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Sample records for acid levels decreased

  1. Pyrazinoic acid decreases the proton motive force, respiratory ATP synthesis activity, and cellular ATP levels.

    PubMed

    Lu, Ping; Haagsma, Anna C; Pham, Hoang; Maaskant, Janneke J; Mol, Selena; Lill, Holger; Bald, Dirk

    2011-11-01

    Pyrazinoic acid, the active form of the first-line antituberculosis drug pyrazinamide, decreased the proton motive force and respiratory ATP synthesis rates in subcellular mycobacterial membrane assays. Pyrazinoic acid also significantly lowered cellular ATP levels in Mycobacterium bovis BCG. These results indicate that the predominant mechanism of killing by this drug may operate by depletion of cellular ATP reserves.

  2. Decreased eicosapentaenoic acid levels in acne vulgaris reveals the presence of a proinflammatory state.

    PubMed

    Aslan, İbrahim; Özcan, Filiz; Karaarslan, Taner; Kıraç, Ebru; Aslan, Mutay

    2017-01-01

    This study aimed to determine circulating levels of polyunsaturated fatty acids (PUFAs), secretory phospholipase A2 (sPLA2), lipoprotein lipase (LPL) and measure circulating protein levels of angiopoietin-like protein 3 (ANGPTL3), ANGPTL4, cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in patients with acne vulgaris. Serum from 21 control subjects and 31 acne vulgaris patients were evaluated for levels of arachidonic acid (AA, C20:4n- 6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3). PUFA levels were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Lipid profile, routine biochemical and hormone parameters were assayed by standard kit methods Serum EPA levels were significantly decreased while AA/EPA and DGLA/EPA ratio were significantly increased in acne vulgaris patients compared to controls. Serum levels of AA, DGLA and DHA showed no significant difference while activity of sPLA2 and LPL were significantly increased in acne vulgaris compared to controls. Results of this study reveal the presence of a proinflammatory state in acne vulgaris as shown by significantly decreased serum EPA levels and increased activity of sPLA2, AA/EPA and DGLA/EPA ratio. Increased LPL activity in the serum of acne vulgaris patients can be protective through its anti-dyslipidemic actions. This is the first study reporting altered EPA levels and increased sPLA2 activity in acne vulgaris and supports the use of omega-3 fatty acids as adjuvant treatment for acne patients.

  3. Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells

    PubMed Central

    Brigandi, Sarah A.; Shao, Hong; Qian, Steven Y.; Shen, Yiping; Wu, Bai-Lin; Kang, Jing X.

    2015-01-01

    Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3–17. Analysis of the fatty acid composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (p < 0.001). In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the autistic participants (n = 20) compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism. PMID:25946342

  4. 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.

  5. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

    PubMed Central

    2016-01-01

    We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects. PMID:27652270

  6. Estradiol decreases taurine level by reducing cysteine sulfinic acid decarboxylase via the estrogen receptor-α in female mice liver.

    PubMed

    Ma, Qiwang; Zhao, Jianjun; Cao, Wei; Liu, Jiali; Cui, Sheng

    2015-02-15

    Cysteine sulfinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO) are two rate-limiting enzymes in taurine de novo synthesis, and their expressions are associated with estrogen concentration. The present study was designed to determine the relationship between 17β-estradiol (E₂) and taurine in female mice liver. We initially observed the mice had lower levels of CSAD, CDO, and taurine during estrus than diestrus. We then, respectively, treated the ovariectomized mice, the cultured hepatocytes, and Hep G2 cells with different doses of E₂, and the CSAD and CDO expressions and taurine levels were analyzed. The results showed that E₂ decreased taurine level in the serum and the cultured cells by inhibiting CSAD and CDO expressions. Furthermore, we identified the molecular receptor types through which E₂ plays its role in regulating taurine synthesis, and our results showed that estrogen receptor-α (ERα) expression was much higher than estrogen receptor-β (ERβ) in the liver and hepatocytes, and the inhibiting effects of E₂ on CSAD, CDO, and taurine level were partially abrogated in the ICI-182,780-pretreated liver and hepatocytes, and in ERα knockout mice. These results indicate that estradiol decreases taurine content by reducing taurine biosynthetic enzyme expression in mice liver.

  7. 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...

  8. Oral folic acid supplementation decreases palate and/or lip cleft occurrence in Pug and Chihuahua puppies and elevates folic acid blood levels in pregnant bitches.

    PubMed

    Domosławska, A; Jurczak, A; Janowski, T

    2013-01-01

    The aim of this study was to compare the frequency of the occurrence of lip and/or palate cleft (CL/CP) in new-borns of two breeds, Pugs and Chihuahuas, and to measure the folic acid blood levels in bitches during gestations both with and without folic acid oral supplementation. Bitches of 13 Pugs and 17 Chihuahuas with CL/CP cases were used in the study. In trial 1, the animals of the experimental group (n=25) were given additional folic acid from the onset of heat till the 40th day of gestation. The females of the control group (n=12) were fed a traditional diet. From all the animals blood was collected at the onset of heat, 14 days later and on the 30th day of the gestation to estimate folic acid concentration. In trial 2, the prevalence of CP/CL cases in litters from pregnancies before and after supplementation was compared. The percentage of puppies with CL/CP after supplementation decreased in both Pugs and Chihuahua puppies (10.86% and 15.78% vs. 4.76% and 4.8% respectively). On Day 0, the concentrations of folic acid were at a low physiological level (around 8 ng/ml) in all the animals. In bitches of the experimental group the blood level of folic acid on day 14th and 30th of the treatment showed an increase in both breeds (13.65 +/- 4.27 ng/ml in Pugs, 10.79 +/- 2.84 ng/ml in Chihuahuas, and 14.94 +/- 3.22 ng/ml in Pugs, 12.95 +/- 3.58 in Chihuahuas, respectively) while in the control group, this level decreased with time of gestation both in Pugs and in Chihuahuas (around 6 ng/ml). Folic acid supplementation seems to be a simple, effective preventive method to reduce the risk of CL/CP, especially in the predisposed breeds.

  9. A single session of exhaustive exercise markedly decreases circulating levels of guanidinoacetic acid in healthy men and women.

    PubMed

    Stajer, Valdemar; Trivic, Tatjana; Drid, Patrik; Vranes, Milan; Ostojic, Sergej M

    2016-07-19

    We evaluated the effects of exercise on circulating concentrations of guanidinoacetic acid (GAA) and creatine in 23 healthy volunteers subjected to running to exhaustion and free-weight bench-press to volitional failure. Blood was taken before and following each exercise session. Running induced a significant decrease in serum GAA by 20.1% (P < 0.001), while free-weight exercise reduced GAA by 11.7% (P < 0.001), suggesting the possible use of serum GAA as a novel biomarker of exhaustion.

  10. Melinjo (Gnetum gnemon L.) Seed Extract Decreases Serum Uric Acid Levels in Nonobese Japanese Males: A Randomized Controlled Study

    PubMed Central

    Kanai, Yoshiaki; Katagiri, Mikiyuki; Mori, Akemi; Tatefuji, Tomoki

    2013-01-01

    Melinjo (Gnetum gnemon L.) seed extract (MSE) containing trans-resveratrol (3,5,4′-trihydroxy-trans-stilbene) and other derivatives exerts various beneficial effects. However, its mechanism of action in humans remains unknown. In this study, we aimed to investigate beneficial effects of MSE in healthy adult males. In this double-blind, randomized controlled study, 30 males aged 35–70 years with ≤10% flow-mediated dilatation received placebo or 750 mg MSE powder for 8 weeks, and twenty-nine males (45.1 ± 8.8 years old) completed the trial. There was a significant difference in the melinjo and placebo groups. Compared with the placebo control, MSE significantly reduced serum uric acid at 4 weeks and 8 weeks (n = 14 and 15, resp.). HDL cholesterol was significantly increased in the melinjo group. To clarify the mechanism of MSE for reducing uric acid, we investigated xanthine oxidase inhibitory activity, angiotensin II type 1 (AT1) receptor binding inhibition rate, and agonistic activities for PPARα and PPARγ. MSE, trans-resveratrol, and a resveratrol dimer, gnetin C (GC), significantly inhibit AT1 receptor binding and exhibit mild agonistic activities for PPARα and PPARγ. In conclusion, MSE may decrease serum uric acid regardless of insulin resistance and may improve lipid metabolism by increasing HDL cholesterol. PMID:24454499

  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

    Sicher, Richard C

    2015-08-05

    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.

  12. Carrot Juice Administration Decreases Liver Stearoyl-CoA Desaturase 1 and Improves Docosahexaenoic Acid Levels, but Not Steatosis in High Fructose Diet-Fed Weanling Wistar Rats

    PubMed Central

    Mahesh, Malleswarapu; Bharathi, Munugala; Reddy, Mooli Raja Gopal; Kumar, Manchiryala Sravan; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M.

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and β-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels. PMID:27752492

  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.

  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.

  15. Can Diuretics Decrease Your Potassium Level?

    MedlinePlus

    ... High blood pressure (hypertension) Can diuretics decrease your potassium level? Answers from Sheldon G. Sheps, M.D. Yes, some diuretics — also called water pills — decrease potassium in the blood. Diuretics are commonly used to ...

  16. Decreased serum levels of polyunsaturated fatty acids and folate, but not brain-derived neurotrophic factor, in childhood and adolescent females with depression.

    PubMed

    Tsuchimine, Shoko; Saito, Manabu; Kaneko, Sunao; Yasui-Furukori, Norio

    2015-01-30

    Evidence from observational studies suggests that there is an association among depression and brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs), and folate; however, this association has yet to be examined in childhood and adolescent depression. The objective was to determine whether the BDNF, PUFAs, and folate in serum differ between first-episode childhood and adolescent depressed patients and healthy controls. We measured the serum levels of BDNF, PUFAs, and folate of cases admitted to the hospital for depression (n=24) and compared it to that of controls (n=26). Subjects and their parents were informed about the nature and the purpose of this study, and a consent form was signed by parents. The ethics committee of Hirosaki University Graduate School of Medicine approved the study protocol. There were significant differences in the docosahexanoic acid (DHA), arachidonic acid (AA), and folate levels between cases and controls. Serum levels of DHA, AA, and folate levels in the patients group were statistically lower than those in the control group, while serum levels of BDNF were not different between cases and controls. These results are in line with findings of previous studies involving adult and elderly subjects, demonstrating lower levels of PUFAs and folate in patients with depression than healthy controls. However, further studies using larger sample size are warranted.

  17. Pyrazinoic acid decreases peritoneal transfer rates.

    PubMed

    Grzegorzewska, A E; Czyzewska, K; Szary, B

    1995-01-01

    It was shown elsewhere that in a peritoneally dialyzed woman with pulmonary tuberculosis, oral treatment with rifampicin and pyrazinamide (11 and 25 mg/kg/day, respectively) caused a decrease in the peritoneal transport of sodium, potassium, urea, uric acid, protein, and ultrafiltration rate by 48% to 75% compared to the pretreatment values. Pyrazinoic acid (PA), a metabolite of pyrazinamide, may account for these changes, because rifampicin was also previously used in this patient without peritoneal function impairment. Thus in the present study the influence of PA on the human peritoneum is examined using the modified Ussing-type chamber. PA (1 mg/dL) was introduced into the medium on the interstitial side of the membrane. After the introduction of PA, uric acid transfer from the interstitial to the mesothelial side decreased by about 50%. There were no significant changes in the urea and albumin transfer rates. In conclusion, PA induces changes in uric acid transfer acting directly on mesothelial cells, whereas a decrease in the peritoneal transfer of other solutes may be caused by a decrease in convective transfer rates due to impaired ultrafiltration.

  18. The Activation Effects of Low Level Isopropyl Alcohol Exposure on Arterial Blood Pressures Are Associated with Decreased 5-Hydroxyindole Acetic Acid in Urine

    PubMed Central

    Zhao, Zhiqiang; Liu, Xinxia; Xing, Xiumei; Lu, Yao; Sun, Yi; Ou, Xiaoyan; Su, Xiaolin; Jiang, Jun; Yang, Yarui; Chen, Jingli; Shen, Biling; He, Yun

    2016-01-01

    Purposes The objectives of this paper are to study the impact of low level isopropyl alcohol exposure on blood pressure and to explore its potential mechanism. Methods This cross-sectional study was based on a prospective occupational cohort in south China, which focusing on occupational risk factors related cardiovascular health problems. A total of 283 participants (200 low isopropyl alcohol exposed workers and 83 controls) was finally enrolled in this study. Linear regression models were used to analyze the relationship between arterial blood pressures and low level isopropyl alcohol exposure. We used mediation method to explore possible mediated roles of neurogenic factors. Results Systolic blood pressure (SBP, 123±10 vs. 118±11), diastolic blood pressure (DBP, 79±7 vs. 74±7) and mean blood pressure (MBP, 93±8 vs. 89±9) were different between the exposed group and the control group (p < 0.01). After adjusting for covariates, the difference was still significant. Besides, isopropyl alcohol and smoking had an interactive effect on DBP and MBP (p < 0.05). Furthermore, we observed a mediated effect of 5-hydroxyindole acetic acid (5-HIAA) on isopropyl alcohol exposure induced arterial blood pressure increase, which accounted for about 25%. Conclusions Our results suggest that low level isopropyl alcohol exposure is a potential risk factor for the increased arterial blood pressure and 5-HIAA partly mediates the association between low level isopropyl alcohol exposure and arterial blood pressures. PMID:27622502

  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).

  20. Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid beta-infused rats relates to the decreases of amyloid beta and cholesterol levels in detergent-insoluble membrane fractions.

    PubMed

    Hashimoto, Michio; Hossain, Shahdat; Agdul, Haqu; Shido, Osamu

    2005-12-30

    We investigated the effects of dietary administration of docosahexaenoic acid (DHA; C22:6n-3) on the levels of amyloid beta (A beta) peptide (1-40) and cholesterol in the nonionic detergent Triton 100 x-insoluble membrane fractions (DIFs) of the cerebral cortex and, also, on learning-related memory in an animal model of Alzheimer's disease (AD) rats infused with A beta peptide (1-40) into the cerebral ventricle. The infusion increased the levels of A beta peptide and cholesterol in the DIFs concurrently with a significant increase in reference memory errors (measured by eight-arm radial-maze tasks) compared with those of vehicle rats. Conversely, the dietary administration of DHA to AD-model rats decreased the levels of A beta peptide and cholesterol in the DIFs, with the decrease being more prominent in the DHA-administered rats. Regression analysis revealed a significant positive correlation between A beta peptide and each of cholesterol, palmitic acid and stearic acid, and between the number of reference memory errors and each of cholesterol, palmitic, stearic and oleic acid; moreover, a significant negative correlation was observed between the number of reference memory errors and the molar ratio of DHA to palmitic plus stearic acid. These results suggest that DHA-induced protection of memory deficits in AD-model rats is related to the interactions of cholesterol, palmitic acid or stearic acid with A beta peptides in DIFs where DHA ameliorates these interactions.

  1. 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...

  2. 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.

  3. Huggable communication medium decreases cortisol levels.

    PubMed

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

    2013-10-23

    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.

  4. Immunity decreases, antioxidant system damages and tight junction changes in the intestine of grass carp (Ctenopharyngodon idella) during folic acid deficiency: Regulation of NF-κB, Nrf2 and MLCK mRNA levels.

    PubMed

    Shi, Lei; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-04-01

    This investigation used the same growth trial as the previous study, which showed that folic acid deficiency retarded growth in young grass carp (the percent weight gain of Groups 1-6 were 102.32 ± 3.41%, 137.25 ± 10.48%, 179.78 ± 3.95%, 164.33 ± 3.21%, 143.35 ± 8.12% and 115.28 ± 2.66%) [1]. In the present study, we investigated the effects of dietary folic acid on the immune response, antioxidant status and tight junctions in the intestine of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp were fed diets containing graded levels of folic acid at 0.10, 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results indicated that acid phosphatase and lysozyme activities, and the complement component 3 content in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) were decreased with folic acid deficiency (0.1 mg kg(-1)) (P < 0.05). Folic acid deficiency (0.1 mg kg(-1)) up-regulated interleukin 1β, interleukin 8, tumor necrosis factor α, nuclear factor κB p65 (NF-κB p65), IκB kinase α (IKK-α), IKK-β and IKK-γ gene expression, meanwhile down-regulated interleukin 10, transforming growth factor β, IκB and target of rapamycin gene expression in the PI, MI and DI (P < 0.05). These data suggested that folic acid deficiency decreased fish intestinal innate immune function may be partly contributed to the regulation of NF-κB p65 pathway. Moreover, the activities and corresponding gene expression of glutathione content, Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferases and glutathione reductase in fish intestine were depressed by deficient folic acid diet (0.1 mg kg(-1)) (P < 0.05). Furthermore, folic acid deficiency (0.1 mg kg(-1)) down-regulated NF-E2-related factor 2 (Nrf2) gene expression, up-regulated Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b gene expression in fish intestine (P < 0.05). These data indicated

  5. Sin3b Interacts with Myc and Decreases Myc Levels*

    PubMed Central

    Garcia-Sanz, Pablo; Quintanilla, Andrea; Lafita, M. Carmen; Moreno-Bueno, Gema; García-Gutierrez, Lucia; Tabor, Vedrana; Varela, Ignacio; Shiio, Yuzuru; Larsson, Lars-Gunnar; Portillo, Francisco; Leon, Javier

    2014-01-01

    Myc expression is deregulated in many human cancers. A yeast two-hybrid screen has revealed that the transcriptional repressor Sin3b interacts with Myc protein. Endogenous Myc and Sin3b co-localize and interact in the nuclei of human and rat cells, as assessed by co-immunoprecipitation, immunofluorescence, and proximity ligation assay. The interaction is Max-independent. A conserved Myc region (amino acids 186–203) is required for the interaction with Sin3 proteins. Histone deacetylase 1 is recruited to Myc-Sin3b complexes, and its deacetylase activity is required for the effects of Sin3b on Myc. Myc and Sin3a/b co-occupied many sites on the chromatin of human leukemia cells, although the presence of Sin3 was not associated with gene down-regulation. In leukemia cells and fibroblasts, Sin3b silencing led to Myc up-regulation, whereas Sin3b overexpression induced Myc deacetylation and degradation. An analysis of Sin3b expression in breast tumors revealed an association between low Sin3b expression and disease progression. The data suggest that Sin3b decreases Myc protein levels upon Myc deacetylation. As Sin3b is also required for transcriptional repression by Mxd-Max complexes, our results suggest that, at least in some cell types, Sin3b limits Myc activity through two complementary activities: Mxd-dependent gene repression and reduction of Myc levels. PMID:24951594

  6. Fibroblast growth factor receptor levels decrease during chick embryogenesis

    PubMed Central

    1990-01-01

    Two putative receptors for fibroblast growth factor (FGF) of approximately 150 and 200 kD were identified in membrane preparations from chick embryos. Specific binding (femtomoles/milligram) of 125I- aFGF to whole chick embryonic membranes was relatively constant from day 2 to 7, then decreased fivefold between days 7 and 13. Day-19 chick embryos retained 125I-aFGF binding at low levels to brain, eye, and liver tissues but not to skeletal muscle or cardiac tissues. The 200-kD FGF receptor began to decline between day 4.5 and 7 and was barely detectable by day 9, whereas the 150-kD FGF receptor began to decline by day 7 but was still detectable in day-9 embryonic membranes. It is not known whether the two FGF-binding proteins represent altered forms of one polypeptide, but it is clear that their levels undergo differential changes during development. Because endogenous chick FGF may remain bound to FGF receptor in membrane preparations, membranes were treated with acidic (pH 4.0) buffers to release bound FGF; such treatment did not affect 125I-aFGF binding and moderately increased the number of binding sites in day-7 and -19 embryos. Consequently, the observed loss of high affinity 125I-aFGF binding sites and FGF-binding polypeptides most likely represents a loss of FGF receptor protein. These experiments provide in vivo evidence to support the hypothesis that regulation of FGF receptor levels may function as a mechanism for controlling FGF-dependent processes during embryonic development. PMID:2153684

  7. 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...

  8. 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.

  9. 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

  10. Decreased plasma arachidonic acid binding capacity in neonates.

    PubMed

    Sadowitz, P D; Walenga, R W; Clark, D; Stuart, M J

    1987-01-01

    Arachidonic acid (AA) metabolites have been implicated in neonatal pathologic states such as respiratory distress syndrome (RDS). Since free (nonprotein bound) AA is the substrate for synthesis of these compounds, a decreased capacity to bind AA in neonatal plasma could contribute to these disorders. AA binding was assayed by equilibrium dialysis in plasma samples from healthy adults and various infant groups. Plasma from these infant groups bound significantly less AA than adult plasma. Premature infants with RDS and premature infants receiving intralipid had the lowest capacity to bind AA. The increased availability of free AA may be important in neonatal pathophysiologic states involving arachidonate metabolites.

  11. 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

  12. 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

  13. Time-course of SKF-81297-induced increase in glutamic acid decarboxylase 65 and 67 mRNA levels in striatonigral neurons and decrease in GABA(A) receptor alpha1 subunit mRNA levels in the substantia nigra, pars reticulata, in adult rats with a unilateral 6-hydroxydopamine lesion.

    PubMed

    Yamamoto, N; Soghomonian, J-J

    2008-06-26

    Striatal projection neurons use GABA as their neurotransmitter and express the rate-limiting synthesizing enzyme glutamic acid decarboxylase (GAD) and the vesicular GABA transporter vGAT. The chronic systemic administration of an agonist of dopamine D1/D5-preferring receptors is known to alter GAD mRNA levels in striatonigral neurons in intact and dopamine-depleted rats. In the present study, the effects of a single or subchronic systemic administration of the dopamine D1/D5-preferring receptor agonist SKF-81297 on GAD65, GAD67, PPD and vGAT mRNA levels in the striatum and GABA(A) receptor alpha1 subunit mRNA levels in the substantia nigra, pars reticulata, were measured in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion. After a single injection of SKF-81297, striatal GAD65 mRNA levels were significantly increased at 3 but not 72 h. In contrast, striatal GAD67 mRNA levels were increased and nigral alpha1 mRNA levels were decreased at 72 but not 3 h. Single cell analysis on double-labeled sections indicated that increased GAD or vGAT mRNA levels after acute SKF-81297 occurred in striatonigral neurons identified by their lack of preproenkephalin expression. Subchronic SKF-81297 induced significant increases in striatal GAD67, GAD65, preprodynorphin and vGAT mRNA levels and decreases in nigral alpha1 mRNA levels. In the striatum contralateral to the 6-OHDA lesion, subchronic but not acute SKF-81297 induced a significant increase in GAD65 mRNA levels. The other mRNA levels were not significantly altered. Finally, striatal GAD67 mRNA levels were negatively correlated with nigral alpha1 mRNA levels in the dopamine-depleted but not dopamine-intact side. The results suggest that different signaling pathways are involved in the modulation by dopamine D1/D5 receptors of GAD65 and GAD67 mRNA levels in striatonigral neurons. They also suggest that the down-regulation of nigral GABA(A) receptors is linked to the increase in striatal GAD67 mRNA levels in the dopamine

  14. 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).

  15. Coated fatty acids alter virulence properties of Salmonella Typhimurium and decrease intestinal colonization of pigs.

    PubMed

    Boyen, F; Haesebrouck, F; Vanparys, A; Volf, J; Mahu, M; Van Immerseel, F; Rychlik, I; Dewulf, J; Ducatelle, R; Pasmans, F

    2008-12-10

    Salmonella Typhimurium infections in pigs are a major source of human foodborne salmonellosis. To reduce the number of infected pigs, acidification of feed or drinking water is a common practice. The aim of the present study was to determine whether some frequently used short- (SCFA) and medium-chain fatty acids (MCFA) are able to alter virulence gene expression and to decrease Salmonella Typhimurium colonization and shedding in pigs using well established and controlled in vitro and in vivo assays. Minimal inhibitory concentrations (MIC) of 4 SCFA (formic acid, acetic acid, propionic acid and butyric acid) and 2 MCFA (caproic and caprylic acid) were determined using 54 porcine Salmonella Typhimurium field strains. MIC values increased at increasing pH-values and were two to eight times lower for MCFA than for SCFA. Expression of virulence gene fimA was significantly lower when bacteria were grown in LB-broth supplemented with sub-MIC concentrations of caproic or caprylic acid (2 mM). Expression of hilA and invasion in porcine intestinal epithelial cells was significantly lower when bacteria were grown in LB-broth containing sub-MIC concentrations of butyric acid or propionic acid (10 mM) and caproic or caprylic acid (2 mM). When given as feed supplement to pigs experimentally infected with Salmonella Typhimurium, coated butyric acid decreased the levels of faecal shedding and intestinal colonization, but had no influence on the colonization of tonsils, spleen and liver. Uncoated fatty acids, however, did not influence fecal shedding, intestinal or tonsillar colonization in pigs. In conclusion, supplementing feed with certain coated fatty acids, such as butyric acid, may help to reduce the Salmonella load in pigs.

  16. Palmitic acid but not palmitoleic acid induces insulin resistance in a human endothelial cell line by decreasing SERCA pump expression.

    PubMed

    Gustavo Vazquez-Jimenez, J; Chavez-Reyes, Jesus; Romero-Garcia, Tatiana; Zarain-Herzberg, Angel; Valdes-Flores, Jesus; Manuel Galindo-Rosales, J; Rueda, Angelica; Guerrero-Hernandez, Agustin; Olivares-Reyes, J Alberto

    2016-01-01

    Palmitic acid is a negative regulator of insulin activity. At the molecular level, palmitic acid reduces insulin stimulated Akt Ser473 phosphorylation. Interestingly, we have found that incubation with palmitic acid of human umbilical vein endothelial cells induced a biphasic effect, an initial transient elevation followed by a sustained reduction of SERCA pump protein levels. However, palmitic acid produced a sustained inhibition of SERCA pump ATPase activity. Insulin resistance state appeared before there was a significant reduction of SERCA2 expression. The mechanism by which palmitic acid impairs insulin signaling may involve endoplasmic reticulum stress, because this fatty acid induced activation of both PERK, an ER stress marker, and JNK, a kinase associated with insulin resistance. None of these effects were observed by incubating HUVEC-CS cells with palmitoleic acid. Importantly, SERCA2 overexpression decreased the palmitic acid-induced insulin resistance state. All these results suggest that SERCA pump might be the target of palmitic acid to induce the insulin resistance state in a human vascular endothelial cell line. Importantly, these data suggest that HUVEC-CS cells respond to palmitic acid-exposure with a compensatory overexpression of SERCA pump within the first hour, which eventually fades out and insulin resistance prevails.

  17. Decreased serum vitamin D levels in early spontaneous pregnancy loss

    PubMed Central

    Hou, W; Yan, X-t; Bai, C-m; Zhang, X-w; Hui, L-y; Yu, X-w

    2016-01-01

    Background/Objectives: Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in childbearing aged women and pregnancy loss (PL) in the first trimester. Subjects/Methods: This is a cross-sectional study. Plasma was collected from 60 nulliparous women with singleton at 7–9 weeks of gestation (30 with viable gestation and 30 with PL) and 60 non-gravid childbearing aged women (30 with a successful pregnancy history, and 30 with one or more spontaneous first-trimester PL history). Quantitation of serum 25-hydroxyvitamin D (25(OH)D) and 25-hydroxyvitamin D-1 alpha hydroxylase (CYP27B1) was assayed. Results: By pregnancy/non-gravid, normal pregnant women had higher 25(OH)D (49.32 μg/l) and CYP27B1 (82.00 pg/ml) than PL women (34.49 μg/l and 37.87 pg/ml, both P<0.01); the non-gravid women with a successful pregnancy history also had higher 25(OH)D (39.56 μg/l) and CYP27B1 (39.04 pg/ml) than women with PL history (12.30 μg/l and 12.35 pg/ml, both P<0.01). The 96.7% of non-gravid women with PL history and 43.3% of PL women had serum 25(OH)D concentrations below 30 μg/l. There was a strong association between low vitamin D levels and PL (odds ratio 1.71; 95% confidence interval: 1.2–2.4, P<0.001). The regression analyses showed that PL was significantly inversely correlated with 25(OH)D (P<0.01) and CYP27B1 levels (P<0.01). Conclusions: Vitamin D deficiency associated with PL in the first trimester of pregnancy. Decreased serum vitamin D levels among childbearing aged women with the failed clinical pregnancies history may predispose to increased risk for PL. PMID:27222154

  18. Low-Level Laser Therapy Decreases Renal Interstitial Fibrosis

    PubMed Central

    Oliveira, Fabiana Aparecida Mayrink; Moraes, Ana Carolina Meneghin; Paiva, Amanda Povoa; Schinzel, Vânia; Correa-Costa, Matheus; Semedo, Patricia; Castoldi, Angêla; Cenedeze, Marcos Antonio; Oliveira, Roberto Sotto-Maior Fortes; Bastos, Marcus Gomes; Câmara, Niels Olsen Saraiva

    2012-01-01

    Abstract Objective: the purpose of this study was to investigate the effect of low-level laser therapy (LLLT) on chronic kidney disease (CKD) in a model of unilateral ureteral obstruction (UUO). Background data: Regardless of the etiology, CKD involves progressive widespread tissue fibrosis, tubular atrophy, and loss of kidney function. This process also occurs in kidney allograft. At present, effective therapies for this condition are lacking. We investigated the effects of LLLT on the interstitial fibrosis that occurs after experimental UUO in rats. Methods: The occluded kidney of half of the 32 Wistar rats that underwent UUO received a single intraoperative dose of LLLT (AlGaAs laser, 780 nm, 22.5 J/cm2, 30 mW, 0.75 W/cm2, 30 sec on each of nine points). After 14 days, renal fibrosis was assessed by Sirius red staining under polarized light. Immunohistochemical analyses quantitated the renal tissue cells that expressed fibroblast (FSP-1) and myofibroblast (α-SMA) markers. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the mRNA expression of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-β1 and Smad3. Results: The UUO and LLLT animals had less fibrosis than the UUO animals, as well having decreased expression inflammatory and pro-fibrotic markers. Conclusions: For the first time, we showed that LLLT had a protective effect regarding renal interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can prevent tubular activation and transdifferentiation, which are the two processes that mainly drive the renal fibrosis of the UUO model. PMID:23134313

  19. 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

  20. Lithium Decreases Glial Fibrillary Acidic Protein in a Mouse Model of Alexander Disease.

    PubMed

    LaPash Daniels, Christine M; Paffenroth, Elizabeth; Austin, Elizabeth V; Glebov, Konstantin; Lewis, Diana; Walter, Jochen; Messing, Albee

    2015-01-01

    Alexander disease is a fatal neurodegenerative disease caused by mutations in the astrocyte intermediate filament glial fibrillary acidic protein (GFAP). The disease is characterized by elevated levels of GFAP and the formation of protein aggregates, known as Rosenthal fibers, within astrocytes. Lithium has previously been shown to decrease protein aggregates by increasing the autophagy pathway for protein degradation. In addition, lithium has also been reported to decrease activation of the transcription factor STAT3, which is a regulator of GFAP transcription and astrogliogenesis. Here we tested whether lithium treatment would decrease levels of GFAP in a mouse model of Alexander disease. Mice with the Gfap-R236H point mutation were fed lithium food pellets for 4 to 8 weeks. Four weeks of treatment with LiCl at 0.5% in food pellets decreased GFAP protein and transcripts in several brain regions, although with mild side effects and some mortality. Extending the duration of treatment to 8 weeks resulted in higher mortality, and again with a decrease in GFAP in the surviving animals. Indicators of autophagy, such as LC3, were not increased, suggesting that lithium may decrease levels of GFAP through other pathways. Lithium reduced the levels of phosphorylated STAT3, suggesting this as one pathway mediating the effects on GFAP. In conclusion, lithium has the potential to decrease GFAP levels in Alexander disease, but with a narrow therapeutic window separating efficacy and toxicity.

  1. Phytic acid plus calcium, but not phytic acid alone, decreases fluoride bioavailability in the rat

    SciTech Connect

    Cerklewski, F.L. )

    1991-03-15

    Results of in vitro studies have suggested that fluoride becomes insoluble when some soy-based infant formulas are diluted with fluoridated water because of the presence of phytate, added calcium or a combination of these factors. The present study was designed to test this hypothesis in vivo. Male albino rats were fed a purified diet containing phytic acid, calcium and fluoride for 4 weeks in a factorial design of treatments. Phytic acid was added to the diet by chemically reacting a phytic acid concentrate with casein prior to diet preparation to mimic a soy-protein. Food intake, weight gain and femur P were unaffected by dietary treatments. Both phytic acid and supplemental calcium alone had little or no effect upon fluoride uptake into either bone or teeth. The combination of phytic acid plus supplemental calcium, however, significantly increased % of fluoride intake found in the feces which was reflected in a significant decrease in fluoride concentration of femur, 2nd molar teeth and vertebrate bone. These results provide evidence that insoluble complex formation produced by a calcium and phytate interaction can explain reduced fluoride solubility in some soy-based infant formulas as well as decreased fluoride absorbability in vivo.

  2. Decreased energy levels can cause and sustain obesity.

    PubMed

    Wlodek, Danuta; Gonzales, Michael

    2003-11-07

    Obesity has reached epidemic proportions and has become one of the major health problems in developed countries. Current theories consider obesity a result of overeating and sedentary life style and most efforts to treat or prevent weight gain concentrate on exercise and food intake. This approach does not improve the situation as may be seen from the steep increase in the prevalence of obesity. This encouraged us to reanalyse existing information and look for biochemical basis of obesity. Our approach was to ignore current theories and concentrate on experimental data which are described in scientific journals and are available from several databases. We developed and applied a Knowledge Discovery in Databases procedure to analyse metabolic data. We began with the contradictory information: in obesity, more calories are consumed than used up, suggesting that obese people should have excess energy. On the other side, obese people experience fatigue and decreased physical endurance that indicates diminished energy supply in the body. The result of our work is a chain of metabolic events leading to obesity. The crucial event is the inhibition of the TCA cycle at the step of aconitase. It disturbs energy metabolism and results in ATP deficiency with simultaneous fat accumulation. Further steps in obesity development are the consequences of diminished energy supply: inhibition of beta-oxidation, leptin resistance, increase in appetite and food intake and a decrease in physical activity. Thus, our theory shows that obesity does not have to be caused by overeating and sedentary life-style but may be the result of the "obese" change in metabolism which is forcing people to overeat and save energy to sustain metabolic functions of cells. This "obese" change is caused by environmental factors that activate chronic low-grade inflammatory process in the body linking obesity with the environment of developed countries.

  3. Decreased Plasma BDNF Levels of Patients with Somatization Disorder

    PubMed Central

    Kang, Nam-In; Park, Jong-Il

    2016-01-01

    Objective Brain-derived neurotrophic factor (BDNF), one of the most abundant and important neurotrophins, is known to be involved in the development, survival, maintenance, and plasticity of neurons in the nervous system. Some studies have suggested that BDNF may play a role in the pathophysiology of several psychiatric illnesses such as depression and schizophrenia. Similarly, it is likely that the alteration of BDNF may be associated with the neuro-modulation that contributes to the development of somatization disorder. Methods The purpose of this study was to determine whether there is an abnormality of plasma BDNF levels in patients with somatization disorder, and to analyze the nature of the alteration after pharmacotherapy using an enzyme-linked immunosorbent assay (ELISA). Results The plasma BDNF levels of the patients with a somatization disorder were significantly lower compared with those of the control volunteers (83.61±89.97 pg/mL vs. 771.36±562.14 pg/mL); moreover, the plasma BDNF levels of those patients who received an antidepressant were significantly increased after the treatment (118.13±91.45 pg/mL vs. 72.92±88.21 pg/mL). Conclusion These results suggest that BDNF may play a role in the pathophysiology of somatization disorder. PMID:27757131

  4. Enteral glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut mucosa.

    PubMed

    Coëffier, Moïse; Claeyssens, Sophie; Hecketsweiler, Bernadette; Lavoinne, Alain; Ducrotté, Philippe; Déchelotte, Pierre

    2003-08-01

    Effects of glutamine on whole body and intestinal protein synthesis and on intestinal proteolysis were assessed in humans. Two groups of healthy volunteers received in a random order enteral glutamine (0.8 mmol.kg body wt(-1)x h(-1)) compared either to saline or isonitrogenous amino acids. Intravenous [2H5]phenylalanine and [13C]leucine were simultaneously infused. After gas chromatography-mass spectrometry analysis, whole body protein turnover was estimated from traced plasma amino acid fluxes and the fractional synthesis rate (FSR) of gut mucosal protein was calculated from protein and intracellular phenylalanine and leucine enrichments in duodenal biopsies. mRNA levels for ubiquitin, cathepsin D, and m-calpain were analyzed in biopsies by RT-PCR. Glutamine significantly increased mucosal protein FSR compared with saline. Glutamine and amino acids had similar effects on FSR. The mRNA level for ubiquitin was significantly decreased after glutamine infusion compared with saline and amino acids, whereas cathepsin D and m-calpain mRNA levels were not affected. Enteral glutamine stimulates mucosal protein synthesis and may attenuate ubiquitin-dependent proteolysis and thus improve protein balance in human gut.

  5. Effect of domoic acid on brain amino acid levels.

    PubMed

    Durán, R; Arufe, M C; Arias, B; Alfonso, M

    1995-03-01

    The administration of Domoic Acid (Dom) in a 0.2 mg/kg i.p. dose induces changes in the levels of amino acids of neurochemical interest (Asp, Glu, Gly, Tau, Ala, GABA) in different rat brain regions (hypothalamus, hippocampus, amygdala, striatum, cortex and midbrain). The most affected amino acid is the GABA, the main inhibitory amino acid neurotransmitter, whereas glutamate, the main excitatory amino acid, is not affected. The rat brain regions that seem to be the main target of the Dom action belong to the limbic system (hippocampus, amygdala). The possible implication of the amino acids in the actions of Dom is also discussed.

  6. 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.

  7. Eicosapentaenoic acid decreases TNF-α and protects dystrophic muscles of mdx mice from degeneration.

    PubMed

    Machado, Rafael Ventura; Mauricio, Adriana Fogagnolo; Taniguti, Ana Paula Tiemi; Ferretti, Renato; Neto, Humberto Santo; Marques, Maria Julia

    2011-03-01

    In dystrophin-deficient fibers of mdx mice and in Duchenne muscular dystrophy, inflammation and increased production of tumor necrosis factor alpha (TNF-α) contribute to myonecrosis. We examined the effects of eicosapentaenoic acid (EPA) on dystrophic muscle degeneration. Mdx mice (14 days old) received EPA for 16 days. The sternomastoid, diaphragm and biceps brachii muscles were removed. Control mdx mice received vehicle. EPA decreased creatine kinase and myonecrosis and reduced the levels of TNF-α. These results suggest that EPA plays a protective role in dystrophic muscle degeneration, possibly by reducing TNF-α, and support further investigations of EPA as a potential therapy for dystrophinopathies.

  8. 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.

  9. Frost decreases content of sugars, ascorbic acid and some quercetin glycosides but stimulates selected carotenes in Rosa canina hips.

    PubMed

    Cunja, Vlasta; Mikulic-Petkovsek, Maja; Zupan, Anka; Stampar, Franci; Schmitzer, Valentina

    2015-04-15

    Primary and secondary metabolites of Rosa canina hips were determined by HPLC/MS during ripening and after frost damage. Rose hips were harvested six times from the beginning of September until the beginning of December. Color parameters a*, b* and L* decreased during maturation. Glucose and fructose were the predominant sugars representing up to 92% total sugars, and citric acid was the major organic acid detected in rose hips (constituting up to 58% total organic acids). Total sugar and ascorbic acid content significantly decreased after frost damage; from 42.2 to 25.9 g 100 g(-1) DW for sugars and from 716.8 to 176.0 mg 100 g(-1) DW for ascorbic acid. Conversely, β-carotene and lycopene levels increased in frostbitten rose hips to 22.1 and 113.2 mg 100 g(-1) DW, respectively. In addition to cyanidin-3-glucoside (highest level in hips was 125.7 μg 100 g (-1) DW), 45 different phenolic compounds have been identified. The most abundant were proanthocyanidins (their levels amounted up to 90% of total flavanol content) and their content showed no significant differences during maturation. The levels of catechin, phloridzin, flavanones and several quercetin glycosides were highest on the first three sampling dates and decreased after frost. Antioxidant capacity similarly decreased in frostbitten rose hips. Total phenolic content increased until the third sampling and decreased on later samplings.

  10. Optimal dose of oral omeprazole for maximal 24 hour decrease of intragastric acidity.

    PubMed Central

    Sharma, B K; Walt, R P; Pounder, R E; Gomes, M D; Wood, E C; Logan, L H

    1984-01-01

    In a series of 59 experiments in nine duodenal ulcer patients, 24 hour intragastric acidity was measured before, during, and after treatment with daily oral omeprazole. Omeprazole 10, 20, and 30 mg/day for one week caused a 37, 90, and 97% decrease of 24 hour intragastric acidity, respectively. No further decrease of acidity was observed when the dose of omeprazole was doubled to 60 mg/day, or after a second week of treatment with 30 mg/day. One week after stopping treatment with omeprazole (14 doses) there was a significant 26% decrease of 24 hour intragastric acidity, with full recovery seven weeks later. Fasting plasma gastrin concentration was significantly raised during treatment with all doses of omeprazole. Omeprazole 30 mg/day is the optimal dose for a maximal decrease of 24 hour intragastric acidity in duodenal ulcer patients. PMID:6469081

  11. Duodenal ulcerogens cysteamine and propionitrile decrease duodenal neutralization of acid in the rat

    SciTech Connect

    Adler, R.S.; Gallagher, G.T.; Szabo, S.

    1983-08-01

    Neutralization of acid was evaluated in rat proximal duodenal segments isolated from biliary and pancreatic secretions. Duodenal ulcerogenic doses of cysteamine produced a significant decrease in acid disposal 0.5-2 hr after treatment. Oral or subcutaneous administration of the duodenal ulcerogen was effective. The potent ulcerogen cysteamine produced a more pronounced decrease than propionitrile (a weak duodenal ulcerogen). The failure of ethanolamine, a nonulcerogenic structural analog of cysteamine to significantly alter acid disposal suggests that the effect is not due to the toxic properties of the duodenal ulcerogen. The results reinforce the concept that the duodenum is able to dispose of significant quantities of acid. The decrease in acid-handling may contribute to duodenal susceptibility to acid after treatment with ulcerogens and possibly reflects pathophysiologic changes early in duodenal ulceration.

  12. Epigallocatechin gallate induces a hepatospecific decrease in the CYP3A expression level by altering intestinal flora.

    PubMed

    Ikarashi, Nobutomo; Ogawa, Sosuke; Hirobe, Ryuta; Kon, Risako; Kusunoki, Yoshiki; Yamashita, Marin; Mizukami, Nanaho; Kaneko, Miho; Wakui, Nobuyuki; Machida, Yoshiaki; Sugiyama, Kiyoshi

    2017-03-30

    In previous studies, we showed that a high-dose intake of green tea polyphenol (GP) induced a hepatospecific decrease in the expression and activity of the drug-metabolizing enzyme cytochrome P450 3A (CYP3A). In this study, we examined whether this decrease in CYP3A expression is induced by epigallocatechin gallate (EGCG), which is the main component of GP. After a diet containing 1.5% EGCG was given to mice, the hepatic CYP3A expression was measured. The level of intestinal bacteria of Clostridium spp., the concentration of lithocholic acid (LCA) in the feces, and the level of the translocation of pregnane X receptor (PXR) to the nucleus in the liver were examined. A decrease in the CYP3A expression level was observed beginning on the second day of the treatment with EGCG. The level of translocation of PXR to the nucleus was significantly lower in the EGCG group. The fecal level of LCA was clearly decreased by the EGCG treatment. The level of intestinal bacteria of Clostridium spp. was also decreased by the EGCG treatment. It is clear that the hepatospecific decrease in the CYP3A expression level observed after a high-dose intake of GP was caused by EGCG. Because EGCG, which is not absorbed from the intestine, causes a decrease in the level of LCA-producing bacteria in the colon, the level of LCA in the liver decreases, resulting in a decrease in the nuclear translocation of PXR, which in turn leads to the observed decrease in the expression level of CYP3A.

  13. 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.

  14. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    PubMed

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.

  15. 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.

  16. Ursodeoxycholic Acid Suppresses Lipogenesis in Mouse Liver: Possible Role of the Decrease in β-Muricholic Acid, a Farnesoid X Receptor Antagonist.

    PubMed

    Fujita, Kyosuke; Iguchi, Yusuke; Une, Mizuho; Watanabe, Shiro

    2017-03-17

    The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR. We observed that the dietary administration of UDCA in mice decreased the expression levels of SREBP1c and its target lipogenic genes. Alpha- and β-muricholic acids (MCA) and cholic acid (CA) were the major bile acids in the mouse liver but their contents decreased upon UDCA administration. The hepatic contents of chenodeoxycholic acid and deoxycholic acid (DCA) were relatively low but were not changed by UDCA. UDCA did not show FXR agonistic or antagonistic potency in in vitro FXR transactivation assay. Taking these together, we deduced that the above-mentioned change in hepatic bile acid composition induced upon UDCA administration might cause the relative increase in the FXR activity in the liver, mainly by the reduction in the content of β-MCA, a farnesoid X receptor antagonist, which suggests a mechanism by which UDCA suppresses lipogenesis and decreases the lipid contents in the mouse liver.

  17. 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.

  18. Homocysteine mediated decrease in bone blood flow and remodeling: role of folic acid.

    PubMed

    Tyagi, Neetu; Kandel, Madhavi; Munjal, Charu; Qipshidze, Natia; Vacek, Jonathan C; Pushpakumar, Sathnur B; Metreveli, Naria; Tyagi, Suresh C

    2011-10-01

    Deficiencies in folate lead to increased serum concentrations of homocysteine (Hcy), which is known as hyperhomocysteinemia (HHcy), is associated with bone disorders. Although, Hcy accumulates collagen in bone and contribute to decrease in bone strength. The mechanism of Hcy induced bone loss and remodeling is unclear. Therefore, the present study was aimed to determine the role of folic acid (FA) in genetically HHcy-associated decrease in bone blood flow and remodeling. Wild type (WT) and cystathionine-β-synthase heterozygous (CBS+/-) mice were used in this study and supplemented with or without FA (300 mg/kg, Hcy reducing agent) in drinking water for 6 weeks. The tibial bone blood flow was measured by laser Doppler and ultrasonic flow probe method. The tibial bone density (BD) was assessed by dual energy X-ray absorptiometry. The bone homogenates were analyzed for oxidative stress, NOX-4 as oxidative marker and thioredoxin-1 (Trx-1) as anti-oxidant marker, bone remodeling (MMP-9) and bio-availability of nitric oxide (eNOS/iNOS/NO) by Western blot method. The results suggested that there was decrease in tibial blood flow in CBS+/- mice. The BD was also reduced in CBS+/- mice. There was an increase in NOX-4, iNOS, MMP-9 protein as well as MMP-9 activity in CBS+/- mice and decrease in Trx-1, eNOS protein levels, in part by decreasing NO bio-availability in CBS+/- mice. Interestingly, these effects were ameliorated by FA and suggested that FA supplementation may have therapeutic potential against genetically HHcy induced bone loss.

  19. 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

  20. 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...

  1. Altered Serum Uric Acid Level in Lichen Planus Patients

    PubMed Central

    Chakraborti, Goutam; Biswas, Rabindranath; Chakraborti, Sandip; Sen, Pradyot Kumar

    2014-01-01

    Background: Lichen planus (LP) is a common disorder whose etiopathogenesis is not clear. Recently, it has been suggested that increased reactive oxygen species (ROS) play important roles in the underlying mechanism of LP. Objectives: The principal aim of this study was to evaluate serum uric acid (UA) levels as a measure of the antioxidant defense status in LP patients. Methods: Serum UA levels were determined in 58 LP patients and 61 controls. Results: Serum UA levels were significantly decreased in patients with respect to controls. Moreover, serum UA level was decreased according to increasing duration of disease. Conclusions: The results of our study suggest that LP is associated with decrease of UA levels in serum. UA may be a potential, useful biomarker of antioxidant status in LP for elaboration of treatment strategy and monitoring. PMID:25484383

  2. Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart.

    PubMed

    Patrick, Casey B; McHowat, Jane; Rosenberger, Thad A; Rapoport, Stanley I; Murphy, Eric J

    2005-06-01

    Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 muCi/kg of either [1-(14)C]palmitic acid ([1-(14)C]16:0) or [1-(14)C]arachidonic acid ([1-(14)C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient lambda was increased in [1-(14)C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-(14)C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of beta-oxidation. In [1-(14)C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60-84%) and turnover value (56-85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A(2) activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A(2) activity.

  3. Dopamine receptor alterations in female rats with diet-induced decreased brain docosahexaenoic acid (DHA): interactions with reproductive status

    PubMed Central

    Davis, Paul F.; Ozias, Marlies K.; Carlson, Susan E.; Reed, Gregory A.; Winter, Michelle K.; McCarson, Kenneth E.; Levant, Beth

    2010-01-01

    Decreased tissue levels of n-3 (omega-3) fatty acids, particularly docosahexaenoic acid (DHA), are implicated in the etiologies of non-puerperal and postpartum depression. This study examined the effects of a diet-induced loss of brain DHA content and concurrent reproductive status on dopaminergic parameters in adult female Long–Evans rats. An α-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 20–22% lower than those fed a control diet containing adequate α-linolenic acid. Decreased brain DHA produced a significant main effect of decreased density of ventral striatal D2-like receptors. Virgin females with decreased DHA also exhibited higher density of D1-like receptors in the caudate nucleus than virgin females with normal DHA. These receptor alterations are similar to those found in several rodent models of depression, and are consistent with the proposed hypodopaminergic basis for anhedonia and motivational deficits in depression. PMID:20670471

  4. 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

  5. A specific protein-enriched enteral formula decreases cortisolemia and improves plasma albumin and amino acid concentrations in elderly patients

    PubMed Central

    2010-01-01

    Background Old age is associated with an involuntary and progressive but physiological loss of muscle mass. The aim of this study was to evaluate the effects of exclusive consumption for 6 months of a protein-enriched enteral diet with a relatively high content of branched-chain amino acids on albuminemia, cortisolemia, plasma amino acids, insulin resistance, and inflammation biomarkers in elderly patients. Methods Thirty-two patients from the Clinical Nutrition Outpatient Unit at our hospital exclusively consumed a protein-enriched enteral diet for 6 months. Data were collected at baseline and at 3 and 6 months on anthropometric and biochemical parameters and on plasma concentrations of amino acids, cortisol, adrenocorticotropic hormone, urea, creatinine, insulin resistance, and inflammation biomarkers. Results The percentage of patients with albumin concentration below normal cut-off values decreased from 18% to 0% by the end of the study. At 6 months, concentrations of total plasma (p = 0.008) and essential amino acids (p = 0.011), especially branched-chain amino acids (p = 0.031), were higher versus baseline values, whereas 3-methylhistidine (p = 0.001), cortisol (p = 0.001) and adrenocorticotropic hormone (p = 0.004) levels were lower. Conclusions Regular intake of specific protein-enriched enteral formula increases plasma essential amino acids, especially branched-chain amino acids, and decreases cortisol and 3-methylhistidine, while plasma urea and creatinine remain unchanged. PMID:20626909

  6. Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus

    PubMed Central

    Bandara, Suren B.; Eubig, Paul A.; Sadowski, Renee N.; Schantz, Susan L.

    2016-01-01

    Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. PMID:26543103

  7. 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.

  8. Fish protein decreases serum cholesterol in rats by inhibition of cholesterol and bile acid absorption.

    PubMed

    Hosomi, Ryota; Fukunaga, Kenji; Arai, Hirofumi; Kanda, Seiji; Nishiyama, Toshimasa; Yoshida, Munehiro

    2011-05-01

    Fish protein has been shown to decrease serum cholesterol content by inhibiting absorption of cholesterol and bile acid in laboratory animals, though the mechanism underlying this effect is not yet fully understood. The purpose of this study was to elucidate the mechanism underlying the inhibition of cholesterol and bile acid absorption following fish protein intake. Male Wistar rats were divided into 2 dietary groups of 7 rats each, 1 group receiving a diet consisting of 20% casein and the other receiving a diet consisting of 10% casein and 10% fish protein. Both experimental diets also contained 0.5% cholesterol and 0.1% sodium cholate. After the rats had been on their respective diets for 4 wk, their serum and liver cholesterol contents and fecal cholesterol, bile acid, and nitrogen excretion contents were measured. Fish protein consumption decreased serum and liver cholesterol content and increased fecal cholesterol and bile acid excretion and simultaneously increased fecal nitrogen excretion. In addition, fish protein hydrolyzate prepared by in vitro digestion had lower micellar solubility of cholesterol and higher binding capacity for bile acids compared with casein hydrolyzate. These results suggest that the hypocholesterolemic effect of fish protein is mediated by increased fecal cholesterol and bile acid excretion, which is due to the digestion products of fish protein having reduced micellar solubility of cholesterol and increased bile acid binding capacity.

  9. Methylphenidate Decreases ATP Levels and Impairs Glutamate Uptake and Na(+),K(+)-ATPase Activity in Juvenile Rat Hippocampus.

    PubMed

    Schmitz, Felipe; Pierozan, Paula; Rodrigues, André F; Biasibetti, Helena; Grings, Mateus; Zanotto, Bruna; Coelho, Daniella M; Vargas, Carmen R; Leipnitz, Guilhian; Wyse, Angela T S

    2016-11-14

    The study of the long-term neurological consequences of early exposure with methylphenidate (MPH) is very important since this psychostimulant has been widely misused by children and adolescents who do not meet full diagnostic criteria for ADHD. The aim of this study was to examine the effect of early chronic exposure with MPH on amino acids profile, glutamatergic and Na(+),K(+)-ATPase homeostasis, as well as redox and energy status in the hippocampus of juvenile rats. Wistar male rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 45th day of age. Results showed that MPH altered amino acid profile in the hippocampus, decreasing glutamine levels. Glutamate uptake and Na(+),K(+)-ATPase activity were decreased after chronic MPH exposure in the hippocampus of rats. No changes were observed in the immunocontents of glutamate transporters (GLAST and GLT-1), and catalytic subunits of Na(+),K(+)-ATPase (α1, α2, and α3), as well as redox status. Moreover, MPH provoked a decrease in ATP levels in the hippocampus of chronically exposed rats, while citrate synthase, succinate dehydrogenase, respiratory chain complexes activities (II, II-III, and IV), as well as mitochondrial mass and mitochondrial membrane potential were not altered. Taken together, our results suggest that chronic MPH exposure at early age impairs glutamate uptake and Na(+),K(+)-ATPase activity probably by decreasing in ATP levels observed in rat hippocampus.

  10. Increased delta aminolevulinic acid and decreased pineal melatonin production. A common event in acute porphyria studies in the rat.

    PubMed

    Puy, H; Deybach, J C; Bogdan, A; Callebert, J; Baumgartner, M; Voisin, P; Nordmann, Y; Touitou, Y

    1996-01-01

    Tryptophan (TRP) is the precursor of melatonin, the primary secretory product of the pineal gland. Hepatic heme deficiency decreases the activity of liver tryptophan pyrrolase, leading to increased plasma TRP and serotonin. As a paradox, patients with attacks of acute intermittent porphyria (AIP), exhibit low nocturnal plasma melatonin levels. This study using a rat experimental model was designed to produce a pattern of TRP and melatonin production similar to that in AIP patients. Pineal melatonin production was measured in response to: (a) a heme synthesis inhibitor, succinylacetone, (b) a heme precursor, delta-aminolevulinic acid (Ala), (c) a structural analogue of Ala, gamma-aminobutyric acid. Studies were performed in intact rats, perifused pineal glands, and pinealocyte cultures. Ala, succinylacetone, and gamma-aminobutyric acid significantly decreased plasma melatonin levels independently of blood TRP concentration. In the pineal gland, the key enzyme activities of melatonin synthesis were unchanged for hydroxyindole-O-methyltransferase and decreased for N-acetyltransferase. Our results strongly suggest that Ala overproduced by the liver acts by mimicking the effect of gamma-aminobutyric acid on pineal melatonin in AIP. They also support the view that Ala acts as a toxic element in the pathophysiology of AIP.

  11. Neither testosterone levels nor aggression decrease when the male Mongolian gerbil (Meriones unguiculatus) displays paternal behavior.

    PubMed

    Juana, Luis; Bárbara, Vázquez-Gaytán; Martín, Martínez-Torres; Agustín, Carmona; Guillermo, Ramos-Blancas; Guadalupe, Ortíz

    2010-03-01

    The first studies that correlated mammalian paternal behavior and testosterone levels indicated that the concentration of this steroid hormone decreases when males exhibit paternal care. However, recent studies have also shown that testosterone levels do not decrease when males display paternal behavior. In this study, we measured testosterone levels in plasma throughout the reproductive cycle of the Mongolian gerbil. Testosterone concentrations were correlated with paternal care as well as aggression. We also examined whether there is a trade-off between paternal behavior and aggression in this mammal. Our results show that Mongolian gerbil testosterone levels do not decrease when the males give paternal care. Likewise, male Mongolian gerbils exhibit high levels of aggression while displaying paternal behavior, indicating that there is no trade-off between aggression and paternal behavior. More studies are needed to determine whether testosterone is involved in the regulation of paternal behavior in this rodent.

  12. 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.

  13. 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.

  14. 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.

  15. Plasma amino acid response to graded levels of escape protein.

    PubMed

    Gibb, D J; Klopfenstein, T J; Britton, R A; Lewis, A J

    1992-09-01

    A trial was conducted to examine the potential of using plasma amino acid responses to graded levels of escape protein to determine limiting amino acids in cattle. Growing calves (n = 120; mean BW = 220 +/- 21 kg) were fed a basal diet of corncob:sorghum silage (61:39) and were individually supplemented with distillers' dried grains (DDG), heat-damaged DDG (H-DDG), feather meal (FTH), or urea. The urea supplement was mixed with DDG and H-DDG to allow 0, 20, 35, 50, 65, or 80% of the supplemental CP to come from distillers' protein and maintain an 11.5% CP diet. Urea supplement was mixed with FTH to allow 0, 22, 39, 56, 73, or 90% of the supplemental CP to come from FTH. Dietary CP ranged from 11.5% at the 0% level to 17.3% at the 90% level. Plasma concentration of most essential plasma amino acids responded (P less than .10) linearly and(or) quadratically to increased escape protein. The broken-line response of plasma methionine at low DDG intake suggested that methionine was limiting at low levels of escape protein. An initial decrease followed by a plateau fit by a broken line indicated that histidine became limiting in FTH diets, and lysine eventually became limiting for DDG, H-DDG, and FTH diets before maximum BW gain was reached. Results indicate that plasma amino acid responses may identify amino acids that become limiting with increasing escape protein.

  16. The loudness of sounds that increase and decrease continuously in level.

    PubMed

    Canévet, G; Scharf, B

    1990-11-01

    A sound at a low level is heard as much softer after having decreased continuously from higher levels than if presented after a period of silence at that same low level. Canévet [Acustica 61, 256-264 (1986)] demonstrated this phenomenon for a tone that (1) decreased from 65 to 20 dB in 180 s; he also presented a tone that (2) increased from 20 dB, or (3) was presented as pairs of bursts at various levels in random order. Below about 40 dB, loudness changed most rapidly in the decreasing condition so that, at 20 dB, the tone was judged ten times softer than in conditions (2) and (3). In the present experiments, magnitude estimation was used to examine the possible role of judgmental biases and adaptation in this rapid loudness decline, which we call decruitment. Results show that decruitment did not come about because subjects made many successive loudness judgments; loudness declined as much when a tone was judged only twice, at the beginning and end of its 180-s decrease. In contrast, interrupting the decreasing tone so that it was heard only at 70 dB and 160 s later at 30 dB greatly diminished the decruitment. Similarly, pairs of 500-ms tone bursts presented at successively lower levels instead of continously decreasing did not show decruitment, suggesting that sequential biases are irrelevant. The likely cause of decruitment is sensory adaptation.

  17. Maternal docosahexaenoic acid supplementation decreases lung inflammation in hyperoxia-exposed newborn mice.

    PubMed

    Rogers, Lynette K; Valentine, Christina J; Pennell, Michael; Velten, Markus; Britt, Rodney D; Dingess, Kelly; Zhao, Xuilan; Welty, Stephen E; Tipple, Trent E

    2011-02-01

    DHA is a long-chain fatty acid that has potent antiinflammatory properties. Whereas maternal DHA dietary supplementation has been shown to improve cognitive development in infants fed DHA-supplemented milk, the antiinflammatory effects of maternal DHA supplementation on the developing fetus and neonate have not been extensively explored. Pregnant C3H/HeN dams were fed purified control or DHA-supplemented diets (~0.25% of total fat) at embryonic d 16 and consumed these diets throughout the study. At birth, the nursing mouse pups were placed in room air (RA; 21% O(2)) or >95% O(2) (hyperoxia) for up to 7 d. These studies tested the hypothesis that maternal DHA supplementation would decrease inflammation and improve alveolarization in the lungs of newborn mouse pups exposed to hyperoxia. Survival, inflammatory responses, and lung growth were compared among control diet/RA, DHA/RA, control/O(2), and DHA/O(2) pups. There were fewer neutrophils and macrophages in lung tissues from pups nursed by DHA-supplemented dams than in those nursed by dams fed the control diet at 7 d of hyperoxia exposure (P < 0.015). Although differences due to hyperoxia exposure were observed, maternal diet did not affect keratinocyte-derived chemokine, macrophage inflammatory protein-2, IL-1β, or TNFα mRNA levels in pup tissues. Hyperoxia also induced NF-κB activity, but maternal diet did not affect NF-κB or PPARγ activities. In mice, DHA supplementation decreases leukocyte infiltration in the offspring exposed to hyperoxia, suggesting a potential role for DHA supplementation as a therapy to reduce inflammation in preterm infants.

  18. Worse Neurological State During Acute Ischemic Stroke is Associated with a Decrease in Serum Albumin Levels.

    PubMed

    Bielewicz, Joanna; Kurzepa, Jacek; Czekajska-Chehab, Elżbieta; Kamieniak, Piotr; Daniluk, Beata; Bartosik-Psujek, Halina; Rejdak, Konrad

    2016-04-01

    High serum albumin levels during ischemic stroke (IS) decrease the risk of a poor outcome. This study aimed to determine whether serum albumin levels within the first days after IS correlate with radiological and biochemical markers of brain tissue damage. Fifty-six IS patients were enrolled into the study. Neurological examinations were based on the National Institute of Health Stroke Scale. Serum albumin levels and S100BB were evaluated using commercially available ELISA kits. The albumin decrease index (ADI) was calculated as the difference between serum albumin levels measured on days 1 and 10 of IS. All parameters were estimated on the 1st, 3rd, 5th, and 10th days of IS, and the volume of ischemic focus was measured on the 10th day. Mean serum albumin levels were decreased during acute IS. There were correlations between the ADI and mean S100BB serum levels (r = 0.36, p < 0.05), the volume of ischemic focus (r = 0.39, p < 0.05), and the patients' neurological state when measured on day 10 of IS (r = 0.59, p < 0.001). A decrease in serum albumin levels during the acute phase of IS corresponds to a worse neurological state as a result of a large ischemic focus with intense catabolic processes.

  19. 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.

  20. Fifteen-month-old infants' cortisol levels decrease after a 30-min-warm-up procedure.

    PubMed

    Zmyj, Norbert; Schneider, Silvia; Seehagen, Sabine

    2017-02-01

    Stress-induction procedures designed to increase cortisol levels in infants have been ineffective in many studies. One reason might be that infants did not have sufficient time to settle into the laboratory environment prior to the start of the stress induction, and thus already had high baseline levels of cortisol. In this study we investigate whether an extended warm-up period reduces infants' (N=22) cortisol levels. Fifteen-month-old infants' saliva cortisol was measured upon arrival at the laboratory. Then, they were allowed to play with their parent. After 30min, cortisol was measured again. There was a decrease in cortisol after 30min of free play. Our study suggests that infants' cortisol levels decrease when infants have the opportunity to acclimatize to the test environment. An extended warm-up phase prior to stress induction procedures might be necessary to reliably increase cortisol levels in infants.

  1. 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

  2. Decrease in serum FGF23 levels after intravenous infusion of pamidronate in patients with osteogenesis imperfecta.

    PubMed

    Kitaoka, Taichi; Namba, Noriyuki; Miura, Kohji; Kubota, Takuo; Ohata, Yasuhisa; Fujiwara, Makoto; Hirai, Haruhiko; Yamamoto, Takehisa; Ozono, Keiichi

    2011-09-01

    Fibroblast growth factor 23 (FGF23) plays a central role in phosphate (P) homeostasis. However, the precise mechanism of how FGF23 secretion is regulated remains to be elucidated. In the present study, we examined the effect of intravenous pamidronate administration on serum levels of FGF23. Thirteen patients with osteogenesis imperfecta were treated with two cycles of 3-day pamidronate infusion. Blood samples at pre- and post-drip pamidronate infusion were evaluated for serum calcium, P, intact PTH (iPTH), 1,25(OH)(2)D, intact FGF23 (FGF23), type I collagen cross-linked N-telopeptides (NTx), bone-specific alkaline phosphatase (BAP), and TmP/GFR. During the two cycles, FGF23 levels decreased significantly preceding the decline in P levels. Although the change in P levels became less apparent during the second cycle, the reduction in FGF23 levels was similar during both cycles. Moreover, absence of correlation between FGF23 and P indicates that FGF23 attenuation is independent of the decrease in P levels during pamidronate infusion. Significant correlation between NTx suppression and the decrease in FGF23 levels during the 1st cycle (r = 0.665, P = 0.013) suggests that inhibition of osteoclast function may have some role in suppressing FGF23 levels. Because pamidronate dose was most associated with the decrease in FGF23 levels during the second cycle, pamidronate may directly attenuate osteocyte/osteoblast-mediated FGF23 production. This is the first evidence of a rapid fall in FGF23 levels following pamidronate infusion, raising the possibility that inhibition of bone resorption and/or direct effects of pamidronate may suppress secretion of FGF23.

  3. Decrease in Circulating Fatty Acids Is Associated with Islet Dysfunction in Chronically Sleep-Restricted Rats

    PubMed Central

    Zhan, Shanshan; Wu, Yangyang; Sun, Peng; Lin, Haiyan; Zhu, Yunxia; Han, Xiao

    2016-01-01

    Previous studies have shown that sleep restriction-induced environmental stress is associated with abnormal metabolism, but the underlying mechanism is poorly understood. In the current study, we investigated the possible lipid and glucose metabolism patterns in chronically sleep-restricted rat. Without changes in food intake, body weight was decreased and energy expenditure was increased in sleep-restricted rats. The effects of chronic sleep disturbance on metabolites in serum were examined using 1H NMR metabolomics and GC-FID/MS analysis. Six metabolites (lipoproteins, triglycerides, isoleucine, valine, choline, and phosphorylcholine) exhibited significant alteration, and all the fatty acid components were decreased, which suggested fatty acid metabolism was impaired after sleep loss. Moreover, increased blood glucose, reduced serum insulin, decreased glucose tolerance, and impaired glucose-stimulated insulin secretion of islets were also observed in sleep-restricted rats. The islet function of insulin secretion could be partially restored by increasing dietary fat to sleep-disturbed rats suggested that a reduction in circulating fatty acids was related to islet dysfunction under sleep deficiency-induced environmental stress. This study provides a new perspective on the relationship between insufficient sleep and lipid/glucose metabolism, which offers insights into the role of stressful challenges in a healthy lifestyle. PMID:27983645

  4. Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice.

    PubMed

    Arendash, Gary W; Mori, Takashi; Cao, Chuanhai; Mamcarz, Malgorzata; Runfeldt, Melissa; Dickson, Alexander; Rezai-Zadeh, Kavon; Tane, Jun; Citron, Bruce A; Lin, Xiaoyang; Echeverria, Valentina; Potter, Huntington

    2009-01-01

    We have recently shown that Alzheimer's disease (AD) transgenic mice given a moderate level of caffeine intake (the human equivalent of 5 cups of coffee per day) are protected from development of otherwise certain cognitive impairment and have decreased hippocampal amyloid-beta (Abeta) levels due to suppression of both beta-secretase (BACE1) and presenilin 1 (PS1)/gamma-secretase expression. To determine if caffeine intake can have beneficial effects in "aged" APPsw mice already demonstrating cognitive impairment, we administered caffeine in the drinking water of 18-19 month old APPsw mice that were impaired in working memory. At 4-5 weeks into caffeine treatment, those impaired transgenic mice given caffeine (Tg/Caff) exhibited vastly superior working memory compared to the continuing impairment of control transgenic mice. In addition, Tg/Caff mice had substantially reduced Abeta deposition in hippocampus (decrease 40%) and entorhinal cortex (decrease 46%), as well as correlated decreases in brain soluble Abeta levels. Mechanistically, evidence is provided that caffeine suppression of BACE1 involves the cRaf-1/NFkappaB pathway. We also determined that caffeine concentrations within human physiological range effectively reduce active and total glycogen synthase kinase 3 levels in SweAPP N2a cells. Even with pre-existing and substantial Abeta burden, aged APPsw mice exhibited memory restoration and reversal of AD pathology, suggesting a treatment potential of caffeine in cases of established AD.

  5. Splicing inhibition decreases phosphorylation level of Ser2 in Pol II CTD

    PubMed Central

    Koga, Mitsunori; Hayashi, Megumi; Kaida, Daisuke

    2015-01-01

    Phosphorylation of the C-terminal domain of the largest subunit of RNA polymerase II (Pol II), especially Ser2 and Ser5 residues, plays important roles in transcription and mRNA processing, including 5′ end capping, splicing and 3′ end processing. These phosphorylation events stimulate mRNA processing, however, it is not clear whether splicing activity affects the phosphorylation status of Pol II. In this study, we found that splicing inhibition by potent splicing inhibitors spliceostatin A (SSA) and pladienolide B or by antisense oligos against snRNAs decreased phospho-Ser2 level, but had little or no effects on phospho-Ser5 level. In contrast, transcription and translation inhibitors did not decrease phospho-Ser2 level, therefore inhibition of not all the gene expression processes cause the decrease of phospho-Ser2. SSA treatment caused early dissociation of Pol II and decrease in phospho-Ser2 level of chromatin-bound Pol II, suggesting that splicing inhibition causes downregulation of phospho-Ser2 through at least these two mechanisms. PMID:26202968

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Consumption of acidic water alters the gut microbiome and decreases the risk of diabetes in NOD mice.

    PubMed

    Wolf, Kyle J; Daft, Joseph G; Tanner, Scott M; Hartmann, Riley; Khafipour, Ehsan; Lorenz, Robin G

    2014-04-01

    Infant formula and breastfeeding are environmental factors that influence the incidence of Type 1 Diabetes (T1D) as well as the acidity of newborn diets. To determine if altering the intestinal microbiome is one mechanism through which an acidic liquid plays a role in T1D, we placed non-obese diabetic (NOD)/ShiLtJt mice on neutral (N) or acidified H2O and monitored the impact on microbial composition and diabetes incidence. NOD-N mice showed an increased development of diabetes, while exhibiting a decrease in Firmicutes and an increase in Bacteroidetes, Actinobacteria, and Proteobacteria from as early as 2 weeks of age. NOD-N mice had a decrease in the levels of Foxp3 expression in CD4(+)Foxp3(+) cells, as well as decreased CD4(+)IL17(+) cells, and a lower ratio of IL17/IFNγ CD4+ T-cells. Our data clearly indicates that a change in the acidity of liquids consumed dramatically alters the intestinal microbiome, the presence of protective Th17 and Treg cells, and the incidence of diabetes. This data suggests that early dietary manipulation of intestinal microbiota may be a novel mechanism to delay T1D onset in genetically pre-disposed individuals.

  11. 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.

  12. 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

  13. 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

  14. The galactose-induced decrease in phosphate levels leads to toxicity in yeast models of galactosemia.

    PubMed

    Machado, Caio M; De-Souza, Evandro A; De-Queiroz, Ana Luiza F V; Pimentel, Felipe S A; Silva, Guilherme F S; Gomes, Fabio M; Montero-Lomelí, Mónica; Masuda, Claudio A

    2017-02-14

    Classic galactosemia is an inborn error of metabolism caused by deleterious mutations in the GALT gene. A number of evidences indicate that the galactose-1-phosphate accumulation observed in patient cells is a cause of toxicity in this disease. Nevertheless, the consequent molecular events caused by the galactose-1-phosphate accumulation remain elusive. Here we show that intracellular inorganic phosphate levels decreased when yeast models of classic galactosemia were exposed to galactose. The decrease in phosphate levels is probably due to the trapping of phosphate in the accumulated galactose-1-phosphate since the deletion of the galactokinase encoding gene GAL1 suppressed this phenotype. Galactose-induced phosphate depletion caused an increase in glycogen content, an expected result since glycogen breakdown by the enzyme glycogen phosphorylase is dependent on inorganic phosphate. Accordingly, an increase in intracellular phosphate levels suppressed the galactose effect on glycogen content and conferred galactose tolerance to yeast models of galactosemia. These results support the hypothesis that the galactose-induced decrease in phosphate levels leads to toxicity in galactosemia and opens new possibilities for the development of better treatments for this disease.

  15. 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

  16. Levels of antioxidant defenses are decreased in bovine spermatozoa after a cycle of freezing and thawing.

    PubMed

    Bilodeau, J F; Chatterjee, S; Sirard, M A; Gagnon, C

    2000-03-01

    Growing evidence suggests that the generation of reactive oxygen species (ROS) and their detoxification by antioxidants plays a very important role in fertility. However, the relationship between the level of antioxidants in spermatozoa and the decreased fecundity following a freeze/thaw cycle remains poorly understood. We assessed the activities of antioxidant enzymes such as catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD), and levels of reduced/oxidized glutathione (GSH/GSSG) in bovine semen. Sperm cells were isolated using a Percoll gradient to avoid contamination from seminal plasma, cellular debris, and other cell types. We found that bovine spermatozoa are poorly adapted to metabolize the toxic hydrogen peroxide (H(2)O(2)). Indeed, very low levels of GPx and an absence of catalase were observed. We also studied the effect of freezing and thawing bovine spermatozoa in a egg yolk-Tris-glycerol extender (EYTG). Cryopreservation significantly reduced sperm GSH levels by 78% and SOD activity by 50%. We also investigated whether the decrease in GSH level could be linked to oxidative metabolism and found that a greater reduction in intracellular GSH level occurred when fresh sperm cells were incubated in EYTG for 6 hr at 38.5 degrees C under aerobic conditions than when incubated under restricted oxygen availability. Our results strongly suggest the involvement of an oxidative stress during a freeze/thaw cycle and are consistent with the hypothesis that ROS generated during such a cycle are detrimental to sperm function.

  17. Decreased level of albumin in peripheral blood mononuclear cells of streptozotocin-induced diabetic rats.

    PubMed

    Park, Ki Tae; Yun, Chul-Ho; Bae, Chun-Sik; Ahn, Taeho

    2014-08-01

    We investigated the phenotypic level of albumin in peripheral blood mononuclear cells (PBMC) of streptozotocin (STZ)-induced diabetic rats. A specific reduction of albumin was identified by 2-dimensional electrophoresis and mass spectrometry. Decreased albumin content was also confirmed by immunoblotting and quantitative real-time PCR. Since albumin is a major and predominant antioxidant in plasma, the PBMC albumin may also contribute to their antioxidant activity. By measuring the amount of H2O2, lipid peroxidation and the redox form of glutathione, it was found that the production of the oxidative stress was elevated in STZ-diabetic rats compared to that of normal control. We suggest, therefore, that decreased albumin content may lead to the decreased antioxidant activity in the PBMC of type 1 diabetic rats.

  18. Formulating gels for decreased mucociliary transport using rheologic properties: polyacrylic acids.

    PubMed

    Shah, Ankur J; Donovan, Maureen D

    2007-04-20

    The purpose of these studies was to identify the rheologic properties of polyacrylic acid gels necessary for optimal reductions in mucociliary clearance. The mucociliary transport of 2 bioadhesive polyacrylic acid polymers, polycarbophil and carbopol, was assessed in vitro by measuring their clearance rates across explants of ciliated bovine tracheal tissue. The viscoelastic properties of polymer gels were measured in the presence of mucus using controlled stress rheometry. Combinations of apparent viscosity (eta) and complex modulus (G*) were found to be the most useful parameters in the identification of polyacrylic acid formulations capable of decreasing mucociliary transport rate (MTR). A narrow range of eta and G* values suitable for reducing mucociliary clearance, while remaining sufficiently fluid for intranasal administration, were identified. The correlations between the rheologic parameters of the polycarbophil gels and their mucociliary transport rates were used to identify other polyacrylic acid gels that also had suitable mucociliary clearance properties, demonstrating that these parameters can be used to direct the optimization of formulations using simple in vitro rheologic testing.

  19. Phenylboronic acid selectively inhibits human prostate and breast cancer cell migration and decreases viability.

    PubMed

    Bradke, Tiffany M; Hall, Casey; Carper, Stephen W; Plopper, George E

    2008-01-01

    We compared the in vitro effect of boric acid (BA) versus phenylboronic acid (PBA) on the migration of prostate and breast cancer cell lines and non-tumorigenic cells from the same tissues. Treatment at 24 hours with BA (< or =500 microM) did not inhibit chemotaxis on fibronectin in any cell line. However, treatment over the same time course with concentrations of PBA as low as 1 muM significantly inhibited cancer cell migration without effecting non-tumorigenic cell lines. The compounds did not affect cell adhesion or viability at 24 hours but did alter morphology; both decreased cancer cell viability at eight days. These results suggest that PBA is more potent than BA in targeting the metastatic and proliferative properties of cancer cells.

  20. 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

  1. n-3 Essential fatty acids decrease weight gain in genetically obese mice.

    PubMed

    Cunnane, S C; McAdoo, K R; Horrobin, D F

    1986-07-01

    1. Lean (ln/ln) and obese (ob/ob) mice were given diets containing a fat source of 100 g evening primrose (Oenothera biennis) oil (fatty acids 18:2n-6, 18:3n-6; EPO) or 100 g cod liver oil (20:5n-3, 22:6n-3; CLO)/kg diet. 2. Weight gain was lower in the ob/ob mice fed on CLO, an effect unrelated to food intake. 3. In the ob/ob mice fed on CLO, thromboxane synthesis by clotting platelets was reduced compared with that in ob/ob mice fed on EPO. 4. The ob/ob CLO-fed mice had lower arachidonic acid but higher levels of n-3 fatty acids in liver, brown adipose tissue and white adipose tissue. 5. The n-3 fatty acids in CLO therefore replaced the n-6 fatty acids in tissue lipids and reduced synthesis of '2 series' prostaglandins in addition to causing lower weight gain in the CLO-fed ob/ob mice.

  2. STRESS LEVELS IN CAPTURED RIVER OTTERS (LONTRA CANADENSIS) DECREASED AFTER TRANSPORTATION TO REINTRODUCTION SITES.

    PubMed

    Taylor, Rebekah T; Wong, Jennifer A; Serfass, Thomas L

    2016-12-01

    The level of stress that animals endure during capture, handling, transportation, and release processes is a major concern of animal reintroduction projects. Animals under chronic stress are more susceptible to disease and other deleterious issues that could reduce their survival in a new environment. Northern river otters ( Lontra canadensis ) have been reintroduced in 22 states in the United States and may be susceptible to developing chronic stress during the reintroduction process. We assessed stress levels in five river otters captured from wild populations in Washington, held in captivity for up to 21 days, and then transported to New Mexico for reintroduction. Glucocorticoid levels in fecal samples of all otters tested decreased from when they were held captive in Washington to the time of release. This outcome suggests that habituation to captivity before transport and release may serve to minimize the likelihood of an otter being released while experiencing a potentially burdensome level of stress.

  3. 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).

  4. Decreasing Free Radicals Level on High Risk Person After Vitamin C and E Supplement Treatment

    NASA Astrophysics Data System (ADS)

    Sitorus, M. S.; Anggraini, D. R.; Hidayat

    2017-03-01

    Has become a global issue that the increase in global warming mainly caused by high air pollution levels which are donated by motor vehicle emissions. As a rapidly developing country, Indonesia becomes vulnerable to health problems related to air pollution. Excessive free radicals that is produced by air pollution can initiate stress oxidative. Already known that, stress oxidative trigger many health problems. Vitamin C and E is a non enzymatic antioxidant that can neutralize free radicals. This study aims to investigate the decreasing free radicals level by administering vitamin C and E. This research using pre and post experimental design study. There are 24 operators gasoline station Pertamina as samples, with an average age of 26 years. The samples were divided into 4 groups. Group 1 (control), group 2, were given vitamin C doses of 500mg / day, group 3 was given vitamin E doses of 250 IU / day and the group 4 was given a combination of vitamins C and E. The treatment was given for 30 days. Free radicals level is obtained from malonaldehyde (MDA) level by spectrophotometer. Before treatment the average of MDA level is 5.540 µm. After the treatment, MDA is significantly decreased become 3.992 µm (T-test, sig<0.05). This result can be used as a sign of side affect of air pollutant in the operator SPBU. As reminding to protect the employee with safety aid and supplement.

  5. 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

  6. Repression of Invasion Genes and Decreased Invasion in a High-Level Fluoroquinolone-Resistant Salmonella Typhimurium Mutant

    PubMed Central

    Fàbrega, Anna; du Merle, Laurence; Le Bouguénec, Chantal; Jiménez de Anta, M. Teresa; Vila, Jordi

    2009-01-01

    Background Nalidixic acid resistance among Salmonella Typhimurium clinical isolates has steadily increased, whereas the level of ciprofloxacin resistance remains low. The main objective of this study was to characterize the fluoroquinolone resistance mechanisms acquired in a S. Typhimurium mutant selected with ciprofloxacin from a susceptible isolate and to investigate its invasion ability. Methodology/Principal Findings Three different amino acid substitutions were detected in the quinolone target proteins of the resistant mutant (MIC of ciprofloxacin, 64 µg/ml): D87G and G81C in GyrA, and a novel mutation, E470K, in ParE. A protein analysis revealed an increased expression of AcrAB/TolC and decreased expression of OmpC. Sequencing of the marRAB, soxRS, ramR and acrR operons did not show any mutation and neither did their expression levels in a microarray analysis. A decreased percentage of invasion ability was detected when compared with the susceptible clinical isolate in a gentamicin protection assay. The microarray results revealed a decreased expression of genes which play a role during the invasion process, such as hilA, invF and the flhDC operon. Of note was the impaired growth detected in the resistant strain. A strain with a reverted phenotype (mainly concerning the resistance phenotype) was obtained from the resistant mutant. Conclusions/Significance In conclusion, a possible link between fluoroquinolone resistance and decreased cell invasion ability may exist explaining the low prevalence of fluoroquinolone-resistant S. Typhimurium clinical isolates. The impaired growth may appear as a consequence of fluoroquinolone resistance acquisition and down-regulate the expression of the invasion genes. PMID:19946377

  7. Investigating the causes for decreased levels of glutathione in individuals with type II diabetes.

    PubMed

    Lagman, Minette; Ly, Judy; Saing, Tommy; Kaur Singh, Manpreet; Vera Tudela, Enrique; 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 M

  8. 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

  9. Decreased training volume and increased carbohydrate intake increases oxidized LDL levels.

    PubMed

    Välimäki, I A; Vuorimaa, T; Ahotupa, M; Kekkonen, R; Korpela, R; Vasankari, T

    2012-04-01

    We studied effects of probiotics and training volume on oxidized LDL lipids (ox-LDL), serum antioxidant potential (s-TRAP) and serum antioxidants (s-α-tocopherol, s-γ-tocopherol, s-retinol, s-β-carotene and s-ubiquinone-10) in marathon runners during 3-months training period, 6-days preparation period and marathon run. Runners (n=127) were recruited for a randomized, double-blind intervention during which they received either Lactobacillus rhamnosus GG (LGG, probiotic group) or placebo drink (placebo group) during whole study. During the preparation period, subjects decreased training and increased carbohydrate intake. Blood samples were taken at baseline, before 6-days preparation, before and immediately after the marathon. Probiotics did not have any effect on ox-LDL, s-TRAP or serum antioxidants levels during the study. Interestingly, ox-LDL increased by 28% and 33% during the preparation period and decreased by 16% and 19% during the marathon run in the placebo and probiotic groups, respectively (in all, P<0.001). No changes were seen in s-TRAP before marathon, but during run s-TRAP raised by 16% in both groups (both, P<0.001). The increase of ox-LDL level during the preparative period after several months' training suggests that aerobic training may reduce the concentration of ox-LDL and that decrease of training together with increased energy intake, mainly carbohydrate, before marathon is capable of increasing the level of ox-LDL.

  10. Hypopituitarism in a neonate with hyperbilirubinemia and decreased level of consciousness: a case report study.

    PubMed

    Mousavi, Hadi; Bakhtiyari, Salar

    2014-01-01

    Decreased level of consciousness in neonates may result from different etiologies, including rare metabolic and hormonal disorder due to anterior pituitary insufficiency. In this case report, a five-day-old newborn boy was referred to the neonatal intensive care unit of Mustafa Khomeini hospital of Ilam, Iran. He had an open anterior fontanel with no history of prenatal and familial diseases. Clinical examination showed decreased level of consciousness so that this patient responded only to painful stimuli. Furthermore, unconsciousness, hyperbilirubinemia, and hypotonia were fully evident. Given the clinical findings and decreased level of consciousness, hormonal diagnostic tests and brain CT scan were performed for any evidence of hypopituitarism. Clinical and experimental findings were consistent with the generalized edema and pituitary insufficiency secondary to central hypothyroidism and cortisol deficiency. Based on the findings, the neonate was put on the hormonal replacement therapy and, as the result, all of the abnormal clinical symptoms disappeared. In conclusion, fatal neonatal diseases may be mistaken with unimportant clinical findings at the first examination. Therefore, comprehensive attention to all potential causes of such symptoms in the neonates should be given for early diagnosis and treatment, and to prevent any fatal and irreversible complications.

  11. 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

  12. Decreased solubilization of Pu(IV) polymers by humic acids under anoxic conditions

    NASA Astrophysics Data System (ADS)

    Xie, Jinchuan; Lin, Jianfeng; Liang, Wei; Li, Mei; Zhou, Xiaohua

    2016-11-01

    Pu(IV) polymer has a very low solubility (log[Pu(IV)aq]total = -10.4 at pH 7.2 and I = 0). However, some aspects of their environmental fate remain unclear. Humic acids are able to complex with Pu4+ ions and their dissolved species (<10 kD) in the groundwater (neutral to alkaline pH) may cause solubilization of the polymers. Also, humic acids have the native reducing capacity and potentially reduce the polymeric Pu(IV) to Pu(III)aq (log[Pu(III)aq]total = -5.3 at pH 7.2 and I = 0). Solubilization and reduction of the polymers can enhance their mobility in subsurface environments. Nevertheless, humic acids readily coat the surfaces of metal oxides via electrostatic interaction and ligand exchange mechanisms. The humic coatings are expected to prevent both solubilization and reduction of the polymers. Experiments were conducted under anoxic and slightly alkaline (pH 7.2) conditions in order to study whether humic acids have effects on stability of the polymers. The results show that the polymeric Pu(IV) was almost completely transformed into aqueous Pu(IV) in the presence of EDTA ligands. In contrast, the dissolved humic acids did not solubilize the polymers but in fact decreased their solubility by one order of magnitude. The humic coatings were responsible for the decreased solubilization. Such coatings limited the contact between the polymers and EDTA ligands, especially at the relatively high concentrations of humic acids (>0.57 mg/L). Solubilization of the humic-coated polymers was thus inhibited to a significant extent although EDTA, having the great complexation ability, was present in the humic solutions. Reduction of Pu(IV) polymers by the humic acids was also not observed in the absence of EDTA. In the presence of EDTA, the polymers were partially reduced to Pu(III)aq by the humic acids of 0.57 mg/L and the percentage of Pu(III)aq accounted for 51.7% of the total aqueous Pu. This demonstrates that the humic acids were able to reduce the aqueous Pu

  13. Ozone oxidation of oleic acid surface films decreases aerosol cloud condensation nuclei activity

    NASA Astrophysics Data System (ADS)

    Schwier, A. N.; Sareen, N.; Lathem, T. L.; Nenes, A.; McNeill, V. F.

    2011-08-01

    Heterogeneous oxidation of aerosols composed of pure oleic acid (C18H34O2, an unsaturated fatty acid commonly found in continental and marine aerosol) by gas-phase O3 is known to increase aerosol hygroscopicity and activity as cloud condensation nuclei (CCN). Whether this trend is preserved when the oleic acid is internally mixed with other electrolytes is unknown and addressed in this study. We quantify the CCN activity of sodium salt aerosols (NaCl and Na2SO4) internally mixed with sodium oleate (SO) and oleic acid (OA). We find that particles containing roughly one monolayer of SO/OA show similar CCN activity to pure salt particles, whereas a tenfold increase in organic concentration slightly depresses CCN activity. O3 oxidation of these multicomponent aerosols has little effect on the critical diameter for CCN activation for unacidified particles at all conditions studied, and the activation kinetics of the CCN are similar in each case to those of pure salts. SO-containing particles which are acidified to atmospherically relevant pH before analysis in order to form oleic acid, however, show depressed CCN activity upon oxidation. This effect is more pronounced at higher organic concentrations. The behavior after oxidation is consistent with the disappearance of the organic surface film, supported by Köhler Theory Analysis (KTA). The κ-Köhler calculations show a small decrease in hygroscopicity after oxidation. The important implication of this finding is that oxidative aging may not always enhance the hygroscopicity of internally mixed inorganic-organic aerosols.

  14. Decreased levels of serum nitric oxide in different forms of dementia.

    PubMed

    Corzo, Lola; Zas, Raquel; Rodríguez, Susana; Fernández-Novoa, Lucía; Cacabelos, Ramón

    2007-06-15

    Nitric oxide is involved in normal physiological functions and also in pathological processes leading to tissue damage due, in part, to its free radical nature (oxidative stress). Oxidative stress and vascular dysfunction have been recognized as contributing factors in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VD). In order to study the possible links between these processes and dementia, we have analysed plasma amyloid-beta(1-42) levels (Abeta) and total nitric oxide (NOx), apolipoprotein E (ApoE), lipids, vitamin B12, and folate concentrations in the serum of 99 patients with dementia and 55 age-matched non-demented controls. Both nitrate and nitrite levels were measured by a colorimetric method using Griess Reagent and plasma Abeta levels were analysed by a hypersensitive ELISA method. Our data showed a significant decrease of serum NOx levels in dementia, especially in probable AD and VD patients, as compared with controls. We observed a weak correlation between serum NOx levels and cognitive deterioration in dementia; however, NOx levels were not associated with ApoE and Abeta levels. In dementia and controls, a similar correlation pattern between HDL-cholesterol versus NOx was found. No apparent association between NOx, Abeta and AD-related genes [APOE (apolipoprotein E), PSEN1 (Presenilin 1)] was observed. Our data suggest that NOx may contribute to the pathogenesis of dementia through a process mediated by HDL-cholesterol.

  15. 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.

  16. 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

  17. Chlorogenic acid decreases intestinal permeability and increases expression of intestinal tight junction proteins in weaned rats challenged with LPS.

    PubMed

    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.

  18. Reduced CSF turnover and decreased ventricular Aβ42 levels are related

    PubMed Central

    2011-01-01

    Background The appearance of Aβ42 peptide deposits is admitted to be a key event in the pathogenesis of Alzheimer's disease, although amyloid deposits also occur in aged non-demented subjects. Aβ42 is a degradation product of the amyloid protein precursor (APP). It can be catabolized by several enzymes, reabsorbed by capillaries or cleared into cerebrospinal fluid (CSF). The possible involvement of a decrease in CSF turnover in A4β2 deposit formation is up to now poorly known. We therefore investigated a possible relationship between a reduced CSF turnover and the CSF levels of the A4β2 peptide. To this aim, CSF of 31 patients with decreased CSF turnover were studied. These patients presented chronic hydrocephalus communicating or obstructive, which required surgery (ventriculostomy or ventriculo-peritoneal shunt). Nine subjects had idiopathic normal pressure hydrocephalus (iNPH), and the other 22 chronic hydrocephalus from other origins (oCH). The Aβ42 peptide concentration was measured by an ELISA test in 31 ventricular CSF samples and in 5 lumbar CSF samples from patients with communicating hydrocephalus. Results The 5 patients with lumbar CSF analysis had similar levels of lumbar and ventricular Aβ42. A significant reduction in Aβ42 ventricular levels was observed in 24 / 31 patients with hydrocephalus. The values were lower than 300 pg/ml in 5 out of 9 subjects with iNPH, and in 15 out of 22 subjects with oCH. Conclusion The decrease of CSF Aβ42 seems to occur independently of the surgical hydrocephalus aetiology. This suggests that a CSF reduced turnover may play an important role in the decrease of CSF Aβ42 concentration. PMID:21569454

  19. 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.

  20. 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.

  1. Decreased expression levels of Nurr1 are associated with chronic inflammation in patients with type 2 diabetes.

    PubMed

    Xu, Ying; Huang, Qi; Zhang, Wenfang; Wang, Yaping; Zeng, Qingling; He, Chunyan; Xue, Junli; Chen, Jin; Hu, Xuemei; Xu, Yancheng

    2015-10-01

    Chronic inflammation is associated with insulin resistance, a characteristic of type 2 diabetes (T2D). Nuclear receptor‑related protein 1 (Nurr1) can regulate inflammation, dependent on the nature of individual diseases. However, whether Nurr1 regulates chronic inflammation during the pathogenic process of T2D in humans remains to be fully elucidated. The present study aimed to investigate the potential association between the expression of Nurr1 in peripheral blood mononuclear cells (PBMCs) and inflammation in patients with T2D. The levels of plasma tumor necrosis factor (TNF)α and interleukin (IL)‑6, the relative expression levels of Nurr1, and glycogen synthase kinase (GSK)‑3β phosphorylation in PBMCs from 40 patients with T2D and 40 healthy controls (HC group) were examined, and their potential association with clinical measures were analyzed. The expression levels of Nurr1, induced by high glucose and palmitic acid, were assessed in the PBMCs from the HC group. Compared with the HC group, significantly higher levels of plasma TNFα and IL‑6 were correlated positively with the degree of insulin resistance in the T2D patients. However, significantly lower expression levels of Nurr1 and GSK‑3β phosphorylation in the PBMCs were correlated negatively with the levels of TNFα, IL‑6, fasting insulin and insulin resistance in the T2D patients. Treatment of the PBMCs with high glucose or palmitic acid inhibited the expression of Nurr1 in a dose‑ and time‑dependent manner. Therefore, decreased expression levels of Nurr1 were associated with chronic inflammation and insulin resistance in patients with T2D.

  2. 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.

  3. Association between Higher Serum Cortisol Levels and Decreased Insulin Secretion in a General Population

    PubMed Central

    Kamba, Aya; Daimon, Makoto; Murakami, Hiroshi; Otaka, Hideyuki; Matsuki, Kota; Sato, Eri; Tanabe, Jutaro; Takayasu, Shinobu; Matsuhashi, Yuki; Yanagimachi, Miyuki; Terui, Ken; Kageyama, Kazunori; Tokuda, Itoyo; Takahashi, Ippei; Nakaji, Shigeyuki

    2016-01-01

    Glucocorticoids (GCs) are well known to induce insulin resistance. However, the effect of GCs on insulin secretion has not been well characterized under physiological conditions in human. We here evaluated the effect of GCs on insulin secretion/ß-cell function precisely in a physiological condition. A population-based study of 1,071 Japanese individuals enrolled in the 2014 Iwaki study (390 men, 681 women; aged 54.1 ± 15.1 years), those excluded individuals taking medication for diabetes or steroid treatment, were enrolled in the present study. Association between serum cortisol levels and insulin resistance/secretion assessed by homeostasis model assessment using fasting blood glucose and insulin levels (HOMA-R and HOMA-ß, respectively) were examined. Univariate linear regression analyses showed correlation of serum cortisol levels with HOMA-ß (ß = -0.134, p <0.001) but not with HOMA-R (ß = 0.042, p = 0.172). Adjustments for age, gender, and the multiple clinical characteristics correlated with HOMA indices showed similar results (HOMA-ß: ß = -0.062, p = 0.025; HOMA-R: ß = -0.023, p = 0.394). The correlation between serum cortisol levels and HOMA-ß remained significant after adjustment for HOMA- R (ß = -0.057, p = 0.034). When subjects were tertiled based on serum cortisol levels, the highest tertile was at greater risk of decreased insulin secretion (defined as lower one third of HOMA-ß (≤70)) than the lowest tertile, after adjustment for multiple factors including HOMA- R (odds ratio 1.26, 95% confidence interval 1.03–1.54). In conclusion, higher serum cortisol levels are significantly associated with decreased insulin secretion in the physiological cortisol range in a Japanese population. PMID:27861636

  4. The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats.

    PubMed

    Yoo, Yeong-Min; Jung, Eui-Man; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

    2011-10-01

    In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pre-treatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.

  5. 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.

  6. Decreased levels of sRAGE in follicular fluid from patients with PCOS.

    PubMed

    Wang, BiJun; Li, Jing; Yang, QingLing; Zhang, FuLi; Hao, MengMeng; Guo, YiHong

    2017-03-01

    This study aimed to explore the association between soluble receptor for advanced glycation end products (sRAGE) levels in follicular fluid and the number of oocytes retrieved and to evaluate the effect of sRAGE on vascular endothelial growth factor (VEGF) in granulosa cells in patients with polycystic ovarian syndrome (PCOS). Two sets of experiments were performed in this study. In part one, sRAGE and VEGF protein levels in follicular fluid samples from 39 patients with PCOS and 35 non-PCOS patients were measured by ELISA. In part two, ovarian granulosa cells were isolated from an additional 10 patients with PCOS and cultured. VEGF and SP1 mRNA and protein levels, as well as pAKT levels, were detected by real-time PCR and Western blotting after cultured cells were treated with different concentrations of sRAGE. Compared with the non-PCOS patients, patients with PCOS had lower sRAGE levels in follicular fluid. Multi-adjusted regression analysis showed that high sRAGE levels in follicular fluid predicted a lower Gn dose, more oocytes retrieved, and a better IVF outcome in the non-PCOS group. Logistic regression analysis showed that higher sRAGE levels predicted favorably IVF outcomes in the non-PCOS group. Multi-adjusted regression analysis also showed that high sRAGE levels in follicular fluid predicted a lower Gn dose in the PCOS group. Treating granulosa cells isolated from patients with PCOS with recombinant sRAGE decreased VEGF and SP1 mRNA and protein expression and pAKT levels in a dose-dependent manner.

  7. Decreased Serotonin Levels and Serotonin-Mediated Osteoblastic Inhibitory Signaling in Patients With Ankylosing Spondylitis.

    PubMed

    Klavdianou, Kalliopi; Liossis, Stamatis-Nick; Papachristou, Dionysios J; Theocharis, Georgios; Sirinian, Chaido; Kottorou, Anastasia; Filippopoulou, Alexandra; Andonopoulos, Andrew P; Daoussis, Dimitrios

    2016-03-01

    Evidence suggests that serotonin is an inhibitor of bone formation. We aimed to assess: 1) serum serotonin levels in patients with ankylosing spondylitis (AS), a prototype bone-forming disease, compared with patients with rheumatoid arthritis (RA) and healthy subjects; 2) the effect(s) of TNFα blockers on serum serotonin levels in patients with AS and RA; and 3) the effect(s) of serum of AS patients on serotonin signaling. Serum serotonin levels were measured in 47 patients with AS, 28 patients with RA, and 40 healthy subjects by radioimmunoassay; t test was used to assess differences between groups. The effect of serum on serotonin signaling was assessed using the human osteoblastic cell line Saos2, evaluating levels of phospho-CREB by Western immunoblots. Serotonin serum levels were significantly lower in patients with AS compared with healthy subjects (mean ± SEM ng/mL 122.9 ± 11.6 versus 177.4 ± 24.58, p = 0.038) and patients with RA (mean ± SEM ng/mL 244.8 ± 37.5, p = 0.0004). Patients with AS receiving TNFα blockers had significantly lower serotonin levels compared with patients with AS not on such treatment (mean ± SEM ng/mL 95.8 ± 14.9 versus 149.2 ± 16.0, p = 0.019). Serotonin serum levels were inversely correlated with pCREB induction in osteoblast-like Saos-2 cells. Serotonin levels are low in patients with AS and decrease even further during anti-TNFα treatment. Differences in serotonin levels are shown to have a functional impact on osteoblast-like Saos-2 cells. Therefore, serotonin may be involved in new bone formation in AS.

  8. Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity.

    PubMed

    Yu, Jinghua; Lo, Jane-L; Huang, Li; Zhao, Annie; Metzger, Edward; Adams, Alan; Meinke, Peter T; Wright, Samuel D; Cui, Jisong

    2002-08-30

    Bile salt export pump (BSEP) is a major bile acid transporter in the liver. Mutations in BSEP result in progressive intrahepatic cholestasis, a severe liver disease that impairs bile flow and causes irreversible liver damage. BSEP is a target for inhibition and down-regulation by drugs and abnormal bile salt metabolites, and such inhibition and down-regulation may result in bile acid retention and intrahepatic cholestasis. In this study, we quantitatively analyzed the regulation of BSEP expression by FXR ligands in primary human hepatocytes and HepG2 cells. We demonstrate that BSEP expression is dramatically regulated by ligands of the nuclear receptor farnesoid X receptor (FXR). Both the endogenous FXR agonist chenodeoxycholate (CDCA) and synthetic FXR ligand GW4064 effectively increased BSEP mRNA in both cell types. This up-regulation was readily detectable at as early as 3 h, and the ligand potency for BSEP regulation correlates with the intrinsic activity on FXR. These results suggest BSEP as a direct target of FXR and support the recent report that the BSEP promoter is transactivated by FXR. In contrast to CDCA and GW4064, lithocholate (LCA), a hydrophobic bile acid and a potent inducer of cholestasis, strongly decreased BSEP expression. Previous studies did not identify LCA as an FXR antagonist ligand in cells, but we show here that LCA is an FXR antagonist with partial agonist activity in cells. In an in vitro co-activator association assay, LCA decreased CDCA- and GW4064-induced FXR activation with an IC(50) of 1 microm. In HepG2 cells, LCA also effectively antagonized GW4064-enhanced FXR transactivation. These data suggest that the toxic and cholestatic effect of LCA in animals may result from its down-regulation of BSEP through FXR. Taken together, these observations indicate that FXR plays an important role in BSEP gene expression and that FXR ligands may be potential therapeutic drugs for intrahepatic cholestasis.

  9. Endogenous Levels of Abscisic Acid and Decanoic Acid in Dutch Iris Bulbs and the Influence of Abscisic Acid and Decanoic Acid on Iris Meristems Cultured In Vitro1

    PubMed Central

    Doss, Robert P.; Kimura, Yosh; Christian, James K.

    1983-01-01

    Abscisic acid (ABA) and decanoic acid inhibited shoot elongation and floral development of Dutch iris (Iris hollandica Hoog. cv Ideal) meristems cultured in vitro. No synergism with respect to inhibition of leaf growth between ABA and decanoic acid was observed. With monthly harvest dates, from July 10, 1981 to October 10, 1981, there was a progressive decrease in endogenous level of free ABA in `Ideal' iris bulbs. Bulbs subjected to a full set of the usual preplanting storage conditions flowered, on average, 46 days after planting versus 194 days after planting for bulbs planted directly after harvest. ABA levels at harvest were 4- to 5-fold those after the preplanting storage treatment. In general, ABA levels did not correlate well with the length of time from planting until flowering of iris bulbs. Endogenous decanoic acid levels did not follow any pattern with respect to harvest date or postharvest treatment. After the postharvest high temperature treatment, there was about a 3-fold increase in nonscale decanoic acid concentration. Decanoic acid levels, in nonscale tissue, remained high after each of the other postharvest treatments. It is concluded that there is no good evidence to support the contention that either ABA or decanoic acid is directly involved in iris bulb dormancy. PMID:16663072

  10. Experimental Hyperthyroidism Decreases Gene Expression and Serum Levels of Adipokines in Obesity

    PubMed Central

    Luvizotto, Renata de Azevedo Melo; do Nascimento, André Ferreira; de Síbio, Maria Teresa; Olímpio, Regiane Marques Castro; Conde, Sandro José; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Cicogna, Antonio Carlos; Nogueira, Célia Regina

    2012-01-01

    Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C)—fed with commercial chow ad libitum—and obese (OB)—fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T3)/100 BW (OT). The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity. PMID:22645452

  11. Heat Stress Decreases Levels of Nutrient-Uptake and -Assimilation Proteins in Tomato Roots

    PubMed Central

    Giri, Anju; Heckathorn, Scott; Mishra, Sasmita; Krause, Charles

    2017-01-01

    Global warming will increase root heat stress, which is already common under certain conditions. Effects of heat stress on root nutrient uptake have rarely been examined in intact plants, but the limited results indicate that heat stress will decrease it; no studies have examined heat-stress effects on the concentration of nutrient-uptake proteins. We grew Solanum lycopersicum (tomato) at 25 °C/20 °C (day/night) and then transferred some plants for six days to 35 °C /30 °C (moderate heat) or 42 °C/37 °C (severe heat) (maximum root temperature = 32 °C or 39 °C, respectively); plants were then moved back to control conditions for seven days to monitor recovery. In a second experiment, plants were grown for 15 days at 28 °C/23 °C, 32 °C/27 °C, 36 °C/31 °C, and 40 °C/35 °C (day/night). Concentrations of nutrient-uptake and -assimilation proteins in roots were determined using protein-specific antibodies and ELISA (enzyme-linked immunosorbent assay). In general, (1) roots were affected by heat more than shoots, as indicated by decreased root:shoot mass ratio, shoot vs. root %N and C, and the level of nutrient metabolism proteins vs. less sensitive photosynthesis and stomatal conductance; and (2) negative effects on roots were large and slow-to-recover only with severe heat stress (40 °C–42 °C). Thus, short-term heat stress, if severe, can decrease total protein concentration and levels of nutrient-uptake and -assimilation proteins in roots. Hence, increases in heat stress with global warming may decrease crop production, as well as nutritional quality, partly via effects on root nutrient relations. PMID:28106834

  12. 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

  13. 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.

  14. [The actual approaches to the analysis of the decrease of population mortality on the territorial level].

    PubMed

    Krasnenkov, V L; Kamruzzaman, Saĭed

    2010-01-01

    The article deals with one of the major medical demographic problems of Tver region's higher population mortality, including mortality of able-bodied population. The prevalence of main causes of death and their structure are analyzed. The prospective forecast of death rate indicators based on extrapolation technique is proposed. The main strategic approaches to the development of target programs of decreasing premature population mortality in Tverskaya oblast on the basis of the expertise of hospital lethality and analysis of demographic situation is presented. The proposed approaches can promote the study of optimal management and organization decision-making by administrations of different levels.

  15. The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid.

    PubMed

    Roesly, Heather B; Khan, Mohammad R; Chen, Hwu Dau Rw; Hill, Kimberly A; Narendran, Nirushan; Watts, George S; Chen, Xiaoxin; Dvorak, Katerina

    2012-04-15

    Beclin-1 has a central role in the regulation of autophagy. Barrett's esophagus (BE) is associated with a significantly increased risk for the development of esophageal adenocarcinoma (EAC). In the current study, we evaluated the role of Beclin-1 and autophagy in the EAC. Biopsies obtained from patients with BE and EAC, tissues from a rat model of BE and EAC, and esophageal cell lines were evaluated for the expression of Beclin-1 by immunohistochemistry, immunoblotting, or RT-PCR. Since reflux of bile acids is important in EAC, we also evaluated the effect of exposure to deoxycholic acid (DCA) on autophagy and Beclin-1 expression. Beclin-1 expression was high in squamous epithelium and nondysplastic BE, whereas its expression was low in dysplastic BE and EAC. The same pattern of expression was observed in rat tissues and in esophageal cell lines. Normal esophageal epithelium and HET-1A cells (derived from normal squamous epithelium) show high levels of Beclin-1, but lower levels of Beclin-1 were found in BE and EAC cell lines (CP-A, CP-C, and OE33). Acute exposure to DCA led to increased Beclin-1 expression and increased autophagy as evaluated by electron microscopy and counting percentage of GFP-LC3-positive BE cells with punctate pattern. In contrast, chronic exposure to DCA did not result in the alteration of Beclin-1 levels or autophagy. In summary, these data suggest that autophagy is initially activated in response to bile acids, but chronic exposure to bile acids leads to decreased Beclin-1 expression and autophagy resistance.

  16. Flaxseed oil supplementation decreases C-reactive protein levels in chronic hemodialysis patients.

    PubMed

    Lemos, Joana R N; Alencastro, Mariana Gascue de; Konrath, Anita Vieceli; Cargnin, Marina; Manfro, Roberto Ceratti

    2012-12-01

    Malnutrition and chronic inflammation in dialysis patients negatively impact their survival prognosis, and nutrients, such as omega-3 oils, are postulated to reduce proinflammatory response. In this randomized, double-blind, multicenter, placebo-controlled trial, we investigated the effects of flaxseed oil (FO) on the inflammatory state of patients with chronic renal failure undergoing renal replacement therapy with hemodialysis (HD). We hypothesized that FO supplementation lowers C-reactive protein (CRP) levels. One hundred sixty patients with chronic renal failure who received HD therapy of 3 dialysis units over a 3-month period in South Brazil were included. The patients received blind doses of FO (1 g twice a day) and placebo (mineral oil, 1 g twice a day) for a period of 120 days. Inflammation was observed in 89 patients (61%) at the beginning of the study. There was a correlation between CRP and the body mass index (R(s) = 0.22; P = .022) and high-density lipoprotein cholesterol (R(s) = -0.23; P = .032), and the CRP levels decreased significantly over time in the group that received FO compared with the control group (P < .001). During the study period, 33.3% of the FO group changed from an inflamed to a not-inflamed category, whereas only 16.9% changed in the mineral oil group (P = .04). We conclude that the administration of FO decreases the CRP levels and that inflammation in HD patients appears to be correlated to their body mass index and reduced high-density lipoprotein cholesterol levels. Studies with a larger number of patients and over a longer duration are necessary to corroborate these findings.

  17. Abscisic acid metabolizing rhizobacteria decrease ABA concentrations in planta and alter plant growth.

    PubMed

    Belimov, Andrey A; Dodd, Ian C; Safronova, Vera I; Dumova, Valentina A; Shaposhnikov, Alexander I; Ladatko, Alexander G; Davies, William J

    2014-01-01

    Although endogenous phytohormones such as abscisic acid (ABA) regulate root growth, and many rhizobacteria can modulate root phytohormone status, hitherto there have been no reports of rhizobacteria mediating root ABA concentrations and growth by metabolising ABA. Using a selective ABA-supplemented medium, two bacterial strains were isolated from the rhizosphere of rice (Oryza sativa) seedlings grown in sod-podzolic soil and assigned to Rhodococcus sp. P1Y and Novosphingobium sp. P6W using partial 16S rRNA gene sequencing and phenotypic patterns by the GEN III MicroPlate test. Although strain P6W had more rapid growth in ABA-supplemented media than strain P1Y, both could utilize ABA as a sole carbon source in batch culture. When rice seeds were germinated on filter paper in association with bacteria, root ABA concentration was not affected, but shoot ABA concentration of inoculated plants decreased by 14% (strain P6W) and 22% (strain P1Y). When tomato (Solanum lycopersicum) genotypes differing in ABA biosynthesis (ABA deficient mutants flacca - flc, and notabilis - not and the wild-type cv. Ailsa Craig, WT) were grown in gnotobiotic cultures on nutrient solution agar, rhizobacterial inoculation decreased root and/or leaf ABA concentrations, depending on plant and bacteria genotypes. Strain P6W inhibited primary root elongation of all genotypes, but increased leaf biomass of WT plants. In WT plants treated with silver ions that inhibit ethylene perception, both ABA-metabolising strains significantly decreased root ABA concentration, and strain P6W decreased leaf ABA concentration. Since these changes in ABA status also occurred in plants that were not treated with silver, it suggests that ethylene was probably not involved in regulating bacteria-mediated changes in ABA concentration. Correlations between plant growth and ABA concentrations in planta suggest that ABA-metabolising rhizobacteria may stimulate growth via an ABA-dependent mechanism.

  18. Treatment of chronic periodontitis decreases serum prohepcidin levels in patients with chronic kidney disease

    PubMed Central

    Vilela, Eduardo Machado; Bastos, Jessica Amaral; Fernandes, Natalia; Ferreira, Ana Paula; Chaoubah, Alfredo; Bastos, Marcus Gomes

    2011-01-01

    OBJECTIVE: To determine the impact of periodontal treatment on serum levels of prohepcidin (the prohormone of hepcidin) and systemic inflammation markers, as well as correlations among these markers, in patients with chronic periodontitis and chronic kidney disease who were not undergoing dialysis. METHODS: We included 56 chronic periodontitis patients, 36 with chronic kidney disease and 20 without systemic diseases and with normal renal function (control group). Chronic kidney disease was defined as suggested by the clinical practice guidelines in the National Kidney Foundation. Chronic periodontitis was defined through clinical attachment level and by probing pocket depth, according to the American Association of Periodontology. The inflammatory markers ultrasensitive C-reactive protein, interleukin-6, and prohepcidin were evaluated before and 3 months after periodontal treatment. RESULTS: The efficacy of periodontal treatment was confirmed by the improvement in clinical parameters of chronic periodontitis in the control and chronic kidney disease groups. Periodontal treatment resulted in significant reductions in ultrasensitive C-reactive protein, interleukin-6 and serum prohepcidin levels in both groups. Moreover, in multivariate linear regression, the reduction in prohepcidin after periodontal treatment was significantly and independently associated with interleukin-6 levels in the control group. CONCLUSIONS: By inducing a decline in the systemic inflammatory response and a decrease in serum prohepcidin, successful periodontal treatment may represent an important means of ameliorating the inflammatory burden seen in patients with chronic kidney disease. Trial registration: ISRCTN59866656. PMID:21655762

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

    PubMed Central

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

    2016-01-01

    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

  20. Cytokine levels affected by gamma-linolenic acid.

    PubMed

    Dirks, J; van Aswegen, C H; du Plessis, D J

    1998-10-01

    This study was undertaken to assess whether gamma-linolenic acid (GLA) in the form of evening primrose oil (EPO) could affect rat serum cytokines, interferon-gamma (IFN-gamma), monocyte chemotactic protein-1 (MCP-1) and tumour necrosis factor-alpha (TNF-alpha). The following diets were administered: control, glucan, Freund's adjuvant and glucan plus Freund's adjuvant with and without GLA. In the presence of GLA, the IFN-gamma and MCP-1 levels were significantly decreased in contrast to the control group of TNF-alpha, which was significantly stimulated. On account of interaction between diets and GLA, the remaining diet groups of TNF-alpha were either not affected or were inhibited in the presence of GLA. The observations indicate that GLA may modulate the level of serum IFN-gamma, MCP-1 and TNF-alpha, which may be a worthwhile line of treatment in certain human diseases.

  1. 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.

  2. Suppression of long chain acyl-CoA synthetase 3 decreases hepatic de novo fatty acid synthesis through decreased transcriptional activity.

    PubMed

    Bu, So Young; Mashek, Mara T; Mashek, Douglas G

    2009-10-30

    Long chain acyl-CoA synthetases (ACSL) and fatty acid transport proteins (FATP) activate fatty acids to acyl-CoAs in the initial step of fatty acid metabolism. Numerous isoforms of ACSL and FATP exist with different tissue distribution patterns, intracellular locations, and substrate preferences, suggesting that each isoform has distinct functions in channeling fatty acids into different metabolic pathways. Because fatty acids, acyl-CoAs, and downstream lipid metabolites regulate various transcription factors that control hepatic energy metabolism, we hypothesized that ACSL or FATP isoforms differentially regulate hepatic gene expression. Using small interference RNA (siRNA), we knocked down each liver-specific ACSL and FATP isoform in rat primary hepatocyte cultures and subsequently analyzed reporter gene activity of numerous transcription factors and performed quantitative mRNA analysis of their target genes. Compared with control cells, which were transfected with control siRNA, knockdown of acyl-CoA synthetase 3 (ACSL3) significantly decreased reporter gene activity of several lipogenic transcription factors such as peroxisome proliferator activation receptor-gamma, carbohydrate-responsive element-binding protein, sterol regulatory element-binding protein-1c, and liver X receptor-alpha and the expression of their target genes. These findings were further supported by metabolic labeling studies that showed [1-(14)C]acetate incorporation into lipid extracts was decreased in cells treated with ACSL3 siRNAs and that ACSL3 expression is up-regulated in ob/ob mice and mice fed a high sucrose diet. ACSL3 knockdown decreased total acyl-CoA synthetase activity without substantially altering the expression of other ACSL isoforms. In summary, these results identify a novel role for ACSL3 in mediating transcriptional control of hepatic lipogenesis.

  3. Decreased long-chain fatty acid oxidation impairs postischemic recovery of the insulin-resistant rat heart.

    PubMed

    Harmancey, Romain; Vasquez, Hernan G; Guthrie, Patrick H; Taegtmeyer, Heinrich

    2013-10-01

    Diabetic patients with acute myocardial infarction are more likely to die than nondiabetic patients. In the present study we examined the effect of insulin resistance on myocardial ischemia tolerance. Hearts of rats, rendered insulin resistant by high-sucrose feeding, were subjected to ischemia/reperfusion ex vivo. Cardiac power of control hearts from chow-fed rats recovered to 93%, while insulin-resistant hearts recovered only to 80% (P<0.001 vs. control). Unexpectedly, impaired contractile recovery did not result from an impairment of glucose oxidation (576±36 vs. 593±42 nmol/min/g dry weight; not significant), but from a failure to increase and to sustain oxidation of the long-chain fatty acid oleate on reperfusion (1878±56 vs. 2070±67 nmol/min/g dry weight; P<0.05). This phenomenon was due to a reduced ability to transport oleate into mitochondria and associated with a 38-58% decrease in the mitochondrial uncoupling protein 3 (UCP3) levels. Contractile function was rescued by replacing oleate with a medium-chain fatty acid or by restoring UCP3 levels with 24 h of food withdrawal. Lastly, the knockdown of UCP3 in rat L6 myocytes also decreased oleate oxidation by 13-18% following ischemia. Together the results expose UCP3 as a critical regulator of long-chain fatty acid oxidation in the stressed heart postischemia and identify octanoate as an intervention by which myocardial metabolism can be manipulated to improve function of the insulin-resistant heart.

  4. 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.

  5. 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

  6. In vivo inhibition of acylpeptide hydrolase by carbapenem antibiotics causes the decrease of plasma concentration of valproic acid in dogs.

    PubMed

    Suzuki, Eiko; Nakai, Daisuke; Ikenaga, Hidenori; Fusegawa, Keiichi; Goda, Ryoya; Kobayashi, Nobuhiro; Kuga, Hiroshi; Izumi, Takashi

    2016-01-01

    1. Our previous in vitro studies suggest that inhibition of the acylpeptide hydrolase (APEH) activity as valproic acid glucuronide (VPA-G) hydrolase by carbapenems in human liver cytosol is a key process for clinical drug-drug interaction (DDI) of valproic acid (VPA) with carbapenems. Here, we investigated whether in vivo DDI of VPA with meropenem (MEPM) was caused via inhibition of APEH in dogs. 2. More rapid decrease of plasma VPA levels and increased urinary excretion of VPA-G were observed after co-administration with MEPM compared with those after without co-administration, whereas the plasma level and bile excretion of VPA-G showed no change. 3. Dog VPA-G hydrolase activity, inhibited by carbapenems, was mainly located in cytosol from both the liver and kidney. APEH-immunodepleted cytosols lacked VPA-G hydrolase activity. Hepatic and renal APEH activity was negligible even at 24 h after dosing of MEPM to a dog. 4. In conclusion, DDI of VPA with carbapenems in dogs is caused by long-lasting inhibition of APEH-mediated VPA-G hydrolysis by carbapenems, which could explain the delayed recovery of plasma VPA levels to the therapeutic window even after discontinuation of carbapenems in humans.

  7. Decreased 16:0/20:4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia

    PubMed Central

    Matsumoto, Junya; Nakanishi, Hiroki; Kunii, Yasuto; Sugiura, Yuki; Yuki, Dai; Wada, Akira; Hino, Mizuki; Niwa, Shin-Ichi; Kondo, Takeshi; Waki, Michihiko; Hayasaka, Takahiro; Masaki, Noritaka; Akatsu, Hiroyasu; Hashizume, Yoshio; Yamamoto, Sakon; Sato, Shinji; Sasaki, Takehiko; Setou, Mitsutoshi; Yabe, Hirooki

    2017-01-01

    The etiology of schizophrenia includes phospholipid abnormalities. Phospholipids are bioactive substances essential for brain function. To analyze differences in the quantity and types of phospholipids present in the brain tissue of patients with schizophrenia, we performed a global analysis of phospholipids in multiple brain samples using liquid chromatography electrospray ionization mass/mass spectrometry (LC-ESI/MS/MS) and imaging mass spectrometry (IMS). We found significantly decreased 16:0/20:4-phosphatidylinositol (PI) levels in the prefrontal cortex (PFC) in the brains from patients with schizophrenia in the LC-ESI/MS/MS, and that the 16:0/20:4-PI in grey matter was most prominently diminished according to the IMS experiments. Previous reports investigating PI pathology of schizophrenia did not identify differences in the sn-1 and sn-2 fatty acyl chains. This study is the first to clear the fatty acid composition of PI in brains from patients with schizophrenia. Alteration in the characteristic fatty acid composition of PI may also affect neuronal function, and could play a role in the etiology of schizophrenia. Although further studies are necessary to understand the role of reduced 16:0/20:4-PI levels within the prefrontal cortex in the etiology of schizophrenia, our results provide insight into the development of a novel therapy for the clinical treatment of schizophrenia. PMID:28332626

  8. Decreased 16:0/20:4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia.

    PubMed

    Matsumoto, Junya; Nakanishi, Hiroki; Kunii, Yasuto; Sugiura, Yuki; Yuki, Dai; Wada, Akira; Hino, Mizuki; Niwa, Shin-Ichi; Kondo, Takeshi; Waki, Michihiko; Hayasaka, Takahiro; Masaki, Noritaka; Akatsu, Hiroyasu; Hashizume, Yoshio; Yamamoto, Sakon; Sato, Shinji; Sasaki, Takehiko; Setou, Mitsutoshi; Yabe, Hirooki

    2017-03-23

    The etiology of schizophrenia includes phospholipid abnormalities. Phospholipids are bioactive substances essential for brain function. To analyze differences in the quantity and types of phospholipids present in the brain tissue of patients with schizophrenia, we performed a global analysis of phospholipids in multiple brain samples using liquid chromatography electrospray ionization mass/mass spectrometry (LC-ESI/MS/MS) and imaging mass spectrometry (IMS). We found significantly decreased 16:0/20:4-phosphatidylinositol (PI) levels in the prefrontal cortex (PFC) in the brains from patients with schizophrenia in the LC-ESI/MS/MS, and that the 16:0/20:4-PI in grey matter was most prominently diminished according to the IMS experiments. Previous reports investigating PI pathology of schizophrenia did not identify differences in the sn-1 and sn-2 fatty acyl chains. This study is the first to clear the fatty acid composition of PI in brains from patients with schizophrenia. Alteration in the characteristic fatty acid composition of PI may also affect neuronal function, and could play a role in the etiology of schizophrenia. Although further studies are necessary to understand the role of reduced 16:0/20:4-PI levels within the prefrontal cortex in the etiology of schizophrenia, our results provide insight into the development of a novel therapy for the clinical treatment of schizophrenia.

  9. Down-regulated resistin level in consequence of decreased neutrophil counts in untreated Grave's disease

    PubMed Central

    Huang, Fengjiao; Chen, Xinxin; Zhou, Yulin; Ye, Lei; Wang, Weiqing; Ning, Guang; Wang, Shu

    2016-01-01

    Resistin, belongs to cysteine-rich secretory protein, is mainly produced by circulating leukocytes, such as neutrophils monocytes and macrophages in humans. To date, few but controversial studies have reported about resistin concentrations in hyperthyroid patients, especially in Graves' disease (GD). We undertaked a controlled, prospective study to explore the serum resistin concentration in GD patients before and after -MMI treatment. In addition, we also investigated the main influencing factor on serum resistin level and discuessed the potential role of serum resistin plays in GD patients. 39 untreated GD (uGD) patients, including 8 males and 31 females, were enrolled in our investigation. All of these patients were prescribed with MMI treatment, in addition to 25 healthy controls. Anthropometric parameters and hormone assessment were measured. Enzyme-linked immunosorbent assay was used to detect serum resistin concentration in different stages of GD patients. Furthermore, neutrophil cell line NB4 with or without T3 treatment to detect the effect of thyroid hormones on resistin expression. The serum resistin level and neutrophil counts in untreated GD patients were significantly declined. And all of these parameters were recovered to normal after MMI treatment in ethyroid GD (eGD) and TRAb-negative conversion (nGD) patients. Resistin concentration exhibited a negative correlation with FT3 and FT4, but a positive correlation with absolute number of neutrophiles in uGD patients, whereas did not correlate with thyroid autoimmune antibodies and BMI. Neutrophile cell line, NB4, produced decreased expression of resistin when stimulated with T3. Our study showed a decrease of serum resistin level in GD patients and we suggested that the serum resistin might primarily secreted from circulating neutrophils and down-regulated by excessive thyroid hormones in GD patients. PMID:27637079

  10. 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

  11. 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

    2016-03-05

    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.

  12. Dandruff: a condition characterized by decreased levels of intercellular lipids in scalp stratum corneum and impaired barrier function.

    PubMed

    Harding, C R; Moore, A E; Rogers, J S; Meldrum, H; Scott, A E; McGlone, F P

    2002-07-01

    Dandruff is a major problem, yet little is known about the underlying mechanism and subsequent biochemical changes occurring in the scalp skin that lead to its manifestation. The characteristic flaking and scaling of the scalp experienced by dandruff sufferers suggests, similar to the changes classically seen in xerosis, that the desquamation process is impaired. We initiated studies to quantify the biochemical nature of the stratum corneum in the scalp of healthy individuals and dandruff sufferers. Total amounts and relative ratios of stratum corneum lipids species were analysed in scalp stratum corneum samples collected during studies conducted in the UK and Thailand in order to examine ethnic differences. In both populations, dandruff was associated with a dramatic decrease in free lipid levels, with significant decreases in ceramides, fatty acids, and cholesterol. Detailed sub-analysis of the major ceramide species within the total ceramide fraction revealed a decrease in ceramide 1 and increased proportions of ceramide 6i and 6ii. In a separate study, we demonstrated that dandruff sufferers show both an elevated blood flow and an increased reported incidence of itch in response to histamine topically applied to the scalp compared with no-dandruff controls. Taken together these two studies indicate that the quality and resilience of the epidermal water barrier is impaired in the scalp of dandruff sufferers. We propose that the perturbed barrier leaves dandruff sufferers more prone to the adverse effects of microbial and fungal toxins, and environmental pollutants, thus perpetuating their impaired barrier.

  13. Decreased glutathione levels and antioxidant enzyme activities in untreated and treated schizophrenic patients.

    PubMed

    Raffa, Monia; Mechri, Anwar; Othman, Leila Ben; Fendri, Chiraz; Gaha, Lotfi; Kerkeni, Abdelhamid

    2009-10-01

    There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the physiopathology of schizophrenia. Previous studies have reported the occurrence of impairments in the glutathione levels and the activities of the antioxidant enzymes in patients suffering from schizophrenia. However, most of these studies were performed on treated patients. The present study evaluated treated schizophrenic patients (n=52) along with neuroleptic-free or untreated schizophrenic patients (n=36) and healthy controls (n=46). The blood glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr), and oxidized glutathione (GSSG) as well as the activities of the antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were measured. The psychopathology of the patients was assessed through the Clinical Global Impressions-severity (CGI-severity). The tests revealed that in comparison with the healthy controls, the schizophrenic patients showed significantly lower levels of GSHr, SOD, and CAT. Among the schizophrenic patients, the activities of the antioxidant enzymes SOD and CAT were recorded to be significantly lower in untreated patients than in the treated ones. In addition, the levels of both GSHt and GSHr were found to be inversely correlated with the obtained CGI-severity score. These results evidently suggest that a decrease in the glutathione levels and the activities of the antioxidant enzymes in patients diagnosed with schizophrenia is not related to neuroleptic treatment and could be considered as a biological indicator of the degree of severity of the symptoms of schizophrenia.

  14. 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

  15. Decrease in NTproBNP plasma levels indicates clinical improvement of acute decompensated heart failure.

    PubMed

    Di Somma, Salvatore; Magrini, Laura; Mazzone, Marinella; De Leva, Raffaella; Tabacco, Fabio; Marino, Rossella; Talucci, Veronica; Ferri, Enrico; Forte, Paola; Cardelli, Patrizia; Gentiloni, Nicola; Pittoni, Valerio

    2007-03-01

    Thirty-seven consecutive patients with acute decompensated heart failure (ADHF) admitted to emergency departments for acute dyspnea were investigated. Ten patients with acute exacerbation of chronic obstructive pulmonary disease and 10 patients with hypertension crisis were also included as controls. For each patient, a plasma amino-terminal pro-B-type natriuretic peptide (NTproBNP) concentration measurement was performed at admission, 4, 12, and 24 hours later, and on the day of discharge. In patients with ADHF, the observation of a progressive reduction to a complete relief of symptoms of heart failure was accompanied by a reduction of 58% of NTproBNP plasma levels on the day of discharge. Amelioration of symptoms was accompanied by improvement of physiologic parameters and New York Heart Association functional class. In the control population (chronic obstructive pulmonary disease and hypertension crisis patients), no significant variation of NTproBNP levels in comparison with those at admission was found at each time point. In conclusion, a plasma profile obtained with sequential measurements indicates that a significant decrease in NTproBNP levels is associated with the clinical improvement of patients with ADHF at the time of discharge.

  16. Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells

    PubMed Central

    Boehmelt, Guido; Wakeham, Andrew; Elia, Andrew; Sasaki, Takehiko; Plyte, Sue; Potter, Julia; Yang, Yingju; Tsang, Eric; Ruland, Jürgen; Iscove, Norman N.; Dennis, James W.; Mak, Tak W.

    2000-01-01

    The hexosamine pathway provides UDP-N-acetylhexosamine donor substrates used in cytosolic and Golgi-mediated glycosylation of proteins and for formation of glycosylphosphatidylinositol (GPI) anchors, which tether proteins to the outer plasma membrane. We have recently identified the murine glucosamine-6-phosphate (GlcN6P) acetyltransferase, EMeg32, as a developmentally regulated enzyme on the route to UDP-N-acetylglucosamine (UDP-GlcNAc). Here we describe embryos and cells that have the EMeg32 gene inactivated by homologous recombination. Homozygous mutant embryos die at around embryonic day (E) 7.5 with a general proliferative delay of development. In vitro differentiated EMeg32–/– ES cells show reduced proliferation. Mouse embryonic fibroblasts (MEFs) deficient for EMeg32 exhibit defects in proliferation and adhesiveness, which could be complemented by stable re-expression of EMeg32 or by nutritional restoration of intracellular UDP-GlcNAc levels. Reduced UDP-GlcNAc levels predominantly translated into decreased O-GlcNAc modifications of cytosolic and nuclear proteins. Interestingly, growth-impaired EMeg32–/– MEFs withstand a number of apoptotic stimuli and express activated PKB/AKT. Thus, EMeg32-dependent UDP-GlcNAc levels influence cell cycle progression and susceptibility to apoptotic stimuli. PMID:11013212

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

    PubMed Central

    Hannukainen, Jarna C; Nuutila, Pirjo; 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 V˙O2,max (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 μmol (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

  18. Decreased susceptibility to copper-induced oxidation of rat-lipoproteins after fibrate treatment: influence of fatty acid composition.

    PubMed

    Vázquez, M; Merlos, M; Adzet, T; Laguna, J C

    1996-03-01

    1. The effect of clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on plasma lipoprotein (VLDL and LDL) concentration, composition and resistance to copper-induced oxidation has been studied in male Sprague-Dawley rats after a 15 day treatment. 2. Plasma triglyceride levels were reduced by CFB (41%) and BFB (39%). This effect was related to a significant reduction (67% for CFB and 56% for BFB) in the amount of circulating VLDL-protein. 3. Plasma total cholesterol was reduced by 28% and 45% in CFB- and BFB-treated animals, respectively, mainly by modification of the cholesteryl ester fraction. In contrast, GFB significantly increased total cholesterol (27%). No modification in the LDL protein or lipid content was introduced by fibrates, although GFB decreased the proportion of LDL-triglycerides, at the expense of an increase in total cholesterol. 4. The fatty acid species carried by VLDL and LDL were affected after fibrate treatment. In general, both particles showed an increase in monounsaturated fatty acids (MUFA) (18:1) and a decrease in polyunsaturated fatty acids (PUFA) species (18:2 n-6, 20:4 n-6, 18:3 n-3, 20:5 n-3). As a consequence, the ratio of PUFA/(SFA+MUFA) for the whole lipoproteins was markedly reduced. 5. The degree of copper-induced VLDL- and LDL-oxidation was assessed by means of the analysis of lysine content, thiobarbituric acid reactive substances (TBARS) production and conjugated dienes formation. Lipoproteins obtained from fibrate-treated rats were more resistant to the oxidative challenge. For each lipoprotein, BFB was the most effective drug, followed by CFB and GFB. 6. The observed antioxidant effect can be ascribed to two independent phenomena produced by fibrates: the reduction of the amount of substrate for the oxidation process due to their hypolipidemic activity, and the alteration in the type of fatty acids transported by the lipoproteins towards an enrichment in species resistant to the oxidation process. 7. As similar

  19. Decreased susceptibility to copper-induced oxidation of rat-lipoproteins after fibrate treatment: influence of fatty acid composition.

    PubMed Central

    Vázquez, M.; Merlos, M.; Adzet, T.; Laguna, J. C.

    1996-01-01

    1. The effect of clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on plasma lipoprotein (VLDL and LDL) concentration, composition and resistance to copper-induced oxidation has been studied in male Sprague-Dawley rats after a 15 day treatment. 2. Plasma triglyceride levels were reduced by CFB (41%) and BFB (39%). This effect was related to a significant reduction (67% for CFB and 56% for BFB) in the amount of circulating VLDL-protein. 3. Plasma total cholesterol was reduced by 28% and 45% in CFB- and BFB-treated animals, respectively, mainly by modification of the cholesteryl ester fraction. In contrast, GFB significantly increased total cholesterol (27%). No modification in the LDL protein or lipid content was introduced by fibrates, although GFB decreased the proportion of LDL-triglycerides, at the expense of an increase in total cholesterol. 4. The fatty acid species carried by VLDL and LDL were affected after fibrate treatment. In general, both particles showed an increase in monounsaturated fatty acids (MUFA) (18:1) and a decrease in polyunsaturated fatty acids (PUFA) species (18:2 n-6, 20:4 n-6, 18:3 n-3, 20:5 n-3). As a consequence, the ratio of PUFA/(SFA+MUFA) for the whole lipoproteins was markedly reduced. 5. The degree of copper-induced VLDL- and LDL-oxidation was assessed by means of the analysis of lysine content, thiobarbituric acid reactive substances (TBARS) production and conjugated dienes formation. Lipoproteins obtained from fibrate-treated rats were more resistant to the oxidative challenge. For each lipoprotein, BFB was the most effective drug, followed by CFB and GFB. 6. The observed antioxidant effect can be ascribed to two independent phenomena produced by fibrates: the reduction of the amount of substrate for the oxidation process due to their hypolipidemic activity, and the alteration in the type of fatty acids transported by the lipoproteins towards an enrichment in species resistant to the oxidation process. 7. As similar

  20. 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.

  1. 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

  2. Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia

    PubMed Central

    Malaguarnera, Mariano; Risino, Corrado; Gargante, Maria Pia; Oreste, Giovanni; Barone, Gloria; Tomasello, Anna Veronica; Costanzo, Mario; Cannizzaro, Matteo Angelo

    2006-01-01

    AIM: To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. METHODS: Fifty-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS: When the cachectic patients with gastro-intestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 μmol/L in free carnitine (P < 0.005), 0.04 μmol/L in long chain acylcarnitine (P < 0.05), 8.7 μmol/L in total carnitine (P < 0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2 μmol/L in free carnitine (P < 0.001), 4.60 μmol/L in short chain acylcarnitine (P < 0.001), and 0.60 μmol /L in long-chain acylcarnitine (P < 0.005) and 17.4 μmol/L in total carnitine (P < 0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 μmol/L in free carnitine (P < 0.001), 5.2 μmol /L in short-chain acylcarnitine (P < 0.001), 1.0 μmol/L in long chain acylcarnitine (P < 0.001), and 21.8 μmol/L in total carnitine (P < 0.001). CONCLUSION: Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients. PMID:16874868

  3. Coumarin effects on amino acid levels in mice prefrontal cortex and hippocampus.

    PubMed

    Pereira, Elaine Cristina; Lucetti, Daniel Luna; Barbosa-Filho, José Maria; de Brito, Eliane Magalhães; Monteiro, Valdécio Silvano; Patrocínio, Manoel Cláudio Azevedo; de Moura, Rebeca Ribeiro; Leal, Luzia Kalyne Almeida Moreira; Macedo, Danielle Silveira; de Sousa, Francisca Cléa Florenço; de Barros Viana, Glauce Socorro; Vasconcelos, Silvânia Maria Mendes

    2009-04-24

    Coumarin is a compound known to be present in a wide variety of plants, microorganisms and animal species. Most of its effects were studied in organs and systems other than the central nervous system. The present work evaluated the effect of coumarin administration on the levels of gamma-aminobutyric acid (GABA), glutamate (GLU), glycine (GLY) and taurine (TAU) in the prefrontal cortex and hippocampus of mice. Male Swiss mice were treated with distilled water (controls), coumarin (20 or 40 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). Results showed that in the prefrontal cortex, coumarin at the lowest dose increased the levels of GLU and TAU, while GABA increased with both doses studied and GLY had its levels increased only at the dose of 40 mg/kg. Diazepam (DZP) increased the levels of GABA and TAU and decreased the levels of GLU and GLY in this area. In the hippocampus, only glutamate had its levels decreased after coumarin treatment, while diazepam increased the levels of GABA and TAU and decreased the levels of GLU in this brain region. We concluded that coumarin stimulates the release of endogenous amino acids, increasing the levels of inhibitory and excitatory amino acids in the prefrontal cortex, and decreasing glutamate levels in the hippocampus. Together, these results are of interest, considering that some neurodegenerative diseases and seizures are related to the imbalance of the amino acid levels in the CNS suggesting a perspective of a therapeutic use of coumarins in these disorders.

  4. Oleic acid increases mitochondrial reactive oxygen species production and decreases endothelial nitric oxide synthase activity in cultured endothelial cells.

    PubMed

    Gremmels, Hendrik; Bevers, Lonneke M; Fledderus, Joost O; Braam, Branko; van Zonneveld, Anton Jan; Verhaar, Marianne C; Joles, Jaap A

    2015-03-15

    Elevated plasma levels of free fatty acids (FFA) are associated with increased cardiovascular risk. This may be related to FFA-induced elevation of oxidative stress in endothelial cells. We hypothesized that, in addition to mitochondrial production of reactive oxygen species, endothelial nitric oxide synthase (eNOS)-mediated reactive oxygen species production contributes to oleic acid (OA)-induced oxidative stress in endothelial cells, due to eNOS uncoupling. We measured reactive oxygen species production and eNOS activity in cultured endothelial cells (bEnd.3) in the presence of OA bound to bovine serum albumin, using the CM-H2DCFDA assay and the L-arginine/citrulline conversion assay, respectively. OA induced a concentration-dependent increase in reactive oxygen species production, which was inhibited by the mitochondrial complex II inhibitor thenoyltrifluoroacetone (TTFA). OA had little effect on eNOS activity when stimulated by a calcium-ionophore, but decreased both basal and insulin-induced eNOS activity, which was restored by TTFA. Pretreatment of bEnd.3 cells with tetrahydrobiopterin (BH4) prevented OA-induced reactive oxygen species production and restored inhibition of eNOS activity by OA. Elevation of OA levels leads to both impairment in receptor-mediated stimulation of eNOS and to production of mitochondrial-derived reactive oxygen species and hence endothelial dysfunction.

  5. Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients

    PubMed Central

    Qundos, Ulrika; Drobin, Kimi; Mattsson, Cecilia; Hong, Mun‐Gwan; Sjöberg, Ronald; Forsström, Björn; Solomon, David; Uhlén, Mathias; Nilsson, Peter; Michaëlsson, Karl

    2015-01-01

    Purpose Affinity proteomic approaches by antibody bead arrays enable multiplexed analysis of proteins in body fluids. In the presented study, we investigated blood plasma within osteoporosis to discovery differential protein profiles and to propose novel biomarkers candidates for subsequent studies. Experimental design Starting with 4608 antibodies and plasma samples from 22 women for an untargeted screening, a set of 72 proteins were suggested for further analysis. Complementing these with targets from literature and other studies, a targeted bead array of 180 antibodies was built to profile for 92 proteins in plasma samples of 180 women from two independent population‐based studies. Results Differential profiles between osteoporosis patients and matched controls were discovered for 12 proteins in at least one of the two study sets. Among these targets, the levels of autocrine motility factor receptor (AMFR) were concordantly lower in plasma of female osteoporosis patients. Subsequently, verification of anti‐AMFR antibody selectivity was conducted using high‐density peptide and protein arrays, and Western blotting. Conclusions and clinical relevance Further validation in additional study sets will be needed to determine the clinical value of the observed decrease in AMFR plasma levels in osteoporosis patients, but AMFR may aid our understanding of disease mechanisms and could support existing tools for diagnosis and monitoring of patient mobility within osteoporosis. PMID:25689831

  6. Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: a randomized clinical trial.

    PubMed

    Taslimi, Shervin; Esteghamati, Alireza; Rashidi, Armin; Tavakkoli, Hosein Moin; Nakhjavani, Manouchehr; Kebriaee-Zadeh, Abbas

    2013-02-01

    The effects of metformin and pioglitazone on ghrelin, a physiologic regulator of appetite and food intake, have not been clearly established. In a randomized clinical trial, we randomly assigned 60 type 2 diabetic patients to either metformin (Group A; n=30) or pioglitazone (Group B; n=30) treatment groups. The groups were similar in their baseline characteristics. A standard fasting 75 g oral glucose tolerance test was performed at time zero before starting metformin or pioglitazone, and 3 months later. After 3 months of treatment, pioglitazone, but not metformin, was significantly associated with weight gain. Both groups experienced a significant reduction in fasting plasma glucose (p<0.01), hemoglobin A1c (p<0.01 in Group A and p<0.05 in Group B), and insulin resistance (p<0.01). The effect of metformin on preprandial ghrelin and its response to glucose challenge was not significant, while the pioglitazone group had a significant reduction in preprandial ghrelin levels after treatment (p<0.05). The effect of pioglitazone on ghrelin was independent of changes in body weight, body mass index, glucose control, insulin resistance, and plasma insulin. In conclusion, treatment with pioglitazone is associated with a decrease in preprandial ghrelin levels and therefore, the weight gain and increased food intake related to pioglitazone use cannot be explained by its effects on ghrelin. The effect of pioglitazone on ghrelin is independent of changes in body weight, body mass index, plasma insulin, insulin resistance, or glucose control.

  7. Decreased levels of Fibroblast Growth Factor 21 are correlated with improved hypoglycemia in patients with insulinoma

    PubMed Central

    Li, Xu; Yu, Haoyong; Yin, Jun; Li, Lianxi; Zhou, Jian; Li, Ming; Li, Qing; Chen, Haibing; Liu, Fang; Bao, Yuqian; Han, Junfeng; Jia, Weiping

    2017-01-01

    Fibroblast growth factor-21 (FGF-21) improves insulin sensitivity and lipid metabolism in obese or diabetic animal models and has been proposed as a potential therapeutic agent for treating T2DM, obesity, and their related complications. However, little is known about the changes of FGF21 levels in response to endogenous hyperinsulinemic hypoglycemia. To explore its relationship with parameters of glucose metabolism in patients with insulinoma, eleven subjects with pathological insulinoma and twenty-two healthy subjects were recruited for this study. Interestingly, we found that the serum FGF21 levels increased significantly in patients with insulinoma at baseline compared with the control group (381.36 ± 107.12 vs. 62.59 ± 10.48 pg/mL; P = 0.001). Furthermore, FGF21 was positively correlated with insulin (r = 0.80, P = 0.003) and proinsulin (r = 0.72, P = 0.012) in subjects with insulinoma. Multiple stepwise regression analysis showed that FGF21 was independently associated with insulin (β = 0.80, P = 0.003). In addition, FGF21 decreased significantly after surgery, and its change was still correlated positively with the changes in insulin (r = 0.61, P = 0.048) and proinsulin (r = 0.84, P = 0.001). These findings suggested that the serum FGF21 levels could be involved in a complex adaptive response to insulin secretion and glucose metabolism in humans. PMID:28225059

  8. 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.

  9. Daidzin, an antioxidant isoflavonoid, decreases blood alcohol levels and shortens sleep time induced by ethanol intoxication.

    PubMed

    Xie, C I; Lin, R C; Antony, V; Lumeng, L; Li, T K; Mai, K; Liu, C; Wang, Q D; Zhao, Z H; Wang, G F

    1994-12-01

    The extract from an edible vine, Pueraria lebata, has been reported to be efficacious in lessening alcohol intoxication. In this study, we have tested the efficacy of one of the major components, daidzin, from this plant extract. When ethanol (40% solution, 3 g/kg body weight) was given to fasted rats intragastrically, blood alcohol concentration (BAC) peaked at 30 min after alcohol ingestion and reached 1.77 +/- 0.14 mg/ml (mean values +/- SD, n = 6). If daidzin (30 mg/kg) was mixed with the ethanol solution and given to animals intragastrically, BAC was found to peak at 90 min after alcohol ingestion and reached only 1.20 +/- 0.30 mg/ml (n = 6) (p < 0.05 vs. controls). The ability of daidzin to delay and decrease peak BAC level after ethanol ingestion was also observed in fed animals. In both fasted and fed rats given alcohol without daidzin, BAC quickly declined after reaching its peak at 30 min. By contrast, BAC levels receded more slowly if daidzin was also fed to the animals. Daidzin showed a chronic effect. Rats fed daidzin for 7 days before ethanol challenge, but not on the day of challenge, also produced lower and later peak BAC levels. Interestingly, daidzin, whether fed to rats only once or chronically for 7 days, did not significantly alter activities of either alcohol dehydrogenase or mitochondrial aldehyde dehydrogenase in the liver. Further experiments demonstrated that daidzin shortened sleep time for rats receiving ethanol intragastrically (7 g/kg) but not intraperitoneally (2 g/kg). To test whether daidzin delayed stomach-emptying, [14C]polyethylene glycol was mixed with ethanol and fed to rats.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Proper exercise decreases plasma carcinoembryonic antigen levels with the improvement of body condition in elderly women.

    PubMed

    Ko, Il-Gyu; Park, Eung-Mi; Choi, Hye-Jung; Yoo, Jaehyun; Lee, Jong-Kyun; Jee, Yong-Seok

    2014-01-01

    Aging increases the risk of chronic diseases including cancers. Physical exercise has the beneficial effects for the elderly susceptible to the development of cancers, through maintaining a healthy body condition and improving the immune system. However, excessive or insufficient exercise might increase the risk for cancer. In the present study, we investigated what exercise frequency improves cancer-related biomarkers, such as carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), red blood cell (RBC), and white blood cell (WBC), and the body composition of elderly women. Fifty-four females, aged 70 to 77 years, were divided into 4 groups: control, 1-day exercise (1E), 2-3-day exercise (2-3E), and 5-day exercise (5E) groups. The control group did not participate in any physical activity, while the subjects in the exercise groups underwent the exercise program for 12 weeks. As results, CEA was significantly decreased in the exercise groups, with the lowest values in 2-3E group. In contrast, AFP, RBC and WBC were not significantly changed. CEA is an oncofetal glycoprotein that is overexpressed in adenocarcinomas. Although the function of CEA has not been fully understood, CEA has been suggested to be involved in the release of pro-inflammatory cytokines via stimulating monocytes and macrophages. Moreover, body weight and body mass index were improved in the exercise groups, with the lowest levels in 5E group. Thus, we suggest that exercise for 2-3 days per week decreases the expression of CEA and improves body condition, without loading fatigue or stress, which may contribute to preventing cancer in the elderly women.

  11. 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

  12. TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity.

    PubMed

    Sosa-Pagán, Jason O; Iversen, Edwin S; Grandl, Jörg

    2017-04-03

    Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. One hypothesized mechanism assumes that temperature activation is driven by the exposure of hydrophobic residues to solvent. This mechanism further predicts that residues are exposed to solvent in a coordinated fashion, but without necessarily being located in close proximity to each other. However, there is little experimental evidence supporting this mechanism in TRP channels. Here, we combined high-throughput mutagenesis, functional screening, and deep sequencing to identify mutations from a total of ~7,300 TRPV1 random mutant clones. We found that strong decreases in hydrophobicity of amino acids are better tolerated for activation by capsaicin than for activation by hot temperature, suggesting that strong hydrophobicity might be specifically required for temperature activation. Altogether, our work provides initial correlative support for a previously hypothesized temperature mechanism in TRP ion channels.

  13. Circulating Levels of Uric Acid and Risk for Metabolic Syndrome.

    PubMed

    Rubio-Guerra, Alberto F; Morales-López, Herlinda; Garro-Almendaro, Ana K; Vargas-Ayala, German; Durán-Salgado, Montserrat B; Huerta-Ramírez, Saul; Lozano-Nuevo, Jose J

    2017-01-01

    Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid, both mechanisms link elevated serum uric acid with metabolic syndrome. The aim of this study is to evaluate the probability for the development of metabolic syndrome in low-income young adults with hyperuricaemia.

  14. 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

  15. Omega-3 fatty acids decreases oxidative stress, tumor necrosis factor-alpha, and interleukin-1 beta in hyperthyroidism-induced hepatic dysfunction rat model.

    PubMed

    Gomaa, Asmaa M S; Abd El-Aziz, Ebtihal A

    2016-12-01

    Hyperthyroidism is associated with abnormalities of the liver. Omega-3 polyunsaturated fatty acids, especially their long-chain forms: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial health effects. The objectives of the present study were to assess hyperthyroidism-induced hepatic dysfunction in adult male rats and to evaluate the ameliorative effects of omega-3 on hyperthyroidism-induced hepatic dysfunction and the underlying mechanisms. Twenty four adult male rats were randomly divided into three equal groups; control group which received water for 6 weeks, hyperthyroid group which received L-thyroxine orally for 6 weeks and hyperthyroid omega-3 treated group which received L-thyroxine for 2 weeks and then co-treated with L-thyroxine and omega-3 oral compound containing 18% of EPA and 12% of DHA for 4 weeks. Hyperthyroid omega-3 treated group showed significantly increased final body weight and body weight gain, decreased liver weight to body weight ratio, decreased serum triiodo-l-thyronine level, increased serum thyroid stimulating hormone level, decreased serum levels of alanine transaminase, aspartate transaminase and tumor necrosis factor-alpha, increased hepatic levels of total antioxidant capacity and decreased hepatic levels of total peroxide and interleukin-1 beta when compared with the hyperthyroid group. Furthermore, histopathological studies revealed also marked improvement. We concluded that omega-3 had encouraging therapeutic effects against hyperthyroidism-induced hepatic dysfunction attributable to more than one mechanism: antioxidant, anti-inflammatory and anti-fibrotic effects.

  16. YM155 reverses cisplatin resistance in head and neck cancer by decreasing cytoplasmic survivin levels

    PubMed Central

    Kumar, Bhavna; Yadav, Arti; Lang, James C.; Cipolla, Michael; Schmitt, Alessandra C.; Arradaza, Nicole; Teknos, Theodoros N.; Kumar, Pawan

    2013-01-01

    Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of head and neck squamous cell carcinoma (HNSCC). However, acquisition of cisplatin resistance is common in patients with HNSCC and it often leads to local and distant failure. In this study, we demonstrate that survivin expression is significantly upregulated in HNSCC primary tumors and cell lines. In addition, survivin levels were significantly higher in HPV negative patients that normally respond poorly to cisplatin treatment. Survivin expression was further increased in cisplatin resistant cells (CAL27-CisR) as compared to its parent cells (CAL27). Therefore, we hypothesize that targeting of survivin in HNSCC could reverse the resistant phenotype in tumor cells thereby enhancing the therapeutic efficacy of cisplatin. We used both in vitro and in vivo models to test the efficacy of YM155, a small molecule survivin inhibitor, either as a single agent or in combination with cisplatin. YM155 significantly decreased survivin levels and cell proliferation in a dose-dependent manner. In addition, YM155 pretreatment significantly reversed cisplatin resistance in cancer cells. Interestingly, YM155 treatment altered the dynamic localization of survivin in cells by inducing a rapid reduction in cytoplasmic survivin, which plays a critical role in its anti-apoptotic function. In a SCID mouse xenograft model, YM155 significantly enhanced the anti-tumor and anti-angiogenic effects of cisplatin with no added systemic toxicity. Taken together, our results suggest a potentially novel strategy to use YM155 to overcome the resistance in tumor cells thereby enhancing the effectiveness of the chemotherapy in HNSCC. PMID:22723337

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

    PubMed

    Louisse, Jochem; Bai, Yanqing; Verwei, Miriam; van de Sandt, Johannes J M; Blaauboer, Bas J; 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(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(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(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(+)/H(+)-antiporter, corroborating an important role of the pH(i) in the embryotoxic mechanism of both compounds. Together, the results presented indicate that a decrease of the pH(i) may be the mechanism of embryotoxicity of the alkoxyacetic acid metabolites of the glycol ethers.

  18. 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.

  19. Social isolation after stroke leads to depressive-like behavior and decreased BDNF levels in mice.

    PubMed

    O'Keefe, Lena M; Doran, Sarah J; Mwilambwe-Tshilobo, Laetitia; Conti, Lisa H; Venna, Venugopal R; McCullough, Louise D

    2014-03-01

    Social isolation prior to stroke leads to poorer outcomes after an ischemic injury in both animal and human studies. However, the impact of social isolation following stroke, which may be more clinically relevant as a target for therapeutic intervention, has yet to be examined. In this study, we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice. Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety. Therefore, it is important to identify patients who have perceived isolation post-stroke to hopefully prevent this exacerbation of histological damage and subsequent depression.

  20. Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.

    PubMed

    Erin, Nuray; Duymuş, Ozlem; Oztürk, Saffet; Demir, Necdet

    2012-11-10

    Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod.

  1. Distraction sneakers decrease the expected level of aggression within groups: a game-theoretic model.

    PubMed

    Dubois, Frédérique; Giraldeau, Luc-Alain; Hamilton, Ian M; Grant, James W A; Lefebvre, Louis

    2004-08-01

    Hawk-dove games have been extensively used to predict the conditions under which group-living animals should defend their resources against potential usurpers. Typically, game-theoretic models on aggression consider that resource defense may entail energetic and injury costs. However, intruders may also take advantage of owners who are busy fighting to sneak access to unguarded resources, imposing thereby an additional cost on the use of the escalated hawk strategy. In this article we modify the two-strategy hawk-dove game into a three-strategy hawk-dove-sneaker game that incorporates a distraction-sneaking tactic, allowing us to explore its consequences on the expected level of aggression within groups. Our model predicts a lower proportion of hawks and hence lower frequencies of aggressive interactions within groups than do previous two-strategy hawk-dove games. The extent to which distraction sneakers decrease the frequency of aggression within groups, however, depends on whether they search only for opportunities to join resources uncovered by other group members or for both unchallenged resources and opportunities to usurp.

  2. 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.

  3. High dietary calcium level decreases colonic phytate degradation in pigs fed a rapeseed diet.

    PubMed

    Sandberg, A S; Larsen, T; Sandström, B

    1993-03-01

    The degradation of phytate (inositol hexaphosphate) in rapeseed meal diet not containing phytase activity was studied in 15 growing ileum-fistulated pigs. Stomach and small intestinal degradation and total gastrointestinal degradation were compared. The effect of addition of calcium carbonate to the rapeseed meal diet at two levels (9.2 and 18.5 g/kg diet) was investigated. A commercial barley-wheat-soybean diet with intrinsic phytase activity was used as reference. Phytate and its hydrolysis products in diets, ileal digesta and feces were determined by HPLC ion-pair chromatography. Hydrolysis of phytate in the stomach and small intestine was 35-45% in pigs fed the rapeseed meal diet independent of calcium addition, and 65% in pigs fed the reference diet. Total gastrointestinal degradation of phytate in pigs fed the rapeseed diet was 97, 77 and 42% (P < 0.001) when calcium intakes were 4.5, 9.9 and 15 g/d, respectively; total gastrointestinal degradation was 72% in pigs fed the reference diet. The intestinal phytate degradation pattern, when rapeseed diet was fed, indicated the activity of an unspecific phosphatase, whereas that of the reference diet indicated intrinsic dietary phytase activity. We conclude that dietary supplementation of calcium carbonate decreases the phytate degradation in the colon of pigs, but not in the stomach and small intestine.

  4. Social isolation after stroke leads to depressive-like behavior and decreased BDNF levels in mice

    PubMed Central

    O’Keefe, Lena M.; Doran, Sarah J.; Mwilambwe-Tshilobo, Laetitia; Conti, Lisa H.; Venna, Venugopal R.; McCullough, Louise D.

    2014-01-01

    Social isolation in the pre-stroke environment leads to poorer outcomes after an ischemic injury in both animal and human studies. However, the impact of social isolation following stroke, which may be more clinically relevant as a target for therapeutic intervention, has yet to be examined. In this study, we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice. Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety. Therefore, it is important to identify patients who have perceived isolation post-stroke to hopefully prevent this exacerbation of histological damage and subsequent depression. PMID:24211537

  5. Spray-dried milk supplemented with alpha-linolenic acid or eicosapentaenoic acid and docosahexaenoic acid decreases HMG Co A reductase activity and increases biliary secretion of lipids in rats.

    PubMed

    Ramaprasad, Talahalli R; Srinivasan, Krishnapura; Baskaran, Vallikannan; Sambaiah, Kari; Lokesh, Belur R

    2006-05-01

    In our earlier study, we have shown that rats fed spray-dried milk containing alpha-linolenic acid (LNA 18:3 n-3) or eicosapentaenoic acid (EPA 20:5 n-3) and docosahexaenoic acid (DHA 22:6 n-3) had significantly lower amounts of serum and liver cholesterol. To evaluate the mechanism for hypocholesterolemic effect of n-3 fatty acids containing milk formulation, we fed male Wistar rats with spray-dried milk containing linseed oil (LSO) (source of LNA) or fish oil (FO) (source of EPA+DHA) for 8 weeks. Feeding n-3 fatty acid containing milk formulation lowered the hepatic 3-hydroxy-methylglutaryl coenzyme A (HMG Co A) activity by 17-22% compared to rats given control diet devoid of n-3 fatty acids. The cholesterol level in liver microsomes was found to be decreased by 16% and 20%, respectively, in LSO and FO containing formulation fed rats. The bile flow was enhanced to an extent of 19-23% in experimental groups compared to control animals. The biliary cholesterol and phospholipid secretion was increased to an extent of 49-55% and 140-146%, respectively, in rats fed n-3 fatty acid containing formulation. The increase in the total bile acids secretion in bile was mainly reflected on an increase in the levels of taurine conjugated bile acids. These results indicated that n-3 fatty acid containing spray-dried milk formulation would bring about the hypocholesterolemic effect by lowering HMG Co A reductase activity in liver and by increasing the secretion of bile constituents.

  6. Milk acidification by Lactococcus lactis is improved by decreasing the level of dissolved oxygen rather than decreasing redox potential in the milk prior to inoculation.

    PubMed

    Jeanson, Sophie; Hilgert, Nadine; Coquillard, Marie-Odile; Seukpanya, Céline; Faiveley, Marc; Neveu, Pascal; Abraham, Christophe; Georgescu, Véra; Fourcassié, Pascal; Beuvier, Eric

    2009-04-30

    Although redox potential is very rarely taken into account in food fermentation it could be as influential as pH on bacterial activities. Lactococcus lactis is already known to exhibit a powerful reducing activity in milk but its reduction activity was shown to occur prior to its acidification activity with a potential interaction between these two lactococcal activities. Therefore, acidification lag-type phase could be shortened by decreasing the redox potential of milk before inoculation. As the redox potential is highly dependent on the dissolved oxygen level, our objective was to study their separate and combined influences on acidification and growth kinetics of pure L. lactis strains in milk. Results showed that high level of dissolved oxygen is significantly more influential on growth, and even more on acidification kinetics, than initial decreased redox potential of milk. Reduction of milk was drastic and mostly due to bacterial activity. The redox potential of milk only dropped when dissolved oxygen was entirely consumed. When there was no dissolved oxygen from the beginning, L. lactis immediately decreased the redox potential of milk and acidified afterwards. When the level of dissolved oxygen was initially high, acidification and reduction of milk occurred at the same time. Acidification kinetics was then biphasic with a slower rate during the aerobic stage and a faster rate during the anaerobic stage. The seven strains tested demonstrated diversity in both their acidification kinetics and their adaptation to high level of dissolved oxygen, independent of their growth kinetics. To conclude, we have shown that the level of dissolved oxygen in milk has a dramatic influence on acidification kinetics and could be used to control acidification kinetics in dairy industries.

  7. Hormone-sensitive lipase activity and triacylglycerol hydrolysis are decreased in rat soleus muscle by cyclopiazonic acid.

    PubMed

    Watt, Matthew J; Steinberg, Gregory R; Heigenhauser, G J F; Spriet, Lawrence L; Dyck, David J

    2003-08-01

    Cyclopiazonic acid (CPA) is a sarcoplasmic reticulum Ca2+-ATPase inhibitor that increases intracellular calcium. The role of CPA in regulating the oxidation and esterification of palmitate, the hydrolysis of intramuscular lipids, and the activation of hormone-sensitive lipase (HSL) was examined in isolated rat soleus muscles at rest. CPA (40 micro M) was added to the incubation medium to levels that resulted in subcontraction increases in muscle tension, and lipid metabolism was monitored using the previously described pulse-chase procedure. CPA did not alter the cellular energy state, as reflected by similar muscle contents of ATP, phosphocreatine, free AMP, and free ADP. CPA increased total palmitate uptake into soleus muscle (11%, P < 0.05) and was without effect on palmitate oxidation. This resulted in greater esterification of exogenous palmitate into the triacylglycerol (18%, P < 0.05) and phospholipid (89%, P < 0.05) pools. CPA decreased (P < 0.05) intramuscular lipid hydrolysis, and this occurred as a result of reduced HSL activity (20%, P < 0.05). Incubation of muscles with 3 mM caffeine, which is also known to increase Ca2+ without affecting the cellular energy state, reduced HSL activity (24%, P < 0.05). KN-93, a calcium/calmodulin-dependent kinase inhibitor (CaMKII), blocked the effects of CPA and caffeine, and HSL activity returned to preincubation values. The results of the present study demonstrate that CPA simultaneously decreases intramuscular triacylglycerol (IMTG) hydrolysis and promotes lipid storage in isolated, intact soleus muscle. The decreased IMTG hydrolysis is likely mediated by reduced HSL activity, possibly via the CaMKII pathway. These responses are not consistent with the increased hydrolysis and decreased esterification observed in contracting muscle when substrate availability and the hormonal milieu are tightly controlled. It is possible that more powerful signals or a higher [Ca2+] may override the lipid-storage effect of the CPA

  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. Yi-gan san restores behavioral alterations and a decrease of brain glutathione level in a mouse model of schizophrenia.

    PubMed

    Makinodan, Manabu; Yamauchi, Takahira; Tatsumi, Kouko; Okuda, Hiroaki; Noriyama, Yoshinobu; Sadamatsu, Miyuki; Kishimoto, Toshifumi; Wanaka, Akio

    2009-01-01

    The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

  10. 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.…

  11. Valproic acid decreases the reparation capacity of irradiated MOLT-4 cells.

    PubMed

    Muthna, D; Vavrova, J; Lukasova, E; Tichy, A; Knizek, J; Kohlerova, R; Mazankova, N; Rezacova, M

    2012-01-01

    The aim of our work was to evaluate mechanisms leading to radiosensitization of MOLT-4 leukemia cells following valproic acid (VA) treatment. Cells were pretreated with 2 mM VA for 24 h followed by irradiation with a dose of 0.5 or 1 Gy. The effect of both noxae, alone and combined, was detected 1 and 24 hours after the irradiation. Induction of apoptosis was evaluated by a flow cytometry. The extent of DNA damage was further determined by phosphorylation of histone H2AX using confocal microscopy. Changes in protein expression were identified by SDS-PAGE/immunoblotting. Two-millimolar VA increased apoptosis induction after irradiation as well as phosphorylation of H2AX and provokes an increase in the level of p53 and its phosphorylation at Ser392 in 4 h post-irradiation. Likewise, p21 protein reached its maximal expression in 4 h after the irradiation of VA-treated cells. Twenty four hours later, only the p53 phosphorylated at Ser15 was detected. At the same time, the protein mdm2 (negative regulator of p53) was maximally activated. The 24-hour treatment of MOLT-4 leukemia cells with 2 mM VA results in radiosensitizing, increases apoptosis induction, H2AX phosphorylation, and also p53 and p21 activation.

  12. 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.

  13. Decreased levels of heat shock proteins in gut epithelial cells after exposure to plant lectins

    PubMed Central

    Ovelgonne, J; Koninkx, J; Pusztai, A; Bardocz, S; Kok, W; Ewen, S; Hendriks, H; van Dijk, J E

    2000-01-01

    of heat induced heat shock protein synthesis, and total protein synthesis was not impaired indicating specific inhibition of HSP synthesis in non-stressed cells.
CONCLUSIONS—We conclude that PHA and WGA decrease levels of stress proteins in rat gut and enterocyte-like Caco-2 cells, leaving these cells less well protected against the potentially harmful content of the gut lumen.


Keywords: gut; rat small intestine; Caco-2 cells; lectins; stress proteins; heat shock proteins; heat shock PMID:10764712

  14. Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels

    PubMed Central

    Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

    2014-01-01

    Objective Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. Methods The [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Results Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Conclusions Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications. PMID:23899625

  15. Synovial fluid lactic acid levels in septic arthritis.

    PubMed

    Riley, T V

    1981-01-01

    Synovial fluid lactic acid estimations were carried out on 50 samples by gas liquid chromatography. Specimens from 4 patients with bacteria arthritis, other than gonococcal, had a mean lactic acid concentration of 215 mg/dl. One patient with gonococcal arthritis had a synovial fluid lactic acid of 30 mg/dl. Forty-one patients with inflammatory arthritis and 4 patients with degenerative arthritis had mean synovial fluid lactic acid levels of 27 and 23 mg/dl respectively. The estimation of synovial fluid lactic acid is reliable in differentiating septic arthritis from inflammatory and degenerative arthritis except when the infecting organism is NEisseria gonorrhoeae.

  16. Chronic Depression of Serum Sialic Acid Levels in Alloxan-Induced Diabetes

    DTIC Science & Technology

    1974-10-01

    Serum L- Fucose , Protein-Bound Hexose, and Total Protein Levels in Alloxan Diabetic and Control Rats at Various Time Intervals After Treatment 5...ABSTRACT This study was performed to determine whether alloxan treatment of rats alters levels of the terminal carbohydrate residues L- fucose and...occurs with no apparent alteration in the level of L- fucose . The depression in sialic acid level may be attributed in part to decreased activities of

  17. Cerebrospinal fluid ascorbic acid levels in neurological disorders.

    PubMed

    Brau, R H; García-Castiñeiras, S; Rifkinson, N

    1984-02-01

    The ascorbic acid/dehydroascorbic acid system was analyzed in the cerebrospinal fluid (CSF) of 41 patients with different neurological disorders. The chi-square test of covariance analysis revealed in this sample significant differences in the CSF levels of total ascorbic acid when patients were classified by diagnostic categories. The population analyzed contained a group of 18 patients (back pain/sciatica group) in whom no overt neurological abnormalities were disclosed upon evaluation. Taking the CSF levels of total ascorbic acid and dehydroascorbic acid in these patients as the reference (3.57 +/- 0.87 (SD)/100 ml and 0.53 +/- 0.19 mg/100 ml, respectively), it was found that head-traumatized patients showed a significant reduction in the concentration of total ascorbic acid in the CSF. CSF ascorbic acid levels were also significantly lower in patients with increased intracranial pressure (noninfected hydrocephalus group) and in patients with cerebral tumors. Although the CSF concentration of dehydroascorbic acid did not correspondingly increase over the reference values in these three groups of patients, the tendency existed for dehydroascorbic acid to represent in them a higher percentage of total ascorbic acid. After examining different alternatives, it is concluded that the hypothesis of free radical damage to the central nervous system after certain types of injury (trauma, ischemia, and tumors) may provide a satisfactory explanation of our findings. A rationale for the use of vitamin C in the management of some neurological patients is also derived from this work.

  18. d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.

    PubMed

    Weatherly, Choyce A; Du, Siqi; Parpia, Curran; Santos, Polan T; Hartman, Adam L; Armstrong, Daniel W

    2017-02-16

    The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels. Total amino acid levels (l- plus d-enantiomers) in brain tissue are up to 10 times higher than in blood. However, all measured d-amino acid levels in brain tissue are typically ∼10 to 2000 times higher than blood levels. There was a 13% reduction in almost all measured d-amino acid levels in the cortex compared to those in the hippocampus. There is an approximate inverse relationship between the prevalence of an amino acid and the percentage of its d-enantiomeric form. Interestingly, glutamic acid, unlike all other amino acids, had no quantifiable level of its d-antipode. The bioneurological reason for the unique and conspicuous absence/removal of this d-amino acid is yet unknown. However, results suggest that d-glutamate metabolism is likely a unidirectional process and not a cycle, as per the l-glutamate/glutamine cycle. The results suggest that there might be unreported d-amino acid racemases in mammalian brains. The regulation and function of specific other d-amino acids are discussed.

  19. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis.

    PubMed

    Svahn, Sara L; Ulleryd, Marcus A; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov; Johansson, Maria E

    2016-04-01

    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics,S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival.

  20. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis

    PubMed Central

    Ulleryd, Marcus A.; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov

    2016-01-01

    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics, S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus. Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival. PMID:26857576

  1. The Effects of Lowering Uric Acid Levels Using Allopurinol on Components of Metabolic Syndrome

    PubMed Central

    Heimbach, Esther J.; Bowden, Rodney G.; Griggs, Jackson O.; Beaujean, A. Alexander; Doyle, Eva I.; Doyle, Robert D.

    2012-01-01

    Background Researchers have reported an independent direct relationship between lipid levels and hyperuricemia with MetS. The purpose of this study was to determine the relationship between serum uric acid levels and lipids among patients on allopurinol. Methods A retrospective secondary data analysis was conducted on 66 adult patients from a family health clinic in Central Texas. Medical records used were recorded during a nine year period (2002 - 2010) ascertaining the relationship between uric acid and lipids. Results Spearman correlations revealed a weak correlation between uric acid and total cholesterol, a weak correlation between uric acid and triglycerides and LDL-C. A weak inverse correlation was discovered between uric acid and HDL-C. A moderate correlation was discovered when all lipid variables combined were compared to uric acid. Conclusions We discovered LDL-C and triglycerides to be significant predictors of uric acid with weak correlations. Additionally, weak correlations existed between uric acid and total cholesterol and HDL-C with an inverse relationship discovered with HDL-C. These findings support the literature suggesting that uric acid is more likely to be associated with total cholesterol and triglycerides. In addition, new discoveries serve as an indication that LDL-C may also be associated with uric acids levels. The mechanism by which uric acid may regulate lipids is elusive but suggestions have included suppression of lipid peroxidase and decreases in critical lipase activity.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. [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.

  8. 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…

  9. Educational level and decreases in leisure time physical activity: predictors from the longitudinal GLOBE study

    PubMed Central

    Droomers, M; Schrijvers, C; Mackenbach, J

    2001-01-01

    STUDY OBJECTIVE—This study describes educational differences in decreases in leisure time physical activity among an adult, physically active population and additionally attempts to identify predictors of these differences from information on health status and individual and environmental factors.
DESIGN—Prospective population based study. Baseline measurement were carried out in 1991 and follow up in 1997.
SETTING—South eastern part of the Netherlands.
PARTICIPANTS—The study included 3793 subjects who were physically active in 1991 and who participated in the follow up.
METHODS—Potential predictors of decreasing physical activity were measured in 1991. Logistic regression analyses were carried out for two age groups (<45 years; ⩾45 years) separately.
MAIN RESULTS—Lower educated respondents experienced statistically significant higher odds to decrease physical activity during follow up, compared with respondents with higher vocational schooling or a university degree. Perceived control was the main predictor of educational differences in decreasing physical activity in both age groups. In the older group, material problems and a poor perceived health experienced by lower educated people additionally predicted educational differences in decreases in physical activity during leisure time.
CONCLUSIONS—These findings have important implications for health promotion practice and policy to prevent socioeconomic differences in physical inactivity and health. There is a need for evidence-based interventions that improve perceived control and reduce material problems in lower educated groups.


Keywords: educational status; physical activity; socioeconomic status PMID:11449013

  10. 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.

  11. 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.

  12. 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

  13. Antibacterial drug treatment increases intestinal bile acid absorption via elevated levels of ileal apical sodium-dependent bile acid transporter but not organic solute transporter α protein.

    PubMed

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

    2015-01-01

    Antibacterial drug treatment increases the bile acid pool size and hepatic bile acid concentration through the elevation of hepatic bile acid synthesis. However, the involvement of intestinal bile acid absorption in the increased bile acid pool size remains unclear. To determine whether intestinal bile acid absorption contributes to the increased bile acid pool in mice treated with antibacterial drugs, we evaluated the levels of bile acid transporter proteins and the capacity of intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) mRNA and protein levels were significantly increased in ampicillin (ABPC)-treated mice, whereas organic solute transporter α (OSTα) mRNA levels, but not protein levels, significantly decreased in mice. Similar alterations in the expression levels of bile acid transporters were observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for intestinal bile acid absorption was evaluated by an in situ loop method. Increased ileal absorption of taurochenodeoxycholic acid was observed in mice treated with ABPC. These results suggest that intestinal bile acid absorption is elevated in an ASBT-dependent manner in mice treated with antibacterial drugs.

  14. Developmental subchronic exposure to diphenylarsinic acid induced increased exploratory behavior, impaired learning behavior, and decreased cerebellar glutathione concentration in rats.

    PubMed

    Negishi, Takayuki; Matsunaga, Yuki; Kobayashi, Yayoi; Hirano, Seishiro; Tashiro, Tomoko

    2013-12-01

    In Japan, people using water from the well contaminated with high-level arsenic developed neurological, mostly cerebellar, symptoms, where diphenylarsinic acid (DPAA) was a major compound. Here, we investigated the adverse effects of developmental exposure to 20mg/l DPAA in drinking water (early period [0-6 weeks of age] and/or late period [7-12]) on behavior and cerebellar development in male rats. In the open field test at 6 weeks of age, early exposure to DPAA significantly increased exploratory behaviors. At 12 weeks of age, late exposure to DPAA similarly increased exploratory behavior independent of the early exposure although a 6-week recovery from DPAA could reverse that change. In the passive avoidance test at 6 weeks of age, early exposure to DPAA significantly decreased the avoidance performance. Even at 12 weeks of age, early exposure to DPAA significantly decreased the test performance, which was independent of the late exposure to DPAA. These results suggest that the DPAA-induced increase in exploratory behavior is transient, whereas the DPAA-induced impairment of passive avoidance is long lasting. At 6 weeks of age, early exposure to DPAA significantly reduced the concentration of cerebellar total glutathione. At 12 weeks of age, late, but not early, exposure to DPAA also significantly reduced the concentration of cerebellar glutathione, which might be a primary cause of oxidative stress. Early exposure to DPAA induced late-onset suppressed expression of NMDAR1 and PSD95 protein at 12 weeks of age, indicating impaired glutamatergic system in the cerebellum of rats developmentally exposed to DPAA.

  15. 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

  16. Victims of lethal hypothermia have decreased levels of thrombomodulin in myocardium and urine.

    PubMed

    Pakanen, Lasse; Kaija, Helena; Kortelainen, Marja-Leena; Särkioja, Terttu; Porvari, Katja

    2015-03-01

    Severe cold stress has been shown to cause changes in the expression and secretion of thrombomodulin (TM), an endothelial protein regulating haemostasis and inflammation. To further evaluate TM as a cold stress indicator, relative TM mRNA and TM protein levels in the myocardium and the concentrations of TM in serum and urine were analysed in different causes of death (hypothermia main cause, n = 80; hypothermia contributory cause, n = 26; cardiovascular disease (CVD) main cause, n = 94; trauma main cause, n = 45; other main cause, n = 25). Urinary catecholamine concentrations and myocardial heat shock factor 1 (HSF1) transcript levels were also studied. The TM mRNA and the TM protein levels in myocardium and urine were significantly lower in hypothermia deaths than those in the controls. Post-mortem interval did not correlate with urinary TM concentration. The sensitivity and specificity of urinary TM assay to detect hypothermia deaths were 70.8 and 70.3 %, respectively. Catecholamine concentrations in urine correlated significantly with TM concentration in urine and TM mRNA levels in all groups excluding CVD deaths. There were no differences in the HSF1 transcript levels and no correlation to TM levels. These findings provide further evidence that cold stress and hypothermia affect TM expression and secretion and that they are possibly linked to catecholamine action. Thus, measuring post-mortem TM levels may provide additional support to diagnosing hypothermia in medico-legal examination. The results may also provide additional knowledge for the treatment of hypothermic patients and the use of hypothermia for medical purposes.

  17. Association between Decreased Klotho Blood Levels and Organic Growth Hormone Deficiency in Children with Growth Impairment

    PubMed Central

    Ben Ami, Michal; Levy-Shraga, Yael; Mazor-Aronovitch, Kineret; Pinhas-Hamiel, Orit; Yeshayahu, Yonatan; Hemi, Rina; Kanety, Hannah; Rubinek, Tami; Modan-Moses, Dalit

    2014-01-01

    Objective Klotho is an aging-modulating protein expressed mainly in the kidneys and choroid plexus, which can also be shed, released into the circulation and act as a hormone. Klotho deficient mice are smaller compared to their wild-type counterparts and their somatotropes show marked atrophy and reduced number of secretory granules. Recent data also indicated an association between klotho levels and growth hormone (GH) levels in acromegaly. We aimed to study the association between klotho levels and GH deficiency (GHD) in children with growth impairment. Design Prospective study comprising 99 children and adolescents (aged 9.0±3.7 years, 49 male) undergoing GH stimulation tests for short stature (height-SDS = −2.1±0.6). Klotho serum levels were measured using an α-klotho ELISA kit. Results Klotho levels were significantly lower (p<0.001) among children with organic GHD (n = 11, 727±273 pg/ml) compared to both GH sufficient participants (n = 59, 1497±754 pg/ml) and those with idiopathic GHD (n = 29, 1645±778 pg/ml). The difference between GHS children and children with idiopathic GHD was not significant. Klotho levels positively correlated with IGF-1- standard deviation scores (SDS) (R = 0.45, p<0.001), but were not associated with gender, pubertal status, age or anthropometric measurements. Conclusions We have shown, for the first time, an association between low serum klotho levels and organic GHD. If validated by additional studies, serum klotho may serve as novel biomarker of organic GHD. PMID:25198618

  18. Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion

    PubMed Central

    Koike, T; Ohara, S; Sekine, H; Iijima, K; Abe, Y; Kato, K; Toyota, T; Shimosegawa, T

    2001-01-01

    BACKGROUND—Helicobacter pylori infection is less prevalent and atrophic gastritis is less extensive in patients with reflux oesophagitis than those without it, but few studies have examined this relationship directly.
AIMS—We investigated the relationship between H pylori infection, acid secretion, and reflux oesophagitis in Japanese subjects.
SUBJECTS—A total of 105 patients with erosive reflux oesophagitis were compared with 105 sex and age matched patients without reflux oesophagitis.
METHODS—The diagnosis of H pylori infection was made by histological examination of gastric mucosal biopsy specimens, rapid urease test, and detection of serum IgG antibodies. Acid secretion was assessed by the endoscopic gastrin test.
RESULTS—H pylori infection was present in 36 patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects (76.2%) (odds ratio 0.163, 95% confidence interval 0.09-0.29). Overall acid secretion was significantly greater in patients with reflux oesophagitis. Among H pylori positive patients, acid secretion was greater in patients with reflux oesophagitis than those without oesophagitis.
CONCLUSION—In Japan, erosive reflux oesophagitis occurs most often in the absence of H pylori infection and gastric hyposecretion. Even in the presence of H pylori infection, reflux oesophagitis is more likely to develop in patients without gastric hyposecretion. H pylori infection may inhibit reflux oesophagitis by inducing hypoacidity.


Keywords: Helicobacter pylori; gastro-oesophageal reflux disease; reflux oesophagitis; acid secretion PMID:11511552

  19. 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.

  20. Decreased levels of muscarinic receptors in bladders from the alcohol preferring rat line

    SciTech Connect

    Smyth, R.J.; Ruggieri, M.R. ); Kiianmaa, K. )

    1992-01-01

    The B{sub max} for ({sup 3}H)QNB binding in the bladders of alcohol preferring (AA) rats was only approximately 60% of that in the alcohol non-preferring (ANA) rats. No significant change in B{sub max} for ({sup 3}H)QNB binding in bladder was observed between alcohol insensitive (AT) and alcohol sensitive (ANT) rats. No significant change in K{sub d} for ({sup 3}H)QNB binding in bladder was observed between the four different rat lines studied. Therefore, alcohol preference but not sensitivity is associated with a decrease in muscarinic receptor density in the rat bladder. Because all of the rats used in this study were ethanol-naive, the decrease in muscarinic receptor density in the bladders of alcohol preferring rats is associated genetic factors inherent to this rat line. Further studies are needed to determine if these observations are tissue specific or specific to the m2 subtype, which predominates in the rat bladder.

  1. High IP-10 levels decrease T cell function in HIV-1-infected individuals on ART

    PubMed Central

    Ramirez, L. A.; Arango, T. A.; Thompson, E.; Naji, M.; Tebas, P.; Boyer, J. D.

    2014-01-01

    HIV-1-infected subjects, despite control of viral replication with ART, have an altered immune cytokine/chemokine milieu. Changes in systemic cytokines and chemokines can alter immune responses. IP-10, in particular, has been associated with pathogenesis in a number of conditions, and we found that IP-10 is increased in serum in subjects who are HIV-1 infected and on stable ART compared with HIV-1-uninfected individuals. In a series of in vitro studies, we found that PBMCs exposed to IP-10 showed a significant decrease in the number of cells capable of secreting IFN-γ, as well as other cytokines, when stimulated with recall antigens. Furthermore, treatment with IP-10 led to decreased antigen-specific calcium signaling and MAPK38 phosphorylation. Importantly, the cytokines, as well as proliferative responses, could be enhanced with an IP-10 Nab. Our findings suggest that IP-10-modulating drugs may potentially enhance T cell responses to vaccination and HIV-1 in HIV+ subjects on ART. PMID:25157027

  2. Amino Acid Correction of Regulatory Volume Decrease Evoked by Hypotonic Stress in Mouse Oocytes In Vitro.

    PubMed

    Pogorelova, M A; Golichenkov, V A; Pogorelova, V N; Panait, A I; Smirnov, A A; Pogorelov, A G

    2015-05-01

    Regulatory volume decrease in response to hypotonic stress is typical of the oocytes and early mouse embryos. Changes in the kinetics of osmotic reaction can be used as a marker of the modulating effect of the incubation medium on transmembrane transport in embryonic cells. Quantitative laser scanning microtomography (QLSM) was used to measure oocyte volume. In this paper, it is shown that addition of 5 μM glycine, taurine, or GABA, as well as ATP to Dulbecco's medium abolished the regulatory volume decrease in mature mouse oocytes.

  3. 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

  4. 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.

  5. 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…

  6. Selection of a Bifidobacterium animalis subsp. lactis Strain with a Decreased Ability To Produce Acetic Acid

    PubMed Central

    Margolles, Abelardo

    2012-01-01

    We have characterized a new strain, Bifidobacterium animalis subsp. lactis CECT 7953, obtained by random UV mutagenesis, which produces less acetic acid than the wild type (CECT 7954) in three different experimental settings: De Man-Rogosa-Sharpe broth without sodium acetate, resting cells, and skim milk. Genome sequencing revealed a single Phe-Ser substitution in the acetate kinase gene product that seems to be responsible for the strain's reduced acid production. Accordingly, acetate kinase specific activity was lower in the low acetate producer. Strain CECT 7953 produced less acetate, less ethanol, and more yoghourt-related volatile compounds in skim milk than the wild type did. Thus, CECT 7953 shows promising potential for the development of dairy products fermented exclusively by a bifidobacterial strain. PMID:22389372

  7. Selection of a Bifidobacterium animalis subsp. lactis strain with a decreased ability to produce acetic acid.

    PubMed

    Margolles, Abelardo; Sánchez, Borja

    2012-05-01

    We have characterized a new strain, Bifidobacterium animalis subsp. lactis CECT 7953, obtained by random UV mutagenesis, which produces less acetic acid than the wild type (CECT 7954) in three different experimental settings: De Man-Rogosa-Sharpe broth without sodium acetate, resting cells, and skim milk. Genome sequencing revealed a single Phe-Ser substitution in the acetate kinase gene product that seems to be responsible for the strain's reduced acid production. Accordingly, acetate kinase specific activity was lower in the low acetate producer. Strain CECT 7953 produced less acetate, less ethanol, and more yoghourt-related volatile compounds in skim milk than the wild type did. Thus, CECT 7953 shows promising potential for the development of dairy products fermented exclusively by a bifidobacterial strain.

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

    PubMed Central

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

    1994-01-01

    We 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. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 Figure 8 PMID:8037208

  9. Failure of various agents to decrease oleic acid pulmonary albumin leak.

    PubMed

    Sugerman, H J; Blocher, C R; Hirsch, J I; Strash, A M; Tatum, J L

    1983-05-01

    Computerized pulmonary gamma scintigraphy has been shown to be a sensitive technique for the measurement of albumin flux in oleic acid pulmonary microvascular injury. In this technique technetium-99m-tagged human serum albumin is administered intravenously and lung:heart radioactivity ratios are constructed. This ratio remains constant unless there is a net flux of albumin from the vascular space into the lung, when a rising ratio is seen, called the "slope of injury" or SI. Gamma scintigraphy provides a method to rapidly screen the ability of various possible therapeutic agents to reduce the flux of albumin in experimental ARDS. In this study, 0.05 ml/kg oleic acid produced a significant increase in the SI. None of the agents tested (30 mg/kg methylprednisolone, 12.5 mg/kg ibuprofen, 4 mg/kg MK-447, a superoxide radical scavenger, or 140 mg/kg calcium gluconate) were able to alter the scintigraphically measured increased albumin flux produced by 0.05 ml/kg oleic acid.

  10. Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats.

    PubMed

    Roglans, Núria; Sanguino, Elena; Peris, Cristina; Alegret, Marta; Vázquez, Manuel; Adzet, Tomás; Díaz, Cristina; Hernández, Gonzalo; Laguna, Juan C; Sánchez, Rosa M

    2002-07-01

    We aimed to investigate the effect of atorvastatin (5 and 30 mg/kg/day for 2 weeks) on hepatic lipid metabolism in a well established model of dietary hypertriglyceridemia, the fructose-fed rat. Fructose feeding (10% fructose in drinking water for 2 weeks) induced hepatic lipogenesis and reduced peroxisome proliferator-activated receptor alpha (PPARalpha) expression and fatty acid oxidation. As a result, plasma and liver triglyceride and plasma apolipoprotein B (apoB) levels were increased. Atorvastatin, 5 and 30 mg/kg during 2 weeks, markedly reduced plasma triglyceride, but decreased apoB levels only at the highest dose tested (50%). Triglyceride biosynthetic enzymes and microsomal triglyceride transfer protein were unchanged, whereas liver PPARalpha, acyl-CoA oxidase, and carnitine palmitoyltransferase I mRNA levels (1.9-, 1.25-, and 3.4-fold, respectively) and hepatic fatty acid beta-oxidation activity (1.25-fold) were increased by atorvastatin at 30 mg/kg. Furthermore, hepatic triglyceride content (45%) and plasma nonesterified fatty acids (NEFAs) (49%) were reduced. These results show for the first time that liver triglyceride increase in fructose-fed rats is linked to decreased expression of PPARalpha, which is prevented by atorvastatin treatment. The increase in PPARalpha expression caused by atorvastatin was associated with reduced liver triglyceride and plasma NEFA levels.

  11. Decreased salivary alpha-amylase levels are associated with performance deficits during sleep loss.

    PubMed

    Pajcin, Maja; Banks, Siobhan; White, Jason M; Dorrian, Jill; Paech, Gemma M; Grant, Crystal; Johnson, Kayla; Tooley, Katie; Fidock, Justin; Kamimori, Gary H; Della Vedova, Chris B

    2017-04-01

    During sleep deprivation, neurobehavioral functions requiring sustained levels of attention and alertness are significantly impaired. Discrepancies between subjective measures of sleepiness and objective performance during sustained operations have led to interest in physiological monitoring of operator performance. Alertness, vigilance, and arousal are modulated by the wake-promoting actions of the central noradrenergic system. Salivary alpha-amylase (sAA) has been proposed as a sensitive peripheral measure of noradrenergic activity, but limited research has investigated the relationship between sAA and performance. In a laboratory-controlled environment, we investigated the relationship between sAA levels, subjective sleepiness, and performance during two days (50h) of total sleep deprivation. Beginning at 09:00, twelve healthy participants (5 females) aged 22.5±2.5years (mean±SD) provided saliva samples, recorded ratings of subjective sleepiness, completed a brief 3-min psychomotor vigilance task (PVT-B) and performed a 40-min simulated driving task, at regular 3h intervals during wakefulness. Ratings of subjective sleepiness exhibited a constant linear increase (p<0.001) during sleep deprivation. In contrast, sAA levels showed a marked diurnal profile, with levels increasing during the day (p<0.001) and steadily declining in the evening and early-morning (p<0.001). PVT-B (mean reaction time and mean slowest 10% reaction time) and simulated driving performance (speed deviation and lane deviation) also exhibited diurnal profiles across the two days of sleep deprivation. Performance peaked in the afternoon (p<0.001) and then steadily worsened as wakefulness continued into the evening and early-morning (p<0.001). Further analysis revealed that higher sAA levels in the hour preceding each performance assessment were associated with better PVT-B and driving performance (p<0.001). These findings suggest that sAA measures may be suitable indicators of performance

  12. Serum uric acid levels and cardiovascular disease: the Gordian knot

    PubMed Central

    Tugores, Antonio; Rodríguez-González, Fayna

    2016-01-01

    Hyperuricemia is defined as serum uric acid level of more than 7 mg/dL and blood levels of uric acid are causally associated with gout, as implicated by evidence from randomized clinical trials using urate lowering therapies. Uric acid as a cardiovascular risk factor often accompanies metabolic syndrome, hypertension, diabetes, dyslipidemia, chronic renal disease, and obesity. Despite the association of hyperuricemia with cardiovascular risk factors, it has remained controversial as to whether uric acid is an independent predictor of cardiovascular disease. To settle this issue, and in the absence of large randomized controlled trials, Mendelian randomization analysis in which the exposure is defined based on the presence or absence of a specific allele that influences a risk factor of interest have tried to shed light on this. PMID:28066631

  13. 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

  14. Decreased glutathione and elevated hair mercury levels are associated with nutritional deficiency-based autism in Oman.

    PubMed

    Hodgson, Nathaniel W; Waly, Mostafa I; Al-Farsi, Yahya M; Al-Sharbati, Marwan M; Al-Farsi, Omar; Ali, Amanat; Ouhtit, Allal; Zang, Tianzhu; Zhou, Zhaohui Sunny; Deth, Richard C

    2014-06-01

    Genetic, nutrition, and environmental factors have each been implicated as sources of risk for autism. Oxidative stress, including low plasma levels of the antioxidant glutathione, has been reported by numerous autism studies, which can disrupt methylation-dependent epigenetic regulation of gene expression with neurodevelopmental consequences. We investigated the status of redox and methylation metabolites, as well as the level of protein homocysteinylation and hair mercury levels, in autistic and neurotypical control Omani children, who were previously shown to exhibit significant nutritional deficiencies in serum folate and vitamin B₁₂. The serum level of glutathione in autistic subjects was significantly below control levels, while levels of homocysteine and S-adenosylhomocysteine were elevated, indicative of oxidative stress and decreased methionine synthase activity. Autistic males had lower glutathione and higher homocysteine levels than females, while homocysteinylation of serum proteins was increased in autistic males but not females. Mercury levels were markedly elevated in the hair of autistic subjects vs. control subjects, consistent with the importance of glutathione for its elimination. Thus, autism in Oman is associated with decreased antioxidant resources and decreased methylation capacity, in conjunction with elevated hair levels of mercury.

  15. Decreased plasma levels of nitric oxide derivatives in obstructive sleep apnoea: response to CPAP therapy

    PubMed Central

    Schulz, R; Schmidt, D; Blum, A; Lopes-Ribeiro, X; Lucke, C; Mayer, K; Olschewski, H; Seeger, W; Grimminger, F

    2000-01-01

    BACKGROUND—Reduced endothelium dependent vasodilation has been reported in patients with obstructive sleep apnoea (OSA) but direct measurements of the most potent naturally occurring vasodilator, nitric oxide (NO) or its derivatives (nitrate and nitrite, NOx), have not yet been performed in these patients.
METHODS—In 21 patients with OSA of mean (SE) age 54 (2) years, body mass index (BMI) 30.9 (1.1) kg/m2, and apnoea-hypopnoea index (AHI) 37 (4)/h, NOx levels were measured in peripheral venous blood samples by chemiluminescence. Blood samples were obtained before and after two nights of continuous positive airway pressure (CPAP) and after 5.5 (1.5) months of follow up. Thirteen age matched, healthy volunteers and 18 patients without OSA but with a similar spectrum of comorbidity served as controls (control groups 1 and 2).
RESULTS—Before CPAP NOx levels were 21.7 (1.5) µM in patients with OSA compared with 42.6 (2.2) µM and 36.7 (1.7) µM in control groups 1 and 2, respectively (p<0.01 for each comparison). NOx concentrations increased to 32.1 (2.7) µM after two nights of CPAP and remained constant at 32.9 (2.3) µM at follow up (p<0.01 compared with levels before CPAP).
CONCLUSIONS—Plasma NOx levels are reduced in OSA and can be increased by short and long term CPAP therapy. Although the precise mechanism underlying this observation remains to be clarified, it may have important implications for the development of cardiovascular disease in patients with OSA and for the life saving effect of CPAP.

 PMID:11083891

  16. Intervening to decrease alcohol abuse at university parties: differential reinforcement of intoxication level.

    PubMed

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

    2004-03-01

    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 intervention parties at the same fratenity house. At the intervention parties, the students were informed they could win a cash prize if their BAC was below .05, and they were given nomograms to aid in monitoring their levels of intoxication. Mean BAC and the percentage of partiers with intoxication levels above .05 were significantly lower at the two intervention parties. More than twice as many partygoers were legally intoxicated (i.e., BAC > .08) at the two baseline parties than at the two intervention parties. indicating a clinically significant impact of the incentive/reward intervention. Greek-life students, in particular, were significantly less intoxicated at intervention parties, compared to baseline parties (p < .001).

  17. Independence of sialic acid levels in normal and malignant growth.

    PubMed

    Khadapkar, S V; Sheth, N A; Bhide, S V

    1975-06-01

    Sialic acid content in breast or tumor tissue and serum of mouse strains that are either susceptible or resistant to breast cancer was measured at various age periods. Sialic acid content was also studied in normal lung tissue and in lung adenoma and hepatoma. Sialic acid levels during nonmalignant growth of a tissue were measured in breast tissue during pregnancy and lactation, and in regenerating liver, as well as in newborn and postnatal liver. The sialic acid content, when expressed per mg of protein, increased in mammary tumor, lung adenoma, and hepatoma. It also increased in nonmalignant growth of breast tissue during pregnancy and lactation and of regenerating liver and postnatal liver. Increase in sialic acid per mg DNA was observed only in lung tumors, regenerating liver, and postnatal liver. It appears that the changes in sialic acid level are independent of the normal or malignant growth of a tissue and that these changes might be the function of the parameter used to express the sialic acid values, i.e., either the DNA content or protein content of a given tissue.

  18. Dietary combination of fish oil and taurine decreases fat accumulation and ameliorates blood glucose levels in type 2 diabetic/obese KK-A(y) mice.

    PubMed

    Mikami, Nana; Hosokawa, Masashi; Miyashita, Kazuo

    2012-06-01

    n-3 Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and taurine are functional compounds abundantly present in seafoods. In this study, we examined the combined effects of EPA- and DHA-rich fish oil and taurine on white adipose tissue (WAT) weight and blood glucose levels in diabetic/obese KK-A(y) mice. After a 4-wk administration of experimental diets (soybean oil or fish oil, supplemented with 0%, 2%, or 4% taurine), the increase in WAT weight of the mice fed the "fish oil + 4% taurine" diet was significantly suppressed compared to the "soybean oil + 4% taurine" and "fish oil only" diets. Serum triglycerides, free fatty acids, and total cholesterol levels decreased by fish oil administration. In addition, fish oil and taurine increased the activity of acyl-CoA oxidase, which is the rate-limiting enzyme of peroxisomal β-oxidation, increased in the liver of KK-A(y) mice. The activity of fatty acid synthase decreased by fish oil diets. Furthermore, blood glucose and insulin levels were significantly lower in the mice fed fish oil than in the soybean oil-fed mice. In fish oil + 4% taurine group, hyperglycemia and hyperinsulinemia were effectively improved in KK-A(y) mice compared to the fish oil only groups. In particular, the combination of fish oil and taurine enhanced the glucose transporter 4 (GLUT4) distribution in the plasma membrane of muscle tissue. These results suggest that EPA- and DHA-rich fish oil, especially in combination with taurine, exhibits preventive effects on WAT weight gain and hyperglycemia in diabetic/obese KK-A(y) mice.

  19. Polyunsaturated Fatty Acid Levels in Maternal Erythrocytes of Japanese Women during Pregnancy and after Childbirth

    PubMed Central

    Kawabata, Terue; Kagawa, Yasuo; Kimura, Fumiko; Miyazawa, Teruo; Saito, Shoji; Arima, Takahiro; Nakai, Kunihiko; Yaegashi, Nobuo

    2017-01-01

    Background: The transport of polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), to the fetus from maternal stores increases depending on the fetal requirements for PUFA during the last trimester of pregnancy. Therefore, maternal blood PUFA changes physiologically with gestational age. However, the changes in PUFA levels in maternal blood erythrocytes during pregnancy and after childbirth have not been fully investigated in a fish-eating population. Objective: To examine the changes of ARA and DHA levels in maternal erythrocytes with the progress of pregnancy and the relationship between maternal and umbilical cord erythrocyte PUFA levels in pregnant Japanese women who habitually eat fish and shellfish. Design: This study was performed as a part of the adjunct study of the Japan Environment and Children’s Study (JECS). The participants were 74 pregnant women. The maternal blood samples were collected at 27, 30, and 36 weeks of pregnancy, and 2 days and 1 month after delivery, and umbilical cord blood was collected at delivery. The fatty acid levels of erythrocytes in these blood samples were determined. Results: ARA and DHA levels in maternal erythrocytes tended to decrease with the progress of pregnancy. While the DHA level decreased further after delivery, the ARA level returned to the value at 27 weeks of pregnancy within 1 month after delivery. The n-3 and n-6 PUFA levels in maternal erythrocytes at 27, 30, and 36 weeks of pregnancy were significantly positively correlated with the corresponding fatty acid levels in umbilical cord erythrocytes. Conclusion: The present findings showed a significant change in erythrocyte PUFA levels during pregnancy and after childbirth in a fish-eating population. The PUFA levels of maternal blood after the second trimester may be a reliable marker for predicting PUFA levels in infants’ circulating blood. PMID:28272345

  20. 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.

  1. Beta-alanine and beta-aminoisobutyric acid levels in two siblings with dihydropyrimidinase deficiency.

    PubMed

    van Kuilenburg, A B P; Stroomer, A E M; Bosch, A M; Duran, M

    2008-06-01

    Dihydropyrimidinase (DHP) deficiency is an inborn error of the pyrimidine degradation pathway, affecting the hydrolytic ring opening of the dihydropyrimidines. In two siblings with a complete DHP deficiency and a variable clinical presentation, a normal concentration of beta-alanine and strongly decreased levels of beta-aminoisobutyric acid were observed in plasma, urine and CSF. No major differences were observed for the concentrations of the beta-amino acids in plasma and urine between the symptomatic and asymptomatic sibling. Thus, the relevance of the shortage of beta-aminoisobutyric acid for the onset of a clinical phenotype in patients with DHP deficiency remains to be established.

  2. Mouse lymphomyeloid cells can function with significantly decreased expression levels of cytochrome C.

    PubMed

    Shilov, E S; Kislyakov, I V; Gorshkova, E A; Zvartsev, R V; Drutskaya, M S; Mufazalov, I A; Skulachev, V P; Nedospasov, S A

    2014-12-01

    Cytochrome c is an indispensable electron carrier in the mitochondrial respiratory chain and also an important mediator of the internal pathway triggering apoptosis. Mice with a complete deficiency of the Cycs gene encoding the somatic cytochrome c die during the embryogenesis. Using the technology of LoxP-cre-dependent tissue-specific recombination, we obtained some mouse strains with significantly reduced expression of cytochrome c in certain cell types ("conditional genetic knockdown"). This knockdown was achieved by abrogation of the normal splicing of the Cycs locus pre-mRNA due to an additional acceptor site inside the stop-cassette neo(r). Previously, we observed embryonic lethality in homozygous mice with the same knockdown of cytochrome c in all cells of the organism. In the present work we studied two novel mouse strains with conditional knockdown of the Cycs gene in T lymphocytes and macrophages. Somewhat surprisingly, the mice of these two strains under normal conditions were not phenotypically different from the wild-type mice, either on the whole organism level or on the level of activity of individual target cells. Thus, the amount of cytochrome c in lymphomyeloid cells does not affect their development and normal functioning.

  3. 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

  4. 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.

  5. Increased anaplerosis of the tricarboxylic acid cycle decreased meal size and energy intake of cows in the postpartum period.

    PubMed

    Gualdrón-Duarte, Laura B; Allen, Michael S

    2017-03-22

    The objective of this study was to determine the effects of anaplerosis of the tricarboxylic acid cycle on feeding behavior and energy intake of cows in the postpartum period. We infused propionic acid (PA) and glycerol (GL) continuously into the abomasum and hypothesized that PA will decrease meal size and energy intake compared with GL because PA enters the tricarboxylic acid cycle, likely stimulating oxidation of acetyl CoA and satiety compared with GL. Three experiments (Exp.) were conducted using 20 Holstein cows between 3 and 22 d postpartum (8 cows in Exp. 1 and 6 cows each for Exp. 2 and 3). Treatments were compared using isoenergetic (Exp. 1, 193 kcal/h) and isomolar (Exp. 2, ∼0.5 mol/h) continuous infusions of PA (99.5%) and GL (99.7%) to the abomasum using a double crossover design with four 2-d infusion periods each, and 2 mol of PA or GL pulse-dosed to the abomasum using a crossover design (Exp. 3). Treatment sequences were assigned alternately to cows based upon date of parturition. Feeding behavior was recorded by a computerized data acquisition system for Exp. 1 and 2. Propionic acid decreased dry matter intake (DMI) compared with GL 16.7 and 23.4% in Exp. 1 and 2, respectively. The decrease in DMI was because PA decreased meal size compared with GL by 12.6 and 15.3% in Exp. 1 and 2, respectively. Propionic acid decreased total metabolizable energy intake (diet plus treatment infusions) compared with GL for both experiments. Compared with PA, GL increased plasma glucose and insulin concentrations for Exp. 2 only. In Exp. 3, PA decreased hepatic acetyl CoA content 34%, whereas GL increased hepatic acetyl CoA content 32%, resulting in lower hepatic acetyl CoA content for PA compared with GL at 30 min (18.0 vs. 36.9 nmol/g), which persisted at 60 min after dosing (21.9 vs. 32.8 nmol/g). Consistent with our hypothesis, the obligatory anaplerotic metabolite PA decreased meal size, DMI, and total metabolizable energy intake compared with GL, likely

  6. Flufenamic acid decreases neuronal excitability through modulation of voltage-gated sodium channel gating.

    PubMed

    Yau, Hau-Jie; Baranauskas, Gytis; Martina, Marco

    2010-10-15

    The electrophysiological phenotype of individual neurons critically depends on the biophysical properties of the voltage-gated channels they express. Differences in sodium channel gating are instrumental in determining the different firing phenotypes of pyramidal cells and interneurons; moreover, sodium channel modulation represents an important mechanism of action for many widely used CNS drugs. Flufenamic acid (FFA) is a non-steroidal anti-inflammatory drug that has been long used as a blocker of calcium-dependent cationic conductances. Here we show that FFA inhibits voltage-gated sodium currents in hippocampal pyramidal neurons; this effect is dose-dependent with IC(50) = 189 μm. We used whole-cell and nucleated patch recordings to investigate the mechanisms of FFA modulation of TTX-sensitive voltage-gated sodium current. Our data show that flufenamic acid slows down the inactivation process of the sodium current, while shifting the inactivation curve ~10 mV toward more hyperpolarized potentials. The recovery from inactivation is also affected in a voltage-dependent way, resulting in slower recovery at hyperpolarized potentials. Recordings from acute slices demonstrate that FFA reduces repetitive- and abolishes burst-firing in CA1 pyramidal neurons. A computational model based on our data was employed to better understand the mechanisms of FFA action. Simulation data support the idea that FFA acts via a novel mechanism by reducing the voltage dependence of the sodium channel fast inactivation rates. These effects of FFA suggest that it may be an effective anti-epileptic drug.

  7. 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.

  8. Short-term manganese inhalation decreases brain dopamine transporter levels without disrupting motor skills in rats.

    PubMed

    Saputra, Devina; Chang, JuOae; Lee, Byeong-Jae; Yoon, Jin-Ha; Kim, Jonghan; Lee, Kyuhong

    2016-01-01

    Manganese (Mn) is used in industrial metal alloys and can be released into the atmosphere during methylcyclopentadienyl manganese tricarbonyl combustion. Increased Mn deposition in the brain after long-term exposure to the metal by inhalation is associated with altered dopamine metabolism and neurobehavioral problems, including impaired motor skills. However, neurotoxic effects of short-term exposure to inhaled Mn are not completely characterized. The purpose of this study is to define the neurobehavioral and neurochemical effects of short-term inhalation exposure to Mn at a high concentration using rats. Male Sprague-Dawley rats were exposed to MnCl2 aerosol in a nose-only inhalation chamber for 3 weeks (1.2 µm, 39 mg/m(3)). Motor coordination was tested on the day after the last exposure using a rotarod device at a fixed speed of 10 rpm for 2 min. Also, dopamine transporter and dopamine receptor protein expression levels in the striatum region of the brain were determined by Western blot analysis. At a rotarod speed of 10 rpm, there were no significant differences in the time on the bar before the first fall or the number of falls during the two-minute test observed in the exposed rats, as compared with controls. The Mn-exposed group had significantly higher Mn levels in the lung, blood, olfactory bulb, prefrontal cortex, striatum, and cerebellum compared with the control group. A Mn concentration gradient was observed from the olfactory bulb to the striatum, supporting the idea that Mn is transported via the olfactory pathway. Our results demonstrated that inhalation exposure to 39 mg/m(3) Mn for 3 weeks induced mild lung injury and modulation of dopamine transporter expression in the brain, without altering motor activity.

  9. 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.

  10. Association of Renal Manifestations with Serum Uric Acid in Korean Adults with Normal Uric Acid Levels

    PubMed Central

    Jung, Dong-Hyuk; Lee, Yong-Jae; Lee, Hye-Ree; Lee, Jung-Hyun

    2010-01-01

    Several studies have reported that hyperuricemia is associated with the development of hypertension and cardiovascular disease. Increasing evidences also suggest that hyperuricemia may have a pathogenic role in the progression of renal disease. Paradoxically, uric acid is also widely accepted to have antioxidant activity in experimental studies. We aimed to investigate the association between glomerular filtration rate (GFR) and uric acid in healthy individuals with a normal serum level of uric acid. We examined renal function determined by GFR and uric acid in 3,376 subjects (1,896 men; 1,480 women; aged 20-80 yr) who underwent medical examinations at Gangnam Severance Hospital from November 2006 to June 2007. Determinants for renal function and uric acid levels were also investigated. In both men and women, GFR was negatively correlated with systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, uric acid, log transformed C reactive protein, and log transformed triglycerides. In multivariate regression analysis, total uric acid was found to be an independent factor associated with estimated GFR in both men and women. This result suggests that uric acid appears to contribute to renal impairment in subjects with normal serum level of uric acid. PMID:21165292

  11. Metformin impairs systemic bile acid homeostasis through regulating SIRT1 protein levels.

    PubMed

    Chen, Qi; Yang, Xiaoying; Zhang, Huabing; Kong, Xingxing; Yao, Lu; Cui, Xiaona; Zou, Yongkang; Fang, Fude; Yang, Jichun; Chang, Yongsheng

    2017-01-01

    Metformin is widely used to treat hyperglycemia. However, metformin treatment may induce intrahepatic cholestasis and liver injury in a few patients with type II diabetes through an unknown mechanism. Here we show that metformin decreases SIRT1 protein levels in primary hepatocytes and liver. Both metformin-treated wild-type C57 mice and hepatic SIRT1-mutant mice had increased hepatic and serum bile acid levels. However, metformin failed to change systemic bile acid levels in hepatic SIRT1-mutant mice. Molecular mechanism study indicates that SIRT1 directly interacts with and deacetylates Foxa2 to inhibit its transcriptional activity on expression of genes involved in bile acids synthesis and transport. Hepatic SIRT1 mutation elevates Foxa2 acetylation levels, which promotes Foxa2 binding to and activating genes involved in bile acids metabolism, impairing hepatic and systemic bile acid homeostasis. Our data clearly suggest that hepatic SIRT1 mediates metformin effects on systemic bile acid metabolism and modulation of SIRT1 activity in liver may be an attractive approach for treatment of bile acid-related diseases such as cholestasis.

  12. High levels of neuroticism are associated with decreased cortical folding of the dorsolateral prefrontal cortex.

    PubMed

    Christoph Schultz, C; Warziniak, Heide; Koch, Kathrin; Schachtzabel, Claudia; Güllmar, Daniel; Reichenbach, Jürgen R; Schlösser, Ralf G; Sauer, Heinrich; Wagner, Gerd

    2017-04-06

    The personality trait neuroticism has been identified as a vulnerability factor for common psychiatric diseases and defining potential neuroanatomical markers for early recognition and prevention strategies is mandatory. Because both personality traits and cortical folding patterns are early imprinted and timely stable there is reason to hypothesize an association between neuroticism and cortical folding. Thus, to identify a putative linkage, we tested whether the degree of neuroticism is associated with local cortical folding in a sample of 109 healthy individuals using a surface-based MRI approach. Based on previous findings we additionally tested for a potential association with cortical thickness. We found a highly significant negative correlation between the degree of neuroticism and local cortical folding of the left dorsolateral prefrontal cortex (DLPFC), i.e., high levels of neuroticism were associated with low cortical folding of the left DLPFC. No association was found with cortical thickness. The present study is the first to describe a linkage between the extent of local cortical folding and the individual degree of neuroticism in healthy subjects. Because neuroticism is a vulnerability factor for common psychiatric diseases such as depression our finding indicates that alterations of DLPFC might constitute a neurobiological marker elevating risk for psychiatric burden.

  13. 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.

  14. 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

  15. Conditioned opioid withdrawal decreases nociceptin/orphanin FQ levels in the frontal cortex and olfactory tubercle.

    PubMed

    Walker, John R; Terenius, Lars; Koob, George F

    2002-08-01

    Clinical evidence suggests that individuals experiencing drug withdrawal can become conditioned to environmental situations, whereby previously neutral stimuli can produce symptoms of withdrawal. It is believed that this "conditioned withdrawal" can have motivational significance, but the neurobiological basis for conditioned withdrawal is unknown. The goal of this study was to determine adaptations in endogenous opioid systems that may be responsible for expression of conditioned withdrawal. Opioid-dependent rats trained to lever press for food were exposed to tone and scent cues in the presence of naloxone or saline. Naloxone but not saline predictably suppressed responding for food. One month later and in a post-dependent state, all rats again were exposed to the cues but not naloxone. The conditioned cues alone suppressed responding for food in the rats previously paired with naloxone, but no suppression was seen in rats previously paired with saline. Radioimmunoassay (RIA) analysis for nociceptin/orphanin FQ (nociceptin), met-enkephalin-Arg-Phe (MEAP), and dynorphin A (dyn A) was performed from dissections of various brain regions of the rats undergoing conditioned withdrawal. Significant reductions in nociceptin peptide levels were seen in the frontal cortex and olfactory tubercle of these rats. Unconditioned opioid withdrawal and unconditioned footshock stress produced different patterns of opioid peptide regulation in separate groups of rats. These results shed light on adaptations of endogenous opioid systems to conditioned cues, stress, and withdrawal, all factors that play a role in motivating drug intake.

  16. 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.

  17. Decreased ovarian reserve in female Sprague-Dawley rats induced by isotretinoin (retinoic acid) exposure.

    PubMed

    Abali, Remzi; Yuksel, Mehmet Aytac; Aktas, Cevat; Celik, Cem; Guzel, Savas; Erfan, Gamze; Sahin, Onder

    2013-08-01

    Isotretinoin is a retinoid widely used for the treatment of severe nodulocystic acne. Although it has broad side effects, there is no well-designed study about its effects on the ovary. This study investigated possible toxic effects of isotretinoin on female gonads. A total of 30 female rats were randomly divided into three equal groups according to the dose of isotretinoin they were administered: 0 mg/kg/day (group 1), 7.5 mg/kg/day (group 2) or 15 mg/kg/day (group 3). Thirty days after the treatment, the effects of isotretinoin on the ovaries were evaluated with serum anti-Müllerian hormone (AMH) concentrations, apoptosis by TUNEL assay and immunohistochemical observations by proliferating cell nuclear antigen (PCNA). The percentage of atretic follicles was calculated for each stage of folliculogenesis. The serum AMH concentrations were found to be lower in both isotretinoin groups. The percentage of atretic follicles in both isotretinoin groups was higher than the control. The number of PCNA-positive granulosa cells was decreased in the isotretinoin groups. The number of ovarian follicles with apoptotic granulosa cells was increased in the experimental groups. These data are the first to identify that exposure of isotretinoin may be responsible for decreased ovarian reserve and toxic effects on rat ovaries.

  18. Sleep and GABA levels in the oral part of rat pontine reticular formation are decreased by local and systemic administration of morphine.

    PubMed

    Watson, C J; Lydic, R; Baghdoyan, H A

    2007-01-05

    Morphine, a mu-opioid receptor agonist, is a commonly prescribed treatment for pain. Although highly efficacious, morphine has many unwanted side effects including disruption of sleep and obtundation of wakefulness. One mechanism by which morphine alters sleep and wakefulness may be by modulating GABAergic signaling in brain regions regulating arousal, including the pontine reticular nucleus, oral part (PnO). This study used in vivo microdialysis in unanesthetized Sprague-Dawley rat to test the hypothesis that mu-opioid receptors modulate PnO GABA levels. Validation of the high performance liquid chromatographic technique used to quantify GABA was obtained by dialyzing the PnO (n=4 rats) with the GABA reuptake inhibitor nipecotic acid (500 microM). Nipecotic acid caused a 185+/-20% increase in PnO GABA levels, confirming chromatographic detection of GABA and demonstrating the existence of functional GABA transporters in rat PnO. Morphine caused a concentration-dependent decrease in PnO GABA levels (n=25 rats). Coadministration of morphine (100 microM) with naloxone (1 microM), a mu-opioid receptor antagonist, blocked the morphine-induced decrease in PnO GABA levels (n=5 rats). These results show for the first time that mu-opioid receptors in rat PnO modulate GABA levels. A second group of rats (n=6) was used to test the hypothesis that systemically administered morphine also decreases PnO GABA levels. I.v. morphine caused a significant (P<0.05) decrease (19%) in PnO GABA levels relative to control i.v. infusions of saline. Finally, microinjections followed by 2 h recordings of electroencephalogram and electromyogram tested the hypothesis that PnO morphine administration disrupts sleep (n=8 rats). Morphine significantly (P<0.05) increased the percent of time spent in wakefulness (65%) and significantly (P<0.05) decreased the percent of rapid eye movement (REM) sleep (-53%) and non-REM sleep (-69%). The neurochemical and behavioral data suggest that morphine may

  19. 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

  20. Apolipoprotein E4 Elicits Lysosomal Cathepsin D Release, Decreased Thioredoxin-1 Levels, and Apoptosis

    PubMed Central

    Persson, Torbjörn; Lattanzio, Francesca; Calvo-Garrido, Javier; Rimondini, Roberto; Rubio-Rodrigo, Marta; Sundström, Erik; Maioli, Silvia; Sandebring-Matton, Anna; Cedazo-Mínguez, Ángel

    2016-01-01

    The major genetic risk factor for Alzheimer’s disease (AD), apolipoprotein E4 (ApoE4), has been suggested to have detrimental effects on neurons, including direct toxicity via apoptosis. Thioredoxin-1 (Trx1) is an endogenous antioxidant protein important for redox regulation and participates in the regulation of apoptosis through the inhibition of apoptosis signal-regulating kinase-1 (Ask-1). In this study, we have investigated the effects of ApoE on Trx1 in the brain. Our results showed that the protein levels of Trx1 were reduced in the hippocampus of ApoE4 targeted replacement (TR) mice compared to ApoE3 TR mice. The reduction was also seen in vitro after treatment of both human primary cortical neurons and neuroblastoma cells with human recombinant ApoE4 (rApoE4). Furthermore, ApoE4 caused a disruption of lysosomal integrity and a shift in the localization of Cathepsin D, an enzyme known to degrade Trx1. ApoE4 treatment induced in addition apoptosis through translocation of Death-domain associated protein-6 (Daxx) from the nucleus to the cytosol, suggesting an activation of the Ask-1 pathway. This toxicity was prevented by overexpression of Trx1 and other endogenous Ask-1 inhibitors. Our data suggests that down-regulation of Trx1 is involved in the toxicity caused by ApoE4. An activated ASK-1 pathway might indeed make cells more vulnerable to other insults such as amyloid-β, which could partially explain the mechanism behind the strongest genetic risk factor for AD. PMID:28035917

  1. Decreased levels of inflammatory cytokines in immunoglobulin-resistant Kawasaki disease after plasma exchange.

    PubMed

    Fujimaru, Takuya; Ito, Shuichi; Masuda, Hiroshi; Oana, Shinji; Kamei, Koichi; Ishiguro, Akira; Kato, Hitoshi; Abe, Jun

    2014-12-01

    The pathogenesis of coronary artery aneurysm (CAA) formation in Kawasaki disease (KD) remains unknown. However, inflammatory cytokines are thought to play an important role in KD. Patients with intravenous immunoglobulin (IVIG)-resistant KD are more likely to develop CAA. For such refractory patients, steroids and emerging infliximab (IFX) are used; however, further verification is required for their efficacy and safety. Plasma exchange (PE), which removes various inflammatory cytokines, has been used in Japan for over 15 years to prevent CAA in IVIG-resistant KD patients. The sequential change in inflammatory cytokines during the time course of PE has yet to be investigated. In this study, we measured plasma levels of 13 cytokines in nine children with IVIG-resistant KD before the start of PE (day 0: D0), as well as at 1 or 2 days (D1/2), and 4 or 5 days (D4/5) after starting PE. The median age of onset was 8 months (range: 3-53 months). Before PE, patients were treated with IVIG (median dose: 4 g/kg, range: 3-4 g/kg). The median starting period of PE was 8 days after the onset of fever (range: 6-21 days), while its duration was 3 days (range: 2-5 days). Among the 13 cytokines, interleukin-6, tumor necrosis factor-α, tumor necrosis factor receptor I (TNFR1), TNFR2, granulocyte colony-stimulating factor, and IL-17 were significantly lower at D4/5 compared with D0 and/or D1/2, reflecting the potential central efficacy of PE. While three patients developed moderate CAA, their condition regressed within 1 year. The removal of inflammatory cytokines could be the central efficacy of PE against refractory KD.

  2. High Insulin Combined With Essential Amino Acids Stimulates Skeletal Muscle Mitochondrial Protein Synthesis While Decreasing Insulin Sensitivity in Healthy Humans

    PubMed Central

    Robinson, Matthew M.; Soop, Mattias; Sohn, Tae Seo; Morse, Dawn M.; Schimke, Jill M.; Klaus, Katherine A.

    2014-01-01

    Context: Insulin and essential amino acids (EAAs) regulate skeletal muscle protein synthesis, yet their independent effects on mitochondrial protein synthesis (MiPS) and oxidative function remain to be clearly defined. Objective: The purpose of this study was to determine the effects of high or low insulin with or without EAAs on MiPS. Design: Thirty participants were randomized to 3 groups of 10 each with each participant studied twice. Study groups comprised (1) low and high insulin, (2) low insulin with and without EAAs, and (3) high insulin with and without EAAs. Setting: The study was conducted in an in-patient clinical research unit. Participants: Eligible participants were 18 to 45 years old, had a body mass index of <25 kg/m2, and were free of diseases and medications that might impair mitochondrial function. Intervention: Low (∼6 μU/mL) and high (∼40 μU/mL) insulin levels were maintained by iv insulin infusion during a somatostatin clamp while maintaining euglycemia (4.7–5.2 mM) and replacing GH and glucagon. The EAA infusion was 5.4% NephrAmine. l-[ring-13C6]Phenylalanine was infused, and muscle needle biopsies were performed. Main Outcomes: Muscle MiPS, oxidative enzymes, and plasma amino acid metabolites were measured. Results: MiPS and oxidative enzyme activities did not differ between low and high insulin (MiPS: 0.07 ± 0.009 vs 0.07 ± 0.006%/h, P = .86) or between EAAs and saline during low insulin (MiPS: 0.05 ± 0.01 vs 0.07 ± 0.01, P = .5). During high insulin, EAAs in comparison with saline increased MiPS (0.1 ± 0.01 vs 0.06 ± 0.01, P < .05) and cytochrome c oxidase activity (P < .05) but not citrate synthase (P = .27). EAA infusion decreased (P < .05) the glucose infusion rates needed to maintain euglycemia during low (∼40%) and high insulin (∼24%). Conclusion: EAAs increased MiPS and oxidative enzyme activity only with high insulin concentrations. PMID:25222757

  3. Fatty acid and prostaglandin metabolism in children with diabetes mellitus. II. The effect of evening primrose oil supplementation on serum fatty acid and plasma prostaglandin levels.

    PubMed

    Arisaka, M; Arisaka, O; Yamashiro, Y

    1991-07-01

    Our previous study demonstrated that levels of dihomo-gamma-linolenic acid (DGLA) and arachidonic acid in serum total lipids decreased in association with increased plasma levels of prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) in patients with insulin-dependent diabetes mellitus. In this study, 11 children with insulin-dependent diabetes mellitus completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid (GLA) on serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. GLA was given as the seed oil from the evening primrose (EPO) and all patients received either EPO capsules (containing 45 mg of GLA and 360 mg of linoleic acid) or indistinguishable placebo capsules for 8 months. Initially patients took 2 capsules daily for 4 months then 4 capsules daily for a further 4 months. All patients were assessed at the start of the study, after 4 months and at the end of the study, by measuring serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. After administration of 4 capsules daily the DGLA levels increased and PGE2 levels decreased significantly (p less than 0.01) in the EPO compared with the placebo group. Neither fatty acid nor PGE2 and PGF2 alpha levels were altered by administration of 2 EPO capsules daily. This suggests that the altered essential fatty acid and PG metabolism in diabetes may be reversed by direct GLA supplementation.

  4. Mutations in the Arabidopsis Lst8 and Raptor genes encoding partners of the TOR complex, or inhibition of TOR activity decrease abscisic acid (ABA) synthesis.

    PubMed

    Kravchenko, Alena; Citerne, Sylvie; Jéhanno, Isabelle; Bersimbaev, Rakhmetkazhi I; Veit, Bruce; Meyer, Christian; Leprince, Anne-Sophie

    2015-11-27

    The Target of Rapamycin (TOR) kinase regulates essential processes in plant growth and development by modulation of metabolism and translation in response to environmental signals. In this study, we show that abscisic acid (ABA) metabolism is also regulated by the TOR kinase. Indeed ABA hormone level strongly decreases in Lst8-1 and Raptor3g mutant lines as well as in wild-type (WT) Arabidopsis plants treated with AZD-8055, a TOR inhibitor. However the growth and germination of these lines are more sensitive to exogenous ABA. The diminished ABA hormone accumulation is correlated with lower transcript levels of ZEP, NCED3 and AAO3 biosynthetic enzymes, and higher transcript amount of the CYP707A2 gene encoding a key-enzyme in abscisic acid catabolism. These results suggest that the TOR signaling pathway is implicated in the regulation of ABA accumulation in Arabidopsis.

  5. The TOC159 mutant of Arabidopsis thaliana accumulates altered levels of saturated and polyunsaturated fatty acids.

    PubMed

    Afitlhile, Meshack; Fry, Morgan; Workman, Samantha

    2015-02-01

    We evaluated whether the TOC159 mutant of Arabidopsis called plastid protein import 2-2 (ppi2-2) accumulates normal levels of fatty acids, and transcripts of fatty acid desaturases and galactolipid synthesis enzymes. The ppi2-2 mutant accumulates decreased pigments and total fatty acid content. The MGD1 gene was downregulated and the mutant accumulates decreased levels of monogalactosyldiacylglycerol (MGDG) and 16:3, which suggests that the prokaryotic pathway was impaired in the mutant. The HY5 gene, which encodes long hypocotyl5 transcription factor, was upregulated in the mutant. The DGD1 gene, an HY5 target was marginally increased and the mutant accumulates digalactosyldiacylglycerol at the control level. The mutant had increased expression of 3-ketoacyl-ACP synthase II gene, which encodes a plastid enzyme that elongates 16:0 to 18:0. Interestingly, glycerolipids in the mutant accumulate increased levels of 18:0. A gene that encodes stearoyl-ACP desaturase (SAD) was expressed at the control level and 18:1 was increased, which suggest that SAD may be strongly regulated at the posttranscriptional level. The molar ratio of MGDG to bilayer forming plastid lipids was decreased in the cold-acclimated wild type but not in the ppi2-2 mutant. This indicates that the mutant was unresponsive to cold-stress, and is consistent with increased levels of 18:0, and decreased 16:3 and 18:3 in the ppi2-2 mutant. Overall, these data indicate that a defective Toc159 receptor impaired the synthesis of MGDG, and affected desaturation of 16 and 18-carbon fatty acids. We conclude that expression of the MGD1 gene and synthesis of MGDG are tightly linked to plastid biogenesis.

  6. 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…

  7. 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.

  8. Deletion of fabN in Enterococcus faecalis results in unsaturated fatty acid auxotrophy and decreased release of inflammatory cytokines.

    PubMed

    Diederich, Ann-Kristin; Duda, Katarzyna A; Romero-Saavedra, Felipe; Engel, Regina; Holst, Otto; Huebner, Johannes

    2016-05-01

    The Gram-positive bacterium Enterococcus faecalis can cause life-threatening infections and is resistant to several commonly used antibiotics. The type II fatty acid pathway in bacteria is discussed as a potential target for antimicrobial therapy. However, it was shown that inhibition or deletion of its enzymes can be rescued in Gram-positive bacteria by supplementation with fatty acids. Here we show that by deletion of the fabN gene, which is essential for unsaturated fatty acid (UFA) synthesis in E. faecalis, growth is impaired but can be rescued by supplementation with oleic acid or human serum. Nonetheless, we demonstrate alterations of the UFA profile after supplementation with oleic acid in the ΔfabN mutant using a specific glycolipid. In addition, we demonstrate that cytokine release in vitro is almost abolished after stimulation of mouse macrophages by the mutant in comparison to the wild type. The results indicate that fabN is not a suitable target for antimicrobials as UFA auxotrophy can be overcome. However, deletion of fabN resulted in a decreased inflammatory response indicating that fabN and resulting UFA synthesis are relevant for virulence.

  9. Isoflavone supplements stimulated the production of serum equol and decreased the serum dihydrotestosterone levels in healthy male volunteers

    PubMed Central

    Tanaka, M; Fujimoto, K; Chihara, Y; Torimoto, K; Yoneda, T; Tanaka, N; Hirayama, A; Miyanaga, N; Akaza, H; Hirao, Y

    2009-01-01

    The aim of this study was to evaluate the effect of supplementing healthy men with soy isoflavones on the serum levels of sex hormones implicated in prostate cancer development. A total of 28 Japanese healthy volunteers (18 equol producers and 10 equol non-producers) between 30 and 59 years of age were given soy isoflavones (60 mg daily) supplements for 3 months, and the changes in their sex hormone levels were investigated at the baseline and after administration. The serum and urine concentrations of daidzein, genistein, and the levels of equol in the fasting blood samples and 24-h stored urine samples were also measured. All 28 volunteers completed the 3-month supplementation with isoflavone. No changes in the serum levels of estradiol and total testosterone were detected after 3-month supplementation. The serum levels of sex hormone-binding globulin significantly increased, and the serum levels of free testosterone and dihydrotestosterone (DHT) decreased significantly after 3-month supplementation. Among the 10 equol non-producers, equol became detectable in the serum of two healthy volunteers after 3-month supplementation. This study revealed that short-term administration of soy isoflavones stimulated the production of serum equol and decreased the serum DHT level in Japanese healthy volunteers. These results suggest the possibility of converting equol non-producers to producers by prolonged and consistent soy isoflavones consumption. PMID:19597532

  10. Hypouricemia in severely disabled children II: influence of elemental enteral nutrition on the serum uric acid levels.

    PubMed

    Yoshikawa, Hideto; Yamazaki, Sawako; Abe, Tokinari

    2004-01-01

    The previous study showed that both valproic acid (VPA) and a bedridden state decreased the serum uric acid level, and VPA-induced renal tubular dysfunction was suspected to be one cause of hypouricemia in severely disabled children. However, it was uncertain what factor of bedridden state influences the uric acid level in severely disabled children. Among many factors of a bedridden state that might influence the uric acid level, we examined the influence of elemental nutrition on the serum uric acid level in severely disabled children because many severely disabled children with marked hypouricemia receive elemental nutrition. Thirty-one severely disabled children were included in this study, who were divided into two groups-group A: 11 patients with elemental nutrition; group B: 20 patients with non-elemental nutrition. The laboratory data in both groups were analyzed statistically, using the t-test. The uric acid level was significantly decreased in group A compared with group B (p < 0.01) without elevation of urinary excretion of uric acid. Other laboratory data, except phosphate and potassium, did not differ between the two groups significantly. An elemental diet may be one factor that decreases the uric acid level in severely disabled children.

  11. Dry matter intake is decreased more by abomasal infusion of unsaturated free fatty acids than by unsaturated triglycerides.

    PubMed

    Litherland, N B; Thire, S; Beaulieu, A D; Reynolds, C K; Benson, J A; Drackley, J K

    2005-02-01

    Previous experiments from our group have demonstrated that abomasal infusion of unsaturated free fatty acids (FFA) markedly decreases dry matter intake (DMI) in dairy cows. In contrast, experiments from other groups have noted smaller decreases in DMI when unsaturated triglycerides (TG) were infused postruminally. Our hypothesis was that unsaturated FFA would be more potent inhibitors of DMI than an equivalent amount of unsaturated TG. Four Holstein cows in late lactation were used in a single reversal design. Cows were fed a total mixed ration containing (DM basis) 23% alfalfa silage, 23% corn silage, 40.3% ground shelled corn, and 10.5% soybean meal. Two cows received soy FFA (UFA; 0, 200, 400, 600 g/d) and 2 received soy oil (TG) in the same amounts; cows then were switched to the other lipid source. Cows were abomasally infused with each amount for 5-d periods. The daily amount of lipid was pulse-dosed in 4 equal portions at 0600, 1000, 1700, and 2200 h; no emulsifiers were used and there was no sign of digestive disturbance. Both lipid sources linearly decreased DMI, with a significant interaction between lipid source and amount. Slope-ratio analysis indicated that UFA were about 2 times more potent in decreasing DMI than were TG. Decreased DMI led to decreased milk production. Milk fat content was increased linearly by lipid infusion. Milk fat yield decreased markedly for UFA infusion but was relatively unaffected by infusion of TG. Contents of short- and medium-chain fatty acids in milk fat decreased as the amount of either infusate increased. Contents of C(18:2) and C(18:3) in milk fat were increased linearly by abomasal infusion of either fat source; cis-9 C(18:1) was unaffected. Transfer of infused C(18:2) to milk fat was 35.6, 42.5, and 27.8% for 200, 400, and 600 g/d of UFA, and 34.3, 39.6, and 34.0% for respective amounts of TG. Glucagon-like peptide-1 (7-36) amide (GLP-1) concentration in plasma significantly increased as DMI decreased with increasing

  12. Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cells.

    PubMed

    Rzeski, Wojciech; Stepulak, Andrzej; Szymański, Marek; Sifringer, Marco; Kaczor, Józef; Wejksza, Katarzyna; Zdzisińska, Barbara; Kandefer-Szerszeń, Martyna

    2006-10-01

    Betulinic acid (BA) is a pentacyclic triterpene found in many plant species, among others in the bark of white birch Betula alba. BA was reported to display a wide range of biological effects, including antiviral, antiparasitic, antibacterial and anti-inflammatory activities, and in particular to inhibit growth of cancer cells. The aim of the study was further in vitro characterization of BA anticancer activity. In this study, we demonstrated a remarkable antiproliferative effect of BA in all tested tumor cell cultures including neuroblastoma, rabdomyosarcoma-medulloblastoma, glioma, thyroid, breast, lung and colon carcinoma, leukemia and multiple myeloma, as well as in primary cultures isolated from ovarian carcinoma, cervical carcinoma and glioblastoma multiforme. Furthermore, we have shown that BA decreased cancer cell motility and induced apoptotic cell death. We also observed decrease of bcl2 and cyclin D1 genes expression, and increase of bax gene expression after betulinic acid treatment. These findings demonstrate the anticancer potential of betulinic acid and suggest that it may be taken into account as a supportive agent in the treatment of cancers with different tissue origin.

  13. Lamotrigine, carbamazepine and phenytoin differentially alter extracellular levels of 5-hydroxytryptamine, dopamine and amino acids.

    PubMed

    Ahmad, Shagufta; Fowler, Leslie J; Whitton, Peter S

    2005-02-01

    We have studied the effects of treatment with the anticonvulsants lamotrigine (LTG), phenytoin (PHN) and carbamazepine (CBZ) on basal and stimulated extracellular aspartate (ASP), glutamate (GLU), taurine (TAU), GABA, 5-hydroxytryptamine (5-HT) and dopamine (DA) in the hippocampus of freely moving rats using microdialysis. All of the drugs investigated have had inhibition of Na(+) channel activity implicated as their principal mechanism of action. Neither LTG (10-20 mg/kg), PHN (20-40 mg/kg) or CBZ (10-20 mg/kg) had an effect on the basal extracellular concentrations of any of the amino acids studied with the exception of glutamate, which was decreased at the highest LTG dose. However, when amino acid transmitter levels were increased with 50 microM veratridine, LTG was found to cause a dose-dependent decrease in dialysate levels of all four amino acids, with the effect being most pronounced for glutamate. In contrast, PHN decreased extracellular aspartate levels but had no effect on evoked-extracellular GLU, TAU or GABA. Somewhat unexpectedly, CBZ did not alter the stimulated increase in the excitatory amino acids, GLU and ASP, but, rather surprisingly for an antiepileptic drug, markedly decreased that of the inhibitory substances TAU and GABA. The three drugs had differing effects on basal extracellular 5-HT and DA. LTG caused a dose-dependent decrease in both, while CBZ and PHN both increased extracellular 5-HT and DA. When extracellular 5-HT and DA was evoked by veratridine LTG had no significant effect on this, while PHN but not CBZ increased stimulated extracellular 5-HT and both PHN and CBZ augmented DA. Thus, the effects of the three drugs studied seemed to depend on whether extracellular transmitter levels are evoked or basal and the particular transmitter in question. This suggests that there are marked differences in the neurochemical mechanisms of antiepileptic drug action of the three compounds studied.

  14. 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

  15. Decreased Glutathione S-transferase Level and Neonatal Hyperbilirubinemia Associated with Glucose-6-phosphate Dehydrogenase Deficiency: A Perspective Review.

    PubMed

    Al-Abdi, Sameer Yaseen

    2017-02-01

    Classically, genetically decreased bilirubin conjugation and/or hemolysis account for the mechanisms contributing to neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, these mechanisms are not involved in most cases of this hyperbilirubinemia. Additional plausible mechanisms for G6PD deficiency-associated hyperbilirubinemia need to be considered. Glutathione S-transferases (GST) activity depends on a steady quantity of reduced form of glutathione (GSH). If GSH is oxidized, it is reduced back by glutathione reductase, which requires the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH). The main source of NADPH is the pentose phosphate pathway, in which G6PD is the first enzyme. Rat kidney GSH, rat liver GST, and human red blood cell GST levels have been found to positively correlate with G6PD levels in their respective tissues. As G6PD is expressed in hepatocytes, it is expected that GST levels would be significantly decreased in hepatocytes of G6PD-deficient neonates. As hepatic GST binds bilirubin and prevents their reflux into circulation, hypothesis that decreased GST levels in hepatocytes is an additional mechanism contributing to G6PD deficiency-associated hyperbilirubinemia seems plausible. Evidence for and against this hypothesis are discussed in this article hoping to stimulate further research on the role of GST in G6PD deficiency-associated hyperbilirubinemia.

  16. Serum ZAG Levels Were Associated with eGFR Mild Decrease in T2DM Patients with Diabetic Nephropathy

    PubMed Central

    Xu, Lingling; Yu, Weihong; Niu, Meng; Zheng, Caixia; Qu, Bin; Li, Yan; Wang, Jing; Huang, Ping; Wang, O.

    2017-01-01

    Objective. To investigate the changes of serum zinc-α2-glycoprotein (ZAG) in type 2 diabetes mellitus (T2DM) with eGFR mild decrease. Subjects and Methods. A total of 438 T2DM patients (61.3 ± 4.0 y) were recruited and the demographic, anthropometric, and biochemical parameters were all collected. Serum ZAG levels were determined by commercially available ELISA kits. Results. The proportion of T2DM patients with the high tertile ZAG levels was 11.9% higher in patients with mildly decreased estimated glomerular filtration rate (eGFR) (<90 mL/min/1.73 m2) than those with the low tertile ZAG levels (P = 0.038). The probability of the eGFR < 90 mL/min/1.73 m2 in patients with the high ZAG levels was 94% higher than those with the low serum ZAG levels after adjusting for age, gender, and education [OR = 1.94, 95% CI (1.17–3.23), P = 0.0094]. This phenomenon was more likely to be observed in the condition of uACR ≥ 2.7 mg/mmol, WC ≥ 90 cm for men, or WC ≥ 85 cm for women. Conclusion. Serum ZAG levels were firstly found to be related with eGFR in T2DM patients. The patients with the high tertile ZAG levels were more likely to have mildly eGFR decrease, especially for female patients with higher uACR and bigger WC. PMID:28352283

  17. Word recognition in noise at higher-than-normal levels: Decreases in scores and increases in masking

    NASA Astrophysics Data System (ADS)

    Dubno, Judy R.; Horwitz, Amy R.; Ahlstrom, Jayne B.

    2005-08-01

    Under certain conditions, speech recognition in noise decreases above conversational levels when signal-to-noise ratio is held constant. The current study was undertaken to determine if nonlinear growth of masking and the subsequent reduction in ``effective'' signal-to-noise ratio accounts for this decline. Nine young adults with normal hearing listened to monosyllabic words at three levels in each of three levels of a masker shaped to match the speech spectrum. An additional low-level noise equated audibility by producing equivalent masked thresholds for all subjects. If word recognition was determined entirely by signal-to-noise ratio and was independent of overall speech and masker levels, scores at a given signal-to-noise ratio should remain constant with increasing level. Masked pure-tone thresholds measured in the speech-shaped maskers increased linearly with increasing masker level at lower frequencies but nonlinearly at higher frequencies, consistent with nonlinear growth of upward spread of masking that followed the peaks in the spectrum of the speech-shaped masker. Word recognition declined significantly with increasing level when signal-to-noise ratio was held constant which was attributed to nonlinear growth of masking and reduced ``effective'' signal-to-noise ratio at high speech-shaped masker levels, as indicated by audibility estimates based on the Articulation Index.

  18. 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.

  19. 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.

  20. Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study

    SciTech Connect

    Bergstroem, M.M.; Muhr, C.; Lundberg, P.O.; Bergstroem, K.G.; Gee, A.D.; Fasth, K.J.; Langstroem B5

    1987-09-01

    Four patients with prolactin-secreting pituitary adenomas were examined with positron emission tomography using L-(/sup 11/C)methionine to monitor the effect of dopamine agonist treatment on the amino acid metabolism in the tumors. Within the first few hours after intramuscular injection of bromocriptine retard (50 mg) the amino acid metabolism decreased by 40%. Two of the patients were reexamined 7 and 9 days later and showed a 70% reduction in the metabolism of the adenomas. This metabolic effect was later accompanied by significant tumor shrinkage in all adenomas. It is suggested that bromocriptine has a general and rapid effect on the protein synthesis of the prolactin-secreting pituitary adenoma cells.

  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

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

    2015-09-24

    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

  2. Acute starvation in C57BL/6J mice increases myocardial UCP2 and UCP3 protein expression levels and decreases mitochondrial bio-energetic function.

    PubMed

    Wang, Chun-Ming; Almsherqi, Zakaria A; McLachlan, Craig S; Matthews, Slade; Ramachandran, Malarmathy; Tay, Stacey Kh; Deng, Yuru

    2011-01-01

    Associations between uncoupling protein (UCP) expression and functional changes in myocardial mitochondrial bio-energetics have not been well studied during periods of starvation stress. Our aim was to study the effects of acute starvation, for 24 or 48 h, on combined cardiac mitochondrial function and UCP expression in mice. Isolated heart mitochondria from female mice starved for 48 h compared to that from mice fed revealed a significantly (p < 0.05) decreased adenosine diphosphate-to-oxygen ratio, a significantly increased proton leak and an increased GTP inhibition on palmitic acid-induced state 4 oxygen consumption (p < 0.05). These bio-energetic functional changes were associated with increases in mitochondrial UCP2 and UCP3 protein expression. In conclusion, our findings suggest that increased UCP2 and UCP3 levels may contribute to decreased myocardial mitochondrial bio-energetic function due to starvation.

  3. Decreased aortic early atherosclerosis in hypercholesterolemic hamsters fed oleic acid-rich TriSun oil compared to linoleic acid-rich sunflower oil.

    PubMed

    Nicolosi, Robert J.; Wilson, Thomas A.; Handelman, Garry; Foxall, Thomas; Keaney, John F.; Vita, Joseph A.

    2002-07-01

    Previous studies have demonstrated that low density lipoprotein (LDL) enriched in polyunsaturated fatty acids (PUFA) are more susceptible to oxidation (ex vivo) than those containing monounsaturated fatty acids (MUFA). To test whether this observation was associated with various parameters considered to be related with the development of early aortic atherosclerosis, hamsters were fed commercial hypercholesterolemic diets (HCD) containing either the PUFA, sunflower oil (SF) or the MUFA, TriSun oil (TS) at 10% with 0.4% cholesterol (wt/wt). LDL isolated from hamsters fed TS had significantly longer lag phase (30%, P < 0.05), a decreased propagation phase (-62%, P < 0.005), and fewer conjugated dienes formed (-37%, P < 0.007) compared to hamsters fed SF. Aortic vasomotor function, measured as degree of aortic relaxation, was significantly greater in the TS vs SF-fed hamsters whether acetylcholine or the calcium ionophore A23187 was used as the endothelium-dependent agonist. As a group, the SF-fed hamsters had significantly more early atherosclerosis than hamsters fed TS (46%, P < 0.006). When animals across the two diets were pair-matched by plasma LDL-C levels, there was an 82% greater mean difference (P < 0.002) in early atherosclerosis in the SF versus the TS-fed hamsters. While there were no significant associations with plasma lipids and lipoprotein cholesterol, early atherosclerosis was significantly correlated with lag phase (r = -0.67, p < 0.02), rate of LDL conjugated diene formation (r = 0.74, p < 0.006) and maximum dienes formed (r = 0.67, p < 0.02). Compared to TS-fed animals, aortic sections from hamsters fed the SF-containing diet revealed that the cytoplasm of numerous foam cells in the subendothelial space reacted positively with the monoclonal anti-bodies MDA-2 and NA59 antibody, epitopes found on oxidized forms of LDL. The present study suggests that compared to TS, hamsters fed the SF-diet demonstrated enhanced LDL oxidative susceptibility, reduced

  4. A Mutant of Arabidopsis with Increased Levels of Stearic Acid.

    PubMed Central

    Lightner, J.; Wu, J.; Browse, J.

    1994-01-01

    A mutation at the fab2 locus of Arabidopsis caused increased levels of stearate in leaves. The increase in leaf stearate in fab2 varied developmentally, and the largest increase occurred in young leaves, where stearate accounted for almost 20% of total leaf fatty acids. The fatty acid composition of leaf lipids isolated from the fab2 mutant showed increased stearate in all the major glycerolipids of both the chloroplast and extrachloroplast membranes. Although the stearate content was increased, the fab2 mutant still contained abundant amounts of 18:1, 18:2, and 18:3 fatty acids. These results are consistent with the expectations for a mutation partially affecting the action of the stromal stearoyl-acyl carrier protein desaturase. Positional analysis indicated that the extra 18:0 is excluded with high specificity from the sn-2 position of both chloroplast and extrachloroplast glycerolipids. Although stearate content was increased in all the major leaf membrane lipids, the amount of increase varied considerably among the different lipids, from a high of 25% of fatty acids in phosphatidylcholine to a low of 2.9% of fatty acids in monogalactosyldiacylglycerol. PMID:12232421

  5. 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.

  6. 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

  7. 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

  8. Hypocalcemia increases and hypercalcemia decreases the steady-state level of parathyroid hormone messenger RNA in the rat.

    PubMed Central

    Yamamoto, M; Igarashi, T; Muramatsu, M; Fukagawa, M; Motokura, T; Ogata, E

    1989-01-01

    To examine the effects of serum calcium concentrations on PTH biosynthesis, rats were made hyper- (serum total calcium, approximately 3.5 mM) or hypocalcemic (approximately 1.25 mM) and steady-state levels of PTH mRNA in parathyroid cells were measured by the primer extension method using a 32P-labeled synthetic oligomer. PTH mRNA levels increased about twofold in the rats made slightly hypocalcemic by infusion of calcium-free solution and decreased slightly in those made hypercalcemic by CaCl2 infusion (120-150 mumol/h) compared with the levels present in nonfasting control rats. Infusion of calcitonin (0.5 U/h) or EGTA (90 mumol/h) with calcium-free solution increased PTH mRNA levels further (two- to sevenfold) above the levels present in animals infused with calcium-free solution alone. These changes in PTH mRNA levels were observed after 48- but not 24-h infusion, and there was an inverse correlation between PTH mRNA levels and serum calcium concentrations. The results suggest that changes in serum calcium concentrations in the near physiological range regulate the biosynthesis of PTH by affecting steady-state levels of PTH mRNA when hypercalcemia or hypocalcemia continues for a relatively long period. Images PMID:2493484

  9. Serum iron, vitamin B12 and folic acid levels in Parkinson's disease.

    PubMed

    Madenci, Gulizar; Bilen, Sule; Arli, Berna; Saka, Mustafa; Ak, Fikri

    2012-07-01

    We aimed to investigate possible associations between systemic iron metabolism deficiency and Parkinson's disease, and also to research any possible correlations between stage of the disease and vitamin B12 and folic acid levels. 33 male and 27 female patients diagnosed with idiopathic Parkinson's disease and 22 male and 20 female age- and sex-matched controls were enrolled in the study. Having the diagnosis of secondary Parkinsonism or Parkinson plus syndromes, and for the females, not being in the menopausal stage were considered as exclusion criteria. Recordings of blood samples of both groups collected after 8 h fasts were assessed in terms of serum iron, ferritin levels and iron-binding capacity, vitamin B12 and folic acid levels. The Hoehn and Yahr scale was used to determine the stage of the disease. No statistically significant difference was found with respect to mean serum iron, median serum ferritin levels and median serum iron-binding capacity between the groups. A statistically significant but inverse correlation was found between symptoms' duration and serum iron and ferritin levels. There was no statistically significant difference between the groups with respect to vitamin B12 and folic acid levels. However, a statistically significant but inverse correlation was determined between the patients' vitamin B12 levels and the Hoehn and Yahr scores. As Parkinson's disease progresses, serum iron, ferritin and vitamin B12 levels may decrease. The lower levels of these parameters may be the cause of the progression or may be the result of it.

  10. 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.

  11. Folic acid protects against lead acetate-induced hepatotoxicity by decreasing NF-κB, IL-1β production and lipid peroxidation mediataed cell injury.

    PubMed

    Abd Allah, Eman S H; Badary, Dalia M

    2017-03-01

    Folic acid plays an important role in cellular metabolic activities. The present study was designed to investigate the protective effect of folic acid against lead acetate-induced hepatotoxicity. Twenty four male Wistar albino rats were randomly divided into four groups, six animals each. Negative control group received the vehicle, positive control group received 1mg/kg folic acid for five consecutive days/week for 4 weeks orally, lead-exposed group received 10mg/kg lead acetate intraperitoneally (IP) for five consecutive days/week for 4 weeks, and lead-treated group received 10mg/kg lead acetate IP and 1mg/kg folic acid orally for five consecutive days/week for 4 weeks concurrently. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ- glutamyltransferase (GGT) were measured. Hepatic total peroxide and interleukin-1β (IL-1β) were also investigated. Histopathological studies using hematoxylin-eosin (H&E) and periodic acid shiff's (PAS) were carried out. The expression of nuclear factor kappa B (NF-κB) was evaluated using immunohistochemistry. Serum AST, ALT and GGT and hepatic total peroxide and IL-1β were significantly increased in lead-exposed group and were positively correlated with hepatic lead level. Moreover, lead-exposed rats showed hydropic degeneration, nuclear vesiculation, high lymphocytic infiltration, depletion of glycogen content and NF-κB expression. Concomitant folic acid administration resulted in a significant alleviation of biochemical and structural alteration-induced by lead. This was associated with reduction of hepatic total peroxide and IL-1β and reduction of NF-κB expression. In conclusion, folic acid protects against lead acetate-induced hepatotoxicity by decreasing NF-κB, IL-1β production and lipid peroxidation mediataed cell injury.

  12. 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

  13. 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.

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

    PubMed

    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.

  15. The environmental light influences the circulatory levels of retinoic acid and associates with hepatic lipid metabolism.

    PubMed

    Pang, Wenqiang; Li, Chunying; Zhao, Yue; Wang, Shiming; Dong, Wei; Jiang, Pengjiu; Zhang, Jianfa

    2008-12-01

    Environmental light is involved in the regulation of photochemical reaction in mouse retina. It remains unclear whether light-mediated increase in all-trans retinoic acid (ATRA) synthesis in retina will result in altering the circulatory levels of ATRA and regulating downstream gene expression and physiological function. Here we showed circulatory levels of ATRA decreased in mice under constant darkness and elevated by light exposure. Fat gene pancreatic lipase-related protein 2 (mPlrp2) and its partner procolipase (mClps), but not hepatic lipase (mHl), activated in livers for responding to lack of light illuminating. Light-triggered alterations in circulatory ATRA levels regulated ecto-5'-nucleotidase gene expression by retinoic acid receptor retinoic acid receptor-alpha and modulated 5'-AMP levels in blood and were associated with mPlrp2 and mClps expression in the livers. Mice deficient in adenosine receptors displayed mPlrp2 and mClps expression in livers under 12-h light, 12-h dark cycles. Caffeine blocked adenosine receptors and induced hepatic mPlrp2 and mClps expression in wild-type mice. Mice activated in hepatic mPlrp2 and mClps expression lowered hepatic and serum lipid levels and markedly elevated circulatory levels of all-trans retinol. Our results suggest environmental light influence hepatic lipid homeostasis by light-modulated retinoic acid signaling associated with mPlrp2 and mClps gene expression in livers.

  16. A single amino acid substitution in ORF1 dramatically decreases L1 retrotransposition and provides insight into nucleic acid chaperone activity

    PubMed Central

    Martin, Sandra L.; Bushman, Diane; Wang, Fei; Li, Patrick Wai-Lun; Walker, Ann; Cummiskey, Jessica; Branciforte, Dan; Williams, Mark C.

    2008-01-01

    L1 is a ubiquitous interspersed repeated sequence in mammals that achieved its high copy number by autonomous retrotransposition. Individual L1 elements within a genome differ in sequence and retrotransposition activity. Retrotransposition requires two L1-encoded proteins, ORF1p and ORF2p. Chimeric elements were used to map a 15-fold difference in retrotransposition efficiency between two L1 variants from the mouse genome, TFC and TFspa, to a single amino acid substitution in ORF1p, D159H. The steady-state levels of L1 RNA and protein do not differ significantly between these two elements, yet new insertions are detected earlier and at higher frequency in TFC, indicating that it converts expressed L1 intermediates more effectively into new insertions. The two ORF1 proteins were purified and their nucleic acid binding and chaperone activities were examined in vitro. Although the RNA and DNA oligonucleotide binding affinities of these two ORF1 proteins were largely indistinguishable, D159 was significantly more effective as a nucleic acid chaperone than H159. These findings support a requirement for ORF1p nucleic acid chaperone activity at a late step during L1 retrotransposition, extend the region of ORF1p that is known to be critical for its functional interactions with nucleic acids, and enhance understanding of nucleic acid chaperone activity. PMID:18790804

  17. 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.

  18. Decreases in postural change in finger blood flow in ceramic painters chronically exposed to low level lead.

    PubMed

    Ishida, M; Ishizaki, M; Yamada, Y

    1996-05-01

    To elucidate the effect of low level lead (Pb) exposure on somatic and autonomic peripheral nerve functions in ceramic painters, 58 males and 70 females, aged 29-75 years (mean 53.3 years), with lead concentrations in blood (Pb-B) ranging from 2.1 to 69.5 micrograms/dl (geometric mean 13.3 micrograms/dl), were examined for median nerve maximal conduction velocity as a measure of motor nerve function, the coefficient of variation of R-R interval on electrocardiography as a measure of parasympathetic function, and postural changes in finger blood flow volume (delta FBF), and changes in finger blood flow drop velocity (FDV) from the supine to standing position as a measure of sympathetic function. No significant association was found between Pb-B levels and the results of the neurophysiological tests, however, except for that between Pb-B and delta FBF was decreased linearly with increasing Pb-B levels. However, this association could not be concluded to be a reflection of sympathetic nerve dysfunction due to Pb exposure in the subjects, since delta FBF was not a specific parameter of sympathetic nerve function. The possibility that the decrease in delta FBF is a reflection of the atherosclerotic effect of chronic low level Pb exposure should be further investigated.

  19. 3-Deoxyschweinfurthin B Lowers Cholesterol Levels by Decreasing Synthesis and Increasing Export in Cultured Cancer Cell Lines.

    PubMed

    Kuder, Craig H; Weivoda, Megan M; Zhang, Ying; Zhu, Junjia; Neighbors, Jeffrey D; Wiemer, David F; Hohl, Raymond J

    2015-12-01

    The schweinfurthins have potent antiproliferative activity in multiple glioblastoma multiforme (GBM) cell lines; however, the mechanism by which growth is impeded is not fully understood. Previously, we demonstrated that the schweinfurthins reduce the level of key isoprenoid intermediates in the cholesterol biosynthetic pathway. Herein, we describe the effects of the schweinfurthins on cholesterol homeostasis. Intracellular cholesterol levels are greatly reduced in cells incubated with 3-deoxyschweinfurthin B (3dSB), an analog of the natural product schweinfurthin B. Decreased cholesterol levels are due to decreased cholesterol synthesis and increased cholesterol efflux; both of these cellular actions can be influenced by liver X-receptor (LXR) activation. The effects of 3dSB on ATP-binding cassette transporter 1 levels and other LXR targets are similar to that of 25-hydroxycholesterol, an LXR agonist. Unlike 25-hydroxycholesterol, 3dSB does not act as a direct agonist for LXR α or β. These data suggest that cholesterol homeostasis plays a significant role in the growth inhibitory activity of the schweinfurthins and may elucidate a mechanism that can be targeted in human cancers such as GBM.

  20. Short-term magnesium deficiency results in decreased levels of serum sphingomyelin, lipid peroxidation, and apoptosis in cardiovascular tissues.

    PubMed

    Altura, Burton M; Shah, Nilank C; Jiang, Xian-Cheng; Li, Zhiqiang; Perez-Albela, José Luis; Sica, Anthony C; Altura, Bella T

    2009-07-01

    The present study tested the hypothesis that short-term dietary deficiency of magnesium (Mg) (21 days) in rats would 1) result in decreased serum(s) [the present study tested the levels of Mg, sphingomyelin (SM), and phosphatidylcholine (PC)]; 2) promote DNA fragmentation, lipid peroxidation (LP), and activation of caspase-3 in cardiac (ventricular and atrial) and vascular(aortic) muscle; and 3) low levels of Mg(2+) added to drinking water would either prevent or greatly ameliorate these manifestations. The data indicate that short-term Mg deficiency (10% normal dietary intake) resulted in profound reductions in serum-ionized Mg and total Mg with an elevation in serum-ionized calcium (Ca(2+)), significant lowering of serum SM and serum PC, with concomitant LP, DNA fragmentation, and activation of caspase-3 in ventricular (right and left chambers), atrial (right and left chambers) and abdominal aortic smooth muscle. The greater the reduction in serum-ionized Mg, the greater the effects on DNA fragmentation, LP, and caspase-3 activity. The intake of water-borne Mg(2+) at all levels greatly attenuated or inhibited the reductions in serum SM and serum PC, activation of LP, DNA fragmentation, and the activation of caspase-3; even very low levels of Mg(2+) in drinking water (i.e., 15 parts.million(-1).day(-1)) were cardio- and vascular protective. In addition, we demonstrate that short-term dietary deficiency of Mg probably results in a downregulation of SM synthase and a decreased synthesis of PC.

  1. Acute decrease in circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis.

    PubMed

    Nascif, S O; Senger, M H; Ramos-Dias, J C; Lengyel, A M J

    2003-08-01

    In thyrotoxicosis there is an impaired GH response to GHRH, normal GH responsiveness to GHRP-6 and lack of synergistic GH response after simultaneous administration of both peptides. We have previously shown that the GHRH-induced GH release in these patients increases after an acute reduction of circulating T3 values with administration of iopanoic acid, a compound that inhibits peripheral conversion of T4 to T3. We have now studied the effect of a decrease in serum T3 levels on the GH response to GHRP-6 (1 microg/kg) plus GHRH (100 microg) in 9 hyperthyroid patients before and after 15 days of treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (600 mg/day). Nine normal subjects were also studied. In all hyperthyroid patients iopanoic acid induced a rapid decrease and normalisation of serum T3 levels. In these subjects peak GH (microg/l; mean +/- SE) and AUC (microg/l x 120 min) values after GHRP-6 plus GHRH were significantly higher on day 15 compared to pretreatment values (peak, 18.3 +/- 3.0 vs 13.4 +/- 1.9; AUC, 1227.9 +/- 212.9 vs 968.5 +/- 160.4; p<0.05). Despite the significant enhancement of the GH responsiveness to GHRP-6 plus GHRH after treatment with iopanoic acid, this response remained significantly blunted when compared to controls both in terms of peak GH (18.3 +/- 3.0 vs 83.7 +/- 15.2; p<0.05) and AUC values (1227.9 +/- 212.9 vs 4956.5 +/- 889.3; p<0.05). In conclusion, our results show that an acute decrease of circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis. This could suggest that circulating T3 does not have a major role in the mechanisms involved in the synergistic effect of these peptides.

  2. 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.

  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.

  4. Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction.

    PubMed

    Naidoo, V; Swan, G E

    2009-04-01

    Diclofenac (DF), a non-steroidal anti-inflammatory drug (NSAID), is largely regarded as one of the most devastating environmental toxicant in recent times, after accidental exposure via their food-chain lead to massive mortalities in three vulture species on the Asian subcontinent. Although the use of diclofenac was recently banned on the Indian subcontinent, following the favourable safety profile of meloxicam, its mechanism of toxicity remains unknown. In an attempt to establish this mechanism, we test three hypotheses using models established from either the domestic chicken (Gallus domesticus) or the African White-backed vulture (Gyps africanus). We demonstrate that both DF and meloxicam are toxic to renal tubular epithelial (RTE) cells following 12 h of exposure, due to an increase in production of reactive oxygen species (ROS), which could be temporarily ameliorated by pre-incubation with uric acid (UA). When cultures were incubated with either drug for only 2 h, meloxicam showed no toxicity in contrast to diclofenac. In both cases no increase in ROS production was evident. In addition, diclofenac decreased the transport of uric acid, by interfering with the p-amino-hippuric acid (PAH) channel. We conclude that vulture susceptibility to diclofenac results from a combination of an increased ROS, interference with UA transport and the duration of exposure.

  5. cAMP and forskolin decrease. gamma. -aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes

    SciTech Connect

    Heuschneider, G.; Schwartz, R.D. )

    1989-04-01

    The effects of the cyclic nucleotide cAMP on {gamma}-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N{sup 6}, O{sup 2{prime}}-dibutyryladenosine 3{prime},5{prime}-cyclic monophosphate inhibited muscimol-induced {sup 36}Cl{sup {minus}} uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner. The inhibition was due to a decrease in the maximal effect of muscimol, with no change in potency. Similar effects were observed with 8-(4-chlorophenylthio)adenosine 3{prime},5{prime}-cyclic monophosphate, 8-bromoadenosine 3{prime},5{prime}-cyclic monophosphate, and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the {gamma}-aminobutyric acid-gated Cl{sup {minus}} channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced {sup 36}Cl{sup {minus}} uptake and generated cAMP with similar potencies. Surprisingly, 1,9-dideoxyforskolin, which does not activate adenylate cyclase, also inhibited the muscimol response, suggesting that forskolin and its lipophilic derivatives may interact with the Cl{sup {minus}} channel directly. The data suggest that {gamma}-aminobutyric acid (GABA{sub A}) receptor function in brain can be regulated by cAMP-dependent phosphorylation.

  6. Decreased 5-hydroxymethylcytosine levels correlate with cancer progression and poor survival: a systematic review and meta-analysis

    PubMed Central

    Guo, Lanwei; Li, Yuan; Luo, Mei; He, Jie

    2017-01-01

    Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) and then to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), resulting in genomic DNA demethylation. Decreased 5-hmC levels have been reported in a variety of cancers, and loss of 5-hmC might be considered an epigenetic hallmark of cancer. However, the prognostic value of decreased 5-hmC in cancers remain controversial. Here, a systematic review was performed by conducting an electronic search of PubMed, EMBASE, Web of Science and the Cochrane Library. Finally, ten studies with a total of 1736 patients with cancer were included in the present study. Negative/low 5-hmC levels were significantly associated with lymph node metastasis [OR=2.20, 95% CI=1.23-3.96, P=0.008] and advanced TNM stage [OR=2.89, 95% CI=1.21-6.92, P=0.017]. More importantly, negative/low 5-hmC levels were significantly associated with poor prognosis of cancer patients [overall survival: HR=1.76, 95% CI=1.41-2.11, P < 0.001; disease free survival: HR=1.28, 95% CI=0.60-1.96, P < 0.001]. The results of this meta-analysis indicate that decreased 5-hmC levels are an indicator of poor survival of cancer patients. Given variability related to ethnicity, cancer types and detection methods, additional well-designed studies with larger sample sizes are required to further confirm our findings. PMID:27911867

  7. Liver-specific Deficiency of Serine Palmitoyltransferase Subunit 2 Decreases Plasma Sphingomyelin and Increases Apolipoprotein E Levels*

    PubMed Central

    Li, Zhiqiang; Li, Yan; Chakraborty, Mahua; Fan, Yifan; Bui, Hai H.; Peake, David A.; Kuo, Ming-Shang; Xiao, Xiao; Cao, Guoqing; Jiang, Xian-Cheng

    2009-01-01

    Sphingomyelin (SM) is one of the major lipid components of plasma lipoproteins. Serine palmitoyltransferase (SPT) is the key enzyme in SM biosynthesis. Mice totally lacking in SPT are embryonic lethal. The liver is the major site for plasma lipoprotein biosynthesis, secretion, and degradation, and in this study we utilized a liver-specific knock-out approach for evaluating liver SPT activity and also its role in plasma SM and lipoprotein metabolism. We found that a deficiency of liver-specific Sptlc2 (a subunit of SPT) decreased liver SPT protein mass and activity by 95 and 92%, respectively, but had no effect on other tissues. Liver Sptlc2 deficiency decreased plasma SM levels (in both high density lipoprotein and non-high density lipoprotein fractions) by 36 and 35% (p < 0.01), respectively, and increased phosphatidylcholine levels by 19% (p < 0.05), thus increasing the phosphatidylcholine/SM ratio by 77% (p < 0.001), compared with controls. This deficiency also decreased SM levels in the liver by 38% (p < 0.01) and in the hepatocyte plasma membranes (based on a lysenin-mediated cell lysis assay). Liver-specific Sptlc2 deficiency significantly increased hepatocyte apoE secretion and thus increased plasma apoE levels 3.5-fold (p < 0.0001). Furthermore, plasma from Sptlc2 knock-out mice had a significantly stronger potential for promoting cholesterol efflux from macrophages than from wild-type mice (p < 0.01) because of a greater amount of apoE in the circulation. As a result of these findings, we believe that the ability to control liver SPT activity could result in regulation of lipoprotein metabolism and might have an impact on the development of atherosclerosis. PMID:19648608

  8. Hippocampal interneurons expressing glutamic acid decarboxylase and calcium-binding proteins decrease with aging in Fischer 344 rats.

    PubMed

    Shetty, A K; Turner, D A

    1998-05-04

    Aging leads to alterations in the function and plasticity of hippocampal circuitry in addition to behavioral changes. To identify critical alterations in the substrate for inhibitory circuitry as a function of aging, we evaluated the numbers of hippocampal interneurons that were positive for glutamic acid decarboxylase and those that expressed calcium-binding proteins (parvalbumin, calbindin, and calretinin) in young adult (4-5 months old) and aged (23-25 months old) male Fischer 344 rats. Both the overall interneuron population and specific subpopulations of interneurons demonstrated a commensurate decline in numbers throughout the hippocampus with aging. Interneurons positive for glutamic acid decarboxylase were significantly depleted in the stratum radiatum of CA1, the strata oriens, radiatum and pyramidale of CA3, the dentate molecular layer, and the dentate hilus. Parvalbumin interneurons showed significant reductions in the strata oriens and pyramidale of CA1, the stratum pyramidale of CA3, and the dentate hilus. The reductions in calbindin interneurons were more pronounced than other calcium-binding protein-positive interneurons and were highly significant in the strata oriens and radiatum of both CA1 and CA3 subfields and in the dentate hilus. Calretinin interneurons were decreased significantly in the strata oriens and radiatum of CA3, in the dentate granule cell and molecular layers, and in the dentate hilus. However, the relative ratio of parvalbumin-, calbindin-, and calretinin-positive interneurons compared with glutamic acid decarboxylase-positive interneurons remained constant with aging, suggesting actual loss of interneurons expressing calcium-binding proteins with age. This loss contrasts with the reported preservation of pyramidal neurons with aging in the hippocampus. Functional decreases in inhibitory drive throughout the hippocampus may occur due to this loss, particularly alterations in the processing of feed-forward information through the

  9. 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.

  10. Experimental nonalcoholic steatohepatitis increases exposure to simvastatin hydroxy acid by decreasing hepatic organic anion transporting polypeptide expression.

    PubMed

    Clarke, John D; Hardwick, Rhiannon N; Lake, April D; Canet, Mark J; Cherrington, Nathan J

    2014-03-01

    Simvastatin (SIM)-induced myopathy is a dose-dependent adverse drug reaction (ADR) that has been reported to occur in 18.2% of patients receiving a 40- to 80-mg dose. The pharmacokinetics of SIM hydroxy acid (SIMA), the bioactive form of SIM, and the occurrence of SIM-induced myopathy are linked to the function of the organic anion transporting polypeptide (Oatp) hepatic uptake transporters. Genetic polymorphisms in SLCO1B1, the gene for human hepatic OATP1B1, cause decreased elimination of SIMA and increased risk of developing myopathy. Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease, and is known to alter drug transporter expression and drug disposition. The purpose of this study was to assess the metabolism and disposition of SIM in a diet-induced rodent model of NASH. Rats were fed a methionine- and choline-deficient diet for 8 weeks to induce NASH and SIM was administered intravenously. Diet-induced NASH caused increased plasma retention and decreased biliary excretion of SIMA due to decreased protein expression of multiple hepatic Oatps. SIM exhibited increased volume of distribution in NASH as evidenced by increased muscle, decreased plasma, and no change in biliary concentrations. Although Cyp3a and Cyp2c11 proteins were decreased in NASH, no alterations in SIM metabolism were observed. These data, in conjunction with our previous data showing that human NASH causes a coordinated downregulation of hepatic uptake transporters, suggest that NASH-mediated transporter regulation may play a role in altered SIMA disposition and the occurrence of myopathy.

  11. 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

  12. 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.

  13. The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates reduced levels of hexadecatrienoic acid.

    PubMed

    Afitlhile, Meshack; Duffield-Duncan, Kayla; Fry, Morgan; Workman, Samantha; Hum-Musser, Sue; Hildebrand, David

    2015-11-01

    A null and heterozygous mutant for the Arabidopsis thaliana TOC132 and TOC120 genes accumulates increased levels of 16:0 and decreased 16:3, suggesting altered homeostasis in fatty acid synthesis. The FAD5 gene encodes a plastid desaturase that catalyzes the first step in the synthesis of 16:3 in monogalactosyldiacylglycerol (MGDG). In non-acclimated toc132toc120+/- mutant plants, the FAD5 gene was repressed and this correlated with decreased levels of 16:3. In cold-acclimated mutant however, the FAD5 gene was upregulated and there was a small increase in 16:3 levels relative to the non-acclimated mutant plants. The MGD1 gene was expressed at control levels and the mutant accumulated levels of MGDG that were similar to the wild type. In the mutant however, MGDG had decreased 16:3 levels, suggesting that the activity of FAD5 desaturase was compromised. In the mutant, the FAD2 and FAD3 genes were downregulated but levels of 18:3-PC were increased, suggesting posttranscriptional regulation for the ER-localized fatty acid desaturases. The Toc120 or Toc159 receptor is likely to compensate for a defective Toc132 receptor. In the cold-acclimated mutant, the TOC159 gene was repressed ca. 300-fold, whereas the TOC120 gene was repressed 7-fold relative to the non-acclimated wild type. Thus, the TOC159 gene is more sensitive to cold-stress and might not compensate for defect in the TOC132 gene under these conditions. Overall, these data show that a mutation in the TOC132 gene results in decreased 16:3 levels, indicating the need for an intact Toc132/Toc120 receptor, presumably to facilitate the import of the FAD5 preprotein into chloroplasts.

  14. 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

  15. 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

  16. Elevated Dopamine Levels During Gestation Produce Region-specific Decreases in Neurogenesis and Subtle Deficits in Neuronal Numbers

    PubMed Central

    McCarthy, Deirdre; Lueras, Paula; Bhide, Pradeep G.

    2007-01-01

    Dopamine levels in the fetal brain were increased by administering the dopamine precursor 3,4-dihydroxy-L-phenylalanine (L-DOPA) to pregnant mice in drinking water. The L-DOPA exposure decreased bromodeoxyuridine (BrdU) labeling in the lateral ganglionic eminence and frontal cortical neuroepithelium but not medial or caudal ganglionic eminences. The regional differences appear to reflect heterogeneity in precursor cells’ responses to dopamine receptor activation. Relative numbers of E15 generated neurons were decreased at postnatal day 21 (P21) in the caudate-putamen, nucleus accumbens and frontal cortex but not globus pallidus in the L-DOPA group. TUNEL labeling did not show significant differences on P0, P7 or P14 in the caudate-putamen or frontal cortex, suggesting that cell death was not altered. Although virtually all cells in the P21 brains that were labeled with the E15 BrdU injection were NeuN-positive, stereological analyses showed no significant changes in total numbers of NeuN-positive or NeuN-negative cells in the P21 caudate-putamen or frontal cortex. Thus persisting deficits in neuronal numbers were evident in the L-DOPA group only by birth-dating analyses and not upon gross histological examination of brain sections or analysis of total numbers of neurons or glia. One explanation for this apparent discrepancy is that L-DOPA exposure decreased cell proliferation at E15 but not at E13. By E15, expansion of the neuroepithelial precursor pool is complete and any decrease in cell proliferation likely produces only marginal decreases in the total numbers of cells generated. Our L-DOPA exposure model may be pertinent to investigations of neurological dysfunction produced by developmental dopamine imbalance. PMID:17950709

  17. Decreased serum fibroblast growth factor - 2 levels in pre- and post-treatment patients with major depressive disorder.

    PubMed

    He, Shen; Zhang, Tianhong; Hong, Bo; Peng, Daihui; Su, Hui; Lin, Zhiguang; Fang, Yiru; Jiang, Kaida; Liu, Xiaohua; Li, Huafang

    2014-09-05

    Increasing evidence indicates that neurotrophic factor dysfunction might be involved in the pathophysiology and treatment of major depressive disorder (MDD). Fibroblast growth factor (FGF)-2, one of the major neurotrophins, plays an important role in the central nervous system (CNS). The aim of this study was to explore whether the FGF-2 in serum was associated with MDD and to evaluate the effects of antidepressant treatment on serum FGF-2 levels. Serum FGF-2 levels were determined in 28 pre- and post-treatment MDD patients and 30 healthy controls using ELISA. The results of the current study revealed that serum FGF-2 levels in MDD patients were significantly lower than those in healthy controls (p=0.005), and the serum FGF-2 levels decreased significantly but marginally following treatment for 8 weeks (p=0.005). These findings demonstrate that the lower serum FGF-2 levels contribute to the pathophysiology of MDD and that FGF-2 may be used as a peripheral biological marker for MDD.

  18. Decreased ADAMTS-13 level is related to inflammation factors and risk stratification of acute lymphoblastic leukemia patients

    PubMed Central

    Liu, Chen; Zhao, Lei; Zhao, Jingzhong; Xu, Qinzhu; Song, Ying; Wang, Hui

    2017-01-01

    Abstract As a kind of metalloprotease of the ADAMTS family, ADAMTS-13 is crucial for maintaining the normal size of von Willebrand factor. Reduced ADAMTS-13 had been reported in patients with both localized and disseminated malignancies. However, the expression and potential role of ADAMTS-13 in hematological malignancies remain unclear. In this research, we measured and compared ADAMTS-13 levels in plasma of 35 acute lymphoblastic leukemia (ALL) patients and 30 healthy controls and found that ALL patients possessed lower level of ADAMTS-13 than controls. Correlations between ADAMTS-13 and inflammation factors were calculated and ADAMTS-13 was negatively correlated with C-reactive protein and interleukin-1β. ALL patients with infections had lower level of ADAMTS-13 than patients without infections. In addition, high-risk ALL patients possessed lower ADAMTS-13 than patients at low risk. To conclude, ADAMTS-13 level is decreased in the plasma of ALL patients and the level of ADAMTS-13 is related to plasma inflammation factors and risk stratification of ALL patients, which could contribute to better understanding of the clinical significance of ADAMTS-13. PMID:28207543

  19. Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

    PubMed

    Everman, Sarah; Meyer, Christian; Tran, Lee; Hoffman, Nyssa; Carroll, Chad C; Dedmon, William L; Katsanos, Christos S

    2016-10-01

    Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P < 0.01) whole body phenylalanine rate of appearance (μmol·kg(-1)·min(-1)), indicating suppression of muscle proteolysis, in both the control (1.02 ± 0.04 vs 0.76 ± 0.04) and the BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA.

  20. A decrease in intact parathyroid hormone (iPTH) levels is associated with higher mortality in prevalent hemodialysis patients

    PubMed Central

    Villa-Bellosta, Ricardo; Rodriguez-Osorio, Laura; Mas, Sebastian; Abadi, Younes; Rubert, Mercedes; de la Piedra, Concepción; Gracia-Iguacel, Carolina; Mahillo, Ignacio; Ortiz, Alberto; Egido, Jesús; González-Parra, Emilio

    2017-01-01

    Background The mortality of dialysis patients is 10- to 100-fold higher than in the general population. Baseline serum PTH levels, and more recently, changes in serum PTH levels (ΔPTH) over time, have been associated to mortality in dialysis patients. Methods We explored the relationship between ΔPTH over 1 year with mortality over the next year in a prospective cohort of 115 prevalent hemodialysis patients from a single center that had median baseline iPTH levels within guideline recommendations. Results Median baseline iPTH levels were 205 (116.5, 400) pg/ml. ΔiPTH between baseline and 1 year was 85.2 ± 57.1 pg/ml. During the second year of follow-up, 27 patients died. ΔiPTH was significantly higher in patients who survived (+157.30 ± 25.82 pg/ml) than in those who died (+39.03 ± 60.95 pg/ml), while baseline iPTH values were not significantly different. The highest mortality (48%) was observed in patients with a decrease in ΔiPTH (ΔiPTH quartile 1, negative ΔiPTH) and the lowest (12%) mortality in quartile 3 ΔiPTH (ΔiPTH increase 101–300 pg/ml). In a logistic regression model, ΔiPTH was associated with mortality with an odds ratio (OR) of 0.998 (95% CI 0.996–0999, p = 0.038). In multivariable analysis, mortality risk was 73% and 88% lower for patients with ΔiPTH 0–100 pg/ml and 101–300 pg/ml, respectively, than for those with a decrease in ΔiPTH. In patients with a decrease in ΔiPTH, the OR for death was 4.131 (1.515–11.27)(p = 0.006). Conclusions In prevalent hemodialysis patients with median baseline iPTH values within the guideline recommended range, a decrease in ΔiPTH was associated with higher mortality. Further studies are required to understand the mechanisms and therapeutic implications of this observation that challenges current clinical practice. PMID:28339474

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Behavioral and serotonergic consequences of decreasing or increasing hippocampus brain-derived neurotrophic factor protein levels in mice.

    PubMed

    Deltheil, T; Guiard, B P; Cerdan, J; David, D J; Tanaka, K F; Repérant, C; Guilloux, J-P; Coudoré, F; Hen, R; Gardier, A M

    2008-11-01

    Antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRI) act as indirect agonists of serotonin (5-HT) receptors. Although these drugs produce a rapid blockade of serotonin transporters (SERTs) in vitro, several weeks of treatment are necessary to observe clinical benefits. This paradox has not been solved yet. Recent studies have identified modifications of intracellular signaling proteins and target genes that could contribute to antidepressant-like activity of SSRI (e.g., increases in neurogenesis and BDNF protein levels), and may explain, at least in part, their long delay of action. Although these data suggest a positive regulation of 5-HT on the expression of the gene coding for BDNF, the reciprocal effects of BDNF on brain 5-HT neurotransmission remains poorly documented. To study the impact of BDNF on serotonergic activity, a dual experimental strategy was used to analyze neurochemical and behavioral consequences of its decrease (strategy 1) or increase (strategy 2) in the brain of adult male mice. (1) In heterozygous BDNF+/- mice in which brain BDNF protein levels were decreased by half, an enhancement of basal extracellular 5-HT levels (5-HText) that induced a down-regulation of SERT, i.e., a decrease in its capacity to reuptake 5-HT, was found in the hippocampus. In addition, the SSRI, paroxetine, failed to increase hippocampal 5-HText in BDNF+/- mice, while it produces robust effects in wild-type littermates. Thus, BDNF+/- mice can be viewed as an animal model of genetic resistance to serotonergic antidepressant drugs. (2) In wild-type BDNF+/+ mice, the effects of intra-hippocampal (vHi) injection of BDNF (100 ng) in combination with a SSRI was examined by using intracerebral microdialysis and behavioral paradigms that predict an antidepressant- and anxiolytic-like activity of a molecule [the forced swim test (FST) and the open field paradigm (OF) respectively]. BDNF induced a rapid and transient increase in paroxetine response on 5-HText

  6. A high-fat diet impairs reproduction by decreasing the IL1β level in mice treated at immature stage.

    PubMed

    Zhang, Jie; Li, Kai; Yuan, Miao; Zhang, Jie; Huang, Guizen; Ao, Jie; Tan, Haoze; Li, Yanyan; Gong, Di; Li, Jun; Kang, Lei; An, Nini; Li, Fei; Lin, Ping; Huang, Lugang

    2017-04-03

    Obesity causes low-grade inflammation that is involved in male infertility. Interleukin 1 beta (IL1β) plays an important role in this process. A high-fat diet (HFD) is the most common cause of obesity. However, the effect of a HFD on IL1β and its consequence in reproduction remain unclear. We established a HFD model in mice treated at immature stage (mice-TIS) and mice treated at mature stage (mice-TMS). Surprisingly, we found that a HFD decreased IL1β levels and was accompanied by an increase in testosterone in mice-TIS, while the reverse results were observed in mice-TMS. In addition, a HFD caused a reduction in testis macrophages and in the expression of inflammasome-related genes and proteins in mice-TIS. Furthermore, we found that IL1β inhibited testosterone secretion through down-regulating the gene expression of P450SCC and P450c17. However, the influence on mice-TIS that were induced by a HFD was recovered by stopping the HFD. In this study, we are the first to report that a HFD impairs the reproductive system by decreasing IL1β and enhancing testosterone levels in mice-TIS, which are different from the effects in mice-TMS. This provides new ideas for the treatment of obesity-induced infertility.

  7. Decrease of Population Divergence in Eurasian Perch (Perca fluviatilis) in Browning Waters: Role of Fatty Acids and Foraging Efficiency

    PubMed Central

    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

  8. 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.

  9. Cerebrospinal fluid histamine levels are decreased in patients with narcolepsy and excessive daytime sleepiness of other origin.

    PubMed

    Bassetti, Claudio L; Baumann, Christian R; Dauvilliers, Yves; Croyal, Michael; Robert, Philippe; Schwartz, Jean-Charles

    2010-12-01

    Histaminergic neurons of the hypothalamic tuberomammillary nucleus constitute a major wake-promoting system. In animals, cerebrospinal fluid (CSF) histamine levels are increased during wakefulness and after sleep deprivation and decreased during sleep. An involvement of the histamine system in human disorders has not, to our knowledge, been reported. We measured hypocretin-1 and histamine levels in the lumbar CSF of 28 patients with and without excessive daytime sleepiness (EDS) as assessed by the Epworth Sleepiness Scale (ESS). There were 10 patients with EDS (ESS > 10, mean ESS = 14). Diagnoses included narcolepsy (n = 4), idiopathic hypersomnia (n = 2), sleep apnoea (n = 2) and multiple sclerosis (n = 2). Three patients were treated with stimulants. Their mean CSF histamine was 258 ± 159 PM. There were 18 patients without EDS (ESS < 9, mean ESS = 5). No patients were treated with stimulants. Their mean CSF histamine was significantly higher (624 ± 481 PM, P = 0.007). There was a significant inverse correlation (r = -0.48, P = 0.02) between ESS and both CSF histamine and hypocretin-1 levels. These observations suggest that narcolepsy and EDS of other origin are associated in humans with lower CSF histamine levels and therefore with a reduced activity of the wake-promoting histaminergic neuronal system.

  10. 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

  11. The antidiabetic drug metformin decreases mitochondrial respiration and tricarboxylic acid cycle activity in cultured primary rat astrocytes.

    PubMed

    Hohnholt, Michaela C; Blumrich, Eva-Maria; Waagepetersen, Helle S; Dringen, Ralf

    2017-03-19

    Metformin is an antidiabetic drug that is used daily by millions of patients worldwide. Metformin is able to cross the blood-brain barrier and has recently been shown to increase glucose consumption and lactate release in cultured astrocytes. However, potential effects of metformin on mitochondrial tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping (13) C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U-(13) C]glucose. The presence of metformin did not compromise the viability of cultured astrocytes during 4 hr of incubation, but almost doubled cellular glucose consumption and lactate release. Compared with control cells, the presence of metformin dramatically lowered the molecular (13) C carbon labeling (MCL) of the cellular TCA cycle intermediates citrate, α-ketoglutarate, succinate, fumarate, and malate, as well as the MCL of the TCA cycle intermediate-derived amino acids glutamate, glutamine, and aspartate. In addition to the total molecular (13) C labeling, analysis of the individual isotopomers of TCA cycle intermediates confirmed a severe decline in labeling and a significant lowering in TCA cycling ratio in metformin-treated astrocytes. Finally, the oxygen consumption of mitochondria isolated from metformin-treated astrocytes was drastically reduced in the presence of complex I substrates, but not of complex II substrates. These data demonstrate that exposure to metformin strongly impairs complex I-mediated mitochondrial respiration in astrocytes, which is likely to cause the observed decrease in labeling of mitochondrial TCA cycle intermediates and the stimulation of glycolytic lactate production. © 2017 Wiley Periodicals, Inc.

  12. Serum and Muscle Interleukin-15 Levels Decrease in Aging Mice; Correlation with Declines in Soluble Interleukin-15 Receptor Alpha Expression

    PubMed Central

    Quinn, LeBris S.; Anderson, Barbara G.; Strait-Bodey, Lena; Wolden-Hanson, Tami

    2009-01-01

    Interleukin-15 (IL-15) is a skeletal muscle-derived cytokine with favorable effects on muscle mass and body composition. Modulation of IL-15 levels has been suggested as a treatment for sarcopenia and age-associated increases in adiposity. However, it is unclear whether IL-15 levels change during aging, as measurement of IL-15 at physiological concentrations in mice has been technically difficult, and translational regulation of IL-15 is complex. Moreover, the IL-15 receptor alpha (IL-15Rα) can comprise part of a membrane-associated receptor complex, or appear as a soluble form which stabilizes IL-15 and facilitates IL-15 secretion. Here, we report measurement of physiological levels of murine IL-15, and determine that muscle and serum IL-15 levels decline progressively with age. However, expression of IL-15 mRNA and membrane-associated subunits of the IL-15 receptor did not change with age in muscle. Expression of soluble IL-15Rα (sIL-15Rα) mRNA declined 5-fold with age, and serum IL-15 levels correlated highly with muscle sIL-15 mRNA expression, suggesting declines in sIL-15Rα expression lead to decreased circulating IL-15 levels during aging. These findings complement studies which described several single-nucleotide polymorphisms in the human IL-15Rα gene which impact muscularity and adiposity, and provide a technical basis for further investigation of IL-15 and the sIL-15Rα in determining body composition in aging mice, as a model for humans. PMID:19854259

  13. Human cytomegalovirus decreases constitutive transcription of MHC class II genes in mature Langerhans cells by reducing CIITA transcript levels.

    PubMed

    Lee, Andrew W; Wang, Nan; Hornell, Tara M C; Harding, James J; Deshpande, Chetan; Hertel, Laura; Lacaille, Vashti; Pashine, Achal; Macaubas, Claudia; Mocarski, Edward S; Mellins, Elizabeth D

    2011-05-01

    Human cytomegalovirus (HCMV) productively infects CD34(+) progenitor-derived, mature Langerhans-type dendritic cells (matLC) and reduces surface expression of MHC class II complexes (MHC II) by increasing intracellular retention of these molecules. To determine whether HCMV also inhibits MHC II expression by other mechanisms, we assessed mRNA levels of the class II transcriptional regulator, CIITA, and several of its target genes in infected matLC. Levels of CIITA, HLA-DRA (DRA) and DRB transcripts, and new DR protein synthesis were compared in mock-infected and HCMV-infected cells by quantitative PCR and pulse-chase immunoprecipitation analyses, respectively. CIITA mRNA levels were significantly lower in HCMV-infected matLC as compared to mock-infected cells. When assessed in the presence of Actinomycin D, the stability of CIITA transcripts was not diminished by HCMV. Analysis of promoter-specific CIITA isoforms revealed that types I, III and IV all were decreased by HCMV, a result that differs from changes after incubation of these cells with lipopolysaccharide (LPS). Exposure to UV-inactivated virus failed to reduce CIITA mRNA levels, implicating de novo viral gene expression in this effect. HCMV-infected matLC also expressed lower levels of DR transcripts and reduced DR protein synthesis rates compared to mock-infected matLC. In summary, we demonstrate that HCMV infection of a human dendritic cell subset inhibits constitutive CIITA expression, most likely at the transcriptional level, resulting in reduced MHC II biosynthesis. We suggest this represents a new mechanism of modulation of mature LC by HCMV.

  14. Decreased incidence of acute graft-versus-host disease by continuous infusion of cyclosporine with a higher target blood level.

    PubMed

    Oshima, Kumi; Kanda, Yoshinobu; Nakasone, Hideki; Arai, Shunya; Nishimoto, Nahoko; Sato, Hiroyuki; Watanabe, Takuro; Hosoya, Noriko; Izutsu, Koji; Asai, Takashi; Hangaishi, Akira; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-03-01

    Cyclosporine A (CsA) is the mainstay of pharmacologic prevention of acute graft-versus-host disease (GVHD). We previously reported that continuous infusion of CsA with a target blood level between 250 and 400 ng/ml significantly increased the incidence of acute GVHD compared to twice-daily infusion with a target trough level between 150 and 300 ng/ml. Thus, we raised the target level of CsA continuous infusion to 450-550 ng/ml. We treated 33 patients with the higher target level (CsA500) and compared the efficacy and toxicity with those in the 33 historical control patients (CsA300 group). Other transplantation procedures were not changed. The patients' characteristics were equivalent. The average CsA concentration was adjusted around 500 ng/ml and the actual daily dose was maintained at the initial dose (CsA 3mg/kg/day). Toxicities were equivalently observed among the two groups. The incidence of grades II-IV acute GVHD was significantly lower in the CsA500 group (27 vs. 52%, P = 0.033). The target level of CsA was identified as an independent significant risk factor for grades II-IV acute GVHD (P = 0.039), adjusted for the presence of HLA mismatch. The incidence of chronic GVHD was also decreased in the CsA500 group (47 vs. 73%, P = 0.016). We conclude that the toxicity of the continuous CsA infusion with a target level of 450-550 ng/ml is acceptable and the efficacy to prevent acute GVHD is significant. A larger comparative study is warranted to confirm these findings.

  15. 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.

  16. Ocean acidification increases fatty acids levels of larval fish

    PubMed Central

    Díaz-Gil, Carlos; Catalán, Ignacio A.; Palmer, Miquel; Faulk, Cynthia K.; Fuiman, Lee A.

    2015-01-01

    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

  17. 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.

  18. Response of drinking-water reservoir ecosystems to decreased acidic atmospheric deposition in SE Germany: trends of chemical reversal.

    PubMed

    Ulrich, Kai-Uwe; Paul, Lothar; Meybohm, Andreas

    2006-05-01

    This study evaluates chemical trends of seven acidified reservoirs and 22 tributaries in the Erzgebirge from 1993 to 2003. About 85% of these waters showed significantly (p < 0.05) declining concentrations of protons (-69%), nitrate (-41%), sulfate (-27%), and reactive aluminum (-50% on average). This reversal is attributed to the intense reduction of industrial SO2 and NOx emissions from formerly high levels, which declined by 99% and 82% in the German-Czech border region between 1993 and 1999. The deposition rates of protons and sulfur decreased by 70-90%. Since 1993, the dry deposition of total inorganic nitrogen diminished to a minor degree, but the wet deposition remained unchanged. The surface waters reflect a substantial decrease in Al exchange processes, a release of sulfur previously stored in soils, and an uptake of nitrate by forest vegetation. The latter effect may be supported by soil protection liming which contributed to the chemical reversal in almost 20% of the study waters.

  19. A rotamer energy level study of sulfuric acid.

    PubMed

    Partanen, Lauri; Pesonen, Janne; Sjöholm, Elina; Halonen, Lauri

    2013-10-14

    It is a common approach in quantum chemical calculations for polyatomic molecules to rigidly constrain some of the degrees of freedom in order to make the calculations computationally feasible. However, the presence of the rigid constraints also affects the kinetic energy operator resulting in the frozen mode correction, originally derived by Pesonen [J. Chem. Phys. 139, 144310 (2013)]. In this study, we compare the effects of this correction to several different approximations to the kinetic energy operator used in the literature, in the specific case of the rotamer energy levels of sulfuric acid. The two stable conformers of sulfuric acid are connected by the rotations of the O-S-O-H dihedral angles and possess C2 and Cs symmetry in the order of increasing energy. Our results show that of the models tested, the largest differences with the frozen mode corrected values were obtained by simply omitting the passive degrees of freedom. For the lowest 17 excited states, this inappropriate treatment introduces an increase of 9.6 cm(-1) on average, with an increase of 8.7 cm(-1) in the zero-point energies. With our two-dimensional potential energy surface calculated at the CCSD(T)-F12a/VDZ-F12 level, we observe a radical shift in the density of states compared to the harmonic picture, combined with an increase in zero point energy. Thus, we conclude that the quantum mechanical inclusion of the different conformers of sulfuric acid have a significant effect on its vibrational partition function, suggesting that it will also have an impact on the computational values of the thermodynamic properties of any reactions where sulfuric acid plays a role. Finally, we also considered the effect of the anharmonicities for the other vibrational degrees of freedom with a VSCF-calculation at the DF-MP2-F12/VTZ-F12 level of theory but found that the inclusion of the other conformer had the more important effect on the vibrational partition function.

  20. Novel sandwich ELISAs for rat DMP1: age-related decrease of circulatory DMP1 levels in male rats.

    PubMed

    Sato, Sunao; Hashimoto, Jun; Usami, Yu; Ohyama, Kaname; Isogai, Yukihiro; Hagiwara, Yoshiaki; Maruyama, Nobuhiro; Komori, Toshihisa; Kuroda, Tatsuhiko; Toyosawa, Satoru

    2013-12-01

    Dentin matrix protein 1 (DMP1), a noncollagenous bone matrix protein produced by osteocytes, regulates matrix mineralization and phosphate homeostasis. The lack of a precise assay for circulating DMP1 levels impairs further investigation of the protein's biological significance. Because full-length precursor DMP1 is cleaved into NH2- and COOH-terminal fragments during the secretory process, we developed two new sandwich ELISAs for the NH2- and COOH-terminal fragments of rat DMP1. One of these ELISAs, ELISA 1-2, is based on two affinity-purified polyclonal antibodies against the DMP1-1 and DMP1-2 peptides of the NH2-terminal fragment, whereas the other, ELISA 4-3, is based on two affinity-purified polyclonal antibodies against the DMP1-3 and DMP1-4 peptides of the COOH-terminal fragment. The polyclonal antibodies were characterized in immunohistochemical and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) studies. Immunohistochemical analyses of rat bone using these polyclonal antibodies revealed DMP1 immunoreactivity in osteocytes and pericanalicular matrix, consistent with the previously reported osteocyte-specific expression of DMP1. LC-MS/MS analyses of rat plasma-derived immunoreactive products affinity-extracted with these antibodies revealed the presence of DMP1 in circulating blood. The ELISAs established with these antibodies met accepted standards for reproducibility, repeatability, precision, and accuracy. Circulating DMP1 and levels of other biochemical markers (osteocalcin, Trap5b, Dkk-1, and SOST) were measured in 2-, 4-, 8-, 12-, 18-, 24-, 72-, and 96-week-old Wistar male rats. Circulating DMP1 levels determined by ELISAs 1-2 and 4-3 significantly decreased with age. During rapid skeletal growth (2-12weeks), DMP1 levels measured by ELISA 4-3 were over three times higher than those measured by ELISA 1-2; however, DMP1 levels in old animals (72 and 96weeks) were almost the same when measured by either ELISA. DMP1 levels

  1. Protective effect of taurine on the decreased biogenic amine neurotransmitter levels in the brain of mice exposed to arsenic.

    PubMed

    Liu, Xiaohui; Piao, Fengyuan; Li, Yachen

    2013-01-01

    Arsenic (As) exposure has a toxic effect on the central nervous system, especially on learning and memory. Norepinephrine (NE), dopamine (DA), and serotonin (5-HT) play an important role in learning and memory function of the brain. In the present study, the protective effect of taurine on the disturbed biogenic amine neurotransmitter levels in the mouse brain induced by arsenic was examined. Sixty SPF mice were divided into three groups. The As exposure group was administered with 4 ppm As(2)O(3) through drinking water for 60 days. The protective group was treated with both 4 ppm As(2)O(3) and 150 mg/kg taurine. The control group was given drinking water alone. The levels of NE, DA, and 5-HT were determined by HPLC in the cerebrum and cerebellum of mice. Ultrastructure of synapses in brain tissue of mice was observed in these groups by transmission electron microscopy. The mRNA expressions of dopamine beta hydroxylase (DBH), tyrosine hydroxylase (TH), and tryptophan hydroxylase (TPH) as NE, DA, and 5-HT synzymes were also analyzed by real-time RT-PCR. The results showed that the concentrations of NE, DA, and 5-HT; the number of synaptic vesicles; and the expressions of TH, TPH, and DBH genes in the brains of mice exposed to As alone were significantly decreased. However, administration of taurine significantly alleviated the toxic effect on biochemicals detected in the experiment, compared with that in the brain of mice exposed to As alone. These results indicated that taurine was effective in counteracting the decreased biogenic amine neurotransmitter level and the mRNA expressions of their synzymes induced by arsenic.

  2. Decreased Level of Klotho Contributes to Drug Resistance in Lung Cancer Cells: Involving in Klotho-Mediated Cell Autophagy.

    PubMed

    Chen, TianJun; Ren, Hui; Thakur, Asmitanand; Yang, Tian; Li, Yang; Zhang, Shuo; Wang, Ting; Chen, MingWei

    2016-12-01

    Klotho is originally discovered as an anti-aging gene and recently identified as a tumor suppressor in various human cancers. Drug resistance is a major obstacle to affect the treatment of chemotherapy. In the present study, we explore the role of klotho on drug resistance in human lung cancers and investigate the mechanism of klotho on drug resistance in lung cancer cells. First, we detected a panel of six human lung cancer cell lines, including H460, SK-MES-1, cisplatin (DDP)-resistant A549/DDP, its parental subline A549, docetaxel (DTX)-resistant SPC-A-1/DTX, and SPC-A-1 by western blotting analysis. The results showed that klotho level was significantly decreased in chemotherapeutic drug-resistant lung cancer cells. Next, klotho was overexpressed in drug-resistant cancer cell lines and the results showed that overexpression of klotho significantly inhibited cell proliferation of A549/DDP and SPC-A-1/DTX. Conversely, knockdown of the expression of klotho significantly promoted cell growth of lung cancer cells. Furthermore, overexpression of klotho had synergistic effects with cisplatin to inhibit the proliferation of drug-resistant lung cancer cells in a dose- and time-dependent manner. The molecular mechanism was explored by western blotting analysis and the results revealed that the levels of beclin 1 and LC3-II were obviously increased, suggesting cell autophagy enhanced in drug-resistant cancer cells. Importantly, overexpression of klotho would inhibit cell autophagy in A549/DDP cells. All the results demonstrated that the levels of klotho were significantly decreased, which was accompanied by the increased cell autophagy in drug-resistant lung cancer cells. Overexpression of klotho would inhibit cell autophagy in drug-resistant lung cancers, which may probably contribute to reverse drug resistance in lung cancer cells.

  3. 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

  4. 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

  5. Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth?

    PubMed

    Alkabbani, Abdulrahman G; Mon, Sann Y; Hatipoglu, Betul; Kennedy, Laurence; Faiman, Charles; Weil, Robert J; Hamrahian, Amir H

    2014-04-01

    The optimal interval for follow-up imaging of patients with prolactinomas is unclear. We wish to determine the likelihood of tumor enlargement in patients with prolactinomas who have a stable or reduced prolactin (PRL) level over time, whether or not they are treated with a dopamine agonist (DA). We identified 80 patients with prolactinomas (34 men, 46 women) who had at least two paired sets of serum PRL levels and pituitary MRIs, 3 or more months apart. Patients with hyperprolactinemia due to drug or stalk effects were excluded. The median (range) age was 45 (25-77) years. Sixty-three patients (78.8%) were treated with DA. PRL levels (ng/mL) at the initial and latest sets were 114 (0.3-15,732) and 16 (0.3-1,204), respectively. In patients with identifiable tumors, the maximum tumor diameters (mm) at the initial and latest MRI studies were 12.5 (2-60) and 12.5 (2-39) respectively, with an interval of 2.9 (0.3-9.7) years. Sixty percent of patients (n = 48) had a macroadenoma. Forty-two (52.5%) patients had either disappearance of the tumor (n = 22) or reduction (n = 20) in tumor size. In the remainder, tumor size was stable in 35 but increased in 3 patients. One of these patients, observed off therapy had a concomitant rise in PRL level. The other 2 had evidence of pituitary hemorrhage with no PRL increase. Tumor growth in prolactinoma patients with a stable or decreasing PRL level, regardless of size, is a rare event. Repetitive pituitary imaging in these patients may not be warranted.

  6. C3a Increases VEGF and Decreases PEDF mRNA Levels in Human Retinal Pigment Epithelial Cells.

    PubMed

    Long, Qin; Cao, Xiaoguang; Bian, Ailing; Li, Ying

    2016-01-01

    Complement activation, specifically complement 3 (C3) activation and C3a generation, contributes to an imbalance between angiogenic stimulation by vascular endothelial growth factor (VEGF) and angiogenic inhibition by pigment epithelial derived factor (PEDF), leading to pathological angiogenesis. This study aimed to investigate the effects of C3a and small interfering RNA (siRNA) targeting C3 on the levels of VEGF and PEDF mRNAs in human retinal pigment epithelial (RPE) cells. ARPE-19 cells were cultured in the presence of exogenous C3a at 0.1 μM and 0.3 μM C3a for 24, 48, and 72 hours. 0.1 pmol/μL duplexes of siRNA targeting C3 were applied for C3a inhibition by transfecting ARPE-19 cells for 48 hours. RT-PCR was performed to examine the level of VEGF and PEDF mRNA. A random siRNA duplex was set for control siRNA. Results demonstrated that exogenous C3a significantly upregulated VEGF and downregulated PEDF mRNA levels in cultured ARPE-19 cells, and siRNA targeting C3 transfection reversed the above changes, significantly reducing VEGF and enhancing PEDF mRNAs level in ARPE-19 cells compared to the control. The present data provided evidence that reducing C3 activation can decreases VEGF and increase PEDF mRNA level in RPE and may serve as a potential therapy in pathological angiogenesis.

  7. C3a Increases VEGF and Decreases PEDF mRNA Levels in Human Retinal Pigment Epithelial Cells

    PubMed Central

    Long, Qin; Cao, Xiaoguang; Bian, Ailing

    2016-01-01

    Complement activation, specifically complement 3 (C3) activation and C3a generation, contributes to an imbalance between angiogenic stimulation by vascular endothelial growth factor (VEGF) and angiogenic inhibition by pigment epithelial derived factor (PEDF), leading to pathological angiogenesis. This study aimed to investigate the effects of C3a and small interfering RNA (siRNA) targeting C3 on the levels of VEGF and PEDF mRNAs in human retinal pigment epithelial (RPE) cells. ARPE-19 cells were cultured in the presence of exogenous C3a at 0.1 μM and 0.3 μM C3a for 24, 48, and 72 hours. 0.1 pmol/μL duplexes of siRNA targeting C3 were applied for C3a inhibition by transfecting ARPE-19 cells for 48 hours. RT-PCR was performed to examine the level of VEGF and PEDF mRNA. A random siRNA duplex was set for control siRNA. Results demonstrated that exogenous C3a significantly upregulated VEGF and downregulated PEDF mRNA levels in cultured ARPE-19 cells, and siRNA targeting C3 transfection reversed the above changes, significantly reducing VEGF and enhancing PEDF mRNAs level in ARPE-19 cells compared to the control. The present data provided evidence that reducing C3 activation can decreases VEGF and increase PEDF mRNA level in RPE and may serve as a potential therapy in pathological angiogenesis. PMID:27747237

  8. 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.

  9. Influence of age, dietary cholic acid, and calcium levels on performance, utilization of free fatty acids, and bone mineralization in broilers.

    PubMed

    Atteh, J O; Leeson, S

    1985-10-01

    The effects of age on the utilization of dietary palmitic or a 50/50 mixture of palmitic and oleic acid at the 8% inclusion level in the absence or presence of .2% cholic acid and also in the presence of low (.8%) or high (1.2%) calcium were investigated using broiler chicks from 1 to 56 days of age. Significant interactions (P less than .01) were observed between the type of fatty acid supplemented and the presence or absence of cholic acid on weight gain and feed efficiency. Supplementing diets with a mixture of equal weights of palmitic and oleic acid, reduced feed intake relative to control diets and diets supplemented with palmitic acid alone. There was an interaction between the age of the bird and the type of fatty acid supplemented on fat retention and metabolizable energy (ME) of diets (P less than .01). There was also a significant interaction between the type of fatty acid supplemented and the addition of cholic acid on fat retention and ME of diets. While cholic acid reduced soap formation during the process of digestion (P less than .05), increasing dietary calcium level increased the proportion of the digesta fat that was present as soap (P less than .01). The proportion of digesta and excreta fat, present as soap, depended on the type of fatty acid supplemented. The addition of free fatty acids to broiler diets resulted in a decrease in bone ash and bone calcium content relative to those birds fed the control diet. It is concluded that the ability of broilers to utilize dietary free fatty acids depends on the age at which they are fed, although in all cases supplemental cholic acid enhances fatty acid utilization.

  10. Effects of domoic acid on serum levels of TSH and thyroid hormones.

    PubMed

    Arufe, M C; Arias, B; Durán, R; Alfonso, M

    1995-08-01

    The actions of Domoic Acid (Dom), a marine toxin, on the levels of serum TSH and thyroid hormones (T4 and T3) has been studied to determine if these actions could be mediated by the serotoninergic system. In all the experiments, adult male Wistar rats were used. The Dom dissolved in saline was administered via i.p. in doses of 0.5 and 1 mg/kg. The T4 and T3 concentrations were determined by enzimoinmunoassay and TSH concentration was determined by radioinmunoassay. The results show that Dom 1 mg/kg increases the serum T4 levels one hour after treatment and decreases these levels 2 and 3 hr after treatment. Dom 0.5 mg/kg decreased the serum T4 levels 2 and 3 hr after treatment. The concentrations of T3 in serum were unchanged by both doses of Dom. The concentration of TSH was increased by Dom. In order to study the possible mediation of the serotoninergic system in the effect of Dom on the hormone levels, PCPA, a tryptophan hydroxylase inhibitor, was administered i.p. 90 min before blood sampling. In this case, with both doses of Dom a decrease in the levels of both hormones occurred with respect to the PCPA group. These results indicate that the serotoninergic system could affect the actions of Dom on TSH and thyroid hormone secretion.

  11. Serum hyaluronic acid levels in patients with ankylosing spondylitis.

    PubMed

    Duruöz, Mehmet Tuncay; Turan, Yasemin; Cerrahoglu, Lale; Isbilen, Banu

    2008-05-01

    Our aim in this study was to investigate serum hyaluronic acid (HA) levels and the relationship between clinical parameters in ankylosing spondylitis (AS). Approximately 30 patients with AS and 30 healthy individuals were recruited in this study consecutively. Cross-sectional study was planned, and demographic, clinical, functional, radiological, and laboratory data of patients were evaluated. Disease activity, functional status, and quality of life were assessed, respectively, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Short-Form 36 (SF-36). Mander Enthesis Index (MEI) was used for evaluation of enthesis involvement. We examined serum concentrations of HA (ng/ml) in patients with AS and controls. The mean ages of patients and control group were 38.3 (SD=10.8) and 42.7 (SD=10.6) years, respectively. The mean of serum HA levels in AS patients was 40.4 (SD=34.8) ng/ml and in controls was 24.9 (SD=20.2). There was significant difference of HA levels between two groups (p=0.04). Furthermore, there was a significant correlation between HA level and distance of hand-floor (r=0.444, p=0.014), modified lumbar Schober's (r= -0.413, p=0.023), distance of chin to chest (r=0.436, p=0.016), right sacroiliit grade (r=0.601, p<0.001), left sacroiliit grade (r=0.610, p<0.001), C reactive protein level (r=0.404, p=0.027), albumin (r= -0.464, p=0.010), C3 (p=0.449, p=0.013), and IgA levels (r=0.369, p=0.045). However, there was no significant correlation between HA levels with MEI, BASFI, BASDAI, and SF-36 (p >or= 0.05). Serum HA level was significantly higher in AS patients than controls. However, there was no significant correlation between serum HA level and disease-specific measures as BASFI and BASDAI; it had significant relation with spinal mobility limitation, sacroiliitis, and laboratory parameters related with acute inflammation. The serum HA level may be a potential biomarker of axial

  12. Streptozotocin-Induced Diabetes Decreases Mammary Gland Lipoprotein Lipase Activity and Messenger Ribonucleic Acid in Pregnant and Nonpregnant Rats

    PubMed Central

    Blanco-Dolado, Laura; Martín-Hidalgo, Antonia; Herrera, Emilio

    2002-01-01

    Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity in adipose tissue and development of hypertriglyceridemia. To determine how a condition of severe insulin deficiency affects mammary gland LPL activity and mRNA expression during late pregnancy, streptozotocin (STZ) treated (40 mg/kg) and non-treated (control) virgin and 20 day pregnant rats were studied. In control rats, both LPL activity and mRNA were higher in pregnant than in virgin rats. When compared to control rats, STZ-treated rats, either pregnant or virgin, showed decreased LPL activity and mRNA content. Furthermore, mammary gland LPL activity was linearly correlated with mRNA content, and either variable was linearly correlated with plasma insulin levels. Thus, insulin deficiency impairs the expression of LPL in mammary glands, revealing the role of insulin as a modulator of the enzyme at the mRNA expression level. PMID:11900280

  13. Differences in the fatty-acid composition of rodent spermatozoa are associated to levels of sperm competition.

    PubMed

    delBarco-Trillo, Javier; Mateo, Rafael; Roldan, Eduardo R S

    2015-03-20

    Sperm competition is a prevalent phenomenon that drives the evolution of sperm function. High levels of sperm competition lead to increased metabolism to fuel higher sperm velocities. This enhanced metabolism can result in oxidative damage (including lipid peroxidation) and damage to the membrane. We hypothesized that in those species experiencing high levels of sperm competition there are changes in the fatty-acid composition of the sperm membrane that makes the membrane more resistant to oxidative damage. Given that polyunsaturated fatty acids (PUFAs) are the most prone to lipid peroxidation, we predicted that higher sperm competition leads to a reduction in the proportion of sperm PUFAs. In contrast, we predicted that levels of sperm competition should not affect the proportion of PUFAs in somatic cells. To test these predictions, we quantified the fatty-acid composition of sperm, testis and liver cells in four mouse species (genus Mus) that differ in their levels of sperm competition. Fatty-acid composition in testis and liver cells was not associated to sperm competition levels. However, in sperm cells, as predicted, an increase in sperm competition levels was associated with an increase in the proportion of saturated fatty-acids (the most resistant to lipid peroxidation) and by a concomitant decrease in the proportion of PUFAs. Two particular fatty acids were most responsible for this pattern (arachidonic acid and palmitic acid). Our findings thus indicate that sperm competition has a pervasive influence in the composition of sperm cells that ultimately may have important effects in sperm function.

  14. Decreased levels of nitrosothiols in the lower airways of patients with cystic fibrosis and normal pulmonary function.

    PubMed

    Grasemann, H; Gaston, B; Fang, K; Paul, K; Ratjen, F

    1999-12-01

    Airway S-nitrosothiols (SNOs) are naturally occurring bronchodilators. SNOs, nitrate, and nitrite were measured in bronchoalveolar lavage fluid of 23 patients with cystic fibrosis (CF) and mild pulmonary disease (aged 6-16 years) and 13 healthy children (aged 8-15 years). Concentrations of SNOs were decreased in the lower airways of patients with CF and mild pulmonary disease (median, range: 0, 0-320 nmol/L vs 80, 0-970 nmol/L) despite normal levels of the inert nitric oxide metabolites nitrate and nitrite (mean +/- SEM: 3.7 +/- 0.5 micromol/L vs 4.8 +/- 0.9 micromol/L). S-nitrosolation- mediated bioreactivities may be impaired by depletion of the CF airway SNO reservoir.

  15. 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

  16. Beta-adrenergic receptor agonist decreases VEGF levels through altered eNOS and PKC signaling in diabetic retina

    PubMed Central

    Jiang, Youde; Zhang, Qiuhua; Steinle, Jena J.

    2015-01-01

    Vascular endothelial cell growth factor (VEGF) is increased in diabetic macular edema. Compound 49b, a novel β-adrenergic receptor agonist, is protective in a type 1 diabetic rat model. We questioned whether Compound 49b could decrease VEGF levels, suggesting that Compound 49b may be effective against edema. Two-month diabetic rats received topical Compound 49b for 7 days only and/or insulin-like growth factor binding protein 3 (IGFBP-3) siRNA. We also measured endothelial nitric oxide synthase (eNOS) and protein kinase C (PKC)ζ and PKCδ phosphorylation. Retinal endothelial cells (RECs) cultured in high glucose were treated with Compound 49b and IGFBP-3 siRNA for evaluation of the same signaling pathways. Compound 49b significantly decreased VEGF through increased IGFBP-3 in the diabetic retina. Compound 49b also reduced eNOS, PKCζ and PKCδ phosphorylation in the diabetic retina and REC. Compound 49b regulated a number of proteins involved in REC barrier properties. PMID:26115368

  17. Alpha-synuclein modulates NR2B-containing NMDA receptors and decreases their levels after rotenone exposure.

    PubMed

    Navarria, Laura; Zaltieri, Michela; Longhena, Francesca; Spillantini, Maria Grazia; Missale, Cristina; Spano, PierFranco; Bellucci, Arianna

    2015-01-01

    Alpha-synuclein (α-syn) is the main protein component of Lewy bodies (LBs), that together with nigrostriatal dopamine neuron loss constitute typical pathological hallmarks of Parkinson's disease (PD). Glutamate N-methyl-d-aspartate receptor (NMDAR) abnormalities, peculiarly involving NR2B-containing NMDAR, have been observed in the brain of PD patients and in several experimental models of the disease. Recent findings, indicating that α-syn can modulate NMDAR trafficking and function, suggest that this protein may be a pivotal regulator of NMDAR activity. Prompted by these evidences, we used fluorescence immunocytochemistry, western blotting and ratiometric Ca(2+) measurements to investigate whether wild type (wt) or C-terminally truncated α-syn can specifically modulate NR2B-containing NMDAR levels, subcellular trafficking and function. In addition, we evaluated whether the exposure of primary cortical neurons to increasing concentrations of rotenone could differentially regulate NR2B levels and cell viability in the presence or in the absence of α-syn. Our results indicate that both wt and C-terminally truncated α-syn negatively modulate NR2B-containing NMDAR levels, membrane translocation and function. Moreover, we found that absence of α-syn abolishes the rotenone-dependent decrease of NR2B levels and reduces neuronal vulnerability in primary cortical neurons. These findings suggest that α-syn can modulate neuronal resilience by regulating NR2B-containing NMDAR, whose specific alterations could connect α-syn pathology to neuronal degeneration in PD.

  18. Effects of copper on chlorophyll, proline, protein and abscisic acid level of sunflower (Helianthus annuus L.) seedlings.

    PubMed

    Zengin, Fikriye Kirbag; Kirbag, Sevda

    2007-07-01

    The effect of copperchloride (CuCl2) on the level of chlorophyll (a+b), proline, protein and abscisic acid in sunflower (Helianthus annuus L.) seedlings were investigated Control and copper treated (0.4, 0.5 and 0.6 mM) seedlings were grown for ten days in Hoagland solution. Abscisic acid content was determined in root, shoot and leaf tissues of seedlings by HPLC. Copper stress caused significant increase of the abscisic acid contents in roots, shoots and leaves of seedlings. The increase was dependent on the copper salt concentration. Enhanced accumulation of proline in the leaves of seedlings exposed to copper was determined, as well as a decrease of chlorophyll (a+b) and total protein (p < 0.05 or p < 0.01). It was observed that the level of chlorophyll (a+b) and total protein (p < 0.05 or p < 0.01) remarkably decreased as copper concentration increased to 0.6 mM, although the levels of proline and abscisic acid in the leaves of plants were increased--a dose-depended behavior The same trends were also observed with the level of abscisic acid of stems and roots. Copper has dose- depended effects on chlorophyll, proline, protein and abscisic acid level of sunflower (Helianthus annuus L.) seedlings. Thus, we assumed that copper levels increase above some critical points seedling growth get negative effects. This assumption is in line with previous findings.

  19. Anti-ageing properties of Khelma Longevity™: Treatment of human fibroblasts increases proteasome levels and decreases the levels of oxidized proteins.

    PubMed

    Voutetakis, Konstantinos; Delitsikou, Vasiliki; Magouritsas, Michel Georges; Gonosa, Efstathios S

    2017-03-05

    We have determined the putative anti-ageing properties of Khelma Longevity™, a formula based on various natural compounds from the Mediterranean area. Human primary fibroblast cultures were treated with a wide range of concentrations of Khelma Longevity™ for 1 day or 3 consecutive days. Following these treatments, two major and complementary biomarkers of ageing where measured, namely, the proteasome and the amount of oxidized proteins. It was observed that 24hours of treatment with Khelma Longevity™ resulted in a maximum increase of about 41% of the total protein levels of 20S proteasome. Levels of oxidized proteins were reduced by almost 6.5-fold following longer treatments. Specifically we have observed a maximum decrease of protein carbonyls to 84.7% in comparison with nontreated control cells following 3 days of continuous treatment with Khelma Longevity™. These results support the notion that formulas rich in natural compounds from the Mediterranean area possess anti-ageing properties.

  20. 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.

  1. Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects

    PubMed Central

    Neuhaus, Andres H.; Goldberg, Terry E.; Hassoun, Youssef; Bates, John A.; Nassauer, Katharine W.; Sevy, Serge; Opgen-Rhein, Carolin; Malhotra, Anil K.

    2013-01-01

    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

  2. Lower ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Decrease Fat Deposition by Inhibiting Fat Synthesis in Gosling

    PubMed Central

    Yu, Lihuai; Wang, Shunan; Ding, Luoyang; Liang, Xianghuan; Wang, Mengzhi; Dong, Li; Wang, Hongrong

    2016-01-01

    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

  3. 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.

  4. Spinal nerve ligation decreases γ-aminobutyric acidB receptors on specific populations of immunohistochemically identified neurons in L5 dorsal root ganglion of the rat.

    PubMed

    Engle, Mitchell P; Merrill, Michelle A; Marquez De Prado, Blanca; Hammond, Donna L

    2012-06-01

    This study examined the distribution of γ-aminobutyric acid (GABA)(B) receptors on immunohistochemically identified neurons, and levels of GABA(B(1)) and GABA(B(2)) mRNA, in the L4 and L5 dorsal root ganglia (DRG) of the rat in the absence of injury and 2 weeks after L5 spinal nerve ligation. In uninjured DRG, GABA(B(1)) immunoreactivity colocalized exclusively with the neuronal marker (NeuN) and did not colocalize with the satellite cell marker S-100. The GABA(B(1)) subunit colocalized to >97% of DRG neurons immunoreactive (IR) for neurofilament 200 (N52) or calcitonin gene-related peptide (CGRP), or labeled by isolectin B4 (IB4). Immunoreactivity for GABA(B(2)) was not detectable. L5 spinal nerve ligation did not alter the number of GABA(B(1)) -IR neurons or its colocalization pattern in the L4 DRG. However, ligation reduced the number of GABA(B(1)) -IR neurons in the L5 DRG by ≈38% compared with sham-operated and naïve rats. Specifically, ligation decreased the number of CGRP-IR neurons in the L5 DRG by 75%, but did not decrease the percent colocalization of GABA(B(1)) in those that remained. In the few IB4-positive neurons that remained in the L5 DRG, colocalization of GABA(B(1)) -IR decreased to 75%. Ligation also decreased levels of GABA(B(1)) and GABA(B(2)) mRNA in the L5, but not the L4 DRG compared with sham-operated or naïve rats. These findings indicate that the GABA(B) receptor is positioned to presynaptically modulate afferent transmission by myelinated, unmyelinated, and peptidergic afferents in the dorsal horn. Loss of GABA(B) receptors on primary afferent neurons may contribute to the development of mechanical allodynia after L5 spinal nerve ligation.

  5. Combined treatment of betulinic acid, a PTP1B inhibitor, with Orthosiphon stamineus extract decreases body weight in high-fat-fed mice.

    PubMed

    Choi, Yoon-Jung; Park, So-Young; Kim, Jong-Yeon; Won, Kyu-Chang; Kim, Bo-Ra; Son, Jong-Keun; Lee, Seung-Ho; Kim, Yong-Woon

    2013-01-01

    Leptin resistance is a common feature of obesity and is accompanied by hyperleptinemia. Although leptin sensitizers improve leptin resistance, they also decrease plasma leptin levels that attenuate the leptin-associated antiobesity effect. We hypothesized that the combinational treatment of leptin sensitizer and endogenous leptin expression stimulant would synergistically induce an antiobesity effect in high-fat-fed obese animals. Betulinic acid (BA) isolated from Saussurea lappa suppressed the hypothalamic protein tyrosine phosphatase 1B in mice and enhanced the antiobesity effect of leptin in obese rats. Ethanol extract of Orthosiphon stamineus (OS) induced leptin expressions in both 3T3-L1 adipocytes and mice in a dose-dependent manner. To evaluate our hypothesis, we treated obese mice induced by 6 weeks of high-fat-diet feeding with BA and OS for 2 weeks. Although BA or OS alone did not decrease body weight in obese mice, the combinational treatment of BA and OS decreased body weight significantly compared to either BA- or OS-treated obese mice. These results suggest that combinational treatment of BA and OS would be effective for the treatment of obesity.

  6. Keto analogues and amino acids supplementation induces a decrease of white blood cell counts and a reduction of muscle damage during intense exercise under thermoneutral conditions.

    PubMed

    Lima, R C P; Camerino, S R A S; França, T C L; Rodrigues, D S A; Gouveia, M G S; Ximenes-da-Silva, A; Bassini, A; Prado, E S; Cameron, L C

    2017-04-05

    This study evaluated the acute effect of keto analogue and amino acid (AA-KAAA) supplementation on both white blood cell counts and the established biomarkers of muscle damage during exercise under thermoneutral conditions. Sixteen male cyclists received a ketogenic diet for two days and were divided into two equal groups: a group taking AA-KAAA (KA) or a control group (PL). The athletes performed a two hour cycling session followed by a maximum incremental test until voluntary exhaustion (VExh). Blood samples were obtained at rest and during exercise for further hematological and biochemical analyses. Exercise-induced ammonemia increased in the PL group at VExh (75%) but remained unchanged in the KA group. Both groups exhibited a significant increase in leukocyte and neutrophil counts of ∼85% (∼13 × 10(9) L(-1)), but the shape of the lymphocytes and the eosinophil counts suggest that AA-KAAA supplementation helps prevent lymphocytosis. AA-KAAA supplementation induced a decrease in creatine kinase and aspartate aminotransferase levels at VExh while showing a significant decrease in lactate dehydrogenase at 120 min. We found that AA-KAAA supplementation decreases both the lymphocyte count response in blood and the established biomarkers of muscle damage after intense exercise under a low heat stress environment.

  7. Manganese accumulation in membrane fractions of primary astrocytes is associated with decreased γ-aminobutyric acid (GABA) uptake, and is exacerbated by oleic acid and palmitate.

    PubMed

    Fordahl, Steve C; Erikson, Keith M

    2014-05-01

    Manganese (Mn) exposure interferes with GABA uptake; however, the effects of Mn on GABA transport proteins (GATs) have not been identified. We sought to characterize how Mn impairs GAT function in primary rat astrocytes. Astrocytes exposed to Mn (500 μM) had significantly reduced (3)H-GABA uptake despite no change in membrane or cytosolic GAT3 protein levels. Co-treatment with 100 μM oleic or palmitic acids (both known to be elevated in Mn neurotoxicity), exacerbated the Mn-induced decline in (3)H-GABA uptake. Mn accumulation in the membrane fraction of astrocytes was enhanced with fatty acid administration, and was negatively correlated with (3)H-GABA uptake. Furthermore, control cells exposed to Mn only during the experimental uptake had significantly reduced (3)H-GABA uptake, and the addition of GABA (50 μM) blunted cytosolic Mn accumulation. These data indicate that reduced GAT function in astrocytes is influenced by Mn and fatty acids accumulating at or interacting with the plasma membrane.

  8. Effects of dietary saturated or unsaturated fatty acids and calcium levels on performance and mineral metabolism of broiler chicks.

    PubMed

    Atteh, J O; Leeson, S

    1984-11-01

    The effects of inclusion of 8% oleic, palmitic, or a 50/50 mixture of oleic and palmitic acids as the major source of fat in the presence of .8, 1.2, or 1.6% calcium in broiler diets was investigated using broiler chicks from day-old to 3 weeks of age. Supplementation of broiler diets with oleic acid reduced feed intake (P less than .05) and improved feed efficiency (P less than .01) compared to other treatments. Chicks fed diets supplemented with oleic acid or a mixture of oleic and palmitic acid gained more weight (P less than .01) over a 3-week period. Significant interactions were observed between type of dietary fatty acid and calcium level on metabolizable energy of diets (P less than .01), magnesium retention (P less than .05), calcium and fat retention (P less than .01), and proportion of excreta fatty acid that was present as soap (P less than .01). Although all fatty acids tested formed soap in the small intestine, soaps of oleic acid were efficiently utilized as opposed to soaps of palmitic acid. There was a significant (P less than .05) reduction in bone ash and bone calcium content of chicks fed diets supplemented with palmitic acid. There was a significant interaction (P less than .05) between type of fatty acid and calcium level on bone magnesium content. Increasing the calcium content of diets aggravated the decrease in calcium retention and bone calcium content associated with addition of fat.

  9. 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.

  10. Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice.

    PubMed

    Li, F; Dong, H X; Gong, Q H; Wu, Q; Jin, F; Shi, J S

    2015-09-24

    Icariin is derived most commonly from the traditional Chinese herb Epimedium brevicornum Maxim. Our previous studies have shown that icariin protects neurons from neurotoxic and ischemic conditions. This study aims to investigate the effect of icariin on the expression of amyloid precursor protein (APP) and the level of amyloid-β peptide (Aβ), as well as neurogenesis in the brain of Tg2576 mice, an animal model of Alzheimer's disease (AD). Tg2576 mice and wild-type littermates (WT) were randomized into the following three groups: Tg2576, Tg2576+icariin, and WT groups. All 9-month-old mice were treated with icariin (60mg/kg/d) or distilled water for 3months. Following this, the spatial working memory of Tg2576+icariin mice, as examined in the Y-maze task, was found to improve. Furthermore, reduced levels of insoluble Aβ1-40 (69%) and Aβ1-42 (50%) after icariin treatment were determined in the brain by enzyme-linked immunosorbent assay (ELISA). Western blot analysis indicated the downregulation of APP expression after icariin treatment, and double staining showed an increased number of 5-bromo-2-deoxyuridine (BrdU)/Neuron-specific nuclear protein (NeuN) double-positive cells in the dentate gyrus region of the hippocampus in Tg2576+icariin mice compared with the Tg2576 mice. The current study demonstrated that icariin improved memory function, decreased the levels of Aβ and APP in the brain, and enhanced neurogenesis in the hippocampus of Tg2576 mice. Collectively, these results suggest the potential therapeutic value of icariin in AD.

  11. Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients

    PubMed Central

    2011-01-01

    Background The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects. Methods It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry. Results GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls. Conclusion This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages. PMID:21810251

  12. Elevated corticosterone levels and severe weather conditions decrease parental investment of incubating Adélie penguins.

    PubMed

    Thierry, Anne-Mathilde; Massemin, Sylvie; Handrich, Yves; Raclot, Thierry

    2013-03-01

    Corticosterone, the main stress hormone in birds, mediates resource allocation, allowing animals to adjust their physiology and behaviour to changes in the environment. Incubation is a time and energy-consuming phase of the avian reproductive cycle. It may be terminated prematurely, when the parents' energy stores are depleted or when environmental conditions are severe. In this study, the effects of experimentally elevated baseline corticosterone levels on the parental investment of incubating male Adélie penguins were investigated. Incubation duration and reproductive success of 60 penguins were recorded. The clutches of some birds were replaced by dummy eggs, which recorded egg temperatures and rotation rates, enabling a detailed investigation of incubation behaviour. Corticosterone levels of treated birds were 2.4-fold higher than those of controls 18 days post treatment. Exogenous corticosterone triggered nest desertion in 61% of the treated birds; consequently reducing reproductive success, indicating that corticosterone can reduce or disrupt parental investment. Regarding egg temperatures, hypothermic events became more frequent and more pronounced in treated birds, before these birds eventually abandoned their nest. The treatment also significantly decreased incubation temperatures by 1.3°C and lengthened the incubation period by 2.1 days. However, the number of chicks at hatching was similar among successful nests, regardless of treatment. Weather conditions appeared to be particularly important in determining the extent to which corticosterone levels affected the behaviour of penguins, as treated penguins were more sensitive to severe weather conditions. This underlines the importance of considering the interactions of organisms with their environment in studies of animal behaviour and ecophysiology.

  13. Nitric oxide signaling in Pseudomonas aeruginosa biofilms mediates phosphodiesterase activity, decreased cyclic di-GMP levels, and enhanced dispersal.

    PubMed

    Barraud, Nicolas; Schleheck, David; Klebensberger, Janosch; Webb, Jeremy S; Hassett, Daniel J; Rice, Scott A; Kjelleberg, Staffan

    2009-12-01

    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.

  14. 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).

  15. MicroRNA-181a-mediated downregulation of AC9 protein decreases intracellular cAMP level and inhibits ATRA-induced APL cell differentiation.

    PubMed

    Zhuang, L K; Xu, G P; Pan, X R; Lou, Y J; Zou, Q P; Xia, D; Yan, W W; Zhang, Y T; Jia, P M; Tong, J H

    2014-04-10

    AC9 is one of the adenylate cyclase (AC) isoforms, which catalyze the conversion of ATP to cAMP, an important second messenger. We previously found that the integration of cAMP/PKA pathway with nuclear receptor-mediated signaling was required during all-trans retinoic acid (ATRA)-induced maturation of acute promyelocytic leukemia (APL) cells. Here we showed that AC9 could affect intracellular cAMP level and enhance the trans-activity of retinoic acid receptor. Knockdown of AC9 in APL cell line NB4 could obviously inhibit ATRA-induced differentiation. We also demonstrated that miR-181a could decrease AC9 expression by targeting 3'UTR of AC9 mRNA, finally controlling the production of intracellular cAMP. The expression of miR-181a itself could be inhibited by CEBPα, probably accounting for the differential expression of miR-181a in NB4 and ATRA-resistant NB4-R1 cells. Moreover, we found that AC9 expression was relatively lower in newly diagnosed or relapsed APL patients than in both complete remission and non-leukemia cases, closely correlating with the leukemogenesis of APL. Taken together, our studies revealed for the first time the importance of miR-181a-mediated AC9 downregulation in APL. We also suggested the potential value of AC9 as a biomarker in the clinical diagnosis and treatment of leukemia.

  16. Deficiency of glycerol-3-phosphate acyltransferase 1 decreases triacylglycerol storage and induces fatty acid oxidation in insect fat body.

    PubMed

    Alves-Bezerra, Michele; Ramos, Isabela B; De Paula, Iron F; Maya-Monteiro, Clarissa M; Klett, Eric L; Coleman, Rosalind A; Gondim, Katia C

    2017-03-01

    Glycerol-3-phosphate acyltransferases (GPAT) catalyze the initial and rate-limiting step for the de novo synthesis of triacylglycerol (TAG). Four mammalian GPAT isoforms have been identified: the mitochondria-associated GPAT1 and 2, and the endoplasmic reticulum (ER)-associated GPAT3 and 4. In the insect Rhodnius prolixus, a vector of Chagas' disease, we previously predicted a mitochondrial-like isoform (RhoprGPAT1) from genomic data. In the current study, we clone the RhoprGPAT1 coding sequence and identify an ER-associated GPAT (RhoprGPAT4) as the second isoform in the insect. RhoprGPAT1 contributes 15% of the total GPAT activity in anterior midgut, 50% in posterior midgut and fat body, and 70% in the ovary. The RhoprGpat1 gene is the predominant transcript in the midgut and fat body. To evaluate the physiological relevance of RhoprGPAT1, we generate RhoprGPAT1-deficient insects. The knockdown of RhoprGpat1 results in 50% and 65% decrease in TAG content in the posterior midgut and fat body, respectively. RhoprGpat1-deficient insects also exhibits impaired lipid droplet expansion and a 2-fold increase in fatty acid β-oxidation rates in the fat body. We propose that the RhoprGPAT1 mitochondrial-like isoform is required to channel fatty acyl chains towards TAG synthesis and away from β-oxidation. Such a process is crucial for the insect lipid homeostasis.

  17. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis

    PubMed Central

    Pinkosky, Stephen L.; Newton, Roger S.; Day, Emily A.; Ford, Rebecca J.; Lhotak, Sarka; Austin, Richard C.; Birch, Carolyn M.; Smith, Brennan K.; Filippov, Sergey; Groot, Pieter H.E.; Steinberg, Gregory R.; Lalwani, Narendra D.

    2016-01-01

    Despite widespread use of statins to reduce low-density lipoprotein cholesterol (LDL-C) and associated atherosclerotic cardiovascular risk, many patients do not achieve sufficient LDL-C lowering due to muscle-related side effects, indicating novel treatment strategies are required. Bempedoic acid (ETC-1002) is a small molecule intended to lower LDL-C in hypercholesterolemic patients, and has been previously shown to modulate both ATP-citrate lyase (ACL) and AMP-activated protein kinase (AMPK) activity in rodents. However, its mechanism for LDL-C lowering, efficacy in models of atherosclerosis and relevance in humans are unknown. Here we show that ETC-1002 is a prodrug that requires activation by very long-chain acyl-CoA synthetase-1 (ACSVL1) to modulate both targets, and that inhibition of ACL leads to LDL receptor upregulation, decreased LDL-C and attenuation of atherosclerosis, independently of AMPK. Furthermore, we demonstrate that the absence of ACSVL1 in skeletal muscle provides a mechanistic basis for ETC-1002 to potentially avoid the myotoxicity associated with statin therapy. PMID:27892461

  18. 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.

  19. Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity.

    PubMed

    Fujikawa, Teppei; Fujita, Ryo; Iwaki, Yoko; Matsumura, Shigenobu; Fushiki, Tohru; Inoue, Kazuo

    2010-10-05

    We have previously reported that transforming growth factor (TGF)-beta in the cerebrospinal fluid (CSF) is involved in the mechanism underlying the regulation of spontaneous motor activity (SMA) by the central nervous system after exercise. However, it remained unclear what physiological condition triggers the activation of TGF-beta. We hypothesized that the shortage of energy derived from fatty acid (FA) oxidation observed in the early phase of exercise activated TGF-beta in the CSF. To test this hypothesis, we investigated whether mercaptoacetate (MA), an inhibitor of FA oxidation, could induce an activation of TGF-beta in the CSF and a decrease in SMA. Intraperitoneal (i.p.) administration of MA activated TGF-beta in CSF in rats and depressed SMA; 2-deoxyglucose, an inhibitor of carbohydrate oxidation, on the other hand, depressed SMA but failed to activate CSF TGF-beta. Intracisternal administration of anti-TGF-beta antibody abolished the depressive effect of MA on SMA. We also found that the depression of SMA and the activation of TGF-beta in the CSF by i.p. MA administration were eliminated by vagotomy. Our data suggest that TGF-beta in the CSF is activated by the inhibition of FA oxidation via the vagus nerve and that this subsequently induces depression of SMA.

  20. Clavulanic acid enhances glutamate transporter subtype I (GLT-1) expression and decreases reinforcing efficacy of cocaine in mice

    PubMed Central

    Kim, Jae; John, Joel; Langford, Dianne; Walker, Ellen; Ward, Sara; Rawls, Scott M.

    2015-01-01

    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

  1. Correlation between maternal and childhood VitB12, folic acid and ferritin levels

    PubMed Central

    Zeeshan, Fatima; Bari, Attia; Farhan, Saima; Jabeen, Uzma; Rathore, Ahsan Waheed

    2017-01-01

    Objective: To determine the correlation between serum folic acid, vitamin B12 and ferritin of mother and child and to study various neonatal risk factors as a cause of anemia in children. Methods: One hundred eighty children two months to two years of age admitted in the department of Pediatric Medicine of The Children’s Hospital and The Institute of Child Health Lahore from January 2013 to January 2015 with common medical conditions having anemia were included. Complete blood count (CBC), serum ferritin level, folic acid and Vitamin (Vit) B12 level were sent of children and their mothers. Data was analyzed using SPSS version 20. Results: Out of 180 children with anemia, 66.7% were males. Mean age of children was 7.3months. Fifty-five percent children were malnourished according to z scoring. The mean Hemoglobin (Hb) of children was 8 g/dl. Only 4% children had low ferritin level while 60% had low folic acid and 45% had decreased VitB12. There was significant correlation between Hb of mother and child (p =0.02), Vit B12 deficiency (p=0.008) and iron deficiency (p<0.001). Premature children had lower folic acid levels (p =0.02), while prematurity, IUGR, previous admission and history of sepsis showed no association with anemia in our study. Both breast-feeding and top feeding showed significant association with anemia with p-value of 0.042 and 0.003 respectively while dilution showed no impact on anemia. Conclusion: Maternal anemia has a significant impact on child’s hemoglobin. As compared to previous concept of increased iron deficiency in children we found increased occurrence of folic acid and VitB12 deficiency in children and their mothers. PMID:28367192

  2. Alterations of amino Acid level in depressed rat brain.

    PubMed

    Yang, Pei; Li, Xuechun; Ni, Jian; Tian, Jingchen; Jing, Fu; Qu, Changhai; Lin, Longfei; Zhang, Hui

    2014-10-01

    Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and γ-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-α-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, γ-amino-n-butyric acid and L-α-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant.

  3. Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer.

    PubMed

    Rosenblatt, Adena E; Garcia, Maria Ines; Lyons, Leah; Xie, Yingqiu; Maiorino, Carol; Désiré, Laurent; Slingerland, Joyce; Burnstein, Kerry L

    2011-04-01

    Rac1, a Rho GTPase, modulates diverse cellular processes and is hyperactive in some cancers. Estrogen receptor-alpha (ERα) in concert with intracellular signaling pathways regulates genes associated with cell proliferation, tumor development, and breast cancer cell survival. Therefore, we examined the possibility of Rac1 and ERα crosstalk in breast cancer cells. We found that Rac1 enhanced ERα transcriptional activity in breast cancer cells. Vav3, a Rho guanine nucleotide exchange factor that activates Rac1, was an upstream mediator, and P21/Cdc42/Rac1 activating kinase-1 (Pak-1) was a downstream effector of Rac1 enhancement of ERα activity. These results suggest that Rac1 may prove to be a therapeutic target. To test this hypothesis, we used a small molecule Rac inhibitor, EHT 1864, and found that EHT 1864 inhibited ERα transcriptional activity. Furthermore, EHT 1864 inhibited estrogen-induced cell proliferation in breast cancer cells and decreased tamoxifen-resistant breast cancer cell growth. EHT 1864 decreased activity of the promoter of the ERα gene resulting in down-regulation of ERα mRNA and protein levels. Therefore, ERα down-regulation by EHT 1864 is the likely mechanism of EHT 1864-mediated inhibition of ERα activity and estrogen-stimulated breast cancer cell proliferation. Since ERα plays a critical role in the pathogenesis of breast cancer and the Rac inhibitor EHT 1864 down-regulates ERα expression and breast cancer cell proliferation, further investigation of the therapeutic potential of Rac1 targeting in the treatment of breast cancer is warranted.

  4. Omega-3 Polyunsaturated Fatty Acids Inhibited Tumor Growth via Preventing the Decrease of Genomic DNA Methylation in Colorectal Cancer Rats.

    PubMed

    Huang, Qionglin; Wen, Juan; Chen, Guangzhao; Ge, Miaomiao; Gao, Yihua; Ye, Xiaoxia; Liu, Chunan; Cai, Chun

    2016-01-01

    Omge-3 polyunsaturated fatty acids (PUFAs) exhibited significant effect in inhibiting various tumors. However, the mechanisms of its anticancer role have not been fully demonstrated. The declination of 5-methylcytosine (5 mC) was closely associated with poor prognosis of tumors. To explore whether omega-3 PUFAs influences on DNA methylation level in tumors, colorectal cancer (CRC) rat model were constructed using N-methyl phosphite nitrourea and omega-3 PUFAs were fed to part of the rats during tumor induction. The PUFAs contents in the rats of 3 experimental groups were measured using gas chromatography and 5 mC level were detected by liquid chromatography tandem mass spectrometry. The results showed that tumor incidence in omega-3 treated rats was much lower than in CRC model rats, which confirmed significant antitumor role of omega-3 PUFAs. Six PUFA members categorized to omega-3 and omega-6 families were quantified and the ratio of omega-6/omega-3 PUFAs was remarkably lower in omega-3 PUFAs treatment group than in CRC model group. 5 mC content in omega-3 PUFAs treated rats was higher than in CRC model rats, suggesting omega-3 PUFAs promoted 5 mC synthesis. Therefore, omega-3 PUFAs probably inhibited tumor growth via regulating DNA methylation process, which provided a novel anticancer mechanism of omega-3 PUFAs from epigenetic view.

  5. Effect of somatostatin on nonesterified fatty acid levels modifies glucose homeostasis during fasting

    SciTech Connect

    Hendrick, G.K.; Frizzell, R.T.; Cherrington, A.D. )

    1987-10-01

    In the 7-days fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (R{sub d}) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in R{sub d}. In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportal replacement amounts of insulin and glucagon (hormone replacement), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion. Glucose turnover was assessed using (3-{sup 3}H)glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. After a prolonged fast in the dog, (1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and (2) this decrease in the NEFA level causes an increase in R{sub d}.

  6. 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

  7. Abscisic acid signalling when soil moisture is heterogeneous: decreased photoperiod sap flow from drying roots limits abscisic acid export to the shoots.

    PubMed

    Dodd, Ian C; Egea, Gregorio; Davies, William J

    2008-09-01

    To investigate the contribution of different parts of the root system to total sap flow and leaf xylem abscisic acid (ABA) concentration ([X-ABA](leaf)), individual sunflower (Helianthus annuus L.) shoots were grafted onto the root systems of two plants grown in separate pots and sap flow through each hypocotyl measured below the graft union. During deficit irrigation (DI), both pots received the same irrigation volumes, while during partial root zone drying (PRD) one pot ('wet') was watered and another ('dry') was not. During PRD, once soil water content (theta) decreased below a threshold, the fraction of sap flow from drying roots declined. As theta declined, root xylem ABA concentration increased in both irrigation treatments, and [X-ABA](leaf) increased in DI plants, but [X-ABA](leaf) of PRD plants actually decreased within a certain theta range. A simple model that weighted ABA contributions of wet and dry root systems to [X-ABA](leaf) according to the sap flow from each, better predicted [X-ABA](leaf) of PRD plants than either [X-ABA](dry), [X-ABA](wet) or their mean. Model simulations revealed that [X-ABA](leaf) during PRD exceeded that of DI with moderate soil drying, but continued soil drying (such that sap flow from roots in drying soil ceased) resulted in the opposite effect.

  8. Nicotine withdrawal produces a decrease in extracellular levels of dopamine in the nucleus accumbens that is lower in adolescent versus adult male rats.

    PubMed

    Natividad, Luis A; Tejeda, Hugo A; Torres, Oscar V; O'Dell, Laura E

    2010-02-01

    The behavioral effects of nicotine withdrawal are lower in adolescent versus adult rats. However, the neurochemical mechanisms that mediate these developmental differences are unknown. Previous studies have shown that extracellular levels of dopamine in the nucleus accumbens (NAcc) are reduced in adult rats experiencing withdrawal. This study compared dopamine levels in the NAcc of male adolescent and adult rats experiencing nicotine withdrawal. Animals were prepared with subcutaneous pumps that delivered an equivalent nicotine dose in these age groups. Following 13 days of nicotine exposure, rats were implanted unilaterally with microdialysis probes into the NAcc and ipsilateral ventral tegmental area (VTA). The next day, dialysate levels were collected following systemic administration of the nicotinic-receptor antagonist mecamylamine to precipitate withdrawal. Mecamylamine produced an average % decrease in NAcc dopamine that was lower in adolescents (20%) versus adults (44%). Similar developmental differences were observed with the dopaminergic (DOPAC and HVA) but not serotonergic (5-HIAA) metabolites. A follow-up study compared NAcc dopamine in adolescent and adult rats receiving intra-VTA administration of bicuculline, which reduces gamma-aminobutyric acid (GABA) inhibition of dopamine transmission. The results revealed that blockade of GABA(A) receptors in the VTA produced a two-fold increase in NAcc dopamine of adults but not adolescents. These results provide a potential mechanism involving dopamine that mediates developmental differences in nicotine withdrawal. Specifically, they suggest that GABA systems are underdeveloped during adolescence and this reduced inhibition of dopamine neurons in the VTA may lead to reduced decreases in NAcc dopamine of young animals experiencing withdrawal.

  9. Nicotine withdrawal produces a decrease in extracellular levels of dopamine in the nucleus accumbens that is lower in adolescent versus adult male rats

    PubMed Central

    Natividad, Luis A.; Tejeda, Hugo A.; Torres, Oscar V.; O’Dell, Laura E.

    2010-01-01

    The behavioral effects of nicotine withdrawal are lower in adolescent versus adult rats. However, the neurochemical mechanisms that mediate these developmental differences are unknown. Previous studies have shown that extracellular levels of dopamine in the nucleus accumbens (NAcc) are reduced in adult rats experiencing withdrawal. This study compared dopamine levels in the NAcc of male adolescent and adult rats experiencing nicotine withdrawal. Animals were prepared with subcutaneous pumps that delivered an equivalent nicotine dose in these age groups. Following 13 days of nicotine exposure, rats were implanted unilaterally with microdialysis probes into the NAcc and ipsilateral ventral tegmental area (VTA). The next day, dialysate levels were collected following systemic administration of the nicotinic-receptor antagonist mecamylamine to precipitate withdrawal. Mecamylamine produced an average % decrease in NAcc dopamine that was lower in adolescents (20%) versus adults (44%). Similar developmental differences were observed with the dopaminergic (DOPAC and HVA) but not serotonergic (5-HIAA) metabolites. A follow up study compared NAcc dopamine in adolescent and adult rats receiving intra-VTA administration of bicuculline, which reduces gamma-aminobutyric acid (GABA) inhibition of dopamine transmission. The results revealed that blockade of GABAA receptors in the VTA produced a 2-fold increase in NAcc dopamine of adults but not adolescents. These results provide a potential mechanism involving dopamine that mediates developmental differences in nicotine withdrawal. Specifically, they suggest that GABA systems are underdeveloped during adolescence and this reduced inhibition of dopamine neurons in the VTA may lead to reduced decreases in NAcc dopamine of young animals experiencing withdrawal. PMID:19771590

  10. Elevation of serum levels of beta-aminoisobutyric acid in uremic patients and the toxicity of the amino acid.

    PubMed

    Gejyo, F; Kinoshita, Y; Ikenaka, T

    1977-12-01

    A reliable method for the determination of beta-aminoisobutyric acid in serum was developed utilizing an automated amino acid analyzer. The serum concentrations of beta-aminoisobutyric acid were determined in 20 normal subjects and in 71 uremic patients. The mean serum level of beta-aminoisobutyric acid was markedly increased in the uremic patients to 0.856 +/- 0.910 (mean +/- SD) mg/100 ml as compared with a normal value of 0.026 +/- 0.027 mg/100 ml. The distribution of serum beta-aminoisobutyric acid level in uremic patients was wide-spread, and there was no correlation between the serum levels of the amino acid and those of urea nitrogen, creatinine and uric acid. The toxicity of beta-aminoisobutyric acid on mice with acute renal failure induced by uranyl acetate was investigated and compared with that of alpha-amino-n-butyric acid and gamma-amino-n-butyric acid. All mice given more than 4 g/kg body wt of beta-aminoisobutyric acid showed twitching and cramps, and some of them died. However, the control mice given an equivalent dose of alpha-amino-n-butyric acid or gamma-amino-n-butyric acid showed no change. These results suggest that beta-aminoisobutyric acid might be a factor influencing the development and progression of uremic toxemia.

  11. Elevated Inducible Nitric Oxide Levels and Decreased Hydrogen Sulfide Levels Can Predict the Risk of Coronary Artery Ectasia in Kawasaki Disease.

    PubMed

    Song, Ruixia; Liu, Guiying; Li, Xiaohui; Xu, Wenya; Liu, Jia; Jin, Hongfang

    2016-02-01

    Kawasaki disease (KD) is a vasculitis disease in children that is associated with coronary artery ectasia (CAE). We investigated whether inducible nitric oxide synthase (i-NOS) and hydrogen sulfide (H2S) could be used to predict CAE secondary to KD. We enrolled 65 children with KD (35 cases with CAE and 30 cases without CAE), 33 healthy children, and 32 children with fever but without vasculitis disease (febrile group). We measured plasma nitric oxide (NO), total nitric oxide synthase (Total-NOS), i-NOS, constructive nitric oxide synthase (c-NOS) levels, and H2S content in all patients. Plasma NO, Total-NOS, i-NOS, and H2S were higher in KD children than in healthy and febrile children (P < 0.05). The i-NOS level was higher in KD children with CAE compared to those without CAE, while the H2S was lower (both P < 0.05). Using a combination of i-NOS (higher than 10 U/mL) and H2S (lower than 3.31 μmol/L) to predict CAE had 80 % sensitivity and 81 % specificity (P < 0.05). Elevated plasma i-NOS and decreased plasma H2S levels in the acute phase of KD have good predictive value for CAE and may be used to guide appropriate clinical treatment and prevent future cardiovascular complications.

  12. 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.

  13. 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.

  14. 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.

  15. ∆(9)-Tetrahydrocannabinol decreases NOP receptor density and mRNA levels in human SH-SY5Y cells.

    PubMed

    Cannarsa, Rosalia; Carretta, Donatella; Lattanzio, Francesca; Candeletti, Sanzio; Romualdi, Patrizia

    2012-02-01

    Several studies demonstrated a cross-talk between the opioid and cannabinoid system. The NOP receptor and its endogenous ligand nociceptin/orphanin FQ represent an opioid-related functional entity that mediates some non-classical opioid effects. The relationship between cannabinoid and nociceptin/NOP system is yet poorly explored. In this study, we used the neuroblastoma SH-SY5Y cell line to investigate the effect of delta-9-tetrahydrocannabinol (∆(9)-THC) on nociceptin/NOP system. Results revealed that the exposure to ∆(9)-THC (100, 150, and 200 nM) for 24 h produces a dose-dependent NOP receptor B (max) down-regulation. Moreover, ∆(9)-THC caused a dose-dependent decrease in NOP mRNA levels. The selective cannabinoid receptor CB1 antagonist AM251 (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide) reduces both effects, suggesting that ∆(9)-THC activation of CB1 receptor is involved in the observed effects. These data show evidence of a cross-talk between NOP and CB1 receptors, thus suggesting a possible interplay between cannabinoid and nociceptin/NOP system.

  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. Acetic acid vapor levels associated with facial prosthetics

    SciTech Connect

    McElroy, T.H.; Guerra, O.N.; Lee, S.A.

    1985-01-01

    The use of Silastic Medical Adhesive Type A in the fabrication of facial prostheses may cause health hazards to the patient and the operator because of acetic acid emissions. Caution must be exercised to remove acetic acid vapors from the air and unliberated acetic acid from material applied directly to the skin.

  18. Lower serum uric acid level predicts mortality in dialysis patients

    PubMed Central

    Bae, Eunjin; Cho, Hyun-Jeong; Shin, Nara; Kim, Sun Moon; Yang, Seung Hee; Kim, Dong Ki; Kim, Yong-Lim; Kang, Shin-Wook; Yang, Chul Woo; Kim, Nam Ho; Kim, Yon Su; Lee, Hajeong

    2016-01-01

    Abstract We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5–6.4, 6.5–7.4, 7.5–8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007–2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis. PMID:27310949

  19. Growth inhibition of fungus Phycomyces blakesleeanus by anion channel inhibitors anthracene-9-carboxylic and niflumic acid attained through decrease in cellular respiration and energy metabolites.

    PubMed

    Stanić, Marina; Križak, Strahinja; Jovanović, Mirna; Pajić, Tanja; Ćirić, Ana; Žižić, Milan; Zakrzewska, Joanna; Cvetić Antić, Tijana; Todorović, Nataša; Živić, Miroslav

    2017-01-18

    Increasing resistance of fungal strains to known fungicides has prompted identification of new candidates for fungicides among substances previously used for other purposes. We have tested the effects of known anion channel inhibitors anthracene-9-carboxylic (A9C) and niflumic acid (NFA) on growth, energy metabolism and anionic current of mycelium of fungus Phycomyces blakesleeanus. Both inhibitors significantly decreased growth and respiration of mycelium, but complete inhibition was only achieved by 100 or 500 µM NFA, for growth and respiration, respectively. A9C had no effect on respiration of human NCI-H460 cell line, and very little effect on cucumber root sprout clippings, which nominates this inhibitor for further investigation as a potential new fungicide. Effects of A9C and NFA on respiration of isolated mitochondria of P. blakesleeanus were significantly smaller, which indicates that their inhibitory effect on respiration of mycelium is indirect. NMR spectroscopy showed that both A9C and NFA decrease the levels of ATP and polyphosphates in the mycelium of P. blakesleanus, but only A9C caused intracellular acidification. Outwardly rectifying, fast inactivating instantaneous anionic current (ORIC) was also reduced to 33±5% and 21±3% of its pre-treatment size by A9C and NFA, respectively, but only in the absence of ATP. It can be assumed from our results that the regulation of ORIC is tightly linked to cellular energy metabolism in P. blakesleeanus, and the decrease in ATP and polyphosphate levels could be a direct cause of growth inhibition.

  20. 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

  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. 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'.

  3. 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

  4. Interaction of aminooxyacetic acid and ethacrynic acid with intense sound at the level of the cochlea.

    PubMed

    Kisiel, D L; Bobbin, R P

    1982-02-01

    Results of previous investigation of the interaction of intense sound and drugs have, in general, failed to show a protective effect mediated by pre-administration with a drug having transient ototoxic effects. The present investigation was designed to further evaluate a protective effect found previously at the anatomical level and explained with an electrochemical theory of noise damage. The alternating current (a.c) potential and compound eighth nerve action potential (CAP) amplitude were monitored in aminooxyacetic acid (AOAA)- or ethacrynic acid (EA)-treated guinea pigs exposed to either moderate or high levels of intense sound and compared to changes observed in the same potentials in animals exposed to the intense sounds alone. Results showed protective effects only in the moderate--intense sound-exposure groups, with changes in sensitivity and voltage on the linear part of the input--output curve of the a.c cochlear potential found to be the only conditions where differences occurred. These results were difficult to interpret in terms of a protective effect and point to the need for obtaining additional data before an electrochemical mechanism is shown to play a role in the effect of intense sound on the cochlea.

  5. 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

  6. Consumption of synbiotic bread decreases triacylglycerol and VLDL levels while increasing HDL levels in serum from patients with type-2 diabetes.

    PubMed

    Shakeri, Hossein; Hadaegh, Haleh; Abedi, Fatemeh; Tajabadi-Ebrahimi, Maryam; Mazroii, Navid; Ghandi, Yaser; Asemi, Zatollah

    2014-07-01

    To our knowledge, no reports are available indicating the favorable effects of synbiotic bread consumption on blood lipid profiles among patients with type 2 diabetes mellitus (T2DM). This study was conducted to evaluate the effects of the daily consumption of synbiotic bread on blood lipid profiles of patients with T2DM. This randomized double-blinded controlled clinical trial was performed with 78 diabetic patients, aged 35-70 years. After a 2-week run-in period, subjects were randomly assigned to consume either synbiotic (n = 26), probiotic (n = 26) or control bread (n = 26) for 8 weeks. The synbiotic bread contained viable and heat-resistant probiotic Lactobacillus sporogenes (1 × 10(8) CFU) and 0.07 g inulin (HPX) as prebiotic per 1 g. The probiotic bread contained L. sporogenes (1 × 10(8) CFU) per 1 g. Patients were asked to consume the synbiotic, probiotic and control breads three times a day in a 40 g package for a total of 120 g/day. Biochemical measurements including blood lipid profiles were conducted before and after 8 weeks of intervention. Consumption of the synbiotic bread, compared to the probiotic and control breads, led to a significant decrease in serum TAG (P = 0.005), VLDL-C (P = 0.005), TC/HDL-C (P = 0.002) and a significant increase in serum HDL-C levels (P = 0.01). No significant effect of synbiotic bread consumption on FPG, TC, LDL-C and non-HDL-C levels was seen compared to the probiotic and control breads (P > 0.05). Trial registry code: http://www.irct.ir IRCT201311215623N13.

  7. 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 ...

  8. Insulin Signaling Regulates Fatty Acid Catabolism at the Level of CoA Activation

    PubMed Central

    Xu, Xiaojun; Gopalacharyulu, Peddinti; Seppänen-Laakso, Tuulikki; Ruskeepää, Anna-Liisa; Aye, Cho Cho; Carson, Brian P.; Mora, Silvia; Orešič, Matej; Teleman, Aurelio A.

    2012-01-01

    The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG) catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS). We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis. PMID:22275878

  9. Salicylic acid treatment via the rooting medium interferes with stomatal response, CO2 fixation rate and carbohydrate metabolism in tomato, and decreases harmful effects of subsequent salt stress.

    PubMed

    Poór, P; Gémes, K; Horváth, F; Szepesi, A; Simon, M L; Tari, I

    2011-01-01

    Salicylic acid (SA) applied at 10(-3) m in hydroponic culture decreased stomatal conductance (g(s)), maximal CO(2) fixation rate (A(max) ) and initial slopes of the CO(2) (A/C(i)) and light response (A/PPFD) curves, carboxylation efficiency of Rubisco (CE) and photosynthetic quantum efficiency (Q), resulting in the death of tomato plants. However, plants could acclimate to lower concentrations of SA (10(-7) -10(-4) m) and, after 3 weeks, returned to control levels of g(s), photosynthetic performance and soluble sugar content. In response to high salinity (100 mm NaCl), the pre-treated plants exhibited higher A(max) as a function of internal CO(2) concentration (C(i) ) or photosynthetic photon flux density (PPFD), and higher CE and Q values than salt-treated controls, suggesting more effective photosynthesis after SA treatment. Growth in 10(-7) or 10(-4) m SA-containing solution led to accumulation of soluble sugars in both leaf and root tissues, which remained higher in both plant parts during salt stress at 10(-4) m SA. The activity of hexokinase (HXK) with glucose, but not fructose, as substrate was reduced by SA treatment in leaf and root samples, leading to accumulation of glucose and fructose in leaf tissues. HXK activity decreased further under high salinity in both plant organs. The accumulation of soluble sugars and sucrose in roots of plants growing in the presence of 10(-4) m SA contributed to osmotic adjustment and improved tolerance to subsequent salt stress. Apart from its putative role in delaying senescence, decreased HXK activity may divert hexoses from catabolic reactions to osmotic adaptation.

  10. Uric acid plasma level and urine pH in rats treated with ambroxol.

    PubMed

    Drewa, Tomasz; Wolski, Zbigniew; Gruszka, Marzena; Misterek, Bartosz; Lysik, Joanna

    2007-01-01

    It was a chance discovery that ambroxol parenteral administration led to urinary bladder stone formation in rats. This study was undertaken to examine the serum uric acid levels and urine pH in rats after ambroxol parenteral treatment. Ambroxol influence on the uric acid level was measured in 5 rats (Rattus sp.) treated with 60 mg/kg (dissolved in injection water, sc, daily) during 2 weeks. Ambroxol influence on urine pH was examined on 45 rats divided into 3 groups. Rats from the 1st and 2nd group received 30 and 60 mg/kg/24h ambroxol, respectively. Urine was collected once daily and measured with strip kit. All values were presented as the means with standard deviations. The Student t test was used to compare the means, p < 0.05 was considered as significant. Dynamics of pH changes was measured in 4 rats treated with 60 mg/kg/24h of ambroxol. Controls received 1 mL of injection water sc. Serum uric acid level increased up to 8.7 +/- 1.0 mg/dL vs. 5.7 +/- 1.0 mg/dL in control (p < 0.002). In the 1st and 2nd group urine pH increased up to 7.5 +/- 0.5 and 7.6 +/- 0.5 vs. 6.7 +/- 0.4 (p < 0.05). Ambroxol withdrawal resulted in sequential urine pH decrease. 11 days after interruption of ambroxol therapy pH reached the starting value. Urine pH changes and possible disturbances in uric acid metabolic pathway may influence on the stone formation in rats after ambroxol parenteral treatment. The influence of ambroxol on urinary tract GAG layer and the balance between xanthine and CaOx in the urine should be checked.

  11. Functional decreases in P2X7 receptors are associated with retinoic acid-induced neuronal differentiation of Neuro-2a neuroblastoma cells.

    PubMed

    Wu, Pei-Yu; Lin, Yu-Chia; Chang, Chia-Ling; Lu, Hsing-Tsen; Chin, Chia-Hsuan; Hsu, Tsan-Ting; Chu, Dachen; Sun, Synthia H

    2009-06-01

    Neuro-2a (N2a) cells are derived from spontaneous neuroblastoma of mouse and capable to differentiate into neuronal-like cells. Recently, P2X7 receptor has been shown to sustain growth of human neuroblastoma cells but its role during neuronal differentiation remains unexamined.We characterized the role of P2X7 receptors in the retinoic acid (RA)-differentiated N2a cells. RA induced N2a cells differentiation into neurite bearing and neuronal specific proteins, microtubule-associated protein 2 (MAP2) and neuronal specific nuclear protein (NeuN), expressing neuronal-like cells. Interestingly, the RA-induced neuronal differentiation was associated with decreases in the expression and function of P2X7 receptors. Functional inhibition of P2X7 receptors by P2X7 receptor selective antagonists, 5'-triphosphate, periodate-oxidized 2',3'-dialdehyde ATP (oATP), brilliant blue G (BBG) or A438079 induced neurite outgrowth. In addition, RA and oATP treatment stimulated the expression of neuron-specific class III beta-tubulin (TuJ1), and knockdown of P2X7 receptor expression by siRNA induced neurite outgrowth. To elucidate the possible mechanism, we found the levels of basal intracellular Ca2+ concentrations ([Ca2+]i) were decreased in either RA- or oATP-differentiated or P2X7receptor knockdown N2a cells. Simply cultured N2a cells in low Ca2+ medium induced a 2-fold increase in neurite length. Treatment of N2a cells with ATP hydrolase apyrase and the P2X7 receptors selective antagonist oATP or BBG decreased cell viability and cell number. Nevertheless, oATP but not BBG decreased cell proliferation and cell cycle progression. These results suggest for the first time that decreases in expression/function of P2X7 receptors are involved in neuronal differentiation.We provide additional evidence shown that the ATP release-activated P2X7 receptor is important in maintaining cell survival of N2a neuroblastoma cells.

  12. Lifelong treatment with atenolol decreases membrane fatty acid unsaturation and oxidative stress in heart and skeletal muscle mitochondria and improves immunity and behavior, without changing mice longevity.

    PubMed

    Gómez, Alexia; Sánchez-Roman, Ines; Gomez, Jose; Cruces, Julia; Mate, Ianire; Lopez-Torres, Mónica; Naudi, Alba; Portero-Otin, Manuel; Pamplona, Reinald; De la Fuente, Monica; Barja, Gustavo

    2014-06-01

    The membrane fatty acid unsaturation hypothesis of aging and longevity is experimentally tested for the first time in mammals. Lifelong treatment of mice with the β1-blocker atenolol increased the amount of the extracellular-signal-regulated kinase signaling protein and successfully decreased one of the two traits appropriately correlating with animal longevity, the membrane fatty acid unsaturation degree of cardiac and skeletal muscle mitochondria, changing their lipid profile toward that present in much more longer-lived mammals. This was mainly due to decreases in 22:6n-3 and increases in 18:1n-9 fatty acids. The atenolol treatment also lowered visceral adiposity (by 24%), decreased mitochondrial protein oxidative, glycoxidative, and lipoxidative damage in both organs, and lowered oxidative damage in heart mitochondrial DNA. Atenolol also improved various immune (chemotaxis and natural killer activities) and behavioral functions (equilibrium, motor coordination, and muscular vigor). It also totally or partially prevented the aging-related detrimental changes observed in mitochondrial membrane unsaturation, protein oxidative modifications, and immune and behavioral functions, without changing longevity. The controls reached 3.93 years of age, a substantially higher maximum longevity than the best previously described for this strain (3.0 years). Side effects of the drug could have masked a likely lowering of the endogenous aging rate induced by the decrease in membrane fatty acid unsaturation. We conclude that it is atenolol that failed to increase longevity, and likely not the decrease in membrane unsaturation induced by the drug.

  13. Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements.

    PubMed

    Ma, Ai G; Schouten, Evert G; Zhang, Feng Z; Kok, Frans J; Yang, Fang; Jiang, Dian C; Sun, Yong Y; Han, Xiu X

    2008-10-01

    In rural China, many pregnant women in their third trimester suffer from anemia (48%) and iron deficiency (ID; 42%), often with coexisting deficiencies of retinol and riboflavin. We investigated the effect of retinol and riboflavin supplementation in addition to iron plus folic acid on anemia and subjective well-being in pregnant women. The study was a 2-mo, double-blind, randomized trial. Subjects (n = 366) with anemia [hemoglobin (Hb) acid. The iron+folic acid (IF) group (n = 93) served as reference, the iron+folic acid+retinol group (IFA) (n = 91) was treated with 2000 mug retinol, the iron+folic acid+riboflavin group (IFB) (n = 91) with 1.0 mg riboflavin, and the iron+folic acid+retinol+riboflavin group (IFAB) (n = 91) with retinol and riboflavin. After the 2-mo intervention, the Hb concentration increased in all 4 groups (P < 0.001). The increase in the IFAB group was 5.4 +/- 1.1 g/L greater than in the IF group (P < 0.001). The reduced prevalence of anemia (Hb < 110g/L) and ID anemia were significantly greater in the groups supplemented with retinol and /or riboflavin than in the IF group. Moreover, gastrointestinal symptoms were less prevalent in the IFA group than in the IF group (P < 0.05) and improved well-being was more prevalent in the groups receiving additional retinol and/or riboflavin than in the IF group (P < 0.05). Thus, a combination of iron, folic acid, retinol, and riboflavin was more effective than iron plus folic acid alone. Multimicronutrient supplementation may be worthwhile for pregnant women in rural China.

  14. 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 Central

    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

  15. Low Temperature-Induced Decrease in trans-Δ3-Hexadecenoic Acid Content Is Correlated with Freezing Tolerance in Cereals 1

    PubMed Central

    Huner, Norman P. A.; Williams, John P.; Maissan, Ellen E.; Myscich, Elizabeth G.; Krol, Marianna; Laroche, Andre; Singh, Jasbir

    1989-01-01

    The effect of growth at 5°C on the trans-Δ3-hexadecenoic acid content of phosphatidyl(d)glycerol was examined in a total of eight cultivars of rye (Secale cereale L.) and what (Triticum aestivum L.) of varying freezing tolerance. In these monocots, low temperature growth caused decreases in the trans-Δ3-hexadecenoic acid content of between 0 and 74% with concomitant increases in the palmitic acid content of phosphatidyl(d)glycerol. These trends were observed for whole leaf extracts as well as isolated thylakoids. The low growth temperature-induced decrease in the trans-Δ3-hexadecenoic acid content was shown to be a linear function (r2 = 0.954) of freezing tolerance in these cultivars. Of the six cold tolerant dicotyledonous species examined, only Brassica and Arabidopsis thaliana L. cv Columbia exhibited a 42% and 65% decrease, respectively, in trans-Δ3-hexadecenoic acid content. Thus, the relationship between the change in trans-Δ3-hexadecenoic acid content of phosphatidyl(d)glycerol and freezing tolerance cannot be considered a general one for all cold tolerant plant species. However, species which exhibited a low growth temperature-induced decrease in trans-Δ3-hexadecenoic acid also exhibited a concomitant shift in the in vitro organization of the light harvesting complex II from a predominantly oligomeric form to the monomeric form. We conclude that the proposed role of phosphatidyl(d)glycerol in modulating the organization of light harvesting complex II as a function of growth temperature manifests itself to varying degrees in different plant species. A possible physiological role for this phenomenon with respect to low temperature acclimation and freezing tolerance in cereals is discussed. PMID:16666505

  16. Blood lead levels among rural Thai children exposed to lead-acid batteries from solar energy conversion systems.

    PubMed

    Swaddiwudhipong, Witaya; Tontiwattanasap, Worawit; Khunyotying, Wanlee; Sanreun, Cherd

    2013-11-01

    We evaluate blood lead levels among Thai children to determine if exposure to lead-acid batteries is associated with elevated blood lead levels (EBLL). We screened 254 children aged 1-14 years old from 2 rural Thai villages for blood lead levels. We also screened 18 of 92 houses in these 2 villages for the presence of environmental lead. The overall prevalence of EBLL (> or = 10 microg/dl) was 43.3% and the mean lead level among study subjects was 9.8 +/- 5.1 microg/dl. The blood lead levels significantly decreased with increasing age. Fifty point eight percent of children who lived in a house with vented lead-acid batteries had EBLL while 23.3% of children who lived in a house without vented lead-acid batteries had EBLL. Multiple logistic regression analysis revealed a significant positive association between the presence of vented lead-acid batteries and EBLL, after adjusting for other variables. Forty-two point nine percent of house floor dust samples collected near the batteries had elevated lead levels, 7.1% of house floor dust samples collected from other areas in the house had elevated lead levels and 0% of the house floor dust samples collected in houses without vented lead-acid batteries had elevated lead levels. In the sampled houses with vented lead-acid batteries, lead contamination was found in the drinking-water kept in household containers, but not in the tap water or other village sources of water. Improper care and placement of vented lead-acid batteries can result in lead contamination in the home environment causing EBLL in exposed children.

  17. 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.

  18. Decreased serum vitamin D levels are associated with diabetic peripheral neuropathy in a rural area of Turkey.

    PubMed

    Celikbilek, Asuman; Gocmen, Ayse Yesim; Tanik, Nermin; Borekci, Elif; Adam, Mehmet; Celikbilek, Mehmet; Suher, Murat; Delibas, Namik

    2015-03-01

    Data examining the association between vitamin D and diabetic peripheral neuropathy are limited. This study investigated the serum levels of vitamin D, vitamin D-binding protein (VDBP), and vitamin D receptor (VDR) in diabetics in the Yozgat region of Turkey, and assessed their relationships with diabetic peripheral neuropathy. 69 diabetic patients and 49 age- and sex-matched control subjects were enrolled in this clinical prospective study. All the diabetics underwent conventional sensory and motor nerve conduction studies, and diabetic peripheral neuropathy was confirmed or ruled out according to the electromyography findings and Douleur Neuropathique 4 questions. Serum vitamin D, VDBP and VDR levels were measured using commercial enzyme-linked immunosorbent assay kits. The serum vitamin D levels (p = 0.001) were significantly lower, while the VDR levels (p = 0.003) were higher, in diabetics than in controls. The serum VDBP levels were similar in both groups (p > 0.05). The serum vitamin D levels were significantly lower in diabetics with diabetic peripheral neuropathy than in those without (p = 0.032), whereas the serum VDBP and VDR levels were similar in these two groups (p > 0.05). The lower serum vitamin D levels in diabetics, especially in those with peripheral neuropathy, may suggest a neurotrophic effect of vitamin D.

  19. 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

  20. Decreased preoperative serum 25-Hydroxyvitamin D levels in colorectal cancer are associated with systemic inflammation and serrated morphology

    PubMed Central

    Väyrynen, Juha P.; Mutt, Shivaprakash J.; Herzig, Karl-Heinz; Väyrynen, Sara A.; Kantola, Tiina; Karhu, Toni; Karttunen, Tuomo J.; Klintrup, Kai; Mäkelä, Jyrki; Mäkinen, Markus J.; Tuomisto, Anne

    2016-01-01

    Deficiency of vitamin D is associated with increased risk of several types of cancer including colorectal cancer (CRC). However, factors contributing to low levels of 25-hydroxyvitamin D [25(OH)D] in CRC are not clear. Therefore, in this study serum 25(OH)D levels in 117 CRC patients and 86 controls were analyzed and correlated with the clinicopathological data including morphological subtype (serrated or conventional), quantity of tumor infiltrating immune cells, levels of systemic inflammatory markers, and disease outcome. We found that the patients had lower serum 25(OH)D levels compared to the controls. Interestingly, among the patients mismatch repair deficiency, serrated morphology, and high body mass index associated with lowest serum 25(OH)D levels. In addition, patients operated in summer or autumn had higher serum 25(OH)D levels. Furthermore, serum 25(OH)D levels inversely correlated with several systemic inflammatory markers, e.g. serum C reactive protein, but did not associate with prognosis. Mechanism leading to vitamin D deficiency in these patients are not clear but could be related to the effects of systemic inflammation. Longitudinal studies are warranted to assess vitamin D deficiency as a potential risk factor for serrated colorectal polyps and adenocarcinoma. PMID:27819306

  1. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine.

    PubMed

    Naithani, Manisha; 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.

  2. 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

  3. Decreased serum IL-27 and IL-35 levels are associated with disease severity in neuromyelitis optica spectrum disorders.

    PubMed

    Zhang, Da-Qi; Jia, Kun; Wang, Rong; Li, Ting; Zhao, Ning; Yang, Li-Na; Yang, Li

    2016-04-15

    The interleukin 12 (IL-12) family plays important roles in autoimmune diseases. To explore the roles of the IL-12 family members IL-27 and IL-35 in the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD), we determined their serum and cerebral spinal fluid levels and assessed potential correlations with clinical characteristics. Serum IL-27 levels were negatively correlated with disease severity and spinal cord lesion length, while serum IL-35 levels were negatively correlated with disease severity and annual relapse rate. Thus, IL-27 and IL-35 may be important biomarkers of NMOSD severity and these molecules might represent potential therapeutic cytokines for treating NMOSD.

  4. Are Uric Acid Levels Different from Healthy Subjects in Bipolar Affective Disorder and S