age group did not show any significant result. Conclusion: The mean serum sialic acid and fucose levels showed an increasing trend from controls to malignant group and their corresponding ratio showed decreasing trend from controls to malignant group. The ratio of sialic acid to fucose can be a useful diagnostic aid for oral cancer patients. PMID:26759796

  17. Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

    PubMed Central

    Hämäläinen, Anssi; Sipponen, Taina; Kolho, Kaija-Leena

    2011-01-01

    AIM: To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. METHODS: Thirty-six pediatric patients with IBD [23 Crohn’s disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the patient was doing well. RESULTS: At introduction of infliximab, median fecal calprotectin level was 1150 μg/g (range 54-6032 μg/g). By week 2, the fecal calprotectin level had declined to a median 261 μg/g (P < 0.001). In 37% of the patients, fecal calprotectin was normal (< 100 μg/g) at 2 wk. By week 6, there was no additional improvement in the fecal calprotectin level (median 345 μg/g). In 22% of the patients, fecal calprotectin levels increased by week 6 to pretreatment levels or above, suggesting no response (or a loss of early response). Thus, in CD, the proportion of non-responsive patients by week 6 seemed lower, because only 9% showed no improvement in their fecal calprotectin level when compared to the respective figure of 46% of the UC patients (P < 0.05). CONCLUSION: When treated with infliximab, fecal calprotectin levels reflecting intestinal inflammation normalized rapidly in one third of pediatric patients suggesting complete mucosal healing. PMID:22215940

  18. Argon laser trabeculoplasty as a means of decreasing intraocular pressure from ''normal'' levels in glaucomatous eyes

    SciTech Connect

    Sharpe, E.D.; Simmons, R.J.

    1985-06-15

    The authors conducted a retrospective study of 67 patients (85 eyes) with severe glaucoma to determine whether argon laser trabeculoplasty could reduce intraocular pressures below the ''normal'' range. All patients had initial intraocular pressures of less than or equal to 19 mm Hg. Success was defined as a decrease in intraocular pressure of at least 20%, no increase in medications, stable visual field, and no subsequent glaucoma surgery. After an average follow-up period of 30 months, treatment was successful in 31 cases. One half of the failures occurred by six months and 11 failures (30%) occurred after 12 months. Sixteen patients were able to decrease their medications. Two patients achieved intraocular pressures between 6 and 9 mm Hg and 20 between 10 and 12 mm Hg.

  19. Increased Interleukin-17 and decreased BAFF serum levels in drug-free acute schizophrenia.

    PubMed

    El Kissi, Yousri; Samoud, Samar; Mtiraoui, Ahlem; Letaief, Leila; Hannachi, Neila; Ayachi, Mouna; Ali, Bechir Ben Hadj; Boukadida, Jalel

    2015-01-30

    Hypotheses regarding an immune-cytokine basis of schizophrenia have been postulated with controversial findings and a lack of data related to many cytokines. The aim of this study was to assess serum levels of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Transforming Growth Factor-β (TGF-β), Interleukin-17 (IL-17) and B-cell Activating Factor (BAFF) in schizophrenic patients and to determine correlations between cytokine levels and clinical parameters. Serum cytokine levels were measured with ELISA techniques in 60 neuroleptic-free patients on acute phase of the disease (BPRS≥40) and 28 healthy controls matched for age and sex. Current symptoms were assessed with Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). No significant difference was found between patients and controls regarding IFN-γ serum levels. IL-4 was not detected in both groups. Patients exhibited significantly higher IL-17 and lower BAFF serum levels. IL-17 and BAFF levels were negatively correlated in schizophrenic patients. SANS global score was negatively correlated with IL-17 and positively correlated with IFN-γ serum levels. These results argue against the involvement of Th1 or Th2 population cells in schizophrenia. IL-17 and BAFF could be valuable markers for schizophrenia. PMID:25453636

  20. Decreased Polycystin 2 Levels Result in Non-Renal Cardiac Dysfunction with Aging

    PubMed Central

    Kuo, Ivana Y.; Duong, Sophie L.; Nguyen, Lily; Ehrlich, Barbara E.

    2016-01-01

    Mutations in the gene for polycystin 2 (Pkd2) lead to polycystic kidney disease, however the main cause of mortality in humans is cardiac related. We previously showed that 5 month old Pkd2+/- mice have altered calcium-contractile activity in cardiomyocytes, but have preserved cardiac function. Here, we examined 1 and 9 month old Pkd2+/- mice to determine if decreased amounts of functional polycystin 2 leads to impaired cardiac function with aging. We observed changes in calcium handling proteins in 1 month old Pkd2+/- mice, and these changes were exacerbated in 9 month old Pkd2+/- mice. Anatomically, the 9 month old Pkd2+/- mice had thinner left ventricular walls, consistent with dilated cardiomyopathy, and the left ventricular ejection fraction was decreased. Intriguingly, in response to acute isoproterenol stimulation to examine β-adrenergic responses, the 9 month old Pkd2+/- mice exhibited a stronger contractile response, which also coincided with preserved localization of the β2 adrenergic receptor. Importantly, the Pkd2+/- mice did not have any renal impairment. We conclude that the cardiac-related impact of decreased polycystin 2 progresses over time towards cardiac dysfunction and altered adrenergic signaling. These results provide further evidence that polycystin 2 provides a critical function in the heart, independent of renal involvement. PMID:27081851

  1. Molecular basis of maple syrup urine disease: Novel mutations at the E1[alpha] locus that impair E1([alpha][sub 2][beta][sub 2]) assembly or decrease steady-state E1[alpha] mRNA levels of branched-chain [alpha]-keto acid dehydrogenase complex

    SciTech Connect

    Chuang, J.L.; Fisher, C.R.; Chuang, D.T.; Cox, R.P. )

    1994-08-01

    The authors report the occurrence of three novel mutations in the E1[alpha] (BCKDHA) locus of the branched-chain [alpha]-keto acid dehydrogenase (BCKAD) complex that cause maple syrup urine disease (MSUD). An 8-bp deletion in exon 7 is present in one allele of a compound-heterozygous patient (GM-649). A single C nucleotide insertion in exon 2 occurs in one allele of an intermediate-MSUD patient (Lo). The second allele of patient Lo carries an A-to-G transition in exon 9 of the E1[alpha] gene. This missense mutation changes Tyr-368 to Cys (Y368C) in the E1[alpha] subunit. Both the 8-bp deletion and the single C insertion generate a downstream nonsense codon. Both mutations appear to be associated with a low abundance of the mutant E1[alpha] mRNA, as determined by allele-specific oligonucleotide probing. Transfection studies strongly suggest that the Y368C substitution in the E1[alpha] subunit impairs its proper assembly with the normal E1[beta]. Unassembled as well as misassembled E1[alpha] and E1[beta] subunits are degraded in the cell. 32 refs., 8 figs.

  2. Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels.

    PubMed

    Liu, Min; Yao, Xu-Dong; Li, Wei; Geng, Jiang; Yan, Yang; Che, Jian-Ping; Xu, Yun-Fei; Zheng, Jun-Hua

    2015-01-01

    Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy. PMID:25728635

  3. Amino acid limitation induces down-regulation of WNT5a at transcriptional level

    SciTech Connect

    Wang Zuguang; Chen Hong

    2009-01-23

    An aberrant WNT signaling contributes to the development and progression of multiple cancers. WNT5a is one of the WNT signaling molecules. This study was designed to test the hypothesis that amino acid deprivation induces changes in the WNT signaling pathway in colon cancer cells. Results showed that targets of the amino acid response pathway, ATF3 and p21, were induced in the human colon cancer cell line SW480 during amino acid limitation. There was a significant decrease in the WNT5a mRNA level following amino acid deprivation. The down-regulation of WNT5a mRNA by amino acid deprivation is not due to mRNA destabilization. There is a reduction of nuclear {beta}-catenin protein level by amino acid limitation. Under amino acid limitation, phosphorylation of ERK1/2 was increased and the blockage of ERK1/2 by the inhibitor U0126 partially restored WNT5a mRNA level. In conclusion, amino acid limitation in colon cancer cells induces phosphorylation of ERK1/2, which then down-regulates WNT5a expression.

  4. Birdsong decreases protein levels of FoxP2, a molecule required for human speech.

    PubMed

    Miller, Julie E; Spiteri, Elizabeth; Condro, Michael C; Dosumu-Johnson, Ryan T; Geschwind, Daniel H; White, Stephanie A

    2008-10-01

    Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability. PMID:18701760

  5. Birdsong Decreases Protein Levels of FoxP2, a Molecule Required for Human Speech

    PubMed Central

    Miller, Julie E.; Spiteri, Elizabeth; Condro, Michael C.; Dosumu-Johnson, Ryan T.; Geschwind, Daniel H.; White, Stephanie A.

    2008-01-01

    Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability. PMID:18701760

  6. Daily walking decreases casual glucose level among pregnant women in the second trimester.

    PubMed

    Hayashi, Ayako; Matsuzaki, Masayo; Kusaka, Momoko; Shiraishi, Mie; Haruna, Megumi

    2016-01-01

    The objective of this study was to explore the relationship between carbohydrate metabolism and the number of steps walked daily, as evaluated by accelerometer, among Japanese women in the second trimester of pregnancy. This longitudinal study was conducted at a university hospital in Tokyo, Japan, from August 2012 to January 2013. Healthy pregnant women at 14 to 18 gestational weeks were recruited. Participants wore accelerometers on the waist for 4 weeks. Casual glucose and hemoglobin A1c (HbA1c) levels were compared between two groups based on whether participants habitually walked ≥ 6,000 steps/day or < 6,000 steps/day. Fifty-one pregnant women were included in the present study; data from 35 were analyzed. There were 22 women in the group that habitually walked ≥ 6,000 steps/day and 13 in the group habitually walking < 6,000 steps/day. Although the median serum casual glucose level at the end of the investigation was 90.0 mg/dL in the group walking < 6,000 steps/day, the level in the group walking ≥ 6000 steps/day was 83.5 mg/dL (p = 0.01). HbA1c levels were not significantly different between the two groups. Our results suggest that walking as a daily habitual physical activity is effective for controlling casual glucose levels in the second trimester of pregnancy. PMID:27594297

  7. Therapeutic Plasma Exchange Decreases Levels of Routinely Used Cardiac and Inflammatory Biomarkers

    PubMed Central

    Beutel, Gernot; Bauersachs, Johann; David, Sascha; Schmidt, Bernhard M. W.; Lichtinghagen, Ralf; Kielstein, Jan T.

    2012-01-01

    Background Therapeutic plasma exchange (TPE) plays a key role in the management of various diseases, from thrombotic thrombocytopenic purpura and Goodpasture's syndrome to cardiac allograft rejection. In many of these disease states cardiac and inflammatory involvement is common and biomarkers are routinely used for diagnosis or assessment of therapeutic success. The effect of TPE on biomarkers used in the clinical routine has not been investigated. Methods TPE was initiated for established clinical conditions in 21 patients. Troponin T, NT-proBNP, C-reactive protein, procalcitonin and routine chemistry were drawn before and after TPE, as well as before and after the 2nd TPE. The total amount of these markers in the waste bag was also analyzed. Results In 21 patients 42 TPEs were performed. The procedure reduced plasma levels of the examined biomarkers: 23% for NT-proBNP (pre vs. post: 4637±10234 ng/l to 3565±8295 ng/l, p<0.001), 64% for CRP (21.9±47.0 mg/l vs. 7.8±15.8 mg/l, p<0.001) and 31% for procalcitonin (0.39±1.1 µg/l vs. 0.27±0.72 µg/l, p=0.004). TPE also tended to reduce plasma levels of troponin T by about 14% (60.7±175.5 ng/l vs. 52.2±141.3 ng/l), however this difference was not statistical significant (p=0.95). There was a significant correlation between the difference of pre TPE levels to post TPE levels of all examined biomarkers and the total amount of the removed biomarker in the collected removed plasma. Conclusions TPE significantly reduces plasma levels of inflammatory and cardiac biomarkers. Therefore, post TPE levels of cardiac and inflammatory biomarkers should be viewed with caution. PMID:22685586

  8. Warming decreased and grazing increased plant uptake of amino acids in an alpine meadow.

    PubMed

    Ma, Shuang; Zhu, Xiaoxue; Zhang, Jing; Zhang, Lirong; Che, Rongxiao; Wang, Fang; Liu, Hanke; Niu, Haishan; Wang, Shiping; Cui, Xiaoyong

    2015-09-01

    Organic nitrogen (N) uptake by plants has been recognized as a significant component of terrestrial N cycle. Several studies indicated that plants have the ability to switch their preference between inorganic and organic forms of N in diverse environments; however, research on plant community response in organic nitrogen uptake to warming and grazing is scarce. Here, we demonstrated that organic N uptake by an alpine plant community decreased under warming with (13)C-(15)N-enriched glycine addition method. After 6 years of treatment, warming decreased plant organic N uptake by 37% as compared to control treatment. Under the condition of grazing, warming reduced plant organic N uptake by 44%. Grazing alone significantly increased organic N absorption by 15%, whereas under warming condition grazing did not affect organic N uptake by the Kobresia humilis community on Tibetan Plateau. Besides, soil NO 3-N content explained more than 70% of the variability observed in glycine uptake, and C:N ratio in soil dissolved organic matter remarkably increased under warming treatment. These results suggested warming promoted soil microbial activity and dissolved organic N mineralization. Grazing stimulated organic N uptake by plants, which counteracted the effect of warming. PMID:26442646

  9. Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model.

    PubMed

    Bindels, Laure B; Beck, Raphaël; Schakman, Olivier; Martin, Jennifer C; De Backer, Fabienne; Sohet, Florence M; Dewulf, Evelyne M; Pachikian, Barbara D; Neyrinck, Audrey M; Thissen, Jean-Paul; Verrax, Julien; Calderon, Pedro Buc; Pot, Bruno; Grangette, Corinne; Cani, Patrice D; Scott, Karen P; Delzenne, Nathalie M

    2012-01-01

    The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl), characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis) in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L) in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay). These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle. PMID:22761662

  10. Intervening to Decrease Alcohol Abuse at University Parties: Differential Reinforcement of Intoxication Level

    ERIC Educational Resources Information Center

    Fournier, Angela K.; Ehrhart, Ian J.; Glindemann, Kent E.; Geller, E. Scott

    2004-01-01

    This quasi-experimental field study assessed whether an incentive/reward intervention can change the drinking behavior and the subsequent levels of intoxication among college students attending fraternity parties. A total of 356 blood alcohol concentration (BAC) assessments, using hand-held breathalyzers, were obtained at two baseline and at two…

  11. Decreased level of cord blood circulating endothelial colony-forming cells in preeclampsia.

    PubMed

    Muñoz-Hernandez, Rocio; Miranda, Maria L; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M; Dominguez-Simeon, Maria J; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M

    2014-07-01

    Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation, and migration toward vascular endothelial growth factor-A and fibroblast growth factor-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P=0.04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events. PMID:24752434

  12. DECREASED LEVEL OF CORD BLOOD CIRCULATING ENDOTHELIAL COLONY-FORMING CELLS IN PREECLAMPSIA

    PubMed Central

    Muñoz-Hernandez, Rocio; Miranda, Maria L.; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M.; Dominguez-Simeon, Maria J.; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M.

    2014-01-01

    Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation and migration towards VEGF-A and FGF-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P = .04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events. PMID:24752434

  13. Ileal apical sodium-dependent bile acid transporter protein levels are down-regulated through ubiquitin-dependent protein degradation induced by bile acids.

    PubMed

    Miyata, Masaaki; Yamakawa, Hiroki; Hayashi, Kenjiro; Kuribayashi, Hideaki; Yamazoe, Yasushi; Yoshinari, Kouichi

    2013-08-15

    The ileal apical sodium-dependent bile acid transporter (ASBT or SLC10A2) has a crucial role in intestinal bile acid absorption. We previously reported that enterobacteria-mediated bile acid conversion was involved in the alteration of ileal ASBT expression levels. In the present study, to investigate the hypothesis that ileal ASBT protein levels are post-translationally regulated by enterobacteria-associated bile acids, alteration of ileal ASBT protein levels was analysed in mice 12 h and 24 h after anti-bacterial drug ampicillin (ABPC) treatment (100 mg/kg, single shot) that altered bile acid composition in the intestinal lumen. In ABPC-treated mice, enterobacteria-biotransformed bile acid, taurodeoxycholic acid (TDCA) and cholic acid (CA) levels were decreased, whereas taurocholic acid (TCA) and tauro-β-muricholic acid levels were increased in the intestinal lumen. Ileal ASBT protein levels in brush-border membrane vesicles (BBMVs), but not ileal Asbt mRNA levels, were significantly increased in the ABPC-treated mice, and the extent of ubiquitination of the ileal ASBT protein was reduced in the ABPC-treated mice. Treatment of ABPC-pretreated mice with CA or TDCA, but not TCA, significantly decreased ileal ASBT protein levels and increased the extent of ubiquitination of ileal ASBT protein. Treatment of mice with the lysosome inhibitor, chloroquine, or the proteasome inhibitor, MG132, increased ileal ASBT protein levels in BBMVs. CA-mediated reduction of ASBT protein levels in the ABPC-pretreated mice was attenuated by co-treatment with chloroquine or MG132. These results suggest that ileal ASBT protein is degraded by a ubiquitin-dependent pathway in response to enterobacteria-associated bile acids. PMID:23872411

  14. PPAR-α Agonist Fenofibrate Decreased Serum Irisin Levels in Type 2 Diabetes Patients with Hypertriglyceridemia

    PubMed Central

    Feng, Xiaomeng; Gao, Xia; Jia, Yumei; Zhang, Heng; Pan, Qingrong; Yao, Zhi; Yang, Ning; Liu, Jia; Xu, Yuan; Wang, Guang; Yang, Xinchun

    2015-01-01

    Irisin is related to insulin resistance and metabolic disorders. The physiologic effects of irisin are partially mediated through peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the effect of fenofibrate, a PPAR-α agonist, on serum irisin in type 2 diabetes patients with hypertriglyceridemia. This study evaluated cross-sectional and interventional studies of 25 type 2 diabetes patients with hypertriglyceridemia (group A) and 40 controls (group B). Group A was treated with fenofibrate (200 mg/day) for 8 weeks. Serum irisin and clinical characteristics were examined. Serum irisin was significantly higher in group A compared with group B (45.15 ± 10.48 versus 35.38 ± 9.97 ng/ml, P < 0.001) and correlated with body mass index (r = 0.314, P = 0.011), fasting blood glucose (r = 0.399, P = 0.001), total cholesterol (r = 0.256, P = 0.040), and high-density lipoprotein cholesterol (r = 0.247, P = 0.047). In multiple regression analysis after controlling for confounders, only fasting blood glucose (β = 5.615, P < 0.001) and high-density lipoprotein cholesterol (β = 19.483, P < 0.001) were independently related to serum irisin. After 8 weeks of fenofibrate treatment, serum irisin significantly decreased in group A compared with baseline (45.15 ± 10.48 versus 38.74 ± 12.54 ng/ml, P = 0.011). Conclusively, fenofibrate decreased serum irisin in type 2 diabetes patients with hypertriglyceridemia, indicating that PPAR-α agonists may protect against metabolic disorders by improving irisin resistance. PMID:26693220

  15. Elevated natural killer cell levels and autoimmunity synergistically decrease uterine blood flow during early pregnancy

    PubMed Central

    Yi, Hyun Jeong; Kim, Jung Hyun; Koo, Hwa Seon; Bae, Ju Youn; Cha, Sun Wha

    2014-01-01

    Objective To investigate whether natural killer (NK) cell and autoimmune antibody acts synergistically, by the action of autoantibodies to increase NK cell number and cytotoxicity, to decrease uterine blood flow during early pregnancy in pregnant women with a history of recurrent spontaneous abortion (RSA). Methods Seventy-five pregnant women (between 5 and 7 weeks gestation) with a history of unexplained RSA were included in the study group. Forty-one pregnant women without a history of RSA were included as controls. All women with a history of RSA were tested for autoantibodies and number of peripheral blood natural killer (pbNK) cell by flow cytometry. Study populations were stratified into four groups by existence of autoantibody and degree of increase of pbNK cells. The uterine radial artery resistance index (RI) was measured by color-pulsed Doppler transvaginal ultrasound. Results The mean RI of the autoimmune antibody-positive (AA+) group (0.63±0.09) was significantly higher than that of the normal control group (0.53±0.10, P=0.001). The mean RI of the AA+/only-NK elevated (eNK) group (0.63±0.09) was significantly higher than those of the only-AA+ group (0.55±0.07, P=0.019) and the only-eNK group (0.57±0.07, P=0.021). Conclusion Concurrent elevation in NK cells and autoimmunity results in decreased uterine blood flow during early pregnancy. However, the majority of cases of RSA remain unexplained and larger scale studies are needed to confirm our conclusion and to develop diagnostic and therapeutic plans for women with a history of RSA. PMID:24883292

  16. PPAR-α Agonist Fenofibrate Decreased Serum Irisin Levels in Type 2 Diabetes Patients with Hypertriglyceridemia.

    PubMed

    Feng, Xiaomeng; Gao, Xia; Jia, Yumei; Zhang, Heng; Pan, Qingrong; Yao, Zhi; Yang, Ning; Liu, Jia; Xu, Yuan; Wang, Guang; Yang, Xinchun

    2015-01-01

    Irisin is related to insulin resistance and metabolic disorders. The physiologic effects of irisin are partially mediated through peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the effect of fenofibrate, a PPAR-α agonist, on serum irisin in type 2 diabetes patients with hypertriglyceridemia. This study evaluated cross-sectional and interventional studies of 25 type 2 diabetes patients with hypertriglyceridemia (group A) and 40 controls (group B). Group A was treated with fenofibrate (200 mg/day) for 8 weeks. Serum irisin and clinical characteristics were examined. Serum irisin was significantly higher in group A compared with group B (45.15 ± 10.48 versus 35.38 ± 9.97 ng/ml, P < 0.001) and correlated with body mass index (r = 0.314, P = 0.011), fasting blood glucose (r = 0.399, P = 0.001), total cholesterol (r = 0.256, P = 0.040), and high-density lipoprotein cholesterol (r = 0.247, P = 0.047). In multiple regression analysis after controlling for confounders, only fasting blood glucose (β = 5.615, P < 0.001) and high-density lipoprotein cholesterol (β = 19.483, P < 0.001) were independently related to serum irisin. After 8 weeks of fenofibrate treatment, serum irisin significantly decreased in group A compared with baseline (45.15 ± 10.48 versus 38.74 ± 12.54 ng/ml, P = 0.011). Conclusively, fenofibrate decreased serum irisin in type 2 diabetes patients with hypertriglyceridemia, indicating that PPAR-α agonists may protect against metabolic disorders by improving irisin resistance. PMID:26693220

  17. Hypothermia Decreases Cerebrospinal Fluid Asymmetric Dimethylarginine Levels in Traumatic Brain Injury Children

    PubMed Central

    Thampatty, Bhavani P; Klamerus, Megan M; Oberly, Patrick J; Feldman, Kerri L; Bell, Michael J; Tyler-Kabara, Elizabeth C; Adelson, P. David; Clark, Robert SB; Kochanek, Patrick M; Poloyac, Samuel M

    2014-01-01

    Objectives Pathological increases in asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, have been implicated in endothelial dysfunction and vascular diseases. Reduced NO early after traumatic brain injury (TBI) may contribute to hypoperfusion. Currently, methods to quantify ADMA in the cerebrospinal fluid (CSF) have not been fully explored. We aimed to develop and validate a method to determine ADMA in the CSF of a pediatric TBI population and to use this method to assess the effects of (i) TBI and (ii) therapeutic hypothermia (TH) on this mediator. Design, Setting, Patients An ancillary study to a prospective, phase II randomized clinical trial (RCT) of early hypothermia in a tertiary care pediatric intensive care unit for children with TBI admitted to Children's Hospital of Pittsburgh. Interventions None Measurements and Main Results A UPLC-MS/MS method was developed and validated to quantitate ADMA. A total of 56 samples collected over 3 days starting with injury onset were analyzed from the CSF of consented therapeutic hypothermia (n=9) and normothermia (n=10) children. Children undergoing diagnostic lumbar puncture (n=5) were controls. ADMA was present at a quantifiable level in all samples. Mean ADMA levels were significantly increased in normothermic TBI children compared to control (0.19± 0.08 μmol/L and 0.11± 0.02μmol/L respectively, p=0.01), and hypothermic children had significantly reduced mean ADMA levels (0.11 ± 0.05 μmol/L) vs. normothermic (p=0.03) measured on day 3. Patient demographics including age, gender, and NO levels (measured as nitrite and nitrate using liquid chromatography coupled with Griess reaction) did not significantly differ between normothermia and hypothermia groups. Also, NO levels did not correlate with ADMA concentrations. Conclusions ADMA levels were significantly increased in the CSF of TBI children. Early hypothermia attenuated this increase. The implications of attenuated ADMA on

  18. Lipoic Acid Decreases Inflammation and Confers Neuroprotection in Experimental Autoimmune Optic Neuritis

    PubMed Central

    Chaudhary, Priya; Marracci, Gail; Yu, Xiaolin; Galipeau, Danielle; Morris, Brooke; Bourdette, Dennis

    2016-01-01

    Lipoic acid (LA) is an antioxidant that is effective in treating experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). C57BL/6 mice with EAE develop experimental autoimmune optic neuritis (EAON), which models acute optic neuritis in humans. Here we determined whether LA is therapeutically effective in EAON. We immunized C57BL/6 mice with MOG 35–55 peptide. Mice received either daily subcutaneous injections of LA (100 mg/kg) or saline in early or late suppression paradigms. In the early suppression paradigm, optic nerve cross sections showed 14.9 ± 3.8% (mean ± SEM) damage in mice receiving saline (n = 7) and 2.0 ± 0.4 % damage in mice given LA (n = 7, p = 0.001). In the late suppression paradigm, optic nerve sections showed 24.6 ± 3.5% damage in mice treated with saline (n = 7) and 8.4 ± 2.5% in mice treated with LA (n = 7, p = 0.004). Thus a dramatic reduction in axonal injury was seen after LA administration in both experimental paradigms. Compared with saline treated mice with EAON, optic nerves from mice receiving LA had significantly fewer CD4+ and CD11b+ cells in both paradigms. This study provides a rationale for investigating the therapeutic efficacy of LA in acute optic neuritis in humans. PMID:21215462

  19. Selenium supplementation restores the decreased albumin level of peripheral blood mononuclear cells in streptozotocin-induced diabetic mice.

    PubMed

    Ahn, Taeho; Bae, Chun-Sik; Yun, Chul-Ho

    2016-05-01

    Previously, it has been suggested that the phenotypic level of albumin in peripheral blood mononuclear cells (PBMC) decreased in streptozotocin (STZ)-induced diabetic rats. Concomitantly, the production of oxidative stresses was also elevated in the diabetic PBMC compared to that of normal control. These results suggest the close relationship between PBMC-albumin and its antioxidant roles. Here, we expanded the previous studies and investigated the effect of selenium supplementation as inorganic (sodium selenate) forms on the levels of albumin expression and oxidative stress in PBMC of STZ-induced diabetic mice. Selenium intake recovered the decreased albumin levels to those of normal mice and reduced the production of reactive oxygen species (ROS). These results support that selenium intake may alleviate the etiology and pathology of PBMC in type 1 diabetic mice by restoring the decrease in albumin contents and the production of ROS. PMID:26726102

  20. Selenium supplementation restores the decreased albumin level of peripheral blood mononuclear cells in streptozotocin-induced diabetic mice

    PubMed Central

    AHN, Taeho; BAE, Chun-Sik; YUN, Chul-Ho

    2016-01-01

    Previously, it has been suggested that the phenotypic level of albumin in peripheral blood mononuclear cells (PBMC) decreased in streptozotocin (STZ)-induced diabetic rats. Concomitantly, the production of oxidative stresses was also elevated in the diabetic PBMC compared to that of normal control. These results suggest the close relationship between PBMC-albumin and its antioxidant roles. Here, we expanded the previous studies and investigated the effect of selenium supplementation as inorganic (sodium selenate) forms on the levels of albumin expression and oxidative stress in PBMC of STZ-induced diabetic mice. Selenium intake recovered the decreased albumin levels to those of normal mice and reduced the production of reactive oxygen species (ROS). These results support that selenium intake may alleviate the etiology and pathology of PBMC in type 1 diabetic mice by restoring the decrease in albumin contents and the production of ROS. PMID:26726102

  1. Tranexamic acid decreases blood loss during transurethral resection of the prostate (TUR -P)

    PubMed Central

    Kumsar, Şükrü; Dirim, Ayhan; Toksöz, Serdar; Sağlam, Hasan S.

    2011-01-01

    Introduction Postoperative blood loss after prostate surgery is thought to be associated with an increase in urinary fibrinolytic activity. Tranexamic acid (TXA) is both a potent inhibitor of plasminogen and urokinase activators and a low molecular weight substance that is excreted unchanged in the urinary tract and can be administered both orally and intravenously. We investigated the effect of TXA on the amount of blood loss during transurethral resection of the prostate (TURP). Materials and methods Forty patients with registry numbers ending in even numbers were allocated to the treatment group; those ending in odd numbers were used as controls and received no treatment. The treatment group received 10 mg/kg TXA by intravenous infusion during the first half hour of the operation, while the control group of patients received no medication. Serum hemoglobin was measured before and after surgery. The volume and hemoglobin concentration of the irrigation fluid, resected prostate weight, and duration of resection were recorded. Results The mean loss of hemoglobin per gram of resected prostate tissue was 1.25 g in the TXA group and 2.84 g in the control group. Total hemoglobin loss in the irrigating fluid and hemoglobin loss per 1 gram of prostate tissue was lower in the group of patients given TXA than in the control group (p = 0.018 and p <0.001). Conclusion Reduced bleeding during TURP as a result of TXA treatment may lead to better surgical conditions and, as a consequence, shorter operative times and lower irrigating fluid volumes. PMID:24578884

  2. Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence: correlation with plasma testosterone levels

    SciTech Connect

    Kirkland, R.T.; Keenan, B.S.; Probstfield, J.L.; Patsch, W.; Lin, T.L.; Clayton, G.W.; Insull, W. Jr.

    1987-01-23

    A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate. Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant of plasma HDL-C levels during pubertal development.

  3. Significance of decreased serum interleukin-10 levels in the progression of cerebral infarction.

    PubMed

    Diao, Zeng-Yan; Wang, Cui-Lan; Qi, Hong-Shun; Jia, Guo-Yong; Yan, Chuan-Zhu

    2016-05-01

    Anti-inflammatory cytokine and its serological detection may have an important role in the process of cardiovascular and cerebrovascular diseases. We investigated whether serum interleukin-10 (IL-10) is associated with cerebral infarction or not in the general population. Identified comprehensive searching was performed covering PubMed, EMBASE, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine, and China National Knowledge Infrastructure databases. Two reviewers extracted data and assessed studies independently. Information was extracted separately and classed into Asians and Caucasians. Summary standardized mean differences (SMDs) with 95 % confidence intervals (CI) were used with the utilization of Z test. Nine studies ranged from 2003 to 2014 were collected for meta-analysis. Results identified a negative association between serum IL-10 levels and cerebral infarction (SMD = 1.80, 95 % CI 0.79-2.81, P < 0.001). Country-subgroup analysis showed that low IL-10 level may be the main risk factor for cerebral infarction in India (SMD = 1.44, 95 % CI 1.13-1.75, P < 0.001) and Croatia (SMD = 2.96, 95 % CI 2.48-3.44, P < 0.001). In the ethnicity-stratified subgroup analysis, serum IL-10 levels were negatively correlated with cerebral infarction in Asians (SMD = 2.52, 95 % CI 0.47-4.57, P = 0.016), while not in Caucasians (P > 0.05). The lower serum IL-10 concentration was significantly associated with an increased likelihood of cerebral infarction in this meta-analysis. More prospective studies should be conducted to provide stronger evidence justifying the use of IL-10 as new biomarker to identify a predisposition toward cerebral infarction. PMID:25847570

  4. Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation.

    PubMed

    Silaste, Marja-Leena; Alfthan, Georg; Aro, Antti; Kesäniemi, Y Antero; Hörkkö, Sohvi

    2007-12-01

    High dietary intakes of tomato products are often associated with a reduced risk of CVD, but the atheroprotective mechanisms have not been established. This study was conducted to investigate the effects of increased dietary intake of tomato products on plasma lipids and LDL oxidation. The diet intervention included a baseline period, a 3-week low tomato diet (no tomato products allowed) and a 3-week high tomato diet (400 ml tomato juice and 30 mg tomato ketchup daily). Twenty-one healthy study subjects participated in the study. Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet. The changes in total and LDL cholesterol concentrations correlated significantly with the changes in serum lycopene (r 0.56, P = 0.009; r 0.60, P = 0.004, total and LDL, respectively), beta-carotene (r 0.58, P = 0.005; r 0.70, P < 0.001) and gamma-carotene concentrations (r 0.64, P = 0.002; r 0.64, P = 0.002). The level of circulating LDL to resist formation of oxidized phospholipids increased 13 % (P = 0.02) in response to the high tomato diet. In conclusion, a high dietary intake of tomato products had atheroprotective effects, it significantly reduced LDL cholesterol levels, and increased LDL resistance to oxidation in healthy normocholesterolaemic adults. These atheroprotective features associated with changes in serum lycopene, beta-carotene and gamma-carotene levels. PMID:17617941

  5. Creatine kinase and alpha-actin mRNA levels decrease in diabetic rat hearts

    SciTech Connect

    Popovich, B.; Barrieux, A.; Dillmann, W.H.

    1987-05-01

    Diabetic cardiomyopathy is associated with cardiac atrophy and isoenzyme redistribution. To determine if tissue specific changes occur in mRNAs coding for ..cap alpha..-actin and creatine kinase (CK), they performed RNA blot analysis. Total ventricular RNA from control (C) and 4 wk old diabetic (D) rats were hybridized with /sup 32/P cDNA probes for ..cap alpha..-actin and CK. A tissue independent cDNA probe, CHOA was also used. Signal intensity was quantified by photodensitometry. D CK mRNA was 47 +/- 16% lower in D vs C. Insulin increases CK mRNA by 20% at 1.5 hs, and completely reverses the deficit after 4 wks. D ..cap alpha..-actin mRNA is 66 +/- 18% lower in D vs C. Insulin normalized ..cap alpha..-actin mRNA by 5 hs. CHOA mRNA is unchanged in D vs C, but D + insulin CHOA mRNA is 30 +/- 2% lower than C. In rats with diabetic cardiomyopathy, muscle specific CK and ..cap alpha..-actin mRNAs are decreased. Insulin treatment reverses these changes.

  6. Regulation of Invertase Levels in Avena Stem Segments by Gibberellic Acid, Sucrose, Glucose, and Fructose 1

    PubMed Central

    Kaufman, Peter B.; Ghosheh, Najati S.; Lacroix, J. Donald; Soni, Sarvjit L.; Ikuma, Hiroshi

    1973-01-01

    Gibberellic acid and sucrose play significant roles in the increases in invertase and growth in Avena stem segments. About 80% of invertase is readily solubilized, whereas the rest is in the cell wall fraction. The levels of both types of invertase change in a similar manner in the response to gibberellic acid and sucrose treatment. The work described here was carried out with only the soluble enzyme. In response to a treatment, the level of invertase activity typically follows a pattern of increase followed by decrease; the increase in activity is approximately correlated with the active growth phase, whereas the decrease in activity is initiated when growth of the segments slows. A continuous supply of gibberellic acid retards the decline of enzyme activity. When gibberellic acid was pulsed to the segments treated with or without sucrose, the level of invertase activity increased at least twice as high in the presence of sucrose as in its absence, but the lag period is longer with sucrose present. Cycloheximide treatments effectively abolish the gibberellic acid-promoted growth, and the level of enzyme activity drops rapidly. Decay of invertase activity in response to cycloheximide treatment occurs regardless of gibberellic acid or sucrose treatment or both, and it is generally faster when the inhibitor is administered at the peak of enzyme induction than when given at its rising phase. Pulses with sucrose, glucose, fructose, or glucose + fructose elevate the level of invertase significantly with a lag of about 5 to 10 hours. The increase in invertase activity elicited by a sucrose pulse is about one-third that caused by a gibberellic acid pulse given at a comparable time during mid-phase of enzyme induction, and the lag before the enzyme activity increases is nearly twice as long for sucrose as for gibberellic acid. Moreover, the gibberellic acid pulse results in about three times more growth than the sucrose pulse. Our studies support the view that gibberellic

  7. Human mast cells decrease SLPI levels in type II – like alveolar cell model, in vitro

    PubMed Central

    Hollander, Camilla; Nyström, Max; Janciauskiene, Sabina; Westin, Ulla

    2003-01-01

    Background Mast cells are known to accumulate at sites of inflammation and upon activation to release their granule content, e.g. histamine, cytokines and proteases. The secretory leukocyte protease inhibitor (SLPI) is produced in the respiratory mucous and plays a role in regulating the activity of the proteases. Result We have used the HMC-1 cell line as a model for human mast cells to investigate their effect on SLPI expression and its levels in cell co-culture experiments, in vitro. In comparison with controls, we found a significant reduction in SLPI levels (by 2.35-fold, p < 0.01) in a SLPI-producing, type II-like alveolar cell line, (A549) when co-cultured with HMC-1 cells, but not in an HMC-1-conditioned medium, for 96 hours. By contrast, increased SLPI mRNA expression (by 1.58-fold, p < 0.05) was found under the same experimental conditions. Immunohistochemical analysis revealed mast cell transmigration in co-culture with SLPI-producing A549 cells for 72 and 96 hours. Conclusion These results indicate that SLPI-producing cells may assist mast cell migration and that the regulation of SLPI release and/or consumption by mast cells requires interaction between these cell types. Therefore, a "local relationship" between mast cells and airway epithelial cells might be an important step in the inflammatory response. PMID:12952550

  8. Relationship between Uric Acid Level and Achievement Motivation. Final Report.

    ERIC Educational Resources Information Center

    Mueller, Ernst F.; French, John R. P., Jr.

    In an investigation of the relationship of uric acid (a metabolic end product) to achievement, this study hypothesized that a person's serum urate level (a factor often associated with gout) is positively related to achievement need as well as indicators of actual achievement. (Speed of promotion and number of yearly publications were chosen as…

  9. Caffeic acid phenethyl ester decreases cholangiocarcinoma growth by inhibition of NF-κB and induction of apoptosis

    PubMed Central

    Onori, Paolo; DeMorrow, Sharon; Gaudio, Eugenio; Franchitto, Antonio; Mancinelli, Romina; Venter, Julie; Kopriva, Shelley; Ueno, Yoshiyuki; Alvaro, Domenico; Savage, Jennifer; Alpini, Gianfranco; Francis, Heather

    2011-01-01

    Caffeic acid phenethyl ester (CAPE) inhibits the growth of tumor cells and is a known inhibitor of NF-κB that is constitutively active in cholangiocarcinoma (CCH) cells. We evaluated the effects of CAPE on CCH growth both in vitro and in vivo. Inhibition of NF-κB DNA-binding activity was confirmed in nuclear extracts treated with CAPE at 50, 40 and 20 μM. CAPE decreases the expression of NF-κB1 (p50) and RelA (p65). CAPE decreased the growth of a number of CCH cells but not normal cholangiocytes. Cell cycle decrease was seen by a decrease in PCNA protein expression and the number of BrdU-positive cells treated with CAPE at 20 μM compared to vehicle. Inhibition of growth and increased cell cycle arrest of Mz-ChA-1 cells by CAPE were coupled with increased apoptosis. Bax expression was increased, whereas Bcl-2 was decreased in cells treated with CAPE compared to vehicle. In vivo studies were performed in BALB/c nude (nu/nu) mice implanted subcutaneously with Mz-ChA-1 cells and treated with daily IP injections of DMSO or CAPE (10 mg/kg body weight in DMSO) for 77 days. Tumor growth was decreased and tumor latency was increased 2-fold in CAPE compared to vehicle-treated nude mice. In tumor samples, decreased CCH growth by CAPE was coupled with increased apoptosis. CAPE both in vivo and in vitro decreases the growth of cholangiocarcinoma cells by increasing apoptosis. These results demonstrate that CAPE might be an important therapeutic tool in the treatment of CCH. PMID:19358267

  10. Novel thigmomorphogenetic responses in Carica papaya: touch decreases anthocyanin levels and stimulates petiole cork outgrowths

    PubMed Central

    Porter, Brad W.; Zhu, Yun J.; Webb, David T.; Christopher, David A.

    2009-01-01

    Background and Aims Because of its rapid growth rate, relative ease of transformation, sequenced genome and low gene number relative to Arabidopsis, the tropical fruit tree, Carica papaya, can serve as a complementary genetic model for complex traits. Here, new phenotypes and touch-regulated gene homologues have been identified that can be used to advance the understanding of thigmomorphogenesis, a multigenic response involving mechanoreception and morphological change. Methods Morphological alterations were quantified, and microscopy of tissue was conducted. Assays for hypocotyl anthocyanins, lignin and chlorophyll were performed, and predicted genes from C. papaya were compared with Arabidopsis touch-inducible (TCH) and Mechanosensitive channel of Small conductance-like genes (MscS-like or MSL). In addition, the expression of two papaya TCH1 homologues was characterized. Key Results On the abaxial side of petioles, treated plants were found to have novel, hypertrophic outgrowths associated with periderm and suberin. Touched plants also had higher lignin, dramatically less hypocotyl anthocyanins and chlorophyll, increased hypocotyl diameter, and decreased leaf width, stem length and root fresh weight. Papaya was found to have fewer MSL genes than Arabidopsis, and four touch-regulated genes in Arabidopsis had no counterparts in papaya. Water-spray treatment was found to enhance the expression of two papaya TCH1 homologues whereas induction following touch was only slightly correlated. Conclusions The novel petiole outgrowths caused by non-wounding, mechanical perturbation may be the result of hardening mechanisms, including added lignin, providing resistance against petiole movement. Inhibition of anthocyanin accumulation following touch, a new phenotypic association, may be caused by diversion of p-coumaroyl CoA away from chalcone synthase for lignin synthesis. The absence of MSL and touch-gene homologues indicates that papaya may have a smaller set of touch

  11. Decreased tryptophan and increased kynurenine levels in mastocytosis associated with digestive symptoms.

    PubMed

    Georgin-Lavialle, S; Launay, J-M; Côté, F; Soucié, E; Soria, A; Damaj, G; Moura, D S; Canioni, D; Hanssens, K; Chandesris, M-O; Barète, S; Dubreuil, P; Lortholary, O; Hermine, O; Sokol, H

    2016-03-01

    The main metabolism pathway of tryptophan is protein formation, but it can also be metabolized into serotonin and kynurenine. Indoleamine 2,3-dioxygenase (IDO) is the enzyme that catalyzes the degradation of tryptophan into kynurenine. Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in various tissues with 57% of patients having gastrointestinal involvement. We studied tryptophan metabolism in mastocytosis patients displaying or not gastrointestinal features and healthy subjects (n = 26 in each group). Mastocytosis patients with digestive symptoms displayed significantly increased kynurenine level and IDO activity as compared to healthy controls and mastocytosis patients without digestive symptoms. This could be linked to mast cell-mediated digestive inflammation among patients with mastocytosis. This work is the first focusing on kynurenine pathway in a mast cell disease and could help to understand the pathogenesis of digestive features in mastocytosis as well as in other mast cell-mediated diseases. PMID:26841279

  12. Decreased levels of peripheral leukocytes following sodium selenite treatment in female mice

    SciTech Connect

    Hogan, G.R.

    1986-08-01

    Selenium is known to be an essential micronutrient to a number of animal species (Schwarz 1961). Above its trace levels, however, selenium accumulation has long been known to induce deleterious conditions in domestic animals and in humans. Selenium has been reported to induce a hemolytic anemia, alter the configuration of plasma protein, reduce the synthesis of hemoglobin, depress packed red blood cell volume, and accumulate in renal and hepatic tissues. There are substantial data in regard to selenium effects on the erythrocyte component of peripheral blood, but there is an obvious deficiency in such information concerning the effects of selenium on the leukocyte component of blood. The major purpose of this investigation is to focus upon the effects of selenium on formed elements of the blood, and specifically, the leukocytes. Following three separate treatments of selenium, the number and class of peripheral leukocytes were determined as a function of time following administration of the selenium salt.

  13. Decreased Level of IgE is Associated with Breast Cancer and Allergic Diseases

    PubMed Central

    Zhang, Huayi; Guo, Gang; Jianzhong, Cao; Zheng, Yaqin

    2016-01-01

    Background The aim of this study was to explore the prevalence of type I allergic diseases in patients with breast cancer by carrying out a questionnaire survey and IgE detection in a healthy population and in patients with breast cancer. Material/Method There were 309 patients enrolled and they were further divided into the type I allergic disease group, the newly diagnosed breast cancer with type I allergic disease group, the re-visit breast cancer with type I allergic disease group, and the re-visit breast cancer without type I allergic disease group, as well as a healthy control group. Serum total IgE level was detected by immunoassay. Results The IgE value in the healthy population with type I allergic diseases (89.3±51.4 IU/ml) was significantly higher than in those without type I allergic diseases (45.6±65.1 IU/ml). There was no significant difference between IgE values in the re-visit breast cancer patients with type I allergic disease (25.1±65.1 IU/ml) and those without type I allergic disease (23.0±45.9 IU/ml). The area under the ROC curve was 0.618±0.04, sensitivity was 78%, specificity was 47.1%, Youden index was 0.251, and IgE threshold was 32.6 IU/ml. Conclusions The patients with newly diagnosed breast cancer were susceptible to type I allergic disease at about the same levels as in the healthy population. There was no correlation between breast cancer and type I allergic disease. PMID:26901362

  14. Total and free valproic acid: plasma level/dose ratio in monotherapy.

    PubMed

    Abadín, J A; Durán, J A; Sánchez, A; Serrano, J S

    1991-04-01

    Free plasma level/dose ratio of valproic acid (L/D-F) can be more effective than total plasma level/dose ratio (L/D-T) in adjusting dosage regimens. The influence of age, dose, and plasma concentration have been studied on L/D-T and L/D-F ratios. L/D-T and L/D-F ratios from 67 outpatients under long-term monotherapy were obtained. Analytical data was carried out by fluorescent polarized immunoassay. L/D-T and L/D-F ratios do not vary according to age. L/D-T and L/D-F ratios decreased while the dosage increased; both ratios increased with an increase in total plasma level of valproic acid. Significant differences were found between L/D-T and L/D-F ratios. Dose and interindividual variations are the factors which most influence L/D ratios of valproic acid. PMID:2051846

  15. cGMP decreases surface NKCC2 levels in the thick ascending limb: role of phosphodiesterase 2 (PDE2)

    PubMed Central

    Ares, Gustavo R.; Caceres, Paulo; Alvarez-Leefmans, Francisco J.; Ortiz, Pablo A.

    2008-01-01

    NaCl absorption in the medullary thick ascending limb of the loop of Henle (THAL) is mediated by the apical Na/K/2Cl cotransporter (NKCC2). Hormones that increase cGMP, such as nitric oxide (NO) and natriuretic peptides, decrease NaCl absorption by the THAL. However, the mechanism by which cGMP decreases NaCl absorption in THALs is not known. We hypothesized that cGMP decreases surface NKCC2 levels in the THAL. We used surface biotinylation to measure surface NKCC2 levels in rat THAL suspensions. We tested the effect of the membrane-permeant cGMP analog dibutyryl-cGMP (db-cGMP) on surface NKCC2 levels. Incubating THALs with db-cGMP for 20 min decreased surface NKCC2 levels in a concentration-dependent manner (basal = 100%; db-cGMP 100 μM = 77 ± 7%; 500 μM = 54 ± 10% and 1,000 μM = 61 ± 8%). A different cGMP analog 8-bromo-cGMP (8-Br-cGMP) also decreased surface NKCC2 levels by 25%, (basal = 100%; 8-Br-cGMP = 75 ± 5%). Incubation of isolated, perfused THALs with db-cGMP decreased apical surface NKCC2 labeling levels as measured by immunofluorescence and confocal microscopy. cGMP-stimulated phosphodiesterase 2 (PDE2) mediates the inhibitory effect of NO on NaCl absorption by THALs. Thus we examined the role of PDE2 and found that PDE2 inhibitors blocked the effect of db-cGMP on surface NKCC2. Also, a nonstimulatory concentration of db-cAMP blocked the cGMP-induced decrease in surface NKCC2. Finally, db-cGMP inhibited THAL net Cl absorption by 48 ± 4%, and this effect was completely blocked by PDE2 inhibition. We conclude that cGMP decreases NKCC2 levels in the apical membrane of THALs and that this effect is mediated by PDE2. This is an important mechanism by which cGMP inhibits NaCl absorption by the THAL. PMID:18684888

  16. Sevelamer Does Not Decrease Lipopolysaccharide or Soluble CD14 Levels But Decreases Soluble Tissue Factor, Low-Density Lipoprotein (LDL) Cholesterol, and Oxidized LDL Cholesterol Levels in Individuals With Untreated HIV Infection

    PubMed Central

    Sandler, Netanya G.; Zhang, Xinyan; Bosch, Ronald J.; Funderburg, Nicholas T.; Choi, Andrew I.; Robinson, Janet K.; Fine, Derek M.; Coombs, Robert W.; Jacobson, Jeffrey M.; Landay, Alan L.; Douek, Daniel C.; Tressler, Randall; Read, Sarah W.; Wilson, Cara C.; Deeks, Steven G.; Lederman, Michael M.; Gandhi, Rajesh T.

    2014-01-01

    Abnormal levels of inflammation are associated with cardiovascular disease and mortality in human immunodeficiency virus (HIV)–infected patients. Microbial translocation, which may cause inflammation, is decreased by sevelamer in patients undergoing hemodialysis. In this single-arm study, we evaluated the effects of 8 weeks of sevelamer therapy on 36 HIV-infected subjects who were not receiving antiretroviral therapy. Sevelamer did not significantly change markers of microbial translocation, inflammation, or T-cell activation. During sevelamer treatment, however, levels of soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol decreased significantly, whereas D-dimer levels increased. Thus, in this study population, sevelamer did not reduce microbial translocation but may have yielded cardiovascular benefits. Clinical Trials Registration. NCT 01543958. PMID:24864123

  17. Decreasing Enterobacter sakazakii (Cronobacter spp.) food contamination level with bacteriophages: prospects and problems

    PubMed Central

    Zuber, Sophie; Boissin‐Delaporte, Catherine; Michot, Lise; Iversen, Carol; Diep, Benjamin; Brüssow, Harald; Breeuwer, Pieter

    2008-01-01

    Summary Enterobacter sakazakii (Cronobacter spp.) is an opportunistic pathogen, which can cause rare, but life‐threatening infections in neonates and infants through feeding of a contaminated milk formula. We isolated 67 phages from environmental samples and tested their lytic host range on a representative collection of 40 E. sakazakii strains. A cocktail of five phages prevented the outgrowth of 35 out of 40 test strains in artificially contaminated infant formula. Two E. sakazakii phages represented prolate head Myoviridae. Molecular tests identified them as close relatives of Escherichia coli phage T4. The remaining three phages represented isometric head Myoviridae with large genome size of 140 and 200 kb, respectively, which belonged to two different DNA hybridization groups. A high dose of 108 pfu ml−1 of phage could effectively sterilize a broth contaminated with both high and low pathogen counts (106 and 102 cfu ml−1). In contrast, broth inoculated with 104 phage and 102 bacteria per ml first showed normal bacterial growth until reaching a cell titre of 105 cfu ml−1. Only when crossing this threshold, phage replication started, but it could not reduce the contamination level below 100 cfu ml−1. Phages could be produced with titres of 1010 pfu ml−1 in broth culture, but they were not stable upon freeze‐drying. Addition of trehalose or milk formula stabilized the phage preparation, which then showed excellent storage stability even at elevated temperature. PMID:21261874

  18. Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits

    PubMed Central

    Acosta-Alvear, Diego; Cho, Min Y; Wild, Thomas; Buchholz, Tonia J; Lerner, Alana G; Simakova, Olga; Hahn, Jamie; Korde, Neha; Landgren, Ola; Maric, Irina; Choudhary, Chunaram; Walter, Peter; Weissman, Jonathan S; Kampmann, Martin

    2015-01-01

    Hallmarks of cancer, including rapid growth and aneuploidy, can result in non-oncogene addiction to the proteostasis network that can be exploited clinically. The defining example is the exquisite sensitivity of multiple myeloma (MM) to 20S proteasome inhibitors, such as carfilzomib. However, MM patients invariably acquire resistance to these drugs. Using a next-generation shRNA platform, we found that proteostasis factors, including chaperones and stress-response regulators, controlled the response to carfilzomib. Paradoxically, 19S proteasome regulator knockdown induced resistance to carfilzomib in MM and non-MM cells. 19S subunit knockdown did not affect the activity of the 20S subunits targeted by carfilzomib nor their inhibition by the drug, suggesting an alternative mechanism, such as the selective accumulation of protective factors. In MM patients, lower 19S levels predicted a diminished response to carfilzomib-based therapies. Together, our findings suggest that an understanding of network rewiring can inform development of new combination therapies to overcome drug resistance. DOI: http://dx.doi.org/10.7554/eLife.08153.001 PMID:26327694

  19. Decreasing Enterobacter sakazakii (Cronobacter spp.) food contamination level with bacteriophages: prospects and problems.

    PubMed

    Zuber, Sophie; Boissin-Delaporte, Catherine; Michot, Lise; Iversen, Carol; Diep, Benjamin; Brüssow, Harald; Breeuwer, Pieter

    2008-11-01

    Enterobacter sakazakii (Cronobacter spp.) is an opportunistic pathogen, which can cause rare, but life-threatening infections in neonates and infants through feeding of a contaminated milk formula. We isolated 67 phages from environmental samples and tested their lytic host range on a representative collection of 40 E. sakazakii strains. A cocktail of five phages prevented the outgrowth of 35 out of 40 test strains in artificially contaminated infant formula. Two E. sakazakii phages represented prolate head Myoviridae. Molecular tests identified them as close relatives of Escherichia coli phage T4. The remaining three phages represented isometric head Myoviridae with large genome size of 140 and 200 kb, respectively, which belonged to two different DNA hybridization groups. A high dose of 10(8) pfu ml(-1) of phage could effectively sterilize a broth contaminated with both high and low pathogen counts (10(6) and 10(2) cfu ml(-1)). In contrast, broth inoculated with 10(4) phage and 10(2) bacteria per ml first showed normal bacterial growth until reaching a cell titre of 10(5) cfu ml(-1). Only when crossing this threshold, phage replication started, but it could not reduce the contamination level below 100 cfu ml(-1). Phages could be produced with titres of 10(10) pfu ml(-1) in broth culture, but they were not stable upon freeze-drying. Addition of trehalose or milk formula stabilized the phage preparation, which then showed excellent storage stability even at elevated temperature. PMID:21261874

  20. Suppression of Aflatoxin Biosynthesis in Aspergillus flavus by 2-Phenylethanol Is Associated with Stimulated Growth and Decreased Degradation of Branched-Chain Amino Acids.

    PubMed

    Chang, Perng-Kuang; Hua, Sui Sheng T; Sarreal, Siov Bouy L; Li, Robert W

    2015-10-01

    The saprophytic soil fungus Aspergillus flavus infects crops and produces aflatoxin. Pichia anomala, which is a biocontrol yeast and produces the major volatile 2-phenylethanol (2-PE), is able to reduce growth of A. flavus and aflatoxin production when applied onto pistachio trees. High levels of 2-PE are lethal to A. flavus and other fungi. However, at low levels, the underlying mechanism of 2-PE to inhibit aflatoxin production remains unclear. In this study, we characterized the temporal transcriptome response of A. flavus to 2-PE at a subinhibitory level (1 μL/mL) using RNA-Seq technology and bioinformatics tools. The treatment during the entire 72 h experimental period resulted in 131 of the total A. flavus 13,485 genes to be significantly impacted, of which 82 genes exhibited decreased expression. They included those encoding conidiation proteins and involved in cyclopiazonic acid biosynthesis. All genes in the aflatoxin gene cluster were also significantly decreased during the first 48 h treatment. Gene Ontology (GO) analyses showed that biological processes with GO terms related to catabolism of propionate and branched-chain amino acids (valine, leucine and isoleucine) were significantly enriched in the down-regulated gene group, while those associated with ribosome biogenesis, translation, and biosynthesis of α-amino acids OPEN ACCESS Toxins 2015, 7 3888 were over-represented among the up-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that metabolic pathways negatively impacted among the down-regulated genes parallel to those active at 30 °C, a condition conducive to aflatoxin biosynthesis. In contrast, metabolic pathways positively related to the up-regulated gene group resembled those at 37 °C, which favors rapid fungal growth and is inhibitory to aflatoxin biosynthesis. The results showed that 2-PE at a low level stimulated active growth of A. flavus but concomitantly rendered decreased activities in

  1. Suppression of Aflatoxin Biosynthesis in Aspergillus flavus by 2-Phenylethanol Is Associated with Stimulated Growth and Decreased Degradation of Branched-Chain Amino Acids

    PubMed Central

    Chang, Perng-Kuang; Hua, Sui Sheng T.; Sarreal, Siov Bouy L.; Li, Robert W.

    2015-01-01

    The saprophytic soil fungus Aspergillus flavus infects crops and produces aflatoxin. Pichia anomala, which is a biocontrol yeast and produces the major volatile 2-phenylethanol (2-PE), is able to reduce growth of A. flavus and aflatoxin production when applied onto pistachio trees. High levels of 2-PE are lethal to A. flavus and other fungi. However, at low levels, the underlying mechanism of 2-PE to inhibit aflatoxin production remains unclear. In this study, we characterized the temporal transcriptome response of A. flavus to 2-PE at a subinhibitory level (1 µL/mL) using RNA-Seq technology and bioinformatics tools. The treatment during the entire 72 h experimental period resulted in 131 of the total A. flavus 13,485 genes to be significantly impacted, of which 82 genes exhibited decreased expression. They included those encoding conidiation proteins and involved in cyclopiazonic acid biosynthesis. All genes in the aflatoxin gene cluster were also significantly decreased during the first 48 h treatment. Gene Ontology (GO) analyses showed that biological processes with GO terms related to catabolism of propionate and branched-chain amino acids (valine, leucine and isoleucine) were significantly enriched in the down-regulated gene group, while those associated with ribosome biogenesis, translation, and biosynthesis of α-amino acids were over-represented among the up-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that metabolic pathways negatively impacted among the down-regulated genes parallel to those active at 30 °C, a condition conducive to aflatoxin biosynthesis. In contrast, metabolic pathways positively related to the up-regulated gene group resembled those at 37 °C, which favors rapid fungal growth and is inhibitory to aflatoxin biosynthesis. The results showed that 2-PE at a low level stimulated active growth of A. flavus but concomitantly rendered decreased activities in branched-chain amino acid degradation

  2. Regular Exercise Training Increases the Number of Endothelial Progenitor Cells and Decreases Homocysteine Levels in Healthy Peripheral Blood

    PubMed Central

    Choi, Jeong Kyu; Moon, Ki Myung; Jung, Seok Yun; Kim, Ji Yong; Choi, Sung Hyun; Kim, Da Yeon; Kang, Songhwa; Chu, Chong Woo

    2014-01-01

    Endothelial progenitor cells (EPCs) are known to play an important role in the repair of damaged blood vessels. We used an endothelial progenitor cell colony-forming assay (EPC-CFA) to determine whether EPC numbers could be increased in healthy individuals through regular exercise training. The number of functional EPCs obtained from human peripheral blood-derived AC133 stem cells was measured after a 28-day regular exercise training program. The number of total endothelial progenitor cell colony-forming units (EPC-CFU) was significantly increased compared to that in the control group (p=0.02, n=5). In addition, we observed a significant decrease in homocysteine levels followed by an increase in the number of EPC-CFUs (p=0.04, n=5), indicating that the 28-day regular exercise training could increase the number of EPC colonies and decrease homocysteine levels. Moreover, an inverse correlation was observed between small-endothelial progenitor cell colony-forming units (small-EPC-CFUs) and plasma homocysteine levels in healthy men (r=-0.8125, p=0.047). We found that regular exercise training could increase the number of EPC-CFUs and decrease homocysteine levels, thus decreasing the cardiovascular disease risk in men. PMID:24757379

  3. Regulation of plasma lipoprotein levels by dietary triglycerides enriched with different fatty acids.

    PubMed

    Nicolosi, R J; Rogers, E J

    1997-11-01

    Saturated vegetable oils (coconut, palm, and palm kernel oil) containing predominantly saturated fatty acids, lauric (12:0) or myristic (14:0 and palmitic (16:0), raise plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in animals and humans, presumably by decreasing LDL receptor activity and/or increasing LDL-C production rate. Although stearic acid (18:0) is chemically a saturated fatty acid, both human and animal studies suggest it is biologically neutral (neither raising nor lowering) blood cholesterol levels. Although earlier studies indicated that medium chain fatty acids (8:0-10:0) were also thought to be neutral, more recent studies in animals and humans suggest otherwise. Unsaturated vegetable oils such as corn, soybean, olive, and canola oil, by virtue of their predominant levels of either linoleic acid (18:2) or oleic acid (18:1), are hypocholesterolemic, probably as a result of their ability to upregulate LDL receptor activity and/or decrease LDL-C production rate. Whether trans fatty acids such as trans oleate (t18:1), in hydrogenated products such as margarine, are hypercholesterolemic remains controversial. Studies in humans suggest that their cholesterol-raising potential falls between the native nonhydrogenated vegetable oil and the more saturated dairy products such as butter. Assessment of the magnitude of the cholesterolemic response of trans 18:1 is difficult because in most diet studies its addition is often at the expense of cholesterol-lowering unsaturated fatty acids, making an independent evaluation almost impossible. PMID:9372477

  4. ISOLATED MEDICAGO TRUNCATULA MUTANTS WITH INCREASED CALCIUM OXALATE CRYSTAL ACCUMULATION HAVE DECREASED ASCORBIC ACID LEVELS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mechanisms controlling oxalate biosynthesis and calcium oxalate formation in plants remains largely unknown. As an initial step toward gaining insight into these regulatory mechanisms we initiated a mutant screen to identify plants that over-accumulate crystals of calcium oxalate. Four new mut...

  5. Structure of a Microbial Community in Soil after Prolonged Addition of Low Levels of Simulated Acid Rain

    PubMed Central

    Pennanen, Taina; Fritze, Hannu; Vanhala, Pekka; Kiikkilä, Oili; Neuvonen, Seppo; Bååth, Erland

    1998-01-01

    Humus samples were collected 12 growing seasons after the start of a simulated acid rain experiment situated in the subarctic environment. The acid rain was simulated with H2SO4, a combination of H2SO4 and HNO3, and HNO3 at two levels of moderate acidic loads close to the natural anthropogenic pollution levels of southern Scandinavia. The higher levels of acid applications resulted in acidification, as defined by humus chemistry. The concentrations of base cations decreased, while the concentrations of exchangeable H+, Al, and Fe increased. Humus pH decreased from 3.83 to 3.65. Basal respiration decreased with decreasing humus pH, and total microbial biomass, measured by substrate-induced respiration and total amount of phospholipid fatty acids (PLFA), decreased slightly. An altered PLFA pattern indicated a change in the microbial community structure at the higher levels of acid applications. In general, branched fatty acids, typical of gram-positive bacteria, increased in the acid plots. PLFA analysis performed on the bacterial community growing on agar plates also showed that the relative amount of PLFA specific for gram-positive bacteria increased due to the acidification. The changed bacterial community was adapted to the more acidic environment in the acid-treated plots, even though bacterial growth rates, estimated by thymidine and leucine incorporation, decreased with pH. Fungal activity (measured as acetate incorporation into ergosterol) was not affected. This result indicates that bacteria were more affected than fungi by the acidification. The capacity of the bacterial community to utilize 95 different carbon sources was variable and only showed weak correlations to pH. Differences in the toxicities of H2SO4 and HNO3 for the microbial community were not found. PMID:9603831

  6. Inhibition of neutral sphingomyelinase decreases elevated levels of inducible nitric oxide synthase and apoptotic cell death in ocular hypertensive rats

    SciTech Connect

    Aslan, Mutay; Basaranlar, Goksun; Unal, Mustafa; Ciftcioglu, Akif; Derin, Narin; Mutus, Bulent

    2014-11-01

    Endoplasmic reticulum (ER) stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS2) have been implicated in the pathogenesis of neuronal retinal cell death in ocular hypertension. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression, hence this study determined the role of selective neutral sphingomyelinase (N-SMase) inhibition on retinal NOS2 levels, ER stress, apoptosis and visual evoked potentials (VEPs) in a rat model of elevated intraocular pressure (EIOP). NOS2 expression and retinal protein nitration were significantly greater in EIOP and significantly decreased with N-SMase inhibition. A significant increase was observed in retinal ER stress markers pPERK, CHOP and GRP78 in EIOP, which were not significantly altered by N-SMase inhibition. Retinal TUNEL staining showed increased apoptosis in all EIOP groups; however N-SMase inhibition significantly decreased the percent of apoptotic cells in EIOP. Caspase-3, -8 and -9 activities were significantly increased in EIOP and returned to baseline levels following N-SMase inhibition. Latencies of all VEP components were significantly prolonged in EIOP and shortened following N-SMase inhibition. Data confirm the role of nitrative injury in EIOP and highlight the protective effect of N-SMase inhibition in EIOP via down-regulation of NOS2 levels and nitrative stress. - Highlights: • Inhibition of N-SMase decreases NOS2 levels in ocular hypertension. • Inhibition of N-SMase decreases protein nitration in ocular hypertension. • Inhibition of N-SMase decreases caspase activation in ocular hypertension. • Inhibition of N-SMase decreases apoptosis in ocular hypertension.

  7. Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

    PubMed Central

    Zhao, Jin-Ping; Levy, Emile; Fraser, William D.; Julien, Pierre; Delvin, Edgard; Montoudis, Alain; Spahis, Schohraya; Garofalo, Carole; Nuyt, Anne Monique; Luo, Zhong-Cheng

    2014-01-01

    Background Arachidonic acid (AA; C20∶4 n-6) and docosahexaenoic acid (DHA; C22∶6 n-3) are important long-chain polyunsaturated fatty acids (LC-PUFA) in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally “programming” this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies. Methods and Principal Findings In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation) and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration) and beta-cell function (proinsulin-to-insulin ratio) in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids) were lower comparing newborns of gestational diabetic (n = 24) vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01). Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = −0.37, P <0.0001). The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity. Conclusion Low circulating DHA levels are associated with compromised

  8. Cochlear ablation effects on amino acid levels in the chinchilla cochlear nucleus.

    PubMed

    Godfrey, D A; Chen, K; Godfrey, M A; Lee, A C; Crass, S P; Shipp, D; Simo, H; Robinson, K T

    2015-06-25

    Inner ear damage can lead to hearing disorders, including tinnitus, hyperacusis, and hearing loss. We measured the effects of severe inner ear damage, produced by cochlear ablation, on the levels and distributions of amino acids in the first brain center of the auditory system, the cochlear nucleus. Measurements were also made for its projection pathways and the superior olivary nuclei. Cochlear ablation produces complete degeneration of the auditory nerve, which provides a baseline for interpreting the effects of partial damage to the inner ear, such as that from ototoxic drugs or intense sound. Amino acids play a critical role in neural function, including neurotransmission, neuromodulation, cellular metabolism, and protein construction. They include major neurotransmitters of the brain - glutamate, glycine, and γ-aminobutyrate (GABA) - as well as others closely related to their metabolism and/or functions - aspartate, glutamine, and taurine. Since the effects of inner ear damage develop over time, we measured the changes in amino acid levels at various survival times after cochlear ablation. Glutamate and aspartate levels decreased by 2weeks in the ipsilateral ventral cochlear nucleus and deep layer of the dorsal cochlear nucleus, with the largest decreases in the posteroventral cochlear nucleus (PVCN): 66% for glutamate and 63% for aspartate. Aspartate levels also decreased in the lateral part of the ipsilateral trapezoid body, by as much as 50%, suggesting a transneuronal effect. GABA and glycine levels showed some bilateral decreases, especially in the PVCN. These results may represent the state of amino acid metabolism in the cochlear nucleus of humans after removal of eighth nerve tumors, which may adversely result in destruction of the auditory nerve. Measurement of chemical changes following inner ear damage may increase understanding of the pathogenesis of hearing impairments and enable improvements in their diagnosis and treatment. PMID:25839146

  9. ASSOCIATIONS BETWEEN INCREASES IN PLASMA N-3 POLYUNSATURATED FATTY ACIDS FOLLOWING SUPPLEMENTATION AND DECREASES IN ANGER AND ANXIETY IN SUBSTANCE ABUSERS

    PubMed Central

    Buydens-Branchey, Laure; Branchey, Marc; Hibbeln, Joseph R.

    2008-01-01

    Objective Mounting evidence indicates that low levels of n-3 polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of a large number of psychiatric disorders. In light of the suboptimal n-3 PUFAs intake due to poor dietary habits among substance abusers and the strong associations between aggression, anxiety and substance use disorders we examined if insurance of adequate intakes of n-3 PUFAs with supplementation would decrease their anger and anxiety scores. Method Substance abusers (n=22) were assigned to either 3 g of n-3 PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or soybean oil in identically looking capsules. The trial was double-blind, randomized and lasted 3 months. Anger and anxiety scales were administered at baseline and once a month thereafter. Blood samples were collected at baseline and at the end of the trial. Results Patients' dietary intakes of n-3 PUFAs fell below recommended levels. Assignment to n-3 PUFA treatment was accompanied by significant decreases in anger and anxiety scores compared to placebo assignment. These changes were associated with increases in plasma levels of both EPA and DHA but an increase in EPA was more robustly correlated with low end-of-trial anxiety scores and an increase in DHA was more robustly correlated with low end-of-trial anger scores. Conclusion These pilot data indicate that ensuring adequate n-3 PUFA intake via supplementation benefits substance abusers by reducing their anger and anxiety levels. The strong correlations between an increase in plasma EPA and lower anxiety scores and between an increase in plasma DHA and lower anger scores suggests a need for the further exploration of the differential responses to these two n-3 PUFAs in different psychiatric conditions. PMID:18060675

  10. Glycodeoxycholic Acid Levels as Prognostic Biomarker in Acetaminophen-Induced Acute Liver Failure Patients

    PubMed Central

    Woolbright, Benjamin L.; McGill, Mitchell R.; Staggs, Vincent S.; Winefield, Robert D.; Gholami, Parviz; Olyaee, Mojtaba; Sharpe, Matthew R.; Curry, Steven C.; Lee, William M.; Jaeschke, Hartmut

    2014-01-01

    Acetaminophen (APAP)-induced acute liver failure (ALF) remains a major clinical problem. Although a majority of patients recovers after severe liver injury, a subpopulation of patients proceeds to ALF. Bile acids are generated in the liver and accumulate in blood during liver injury, and as such, have been proposed as biomarkers for liver injury and dysfunction. The goal of this study was to determine whether individual bile acid levels could determine outcome in patients with APAP-induced ALF (AALF). Serum bile acid levels were measured in AALF patients using mass spectrometry. Bile acid levels were elevated 5–80-fold above control values in injured patients on day 1 after the overdose and decreased over the course of hospital stay. Interestingly, glycodeoxycholic acid (GDCA) was significantly increased in non-surviving AALF patients compared with survivors. GDCA values obtained at peak alanine aminotransferase (ALT) and from day 1 of admission indicated GDCA could predict survival in these patients by receiver-operating characteristic analysis (AUC = 0.70 for day 1, AUC = 0.68 for peak ALT). Of note, AALF patients also had significantly higher levels of serum bile acids than patients with active cholestatic liver injury. These data suggest measurements of GDCA in this patient cohort modestly predicted outcome and may serve as a prognostic biomarker. Furthermore, accumulation of bile acids in serum or plasma may be a result of liver cell dysfunction and not cholestasis, suggesting elevation of circulating bile acid levels may be a consequence and not a cause of liver injury. PMID:25239633

  11. Comparison of oleic acid metabolism in the soybean (Glycine max (L. ) Merr. ) genotypes Williams and A5, a mutant with decreased linoleic acid in the seed

    SciTech Connect

    Martin, B.A.; Rinne, R.W.

    1986-05-01

    The metabolism of oleoyl coenzyme A (CoA) was examined in developing seed from two soybean (Glycine max (L.) Merr.) genotypes: Williams, a standard cultivar and A5, a mutant containing nearly twice the oleic acid (18:1) content of Williams. The in vitro rates of esterification of oleoyl-CoA to lysophosphatides by acyl-CoA: lysophosphatidylcholine acyltransferase was similar in both genotypes and lysophosphatidyl-ethanolamine was a poor substrate. Crude extracts desaturated exogenous (1-/sup 14/C)dioleoyl phosphatidylcholine at 14% of the rate achieved with (1-/sup 14/C)oleoyl-CoA, and 50 micromolar lysophosphaatidylcholine. The desaturase enzyme also required NADH for full activity. Extracts from Williams contained 1.5-fold more oleoyl phosphatidylcholine desaturase activity, on a fresh weight basis, than did A5 and appeared to have a similar affinity for oleoyl-CoA. There was 1.2- to 1.9-fold more linoleic acid (18:2) in phosphatidylcholine from Williams than from A5, measured at two stages of development, but both genotypes had a similar distribution of fatty acids in the one and two positions. Phosphatidylethanolamine in A5 contained relatively more linoleic acid (18:2) in the one position than did Williams. The increased oleic acid (18:1) content in A5 appeared to be a result of decreased rates of 18:1 desaturation of oleoyl-phosphatidylcholine in this genotype.

  12. High Level Waste System Impacts from Acid Dissolution of Sludge

    SciTech Connect

    KETUSKY, EDWARD

    2006-04-20

    This research evaluates the ability of OLI{copyright} equilibrium based software to forecast Savannah River Site High Level Waste system impacts from oxalic acid dissolution of Tank 1-15 sludge heels. Without further laboratory and field testing, only the use of oxalic acid can be considered plausible to support sludge heel dissolution on multiple tanks. Using OLI{copyright} and available test results, a dissolution model is constructed and validated. Material and energy balances, coupled with the model, identify potential safety concerns. Overpressurization and overheating are shown to be unlikely. Corrosion induced hydrogen could, however, overwhelm the tank ventilation. While pH adjustment can restore the minimal hydrogen generation, resultant precipitates will notably increase the sludge volume. OLI{copyright} is used to develop a flowsheet such that additional sludge vitrification canisters and other negative system impacts are minimized. Sensitivity analyses are used to assess the processability impacts from variations in the sludge/quantities of acids.

  13. A Novel Approach to Decrease Sialic Acid Expression in Cells by a C-3-modified N-Acetylmannosamine*

    PubMed Central

    Wratil, Paul R.; Rigol, Stephan; Solecka, Barbara; Kohla, Guido; Kannicht, Christoph; Reutter, Werner; Giannis, Athanassios; Nguyen, Long D.

    2014-01-01

    Due to its position at the outermost of glycans, sialic acid is involved in a myriad of physiological and pathophysiological cell functions such as host-pathogen interactions, immune regulation, and tumor evasion. Inhibitors of cell surface sialylation could be a useful tool in cancer, immune, antibiotic, or antiviral therapy. In this work, four different C-3 modified N-acetylmannosamine analogs were tested as potential inhibitors of cell surface sialylation. Peracetylated 2-acetylamino-2-deoxy-3-O-methyl-d-mannose decreases cell surface sialylation in Jurkat cells in a dose-dependent manner up to 80%, quantified by flow cytometry and enzyme-linked lectin assays. High-performance liquid chromatography experiments revealed that not only the concentration of membrane bound but also of cytosolic sialic acid is reduced in treated cells. We have strong evidence that the observed reduction of sialic acid expression in cells is caused by the inhibition of the bifunctional enzyme UDP-GlcNAc-2-epimerase/ManNAc kinase. 2-Acetylamino-2-deoxy-3-O-methyl-d-mannose inhibits the human ManNAc kinase domain of the UDP-GlcNAc-2-epimerase/ManNAc kinase. Binding kinetics of the inhibitor and human N-acetylmannosamine kinase were evaluated using surface plasmon resonance. Specificity studies with human N-acetylglucosamine kinase and hexokinase IV indicated a high specificity of 2-acetylamino-2-deoxy-3-O-methyl-d-mannose for MNK. This substance represents a novel class of inhibitors of sialic acid expression in cells, targeting the key enzyme of sialic acid de novo biosynthesis. PMID:25278018

  14. A novel approach to decrease sialic acid expression in cells by a C-3-modified N-acetylmannosamine.

    PubMed

    Wratil, Paul R; Rigol, Stephan; Solecka, Barbara; Kohla, Guido; Kannicht, Christoph; Reutter, Werner; Giannis, Athanassios; Nguyen, Long D

    2014-11-14

    Due to its position at the outermost of glycans, sialic acid is involved in a myriad of physiological and pathophysiological cell functions such as host-pathogen interactions, immune regulation, and tumor evasion. Inhibitors of cell surface sialylation could be a useful tool in cancer, immune, antibiotic, or antiviral therapy. In this work, four different C-3 modified N-acetylmannosamine analogs were tested as potential inhibitors of cell surface sialylation. Peracetylated 2-acetylamino-2-deoxy-3-O-methyl-D-mannose decreases cell surface sialylation in Jurkat cells in a dose-dependent manner up to 80%, quantified by flow cytometry and enzyme-linked lectin assays. High-performance liquid chromatography experiments revealed that not only the concentration of membrane bound but also of cytosolic sialic acid is reduced in treated cells. We have strong evidence that the observed reduction of sialic acid expression in cells is caused by the inhibition of the bifunctional enzyme UDP-GlcNAc-2-epimerase/ManNAc kinase. 2-Acetylamino-2-deoxy-3-O-methyl-D-mannose inhibits the human ManNAc kinase domain of the UDP-GlcNAc-2-epimerase/ManNAc kinase. Binding kinetics of the inhibitor and human N-acetylmannosamine kinase were evaluated using surface plasmon resonance. Specificity studies with human N-acetylglucosamine kinase and hexokinase IV indicated a high specificity of 2-acetylamino-2-deoxy-3-O-methyl-D-mannose for MNK. This substance represents a novel class of inhibitors of sialic acid expression in cells, targeting the key enzyme of sialic acid de novo biosynthesis. PMID:25278018

  15. Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver.

    PubMed

    Lickteig, Andrew J; Csanaky, Iván L; Pratt-Hyatt, Matthew; Klaassen, Curtis D

    2016-06-01

    Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect of CAR activation on bile flow, BA profile, as well as expression of BA synthesis and transport genes. Synthetic CAR ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was administered to mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). CAR activation decreases total BAs in livers of male (49%) and female mice (26%), largely attributable to decreases of the 12α-hydroxylated BA taurocholic acid (T-CA) (males (M) 65%, females (F) 45%). Bile flow in both sexes was increased by CAR activation, and the increases were BA-independent. CAR activation did not alter biliary excretion of total BAs, but overall BA composition changed. Excretion of muricholic (6-hydroxylated) BAs was increased in males (101%), and the 12α-OH proportion of biliary BAs was decreased in both males (37%) and females (28%). The decrease of T-CA in livers of males and females correlates with the decreased mRNA of the sterol 12α-hydroxylase Cyp8b1 in males (71%) and females (54%). As a response to restore BAs to physiologic concentrations in liver, mRNA of Cyp7a1 is upregulated following TCPOBOP (males 185%, females 132%). In ilea, mRNA of the negative feedback regulator Fgf15 was unaltered by CAR activation, indicating biliary BA excretion was sufficient to maintain concentrations of total BAs in the small intestine. In summary, the effects of CAR activation on BAs in male and female mice are quite similar, with a marked decrease in the major BA T-CA in the liver. PMID:26984780

  16. Exogenous abscisic acid application decreases cadmium accumulation in Arabidopsis plants, which is associated with the inhibition of IRT1-mediated cadmium uptake

    PubMed Central

    Fan, Shi Kai; Fang, Xian Zhi; Guan, Mei Yan; Ye, Yi Quan; Lin, Xian Yong; Du, Shao Ting; Jin, Chong Wei

    2014-01-01

    Cadmium (Cd) contamination of agricultural soils is an increasingly serious problem. Measures need to be developed to minimize Cd entering the human food chain from contaminated soils. We report here that, under Cd exposure condition, application with low doses of (0.1–0.5 μM) abscisic acid (ABA) clearly inhibited Cd uptake by roots and decreased Cd level in Arabidopsis wild-type plants (Col-0). Expression of IRT1 in roots was also strongly inhibited by ABA treatment. Decrease in Cd uptake and the inhibition of IRT1 expression were clearly lesser pronounced in an ABA-insensitive double mutant snrk2.2/2.3 than in the Col-0 in response to ABA application. The ABA-decreased Cd uptake was found to correlate with the ABA-inhibited IRT1 expression in the roots of Col-0 plants fed two different levels of iron. Furthermore, the Cd uptake of irt1 mutants was barely affected by ABA application. These results indicated that inhibition of IRT1 expression is involved in the decrease of Cd uptake in response to exogenous ABA application. Interestingly, ABA application increased the iron level in both Col-0 plants and irt1 mutants, suggesting that ABA-increased Fe acquisition does not depend on the IRT1 function, but on the contrary, the ABA-mediated inhibition of IRT1 expression may be due to the elevation of iron level in plants. From our results, we concluded that ABA application might increase iron acquisition, followed by the decrease in Cd uptake by inhibition of IRT1 activity. Thus, for crop production in Cd contaminated soils, developing techniques based on ABA application potentially is a promising approach for reducing Cd accumulation in edible organs in plants. PMID:25566293

  17. Loss of Penumbra by Impaired Oxygen Supply? Decreasing Hemoglobin Levels Predict Infarct Growth after Acute Ischemic Stroke

    PubMed Central

    Kellert, L.; Herweh, C.; Sykora, M.; Gussmann, P.; Martin, E.; Ringleb, P.A.; Steiner, T.; Bösel, J.

    2012-01-01

    Background The association of mortality and poor outcome with reduced levels of hemoglobin (Hb) and hematocrit (Hct) in patients admitted for ischemic stroke was recently demonstrated. The mechanisms behind this have remained unclear. Aims Here, we aimed to investigate a putative association between low Hb and Hct levels and infarct growth. Methods All consecutive patients who received intravenous thrombolysis based on multimodal magnetic resonance imaging during the years 1998–2009 were screened. Laboratory data as well as admission magnetic resonance images and follow-up computed tomography scans of 257 patients were assessed. Overall, data of 100 patients were of sufficient quality and further analyzed. Results Decrease in Hb and Hct as well as perfusion-weighted imaging volume, mismatch volume, and final infarct size on follow-up computed tomography were associated with infarct growth. A linear regression model revealed Hb decrease (β = 0.23, p = 0.02) to be a predictor of infarct growth, independent of mismatch volume (β = 0.27, p = 0.004) and minimum sodium (β = -0.21, p = 0.03), and adjusted to the non-predicting variables age, National Institute of Health Stroke Scale score, maximum leucocytes and C-reactive protein, blood glucose, and Hct decrease. Conclusion Hb levels that decrease after admission independently predict infarct growth in thrombolyzed stroke patients. The clinical implications of this relationship remain to be investigated. PMID:23599701

  18. Lipopolysaccharide differentially decreases plasma acyl and desacyl ghrelin levels in rats: potential role of the circulating ghrelin acylating enzyme GOAT

    PubMed Central

    Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Reeve, Joseph R.; Taché, Yvette; Lambrecht, Nils W.G.

    2014-01-01

    Bacterial lipopolysaccharide (LPS) in rodents is an established model for studying innate immune responses to gram-negative bacteria and mimicking symptoms of infections including reduced food intake associated with decreased circulating total ghrelin levels. The ghrelin-acylating enzyme, ghrelin-O-acyltransferase (GOAT) involved in the formation of acyl ghrelin (AG) was recently identified. We investigated changes in circulating AG, desacyl ghrelin (DG) and GOAT induced by intraperitoneal LPS (100μg/kg) and associated changes in food intake. Plasma AG and total ghrelin were assessed by radioimmunoassay, GOAT protein by Western blot and mRNA by RT-qPCR. DG was derived from total minus AG. Plasma AG and DG were decreased at 2h, 5h and 7h (p<0.01) post injection compared to vehicle and recovered at 24h. At 2h there was a significantly greater decrease of AG (-53%) than DG (-28%) resulting in a decreased AG/DG ratio (1:5, p <0.01), which thereafter returned to pre-injection values (1:3). This altered ratio was associated with a 38% decrease in plasma GOAT protein compared to vehicle (p <0.001), whereas gastric GOAT protein was slightly increased by 10% (p<0.05). GOAT mRNA expression was unchanged. Food intake was reduced by 58% measured during the 1.5-2h period post LPS injection. Decreased plasma AG and DG preceded the rise in rectal temperature and blood glucose that peaked at 7h. These data indicate that LPS induces a long-lasting reduction of AG and DG levels that may have a bearing with the decrease in food intake. The faster drop in AG than DG within 2h is associated with reduced circulating GOAT. PMID:20599577

  19. Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease.

    PubMed

    Calon, Frédéric; Lim, Giselle P; Morihara, Takashi; Yang, Fusheng; Ubeda, Oliver; Salem, Norman; Frautschy, Sally A; Cole, Greg M

    2005-08-01

    Epidemiological data indicate that low n-3 polyunsaturated fatty acids (PFA) intake is a readily manipulated dietary risk factor for Alzheimer's disease (AD). Studies in animals confirm the deleterious effect of n-3 PFA depletion on cognition and on dendritic scaffold proteins. Here, we show that in transgenic mice overexpressing the human AD gene APPswe (Tg2576), safflower oil-induced n-3 PFA deficiency caused a decrease in N-methyl-D-aspartate (NMDA) receptor subunits, NR2A and NR2B, in the cortex and hippocampus with no loss of the presynaptic markers, synaptophysin and synaptosomal-associated protein 25 (SNAP-25). n-3 PFA depletion also decreased the NR1 subunit in the hippocampus and Ca2+/calmodulin-dependent protein kinase (CaMKII) in the cortex of Tg2576 mice. These effects of dietary n-3 PFA deficiency were greatly amplified in Tg2576 mice compared to nontransgenic mice. Loss of the NR2B receptor subunit was not explained by changes in mRNA expression, but correlated with p85alpha phosphatidylinositol 3-kinase levels. Most interestingly, n-3 PFA deficiency dramatically increased levels of protein fragments, corresponding to caspase/calpain-cleaved fodrin and gelsolin in Tg2576 mice. This effect was minimal in nontransgenic mice suggesting that n-3 PFA depletion potentiated caspase activation in the Tg2576 mouse model of AD. Dietary supplementation with docosahexaenoic acid (DHA; 22 : 6n-3) partly protected from NMDA receptor subunit loss and accumulation of fodrin and gelsolin fragments but fully prevented CaMKII decrease. The marked effect of dietary n-3 PFA on NMDA receptors and caspase/calpain activation in the cortex of an animal model of AD provide new insights into how dietary essential fatty acids may influence cognition and AD risk. PMID:16101743

  20. Childrens' learning and behaviour and the association with cheek cell polyunsaturated fatty acid levels.

    PubMed

    Kirby, A; Woodward, A; Jackson, S; Wang, Y; Crawford, M A

    2010-01-01

    Increasing interest in the role of omega-3 fatty acids in relation to neurodevelopmental disorders (e.g. ADHD, dyslexia, autism) has occurred as a consequence of some international studies highlighting this link. In particular, some studies have shown that children with ADHD may have lower concentrations of polyunsaturated fatty acids (PUFAs), particularly omega-3, in their red blood cells and plasma, and that supplementation with omega-3 fatty acids may alleviate behavioural symptoms in this population. However, in order to compare levels it seems appropriate to establish fatty acid levels in a mainstream school aged population and if levels relate to learning and behaviour. To date no study has established this. For this study, cheek cell samples from 411 typically developing school children were collected and analysed for PUFA content, in order to establish the range in this population. In addition, measures of general classroom attention and behaviour were assessed in these children by teachers and parents. Cognitive performance tests were also administered in order to explore whether an association between behaviour and/or cognitive performance and PUFA levels exists. Relationships between PUFA levels and socio-economic status were also explored. Measures of reading, spelling and intelligence did not show any association with PUFA levels, but some associations were noted with the level of omega-3 fatty acids and teacher and parental reports of behaviour, with some evidence that higher omega-3 levels were associated with decreased levels of inattention, hyperactivity, emotional and conduct difficulties and increased levels of prosocial behaviour. These findings are discussed in relation to previous findings from omega-3 supplementation studies with children. PMID:20172688

  1. Inhibition of mutant IDH1 decreases D-2-HG levels without affecting tumorigenic properties of chondrosarcoma cell lines

    PubMed Central

    Suijker, Johnny; Oosting, Jan; Koornneef, Annemarie; Struys, Eduard A.; Salomons, Gajja S.; Schaap, Frank G.; Waaijer, Cathelijn J.F.; Wijers-Koster, Pauline M.; Briaire-de Bruijn, Inge H.; Haazen, Lizette; Riester, Scott M.; Dudakovic, Amel; Danen, Erik; Cleton-Jansen, Anne-Marie; van Wijnen, Andre J.; Bovée, Judith V.M.G.

    2015-01-01

    Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found in a subset of benign and malignant cartilage tumors, gliomas and leukaemias. The mutant enzyme causes the production of D-2-hydroxyglutarate (D-2-HG), affecting CpG island and histone methylation. While mutations in IDH1/2 are early events in benign cartilage tumors, we evaluated whether these mutations play a role in malignant chondrosarcomas. Compared to IDH1/2 wildtype cell lines, chondrosarcoma cell lines harboring an endogenous IDH1 (n=3) or IDH2 mutation (n=2) showed up to a 100-fold increase in intracellular and extracellular D-2-HG levels. Specific inhibition of mutant IDH1 using AGI-5198 decreased levels of D-2-HG in a dose dependent manner. After 72 hours of treatment one out of three mutant IDH1 cell lines showed a moderate decrease in viability, while D-2-HG levels decreased >90%. Likewise, prolonged treatment (up to 20 passages) did not affect proliferation and migration. Furthermore, global gene expression, CpG island methylation as well as histone H3K4, -9, and -27 trimethylation levels remained unchanged. Thus, while IDH1/2 mutations cause enchondroma, malignant progression towards central chondrosarcoma renders chondrosarcoma growth independent of these mutations. Thus, monotherapy based on inhibition of mutant IDH1 appears insufficient for treatment of inoperable or metastasized chondrosarcoma patients. PMID:25895133

  2. FoxO1 Deacetylation Decreases Fatty Acid Oxidation in β-Cells and Sustains Insulin Secretion in Diabetes.

    PubMed

    Kim-Muller, Ja Young; Kim, Young Jung R; Fan, Jason; Zhao, Shangang; Banks, Alexander S; Prentki, Marc; Accili, Domenico

    2016-05-01

    Pancreatic β-cell dysfunction contributes to onset and progression of type 2 diabetes. In this state β-cells become metabolically inflexible, losing the ability to select between carbohydrates and lipids as substrates for mitochondrial oxidation. These changes lead to β-cell dedifferentiation. We have proposed that FoxO proteins are activated through deacetylation-dependent nuclear translocation to forestall the progression of these abnormalities. However, how deacetylated FoxO exert their actions remains unclear. To address this question, we analyzed islet function in mice homozygous for knock-in alleles encoding deacetylated FoxO1 (6KR). Islets expressing 6KR mutant FoxO1 have enhanced insulin secretion in vivo and ex vivo and decreased fatty acid oxidation ex vivo Remarkably, the gene expression signature associated with FoxO1 deacetylation differs from wild type by only ∼2% of the >4000 genes regulated in response to re-feeding. But this narrow swath includes key genes required for β-cell identity, lipid metabolism, and mitochondrial fatty acid and solute transport. The data support the notion that deacetylated FoxO1 protects β-cell function by limiting mitochondrial lipid utilization and raise the possibility that inhibition of fatty acid oxidation in β-cells is beneficial to diabetes treatment. PMID:26984405

  3. Dietary conjugated linoleic acids increase intramuscular fat deposition and decrease subcutaneous fat deposition in Yellow Breed × Simmental cattle.

    PubMed

    Zhang, Haibo; Dong, Xianwen; Wang, Zhisheng; Zhou, Aiming; Peng, Quanhui; Zou, Huawei; Xue, Bai; Wang, Lizhi

    2016-04-01

    This study was conducted to estimate the effect of dietary conjugated linoleic acids (CLA) on intramuscular and subcutaneous fat deposition in Yellow Breed × Simmental cattle. The experiment was conducted for 60 days. The results showed that the average backfat thickness, (testicles + kidney + pelvic) fat percentage and subcutaneous fat percentage in dietary CLA were significantly lower than in the control group, while intramuscular the fat percentage was significantly higher. Compared to the control group, the Longissimus muscle enzyme activities of lipoprotein lipase (LPL), fatty acid synthase (FAS) and acetyl-coenzyme A carboxylase (ACC) in dietary CLA and the subcutaneous fat enzyme activities of LPL, hormone-sensitive lipase (HSL) and carnitine palmitoyltransferase-1 (CPT-1) were significantly increased. Similarly, compared to the control group, the Longissimus muscle sterol regulatory element binding protein 1 (SREBP-1), FAS, stearoyl-coenzyme A desaturase (SCD), ACC, peroxisome proliferator-activated receptor γ (PPARγ), heart fatty-acid binding protein (H-FABP) and LPL gene expression in dietary CLA were significant increased, as were the subcutaneous fat of PPARγ, H-FABP, LPL, CPT-1 and HSL in dietary CLA. These results indicated that dietary CLA increases IMF deposition mainly by the up-regulation of lipogenic gene expression, while decreasing subcutaneous fat deposition mainly by the up-regulation of lipolytic gene expression. PMID:26582037

  4. β-Aminobutyric acid increases abscisic acid accumulation and desiccation tolerance and decreases water use but fails to improve grain yield in two spring wheat cultivars under soil drying

    PubMed Central

    Li, Feng-Min

    2012-01-01

    A pot experiment was conducted to investigate the effect of the non-protein amino acid, β-aminobutyric acid (BABA), on the homeostasis between reactive oxygen species (ROS) and antioxidant defence during progressive soil drying, and its relationship with the accumulation of abscisic acid (ABA), water use, grain yield, and desiccation tolerance in two spring wheat (Triticum aestivum L.) cultivars released in different decades and with different yields under drought. Drenching the soil with 100 µM BABA increased drought-induced ABA production, leading to a decrease in the lethal leaf water potential (Ψ) used to measure desiccation tolerance, decreased water use, and increased water use efficiency for grain (WUEG) under moderate water stress. In addition, at severe water stress levels, drenching the soil with BABA reduced ROS production, increased antioxidant enzyme activity, and reduced the oxidative damage to lipid membranes. The data suggest that the addition of BABA triggers ABA accumulation that acts as a non-hydraulic root signal, thereby closing stomata, and reducing water use at moderate stress levels, and also reduces the production of ROS and increases the antioxidant defence enzymes at severe stress levels, thus increasing the desiccation tolerance. However, BABA treatment had no effect on grain yield of wheat when water availability was limited. The results suggest that there are ways of effectively priming the pre-existing defence pathways, in addition to genetic means, to improve the desiccation tolerance and WUEG of wheat. PMID:22859677

  5. Schinus terebinthifolius Raddi extract and linoleic acid from Passiflora edulis synergistically decrease melanin synthesis in B16 cells and reconstituted epidermis.

    PubMed

    Jorge, A T S; Arroteia, K F; Santos, I A; Andres, E; Medina, S P H; Ferrari, C R; Lourenço, C B; Biaggio, R M T T; Moreira, P L

    2012-10-01

    Several treatments for skin whitening are available today, but few of them are completely adequate, especially owing to the carcinogenic potential attributed to classical drugs like hydroquinone, arbutin and kojic acid. To provide an alternative and safer technology for whitening, we developed two botanical compounds originated from Brazilian biodiversity, an extract of Schinus terebinthifolius Raddi and a linoleic acid fraction isolated from Passiflora edulis oil. The whitening effect of these compounds was assessed using biochemical assays and in vitro models including cellular assays and equivalent skin. The results showed that S. terebinthifolius Raddi extract is able to reduce the tyrosinase activity in vitro, and the combination of this extract with linoleic acid is able to decrease the level of melanin produced by B16 cells cultured with melanocyte-stimulating hormone. Furthermore, melanin was also reduced in human reconstituted epidermis (containing melanocytes) treated with the compounds. The combination of the compounds may provide a synergistic positive whitening effect rather than their isolated use. Finally, we demonstrated that the performance of these mixed compounds is comparable to classical molecules used for skin whitening, as kojic acid. This new natural mixture could be considered an alternative therapeutic agent for treating hyperpigmentation and an effective component in whitening cosmetics. PMID:22738140

  6. Inhibition of L-carnitine biosynthesis and transport by methyl-γ-butyrobetaine decreases fatty acid oxidation and protects against myocardial infarction

    PubMed Central

    Liepinsh, E; Makrecka-Kuka, M; Kuka, J; Vilskersts, R; Makarova, E; Cirule, H; Loza, E; Lola, D; Grinberga, S; Pugovics, O; Kalvins, I; Dambrova, M

    2015-01-01

    Background and Purpose The important pathological consequences of ischaemic heart disease arise from the detrimental effects of the accumulation of long-chain acylcarnitines in the case of acute ischaemia-reperfusion. The aim of this study is to test whether decreasing the L-carnitine content represents an effective strategy to decrease accumulation of long-chain acylcarnitines and to reduce fatty acid oxidation in order to protect the heart against acute ischaemia–reperfusion injury. Key Results In this study, we used a novel compound, 4-[ethyl(dimethyl)ammonio]butanoate (Methyl-GBB), which inhibits γ-butyrobetaine dioxygenase (IC50 3 μM) and organic cation transporter 2 (OCTN2, IC50 3 μM), and, in turn, decreases levels of L-carnitine and acylcarnitines in heart tissue. Methyl-GBB reduced both mitochondrial and peroxisomal palmitate oxidation rates by 44 and 53% respectively. In isolated hearts treated with Methyl-GBB, uptake and oxidation rates of labelled palmitate were decreased by 40%, while glucose oxidation was increased twofold. Methyl-GBB (5 or 20 mg·kg−1) decreased the infarct size by 45–48%. In vivo pretreatment with Methyl-GBB (20 mg·kg−1) attenuated the infarct size by 45% and improved 24 h survival of rats by 20–30%. Conclusions and Implications Reduction of L-carnitine and long-chain acylcarnitine content by the inhibition of OCTN2 represents an effective strategy to protect the heart against ischaemia–reperfusion-induced damage. Methyl-GBB treatment exerted cardioprotective effects and increased survival by limiting long-chain fatty acid oxidation and facilitating glucose metabolism. PMID:25363063

  7. Infantile Refsum Disease: Influence of Dietary Treatment on Plasma Phytanic Acid Levels.

    PubMed

    Sá, Maria João Nabais; Rocha, Júlio C; Almeida, Manuela F; Carmona, Carla; Martins, Esmeralda; Miranda, Vasco; Coutinho, Miguel; Ferreira, Rita; Pacheco, Sara; Laranjeira, Francisco; Ribeiro, Isaura; Fortuna, Ana Maria; Lacerda, Lúcia

    2016-01-01

    Infantile Refsum disease (IRD) is one of the less severe of Zellweger spectrum disorders (ZSDs), a group of peroxisomal biogenesis disorders resulting from a generalized peroxisomal function impairment. Increased plasma levels of very long chain fatty acids (VLCFA) and phytanic acid are biomarkers used in IRD diagnosis. Furthermore, an increased plasma level of phytanic acid is known to be associated with neurologic damage. Treatment of IRD is symptomatic and multidisciplinary.The authors report a 3-year-old child, born from consanguineous parents, who presented with developmental delay, retinitis pigmentosa, sensorineural deafness and craniofacial dysmorphisms. While the relative level of plasma C26:0 was slightly increased, other VLCFA were normal. Thus, a detailed characterization of the phenotype was essential to point to a ZSD. Repeatedly increased levels of plasma VLCFA, along with phytanic acid and pristanic acid, deficient dihydroxyacetone phosphate acyltransferase activity in fibroblasts and identification of the homozygous pathogenic mutation c.2528G>A (p.Gly843Asp) in the PEX1 gene, confirmed this diagnosis. Nutritional advice and follow-up was proposed aiming phytanic acid dietary intake reduction. During dietary treatment, plasma levels of phytanic acid decreased to normal, and the patient's development evaluation showed slow progressive acquisition of new competences.This case report highlights the relevance of considering a ZSD in any child with developmental delay who manifests hearing and visual impairment and of performing a systematic biochemical investigation, when plasma VLCFA are mildly increased. During dietary intervention, a biochemical improvement was observed, and the long-term clinical effect of this approach needs to be evaluated. PMID:26303611

  8. The effects of changing dairy intake on trans and saturated fatty acid levels- results from a randomized controlled study

    PubMed Central

    2014-01-01

    Background Dairy food is an important natural source of saturated and trans fatty acids in the human diet. This study evaluates the effect of dietary advice to change dairy food intake on plasma fatty acid levels known to be present in milk in healthy volunteers. Methods Twenty one samples of whole fat dairy milk were analyzed for fatty acids levels. Changes in levels of plasma phospholipid levels were evaluated in 180 healthy volunteers randomized to increase, not change or reduce dairy intake for one month. Fatty acids were measured by gas chromatography–mass spectrometry and levels are normalized to d-4 alanine. Results The long chain fatty acids palmitic (13.4%), stearic (16.7%) and myristic (18.9%) acid were most common saturated fats in milk. Four trans fatty acids constituted 3.7% of the total milk fat content. Increased dairy food intake by 3.0 (± 1.2) serves/ day for 1 month was associated with small increases in plasma levels of myristic (+0.05, 95% confidence level-0.08 to 0.13, p = 0.07), pentadecanoic (+0.014, 95% confidence level -0.016 to 0.048, p = 0.02) and margaric acid (+0.02, -0.03 to 0.05, p = 0.03). There was no significant change in plasma levels of 4 saturated, 4 trans and 10 unsaturated fatty acids. Decreasing dairy food intake by 2.5 (± 1.2) serves per day was not associated with change in levels of any plasma fatty acid levels. Conclusion Dietary advice to change dairy food has a minor effect on plasma fatty acid levels. Trial registration ACTRN12612000574842. PMID:24708591

  9. Molecular analysis of methylmalonic acidemia: Identification of novel mutations in the methylmalonyl-CoA mutase gene with decreased level of mutant mRNA

    SciTech Connect

    Ogasawara, M.; Matsubara, Y.; Mikami, H.; Narisawa, K.

    1994-09-01

    Deficiency of methylmalonyl-CoA mutase (MCM) results in methylmalonic acidemia, which is inherited as an autosomal recessive trait and clinically characterized by metabolic ketoacidosis. Previous studies of Caucasian and African American patients identified seven MCM mutations, and we also detected four missense substitutions (Ala197Thr, Val368Asp, Arg369His and Val669Glu). However, mutations with decreased level of MCM mRNA, which accounts for at least 25% of mutations among Caucasian patients, have not been reported. Our study on eight Japanese patients indicated that 13 of 16 mutant alleles (81%) showed decreased level of MCM mRNA, suggesting that these {open_quotes}low message{close_quotes} alleles are likely to be common contributors to MCM deficiency. Reverse transcription/polymerase chain reaction (RT-PCR) of MCM mRNA followed by analysis on a fluorescent fragment analyzer indicated that the level of these mutant mRNAs was less than 1% controls. We were able to amplify such mutant mRNAs by nested PCR and directly determine the primary structure. Sequence analysis revealed three novel mutations: a G-to-T substitution at nucleotide position 425, a 2 bp deletion at nt 769 and 770, and a G-to-T substitution at nt 326. The first mutation (G425T) resulted in the substitution of a termination codon for glutamic acid at amino acid position 117. The analysis of 17 Japanese patients revealed the presence of G425T in 7 alleles (21%), suggesting a relatively high incidence of the mutation among Japanese patients. This observation is in sharp contrast to previous reports describing diverse heterogeneity of MCM mutations among Caucasians. Our report is the first to identify MCM mutations that decrease the stability of MCM mRNA. Amplification of trace amount of mRNA followed by sequencing analysis may provide useful tool for identifying such mutations.

  10. Orthostatic hypotension is associated with decreased cerebrospinal fluid levels of chromogranin A in early stage of Parkinson disease.

    PubMed

    Kaiserova, Michaela; Prikrylova Vranova, Hana; Galuszka, Jan; Stejskal, David; Mensikova, Katerina; Zapletalova, Jana; Mares, Jan; Kanovsky, Petr

    2015-10-01

    An association between the CSF chromogranin A (CgA) and orthostatic blood pressure changes was investigated in 20 patients in the early stage of Parkinson disease (PD). There was a positive correlation between the CSF CgA and diastolic blood pressure change, when CSF CgA levels were lower in patients with orthostatic hypotension (OH). Decreased CSF CgA may be useful in predicting OH in the early stage of PD. PMID:26359267

  11. Plasma Gelsolin Levels Decrease in Diabetic State and Increase upon Treatment with F-Actin Depolymerizing Versions of Gelsolin

    PubMed Central

    Khatri, Neeraj; Sagar, Amin; Peddada, Nagesh; Choudhary, Vikas; Chopra, Bhupinder Singh; Garg, Veena; Ashish

    2014-01-01

    The study aims to map plasma gelsolin (pGSN) levels in diabetic humans and mice models of type II diabetes and to evaluate the efficacy of gelsolin therapy in improvement of diabetes in mice. We report that pGSN values decrease by a factor of 0.45 to 0.5 in the blood of type II diabetic humans and mice models. Oral glucose tolerance test in mice models showed that subcutaneous administration of recombinant pGSN and its F-actin depolymerizing competent versions brought down blood sugar levels comparable to Sitagliptin, a drug used to manage hyperglycemic condition. Further, daily dose of pGSN or its truncated versions to diabetic mice for a week kept sugar levels close to normal values. Also, diabetic mice treated with Sitagliptin for 7 days, showed increase in their pGSN values with the decrease in blood glucose as compared to their levels at the start of treatment. Gelsolin helped in improving glycemic control in diabetic mice. We propose that gelsolin level monitoring and replacement of F-actin severing capable gelsolin(s) should be considered in diabetic care. PMID:25478578

  12. HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels

    PubMed Central

    López-Dupla, Miguel; Maymó-Masip, Elsa; Martínez, Esteban; Domingo, Pere; Leal, Manuel; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; Arnedo, Mireia; Ferrando-Martínez, Sara; Beltrán-Debón, Raúl; Alba, Verónica; Gatell, Josep Mª; Vendrell, Joan; Vidal, Francesc; Chacón, Matilde R.

    2015-01-01

    Background and Objectives Obesity and HIV-1/HAART–associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163. Methods This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student’s t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables. Results Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001–0.521, p = 0.027). Conclusions HALS is associated with decreased sTWEAK levels. PMID:26658801

  13. Does high serum uric acid level cause aspirin resistance?

    PubMed

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage. PMID:26656902

  14. Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats.

    PubMed

    Kim, Y W; Kim, J Y; Lee, S K

    1999-10-01

    In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 15 weeks of age. The experiments were done four weeks after the surgery. MSG-Ob rats showed increased levels of FFA, insulin, and HGP and decreased Rd compared to normal rats. In the VF group, the FFA level and HGP were decreased to normal values, Rd was partially normalized, but the level of insulin did not change significantly compared to MSG-Ob. In the SF group, FFA and Rd were partially normalized, but HGP was not suppressed significantly compared to MSG-Ob. These results suggest that visceral fat affects the insulin sensitivity of liver and FFA concentration more than subcutaneous fat; however, no significant difference was shown on whole body insulin sensitivity and fasting insulin concentration. PMID:10576150

  15. Soluble TRAIL levels decreased in chronic hepatitis C treatment with pegylated interferon α plus ribavirin: association with viral responses

    PubMed Central

    Seyman, Derya; Yalcin, Arzu Didem; Oztoprak, Nefise; Genc, Gizem Esra; Ozen, Nevgun Sepin; Kizilates, Filiz; Berk, Hande; Gumuslu, Saadet

    2014-01-01

    The molecular mechanisms and pathogenesis of chronic hepatitis C (CHC) infection are unclear. Innate immune cells such as natural killer (NK) cells and dendritic cells are responsible from molecular mechanism of CHC. NK cell cytotoxicity such as TRAIL expression is important pathway for viral clearance. The aim of this study was to evaluate the relationship between HCV RNA and sTRAIL levels during the first 12 weeks of Peg-IFNα and ribavirin treatment. Twelve treatment naive patients with CHC treated with Peg-INFα and ribavirin were included in this study. Circulating sTRAIL and HCV RNA levels were measured at baseline, 4th and 12th week of treatment and their correlation was investigated. sTRAIL and HCV RNA levels decreased gradually with Peg-INFα plus ribavirin treatment. The differences were significant between day 0, 4th week and 12th week of treatment. The expression of sTRAIL was correlated with HCV RNA level at baseline, at 4th and 12th week of treatment (P = 0.021 P = 0.012, P = 0.001 respectively). IFN binds to its receptor on the infected hepatocyte surface during Peg-IFNα and ribavirin treatment. So the polarized phenotype of NK cell is not displayed and NK cell cytotoxicity such as TRAIL expression is blocked. We suggest that the decreased level of circulating sTRAIL may reflect increased binding to its ligand expressed on hepatocyte and decreased TRAIL production under the influence of Peg-IFNα plus ribavirin treatment. Therefore TRAIL may be probably a immunologically predictive factor such as HCV RNA during treatment. PMID:25664085

  16. [Effect of amino acid solutions on the blood ammonia level].

    PubMed

    Sanjo, K; Harihara, Y; Kawasaki, S; Umekita, N; Idezuki, Y

    1985-09-01

    We have carried out several basic experiments on artificial liver support and found that the plasma free amino acid balance was lost after treatment according to this procedure. Application of fluid therapy--Using conventional amino acid preparations available on the market--Is not adequate during and after the treatment with artificial liver. Fluid therapy using mainly special amino acid preparations should have been established; preparations, named Todai Hospital fluid (THF), are intended to correct the deranged aminogram, supply nutrition and promote the improvement in symptoms. Furthermore, experimental animals with acute hepatic insufficiency of diverse severity were prepared and basic experiments were performed which these animals to see how the efficacy of THF developed. In the basic experiments, psychoneurotic symptoms and the electroencephalogram were improved with the lowering of the blood ammonia level. Clinically, THF was not only used as a therapeutic agent after treatment by artificial liver support in patients with fulminant hepatitis, but is also served as a further indication in hepatic encephalopathy accompanying chronic liver diseases in late stages. Improvement in encephalopathy was observed immediately after the administration of THF and persisted while the aminogram pattern returned to the premedication representation. There was more improvement in patients in whom ammonemia was complicated, and the blood ammonia level was reduced markedly. PMID:4088243

  17. Dietary Caprylic Acid (C8:0) Does Not Increase Plasma Acylated Ghrelin but Decreases Plasma Unacylated Ghrelin in the Rat

    PubMed Central

    Lemarié, Fanny; Beauchamp, Erwan; Dayot, Stéphanie; Duby, Cécile; Legrand, Philippe; Rioux, Vincent

    2015-01-01

    Focusing on the caprylic acid (C8:0), this study aimed at investigating the discrepancy between the formerly described beneficial effects of dietary medium chain fatty acids on body weight loss and the C8:0 newly reported effect on food intake via ghrelin octanoylation. During 6 weeks, Sprague-Dawley male rats were fed with three dietary C8:0 levels (0, 8 and 21% of fatty acids) in three experimental conditions (moderate fat, caloric restriction and high fat). A specific dose-response enrichment of the stomach tissue C8:0 was observed as a function of dietary C8:0, supporting the hypothesis of an early preduodenal hydrolysis of medium chain triglycerides and a direct absorption at the gastric level. However, the octanoylated ghrelin concentration in the plasma was unchanged in spite of the increased C8:0 availability. A reproducible decrease in the plasma concentration of unacylated ghrelin was observed, which was consistent with a decrease in the stomach preproghrelin mRNA and stomach ghrelin expression. The concomitant decrease of the plasma unacylated ghrelin and the stability of its acylated form resulted in a significant increase in the acylated/total ghrelin ratio which had no effect on body weight gain or total dietary consumption. This enhanced ratio measured in rats consuming C8:0 was however suspected to increase (i) growth hormone (GH) secretion as an increase in the GH-dependent mRNA expression of the insulin like growth Factor 1 (IGF-1) was measured (ii) adipocyte diameters in subcutaneous adipose tissue without an increase in the fat pad mass. Altogether, these results show that daily feeding with diets containing C8:0 increased the C8:0 level in the stomach more than all the other tissues, affecting the acylated/total ghrelin plasma ratio by decreasing the concentration of circulating unacylated ghrelin. However, these modifications were not associated with increased body weight or food consumption. PMID:26196391

  18. Serum fluoride and sialic acid levels in osteosarcoma.

    PubMed

    Sandhu, R; Lal, H; Kundu, Z S; Kharb, S

    2011-12-01

    Osteosarcoma is a rare malignant bone tumor most commonly occurring in children and young adults presenting with painful swelling. Various etiological factors for osteosarcoma are ionizing radiation, family history of bone disorders and cancer, chemicals (fluoride, beryllium, and vinyl chloride), and viruses. Status of fluoride levels in serum of osteosarcoma is still not clear. Recent reports have indicated that there is a link between fluoride exposure and osteosarcoma. Glycoproteins and glycosaminoglycans are an integral part of bone and prolonged exposure to fluoride for long duration has been shown to cause degradation of collagen and ground substance in bones. The present study was planned to analyze serum fluoride, sialic acid, calcium, phosphorus, and alkaline phosphatase levels in 25 patients of osteosarcoma and age- and sex-matched subjects with bone-forming tumours other than osteosarcoma and musculo-skeletal pain (controls, 25 each). Fluoride levels were analyzed by ISE and sialic acid was analyzed by Warren's method. Mean serum fluoride concentration was found to be significantly higher in patients with osteosarcoma as compared to the other two groups. The mean value of flouride in patients with other bone-forming tumors was approximately 50% of the group of osteosarcoma; however, it was significantly higher when compared with patients of group I. Serum sialic acid concentration was found to be significantly raised in patients with osteosarcoma as well as in the group with other bone-forming tumors as compared to the group of controls. There was, however, no significant difference in the group of patients of osteosarcoma when compared with group of patients with other bone-forming tumors. These results showing higher level of fluoride with osteosarcoma compared to others suggesting a role of fluoride in the disease. PMID:19390788

  19. Fecal levels of short-chain fatty acids and bile acids as determinants of colonic mucosal cell proliferation in humans.

    PubMed

    Dolara, Piero; Caderni, Giovanna; Salvadori, Maddalena; Morozzi, Guido; Fabiani, Roberto; Cresci, Alberto; Orpianesi, Carla; Trallori, Giacomo; Russo, Antonio; Palli, Domenico

    2002-01-01

    We studied the correlation between fecal levels of short-chain fatty acids (SCFA), bile acids (BA), and colonic mucosal proliferation in humans on a free diet. Subjects [n = 43: 27 men and 16 women; 61 +/- 7 and 59 +/- 6 (SE) yr old, respectively] were outpatients who previously underwent resection of at least two sporadic colon polyps. Mucosal proliferation was determined by [3H]thymidine incorporation in vitro in three colorectal biopsies obtained without cathartics and was expressed as labeling index (LI). BA were analyzed in feces by mass spectrometry and SCFA by gas chromatography. We found that increasing levels of BA in feces did not correlate with higher LI. On the contrary, higher levels of SCFA were significantly associated with lower LI in the colonic mucosa (P for trend = 0.02). In conclusion, in humans on a free diet, intestinal proliferation seems to be regulated by the levels of SCFA in feces and not by BA. Because a lower intestinal proliferation is associated with a decreased colon cancer risk, treatments or diets that increase colonic levels of SCFA might be beneficial for colonic mucosa. PMID:12416258

  20. Prognostic Significance of Uric Acid Levels in Ischemic Stroke Patients.

    PubMed

    Zhang, Xia; Huang, Zhi-Chao; Lu, Tao-Sheng; You, Shou-Jiang; Cao, Yong-Jun; Liu, Chun-Feng

    2016-01-01

    The importance and function of serum uric acid (UA) levels in patients with cardiovascular disease or stroke are unclear. We sought to evaluate the appropriate UA levels for stroke patients and the association between endogenous UA levels and clinical outcomes in acute ischemic stroke (AIS) patients, particularly regarding the possible interaction between gender and UA levels with respect to AIS prognosis. We examined 303 patients who had an onset of ischemic stroke within 48 h. Of those, 101 patients received thrombolytic treatment. Serum UA (μmol/L) levels were measured the second morning after admission. Patient prognosis was evaluated 90 days after clinical onset by modified Rankin Scale. Patients were divided into four groups according to serum UA quartiles. A binary multivariate logistic regression model was used to assess clinical relevance in regard to functional outcome and endogenous UA levels. Analysis of subgroups by gender and normal glomerular filtration rate were also been done. Poor functional outcome was associated with older age, history of atrial fibrillation, or higher baseline National Institutes of Health Stroke Scale scores. After adjustment for potential confounders, patients with higher UA levels (>380 μmol/L) or lower UA levels (≤250 μmol/L) were 2-3 times more likely to have a poor outcome (OR 2.95, 95% CI 1.14-7.61; OR 2.78, 95% CI 1.02-7.58, respectively) compared to the baseline group (UA level 316-380 μmol/L). The same results were observed in thrombolyzed patients. Patients with high and low UA levels were 9-18 times more likely to having poor outcomes compared to the baseline group (UA level: 316-380 μmol/L; OR 18.50, 95% CI: 2.041-167.67; OR 9.66, 95% CI 1.42-65.88, respectively). In men, patients with high UA levels were 6 times more likely to have poor outcomes compared to the baseline group (UA level: 279-334 μmol/L; OR 6.10, 95% CI 1.62-22.93). However, female patients with UA level 271-337 μmol/L were seven times more

  1. 17β-Estradiol treatment inhibits breast cell proliferation, migration and invasion by decreasing MALAT-1 RNA level

    SciTech Connect

    Zhao, Ziyi; Chen, Changjin; Liu, Yu; Wu, Chuanfang

    2014-03-07

    Highlights: • E2 affects not only estrogen-receptor α positive breast cells but also negative ones. • 100 nM E2 treatment affects breast cells proliferation, migration. • 100 nM E2 treatment functions in an estrogen-receptor α-independent way. • E2 treatment decreases MALAT-1 RNA level by post-transcriptional regulation. - Abstract: Breast cancer cells, which express estrogen receptor α (ERα), respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. But breast cancer cells without ERα show no effect on low concentration of estrogen treatment. Proliferation, migration and invasion of MCF10a, MCF7 and MB231 cells treated with low (1 nM) or high (100 nM) dose of 17β-Estradiol (E2) was performed. We identified the effects of E2 on these breast cell lines, and looked for the difference in the presence and absence of ERα. Specifically, we looked for the changes of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT-1), which is found extensively and highly expressed in several kinds of tumor cells, including breast carcinoma. It was observed that proliferation, migration and invasion of breast cells were greatly affected by high concentration E2 treatment and were not affected by low concentration E2 treatment in an ERα independent way. We found that the high concentration E2 treatment largely decreased MALAT-1 RNA level. Interestingly, MALAT-1 decreasing by knocking down showed similar effects on proliferation, migration and invasion. E2 treatment affects breast tumor or non-tumor cells proliferation, migration and invasion in an ERα -independent, but a dose-dependent way by decreasing the MALAT-1 RNA level.

  2. Blood Meal-Derived Heme Decreases ROS Levels in the Midgut of Aedes aegypti and Allows Proliferation of Intestinal Microbiota

    PubMed Central

    Oliveira, Jose Henrique M.; Gonçalves, Renata L. S.; Lara, Flavio A.; Dias, Felipe A.; Gandara, Ana Caroline P.; Menna-Barreto, Rubem F. S.; Edwards, Meredith C.; Laurindo, Francisco R. M.; Silva-Neto, Mário A. C.; Sorgine, Marcos H. F.; Oliveira, Pedro L.

    2011-01-01

    The presence of bacteria in the midgut of mosquitoes antagonizes infectious agents, such as Dengue and Plasmodium, acting as a negative factor in the vectorial competence of the mosquito. Therefore, knowledge of the molecular mechanisms involved in the control of midgut microbiota could help in the development of new tools to reduce transmission. We hypothesized that toxic reactive oxygen species (ROS) generated by epithelial cells control bacterial growth in the midgut of Aedes aegypti, the vector of Yellow fever and Dengue viruses. We show that ROS are continuously present in the midgut of sugar-fed (SF) mosquitoes and a blood-meal immediately decreased ROS through a mechanism involving heme-mediated activation of PKC. This event occurred in parallel with an expansion of gut bacteria. Treatment of sugar-fed mosquitoes with increased concentrations of heme led to a dose dependent decrease in ROS levels and a consequent increase in midgut endogenous bacteria. In addition, gene silencing of dual oxidase (Duox) reduced ROS levels and also increased gut flora. Using a model of bacterial oral infection in the gut, we show that the absence of ROS resulted in decreased mosquito resistance to infection, increased midgut epithelial damage, transcriptional modulation of immune-related genes and mortality. As heme is a pro-oxidant molecule released in large amounts upon hemoglobin degradation, oxidative killing of bacteria in the gut would represent a burden to the insect, thereby creating an extra oxidative challenge to the mosquito. We propose that a controlled decrease in ROS levels in the midgut of Aedes aegypti is an adaptation to compensate for the ingestion of heme. PMID:21445237

  3. Ghrelin Decreases Angiogenesis, HIF-1α and VEGF Protein Levels in Chronic Hypoxia in Lung Tissue of Male Rats

    PubMed Central

    Mirzaei Bavil, Fariba; Alipour, Mohammad Reza; Keyhanmanesh, Rana; Alihemmati, Alireza; Ghiyasi, Rafigheh; Mohaddes, Gisou

    2015-01-01

    Purpose: Hypoxia is a condition of decreased availability of oxygen. When cells are exposed to a low oxygen environment, they impel the hypoxia responses to adapt to new situation. The hypoxia response leads to the activation of various cellular signaling pathways. The aim of this study was to evaluate the effect of ghrelin on angiogenesis, Hypoxia-Inducible-Factor-1α (HIF-1) and Vascular endothelial growth factor (VEGF) levels in normobaric hypoxia situation. Methods: Twenty four animals were divided into 4 groups (n=6): control (C), ghrelin (Gh), hypoxia (H), and hypoxic animals that received ghrelin (H+Gh). Hypoxia (11%) was induced by an Environmental Chamber System GO2 Altitude. Animals in ghrelin groups received a subcutaneous injection of ghrelin (150 μg/kg/day) for 14 days. Results: Our results showed that hypoxia significantly (p<0.05) increased angiogenesis without any significant changes on HIF-1 and VEGF levels, whereas ghrelin significantly (p<0.05) decreased angiogenesis, expression of HIF-1 and VEGF in this condition. Ghrelin administration did not show any significant changes in normal conditions. Conclusion: Ghrelin had no effect on angiogenesis, expression of HIF-1 and VEGF in normal oxygen conditions but it reduced angiogenesis process in lung tissue with reducing the level of HIF and VEGF in hypoxic condition. Therefore, effect of ghrelin on angiogenesis could be related to blood oxygen level. PMID:26504752

  4. Serum uric acid level in normal pregnant and preeclamptic ladies: a comparative study.

    PubMed

    Pramanik, T; Khatiwada, B; Pradhan, P

    2014-09-01

    Preeclampsia is a serious pregnancy complication characterized by hypertension, proteinuria with or without pathological edema. According to some studies, serum uric acid lacks sensitivity and specificity as a diagnostic tool whereas another group of the researchers indicated uricemia as a predictor of preeclampsia in pregnant ladies. The present study was designed to assess whether serum uric acid can be used as a biochemical indicator or not in preeclamptic patients. Pre-eclamptic patients admitted in Nepal Medical College Teaching Hospital from June 2012 to June 2013 were included in this study. Age matched normal healthy pregnant ladies served as control. The record of their blood pressure and serum uric acid level was evaluated. Results showed significantly high blood pressure [SBP 149.42±12.35 vs 109.00±7.93 mm Hg; DBP 96.85±8.32 vs 72.5±7.10 mm Hg], and serum uric acid level [6.27±1.37 vs 4.27±0.61 mg/dl] in pre-eclamptic patients compared to their healthy counterparts. Uric acid is a terminal metabolite of the degradation of nucleotides, which increases their blood levels in patients with preeclampsia increasing its synthesis by damage and death of trophoblastic cells and proliferation. Uricemia in preeclampsia likely results from reduced uric acid clearance from diminished glomerular filtration, increased tubular reabsorption and decreased secretion. Results of the present study indicated association of elevated serum uric acid level with preeclampsia which could be used as a biochemical indicator of preeclampsia in pregnant women. PMID:25799807

  5. Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

    NASA Technical Reports Server (NTRS)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

    1997-01-01

    The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in

  6. Decrease of Population Divergence in Eurasian Perch (Perca fluviatilis) in Browning Waters: Role of Fatty Acids and Foraging Efficiency.

    PubMed

    Scharnweber, Kristin; Strandberg, Ursula; Karlsson, Konrad; Eklöv, Peter

    2016-01-01

    Due to altered biogeochemical processes related to climate change, highly colored dissolved organic carbon (DOC) from terrestrial sources will lead to a water "brownification" in many freshwater systems of the Northern Hemisphere. This will create deteriorated visual conditions that have been found to affect habitat-specific morphological variations in Eurasian perch (Perca fluviatilis) in a previous study. So far, potential drivers and ultimate causes of these findings have not been identified. We conducted a field study to investigate the connection between morphological divergence and polyunsaturated fatty acid (PUFA) composition of perch from six lakes across a gradient of DOC concentration. We expected a decrease in the prevalence of PUFAs, which are important for perch growth and divergence with increasing DOC concentrations, due to the restructuring effects of DOC on aquatic food webs. In general, rate of morphological divergence in perch decreased with increasing DOC concentrations. Proportions of specific PUFAs (22:6n-3, 18:3n-3, 20:5n-3, and 20:4n-6) identified to primarily contribute to overall differences between perch caught in clear and brown-water lakes tended to be connected to overall decline of morphological divergence. However, no overall significant relationship was found, indicating no severe limitation of essential fatty acids for perch inhabiting brown water lakes. We further broaden our approach by conducting a laboratory experiment on foraging efficiency of perch. Therefore, we induced pelagic and littoral phenotypes by differences in habitat-structure and feeding mode and recorded attack rate in a feeding experiment. Generally, fish were less efficient in foraging on littoral prey (Ephemeroptera) when visual conditions were degraded by brown water color. We concluded that browning water may have a strong effect on the forager's ability to find particular food resources, resulting in the reduced development of evolutionary traits, such as

  7. Decreased Circulating Interleukin-35 Levels Are Related to Interleukin-4-Producing CD8+ T Cells in Patients with Allergic Asthma.

    PubMed

    Wang, Wei; Li, Ping; Yang, Jiong

    2015-08-01

    Interleukin (IL)-35 is a newly discovered suppressive cytokine and has been shown to alleviate inflammatory and autoimmune diseases. The purpose of this study was to investigate immunomodulatory capacity of IL-35 in patients with allergic asthma. IL-35 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were detected by quantitative real-time PCR (qPCR). The frequencies of cytotoxic T cells (Tc)1, Tc2 and Tc17 cells were measured by flow cytometry. Plasma levels of IL-35, interferon (IFN)-γ, IL-4, and IL-17 were examined by enzyme-linked immunosorbent assay (ELISA). The correlations between plasma IL-35 levels and Tc1, Tc2, and Tc17 cytokine production in allergic asthmatics (n = 25) and healthy controls (n = 12) were analyzed by Pearson's test. IL-35 protein and mRNA expression levels were down-regulated in allergic asthmatics compared with healthy controls. The frequencies of Tc2 and Tc17 cells were significantly increased in patients with asthma, and the frequency of Tc1 cells did not differ between asthmatic patients and healthy controls. Similarly, plasma levels of IL-4 and IL-17 were significantly increased in asthmatic patients, while there was no difference in IFN-γ levels between allergic asthma patients and healthy controls. More importantly, plasma IL-35 protein levels were negatively correlated with the frequency of IL-4-producing CD8+ T (Tc2) cells and with the IL-4 level in patients with allergic asthma. Our results suggest that decreased circulating IL-35 levels could contribute to the pathogenesis of allergic asthma by regulating CD8+ T cells. PMID:26547705

  8. Secretion of three enzymes for fatty acid synthesis into mouse milk in association with fat globules, and rapid decrease of the secreted enzymes by treatment with rapamycin.

    PubMed

    Moriya, Hitomi; Uchida, Kana; Okajima, Tetsuya; Matsuda, Tsukasa; Nadano, Daita

    2011-04-01

    The mammary epithelium produces numerous lipid droplets during lactation and secretes them in plasma membrane-enclosed vesicles known as milk fat globules. The biogenesis of such fat globules is considered to provide a model for clarifying the mechanisms of lipogenesis in mammals. In the present study, we identified acetyl coenzyme A carboxylase, ATP citrate lyase, and fatty acid synthase in mouse milk. Fractionation of milk showed that these three enzymes were located predominantly in milk fat globules. The three enzymes were resistant to trypsin digestion without Triton X-100, indicating that they were not located on the outer surface of the globules and thus associated with the precursors of the globules before secretion. When a low dose of rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), was injected into lactating mice, the levels of the three enzymes in milk were decreased within 3h after injection. Since the protein levels of the three enzymes in tissues were not obviously altered by this short-term treatment, known transcriptional control by mTOR signaling was unlikely to account for this decrease in their levels in milk. Our findings suggest a new, putatively mTOR-dependent localization of the three enzymes for de novo lipogenesis. PMID:21281598

  9. All-trans retinoic acid decreases susceptibility of a gastric cancer cell line to lymphokine-activated killer cytotoxicity.

    PubMed Central

    Chao, T. Y.; Jiang, S. Y.; Shyu, R. Y.; Yeh, M. Y.; Chu, T. M.

    1997-01-01

    All-trans retinoic acid (RA) was previously shown to regulate the growth of gastric cancer cells derived from the cell line SC-M1. This study was designed to investigate the effect of RA on the sensitivity of SC-M1 cells to lymphokine-activated killer (LAK) activity. RA at the concentration range of 0.001-10 microM was shown to induce SC-M1 cells to exhibit resistance to LAK activity in a dose-dependent manner. A kinetics study indicated that a significantly increased resistance was detected after 2 days of co-culturing SC-M1 cells with RA and reached a maximum after 6 days of culture. Similar results were obtained from two other cancer cell lines: promyelocytic leukaemia HL-60 and hepatic cancer Hep 3B. A binding assay demonstrated that the binding efficacy between target SC-M1 cells and effector LAK cells was not altered by RA. Flow cytometric analyses revealed that RA exhibited no effect on the expression of cell surface molecules, including HLA class I and class II antigens, intercellular adhesion molecule-1 and -2, and lymphocyte function antigen-3. Cell cycle analysis revealed that culture of SC-M1 cells with RA resulted in an increase in G0/G1 phase and a decrease in S phase, accompanied by a decrease in cyclin A and cyclin B1 mRNA as determined by Northern blot analysis. Additionally, RA was shown to enhance the expression of retinoic acid receptor alpha (RAR alpha) in SC-M1 cells, and to have no effect on the expression of RARbeta or RARgamma. Taken together, these results indicate that RA can significantly increase gastric cancer cells SC-M1 to resist LAK cytotoxicity by means of a cytostatic effect through a mechanism relating to cell cycle regulation. The prevailing ideas, such as a decrease in effector to target cell binding, a reduced MHC class I antigen expression or an altered RARbeta expression, are not involved. Images Figure 4 Figure 5 PMID:9155047

  10. Effects of pain management program on the length of stay of patients with decreased level of consciousness: A clinical trial

    PubMed Central

    Shahriari, Mohsen; Golshan, Alireza; Alimohammadi, Nasrollah; Abbasi, Saeid; Fazel, Kamran

    2015-01-01

    Background: Critical care patients are at higher risk for untreated pain. Pain has persistent and untreated effects on most of the body systems and results in development of complications, chronic pain, and increased length of stay. The aim of this study was to determine the effects of the implementation of a pain management program on the length of stay in patients with decreased level of consciousness, admitted in Al-Zahra hospital intensive care units (ICUs) in 2013. Materials and Methods: In this clinical trial, 50 subjects with decreased level of consciousness were selected by convenient sampling from the ICU wards of Al-Zahra hospital, Isfahan, Iran and were randomly assigned to two groups of study and control. Pain management program was applied on the study group and routine care was implemented in the control group. Data including demographic data and length of stay of patients in the ICUs were collected and analyzed using descriptive statistics and Chi-square test, independent t-test, and paired t-test. Results: Results showed that out of 50 subjects attending the study, there were 40% female and 60% male subjects in study, and 52% female and 48% male subjects in control group. (P = 0.395). Overall mean length of stay of the patients in the ICUs was significantly lower in the case group [3.2 (1.4)] days compared to the control group [7.4 (4.8) days] (P < 0.001). Conclusions: This study showed that overall mean length of stay of patients in the ICUs was significantly lower in the study group compared to the control group. It is suggested to use this program for patients in ICUs with decreased level of consciousness after a general surgery. PMID:26257808

  11. Don’t Always Prefer My Chosen Objects: Low Level of Trait Autonomy and Autonomy Deprivation Decreases Mere Choice Effect

    PubMed Central

    Shang, Zhe; Tao, Tuoxin; Wang, Lei

    2016-01-01

    Choice effect is a robust phenomenon in which even “mere choice” that does not include actual choosing actions could result in more preference for the self-chosen objects over other-chosen objects. In the current research, we proposed that autonomy would impact the mere choice effect. We conducted two studies to examine the hypothesis. The results showed that the mere choice effect measured by Implicit Association Test (IAT) significantly decreased for participants with lower levels of trait autonomy (Study 1) and when participants were primed to experience autonomy deprivation (Study 2). The theoretical and practical implications are discussed. PMID:27148132

  12. Association between serum folic acid level and erectile dysfunction.

    PubMed

    Karabakan, M; Erkmen, A E; Guzel, O; Aktas, B K; Bozkurt, A; Akdemir, S

    2016-06-01

    This study measured the serum folic acid (FA) level in patients with erectile dysfunction (ED) and evaluated the possible association between the serum FA level and erectile function. The study divided 120 patients with ED into 3 groups of 40 patients each: those with severe, moderate and mild ED. Forty healthy men served as controls. Fasting serum samples were obtained, and the total testosterone, cholesterol and FA levels were measured using chemiluminescent immunoassays. There were no significant differences in the mean age, mean body mass index or mean serum total testosterone and cholesterol levels among the three ED groups and controls (P > 0.05). The mean serum FA concentrations were 7.2 ± 3.7, 7.1 ± 3.2, 10.2 ± 4.6 and 10.7 ± 4.6 ng ml(-1) in the severe, moderate and mild ED and control groups respectively. The mean serum FA concentration was significantly higher in the control group than in the severe and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95). Considering the significant differences in the serum FA levels between the control and ED groups, serum FA deficiency might reflect the severity of ED. PMID:26302884

  13. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  14. Effects of folic acid supplementation on serum homocysteine and lipoprotein (a) levels during pregnancy

    PubMed Central

    Hekmati Azar Mehrabani, Zohreh; Ghorbanihaghjo, Amir; Sayyah Melli, Manizheh; Hamzeh-Mivehroud, Maryam; Fathi Maroufi, Nazila; Bargahi, Nasrin; Bannazadeh Amirkhiz, Maryam; Rashtchizadeh, Nadereh

    2015-01-01

    Introduction:There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. Results: Supplementation of the patients with FA for 36 week decreased the median (minimum– maximum) levels of serum Hcy from 11.40 μmol/L (4.40-28.70) to 9.70 (1.60-20.80) μmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. Conclusion:Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women. PMID:26929921

  15. What is the relationship between gestational age and docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels?

    PubMed

    Baack, Michelle L; Puumala, Susan E; Messier, Stephen E; Pritchett, Deborah K; Harris, William S

    2015-09-01

    Long chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA) and arachidonic acid (ARA) are increasingly transferred from mother to fetus late in pregnancy. Infants born before this transfer is complete are at risk for deficiency. This study determines the relationship between gestational age (GA) and circulating LCPUFA levels to better understand the unique needs of premature infants born at various GAs. Whole blood was collected within the first 7 days of life from 60 preterm (≤34 weeks GA) and 30 term infants (≥38 weeks GA) and FA levels were analyzed. Since concurrent intravenous lipid emulsion can skew composition data, blood LCPUFA concentrations were also measured. Levels were compared among groups, and linear regression models were used to examine the association between FA composition and GA. Preterm infants had significantly lower DHA and ARA levels than term peers, and whether assessed as concentrations or compositions, both directly correlated with GA (p<0.0001). Moreover, FA comparisons suggest that premature infants have impaired synthesis of LCPUFAs from precursors and may require preformed DHA and ARA. This study confirms that essential FA status is strongly related to GA, and that those babies born the earliest are at the greatest risk of LCPUFA deficiency. PMID:26205427

  16. Decreased Phosphorylated Protein Kinase B (Akt) in Individuals with Autism Associated with High Epidermal Growth Factor Receptor (EGFR) and Low Gamma-Aminobutyric Acid (GABA)

    PubMed Central

    Russo, Anthony J

    2015-01-01

    Dysregulation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway could contribute to the pathogenesis of autism spectrum disorders. In this study, phosphorylated Akt concentration was measured in 37 autistic children and 12, gender and age similar neurotypical, controls using an enzyme-linked immunosorbent assay. Akt levels were compared to biomarkers known to be associated with epidermal growth factor receptor (EGFR) and c-Met (hepatocyte growth factor (HGF) receptor) pathways and severity levels of 19 autism-related symptoms. We found phosphorylated Akt levels significantly lower in autistic children and low Akt levels correlated with high EGFR and HGF and low gamma-aminobutyric acid, but not other biomarkers. Low Akt levels also correlated significantly with increased severity of receptive language, conversational language, hypotonia, rocking and pacing, and stimming, These results suggest a relationship between decreased phosphorylated Akt and selected symptom severity in autistic children and support the suggestion that the AKT pathways may be associated with the etiology of autism. PMID:26508828

  17. sHLA-G1 and HLA-G5 levels are decreased in Tunisian women with multiple abortion.

    PubMed

    Zidi, Inès; Rizzo, Roberta; Bouaziz, Aicha; Laaribi, Ahmed Baligh; Zidi, Nour; Di Luca, Dario; Tlili, Henda; Bortolotti, Daria

    2016-04-01

    Pregnancy is associated with increased levels of soluble (s) human leukocyte antigen (HLA)-G molecules, while during abortion these molecules are decreased. To date, little is known about the role of sHLA-G isoforms during abortion. In this study, we investigated the levels of total sHLA-G and its isoforms: HLA-G1 (membrane shedded isoform) and alternative spliced HLA-G5 in plasma samples obtained from 55 women who had experienced spontaneous abortion, 108 pregnant healthy women and 56 non pregnant healthy women. We found that pregnant women exhibited higher amounts of sHLA-G compared to either non pregnant women or women with abortion. Among women who had experienced spontaneous abortion, women with recurrent abortions (RSA) had lower sHLA-G than women with only one abortion. In particular, RSA women were characterized by the absence of sHLA-G1 isoform, suggesting a possible implication in abortion event. PMID:26812178

  18. Tetramethylpyrazine, a Chinese drug, blocks coronary vasoconstriction by endothelin-1 and decreases plasma endothelin-1 levels in experimental animals.

    PubMed

    Zeng, Z; Zhu, W; Zhou, X; Jin, Z; Liu, H; Chen, X; Pan, J; Demura, H; Naruse, M; Shi, Y

    1998-01-01

    The purpose of this study was to investigate effects of tetramethylpyrazine (TMP), a Chinese plant-derived medicine, on coronary vasoconstriction and related electrocardiographic and histologic changes caused by endothelin-1 (ET-1), and on plasma ET-1 levels. ET-1 (75 pmol) was administered into the left coronary artery (LCA) in anesthetized closed-chest dogs with and without prior infusion of TMP (80 mg/kg). Coronary arterial diameter (CAD) was determined by coronary arteriography (CAG). Blood pressure and electrocardiogram (ECG) were monitored continuously. Histologic damage in tissues was ascertained microscopically. Plasma ET-1 and 6-keto-PGF1 levels were determined by RIA 90 min after i.v. injection of TMP (25 mg/kg; n = 5) in rabbits. Intracoronary injection of ET-1 resulted in a significant vasoconstriction of the entire vascular bed of the LCA, with a decrease in CAD of 35.9 +/- 5.7% (n = 5; p < 0.01) and ischemic changes on ECG and in tissues of endocardium, myocardium, coronary endothelial cells, and capillary vessels. Pretreatment with TMP produced a significant increase in CAD by 38.5 +/- 7.8% (n = 5; p < 0.01) and greatly suppressed the vasoconstriction produced by ET-1. The myocardial tissue damage estimated from the ratio of ischemic area for the entire area after ET-1 injection (35.6%) was completely abolished by TMP (0.6%). In addition, TMP injection induced a significant decrease in plasma ET-1 levels and an increase in 6-keto-PGF1 levels in rabbits. The Chinese medicine TMP could be a useful therapeutic agent in ischemic heart disease by suppressing coronary vasoconstriction and ischemic changes in the tissues produced by ET-1. PMID:9595468

  19. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients

    PubMed Central

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-01-01

    α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as “incurable” diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

  20. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

    PubMed

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-08-01

    α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

  1. Novel inhibitors of nuclear transport cause cell cycle arrest and decrease cyst growth in ADPKD associated with decreased CDK4 levels.

    PubMed

    Tan, Matthew; Wettersten, Hiromi I; Chu, Kristy; Huso, David L; Watnick, Terry; Friedlander, Sharon; Landesman, Yosef; Weiss, Robert H

    2014-12-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is a progressive, proliferative renal disease. Kidneys from ADPKD patients are characterized by the presence of cysts that are marked by enhanced proliferation and apoptosis of renal tubular epithelial cells. Current treatment of this disease is supportive, as there are few if any clinically validated targeted therapeutics. Given the parallels between cystic disease and cancer, and in light of our findings of the efficacy of the nuclear transport inhibitors in kidney cancer, which has similarities to ADPKD, we asked whether such inhibitors show utility in ADPKD. In this study, we tested selective inhibitors of nuclear export (SINE) in two human ADPKD cell lines and in an in vivo mouse model of ADPKD. After effective downregulation of a nuclear exporter, exportin 1 (XPO1), with KPT-330, both cell lines showed dose-dependent inhibition of cell proliferation through G₀/G₁ arrest associated with downregulation of CDK4, with minimal apoptosis. To analyze mechanisms of CDK4 decrease by XPO1 inhibition, localization of various XPO1 target proteins was examined, and C/EBPβ was found to be localized in the nucleus by XPO1 inhibition, resulting in an increase of C/EBPα, which activates degradation of CDK4. Furthermore, inhibition of XPO1 with the parallel inhibitor KPT-335 attenuated cyst growth in vivo in the PKD1 mutant mouse model Pkd1(v/v). Thus, inhibition of nuclear export by KPT-330, which has shown no adverse effects in renal serum chemistries and urinalyses in animal models, and which is already in phase 1 trials for cancers, will be rapidly translatable to human ADPKD. PMID:25234309

  2. Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

    PubMed Central

    2013-01-01

    It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. PMID:23442260

  3. Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects.

    PubMed

    Neuhaus, Andres H; Goldberg, Terry E; Hassoun, Youssef; Bates, John A; Nassauer, Katharine W; Sevy, Serge; Opgen-Rhein, Carolin; Malhotra, Anil K

    2009-06-01

    Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research. PMID:19356906

  4. High concentrations of plasma n3 fatty acids are associated with decreased risk for late age-related macular degeneration.

    PubMed

    Merle, Bénédicte M J; Delyfer, Marie-Noëlle; Korobelnik, Jean-François; Rougier, Marie-Bénédicte; Malet, Florence; Féart, Catherine; Le Goff, Mélanie; Peuchant, Evelyne; Letenneur, Luc; Dartigues, Jean-François; Colin, Joseph; Barberger-Gateau, Pascale; Delcourt, Cécile

    2013-04-01

    High dietary intakes of n3 (ω3) polyunsaturated fatty acids (PUFA) and fish have been consistently associated with a decreased risk for age-related macular degeneration (AMD). We assessed the associations of late AMD with plasma n3 PUFA, a nutritional biomarker of n3 PUFA status. The Antioxydants Lipides Essentiels Nutrition et Maladies Occulaires (Alienor) Study is a prospective, population-based study on nutrition and age-related eye diseases performed in 963 residents of Bordeaux (France) aged ≥73 y. Participants had a first eye examination in 2006-2008 and were followed for 31 mo on average. Plasma fatty acids were measured by GC from fasting blood samples collected in 1999-2001. AMD was graded from non-mydriatic color retinal photographs at all examinations and spectral domain optical coherence tomography at follow-up. After adjustment for age, gender, smoking, education, physical activity, plasma HDL-cholesterol, plasma triglycerides, CFH Y402H, apoE4, and ARMS2 A69S polymorphisms, and follow-up time, high plasma total n3 PUFA was associated with a reduced risk for late AMD [OR = 0.62 for 1-SD increase (95% CI: 0.44-0.88); P = 0.008]. Associations were similar for plasma 18:3n3 [OR = 0.62 (95% CI: 0.43-0.88); P = 0.008] and n3 long-chain PUFA [OR = 0.65 (95% CI: 0.46-0.92); P = 0.01]. This study gives further support to the potential role of n3 PUFAs in the prevention of late AMD and highlights the necessity of randomized clinical trials to determine more accurately the value of n3 PUFAs as a means of reducing AMD incidence. PMID:23406618

  5. Lower ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Decrease Fat Deposition by Inhibiting Fat Synthesis in Gosling.

    PubMed

    Yu, Lihuai; Wang, Shunan; Ding, Luoyang; Liang, Xianghuan; Wang, Mengzhi; Dong, Li; Wang, Hongrong

    2016-10-01

    The objective of the current study was to investigate the effects of dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on lipid metabolism in goslings. One hundred and sixty 21-day-old Yangzhou geese of similar weight were randomly divided into 4 groups. They were fed different PUFA-supplemented diets (the 4 diets had ω-6/ω-3 PUFA ratios of 12:1, 9:1, 6:1, or 3:1). The geese were slaughtered and samples of liver and muscle were collected at day 70. The activities and the gene expression of enzymes involved in lipid metabolism were measured. The results show that the activities of acetyl coenzyme A carboxylase (ACC), malic enzyme (ME), and fatty acid synthase (FAS) were lower (p<0.05), but the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were higher (p<0.05), in the liver and the muscle from the 3:1 and 6:1 groups compared with those in the 9:1 and 12:1 groups. Expression of the genes for FAS (p<0.01), ME (p<0.01) and ACC (p<0.05) were higher in the muscle of groups fed diets with higher ω-6/ω-3 PUFA ratios. Additionally, in situ hybridization tests showed that the expression intensities of the high density lipoprotein (HDL-R) gene in the 12:1 and 9:1 groups were significantly lower (p<0.01) than that of the 3:1 group in the muscle of goslings. In conclusion, diets containing lower ω-6/ω-3 PUFA ratios (3:1 or 6:1) could decrease fat deposition by inhibiting fat synthesis in goslings. PMID:27189638

  6. Association of Serum Uric Acid Levels in Psoriasis

    PubMed Central

    Li, Xin; Miao, Xiao; Wang, Hongshen; Wang, Yifei; Li, Fulun; Yang, Qiong; Cui, Rutao; Li, Bin

    2016-01-01

    Abstract High levels of serum uric acid (SUAC) are frequently detected in patients with psoriasis. However, the relationship between psoriasis and hyperuricemia remains unknown. Here we conducted a meta-analysis to identify the SUAC levels in subjects with psoriasis and to determine whether there is an associated risk between psoriasis and hyperuricemia. A comprehensive search of the literature from January 1980 to November 2014 across 7 databases (MEDLINE, Embase, Cochrane Central Register, and 4 Chinese databases) was conducted to determine whether there is an associated risk between psoriasis and hyperuricemia. Among the 170 identified reports, 14 observational studies were included in this meta-analysis. We found a significant higher SUAC level (MD 0.68, 95% CI 0.26–1.09; P = 0.002) in patients with psoriasis in Western Europe, but no significant differences were found between the East Asia and India subgroup (MD 1.22, 95% CI –0.13–2.56; P = 0.08) or the Middle East subgroup (MD 0.48, 95% CI –0.49–1.44; P = 0.33). Similar results were obtained from the meta-analysis of SUAC levels in subjects with severe psoriasis. Our meta-analysis showed that the correlation between psoriasis and hyperuricemia was either ethnicity- or region-dependent and that patients with psoriasis in Western Europe were more likely to have hyperuricemia. PMID:27175702

  7. Decreased blood hepatitis B surface antibody levels linked to e-waste lead exposure in preschool children.

    PubMed

    Xu, Xijin; Chen, Xiaojuan; Zhang, Jian; Guo, Pi; Fu, Tingzao; Dai, Yifeng; Lin, Stanley L; Huo, Xia

    2015-11-15

    Lead (Pb) is a widespread environmental contaminant that can profoundly affect the immune system in vaccinated children. To explore the association between blood Pb and HBsAb levels in children chronically exposed to Pb, we measured hepatitis B surface antibody (HBsAb) titers, to reflect the immune response in the children of Guiyu, an electronic and electrical waste (e-waste) recycling area well known for environmental Pb contamination. We performed secondary exploratory analyses of blood Pb levels and plasma HBsAb titers in samples, taken in two phases between 2011 and 2012, from 590 children from Guiyu (exposed group) and Haojiang (reference group). Children living in the exposed area had higher blood Pb levels and lower HBsAb titers compared with children from the reference area. At each phase, generalized linear mixed models (GLMMs) showed that HBsAb titers were significantly negatively associated with child blood Pb levels. This work shows that a decreased immune response to hepatitis B vaccine and immune system might have potential harm to children with chronic Pb exposure. Importantly, nearly 50% of chronically exposed children failed to develop sufficient immunity to hepatitis in response to vaccination. Thus different vaccination strategies are needed for children living under conditions of chronic Pb exposure. PMID:26022852

  8. Inverse Association Between Serum Uric Acid Levels and Alzheimer's Disease Risk.

    PubMed

    Du, Na; Xu, Donghua; Hou, Xu; Song, Xuejia; Liu, Cancan; Chen, Ying; Wang, Yangang; Li, Xin

    2016-05-01

    The association between Alzheimer's disease and uric acid levels had gained great interest in recent years, but there was still lack of definite evidence. A systematic review and meta-analysis of relevant studies was performed to comprehensively estimate the association. Relevant studies published before October 26, 2014, were searched in PubMed, Embase, and China Biology Medicine (CBM) databases. Study-specific data were combined using random-effects or fixed-effects models of meta-analysis according to between-study heterogeneity. Twenty-four studies (21 case-control and 3 cohort studies) were finally included into the meta-analysis. Those 21 case-control studies included a total of 1128 cases of Alzheimer's disease and 2498 controls without Alzheimer's disease. Those 3 cohort studies included a total of 7327 participants. Meta-analysis showed that patients with Alzheimer's disease had lower levels of uric acid than healthy controls (weighted mean difference (WMD) = -0.77 mg/dl, 95 % CI -2.28 to -0.36, P = 0.0002). High serum uric acid levels were significantly associated with decreased risk of Alzheimer's disease (risk ratio (RR) = 0.66, 95 % CI 0.52-0.85, P = 0.001). There was low risk of publication bias in the meta-analysis. There is an inverse association between serum uric acid levels and Alzheimer's disease. High serum uric acid level is a protective factor of Alzheimer's disease. PMID:26084440

  9. Cerebral level of vGlut1 is increased and level of glycine is decreased in TgSwDI mice.

    PubMed

    Timmer, Nienke M; Metaxas, Athanasios; van der Stelt, Inge; Kluijtmans, Leo A J; van Berckel, Bart N; Verbeek, Marcel M

    2014-01-01

    Amyloid-β (Aβ) deposition, one of the main hallmarks of Alzheimer's disease (AD), has been linked to glutamatergic dysfunction, i.e., increased stimulation of synaptic glutamate receptors that may ultimately result in neuronal loss. It was our aim to study the effect of Aβ on multiple components of the glutamatergic system, and therefore we assessed the expression of several glutamate-related proteins and amino acids in the TgSwDI mouse model for Aβ pathology. We determined that in TgSwDI mice, levels of several amino acids are altered, in particular that of glycine. Protein changes were only found in 9-month-old TgSwDI mice with extensive Aβ deposits, with the most prominent change an increased expression of vesicular glutamate transporter 1 (vGlut1). Autoradiography experiments demonstrated that, while the number of activated N-methyl-D-aspartic acid (NMDA) receptors was unchanged in TgSwDI mice, binding of the NMDA receptor radioligand [3H]MDL-105,519 to the glycine-binding site of these receptors was increased. Although there are some discrepancies between our results and those found in AD patients, our results suggest that several components of the glutamatergic system might serve as meaningful markers to monitor the progression of AD. PMID:24145381

  10. The herpes simplex virus regulatory protein ICP27 contributes to the decrease in cellular mRNA levels during infection.

    PubMed Central

    Hardwicke, M A; Sandri-Goldin, R M

    1994-01-01

    We have previously shown that the herpes simplex virus immediate-early regulatory protein ICP27 acts posttranscriptionally to affect mRNA processing (R. M. Sandri-Goldin and G. E. Mendoza, Genes Dev. 6:848-863, 1992). Specifically, in the presence of ICP27, spliced target mRNAs were decreased 5- to 10-fold in transfections with target genes containing a 5' or 3' intron. Here, we have investigated the effect of ICP27 during herpes simplex virus type 1 (HSV-1) infection on accumulation of spliced cellular mRNAs. ICP27 viral mutants have been shown to be defective in host shutoff (W. R. Sacks, C. C. Greene, D. P. Aschman, and P. A. Schaffer, J. Virol. 55:796-805, 1985). Therefore, we examined whether ICP27 could contribute to this complex process by decreasing cellular mRNA levels through its effects on host cell splicing. It was found that in infections with viral mutants defective in ICP27, the accumulated levels of three spliced host mRNAs were higher than those seen with wild-type HSV-1. The differences occurred posttranscriptionally as shown by nuclear runoff transcription assays. The stabilities of the spliced products during infection with wild-type or ICP27 mutant viruses were similar, and unspliced precursor mRNA for a viral spliced gene was detected in infections with wild-type HSV-1 but not in infections in which ICP27 was not expressed. These results suggest that the reduction in cellular mRNA levels and the accumulation of pre-mRNA are related and may be caused by an impairment in host cell splicing. These data further show that ICP27 is required for these effects to occur. Images PMID:8035480

  11. 1,1,2,2-Tetrachloroethane-induced early decrease of dolichol levels in rat liver microsomes and Golgi apparatus.

    PubMed

    Cottalasso, D; Bellocchio, A; Domenicotti, C; Dapino, D; Pronzato, M A; Nanni, G

    1998-05-22

    Dolichols are long-chain polyprenols containing 14-22 isoprene units, present in mammalian tissues as free dolichol (Free-Dol), fatty acyl dolichyl esters (Dol-FA), and dolichyl phosphate (Dol-P). The hepatic level of Dol-P seems to be a rate-limiting factor for glycosylation processes. Previous studies from our laboratory demonstrated the susceptibility of the dolichol molecule to undergo radical attacks. Since the toxicity of 1,1,2,2-tetrachloroethane (TTCE)is dependent on the free-radical production during hepatic biotrasformation, it was of interest to determine whether this haloalkane might affect glycosylation mechanisms by changing dolichol levels and distribution in rat liver microsomes and Golgi apparatus (GA). Male Sprague-Dawley rats received a single dose of TTCE (574 mg/kg body weight) and were then sacrificed at different times (5, 15, 30, or 60 min). In the TTCE-treated rats both serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and hepatic triglycerides (TG) were significantly higher than control, while microsomal glucose 6-phosphatase (G6Pase) activity was decreased. In total microsomes Dol-P levels considered rate-limiting for the biosynthesis of the N-glycosylated proteins were significantly lower than in the control group 15 min after TTCE treatment. In normal rat liver, F1 secretory fraction of CA is 60-fold enriched in total dolichol content with respect to microsomes. In this compartment the total dolichol content, essential for the increase in membrane fluidity and permeability required for glycoprotein maturation and secretion, decreased significantly 5 min after TTCE treatment. Our results suggest that TTCE may affect dolichol functions in rat liver. PMID:9652549

  12. Cypermethrin alters Glial Fibrillary Acidic Protein levels in the rat brain.

    PubMed

    Malkiewicz, Katarzyna; Koteras, Marcin; Folkesson, Ronnie; Brzezinski, Jacek; Winblad, Bengt; Szutowski, Miroslaw; Benedikz, Eirikur

    2006-01-01

    Pyrethroids, widely used insecticides, are biologically active in neurons. Whether they act on the non-neuronal brain cells remains an open question. Thus, the aim of this study was to examine whether Cypermethrin intoxication affects astroglial cells in the rat brain. The levels of Glial Fibrillary Acidic Protein (GFAP) in different brain regions were measured by ELISA following oral treatment with 5 or 10% of LD(50) of Cypermethrin per day for 6 days. A significant decrease of GFAP was observed in different brain regions of treated animals. The cerebral cortex showed the most pronounced effect with GFAP levels reduced to 81% of the controls 2 days after treatment and 77% 21 days after treatment. Although we did not find profound changes in the morphology of astrocytes in Cypermethrin treated animals, the decrease in GFAP suggests that astrocytes were affected by low doses of pyrethroids. The possible consequences were discussed. PMID:21783638

  13. Low irradiances affect abscisic acid, indole-3-acidic acid, and cytokinin levels of wheat (Triticum aestivum L.) tissues

    NASA Technical Reports Server (NTRS)

    Nan, R.; Carman, J. G.; Salisbury, F. B.

    1999-01-01

    Wheat (Triticum aestivum L.) plants were grown under four irradiance levels: 1,400, 400, 200, and 100 micromol m-2 s-1. Leaves and roots were sampled before, during, and after the boot stage, and levels of abscisic acid (ABA), indole-3-acetic acid (IAA), zeatin, zeatin riboside, dihydrozeatin, dihydrozeatin riboside, isopentenyl adenine, and isopentenyl adenosine were quantified using noncompetitive indirect ELISA systems. Levels of IAA in leaves and roots of plants exposed to 100 micromol m-2 s-1 of irradiance were 0.7 and 2.9 micromol kg-1 dry mass (DM), respectively. These levels were 0.2 and 1.0 micromol kg-1 DM, respectively, when plants were exposed to 1,400 micromol m-2 s-1. Levels of ABA in leaves and roots of plants exposed to 100 micromol m-2 s-1 were 0.65 and 0.55 micromol kg-1 DM, respectively. They were 0.24 micromol kg-1 DM (both leaves and roots) when plants were exposed to 1,400 micromol m-2 s-1. Levels of isopentenyl adenosine in leaves (24.3 nmol kg-1 DM) and roots (29.9 nmol kg-1 DM) were not affected by differences in the irradiance regime. Similar values were obtained in a second experiment. Other cytokinins could not be detected (<10 nmol kg 1 DM) in either experiment with the sample sizes used (150-600 mg DM for roots and shoots, respectively).

  14. Short term tolvaptan increases water intake and effectively decreases urinary calcium oxalate, calcium phosphate, and uric acid supersaturations

    PubMed Central

    Cheungpasitporn, Wisit; Erickson, Stephen B.; Rule, Andrew D.; Enders, Felicity; Lieske, John C.

    2016-01-01

    Purpose Many patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should reduce urinary supersaturation (SS) of stone forming solutes, but this has never been proven. Materials and Methods We conducted a double blind, randomized, placebo-controlled, crossover study in 21 adult calcium urinary stone formers stratified as majority calcium oxalate(CaOx, n=10) or calcium phosphate(CaP, n=11). Patients received tolvaptan 45 mg/day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24h urines was collected at the end of weeks 1 and 3. Results Tolvaptan vs. placebo decreased urinary osmolality (204±96 vs 529±213 mOsm/kg, P<0.001) and increased urinary volume (4.8±2.9 vs 1.8±0.9 L, P<0.001). The majority of urinary solute excretion rates including sodium and calcium did not significantly change, although oxalate secretion slightly increased (23±8 to 15±8 mg/24h, P = 0.009). Urinary CaOx SS (−0.01±1.14 vs 0.95±0.87 DG, P<0.001), CaP SS (−1.66±1.17 vs −0.13±1.02 DG, P<0.001) and Uric Acid SS (−2.05±4.05 vs −5.24±3.12 DG, P=0.04) all dramatically decreased. Effects did not differ between CaOx and CaP groups (P>0.05 for all interactions). Conclusions Tolvaptan increases urine volume and decreases urinary SS in calcium stone formers. Further study is needed to determine if long term use of V2 receptor antagonists results in fewer stone events. PMID:26598423

  15. Clavulanic acid enhances glutamate transporter subtype I (GLT-1) expression and decreases reinforcing efficacy of cocaine in mice.

    PubMed

    Kim, Jae; John, Joel; Langford, Dianne; Walker, Ellen; Ward, Sara; Rawls, Scott M

    2016-03-01

    The β-lactam antibiotic ceftriaxone (CTX) reduces cocaine reinforcement and relapse in preclinical assays through a mechanism involving activation of glutamate transporter subtype 1 (GLT-1). However, its poor brain penetrability and intravenous administration route may limit its therapeutic utility for indications related to CNS diseases. An alternative is clavulanic acid (CA), a structural analog of CTX that retains the β-lactam core required for GLT-1 activity but displays enhanced brain penetrability and oral activity relative to CTX. Here, we tested the hypothesis that CA (1, 10 mg/kg ip) would enhance GLT-1 expression and decrease cocaine self-administration (SA) in mice, but at lower doses than CTX. Experiments revealed that GLT-1 transporter expression in the nucleus accumbens of mice treated with repeated CA (1, 10 mg/kg) was enhanced relative to saline-treated mice. Repeated CA treatment (1 mg/kg) reduced the reinforcing efficacy of cocaine (0.56 mg/kg/inf) in mice maintained on a progressive-ratio (PR) schedule of reinforcement but did not affect acquisition of cocaine SA under fixed-ratio responding or acquisition or retention of learning. These findings suggest that the β-lactamase inhibitor CA can activate the cellular glutamate reuptake system in the brain reward circuit and reduce cocaine's reinforcing efficacy at 100-fold lower doses than CTX. PMID:26543027

  16. Early life trauma is associated with decreased peripheral levels of thyroid-hormone T3 in adolescents.

    PubMed

    Machado, T D; Salum, G A; Bosa, V L; Goldani, M Z; Meaney, M J; Agranonik, M; Manfro, G G; Silveira, P P

    2015-12-01

    An adverse early life environment can induce changes on behavioral and metabolic responses later in life. Recent studies in rats showed that the quality of maternal care as measured by high levels of pup licking and grooming (LG) was associated with changes in the relationship between the precursor thyroid-hormone T4 and the more active T3. Here we investigated if early exposure to childhood abuse is associated with thyroid-hormone levels in human adolescents. Given the empirical evidence from animal models showing that good maternal care was associated with increased conversion of T4 to T3, we hypothesized that early adversity would be associated with a decreased peripheral conversion of T4 to T3. A sample of 80 adolescents (10-18 years) participated in this study. We used the Childhood Trauma Questionnaire to investigate early life stress. We calculate the body mass index (BMI) assessing weight and height and sexual maturation stage was determined by self-assessment. Blood samples were collected to measure T3 and T4 levels. ANCOVA were used to evaluate the influence of the Physical Abuse domain of the Childhood Trauma Questionnaire as the early life stress variable in T3 and T4 separately, adjusted for potential confounders such as pubertal status, gender, socioeconomic status and BMI. Early life trauma was associated with reduced T3 levels in adolescents, when adjusted for potential confounders (p=0.013), but not with peripheral T4 levels (p=0.625). We extended findings from animal models showing that adverse early experience persistently impacts on the individual's responses to stress, which is marked by an abnormal metabolism of thyroid hormones. Further studies are needed to further investigate the nature of such associations. PMID:26521949

  17. Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1)

    PubMed Central

    Beraldo, Flavio H.; Thomas, Anu; Kolisnyk, Benjamin; Hirata, Pedro H.; De Jaeger, Xavier; Martyn, Amanda C.; Fan, Jue; Goncalves, Daniela F.; Cowan, Matthew F.; Masood, Talal; Martins, Vilma R.; Gros, Robert; Prado, Vania F.; Prado, Marco A. M.

    2015-01-01

    ABSTRACT Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes. PMID:26398952

  18. Unsaturated fatty acids supplementation reduces blood lead level in rats.

    PubMed

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: "super lecithin" (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  19. Unsaturated Fatty Acids Supplementation Reduces Blood Lead Level in Rats

    PubMed Central

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: “super lecithin” (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  20. E3 Ubiquitin Ligase NEDD4 Promotes Influenza Virus Infection by Decreasing Levels of the Antiviral Protein IFITM3

    PubMed Central

    Chesarino, Nicholas M.; McMichael, Temet M.; Yount, Jacob S.

    2015-01-01

    Interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cell-intrinsic factor that limits influenza virus infections. We previously showed that IFITM3 degradation is increased by its ubiquitination, though the ubiquitin ligase responsible for this modification remained elusive. Here, we demonstrate that the E3 ubiquitin ligase NEDD4 ubiquitinates IFITM3 in cells and in vitro. This IFITM3 ubiquitination is dependent upon the presence of a PPxY motif within IFITM3 and the WW domain-containing region of NEDD4. In NEDD4 knockout mouse embryonic fibroblasts, we observed defective IFITM3 ubiquitination and accumulation of high levels of basal IFITM3 as compared to wild type cells. Heightened IFITM3 levels significantly protected NEDD4 knockout cells from infection by influenza A and B viruses. Similarly, knockdown of NEDD4 in human lung cells resulted in an increase in steady state IFITM3 and a decrease in influenza virus infection, demonstrating a conservation of this NEDD4-dependent IFITM3 regulatory mechanism in mouse and human cells. Consistent with the known association of NEDD4 with lysosomes, we demonstrate for the first time that steady state turnover of IFITM3 occurs through the lysosomal degradation pathway. Overall, this work identifies the enzyme NEDD4 as a new therapeutic target for the prevention of influenza virus infections, and introduces a new paradigm for up-regulating cellular levels of IFITM3 independently of IFN or infection. PMID:26263374

  1. Decreased Levels of BAG3 in a Family with a Rare Variant and in Idiopathic Dilated Cardiomyopathy†

    PubMed Central

    Feldman, Arthur M.; Begay, Rene L.; Knezevic, Tijana; Myers, Valerie D.; Slavov, Dobromir B.; Zhu, Weizhong; Gowan, Katherine; Graw, Sharon L.; Jones, Kenneth L.; Tilley, Douglas G.; Coleman, Ryan C.; Walinsky, Paul; Cheung, Joseph Y.; Mestroni, Luisa; Khalili, Kamel; Taylor, Mathew R.G.

    2015-01-01

    The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole-exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10-nucleotide deletion in the BCL2-associated athanogene 3 (BAG3) gene ((Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C-terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end-stage HF undergoing cardiac transplantation when compared with non-failing controls. Diminished levels of BAG3 protein may be associated with both familial and non-familial forms of dilated cardiomyopathy. PMID:24623017

  2. Impact of micronised purified flavonoid fraction on increased malondialdehyde and decreased metalloproteinase-2 and metalloproteinase-9 levels in varicocele: outcome of an experimentally induced varicocele.

    PubMed

    Dogan, F; Armagan, A; Oksay, T; Akman, T; Aylak, F; Bas, E

    2014-05-01

    To analyse the levels of an indirect marker of ROS-induced lipid peroxidation [i.e. malondialdehyde (MDA)] in both testes and the levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase inhibitor-1 (TIMP-1) in the left testis after induction of varicocele and investigated the impact of micronised purified flavonoid fraction (MPFF) on these markers. Forty-nine adolescent (6-week-old) male Wistar rats were included in this study. The rats were divided into seven groups as follows:Group-1, control; Group-2, sham; Group-3, left varicocele-induced; Group-4, varicocele + varicocelectomy + MPFF-treated (for 4 weeks); Group-5, varicocele + MPFF-treated (for 8 weeks); Group-6, varicocele-induced and 4 weeks later, MPFF-treated (for 4 weeks); and Group-7, varicocele + varicocelectomy. MDA was measured in the tissues of both testes using the thiobarbituric acid reactivity method. The ELISA method was used for the quantification of MMP-2, MMP-9 and TIMP-1 in the left testicular tissue. The levels of MDA were significantly higher in the varicocele group than in the other groups. The MDA levels in the left testicular tissues of Group-7 were significantly higher than those of Group 4 (P = 0.03). In the varicocele group, the MMP-2 and MMP-9 levels decreased, whereas the levels of TIMP-1 increased. The tissue levels of MMP-2 in Groups 4, 5 and 7 were significantly higher than those in Group 1 (P < 0.05). PMID:23550531

  3. Effects of dietary pantethine levels on contents of fatty acids and thiobarbituric acid reactive substances in the liver of rats orally administered varying amounts of autoxidized linoleate.

    PubMed

    Hiramatsu, N; Kishida, T; Hamano, T; Natake, M

    1991-02-01

    The effects of dietary pantethine levels on the contents and compositions of fatty acids and on the levels of lipid peroxides were investigated with rat liver and its S-9 fraction under administration of 0 (non), 0.2 (low dose), and 0.35 ml (high dose) of autoxidized linoleate (AL) per 100 g body weight of the rats per day for 5 days. AL having 800 meq/kg of peroxide value (PV) and 1,700 meq/kg of carbonyl value (CV) was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25 mg% (adequate), and 125 mg% pantethine (excess). In the pantethine-deficient and -adequate groups, the contents of fatty acids both in the liver homogenate and in the S-9 fraction were correspondingly decreased by increasing dose levels of AL, and the decrease was remarkable especially in the pantethine-deficient group, but was not significant in the pantethine-excess group even by a high dose of AL. Particularly, in the high dose of AL, the notable decreases of oleic acid (C18:1) contents in both the liver and the S-9 fraction were observed in rats of the pantethine-deficient and -adequate groups. The thiobarbituric acid (TBA) values in the liver homogenate and the S-9 fraction were increased correspondingly by increasing dose levels of AL, and the increases were repressed in the pantethine-excess group. PMID:1880633

  4. Decreasing global transcript levels over time suggest that phytoplasma cells enter stationary phase during plant and insect colonization.

    PubMed

    Pacifico, D; Galetto, L; Rashidi, M; Abbà, S; Palmano, S; Firrao, G; Bosco, D; Marzachì, C

    2015-04-01

    To highlight different transcriptional behaviors of the phytoplasma in the plant and animal host, expression of 14 genes of "Candidatus Phytoplasma asteris," chrysanthemum yellows strain, was investigated at different times following the infection of a plant host (Arabidopsis thaliana) and two insect vector species (Macrosteles quadripunctulatus and Euscelidius variegatus). Target genes were selected among those encoding antigenic membrane proteins, membrane transporters, secreted proteins, and general enzymes. Transcripts were detected for all analyzed genes in the three hosts; in particular, those encoding the antigenic membrane protein Amp, elements of the mechanosensitive channel, and two of the four secreted proteins (SAP54 and TENGU) were highly accumulated, suggesting that they play important roles in phytoplasma physiology during the infection cycle. Most transcripts were present at higher abundance in the plant host than in the insect hosts. Generally, transcript levels of the selected genes decreased significantly during infection of A. thaliana and M. quadripunctulatus but were more constant in E. variegatus. Such decreases may be explained by the fact that only a fraction of the phytoplasma population was transcribing, while the remaining part was aging to a stationary phase. This strategy might improve long-term survival, thereby increasing the likelihood that the pathogen may be acquired by a vector and/or inoculated to a healthy plant. PMID:25636844

  5. Decreasing Global Transcript Levels over Time Suggest that Phytoplasma Cells Enter Stationary Phase during Plant and Insect Colonization

    PubMed Central

    Pacifico, D.; Galetto, L.; Rashidi, M.; Abbà, S.; Palmano, S.; Firrao, G.; Bosco, D.

    2015-01-01

    To highlight different transcriptional behaviors of the phytoplasma in the plant and animal host, expression of 14 genes of “Candidatus Phytoplasma asteris,” chrysanthemum yellows strain, was investigated at different times following the infection of a plant host (Arabidopsis thaliana) and two insect vector species (Macrosteles quadripunctulatus and Euscelidius variegatus). Target genes were selected among those encoding antigenic membrane proteins, membrane transporters, secreted proteins, and general enzymes. Transcripts were detected for all analyzed genes in the three hosts; in particular, those encoding the antigenic membrane protein Amp, elements of the mechanosensitive channel, and two of the four secreted proteins (SAP54 and TENGU) were highly accumulated, suggesting that they play important roles in phytoplasma physiology during the infection cycle. Most transcripts were present at higher abundance in the plant host than in the insect hosts. Generally, transcript levels of the selected genes decreased significantly during infection of A. thaliana and M. quadripunctulatus but were more constant in E. variegatus. Such decreases may be explained by the fact that only a fraction of the phytoplasma population was transcribing, while the remaining part was aging to a stationary phase. This strategy might improve long-term survival, thereby increasing the likelihood that the pathogen may be acquired by a vector and/or inoculated to a healthy plant. PMID:25636844

  6. Decreased arachidonic acid content and metabolism in tissues of NZB/W F1 females fed a diet containing 0. 45% dehydroisoandrosterone (DHA)

    SciTech Connect

    Matsunaga, A.; Cottam, G.L.

    1987-05-01

    A diet containing 0.45% DHA fed to NZB/W mice, a model of systemic lupus erythematosus, delays the time of onset, improves survival and decreases the formation of antibodies to ds-DNA. Essential fatty acid-deficient diets or inclusion of eicosapentaenoic acid have similar beneficial effects and led them to investigate arachidonic acid metabolism in response to feeding DHA. The arachidonic acid content of plasma cholesteryl ester decreased from 37.4 +/- 2.2 to 28.2 +/- 1.3 mg%. In total liver phospholipid the value decreased from 18.1 +/- 0.52 to 13.7 +/- 1.3 mg%, in total kidney phospholipid the value decreased from 24.10 +/- 0.87 to 20.7 +/- 0.32 mg% and in resident peritoneal macrophages the value decreased from 15.4 +/- 4.6 to 3.6 +/- 1.4 mg%. The metabolism of exogenous (1-/sup 14/C)arachidonic acid by resident peritoneal macrophages in response to Zymosan stimulation for 2 hr was examined by extraction of metabolites and separation by HPLC. Cells isolated from DHA-fed animals produced less PGE2 than controls, yet similar amounts of 6-keto PGF1..cap alpha.. were produced. Arachidonic acid metabolites have significant effects on the immune system and may be a mechanism involved in the benefits obtained by inclusion of DHA in the diet.

  7. Decreased glycogen synthase kinase 3-beta levels and related physiological changes in Bacillus anthracis lethal toxin-treated macrophages.

    PubMed

    Tucker, Amy E; Salles, Isabelle I; Voth, Daniel E; Ortiz-Leduc, William; Wang, Han; Dozmorov, Igor; Centola, Michael; Ballard, Jimmy D

    2003-08-01

    The lethal factor (LF) component of Bacillus anthracis lethal toxin (LeTx) cleaves mitogen activated protein kinase kinases (MAPKKs) in a variety of different cell types, yet only macrophages are rapidly killed by this toxin. The reason for this selective killing is unclear, but suggests other factors may also be involved in LeTx intoxication. In the current study, DNA membrane arrays were used to identify broad changes in macrophage physiology after treatment with LeTx. Expression of genes regulated by MAPKK activity did not change significantly, yet a series of genes under glycogen synthase kinase-3-beta (GSK-3beta) regulation changed expression following LeTx treatment. Correlating with these transcriptional changes GSK-3beta was found to be below detectable levels in toxin-treated cells and an inhibitor of GSK-3beta, LiCl, sensitized resistant IC-21 macrophages to LeTx. In addition, zebrafish embryos treated with LeTx showed signs of delayed pigmentation and cardiac hypertrophy; both processes are subject to regulation by GSK-3beta. A putative compensatory response to loss of GSK-3beta was indicated by differential expression of three motor proteins following toxin treatment and Kif1C, a motor protein involved in sensitivity to LeTx, increased expression in toxin-sensitive cells yet decreased in resistant cells following toxin treatment. Differential expression of microtubule-associating proteins and a decrease in the level of cellular tubulin were detected in LeTx-treated cells, both of which can result from loss of GSK-3beta activity. These data provide new information on LeTx's overall influence on macrophage physiology and suggest loss of GSK-3beta contributes to cytotoxicity. PMID:12864812

  8. Linolenic acid improves oocyte developmental competence and decreases apoptosis of in vitro-produced blastocysts in goat.

    PubMed

    Veshkini, Arash; Khadem, Ali Akbar; Mohammadi-Sangcheshmeh, Abdollah; Alamouti, Ali Asadi; Soleimani, Masoud; Gastal, Eduardo L

    2016-08-01

    The effects of α-linolenic acid (ALA) on developmental competence of oocytes in goats were evaluated in this study. Initially, the level of ALA in small and large antral follicles was determined to be in a range of 0.018-0.028 mg/ml (64.6-100.6 μM, respectively). In vitro maturation was performed in the presence of various concentrations (10, 50, 100, or 200 μM) of ALA. Cumulus expansion, meiotic maturation, levels of intracellular glutathione (GSH), embryonic cleavage, blastocyst formation following parthenogenetic activation (PA) and in vitro fertilization (IVF), number of total and apoptotic cells in blastocyst, and expression of Bax, Bcl-2, and p53 genes in blastocyst cells were determined. Compared with the control, no improvement was observed in cumulus expansion in ALA-treated groups. At 50 μM concentration, ALA increased meiotic maturation rate but had no effect on GSH level. When oocytes treated with 50 μM ALA were subsequently used for PA or IVF, a higher rate of blastocyst formation was observed, and these embryos had a higher total cell number and a lower apoptotic cell number. Expression analyses of genes in blastocysts revealed lesser transcript abundances for Bax gene, and higher transcript abundances for Bcl-2 gene in 50 μM ALA group. Expression of p53 gene was also less observed in ALA-treated blastocysts. Our results show that ALA treatment at 50 μM during in vitro maturation (IVM) had a beneficial effect on maturation of goat oocytes and this, in turn, stimulated embryonic development and regulated apoptotic gene expression. PMID:26584822

  9. Pseudomembranous Type of Oral Candidiasis is Associated with Decreased Salivary Flow Rate and Secretory Immunoglobulin A Levels.

    PubMed

    Mahajan, Bela; Bagul, Neeta; Desai, Rajiv; Reddy, Mamatha; Mahajan, Amit; Shete, Ashwini; Risbud, Arun; Mane, Arati

    2015-08-01

    Saliva plays an important role in maintaining microbial homeostasis in the oral cavity, while salivary gland hypofunction predisposes the oral mucosa to pathologic alteration and increases the risk for oral candidiasis. This study sought to determine the salivary flow rate (SFR) and secretory immunoglobulin A (SIgA) levels in HIV-positive and HIV-negative individuals and evaluate their relationship with the determinants of oral candidiasis. Sixty HIV-positive (30 with and 30 without oral candidiasis) and 30 healthy HIV-negative individuals were enrolled. Cotton pellet was weighed pre- and post-saliva collection for the assessment of SFR, while SIgA levels were estimated by commercial ELISA (Diametra, Italy) kit. The mean ± SD, SFR and SIgA levels in HIV-positive individuals with candidiasis, without candidiasis and HIV-negative controls were 0.396 ± 0.290, 0.546 ± 0.355 and 0.534 ± 0.214 ml/min and 115.891 ± 37.621, 136.024 ± 51.075 and 149.418 ± 31.765 µg/ml, respectively. A positive correlation between low CD4 counts (indicator of immunodeficiency) and SIgA was observed in HIV-positive individuals with candidiasis (r = 0.373, p = 0.045). We also report here for the first time the significant decrease in SFR and SIgA levels in individuals presenting with pseudomembranous type of oral candidiasis and Candida albicans infection. PMID:25682023

  10. Ingestion of a single serving of saury alters postprandial levels of plasma n-3 polyunsaturated fatty acids and long-chain monounsaturated fatty acids in healthy human adults

    PubMed Central

    2012-01-01

    Background Saury oil contains considerable amounts of n-3 polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) with long aliphatic tails (>18C atoms). Ingestion of saury oil reduces the risk of developing metabolic syndrome concomitant with increases in n-3 PUFA and long-chain MUFA in plasma and organs of mice. We therefore evaluated changes in postprandial plasma fatty acid levels and plasma parameters in healthy human subjects after ingestion of a single meal of saury. Findings Five healthy human adults ingested 150 g of grilled saury. Blood was collected before the meal and at 2, 6, and 24 hr after the meal, and plasma was prepared. Plasma levels of eicosapentaenoic acid, docosahexaenoic acid, and long-chain MUFA (C20:1 and C22:1 isomers combined) increased significantly throughout the postprandial period compared with the pre-meal baseline. Postprandial plasma insulin concentration increased notably, and plasma levels of glucose and free fatty acids decreased significantly and subsequently returned to the pre-meal levels. Conclusions Our study suggests that a single saury meal may alter the postprandial plasma levels of n-3 PUFA and long-chain MUFA in healthy human subjects. PMID:22846384

  11. Nucleophilic compounds decrease advanced glycation end products (AGEs) from ascorbic acid in the hSVCT2 transgenic mouse model of lenticular aging

    PubMed Central

    Fan, Xingjun; Monnier, Vincent M

    2008-01-01

    Purpose Senile cataracts are associated with oxidation, fragmentation, cross-linking, insolubilization, and yellow pigmentation of lens crystallins. This process is partially explained by advanced glycation endproducts (AGEs) from ascorbic acid (ASA), as unequivocally demonstrated in our hSVCT2 transgenic mouse(PNAS 103:16912, 2006). We now present the first pharmacological intervention study against ascorbylation in these mice. Methods Five groups of mice (10 mice/group) were fed from two to nine months a diet containing 0.1% (wt/wt) aminoguanidine (AG), pyridoxamine (PM), penicillamine (PA), and nucleophilic compounds NC-I and NC-II. AGEs were determined in crystallin digests using HPLC, LC-MS or GC-MS. In vitro incubations of lens protein extract with ASA or dehydroascorbic aicd (DHA) were also performed. Results ASA level increased ~10 fold in all groups and was unaffected by treatment. AGEs were several fold increased in transgenic compared to control lenses. Body weight, food intake, lenticular glutathione and glycated lysine level were unaltered. In vitro, all compounds inhibited AGE formation. In vivo, NC-I and NC-II significantly decreased protein fluorescence at λex335/em385 (p=0.045, 0.017, respectively) and λex370/em440 (p=0.029, 0.007, respectively). Other inhibitors had no effect. After 7 months, only NC-1 and NC-2 induced a 50 % reduction in pentosidine (n.s, p=0.035 respectively). NC-1 also decreased carboxymethyllysine (CML) (p=0.032) and carboxyethyllysine (CEL) (p= n.s). Fluorescent crosslink K2P was decreased by NC-1, NC-2, AG and PM (p= n.s). Conclusions Pharmacologically blocking protein ascorbylation with absorbable guanidino compounds is feasible and may represent a new strategy for the delay of age-related nuclear sclerosis of the lens. PMID:18421088

  12. PINK1 Deficiency Decreases Expression Levels of mir-326, mir-330, and mir-3099 during Brain Development and Neural Stem Cell Differentiation.

    PubMed

    Choi, Insup; Woo, Joo Hong; Jou, Ilo; Joe, Eun-Hye

    2016-02-01

    PTEN-induced putative kinase 1 (PINK1) is a Parkinson's disease (PD) gene. We examined miRNAs regulated by PINK1 during brain development and neural stem cell (NSC) differentiation, and found that lvels of miRNAs related to tumors and inflammation were different between 1-day-old-wild type (WT) and PINK1-knockout (KO) mouse brains. Notably, levels of miR-326, miR-330 and miR-3099, which are related to astroglioma, increased during brain development and NSC differentiation, and were significantly reduced in the absence of PINK1. Interestingly, in the presence of ciliary neurotrophic factor (CNTF), which pushes differentiation of NSCs into astrocytes, miR-326, miR-330, and miR-3099 levels in KO NSCs were also lower than those in WT NSCs. Furthermore, mimics of all three miRNAs increased expression of the astrocytic marker glial fibrillary acidic protein (GFAP) during differentiation of KO NSCs, but inhibitors of these miRNAs decreased GFAP expression in WT NSCs. Moreover, these miRNAs increased the translational efficacy of GFAP through the 3'-UTR of GFAP mRNA. Taken together, these results suggest that PINK1 deficiency reduce expression levels of miR-326, miR-330 and miR-3099, which may regulate GFAP expression during NSC differentiation and brain development. PMID:26924929

  13. PINK1 Deficiency Decreases Expression Levels of mir-326, mir-330, and mir-3099 during Brain Development and Neural Stem Cell Differentiation

    PubMed Central

    Choi, Insup; Woo, Joo Hong; Jou, Ilo

    2016-01-01

    PTEN-induced putative kinase 1 (PINK1) is a Parkinson's disease (PD) gene. We examined miRNAs regulated by PINK1 during brain development and neural stem cell (NSC) differentiation, and found that lvels of miRNAs related to tumors and inflammation were different between 1-day-old-wild type (WT) and PINK1-knockout (KO) mouse brains. Notably, levels of miR-326, miR-330 and miR-3099, which are related to astroglioma, increased during brain development and NSC differentiation, and were significantly reduced in the absence of PINK1. Interestingly, in the presence of ciliary neurotrophic factor (CNTF), which pushes differentiation of NSCs into astrocytes, miR-326, miR-330, and miR-3099 levels in KO NSCs were also lower than those in WT NSCs. Furthermore, mimics of all three miRNAs increased expression of the astrocytic marker glial fibrillary acidic protein (GFAP) during differentiation of KO NSCs, but inhibitors of these miRNAs decreased GFAP expression in WT NSCs. Moreover, these miRNAs increased the translational efficacy of GFAP through the 3'-UTR of GFAP mRNA. Taken together, these results suggest that PINK1 deficiency reduce expression levels of miR-326, miR-330 and miR-3099, which may regulate GFAP expression during NSC differentiation and brain development. PMID:26924929

  14. Insertional Inactivation of Branched-Chain α-Keto Acid Dehydrogenase in Staphylococcus aureus Leads to Decreased Branched-Chain Membrane Fatty Acid Content and Increased Susceptibility to Certain Stresses▿

    PubMed Central

    Singh, Vineet K.; Hattangady, Dipti S.; Giotis, Efstathios S.; Singh, Atul K.; Chamberlain, Neal R.; Stuart, Melissa K.; Wilkinson, Brian J.

    2008-01-01

    Staphylococcus aureus is a major community and nosocomial pathogen. Its ability to withstand multiple stress conditions and quickly develop resistance to antibiotics complicates the control of staphylococcal infections. Adaptation to lower temperatures is a key for the survival of bacterial species outside the host. Branched-chain α-keto acid dehydrogenase (BKD) is an enzyme complex that catalyzes the early stages of branched-chain fatty acid (BCFA) production. In this study, BKD was inactivated, resulting in reduced levels of BCFAs in the membrane of S. aureus. Growth of the BKD-inactivated mutant was progressively more impaired than that of wild-type S. aureus with decreasing temperature, to the point that the mutant could not grow at 12°C. The growth of the mutant was markedly stimulated by the inclusion of 2-methylbutyrate in the growth medium at all temperatures tested. 2-Methylbutyrate is a precursor of odd-numbered anteiso fatty acids and bypasses BKD. Interestingly, growth of wild-type S. aureus was also stimulated by including 2-methylbutyrate in the medium, especially at lower temperatures. The anteiso fatty acid content of the BKD-inactivated mutant was restored by the inclusion of 2-methylbutyrate in the medium. Fluorescence polarization measurements indicated that the membrane of the BKD-inactivated mutant was significantly less fluid than that of wild-type S. aureus. Consistent with this result, the mutant showed decreased toluene tolerance that could be increased by the inclusion of 2-methylbutyrate in the medium. The BKD-inactivated mutant was more susceptible to alkaline pH and oxidative stress conditions. Inactivation of the BKD enzyme complex in S. aureus also led to a reduction in adherence of the mutant to eukaryotic cells and its survival in a mouse host. In addition, the mutant offers a tool to study the role of membrane fluidity in the interaction of S. aureus with antimicrobial substances. PMID:18689519

  15. Short-term oral exposure to aluminium decreases glutathione intestinal levels and changes enzyme activities involved in its metabolism.

    PubMed

    Orihuela, Daniel; Meichtry, Verónica; Pregi, Nicolás; Pizarro, Manuel

    2005-09-01

    To study the effects of aluminium (Al) on glutathione (GSH) metabolism in the small intestine, adult male Wistar rats were orally treated with AlCl3.6H2O at doses of 30, 60, 120 and 200 mg/kg body weight (b.w.) per day, during seven days. Controls received deionized water. At doses above 120 mg/kg b.w., Al produced both a significant reduction of GSH content and an increase of oxidized/reduced glutathione ratio (P < 0.05). The index of oxidative stress of the intestine mucosa in terms of lipid peroxidation evaluated by thiobarbituric acid reactive substances was significantly increased (52%) at higher Al dose used. The duodenal expression of the multidrug resistance-associated protein 2 in brush border membranes, determined by Western blot technique, was increased 2.7-fold in rats treated with 200mg AlCl3/kg b.w (P < 0.01). Intestine activities of both GSH-synthase (from 60 mg/kg b.w.) and GSSG-reductase (from 120 mg/kg b.w.) were significantly reduced (26% and 31%, respectively) while glutathione-S-transferase showed to be slightly modified in the Al-treated groups. Conversely, gamma-glutamyltranspeptidase activity was significantly increased (P < 0.05) due to the Al treatment. Al reduced in vitro mucosa-to-lumen GSH efflux (P < 0.05). A positive linear correlation between the intestine GSH depletion and reduction of in situ 45Ca intestinal absorption, both produced by Al, was found (r = 0.923, P = 0.038). Taking as a whole, these results show that Al would alter GSH metabolism in small intestine by decreasing its turnover, leading to an unbalance of redox state in the epithelial cells, thus contributing to deteriorate GSH-dependent absorptive functions. PMID:16084594

  16. Nitric Oxide Signaling in Pseudomonas aeruginosa Biofilms Mediates Phosphodiesterase Activity, Decreased Cyclic Di-GMP Levels, and Enhanced Dispersal▿ †

    PubMed Central

    Barraud, Nicolas; Schleheck, David; Klebensberger, Janosch; Webb, Jeremy S.; Hassett, Daniel J.; Rice, Scott A.; Kjelleberg, Staffan

    2009-01-01

    Bacteria in biofilms often undergo active dispersal events and revert to a free-swimming, planktonic state to complete the biofilm life cycle. The signaling molecule nitric oxide (NO) was previously found to trigger biofilm dispersal in the opportunistic pathogen Pseudomonas aeruginosa at low, nontoxic concentrations (N. Barraud, D. J. Hassett, S. H. Hwang, S. A. Rice, S. Kjelleberg, and J. S. Webb, J. Bacteriol. 188:7344-7353, 2006). NO was further shown to increase cell motility and susceptibility to antimicrobials. Recently, numerous studies revealed that increased degradation of the secondary messenger cyclic di-GMP (c-di-GMP) by specific phosphodiesterases (PDEs) triggers a planktonic mode of growth in eubacteria. In this study, the potential link between NO and c-di-GMP signaling was investigated by performing (i) PDE inhibitor studies, (ii) enzymatic assays to measure PDE activity, and (iii) direct quantification of intracellular c-di-GMP levels. The results suggest a role for c-di-GMP signaling in triggering the biofilm dispersal event induced by NO, as dispersal requires PDE activity and addition of NO stimulates PDE and induces the concomitant decrease in intracellular c-di-GMP levels in P. aeruginosa. Furthermore, gene expression studies indicated global responses to low, nontoxic levels of NO in P. aeruginosa biofilms, including upregulation of genes involved in motility and energy metabolism and downregulation of adhesins and virulence factors. Finally, site-directed mutagenesis of candidate genes and physiological characterization of the corresponding mutant strains uncovered that the chemotaxis transducer BdlA is involved in the biofilm dispersal response induced by NO. PMID:19801410

  17. Dialysis water treated by reverse osmosis decreases the levels of C-reactive protein in uremic patients.

    PubMed

    Thomé, F S; Senger, M; Garcez, C; Garcez, J; Chemello, C; Manfro, R C

    2005-05-01

    Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age +/- SD: 51.3 +/- 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients. PMID:15917962

  18. Higher transcription levels in ascorbic acid biosynthetic and recycling genes were associated with higher ascorbic acid accumulation in blueberry.

    PubMed

    Liu, Fenghong; Wang, Lei; Gu, Liang; Zhao, Wei; Su, Hongyan; Cheng, Xianhao

    2015-12-01

    In our preliminary study, the ripe fruits of two highbush blueberry (Vaccinium corymbosum L.) cultivars, cv 'Berkeley' and cv 'Bluecrop', were found to contain different levels of ascorbic acid. However, factors responsible for these differences are still unknown. In the present study, ascorbic acid content in fruits was compared with expression profiles of ascorbic acid biosynthetic and recycling genes between 'Bluecrop' and 'Berkeley' cultivars. The results indicated that the l-galactose pathway was the predominant route of ascorbic acid biosynthesis in blueberry fruits. Moreover, higher expression levels of the ascorbic acid biosynthetic genes GME, GGP, and GLDH, as well as the recycling genes MDHAR and DHAR, were associated with higher ascorbic acid content in 'Bluecrop' compared with 'Berkeley', which indicated that a higher efficiency ascorbic acid biosynthesis and regeneration was likely to be responsible for the higher ascorbic acid accumulation in 'Bluecrop'. PMID:26041210

  19. The potential effectiveness of mercury minerals in decreasing the level of iodine-129 in a nuclear fuel waste disposal vault

    SciTech Connect

    Oscarson, D.W.; Miller, H.G.; Watson, R.L.

    1986-01-01

    Mercury forms sparingly soluble phases with I under certain conditions. Therefore, Hg minerals have been suggested as potential additives to a clay-based buffer material in nuclear fuel waste disposal vault for the selective removal of /sup 129/I from solution. In oxidizing systems containing HgS, clay (bentonite or kaolinite), and either a synthetic groundwater solution (SGW) or deionized, distilled water, it was found that Hg lowers the concentration of I/sup -/ in solution to approx. =10/sup -6/ mol/L. X-ray diffraction analysis indicated that Hg/sub 2/I/sub 2/(s) is formed in these systems and is the phase controlling the level of I/sup -/ in solution. At levels below approx. = 10/sup -6/ mol/L, all the I/sup -/ is consumed in the formation of HgI/sup 0//sub 2/(aq) and no solid Hg-I phase can form. Bentonite has only a minor effect on the Hg/I system, and kaolinite has little or no effect. Theoretical calculations of the Hg system indicate that, under oxidizing conditions and when the levels of C1/sup -/ or Br/sup -/ are approx. =1 and 0.01 mol/L, respectively (values typical for deep groundwaters in the Canadian Shield), Hg/sub 2/I/sub 2/(s) is not able to decrease the I/sup -/ activity below approx. = 10/sup -5/ mol/L, because of the greater stability of Hg/sub 2/Cl/sup 2/(s) and Hg/sub 2/Br/sub 2/(s) phases (in the experimental study, Hg/sub 2/I/sub 2/(s) is able to lower the level of I/sup -/ below 10/sup -5/ mol/L because the Cl/sup -/ concentration in the SGW was lower (0.18 mol/L) and there was no Br/sup -/ in the system). Further, Hg-I minerals are not stable under reducing to mildly oxidizing conditions. The maximum level of /sup 129/I in disposal vault in Canada is likely to be much less than 10/sup -3.5/ mol/L. Therefore, Hg can in solution. The results of this study indicate the Hg minerals would not be effective additives to a buffer material in a disposal vault in the Canadian shield for the removal of /sup 129/I from solution.

  20. Amino acid and vascular endothelial growth factor levels in subretinal fluid in rhegmatogenous retinal detachment

    PubMed Central

    Buyukuysal, Rifat Levent; Gelisken, Oner; Buyukuysal, Cagatay; Can, Basak

    2014-01-01

    Purpose To study the concentrations of amino acids and vascular endothelial growth factor (VEGF) in subretinal fluid (SRF) of cases with rhegmatogenous retinal detachment (RRD). The relevance of the results with postoperative anatomic and functional success in RRD was investigated. Methods Fifty-three patients were included in this prospective study. The study group consisted of 46 patients who had scleral buckling surgery with the diagnosis of RRD, and SRF was obtained during the surgery. The control specimens consisted of vitreous samples of seven patients who were diagnosed with pars plana vitrectomy without RRD. Study cases were divided into three groups, corresponding to the duration of retinal detachment. Clinical characteristics, including best corrected visual acuity (BCVA) and anatomic status at month 6, were recorded. Concentrations of 15 selected amino acids were quantified by using high performance liquid chromatography, and VEGF levels were measured with enzyme immunoassay. Results When compared with the control group, SRF concentrations of aspartate, citrulline, glutamate, and glycine increased significantly in the study group (p<0.05). Statistical analysis showed that concentrations of alanine, isoleucine, leucine, methionine, phenylalanine, threonine, tyrosine, and valine decreased (p<0.05). SRF levels of glutamine, taurine, and serine had no significant change. SRF VEGF levels were significantly higher than the vitreous samples of the controls (p<0.001). Time-dependent changes and interactions between VEGF and amino acids were observed. There was no correlation between the concentrations of amino acids or VEGF with the parameters of BCVA and anatomical success. Conclusions Significant changes occur in concentrations of amino acids and VEGF in SRF of cases with RRD. Our results suggest that several mechanisms contribute to the pathophysiology. PMID:25352742

  1. The effects of different thermal treatments and organic acid levels on nutrient digestibility in broilers.

    PubMed

    Goodarzi Boroojeni, F; Mader, A; Knorr, F; Ruhnke, I; Röhe, I; Hafeez, A; Männer, K; Zentek, J

    2014-05-01

    Poultry feed is a potential vector for pathogens. Heat processing and organic acid treatments may decontaminate feed and can affect bird performance as well as feed digestibility. The present study was performed to investigate the effect of different thermal treatments including pelleting (P), long-term conditioning at 85°C for 3 min (L), or expanding at 110°C (E110) and 130°C for 3 to 5 s (E130) without or with 0.75 and 1.5% organic acid supplementation (63.75% formic acid, 25.00% propionic acid, and 11.25% water) on performance, nutrient digestibility, and organ weights of broilers. In total, 960 one-day-old broiler chicks were randomly assigned to 8 replicates using a 3 × 4 factorial arrangement. Performance variables were determined, and the relative organ weights and ileal and total amino acid (AA) digestibilities were measured at d 35. The organic acid inclusion linearly improved feed efficiency in the first week (P ≤ 0.05). The acid inclusion levels and thermal treatments had no significant effect on the performance variables at later intervals of the growing period of the birds. The L group showed the lowest ileal AA and CP digestibility. The inclusion of organic acids had a quadratic effect on total and ileal digestibility of isoleucine (P ≤ 0.05), whereas it had no significant effect on the ileal digestibility of other AA and nutrients. The relative weights of the jejunum and small intestine were significantly higher in the E130 group compared with P and L (P ≤ 0.05). In conclusion, our study demonstrated that long-term heat conditioning can decrease ileal nutrient digestibility, whereas pelleting and expansion, independently of organic acid addition, seemed to have no negative impact on broiler performance and nutrient digestibilities. Moreover, adding a blend of organic acids to broiler diets had neither positive nor negative effects on nutrient digestibility and final broiler performance. This indicates the feasibility of short-term thermal

  2. Decreased peroxisome proliferator-activated receptor γ level and signalling in sebaceous glands of patients with acne vulgaris.

    PubMed

    Dozsa, A; Mihaly, J; Dezso, B; Csizmadia, E; Keresztessy, T; Marko, L; Rühl, R; Remenyik, E; Nagy, L

    2016-07-01

    Little is known about the altered lipid metabolism-related transcriptional events occuring in sebaceous glands of patients with acne vulgaris. Peroxisome proliferator-activated receptor (PPAR)γ, a lipid-activated transcription factor, is implicated in differentiation and lipid metabolism of sebocytes. We have observed that PPARγ and its target genes, ADRP (adipose differentiation related protein) and PGAR (PPARγ angioprotein related protein) are expressed at lower levels in sebocytes from patients with acne than in those from healthy controls (HCs) Furthermore, endogenous PPARγ activator lipids such as arachidonic acid-derived keto-metabolites (e.g. 5KETE, 12KETE) are increased in acne-involved and nonacne-involved skin of patients with acne, compared with skin from healthy individuals. Our findings highlight the possible anti-inflammatory role of endogenous ligand-activated PPARγ signaling in human sebocyte biology, and suggest that modulating PPARγ- expression and thereby signaling might be a promising strategy for the clinical management of acne vulgaris. PMID:26800853

  3. c-Myc-mediated expression of nucleophosmin/B23 decreases during retinoic acid-induced differentiation of human leukemia HL-60 cells.

    PubMed

    Yung, Benjamin Y M

    2004-12-17

    The retinoic acid-induced differentiation of human leukemia HL-60 cells towards mature granulocytic cells was accompanied by the decline in the protein levels of c-myc, nucleophosmin/B23 and its promoter activity. These RA-induced effects were further enhanced by the concurrent treatment of HL-60 cells with p38 map kinase inhibitor SB203580 (SB). It seems that there is a strong correlation of nucleophosmin/B23 and c-Myc expressions in cells under RA treatment. Furthermore, nucleophosmin/B23 promoter activity decreased upon c-Myc antisense-mediated reduction of intracellular amount of c-Myc. CHIP assays showed that binding of c-Myc to the nucleophosmin/B23 promoter decreased in RA-treated cells. Thus, nucleophosmin/B23 expression is targeted by c-Myc during RA-induced differentiation. These results provide evidence for a novel mechanism of transcriptional downregulation of nucleophosmin/B23 and the functional role of c-Myc in RA-induced differentiation. PMID:15589822

  4. Reduced levels of NADH-dependent glutamate dehydrogenase decrease the glutamate content of ripe tomato fruit but have no effect on green fruit or leaves.

    PubMed

    Ferraro, Gisela; D'Angelo, Matilde; Sulpice, Ronan; Stitt, Mark; Valle, Estela M

    2015-06-01

    Glutamate (Glu) is a taste enhancer that contributes to the characteristic flavour of foods. In fruit of tomato (Solanum lycopersicum L.), the Glu content increases dramatically during the ripening process, becoming the most abundant free amino acid when the fruit become red. There is also a concomitant increase in NADH-dependent glutamate dehydrogenase (GDH) activity during the ripening transition. This enzyme is located in the mitochondria and catalyses the reversible amination of 2-oxoglutarate to Glu. To investigate the potential effect of GDH on Glu metabolism, the abundance of GDH was altered by artificial microRNA technology. Efficient silencing of all the endogenous SlGDH genes was achieved, leading to a dramatic decrease in total GDH activity. This decrease in GDH activity did not lead to any clear morphological or metabolic phenotype in leaves or green fruit. However, red fruit on the transgenic plants showed markedly reduced levels of Glu and a large increase in aspartate, glucose and fructose content in comparison to wild-type fruit. These results suggest that GDH is involved in the synthesis of Glu in tomato fruit during the ripening processes. This contrasts with the biological role ascribed to GDH in many other tissues and species. Overall, these findings suggest that GDH has a major effect on the control of metabolic composition during tomato fruit ripening, but not at other stages of development. PMID:25878356

  5. Oceanic primary productivity and dissolved oxygen levels at the Cretaceous/Tertiary Boundary: Their decrease, subsequent warming, and recovery

    NASA Astrophysics Data System (ADS)

    Kaiho, Kunio; Kajiwara, Yoshimichi; Tazaki, Kazue; Ueshima, Masato; Takeda, Nobuyori; Kawahata, Hodaka; Arinobu, Tetsuya; Ishiwatari, Ryoshi; Hirai, Akio; Lamolda, Marcos A.

    1999-08-01

    Thirty-six different geochemical and foraminiferal analyses were conducted on samples collected at closely spaced intervals across the Cretaceous/Tertiary (K/T) boundary exposed at Caravaca, Spain. A rapid reduction in the gradient between δ13C values in fine fraction carbonate and benthic foraminiferal calcite and a decrease in the abundance of phosphorus (a proxy for organic carbon) and calcium were recorded in sediments 0-0.5 cm above the K/T boundary. These trends imply that an abrupt mass mortality occurred among pelagic organisms, leading to a significant reduction in the flux of organic carbon to the seafloor. In addition, variations in sulfur isotope ratios, the hydrocarbon-generating potential of kerogen (measured as the hydrogen index), and foraminiferal indices of dissolved oxygen level all imply that a rapid decrease in dissolved oxygen was coincident with the δ13C event. Evidence of the low oxygen event has also been recognized in Japan and New Zealand, suggesting that intermediate water oxygen minima were widely developed during earliest Danian time. A threefold increase in the kaolinite/illite ratio and a 1.2‰ decrease in δ18O (carbonate fine fraction) were recorded in the basal 0.1-2 cm of Danian age sediments. These trends suggest that atmospheric warming and an increase in surface water temperature occurred 0-3 kyr after the δ13C event. Recovery in the difference between δ13C values in the carbonate fine fraction and in benthic foraminiferal calcite as well as increases in phosphorus and calcium contents occur at the base of planktonic foraminiferal Zone Pla, implying that an increase in primary productivity commenced some 13 kyr after the K/T boundary. Tables A1-A3 are available on diskette or via Anonymous FTP from kosmos.agu.org directory APENO (Username = anonymous, Password = guest). Diskette may be ordered from American Geophysical Union, 2000 Florida Avenue, N.W., Washington, DC 20009 or by phone at 800-966-2481; $15.00. Payment must

  6. Serum Glutamate Levels Correlate with Gleason Score and Glutamate Blockade Decreases Proliferation, Migration, and Invasion and Induces Apoptosis in Prostate Cancer Cells

    PubMed Central

    Koochekpour, Shahriar; Majumdar, Sunipa; Azabdaftari, Gissou; Attwood, Kristopher; Scioneaux, Ray; Subramani, Dhatchayini; Manhardt, Charles; Lorusso, Giovanni D.; Willard, Stacey S.; Thompson, Hillary; Shourideh, Mojgan; Rezaei, Katayoon; Sartor, Oliver; Mohler, James L.; Vessella, Robert L.

    2012-01-01

    Purpose During glutaminolysis, glutamine is catabolized to glutamate and incorporated into citric acid cycle and lipogenesis. Serum glutamate levels were measured in patients with primary prostate cancer (PCa) or metastatic castrate-resistant PCa (mCRPCa) to establish clinical relevance. The effect of glutamate-deprivation or blockade by metabotropic glutamate receptor 1 (GRM1)-antagonists was investigated on PCa cells’ growth, migration, and invasion to establish biological relevance. Experimental Design Serum glutamate levels were measured in normal men (n = 60) and patients with primary PCa (n = 197) or mCRPCa (n = 109). GRM1 expression in prostatic tissues was examined using immunohistochemistry (IHC). Cell growth, migration, and invasion were determined using cell cytotoxicity and modified Boyden chamber assays, respectively. Apoptosis was detected using immunoblotting against cleaved caspases, PARP and γ-H2AX. Results Univariate and multivariate analyses demonstrated significantly higher serum glutamate levels in Gleason score ≥ 8 than in the Gleason sscore ≤ 7 and in African Americans than in the Caucasian Americans. African Americans with mCRPCa significantly higher serum glutamate levels than those with primary PCa or benign prostate. However, in Caucasian Americans, serum glutamate levels were similar in normal research subjects and patients with mCRPC. IHC demonstrated weak or no expression of GRM1 in luminal acinar epithelial cells of normal or hyperplastic glands, but high expression in primary or metastatic PCa tissues. Glutamate deprivation or blockade decreased PCa cells’ proliferation, migration, and invasion and led to apoptotic cell death. Conclusions Glutamate expression is mechanistically associated with and may provide a biomarker of PCa aggressiveness. PMID:23072969

  7. Decreased Serum Level of miR-146a as Sign of Chronic Inflammation in Type 2 Diabetic Patients

    PubMed Central

    Baldeón R., Lucy; Weigelt, Karin; de Wit, Harm; Ozcan, Behiye; van Oudenaren, Adri; Sempértegui, Fernando; Sijbrands, Eric; Grosse, Laura; Freire, Wilma; Drexhage, Hemmo A.; Leenen, Pieter J. M.

    2014-01-01

    Background There is increasing evidence that chronic inflammation is an important determinant in insulin resistance and in the pathogenesis of type 2 diabetes (T2D). MicroRNAs constitute a newly discovered system of cell regulation and in particular two microRNAs (miR-146a and miR-155) have been described as regulators and biomarkers of inflammation. Aim To determine a putative association between the levels of miR-146a and miR-155 in serum of T2D patients, clinical parameters and serological indicators of inflammation. Methods We performed quantitative Real Time PCR (qPCR) of microRNAs from serum (56 Ecuadorian T2D ambulatory patients and 40 non-diabetic controls). In addition, we evaluated T2D-related serum cytokines.chemokines and growth factors using a commercially available multi-analyte cytometric bead array system. We correlated outcomes to clinical parameters, including BMI, HbA1c and lipid state. Results The Ecuadorian non-diabetic controls appeared as overweight (BMI>25: patients 85%, controls 82.5%) and as dyslipidemic (hypercholesterolemia: patients 60.7%, controls 67.5%) as the patients. The serum levels of miR-146a were significantly reduced in T2D patients as compared to these non-diabetic, but obese/dyslipidemic control group (mean patients 0.61, mean controls set at 1; p = 0.042), those of miR-155 were normal. The serum levels of both microRNAs correlated to each other (r = 0.478; p<0.001) and to leptin levels. The microRNAs did not correlate to BMI, glycemia and dyslipidemia. From the tested cytokines, chemokines and growth factors, we found IL-8 and HGF significantly raised in T2D patients versus non-diabetic controls (p = 0.011 and 0.023 respectively). Conclusions This study shows decreased serum anti-inflammatory miR-146a, increased pro-inflammatory IL-8 and increased HGF (a vascular/insular repair factor) as discriminating markers of failure of glucose control occurring on the background of obesity and dyslipidemia. PMID:25500583

  8. Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome

    PubMed Central

    Broedl, Uli C; Lehrke, Michael; Fleischer-Brielmaier, Elisabeth; Tietz, Anne B; Nagel, Jutta M; Göke, Burkhard; Lohse, Peter; Parhofer, Klaus G

    2006-01-01

    Background Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2. Aim The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation. Methods We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metabolic syndrome and tested genetic variants for association with glucose, lipid and inflammatory parameters. Results We identified three AdipoR2 variants (+795G/A, +870C/A and +963C/T) in perfect linkage disequilibrium (r2 = 1) with a minor allele frequency of 0.125. This haplotype was associated with higher plasma adiponectin levels and decreased fasting triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. No association, however, was observed between the AdipoR2 SNP cluster and glucose metabolism. Conclusion To our knowledge, this is the first study to identify an association between genetic variants of the adiponectin receptor genes and plasma adiponectin levels. Furthermore, our data suggest that AdipoR2 may play an important role in triglyceride/VLDL metabolism. PMID:16700915

  9. Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study

    PubMed Central

    Chajès, Véronique; Biessy, Carine; Ferrari, Pietro; Romieu, Isabelle; Freisling, Heinz; Huybrechts, Inge; Scalbert, Augustin; Bueno de Mesquita, Bas; Romaguera, Dora; Gunter, Marc J.; Vineis, Paolo; Hansen, Camilla Plambeck; Jakobsen, Marianne Uhre; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verana; Neamat-Allah, Jasmine; Boeing, Heiner; Bachlechner, Ursula; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Pala, Valeria; Masala, Giovanna; Mattiello, Amalia; Skeie, Guri; Weiderpass, Elisabete; Agudo, Antonio; Huerta, Jose Maria; Ardanaz, Eva; Sánchez, Maria Jose; Dorronsoro, Miren; Quirós, Jose Ramon; Johansson, Ingegerd; Winkvist, Anna; Sonested, Emily; Key, Tim; Khaw, Kay-Tee; Wareham, Nicolas J.; Peeters, Petra H.M.; Slimani, Nadia

    2015-01-01

    Background Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. Results In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. Conclusions These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids. PMID:25675445

  10. TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways.

    PubMed

    Jung, Jong Gab; Yi, Sang-A; Choi, Sung-E; Kang, Yup; Kim, Tae Ho; Jeon, Ja Young; Bae, Myung Ae; Ahn, Jin Hee; Jeong, Hana; Hwang, Eun Sook; Lee, Kwan-Woo

    2015-12-01

    The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-phosphoeIF2α-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance. PMID:26537193

  11. TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways

    PubMed Central

    Jung, Jong Gab; Yi, Sang-A; Choi, Sung-E; Kang, Yup; Kim, Tae Ho; Jeon, Ja Young; Bae, Myung Ae; Ahn, Jin Hee; Jeong, Hana; Hwang, Eun Sook; Lee, Kwan-Woo

    2015-01-01

    The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2′-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-phosphoeIF2α-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance. PMID:26537193

  12. A polymorphism in the agouti signalling protein (ASIP) is associated with decreased levels of mRNA.

    PubMed

    Voisey, J; Gomez-Cabrera, M Del C; Smit, D J; Leonard, J H; Sturm, R A; van Daal, A

    2006-06-01

    To date, a role for agouti signalling protein (ASIP) in human pigmentation has not been well characterized. It is known that agouti plays a pivotal role in the pigment switch from the dark eumelanin to the light pheomelanin in the mouse. However, because humans do not have an agouti banded hair pattern, its role in human pigmentation has been questioned. We previously identified a single polymorphism in the 3'-untranslated region (UTR) of ASIP that was found at a higher frequency in African-Americans compared with other population groups. To compare allele frequencies between European-Australians and indigenous Australians, the g.8818A --> G polymorphism was genotyped. Significant differences were seen in allele frequencies between these groups (P < 0.0001) with carriage of the G allele highest in Australian Aborigines. In the Caucasian sample set a strong association was observed between the G allele and dark hair colour (P = 0.004) (odds ratio 4.6; 95% CI 1.4-15.27). The functional consequences of this polymorphism are not known but it was postulated that it might result in message instability and premature degradation of the transcript. To test this hypothesis, ASIP mRNA levels were quantified in melanocytes carrying the variant and non-variant alleles. Using quantitative real-time polymerase chain reaction the mean ASIP mRNA ratio of the AA genotype to the AG genotype was 12 (P < 0.05). This study suggests that the 3'-UTR polymorphism results in decreased levels of ASIP and therefore less pheomelanin production. PMID:16704456

  13. Lovastatin-induced decrease of intracellular cholesterol level attenuates fibroblast-to-myofibroblast transition in bronchial fibroblasts derived from asthmatic patients.

    PubMed

    Michalik, Marta; Soczek, Ewelina; Kosińska, Milena; Rak, Monika; Wójcik, Katarzyna Anna; Lasota, Sławomir; Pierzchalska, Małgorzata; Czyż, Jarosław; Madeja, Zbigniew

    2013-03-15

    Chronic inflammation of the airways and structural changes in the bronchial wall are basic hallmarks of asthma. Human bronchial fibroblasts derived from patients with diagnosed asthma display in vitro predestination towards TGF-β-induced fibroblast-to-myofibroblast transition (FMT), a key event in the bronchial wall remodelling. Statins inhibit 3-hydroxymethyl-3-glutaryl coenzyme A reductase, a key enzyme in the cholesterol synthesis pathway and are widely used as antilipidemic drugs. The pleiotropic anti-inflammatory effects of statins, independent of their cholesterol-lowering capacity, are also well established. Since commonly used anti-asthmatic drugs do not reverse the structural remodelling of the airways and statins have tentative anti-asthmatic activity, we have studied the effect of lovastatin on FMT in populations of human bronchial fibroblasts derived from asthmatic patients. We demonstrate that the intensity of FMT induced by TGF-β1 was strongly and dose-dependently attenuated by lovastatin. Furthermore, we show that neither the suppression of prenylation of signalling proteins nor the effect on reactive oxygen species formation are important for lovastatin-induced inhibition of myofibroblast differentiation. On the other hand, we show that a squalene synthase inhibitor, zaragozic acid A, reduced the TGF-β1-induced FMT to an extent comparable to lovastatin effect. Additionally we demonstrate that in bronchial fibroblast populations, both inhibitors (lovastatin and zaragozic acid A) attenuate the TGF-β1-induced Smad2 nuclear translocation in a manner dependent on intracellular cholesterol level. Our data suggest that statins can directly, by decrease of intracellular cholesterol level, affect basic cell signalling events crucial for asthmatic processes and potentially prevent perilous bronchial wall remodelling associated with intensive myofibroblast formation. PMID:23485731

  14. Caffeic Acid Phenethyl Ester Regulates PPAR's Levels in Stem Cells-Derived Adipocytes.

    PubMed

    Vanella, Luca; Tibullo, Daniele; Godos, Justyna; Pluchinotta, Francesca Romana; Di Giacomo, Claudia; Sorrenti, Valeria; Acquaviva, Rosaria; Russo, Alessandra; Li Volti, Giovanni; Barbagallo, Ignazio

    2016-01-01

    Hypertrophic obesity inhibits activation of peroxisome proliferators-activated receptor gamma (PPARγ), considered the key mediator of the fully differentiated and insulin sensitive adipocyte phenotype. We examined the effects of Caffeic Acid Phenethyl Ester (Cape), isolated from propolis, a honeybee hive product, on Adipose Stem Cells (ASCs) differentiation to the adipocyte lineage. Finally we tested the effects of Cape on insulin-resistant adipocytes. Quantification of Oil Red O-stained cells showed that lipid droplets decreased following Cape treatment as well as radical oxygen species formation. Additionally, exposure of ASC to high glucose levels decreased adiponectin and increased proinflammatory cytokines mRNA levels, which were reversed by Cape-mediated increase of insulin sensitivity. Cape treatment resulted in decreased triglycerides synthesis and increased beta-oxidation. Exposure of ASCs to Lipopolysaccharide (LPS) induced a reduction of PPARγ, an increase of IL-6 levels associated with a well-known stimulation of lipolysis; Cape partially attenuated the LPS-mediated effects. These observations reveal the main role of PPARγ in the adipocyte function and during ASC differentiation. As there is now substantial interest in functional food and nutraceutical products, the observed therapeutic value of Cape in insulin-resistance related diseases should be taken into consideration. PMID:26904104

  15. Caffeic Acid Phenethyl Ester Regulates PPAR's Levels in Stem Cells-Derived Adipocytes

    PubMed Central

    Vanella, Luca; Tibullo, Daniele; Godos, Justyna; Pluchinotta, Francesca Romana; Di Giacomo, Claudia; Sorrenti, Valeria; Acquaviva, Rosaria; Russo, Alessandra; Li Volti, Giovanni; Barbagallo, Ignazio

    2016-01-01

    Hypertrophic obesity inhibits activation of peroxisome proliferators-activated receptor gamma (PPARγ), considered the key mediator of the fully differentiated and insulin sensitive adipocyte phenotype. We examined the effects of Caffeic Acid Phenethyl Ester (Cape), isolated from propolis, a honeybee hive product, on Adipose Stem Cells (ASCs) differentiation to the adipocyte lineage. Finally we tested the effects of Cape on insulin-resistant adipocytes. Quantification of Oil Red O-stained cells showed that lipid droplets decreased following Cape treatment as well as radical oxygen species formation. Additionally, exposure of ASC to high glucose levels decreased adiponectin and increased proinflammatory cytokines mRNA levels, which were reversed by Cape-mediated increase of insulin sensitivity. Cape treatment resulted in decreased triglycerides synthesis and increased beta-oxidation. Exposure of ASCs to Lipopolysaccharide (LPS) induced a reduction of PPARγ, an increase of IL-6 levels associated with a well-known stimulation of lipolysis; Cape partially attenuated the LPS-mediated effects. These observations reveal the main role of PPARγ in the adipocyte function and during ASC differentiation. As there is now substantial interest in functional food and nutraceutical products, the observed therapeutic value of Cape in insulin-resistance related diseases should be taken into consideration. PMID:26904104

  16. A Place to Hide in the Home-Cage Decreases Yolk Androgen Levels and Offspring Emotional Reactivity in Japanese Quail

    PubMed Central

    Guesdon, Vanessa; Bertin, Aline; Houdelier, Cécilia; Lumineau, Sophie; Formanek, Laureline; Kotrschal, Kurt; Möstl, Erich; Richard-Yris, Marie-Annick

    2011-01-01

    An animal's emotional responses are the result of its cognitive appraisal of a situation. This appraisal is notably influenced by the possibility of an individual to exert control over an aversive event. Although the fact that environment controllability decreases emotional responses in animals is well established, far less is known about its potential trans-generational effects. As the levels of avian yolk hormones can vary according to the mother's environment, we hypothesized that housing environment of mothers would modulate the quality of her eggs and in turn her offspring's behaviour. Two groups of female Japanese quail were constituted: a group that had access to a place to hide in their home-cage (Hd, n = 20) and a group that had nowhere to hide (NoHd, n = 20) when stressed. Both groups were submitted to daily human disturbances for a twenty-day-period. Hd females produced eggs with both less testosterone and androstenedione than did NoHd females. The emotional and social reactivity of Hd females' offspring were lower and their growth was slower than those of NoHd females' offspring. Our results show that a minor difference in housing environment had substantial effects on eggs and offspring. The presence of a shelter probably helped quail to cope with daily human disturbances, producing less reactive offspring. This transgenerational effect caused by an opportunity to hide could lead to applications in care of laboratory animals, conservation biology and animal welfare. PMID:21980338

  17. Tanshinone IIA decreases the levels of inflammation induced by Aβ1-42 in brain tissues of Alzheimer's disease model rats.

    PubMed

    Lu, Bei-Ling; Li, Jian; Zhou, Jun; Li, Wen-Wen; Wu, Heng-Fei

    2016-08-17

    To study the pathogenesis of Alzheimer's disease (AD) and explore the possible anti-inflammatory mechanism of tanshinone IIA (TanIIA), we evaluated the quantity of neurons and the expression levels of interleukin-1β (IL-1β), IL-6, glial fibrillary acidic protein, CD11b, C1q, C3c, and C3d in brain tissues of AD rats treated with TanIIA. Thirty male Sprague-Dawley rats were randomized into three groups: sham group, TanIIA treatment group, and Aβ1-42 group. Aβ1-42 treatment was performed by injecting Aβ into the hippocampus of rats and then tagged position. Brain tissue morphological structure has been observed with HE staining and the staining of exogenously injected Aβ1-42 was observed by immunohistochemistry, which confirms the success of the Aβ1-42 group. After TanIIA treatment, levels of IL-1β, IL-6, glial fibrillary acidic protein, CD11b, C1q, C3c, and C3d were measured in paraffinized brain tissue sections from all groups by immunohistochemistry staining. The results showed that no 6E10 was detected in the control group, and the difference in the expression levels of 6E10 between the Aβ1-42 group and the TanIIA treatment group was not significant (P>0.05), suggesting that both the Aβ1-42 group and the TanIIA treatment group received the same amount of Aβ. The Aβ1-42 group showed a significant increase in the expression levels of inflammatory markers compared with the sham group (P<0.05) and the TanIIA treatment group showed a partial improvement in reducing inflammation. Therefore, Aβ triggered brain inflammation and activated the complement system. TanIIA treatment reduced the number of astrocytes and microglial cells, and induced a partial decrease in complement molecules in the brain of AD rats. These findings suggested that TanIIA may represent a potential therapeutic treatment in neurodegenerative diseases such as AD to support the survival of neurons by reducing expression levels of inflammatory factors. PMID:27348015

  18. Decreased levels of genuine large free hCG alpha in men presenting with abnormal semen analysis

    PubMed Central

    2011-01-01

    Background The pregnancy hormone human chorionic gonadotropin (hCG) and its free subunits (hCG alpha, hCG beta) are produced in the male reproductive tract and found in high concentrations in seminal fluid, in particular hCG alpha. This study aimed to elucidate changes in peptide hormone profiles in patients showing abnormal semen analyses and to determine the genuineness of the highly abundant hCG alpha. Methods Seminal plasma was obtained from 45 male patients undergoing semen analysis during infertility workups. Comprehensive peptide hormone profiles were established by a panel of immunofluorometric assays for hCG, hCG alpha, hCG beta and its metabolite hCG beta core fragment, placental lactogen, growth hormone and prolactin in seminal plasma of patients with abnormal semen analysis results (n = 29) versus normozoospermic men (n = 16). The molecular identity of large hyperglycosylated hCG alpha was analyzed by mass-spectrometry and selective deglycosylation. Results hCG alpha levels were found to be significantly lower in men with impaired semen quality (1346 +/- 191 vs. 2753 +/- 533 ng/ml, P = 0.022). Moreover, patients with reduced sperm count had reduced intact hCG levels compared with normozoospermic men (0.097 +/- 0.022 vs. 0.203 +/- 0.040 ng/ml, P = 0.028). Using mass-spectrometry, the biochemical identity of hCG alpha purified from seminal plasma was verified. Under non-reducing conditions in SDS-PAGE, hCG alpha isolated from seminal plasma migrated in a manner comparable with large free hCG alpha with an apparent molecular mass (Mr, app) of 24 kDa, while hCG alpha dissociated from pregnancy-derived holo-hCG migrated at approximately 22 kDa. After deglycosylation with PNGase F under denaturing conditions, all hCG alpha variants showed an Mr, app of 15 kDa, indicating identical amino acid backbones. Conclusions The findings indicate a pathophysiological relevance of hCG, particularly its free alpha subunit, in spermatogenesis. The alternative glycosylation

  19. Chicoric Acid Levels in Basil (Ocimum basilicum L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, we reported the presence of chicoric acid in basil leaves (confirmed by co-chromatography with purchased standard). Chicoric acid being the chief phenolic of the Echinacea purpurea plant which is popularly consumed as a dietary supplement. For this study, basil products commonly purchased ...

  20. Protein Restriction with Amino Acid-Balanced Diets Shrinks Circulating Pool Size of Amino Acid by Decreasing Expression of Specific Transporters in the Small Intestine.

    PubMed

    Qiu, Kai; Qin, Chun Fu; Luo, Min; Zhang, Xin; Sun, Wen Juan; Jiao, Ning; Li, De Fa; Yin, Jing Dong

    2016-01-01

    Dietary protein restriction is not only beneficial to health and longevity in humans, but also protects against air pollution and minimizes feeding cost in livestock production. However, its impact on amino acid (AA) absorption and metabolism is not quite understood. Therefore, the study aimed to explore the effect of protein restriction on nitrogen balance, circulating AA pool size, and AA absorption using a pig model. In Exp.1, 72 gilts weighting 29.9 ± 1.5 kg were allocated to 1 of the 3 diets containing 14, 16, or 18% CP for a 28-d trial. Growth (n = 24), nitrogen balance (n = 6), and the expression of small intestinal AA and peptide transporters (n = 6) were evaluated. In Exp.2, 12 barrows weighting 22.7 ± 1.3 kg were surgically fitted with catheters in the portal and jejunal veins as well as the carotid artery and assigned to a diet containing 14 or 18% CP. A series of blood samples were collected before and after feeding for determining the pool size of circulating AA and AA absorption in the portal vein, respectively. Protein restriction did not sacrifice body weight gain and protein retention, since nitrogen digestibility was increased as dietary protein content reduced. However, the pool size of circulating AA except for lysine and threonine, and most AA flux through the portal vein were reduced in pigs fed the low protein diet. Meanwhile, the expression of peptide transporter 1 (PepT-1) was stimulated, but the expression of the neutral and cationic AA transporter systems was depressed. These results evidenced that protein restriction with essential AA-balanced diets, decreased AA absorption and reduced circulating AA pool size. Increased expression of small intestinal peptide transporter PepT-1 could not compensate for the depressed expression of jejunal AA transporters for AA absorption. PMID:27611307

  1. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats

    PubMed Central

    Hosomi, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-01-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

  2. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats.

    PubMed

    Hosomi, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-03-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

  3. Triploidy does not decrease contents of eicosapentaenoic and docosahexaenoic acids in filets of pink salmon Oncorhynchus gorbuscha.

    PubMed

    Gladyshev, Michail I; Artamonova, Valentina S; Makhrov, Alexander A; Sushchik, Nadezhda N; Kalachova, Galina S; Dgebuadze, Yury Y

    2017-02-01

    Triploid fish has become an important item of commercial aquaculture, but data on its fatty acid (FA) composition are still controversial, especially regarding essential polyunsaturated fatty acids, eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA). We studied FA composition and content of diploid and triploid pink salmon Oncorhynchus gorbuscha, reared in aquaculture in a bay of the White Sea (Russia). FA composition, measured as percentages of total FA of triploids and immature diploid females significantly differed from that of mature diploid fish. Specifically, mature diploids had higher percentage of EPA and DHA in their muscle tissue (filets) compared to that of triploids and immature diploid females. Nevertheless, the contents of EPA and DHA per mass of the filets in diploid and triploid specimens were similar. Thus, no special efforts are needed to improve EPA and DHA contents in filets of triploids. PMID:27596393

  4. THE INTAKE OF FIBER MESOCARP PASSIONFRUIT (PASSIFLORA EDULIS) LOWERS LEVELS OF TRIGLYCERIDE AND CHOLESTEROL DECREASING PRINCIPALLY INSULIN AND LEPTIN

    PubMed Central

    Corrêa, E.M.; Medina, L.; Barros-Monteiro, J.; Valle, N.O.; Sales, R.; Magalães, A.; Souza, F.C.A.; Carvalho, T.B.; Lemos, J.R.; Lira, E.F.; Lima, E.S.; Galeno, D.M.L.; Morales, L.; Ortiz, C.; Carvalho, R.P.

    2014-01-01

    Background Diabetes mellitus (DM) is a major risk factor for coronary artery disease, renal failure, retinopathy, and neuropathy. Over the last years, there has been an increasing demand in folk medicine for natural sources that could help in the treatment of chronic diseases, including diabetes. The rind of passion fruit (Passiflora edulis f. Flavicarpa) is traditionally used as a functional food due to its high concentration of soluble and insoluble fiber. Objective The aim of this study was to determine the effect of high-fiber diet albedo of passion fruit on the metabolic and biochemical profile in diabetic rats induced by alloxan (2%). Design The passion fruit mesocarp fiber was dried in an oven with circulating air at 60°C and pulverized. We used 32 adult male rats, divided into 4 groups: Wistar group 1 control (GC), Wistar group 2, 15% fiber (GF15), Wistar group 3, 30% fiber (GF30), Wistar group 4, fiber disolved in water (GFH2O). The ratio of passion fruit was prepared according to the AIN 93M guidelines, varying only the source of dietary fiber. The corresponding diet for each group was offered to the animals for 60 days. Results There was a statically significant decrease in plasma glucose for GFH2O, GF15%, and GF30% groups with 27.0%, 37.4%, and 40.2%, respectively. Conclusion The use of mesocarp fiber of passion fruit at concentrations of 15% and 30% are an important dietary supplement for the treatment of DM due to its potential hypoglycemic effect, and its ability to reduce triglycerides and VLDL-cholesterol levels with a principal reduction of insulin and leptin. PMID:25346913

  5. Efficacy of a chlorhexidine and a chlorhexidine-fluoride varnish mixture to decrease interdental levels of mutans streptococci.

    PubMed

    Twetman, S; Petersson, L G

    1997-01-01

    The aim of the present study was to evaluate and compare the efficacy of a chlorhexidine/thymol-containing (CHX) and a chlorhexidine/thymol/fluoride-containing (CHX + F) varnish to decrease interdental levels of mutans streptococci (MS). Eighty-two healthy schoolchildren (11-13 years) with high scores of salivary MS were selected by a screening procedure and randomised into two groups. MS were enumerated at all mesial interdental sites of the first permanent molars with the aid of a modified chair-side technique. The interdental molar and premolar sites were treated with either a 1% CHX varnish (Cervitec) or a 1:1 mixture of the CHX varnish and a fluoride varnish containing 0.1% w/w difluorsilane (Fluor Protector; CHX + F) on two occasions within a 2-week period. The varnishes were applied with a small brush after cleaning with dental floss and drying with air. Follow-up samples from the interdental areas were collected after 1 and 3 months. Both groups exhibited a similar statistically significant (p < 0.05) reduction of interdental MS after 1 month when compared with baseline. After 3 months, a significant reduction (p < 0.05) was still found in the CHX + F varnish group but not in the CHX varnish group. In conclusion, the results suggest that the addition of fluoride to an antibacterial varnish might improve the long-term efficacy in diminishing the cariogenic microbial challenge. Thus, the mixed varnish concept should be further developed and warrants an implementation of clinical studies. PMID:9286519

  6. Regulation of auxin, abscisic acid and salicylic acid levels by ascorbate application under heat stress in sensitive and tolerant maize leaves.

    PubMed

    Dinler, Burcu Seckin; Demir, Emel; Kompe, Yasemin Ozdener

    2014-12-01

    In the present study, the effect of ascorbic acid (5 mM) on some physiological parameters and three hormones (auxin, abscisic acid, salicylic acid) was determined under heat stress (40 °C) in maize tolerant cv. (MAY 69) and sensitive cv. SHEMAL (SH) at 0 h, 4 h and 8 h. Heat stress reduced total chlorophyll content (CHL), relative water content (RWC) and stomatal conductance (gs) in SH but did not lead to changes in MAY 69 at 4 h and 8 h. However, pretreatment with ascorbic acid increased (CHL), (RWC) and (gs) in SH under heat stress while it reduced MDA content significantly in both cv. We also observed that heat stress led to a reduction in SA level but increased ABA and IAA levels in SH, whereas it increased SA and IAA levels but did not change ABA level in MAY 69 at 4 h. Furthermore, in SH, ASC application under heat stress increased SA level and decreased IAA and ABA levels at 4 h, but it had no effect on SA and ABA at 8 h. PMID:25475985

  7. Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats.

    PubMed

    Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Kim, Jaehyoung; Ma, Fangrui; Shibata, Noreene; Stanhope, Kimber L; Giulivi, Cecilia; Hansen, Frederik; Jelsing, Jacob; Vrang, Niels; Kowala, Mark; Chouinard, Michael L; Haj, Fawaz G; Havel, Peter J

    2013-03-01

    Post-operative increases in circulating bile acids have been suggested to contribute to the metabolic benefits of bariatric surgery; however, their mechanistic contributions remain undefined. We have previously reported that ileal interposition (IT) surgery delays the onset of type 2 diabetes in UCD-T2DM rats and increases circulating bile acids, independently of effects on energy intake or body weight. Therefore, we investigated potential mechanisms by which post-operative increases in circulating bile acids improve glucose homeostasis after IT surgery. IT, sham or no surgery was performed on 2-month-old weight-matched male UCD-T2DM rats. Animals underwent an oral fat tolerance test (OFTT) and serial oral glucose tolerance tests (OGTT). Tissues were collected at 1.5 and 4.5 months after surgery. Cell culture models were used to investigate interactions between bile acids and ER stress. IT-operated animals exhibited marked improvements in glucose and lipid metabolism, with concurrent increases in postprandial glucagon-like peptide-1 (GLP-1) secretion during the OFTT and OGTTs, independently of food intake and body weight. Measurement of circulating bile acid profiles revealed increases in circulating total bile acids in IT-operated animals, with a preferential increase in circulating cholic acid concentrations. Gut microbial populations were assessed as potential contributors to the increases in circulating bile acid concentrations, which revealed proportional increases in Gammaproteobacteria in IT-operated animals. Furthermore, IT surgery decreased all three sub-arms of ER stress signaling in liver, adipose and pancreas tissues. Amelioration of ER stress coincided with improved insulin signaling and preservation of β-cell mass in IT-operated animals. Incubation of hepatocyte, adipocyte and β-cell lines with cholic acid decreased ER stress. These results suggest that postoperative increases in circulating cholic acid concentration contribute to improvements in

  8. The deposition of conjugated linoleic acids in eggs of laying hens fed diets varying in fat level and fatty acid profile.

    PubMed

    Raes, Katleen; Huyghebaert, Gerard; De Smet, Stefaan; Nollet, Lode; Arnouts, Sven; Demeyer, Daniel

    2002-02-01

    The objective of this study was to investigate the incorporation of conjugated linoleic acid (CLA) into eggs and its effect on the fatty acid metabolism when layers are fed diets with different fat sources and fat levels. Layers were fed either a low fat diet (LF) or one of three high fat diets based on soybean oil (SB), animal fat (AF) or flaxseed oil (FSO). CLA was added at a concentration of 1 g/100 g feed from two different CLA premixes with a different CLA profile. For the trial, 144 laying hens were allocated to 12 treatments (4 basal fat sources x 3 CLA treatments) with 3 replicates of 4 hens each. No significant differences were observed in feed intake, egg weight, feed conversion or laying rate between chickens fed control and CLA-supplemented diets. Differences in yolk fat, cholesterol or yolk color were not clearly related to the dietary CLA. However, the supplementation of CLA to the diets had clear effects on the fatty acid composition, i.e., a decrease in monounsaturated fatty acids (MUFA) and an increase in saturated fatty acids (SFA) was observed, whereas the polyunsaturated fatty acids (PUFA) content were essentially unaffected. The results suggest that CLA may influence the activity of the desaturases to a different extent in the synthesis of (n-6) and (n-3) long-chain fatty acids. These effects of CLA depend on the level of (n-6) and (n-3) fatty acids available in the feed. The apparent deposition rate (%) is clearly higher for the c9, t11 isomer than for the t10, c12 isomer. Adding CLA to layers diets rich in (n-3) fatty acids produces eggs that could promote the health of the consumer in terms of a higher intake of (n-3) fatty acids and CLA. PMID:11823576

  9. Probiotics decreased the bioavailability of the bile acid analog, monoketocholic acid, when coadministered with gliclazide, in healthy but not diabetic rats.

    PubMed

    Al-Salami, Hani; Butt, Grant; Tucker, Ian; Golocorbin-Kon, Svetlana; Mikov, Momir

    2012-06-01

    In recent studies we showed that gliclazide has no hypoglycemic effect on type 1 diabetic (T1D) rats while MKC does, and their combination exerted a better hypoglycemic effect than MKC alone. We also showed that the most hypoglycemic effect was noticed when T1D rats were treated with probiotics then gavaged with MKC + gliclazide (blood glucose decreased from 24 ± 3 to 10 ± 2 mmol/l). The aim of this study is to investigate the influence of probiotics on MKC pharmacokinetics when coadministered with gliclazide, in T1D rats. 80 male Wistar rats (weight 350 ± 50 g) were randomly allocated into 8 groups (10 rats/group), 4 of which were injected with alloxan (30 mg/kg) to induce T1D. Group 1 was healthy and group 2 was diabetic. Groups 3 (healthy) and 4 (diabetic) were gavaged with probiotics (75 mg/kg) every 12 h for 3 days and 12 h later all groups received a single oral dose of MKC + gliclazide (4 and 20 mg/kg respectively). The remaining 4 groups were treated in the same way but administered MKC + gliclazide via the i.v. route. Blood samples collected from T1D rats prior to MKC + gliclazide revealed that probiotic treatment alone reduced blood glucose levels twofold. When coadministered with gliclazide, the bioavailability of MKC was reduced in healthy rats treated with probiotics but remained the same in diabetic pretreated rats. The decrease in MKC bioavailability, when administered with gliclazide, caused by probiotic treatment in healthy but not diabetic rats suggests that probiotic treatment induced MKC metabolism or impaired its absorption, only in healthy animals. The different MKC bioavailability in healthy and diabetic rats could be explained by different induction of presystemic elimination of MKC in the gut by probiotic treatment. PMID:21874525

  10. High basal levels of functional toll-like receptor 3 (TLR3) and noncanonical Wnt5a are expressed in papillary thyroid cancer and are coordinately decreased by phenylmethimazole together with cell proliferation and migration.

    PubMed

    McCall, Kelly D; Harii, Norikazu; Lewis, Christopher J; Malgor, Ramiro; Kim, Won Bae; Saji, Motoyasu; Kohn, Aimee D; Moon, Randall T; Kohn, Leonard D

    2007-09-01

    High basal levels of TLR3 and Wnt5a RNA are present in papillary thyroid carcinoma (PTC) cell lines consistent with their overexpression and colocalization in PTC cells in vivo. This is not the case in thyrocytes from normal tissue and in follicular carcinoma (FC) or anaplastic carcinoma (AC) cells or tissues. The basally expressed TLR3 are functional in PTC cells as evidenced by the ability of double-strand RNA (polyinosine-polycytidylic acid) to significantly increase the activity of transfected NF-kappaB and IFN-beta luciferase reporter genes and the levels of two end products of TLR3 signaling, IFN-beta and CXCL10. Phenylmethimazole (C10), a drug that decreases TLR3 expression and signaling in FRTL-5 thyrocytes, decreases TLR3 levels and signaling in PTC cells in a concentration-dependent manner. C10 also decreased Wnt5a RNA levels coordinate with decreases in TLR3. E-cadherin RNA levels, whose suppression may be associated with high Wnt5a, increased with C10 treatment. C10 simultaneously decreased PTC proliferation and cell migration but had no effect on the growth and migration of FC, AC, or FRTL-5 cells. C10 decreases high basal phosphorylation of Tyr705 and Ser727 on Stat3 in PTC cells and inhibits IL-6-induced Stat3 phosphorylation. IL-6-induced Stat3 phosphorylation is important both in up-regulating Wnt5a levels and in cell growth. In sum, high Wnt5a levels in PTC cells may be related to high TLR3 levels and signaling; and the ability of phenylmethimazole (C10) to decrease growth and migration of PTC cells may be related to its suppressive effect on TLR3 and Wnt5a signaling, particularly Stat3 activation. PMID:17525119

  11. Effect of fluoride exposure on serum glycoprotein pattern and sialic acid level in rabbits.

    PubMed

    Ciftci, Gulay; Cenesiz, Sena; Yarim, Gul Fatma; Nisbet, Ozlem; Nisbet, Cevat; Cenesiz, Metin; Guvenc, Dilek

    2010-01-01

    This study describes the effects of fluoride exposure on the protein profile, glycoprotein pattern, and total sialic acid concentration of serum in rabbits. For this aim; 20 healthy New Zealand rabbits were used. The rabbits were divided into two equal groups each with ten animals according to their weighing: control group and experimental group. The rabbits in control group were given drinking tap water containing 0.29 mg/l sodium fluoride and experimental group received the same tap water to which was added 40 mg/l sodium fluoride for 70 days. Blood samples were taken from each rabbit on day 70. Serum fluoride concentrations were measured by a fluoride-specific ion electrode in serum. The fluoride levels in the serum were found as 18.4 (+/-1.58) microg/L in control and 301.3 (+/-52.18) microg/L in fluoride exposed rabbits. The sialic acid levels were found as 69.2 (+/-0.32) mg/dL in control and 43.4 (+/-0.13) mg/dL in fluoride exposed group. The electrophoretic patterns of serum proteins, glycoproteins, and total sialic acid concentration were determined. Fifteen different protein fractions with molecular weights ranging from 22 to 249 kDa were displayed in the serum protein electrophoretic gel of both groups. The raw concentrations of the protein fractions decreased in fluoride exposed rabbits as compared with the control rabbits. The serum glycoprotein pattern revealed seven major protein bands from 47 to 167 kDa in experimental and control groups. The slight decrease of raw concentration of the protein bands in glycoprotein pattern of serum was observed in fluoride toxication comparing to control. The results suggest that serum TSA determination and serum protein electrophoresis can be used to evaluate prognosis of fluoride exposure as a supplementary laboratory test in combination with clinical and other laboratory findings of fluorosis. PMID:19904501

  12. Association Between Serum Levels of Adipocyte Fatty Acid-binding Protein and Free Thyroxine

    PubMed Central

    Tseng, Fen-Yu; Chen, Pei-Lung; Chen, Yen-Ting; Chi, Yu-Chao; Shih, Shyang-Ron; Wang, Chih-Yuan; Chen, Chi-Ling; Yang, Wei-Shiung

    2015-01-01

    Abstract Adipocyte fatty acid-binding protein (AFABP) has been shown to be a biomarker of body weight change and atherosclerosis. Changes in thyroid function are associated with changes in body weight and risks of cardiovascular diseases. The association between AFABP and thyroid function status has been seldom evaluated. The aim of this study was to compare the serum AFABP concentrations in hyperthyroid patients and those in euthyroid individuals, and to evaluate the associations between serum AFABP and free thyroxine (fT4) levels. For this study, 30 hyperthyroid patients and 30 euthyroid individuals at a referral medical center were recruited. The patients with hyperthyroidism were treated with antithyroid regimens as clinically indicated. No medication was given to the euthyroid individuals. The body weight, body mass index, thyroid function, serum levels of AFABP, and biochemical data of both groups at baseline and at the 6th month were compared. Associations between AFABP and fT4 levels were also analyzed. At the baseline, the hyperthyroid patients had significantly higher serum AFABP levels than the euthyroid individuals (median [Q1, Q3]: 22.8 [19.4, 30.6] ng/mL vs 18.6 [15.3, 23.2] ng/mL; P = 0.038). With the antithyroid regimens, the AFABP serum levels of the hyperthyroid patients decreased to 16.6 (15.0, 23.9) ng/mL at the 6th month. No difference in the AFABP level was found between the hyperthyroid and the euthyroid groups at the 6th month. At baseline, sex (female vs male, ß = 7.65, P = 0.022) and fT4 level (ß = 2.51, P = 0.018) were significantly associated with AFABP levels in the univariate regression analysis. At the 6th month, sex and fT4 level (ß = 8.09, P < 0.001 and ß = 3.61, P = 0.005, respectively) were also significantly associated with AFABP levels. The associations between sex and fT4 level with AFABP levels remained significant in the stepwise multivariate regression analysis, both at baseline and at

  13. A mutant of the Arabidopsis thaliana TOC159 gene accumulates reduced levels of linolenic acid and monogalactosyldiacylglycerol.

    PubMed

    Afitlhile, Meshack; Workman, Samantha; Duffield, Kayla; Sprout, Danielle; Berhow, Mark

    2013-12-01

    Previous studies have shown that a mutant of Arabidopsis that lacks the Toc159 receptor is impaired in chloroplast biogenesis. The mutant is referred as plastid protein import 2 or ppi2 and has an albino phenotype due to its inability to import the photosynthetic proteins. In this study, we measured fatty acid composition and transcript levels of plastid-localized fatty acid desaturases in the wild type and ppi2 mutant. The objective was to evaluate whether the Toc159 receptor was critical in the import of lipid-synthesizing enzymes. The ppi2 mutant accumulated decreased levels of oleic acid (18:1) and α-linolenic acid (18:3). The mutant accumulated drastically reduced amounts of the chloroplast lipid monogalactosyldiacylglycerol (MGDG), which contains more than 80% of 18:3. The expression of genes that encode stearoyl-ACP desaturase and MGD1 synthase were down-regulated in the ppi2 mutant, and this corresponded to decreased levels of 18:1 and MGDG, respectively. We conclude that in the ppi2 mutant the impaired synthesis of MGDG resulted in decreased amounts of 18:3. The mutant however, had a 30-fold increase in fad5 transcript levels; this increase was mirrored by a 16- to 50-fold accumulation of hexadecatrienoic acid (16:3), a fatty acid found exclusively in MGDG. Taken together, these data suggest that the Toc159 receptor is required in the import of stearoyl-ACP desaturase and MGD1 synthase into the chloroplasts. Since the expression of fad5 gene was up-regulated in the ppi2 mutant, we propose that fad5 desaturase is imported into plastids through the atToc132/atToc120 protein import pathway. PMID:24184455

  14. Omega-3 fatty acids protect renal functions by increasing docosahexaenoic acid-derived metabolite levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

    PubMed

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Al Mamun, Abdullah; Tanabe, Yoko; Iwamoto, Ryo; Arita, Makoto; Tsuchikura, Satoru; Shido, Osamu

    2014-01-01

    The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) protect against diabetic nephropathy by inhibiting inflammation. The aim of this study was to assess the effects of highly purified DHA and EPA or EPA only administration on renal function and renal eicosanoid and docosanoid levels in an animal model of metabolic syndrome, SHR.Cg-Lepr(cp)/NDmcr (SHRcp) rats. Male SHRcp rats were divided into 3 groups. Control (5% arabic gum), TAK-085 (300 mg/kg/day, containing 467 mg/g EPA and 365 mg/g DHA), or EPA (300 mg/kg/day) was orally administered for 20 weeks. The urinary albumin to creatinine ratio in the TAK-085-administered group was significantly lower than that in other groups. The glomerular sclerosis score in the TAK-085-administered group was significantly lower than that in the other groups. Although DHA levels were increased in total kidney fatty acids, the levels of nonesterified DHA were not significantly different among the 3 groups, whereas the levels of protectin D1, resolvin D1, and resolvin D2 were significantly increased in the TAK-085-administered group. The results show that the use of combination therapy with DHA and EPA in SHRcp rats improved or prevented renal failure associate with metabolic syndrome with decreasing triglyceride levels and increasing ω-3 PUFA lipid mediators. PMID:24642910

  15. Knockdown of the ionotropic γ-aminobutyric acid receptor (GABAR) RDL gene decreases fipronil susceptibility of the small brown planthopper, Laodelphax striatellus (Hemiptera: Delphacidae).

    PubMed

    Wei, Qi; Wu, Shun-Fan; Niu, Chun-Dong; Yu, Hua-Yang; Dong, Yao-Xue; Gao, Cong-Fen

    2015-04-01

    Insect γ-aminobutyric acid receptors (GABARs) are important molecular targets of cyclodiene and phenylpyrazole insecticides. Previously GABARs encoding rdl (resistant to dieldrin) genes responsible for dieldrin and fipronil resistance were identified in various economically important insect pests. In this study, we cloned the open reading frame cDNA sequence of rdl gene from fipronil-susceptible and fipronil-resistant strains of Laodelphax striatellus (Lsrdl). Sequence analysis confirmed the presence of a previously identified resistance-conferring mutation. Different alternative splicing variants of Lsrdl were noted. Injection of dsLsrdl reduced the mRNA abundance of Lsrdl by 27-82%, and greatly decreased fipronil-induced mortality of individuals from both susceptible and resistant strains. These data indicate that Lsrdl encodes a functional RDL subunit that mediates susceptibility to fipronil. Additionally, temporal and spatial expression analysis showed that Lsrdl was expressed at higher levels in eggs, fifth-instar nymphs, and female adults than in third-instar and fourth-instar nymphs. Lsrdl was predominantly expressed in the heads of 2-day-old female adults. All these results provide useful background knowledge for better understanding of fipronil resistance related ionotropic GABA receptor rdl gene expressed variants and potential functional differences in insects. PMID:25808850

  16. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine

    PubMed Central

    Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti

    2016-01-01

    Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus. PMID:27064332

  17. Chicoric acid binds to two sites and decreases the activity of the YopH bacterial virulence factor

    PubMed Central

    Kuban-Jankowska, Alicja; Sahu, Kamlesh K.; Gorska, Magdalena; Tuszynski, Jack A.; Wozniak, Michal

    2016-01-01

    Chicoric acid (CA) is a phenolic compound present in dietary supplements with a large spectrum of biological properties reported ranging from antioxidant, to antiviral, to immunostimulatory properties. Due to the fact that chicoric acid promotes phagocytic activity and was reported as an allosteric inhibitor of the PTP1B phosphatase, we examined the effect of CA on YopH phosphatase from pathogenic bacteria, which block phagocytic processes of a host cell. We performed computational studies of chicoric acid binding to YopH as well as validation experiments with recombinant enzymes. In addition, we performed similar studies for caffeic and chlorogenic acids to compare the results. Docking experiments demonstrated that, from the tested compounds, only CA binds to both catalytic and secondary binding sites of YopH. Our experimental results showed that CA reduces activity of recombinant YopH phosphatase from Yersinia enterocolitica and human CD45 phosphatase. The inhibition caused by CA was irreversible and did not induce oxidation of catalytic cysteine. We proposed that inactivation of YopH induced by CA is involved with allosteric inhibition by interacting with essential regions responsible for ligand binding. PMID:26735581

  18. Chicoric acid binds to two sites and decreases the activity of the YopH bacterial virulence factor.

    PubMed

    Kuban-Jankowska, Alicja; Sahu, Kamlesh K; Gorska, Magdalena; Tuszynski, Jack A; Wozniak, Michal

    2016-01-19

    Chicoric acid (CA) is a phenolic compound present in dietary supplements with a large spectrum of biological properties reported ranging from antioxidant, to antiviral, to immunostimulatory properties. Due to the fact that chicoric acid promotes phagocytic activity and was reported as an allosteric inhibitor of the PTP1B phosphatase, we examined the effect of CA on YopH phosphatase from pathogenic bacteria, which block phagocytic processes of a host cell. We performed computational studies of chicoric acid binding to YopH as well as validation experiments with recombinant enzymes. In addition, we performed similar studies for caffeic and chlorogenic acids to compare the results. Docking experiments demonstrated that, from the tested compounds, only CA binds to both catalytic and secondary binding sites of YopH. Our experimental results showed that CA reduces activity of recombinant YopH phosphatase from Yersinia enterocolitica and human CD45 phosphatase. The inhibition caused by CA was irreversible and did not induce oxidation of catalytic cysteine. We proposed that inactivation of YopH induced by CA is involved with allosteric inhibition by interacting with essential regions responsible for ligand binding. PMID:26735581

  19. Extra virgin olive oil modulates brain docosahexaenoic acid level and oxidative damage caused by 2,4-Dichlorophenoxyacetic acid in rats.

    PubMed

    Amel, Nakbi; Wafa, Tayeb; Samia, Dabbou; Yousra, Belaid; Issam, Chargui; Cheraif, Imed; Attia, Nebil; Mohamed, Hammami

    2016-03-01

    Oxidative stress is an important pathomechanism of neurological disorders such as Alzheimer disease and Parkinson disease, cardiovascular disorders and many others. This study sought to verify whether extra-virgin olive oil (EVOO), lipophilic fraction (OOLF) and hydrophilic fraction (OOHF) exerted a brain protective effect against the oxidative stress caused by 2,4-dichlorophenoxyacetic acid (2,4-D) pesticide at a dose of 5 mg/kg body weight. 2,4-D, EVOO and its fractions were administered to rats by gavages for four consecutive weeks. Oxidative stress was assessed by measuring brain lipid peroxide level, acetylcholinesterase (AChE), antioxidant enzyme activities and fatty acid composition. 2,4-D induced a decrease in both plasma and brain acetylcholinesterase activity and a rise in Brain TBARS (Thiobarbituric acid reactive substances) level and antioxidant enzyme activities compared with the control group. These changes were partly reversed by either EVOO or its fractions oral administration to 2,4-D treated rats. EVOO enhanced a neuroprotective effect evaluated by the restoration of brain fatty acid composition especially the level of docosahexaenoic acid (DHA). Our results indicate that EVOO exerts a neuroprotective activity against oxidative damage in brain induced by 2,4-D, which could be attributed to its antioxidative property. PMID:27570270

  20. Salivary Sialic Acid Levels in Smokeless Tobacco Users

    PubMed Central

    Farhad Mollashahi, Leila; Honarmand, Marieh; Nakhaee, Alireza; Mollashahi, Ghasem

    2016-01-01

    Background Smokeless tobacco chewing is one of the known risk factors for oral cancer. It is consumed widely by residents of southeastern Iran. Objectives In this study, salivary free and total sialic acid, and total protein were compared in paan consumers and non-consumers. Patients and Methods In this cross-sectional study, unstimulated saliva of 94 subjects (44 paan consumers and 50 non-consumers) who were referred to the oral medicine department of the dentistry school of Zahedan were collected. Salivary free and total sialic acid, and total protein concentration were measured by standard biochemical methods, and the obtained data were analyzed using SPSS 20 through the non-parametric Mann-Whitney test. Results The concentration of salivary free sialic acid (23.21 ± 18.98 mg/L) was significantly increased in paan consumers. The concentration of salivary Total sialic acid (TSA) (39.57 ± 26.58 mg/L) and total protein (0.77 ± 0.81 mg/mL) showed increases in paan consumers, however, the results were not statistically significant. Conclusions Salivary free and total sialic acid, and total protein were higher in the paan consumers compared to non-consumers. Due to the carcinogenic effect of smokeless tobacco, measurement of these parameters in saliva may be useful in early detection of oral cancer. PMID:27622172

  1. Differential effects of cyclosporin A on transport of bile acids by rat hepatocytes: relationship to individual serum bile acid levels.

    PubMed

    Azer, S A; Stacey, N H

    1994-02-01

    Cyclosporin A treatment has been reported to induce hepatotoxicity marked by a rise in total serum bile acid and total bilirubin. The mechanism of cyclosporin A-induced hepatotoxicity seems to be related to interference with hepatocellular transport of these substrates although this remains to be fully substantiated. The purpose of this study was to investigate whether the hepatocellular uptake of the different bile acids, in the presence of cyclosporin A, is consistent with the changes in their respective individual serum bile acid concentrations. High-performance liquid chromatography has been used to assay individual serum bile acids in cyclosporin A-treated rats at doses of 0.1, 1, and 10 mg/kg/day for 4 days. Control rats were treated with Cremophor (1 ml/kg/day). At the higher doses, cyclosporin A produced a significant increase in levels of cholic acid, taurocholic acid, chenodeoxycholic acid, and deoxycholic acid compared with controls. Serum glycocholate was unaffected even at the highest dose. Inhibition of initial rate of uptake and accumulation of [14C]cholic acid, [14C]chenodeoxycholic acid, and [14C]deoxycholic acid by isolated rat hepatocytes was consistent with the changes in their respective serum bile acids. Coincubation of rat hepatocytes with unlabeled cholic acid (100 microM), the major serum bile acid in cyclosporin A-treated rats, showed a further inhibitory effect on [14C]cholic acid and [14C]deoxycholic acid accumulation. The initial rate of uptake of [14C]glycocholate was also inhibited. However, accumulation of glycocholic acid did not show significant changes at the longer incubation times (2-30 min). In addition, coincubation of rat hepatocytes with unlabeled cholic acid (100 microM) plus cyclosporin A did not induce any inhibition of glycocholate accumulation. Together, these differences provide an explanation for the unchanged serum levels of glycocholate. In conclusion, the changes in individual serum bile acids in cyclosporin A

  2. Determination of trans fatty acid levels by FTIR in processed foods in Australia.

    PubMed

    McCarthy, Justine; Barr, Daniel; Sinclair, Andrew

    2008-01-01

    Health authorities around the world advise 'limiting consumption of trans fatty acid', however in Australia the trans fatty acid (TFA) content is not required to be listed in the nutrition information panel unless a declaration or nutrient claim is made about fatty acids or cholesterol. Since there is limited knowledge about trans fatty acid levels in processed foods available in Australia, this study aimed to determine the levels of TFA in selected food items known to be sources of TFA from previously published studies. Food items (n=92) that contain vegetable oil and a total fat content greater than 5% were included. This criterion was used in conjunction with a review of similar studies where food items were found to contain high levels of trans fatty acids. Lipids were extracted using solvents. Gravimetric methods were used to determine total fat content and trans fatty acid levels were quantified by Attenuated Total Reflectance Fourier Transform Infrared spectroscopy. High levels of trans fatty acids were found in certain items in the Australian food supply, with a high degree of variability. Of the samples analysed, 13 contained greater than 1 g of trans fatty acids per serving size, the highest value was 8.1 g/serving. Apart from when the nutrition information panel states that the content is less than a designated low level, food labels sold in Australia do not indicate trans fatty acid levels. We suggested that health authorities seek ways to assist consumers to limit their intakes of trans fatty acids. PMID:18818158

  3. System-level understanding of the potential acid-tolerance components of Acidithiobacillus thiooxidans ZJJN-3 under extreme acid stress.

    PubMed

    Feng, Shoushuai; Yang, Hailin; Wang, Wu

    2015-09-01

    In previous study, two extremely acidophilic strains Acidithiobacillus thiooxidans ZJJN-3 (collection site: bioleaching leachate) and ZJJN-5 (collection site: bioleaching wastewater) were isolated from a typical industrial bio-heap in China. Here, we unraveled the potential acid-tolerance components of ZJJN-3 by comparing the physiological differences with ZJJN-5 under different acid stresses. The parameters used for comparison included intracellular pH (pHin), capsule morphology, fatty acid composition of cell membrane, transcription of key molecular chaperones, H(+)-ATPase activities and NAD(+)/NADH ratio. It was indicated that the acid-tolerance of A. thiooxidans ZJJN-3 was systematically regulated. Capsule first thickened and then shed off along with increased acid stress. Cell membrane maintained the intracellular stability by up-regulating the proportion of unsaturated fatty acid and cyclopropane fatty acids. Meanwhile, the transcription of key repair molecular chaperones (GrpE-DnaK-DnaJ) was up-regulated by 2.2-3.5 folds for ensuring the proper folding of peptide. Moreover, low pHin promoted ZJJN-3 to biosynthesize more H(+)-ATPase for pumping H(+) out of cells. Furthermore, the NAD(+)/NADH ratio increased due to the decreased H(+) concentration. Based on the above physiological analysis, the potential acid-tolerance components of A. thiooxidans ZJJN-3 were first proposed and it would be useful for better understanding how these extremophiles responded to the high acid stress. PMID:26264736

  4. Defectivity decrease in the photolithography process by AMC level reduction through implementation of novel filtration and monitoring solutions

    NASA Astrophysics Data System (ADS)

    Pic, Nicolas; Martin, Christophe; Vitalis, Michel; Calarnou, Thierry; Camlay, Daniel; Grosjean, Catherine; Lanier, Arnaud; Kames, Jost; Acksel, Alexander; Galvez, Christophe

    2010-03-01

    A case study of drastic photolithography defectivity reduction on i-line and Deep-UV (DUV) tools is presented. We show how this result is linked with reduction of Airborne Molecular Contamination (AMC) in clean room by combined installation of novel type of filters on tracks and on the recirculation air treatment. The root cause was identified to be the presence of acetic acid in clean room created by a reaction with the filters (mounted on track tools to exclude ammonia contamination of the process) and the photo solvent itself (here mainly 1-methoxy-2-propanol acetate: PGMEA). Crucial for the project success was the use of a real time monitoring tool to detect the sources of Volatile Organic Compounds (VOC). Finally, a model of chemical reaction of satellite defects creation is discussed based on a Time of Flight Static SIMS (TOF SSIMS) analysis together with new AMC specification for acetic acid for the photolithography area.

  5. Decreased Membrane Integrity in Aging Typha latifolia L.Pollen (Accumulation of Lysolipids and Free Fatty Acids).

    PubMed Central

    Van Bilsen, DGJL.; Hoekstra, F. A.

    1993-01-01

    Aging of cattail (Typha latifolia L.) pollen was studied at 24[deg]C under conditions of 40 and 75% relative humidity (RH). The decline of viability coincides with increased leakage at imbibition; both processes develop much faster at the higher humidity condition. During aging phospholipids are deesterified and free fatty acids (FFAs) and lysophospholipids (LPLs) accumulate, again, much more rapidly at 75% RH than at 40% RH. The fatty acid composition of the remaining phospholipids hardly changes during aging, which suggests limited involvement of lipid peroxidation in the degradation process. Tests with phospholipase A2 revealed that the saturated fatty acids occur at the sn-1 position of the glycerol backbone of the phospholipids. The fatty acid composition of the LPLs is similar to that of the phospholipids from which they were formed, indicating that the deesterification occurs at random. This favors involvement of free radicals instead of phospholipases in the deesterification process. Liposome studies were carried out to characterize components in the lipid fraction that might account for the leakage associated with aging. Entrapped carboxyfluorescein leaked much more from liposomes when they were partly made up from total lipids from aged pollen than from nonaged pollen. The components causing the leakage were found in both the polar and the neutral lipid fractions. Further purification and subsequent interchanging of the FFAs and LPLs between extracts from aged and nonaged pollen revealed that in neutral lipid extracts the FFAs are entirely responsible for the leakage, whereas in the phospholipid fraction the LPLs are largely responsible for the leakage. The leakage from the liposomes is not caused by fusion. We suggest that the observed loss of viability and increased leakage during aging are due to the nonenzymic accumulation of FFAs and LPLs in the pollen membranes. PMID:12231723

  6. Selective inhibition of HDAC8 decreases neuroblastoma growth in vitro and in vivo and enhances retinoic acid-mediated differentiation.

    PubMed

    Rettig, I; Koeneke, E; Trippel, F; Mueller, W C; Burhenne, J; Kopp-Schneider, A; Fabian, J; Schober, A; Fernekorn, U; von Deimling, A; Deubzer, H E; Milde, T; Witt, O; Oehme, I

    2015-01-01

    For differentiation-defective malignancies, compounds that modulate transcription, such as retinoic acid and histone deacetylase (HDAC) inhibitors, are of particular interest. HDAC inhibitors are currently under investigation for the treatment of a broad spectrum of cancer diseases. However, one clinical drawback is class-specific toxicity of unselective inhibitors, limiting their full anticancer potential. Selective targeting of individual HDAC isozymes in defined tumor entities may therefore be an attractive alternative treatment approach. We have previously identified HDAC family member 8 (HDAC8) as a novel target in childhood neuroblastoma. Using small-molecule inhibitors, we now demonstrate that selective inhibition of HDAC8 exhibits antineuroblastoma activity without toxicity in two xenograft mouse models of MYCN oncogene-amplified neuroblastoma. In contrast, the unselective HDAC inhibitor vorinostat was more toxic in the same models. HDAC8-selective inhibition induced cell cycle arrest and differentiation in vitro and in vivo. Upon combination with retinoic acid, differentiation was significantly enhanced, as demonstrated by elongated neurofilament-positive neurites and upregulation of NTRK1. Additionally, MYCN oncogene expression was downregulated in vitro and tumor cell growth was markedly reduced in vivo. Mechanistic studies suggest that cAMP-response element-binding protein (CREB) links HDAC8- and retinoic acid-mediated gene transcription. In conclusion, HDAC-selective targeting can be effective in tumors exhibiting HDAC isozyme-dependent tumor growth in vivo and can be combined with differentiation-inducing agents. PMID:25695609

  7. Selective inhibition of HDAC8 decreases neuroblastoma growth in vitro and in vivo and enhances retinoic acid-mediated differentiation

    PubMed Central

    Rettig, I; Koeneke, E; Trippel, F; Mueller, W C; Burhenne, J; Kopp-Schneider, A; Fabian, J; Schober, A; Fernekorn, U; von Deimling, A; Deubzer, H E; Milde, T; Witt, O; Oehme, I

    2015-01-01

    For differentiation-defective malignancies, compounds that modulate transcription, such as retinoic acid and histone deacetylase (HDAC) inhibitors, are of particular interest. HDAC inhibitors are currently under investigation for the treatment of a broad spectrum of cancer diseases. However, one clinical drawback is class-specific toxicity of unselective inhibitors, limiting their full anticancer potential. Selective targeting of individual HDAC isozymes in defined tumor entities may therefore be an attractive alternative treatment approach. We have previously identified HDAC family member 8 (HDAC8) as a novel target in childhood neuroblastoma. Using small-molecule inhibitors, we now demonstrate that selective inhibition of HDAC8 exhibits antineuroblastoma activity without toxicity in two xenograft mouse models of MYCN oncogene-amplified neuroblastoma. In contrast, the unselective HDAC inhibitor vorinostat was more toxic in the same models. HDAC8-selective inhibition induced cell cycle arrest and differentiation in vitro and in vivo. Upon combination with retinoic acid, differentiation was significantly enhanced, as demonstrated by elongated neurofilament-positive neurites and upregulation of NTRK1. Additionally, MYCN oncogene expression was downregulated in vitro and tumor cell growth was markedly reduced in vivo. Mechanistic studies suggest that cAMP-response element-binding protein (CREB) links HDAC8- and retinoic acid-mediated gene transcription. In conclusion, HDAC-selective targeting can be effective in tumors exhibiting HDAC isozyme-dependent tumor growth in vivo and can be combined with differentiation-inducing agents. PMID:25695609

  8. Alterations of endothelial nucleotide levels by mycophenolic acid result in changes of membrane glycosylation and E-selectin expression.

    PubMed

    Bertalanffy, P; Dubsky, P; Wolner, E; Weigel, G

    1999-03-01

    The effect of the inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH), mycophenolic acid, on intracellular nucleotides and the synthesis of cellular glycoproteins was evaluated in human umbilical vein endothelial cells. A clinically attainable concentration (10 micromol/l) of mycophenolic acid decreased guanosine-5'-triphosphate (GTP) levels significantly and led to a strong elevation of uridine-5'-triphosphate (UTP), whereas intracellular adenosine-5'-triphosphate (ATP) pools remained unaffected. The staining of the endothelial cell membranes with lectins specific for fucose and mannose (Ulex europaeus- and Galanthus nivalis agglutinin, respectively) was reduced, reflecting an inhibition of fucose and mannose incorporation into endothelial glycoproteins. The surface expression of E-selectin, an important determinant for leuko-endothelial interactions decreased significantly. Guanine and guanosine prevented the actions of mycophenolic acid and reversed the drug-induced decrease in GTP and its associated effects. The findings that mycophenolic acid produces alterations in the formation of glycoproteins and in the membrane architecture are indicative of metabolic lesions induced by an agent that depresses guanine nucleotide synthesis through inhibition of IMPDH. The pronounced reduction of E-selectin surface expression on endothelial cells accompanied by changes of endothelial cell fucosylation, a prerequisite for the contact with lymphocytic L-selectin, indicates an inhibitory effect of mycophenolic acid in the rolling phase of leukocyte recruitment and strongly implies a new and additional immunosuppressive mechanism of this agent. PMID:10353469

  9. Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration?

    PubMed

    Cheah, Irwin K; Feng, Lei; Tang, Richard M Y; Lim, Keith H C; Halliwell, Barry

    2016-09-01

    Ergothioneine (ET), a naturally occurring thione, can accumulate in the human body at high concentrations from diet. Following absorption via a specific transporter, OCTN1, ET may accumulate preferentially in tissues predisposed to higher levels of oxidative stress and inflammation. Given its potential cytoprotective effects, we examined how ET levels change with age. We found that whole blood ET levels in elderly individuals decline significantly beyond 60 years of age. Additionally, a subset of these subjects with mild cognitive impairment had significantly lower plasma ET levels compared with age-matched subjects. This decline suggests that deficiency in ET may be a risk factor, predisposing individuals to neurodegenerative diseases. PMID:27444382

  10. Dietary alpha-linolenic acid increases brain but not heart and liver docosahexaenoic acid levels.

    PubMed

    Barceló-Coblijn, Gwendolyn; Collison, Lauren W; Jolly, Christopher A; Murphy, Eric J

    2005-08-01

    Fish oil-enriched diets increase n-3 FA in tissue phospholipids; however, a similar effect by plant-derived n-3 FA is poorly defined. To address this question, we determined mass changes in phospholipid FA, individual phospholipid classes, and cholesterol in the liver, heart, and brain of rats fed diets enriched in flax oil (rich in 18:3n-3), fish oil (rich in 22:6n-3 and 20:5n-3), or safflower oil (rich in 18:2n-6) for 8 wk. In the heart and liver phospholipids, 22:6n-3 levels increased only in the fish oil group, although rats fed flax oil accumulated 20:5n-3 and 22:5n-3. However, in the brain, the flax and fish oil diets increased the phospholipid 22:6n-3 mass. In all tissues, these diets decreased the 20:4n-6 mass, although the effect was more marked in the fish oil than in the flax oil group. Although these data do not provide direct evidence for 18:3n-3 elongation and desaturation by the brain, they demonstrate that 18:3n-3-enriched diets reduced tissue 20:4n-6 levels and increased cellular n-3 levels in a tissue-dependent manner. We hypothesize, based on the lack of increased 22:6n-3 but increased 18:3n-3 in the liver and heart, that the flax oil diet increased circulating 18:3n-3, thereby presenting tissue with this EFA for further elongation and desaturation. PMID:16296397

  11. Plasma Circulating Nucleic Acids Levels Increase According to the Morbidity of Plasmodium vivax Malaria

    PubMed Central

    Franklin, Bernardo S.; Vitorino, Barbara L. F.; Coelho, Helena C.; Menezes-Neto, Armando; Santos, Marina L. S.; Campos, Fernanda M. F.; Brito, Cristiana F.; Fontes, Cor J.; Lacerda, Marcus V.; Carvalho, Luzia H.

    2011-01-01

    Background Given the increasing evidence of Plasmodium vivax infections associated with severe and fatal disease, the identification of sensitive and reliable markers for vivax severity is crucial to improve patient care. Circulating nucleic acids (CNAs) have been increasingly recognized as powerful diagnostic and prognostic tools for various inflammatory diseases and tumors as their plasma concentrations increase according to malignancy. Given the marked inflammatory status of P. vivax infection, we investigated here the usefulness of CNAs as biomarkers for malaria morbidity. Methods and Findings CNAs levels in plasma from twenty-one acute P. vivax malaria patients from the Brazilian Amazon and 14 malaria non-exposed healthy donors were quantified by two different methodologies: amplification of the human telomerase reverse transcriptase (hTERT) genomic sequence by quantitative real time PCR (qPCR), and the fluorometric dsDNA quantification by Pico Green. CNAs levels were significantly increased in plasma from P. vivax patients as compared to healthy donors (p<0.0001). Importantly, plasma CNAs levels were strongly associated with vivax morbidity (p<0.0001), including a drop in platelet counts (p = 0.0021). These findings were further sustained when we assessed CNAS levels in plasma samples from 14 additional P. vivax patients of a different endemic area in Brazil, in which CNAS levels strongly correlated with thrombocytopenia (p = 0.0072). We further show that plasma CNAs levels decrease and reach physiological levels after antimalarial treatment. Although we found both host and parasite specific genomic sequences circulating in plasma, only host CNAs clearly reflected the clinical spectrum of P. vivax malaria. Conclusions Here, we provide the first evidence of increased plasma CNAs levels in malaria patients and reveal their potential as sensitive biomarkers for vivax malaria morbidity. PMID:21611202

  12. Endotoxin-stimulated macrophages decrease bile acid uptake in WIF-B cells, a rat hepatoma hybrid cell line.

    PubMed

    Sturm, E; Zimmerman, T L; Crawford, A R; Svetlov, S I; Sundaram, P; Ferrara, J L; Karpen, S J; Crawford, J M

    2000-01-01

    Endotoxemia leads to cytokine-mediated alterations of the hepatocellular sodium-taurocholate-cotransporting polypeptide (ntcp). We hypothesized that stimulated macrophages are essential transducers for down-regulating hepatocellular bile salt uptake in response to endotoxin (lipopolysaccharide [LPS]) exposure. Using an in vitro model, we exposed mouse macrophages (IC-21 cell line) to LPS for 24 hours. Concentrations of cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 increased 10.6-fold, 12.5-fold, and 444-fold, respectively, in LPS-conditioned IC-21 medium (CM) versus unconditioned IC-21 medium (UM). WIF-B rat hepatoma hybrid cells were incubated with either CM or UM or treated directly with medium containing recombinant TNF-alpha, IL-1beta, and IL-6. [(3)H]Taurocholate ([(3)H]TC) uptake decreased in WIF-B cells exposed to either TNF-alpha (54% of control), IL-1beta (78%), IL-6 (55%) as single additives, or in triple combination (TCC) (43%). A virtually identical decrease was observed after exposing WIF-B cells to CM (52%, P <.001). LPS had no direct effect on [(3)H]TC uptake. CM treatment did not decrease L-alanine transport in WIF-B cells. Blocking antibodies against TNF-alpha, IL-1beta, and IL-6 restored the diminished [(3)H]TC uptake in cells exposed to TCC and CM to 87% and 107% of controls, respectively. Northern blotting revealed that ntcp messenger RNA (mRNA) expression was significantly reduced in WIF-B cells after exposure to CM, and in primary rat hepatocytes exposed to CM or TNF-alpha (68%, 14%, and 29% of control, respectively). We conclude that macrophages and their ability to secrete the cytokines TNF-alpha, IL-1beta, and IL-6 may be essential in mediating the endotoxin-induced cholestatic effect of decreased hepatocellular bile salt uptake. PMID:10613737

  13. Impaired spatial working memory and decreased frontal cortex BDNF protein level in dopamine transporter knock out mice

    PubMed Central

    Li, BingJin; Arime, Yosefu; Hall, F. Scott; Uhl, George R.; Sora, Ichiro

    2010-01-01

    Brain-derived neurotrophic factor (BDNF), one of the key brain neurotrophins, has been implicated in neuronal plasticity and memory. Recent studies document the importance of BDNF for normal long-term memory functions. However, there are few studies of the roles of BDNF in short term memory. Dopamine is likely to play important roles in BDNF gene expression in specific brain regions, including frontal cortical regions that are implicated in short term working memory processes that include spontaneous alternation. We have thus tested spatial working memory in dopamine transporter knockout (DAT KO) and wild-type mice. Spontaneous alternation in the Y-maze, an index of short-term spatial working memory in mice, was significantly decreased in DAT KO mice compared to wildtype mice. BDNF protein was significantly decreased in frontal cortex, though not in striatum or hippocampus, of the DAT KO mice. The data support the hypothesis that impaired spatial working memory in DAT KO mice may be related to decreased frontal cortical BDNF in these animals, and document apparent roles for BDNF in a short term memory process. PMID:19932884

  14. Sensori-motor synchronisation variability decreases as the number of metrical levels in the stimulus signal increases.

    PubMed

    Madison, Guy

    2014-03-01

    Timing performance becomes less precise for longer intervals, which makes it difficult to achieve simultaneity in synchronisation with a rhythm. The metrical structure of music, characterised by hierarchical levels of binary or ternary subdivisions of time, may function to increase precision by providing additional timing information when the subdivisions are explicit. This hypothesis was tested by comparing synchronisation performance across different numbers of metrical levels conveyed by loudness of sounds, such that the slowest level was loudest and the fastest was softest. Fifteen participants moved their hand with one of 9 inter-beat intervals (IBIs) ranging from 524 to 3,125 ms in 4 metrical level (ML) conditions ranging from 1 (one movement for each sound) to 4 (one movement for every 8th sound). The lowest relative variability (SD/IBI<1.5%) was obtained for the 3 longest IBIs (1600-3,125 ms) and MLs 3-4, significantly less than the smallest value (4-5% at 524-1024 ms) for any ML 1 condition in which all sounds are identical. Asynchronies were also more negative with higher ML. In conclusion, metrical subdivision provides information that facilitates temporal performance, which suggests an underlying neural multi-level mechanism capable of integrating information across levels. PMID:24268879

  15. New alleles of FATB-1A to reduce palmitic acid levels in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In wild-type soybeans, palmitic acid typically constitutes 10% of the total seed oil. Palmitic acid is a saturated fat linked to increased cholesterol levels, and reducing levels of saturated fats in soybean oil has been a breeding target. To identify novel and useful variation that could help in re...

  16. 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…

  17. The decrease in Greenland ice-core δ15N of nitrate in the industrial period: influenced by changes in atmospheric acidity?

    NASA Astrophysics Data System (ADS)

    Geng, L.; Cole-Dai, J.; Alexander, B.; Steig, E. J.; Schauer, A. J.; Savarino, J.

    2012-12-01

    Previous study in a central Greenland ice core has revealed a decreasing trend in δ15N of nitrate (δ15N (nitrate)) starting as early as 1850 C.E.. Lake sediment cores from North America show a similar trend in δ15N of total nitrogen starting around 1895 C.E.. The decrease in δ15N has been proposed to be due to the increasing deposition of anthropogenically derived (i.e., fossil fuel combustion) nitrate in the industrial period. However, this interpretation is questioned by measurements of δ15N in NOx and atmospheric nitrate. Here, we present new, annually-resolved records of δ15N (nitrate) and major ion concentrations (Cl-, NO3-, SO42-, Na+, NH4+, K+, Mg2+, and Ca2+) obtained from two central Greenland ice cores. The results (Figure 1) indicate that the significant decrease in δ15N is coincident with an increase in acidity (H+ concentration estimated based on ionic balance) beginning around 1895 C.E., which is about 50 years earlier than the start of the increase in nitrate concentration (~1945 C.E.) . This observation suggests that it is likely the acidity change, instead of the input of anthropogenic nitrate, triggered the decrease in ice-core δ15N (nitrate). Atmospheric aerosol acidity influences the partitioning of atmospheric nitrate between its gaseous (HNO3) and particulate (p-NO3-) phases, resulting in a depletion of δ15N in HNO3 relative to p-NO3-. If atmospheric nitrate is transported to central Greenland preferentially in its gaseous form (HNO3), which is an open question, a decrease in ice-core δ15N (nitrate) would be expected with an increase in atmospheric acidity. We will examine the relationships between δ15N (nitrate) and the ice-core records of acidity, and HNO3, to discern the processes from changes in atmospheric acidity to the observed variability in ice core δ15N (nitrate) during the Industrial era.igure 1. The annual NO3- (blue curve), H+ (black curve) concentrations, and annual δ15N (nitrate) (red curve, y-axis is reversely

  18. Effectiveness of the GnRH agonist Deslorelin as a tool to decrease levels of circulating testosterone in zebra finches.

    PubMed

    Murphy, Karagh; Wilson, David A; Burton, Mark; Slaugh, Shayla; Dunning, Jeffery L; Prather, Jonathan F

    2015-10-01

    Songbirds are widely used in studies of the neurobiology underlying learning, memory and performance of the sounds used in vocal communication. Development and activity of neurons in many brain sites implicated in those behaviors are closely related to levels of circulating testosterone. Approaches to understand the effects of testosterone in songbirds are presently limited to testosterone implants, which elevate testosterone levels to supraphysiological values, or castration, which eliminates gonadal production of testosterone. Previous studies in mammals indicate that GnRH agonists may be an effective tool to reduce testosterone within that range of extremes and without invasive surgery. To evaluate the effectiveness of the GnRH agonist Deslorelin as a tool to modulate levels of testosterone in songbirds, we recorded the effects of Deslorelin in adult male zebra finches. We recorded songs, body mass and blood testosterone levels pre-treatment, then we gave each bird a small subcutaneous implant of Deslorelin. We measured blood plasma testosterone levels weekly and recorded song behavior and gross morphology of brain, testes and heart at the end of each experiment. Testosterone levels were reduced at the 5mg/kg dose, and the very slight song changes we observed at that dose were like those reported for castrated zebra finches. As expected, there were no changes in the number of cells in androgen-sensitive brain structures. Suppression of testosterone at the 5mg/kg dose was reversible through implant removal. Thus, Deslorelin is a new tool to transiently suppress testosterone levels without the invasiveness and undesirable aftereffects of surgical castration. PMID:26391838

  19. Incremental amounts of ground flaxseed decreases milk production but increases n-3 fatty acids and conjugated linoleic acids in dairy cows fed high-forage diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to investigate the effect of incremental amounts of ground flaxseed (GFLAX) on milk yield and fatty acids (FA) profile, ruminal metabolism, and nutrient digestibility in dairy cows fed high-forage diets. Twelve multiparous Jersey cows averaging (mean ± SD) 112 ± 68 da...

  20. Plasma hyaluronic acid level as a prognostic and monitoring marker of metastatic breast cancer.

    PubMed

    Peng, Cike; Wallwiener, Markus; Rudolph, Anja; Ćuk, Katarina; Eilber, Ursula; Celik, Muhabbet; Modugno, Caroline; Trumpp, Andreas; Heil, Jörg; Marmé, Frederik; Madhavan, Dharanija; Nees, Juliane; Riethdorf, Sabine; Schott, Sarah; Sohn, Christof; Pantel, Klaus; Schneeweiss, Andreas; Chang-Claude, Jenny; Yang, Rongxi; Burwinkel, Barbara

    2016-05-15

    Conventional tumor markers have limited value for prognostication and treatment monitoring in metastatic breast cancer (MBC) patients and novel circulating tumor markers therefore need to be explored. Hyaluronic acid (HA) is a major macropolysaccharide in the extracellular matrix and is reported to be associated with tumor progression. In our study, we investigated plasma HA level with respect to progression free survival (PFS) and overall survival (OS), as well as the treatment monitoring value in MBC patients. The prognostic value of plasma HA level was investigated in a discovery cohort of 212 MBC patients with 2.5-year follow-up and validated in an independent validation cohort of 334 patients with 5-year follow-up. The treatment monitoring value of plasma HA level was investigated in 61 MBC patients from discovery cohort who had been radiographically examined after first complete cycle of chemo therapy. We found a robust association between high plasma HA level and poor prognosis of MBC patients in both discovery (pPFS  = 7.92 × 10(-6) and pOS  = 5.27 × 10(-5) ) and validation studies (pPFS  = 3.66 × 10(-4) and pOS  = 1.43 × 10(-4) ). In the discovery cohort, the plasma HA level displayed independent prognostic value after adjusted for age and clinicopathological factors, with respect to PFS and OS. Further, the decrease of plasma HA level displayed good concordance with treatment response evaluated by radiographic examination (AUC = 0.79). Plasma HA level displays prognostic value, as well as treatment monitoring value for MBC patients. PMID:26686298

  1. The Association between Marine n-3 Polyunsaturated Fatty Acid Levels and Survival after Renal Transplantation

    PubMed Central

    Jenssen, Trond; Hartmann, Anders; Diep, Lien M.; Dahle, Dag O.; Reisæter, Anna V.; Bjerve, Kristian S.; Christensen, Jeppe H.; Schmidt, Erik B.; Svensson, My

    2015-01-01

    Background and objectives Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants. Design, setting, participants, & measurements In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation. Results There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with low levels (<7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality. Conclusions Higher plasma phospholipid marine n-3

  2. Folic acid deficiency enhances abeta accumulation in APP/PS1 mice brain and decreases amyloid-associated miRNAs expression.

    PubMed

    Liu, Huan; Tian, Tian; Qin, Shanchun; Li, Wen; Zhang, Xumei; Wang, Xuan; Gao, Yuxia; Huang, Guowei

    2015-12-01

    Recent efforts have revealed the microRNA (miRNA) pathways in the pathogenesis of Alzheimer's disease (AD). Epidemiological studies have revealed an association between folic acid deficiency and AD risk. However, the effects of folic acid deficiency on miRNA expression in AD animals have not been observed. We aimed to find if folic acid deficiency may enhance amyloid-β (Aβ) peptide deposition and regulate amyloid-associated miRNAs and their target genes expression in APP/PS1 mice. APP/PS1 mice and N2a cells were treated with folic acid-deficient diet or medium. Cognitive function of mice was assessed using the Morris water maze. miRNA profile was tested by polymerase chain reaction (PCR) array. Different expressional miRNAs were validated by real-time PCR. The deposition of Aβ plaques was evaluated by immunohistochemistry and enzyme-linked immunosorbent assay. APP and BACE1 proteins in mice brain and N2a cells were determined by Western blot. Folic acid deficiency aggravated amyloid pathology in AD mice. The AD+FD group showed shorter time spent in the target zone during the probe test. Analysis of miRNAs predicted to target these genes revealed several miRNA candidates that were differentially modulated by folic acid deficiency. In APP/PS1 mice brains and N2a cells with folic acid-deficient treatment, miR-106a-5p, miR-200b-3p and miR-339-5p were down-regulated, and their target genes APP and BACE1 were up-regulated. In conclusion, folic acid deficiency can enhance Aβ accumulation in APP/PS1 mice brain and decrease amyloid-associated miRNAs expression. PMID:26345540

  3. Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue

    PubMed Central

    Jadavji, N.M.; Wieske, F.; Dirnagl, U.; Winter, C.

    2015-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is an enzyme key regulator in folate metabolism. Deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAM). In the brain, SAM donates methyl groups to catechol-O-methyltransferase (COMT), which is involved in neurotransmitter analysis. Using the MTHFR-deficient mouse model the purpose of this study was to investigate levels of monoamine neurotransmitters and amino acid levels in brain tissue. MTHFR deficiency affected levels of both glutamate and γ-aminobutyric acid in within the cerebellum and hippocampus. Mthfr−/− mice had reduced levels of glutamate in the amygdala and γ-aminobutyric acid in the thalamus. The excitatory mechanisms of homocysteine through activation of the N-methyl-d-aspartate receptor in brain tissue might alter levels of glutamate and γ-aminobutyric acid. PMID:26937386

  4. Higher Fasting Plasma Glucose Levels, within the Normal Range, are Associated with Decreased Processing Speed in High Functioning Young Elderly.

    PubMed

    Raizes, Meytal; Elkana, Odelia; Franko, Motty; Ravona Springer, Ramit; Segev, Shlomo; Beeri, Michal Schnaider

    2015-01-01

    We explored the association of plasma glucose levels within the normal range with processing speed in high functioning young elderly, free of type 2 diabetes mellitus (T2DM). A sample of 41 participants (mean age = 64.7, SD = 10; glucose 94.5 mg/dL, SD = 9.3), were examined with a computerized cognitive battery. Hierarchical linear regression analysis showed that higher plasma glucose levels, albeit within the normal range (<110 mg/dL), were associated with longer reaction times (p <  0.01). These findings suggest that even in the subclinical range and in the absence of T2DM, monitoring plasma glucose levels may have an impact on cognitive function. PMID:26484908

  5. Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-β levels in female rats

    PubMed Central

    Berry, Anne S.; Tomidokoro, Yasushi; Ghiso, Jorge; Thornton, Jan

    2008-01-01

    Numerous studies have suggested that estradiol (E) improves spatial memory as female rats with E perform better than those without E. However there is an inverse relationship between E and luteinizing hormone (LH) levels and LH could play a role. We examined whether treatment with the LH homologue human chorionic gonadotropin (hCG), would impair spatial memory of adult E-treated female rats. In the Object Location Memory Task, ovariectomized (ovxed) rats treated with E and either a single high dose (400IU/kg) or a lower repeated dose of hCG (75 IU/kg hourly for 8 hours) showed spatial memory disruption compared to ovxed rats treated with estradiol alone. Impairment was attributed to memory disruption as performance improved with shortened delay between task exposure and testing. Tests on another spatial memory task, the Barnes maze, confirmed that hCG (400IU/kg) can impair memory: although E + veh treated animals made significantly fewer hole errors across time, E + hCG treated did not. In humans, high LH levels have been correlated with Alzheimer’s Disease (AD). Because brain amyloid-beta (Aβ) species have been implicated as a toxic factor thought to cause memory loss in AD, we analyzed whether hCG-treated animals had increased Aβ levels. Levels of Aβ from whole brains or hippocampi were assessed by Western Blot. hCG treatment to E-implanted females significantly increased soluble Aβ40 and Aβ42 levels. These results indicate that high levels of LH/hCG can impair spatial memory, and an increase in brain Aβ species may account for the memory impairment in hCG-treated rats. PMID:18413150

  6. Melatonin receptor deficiency decreases and temporally shifts ecto-5'-nucleotidase mRNA levels in mouse prosencephalon.

    PubMed

    Homola, Moran; Pfeffer, Martina; Robson, Simon C; Fischer, Claudia; Zimmermann, Herbert; Korf, Horst-Werner

    2016-07-01

    Ecto-5'-nucleotidase (eN) is the major extracellular adenosine-producing ecto-enzyme in mouse brain. Via the production of adenosine, eN participates in many physiological and pathological processes, such as wakefulness, inflammation, nociception and neuroprotection. The mechanisms regulating the expression of eN are therefore of considerable neurobiological and clinical interest. Having previously described a modulatory effect of melatonin in the regulation of eN mRNA levels, we decided to analyze the melatonin receptor subtype involved in the regulation of eN mRNA levels by comparing eN mRNA patterns in melatonin-proficient transgenic mice lacking either the melatonin receptor subtype 1 (MT1 KO) or both melatonin receptor subtypes (MT1 and MT2; MT1/2 KO) with the corresponding melatonin-proficient wild-type (WT) controls. By means of radioactive in situ hybridization, eN mRNA levels were found to be diminished in both MT1 and MT1/2 KO mice compared with WT controls suggesting stimulatory impacts of melatonin receptors on eN mRNA levels. Whereas eN mRNA levels increased during the day and peaked at night in WT and MT1 KO mice, eN mRNA levels at night were reduced and the peak was shifted toward day-time in double MT1/2 KO mice. These data suggest that the MT2 receptor subtype may play a role in the temporal regulation of eN mRNA availability. Notably, day-time locomotor activity was significantly higher in MT1/2 KO compared with WT mice. Our results suggest melatoninergic signaling as an interface between the purinergic system and the circadian system. PMID:26917036

  7. Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide.

    PubMed

    Speth, Jana; Speth, Clemens; Kaelen, Mendel; Schloerscheidt, Astrid M; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

    2016-04-01

    This paper reports on the effects of LSD on mental time travel during spontaneous mentation. Twenty healthy volunteers participated in a placebo-controlled crossover study, incorporating intravenous administration of LSD (75 μg) and placebo (saline) prior to functional magnetic resonance imaging (fMRI). Six independent, blind judges analysed mentation reports acquired during structured interviews performed shortly after the functional magnetic resonance imaging (fMRI) scans (approximately 2.5 h post-administration). Within each report, specific linguistic references to mental spaces for the past, present and future were identified. Results revealed significantly fewer mental spaces for the past under LSD and this effect correlated with the general intensity of the drug's subjective effects. No differences in the number of mental spaces for the present or future were observed. Consistent with the previously proposed role of the default-mode network (DMN) in autobiographical memory recollection and ruminative thought, decreased resting-state functional connectivity (RSFC) within the DMN correlated with decreased mental time travel to the past. These results are discussed in relation to potential therapeutic applications of LSD and related psychedelics, e.g. in the treatment of depression, for which excessive reflection on one's past, likely mediated by DMN functioning, is symptomatic. PMID:26979587

  8. The effect of N-stearoylethanolamine on cholesterol content, fatty acid composition and protein carbonylation level in rats with alimentary obesity-induced insulin resistance.

    PubMed

    Onopchenko, O V; Kosiakova, G V; Meged, E F; Klimashevsky, V M; Hula, N M

    2014-01-01

    The effect of N-stearoylethanolamine (NSE) on liver free fatty acid composition, cholesterol content and carbonylated protein level in rats with obesity-induced insulin resistance (IR) was studied in the work. The experimental insulin resistance was induced by prolonged high fat diet (58% of energy derived from fat) for 6 months combined with one injection of low-dose (15 mg/kg) of streptozotocin. The lipid assay showed a rise in liver free cholesterol content anda significant reduction in cholesterol esters level. Analyzing liver fatty acid composition, a decrease in polyunsaturated of fatty acid (PUFA) level and an increase in monounsaturated fatty acid (MUFA) content was found. Fatty acid imbalance with high content of MUFA was associated with elevated level ofprotein carbonylation. The NSE administration (50 mg/kg of body weight) for 2 weeks decreased free cholesterol content, increased cholesterol esters level and reduced free oleic fatty acid content in the liver of rats with IR. The effect of NSE on lipid imbalance led to a decrease in protein carbonylation level that may result in improvement of transmembrane protein function under obesity-induced insulin resistance state. PMID:25816612

  9. What is the intrapatient variability of mycophenolic acid trough levels?

    PubMed

    Todorova, Ekaterina K; Huang, Shih-Han S; Kobrzynski, Marta C; Filler, Guido

    2015-11-01

    TDM of MPA, the active compound of MMF, is rarely used despite its substantial intra- and interpatient variability. Little is known about the utility of long-term MPA TDM. Data are expressed as mean (one standard deviation). All available data from 27 renal transplant recipients (mean age at transplantation: 7.7 [5.0] yr) with an average follow-up of 9.3 (4.6) yr were analyzed. MPA levels were measured using the EMIT. GFR was measured using cystatin C and eGFR was calculated using the Filler formula. Intrapatient CV of the trough level was calculated as the ratio of the mean divided by one standard deviation. Mean cystatin C eGFR was 56.9 (24.4) mL/min/1.73 m(2) . There was a weak but significant correlation between the MPA trough level and the AUC (Spearman r = 0.6592, p < 0.0001). A total of 1964 MPA trough levels (73 [45]/patient) were measured, as compared to 3462 Tac trough levels (144 [71]/patient). The average MPA trough level was 3.01 (1.26) mg/L and the average trough Tac level was 7.3 (1.8) ng/mL. Intrapatient CV was statistically higher (p = 0.00093) for MPA at 0.68 (0.29) when compared to Tac with a CV of 0.46 (0.12). CV did not correlate with eGFR. Intrapatient MPA trough level CV is significantly higher than for Tac, while CV for both MPA and Tac was high. MPA trough level monitoring may be a feasible monitoring option to improve patient exposure and possibly outcomes. PMID:26201386

  10. Metabolite profiling of sex developmental steroid conjugates reveals an association between decreased levels of steroid sulfates and adiposity in obese girls.

    PubMed

    Lee, Su Hyeon; Kim, Shin Hye; Lee, Won-Yong; Chung, Bong Chul; Park, Mi Jung; Choi, Man Ho

    2016-09-01

    Free and conjugated steroids coexist in a dynamic equilibrium due to complex biosynthetic and metabolic processes. This may have clinical significance related to va