Purification of a protein from serum of cattle with hepatic lipidosis, and identification of the protein as haptoglobin.

Science.gov (United States)

Yoshino, K; Katoh, N; Takahashi, K; Yuasa, A

1992-06-01

A protein that has 2 subunits with molecular weight of 35,000 and 23,000 was detected in serum of cattle with hepatic lipidosis (fatty liver). The protein was purified from serum obtained from a cow with fatty liver, and was identified as haptoglobin, which is known to have hemoglobin-binding capacity and to be an acute-phase protein. To assess the relevance of haptoglobin in fatty liver, cattle were classified in 3 groups (healthy control, haptoglobin-positive, and haptoglobin-negative); liver triglyceride content and several serum biochemical variables were evaluated for the 3 groups. Compared with the control and haptoglobin-negative cattle, haptoglobin-positive cattle had significantly (P less than 0.01) higher liver triglyceride content, serum bilirubin concentration, and aspartate transaminase activity. Serum haptoglobin concentration was high in slaughter cattle (27 of 40 cattle tested), particularly in cows (20/28).

CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma

DEFF Research Database (Denmark)

Graversen, Jonas Heilskov; Madsen, Mette; Moestrup, Søren K

2002-01-01

as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp). This specific receptor-ligand interaction leading to removal from plasma of the Hp-Hb complex-but not free Hp or Hb-now explains the depletion of circulating Hp in individuals with increased intravascular...

Haptoglobin 2-2 Genotype, Patient, and Graft Survival in Renal Transplant Recipients

DEFF Research Database (Denmark)

Dupont, Laust; Eide, Ivar Anders; Hartmann, Anders

2017-01-01

Background: Cardiovascular disease is the leading cause of death in renal transplant recipients. An association between haptoglobin genotype 2-2 and cardiovascular disease has been found in patients with diabetes mellitus and liver transplant recipients. To date, the role of haptoglobin genotype...... after renal transplantation has not been studied. Methods: In this single-center retrospective cohort study of 1975 adult Norwegian transplant recipients, who underwent transplantation between 1999 and 2011, we estimated the risk of all-cause and cardiovascular mortality and overall and death...... transplant recipients, we could not demonstrate any association between haptoglobin 2-2 genotype and patient or graft survival after renal transplantation....

Polymorphism of human haptoglobin and its clinical importance

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Vânia Peretti de Albuquerque Wobeto

2008-01-01

Full Text Available Haptoglobin (Hp is a plasma glycoprotein, the main biological function of which is to bind free hemoglobin (Hb and prevent the loss of iron and subsequent kidney damage following intravascular hemolysis. Haptoglobin is also a positive acute-phase protein with immunomodulatory properties. In humans, the HP locus is polymorphic, with two codominant alleles (HP1 and HP2 that yield three distinct genotypes/phenotypes (Hp1-1, Hp2-1 and Hp2-2. The corresponding proteins have structural and functional differences that may influence the susceptibility and/or outcome in several diseases. This article summarizes the available data on the structure and functions of Hp and the possible effects of Hp polymorphism in a number of important human disorders.

A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels.

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Philippe Froguel

Full Text Available Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far.We used a genome-wide association study initially conducted in 631 French children followed by a replication in three additional European sample sets and we identified a common single nucleotide polymorphism (SNP, rs2000999 located in the Haptoglobin gene (HP as a strong genetic predictor of circulating Haptoglobin levels (P(overall = 8.1 × 10(-59, explaining 45.4% of its genetic variability (11.8% of Hp global variance. The functional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels (β = 0.23 ± 0.08, P = 0.007. Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789 European children (P(total cholesterol = 0.002 and P(LDL = 0.0008.Given the central position of haptoglobin in many inflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobin concentration should be further investigated in order to improve its diagnostic/therapeutic and/or prevention impact.

Haptoglobin gene polymorphism influences the effect of malaria ...

African Journals Online (AJOL)

uwerhiavwe

2013-03-06

Mar 6, 2013 ... ... to detect parasitemia. Higher plasma haptoglobin level tended to be associated ... malaria in pregnant mothers and children up to five years of age. Participants were .... complications of malaria disease. Elagib et al. (1998).

Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but Recognizes Properdin as a Potential Second Member of the Zonulin Family

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Lucas Scheffler

2018-02-01

Full Text Available BackgroundThere is increasing evidence for the role of impaired intestinal permeability in obesity and associated metabolic diseases. Zonulin is an established serum marker for intestinal permeability and identical to pre-haptoglobin2. Here, we aimed to investigate the relationship between circulating zonulin and metabolic traits related to obesity.MethodsSerum zonulin was measured by using a widely used commercial ELISA kit in 376 subjects from the metabolically well-characterized cohort of Sorbs from Germany. In addition, haptoglobin genotype was determined in DNA samples from all study subjects.ResultsAs zonulin concentrations did not correlate to the haptoglobin genotypes, we investigated the specificity of the zonulin ELISA assay using antibody capture experiments, mass spectrometry, and Western blot analysis. Using serum samples that gave the highest or lowest ELISA signals, we detected several proteins that are likely to be captured by the antibody in the present kit. However, none of these proteins corresponds to pre-haptoglobin2. We used increasing concentrations of recombinant pre-haptoglobin2 and complement C3 as one of the representative captured proteins and the ELISA kit did not detect either. Western blot analysis using both the polyclonal antibodies used in this kit and monoclonal antibodies rose against zonulin showed a similar protein recognition pattern but with different intensity of detection. The protein(s measured using the ELISA kit was (were significantly increased in patients with diabetes and obesity and correlated strongly with markers of the lipid and glucose metabolism. Combining mass spectrometry and Western blot analysis using the polyclonal antibodies used in the ELISA kit, we identified properdin as another member of the zonulin family.ConclusionOur study suggests that the zonulin ELISA does not recognize pre-haptoglobin2, rather structural (and possibly functional analog proteins belonging to the mannose

Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but Recognizes Properdin as a Potential Second Member of the Zonulin Family.

Science.gov (United States)

Scheffler, Lucas; Crane, Alyce; Heyne, Henrike; Tönjes, Anke; Schleinitz, Dorit; Ihling, Christian H; Stumvoll, Michael; Freire, Rachel; Fiorentino, Maria; Fasano, Alessio; Kovacs, Peter; Heiker, John T

2018-01-01

There is increasing evidence for the role of impaired intestinal permeability in obesity and associated metabolic diseases. Zonulin is an established serum marker for intestinal permeability and identical to pre-haptoglobin2. Here, we aimed to investigate the relationship between circulating zonulin and metabolic traits related to obesity. Serum zonulin was measured by using a widely used commercial ELISA kit in 376 subjects from the metabolically well-characterized cohort of Sorbs from Germany. In addition, haptoglobin genotype was determined in DNA samples from all study subjects. As zonulin concentrations did not correlate to the haptoglobin genotypes, we investigated the specificity of the zonulin ELISA assay using antibody capture experiments, mass spectrometry, and Western blot analysis. Using serum samples that gave the highest or lowest ELISA signals, we detected several proteins that are likely to be captured by the antibody in the present kit. However, none of these proteins corresponds to pre-haptoglobin2. We used increasing concentrations of recombinant pre-haptoglobin2 and complement C3 as one of the representative captured proteins and the ELISA kit did not detect either. Western blot analysis using both the polyclonal antibodies used in this kit and monoclonal antibodies rose against zonulin showed a similar protein recognition pattern but with different intensity of detection. The protein(s) measured using the ELISA kit was (were) significantly increased in patients with diabetes and obesity and correlated strongly with markers of the lipid and glucose metabolism. Combining mass spectrometry and Western blot analysis using the polyclonal antibodies used in the ELISA kit, we identified properdin as another member of the zonulin family. Our study suggests that the zonulin ELISA does not recognize pre-haptoglobin2, rather structural (and possibly functional) analog proteins belonging to the mannose-associated serine protease family, with properdin

Haptoglobin gene subtypes in three Brazilian population groups of different ethnicities

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Ana L. Miranda-Vilela

2009-01-01

Full Text Available Haptoglobin is a plasma hemoglobin-binding protein that limits iron loss during normal erythrocyte turnover and hemolysis, thereby preventing oxidative damage mediated by iron excess in the circulation. Haptoglobin polymorphism in humans, characterized by the Hp*1 and Hp*2 alleles, results in distinct phenotypes known as Hp1-1, Hp2-1 and Hp2-2, whose frequencies vary according to the ethnic origin of the population. The Hp*1 allele has two subtypes, Hp*1F and Hp*1S, that also vary in their frequencies among populations worldwide. In this work, we examined the distribution frequencies of haptoglobin subtypes in three Brazilian population groups of different ethnicities. The haptoglobin genotypes of Kayabi Amerindians (n = 56, Kalunga Afro-descendants (n = 70 and an urban population (n = 132 were determined by allele-specific PCR. The Hp*1F allele frequency was highest in Kalunga (29.3% and lowest in Kayabi (2.6%. The Hp*1F/Hp*1S allele frequency ratios were 0.6, 1.0 and 0.26 for the Kayabi, Kalunga and urban populations, respectively. This variation was attributable largely to the Hp*1F allele. However, despite the large variation in Hp*1F frequencies, results of FST (0.0291 indicated slight genetic differentiation among subpopulations of the general Brazilian population studied here. This is the first Brazilian report of variations in the Hp *1F and Hp*1S frequencies among non-Amerindian Brazilians.

Evaluation of an enzyme-linked immunosorbent assay for determination of porcine haptoglobin

DEFF Research Database (Denmark)

Petersen, H. H.; Nielsen, J. P.; Jensen, A.L.

2001-01-01

An enzyme-linked immunosorbent assay for quantification of haptoglobin in porcine serum was evaluated. Tbe detection limit when expressed as the estimated concentration of a blank sample was 0.0003 mg/ml. The precision of the assay was acceptable with intra-assay coefficients of variation below 4...... % and inter-assay coefficient of variation below 5 % for serum concentrations ranging from 1.0 mg/ml and above. For samples with a concentration below 0.8 mg/ml, the inter-assay coefficient of variation was above 10 %. The assay maintained linearity under dilution. Recovery was proportional. Haemolysis.......2. The maximum allowable analytical imprecision was 2.6 % and the maximum analytical inaccuracy was 9.9 %. The number of samples required to determine, the true haptoglobin value in an individual pig when accounting for the day-to-day fluctuation was 5. In conclusion, the haptoglobin assay was found...

1. Association between Presence of Haptoglobin Phenotypes and ...

African Journals Online (AJOL)

RICHY

and hypertension in indigenous Zambian patients attending ... the arteries is chronically elevated, is a common and ... Haptoglobin genes have been cited as risk factors in the. 4 ... Blood pressure Measurement. The auscultator method was used utilising a mercury sphygmomanometer and krotkoff sounds heard at the.

Haptoglobin and serum amyloid a in subacute ruminal acidosis in goats

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F.H.D. González

2010-12-01

Full Text Available Ruminal acidosis is a frequent disorder that occurs in goats as a consequence of feedingmistakes in animals not adapted to a diet of easily fermentable carbohydrates. The subacuteform of the disease is difficult to diagnose because no apparent signs are shownand the acid-base parameters may remain within the normal range. The present studyaimed at testing the hypothesis that haptoglobin (Hp and serum amyloid A (SAA,the two major acute phase proteins in ruminants, may be useful as markers of subacuteacidosis in goats.A subacute acidosis was induced in six Murciano-Granadina goats through a diet of60% mixed feed-40% alfalfa hay offered during 5 days to goats not adapted to eatmixed feed. Two goats were rumen-fistulated to investigate the effect of feeding onruminal pH. Sampling of blood and urine of all animals was done before the inductionof the acidosis, during 5 days after the onset of induction and for 18 days after theinduction (recovery period.Ruminal pH in the fistulated goats dropped to less than 5.5 during the inductionperiod, and half of the goats had diarrhea on the third day after the induction of acidosis.Acid-base parameters showed that the acid-base compensatory mechanisms wereefficient in maintaining the equilibrium. Serum Hp had a moderate increase duringthe induction period, while SAA did not change. These results suggest that Hp mightbe a potential marker for ruminal acidosis in goats.

Is there any relationship between haptoglobin phenotypes and ...

African Journals Online (AJOL)

This study was conducted to examine the possible association between Haptoglobin (Hp) phenotypes and diabetes retinopathy in some Ghanaians to determine whether a specific Hp phenotype predisposes diabetics to retinopathy. A total of 110 diabetics were enrolled into the study. Blood samples were taken from each ...

A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans

DEFF Research Database (Denmark)

Vanhollebeke, Benoit; De Muylder, Géraldine; Nielsen, Marianne J

2008-01-01

The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which...... binds the haptoglobin-hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome...... immunity against the parasite....

Haptoglobin Duplicon, Hemoglobin, and Vitamin C: Analyses in the British Women’s Heart and Health Study and Caerphilly Prospective Study

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Philip A. I. Guthrie

2014-01-01

Full Text Available Background. Haptoglobin acts as an antioxidant by limiting peroxidative tissue damage by free hemoglobin. The haptoglobin gene allele Hp2 comprises a 1.7 kb partial duplication. Relative to allele Hp1, Hp2 carriers form protein multimers, suboptimal for hemoglobin scavenging. Objective. To examine the association of haptoglobin genotype with a range of phenotypes, with emphasis on vitamin C and hemoglobin levels. Methods. We applied a quantitative PCR assay for the duplication junction to two population cohorts including 2747 British women and 1198 British men. We examined the association of haptoglobin duplicon copy number with hemoglobin and vitamin C and used the copy number to complete a phenome scan. Results. Hemoglobin concentrations were greater in those with Hp2,2 genotype, in women only (Hp1,1 13.45 g/dL, Hp1,2 13.49 g/dL, Hp2,2 13.61 g/dL; P=0.002, though statistically there was no evidence of a difference between the sexes (z value = 1.2, P=0.24. Haptoglobin genotype was not associated with vitamin C or any other phenotype in either cohort. Conclusions. Our results do not support association of haptoglobin genotype with vitamin C or with other phenotypes measured in two population cohorts. The apparent association between haptoglobin genotype and hemoglobin in the women’s cohort merits further investigation.

Circulating Apolipoprotein A1, Haptoglobin and Α2 Macroglobulin ...

African Journals Online (AJOL)

α2-MG), Apolipoprotein A1 (Apo-1) and Haptoglobin (HP) as non-invasive index of the presence of cirrhosis in chronic hepatitis C patients in relation to the histopathological findings. Subjects and Methods: The study was carried out on 20 ...

Haptoglobin phenotypes as a risk factor for coronary artery disease ...

African Journals Online (AJOL)

Haptoglobin phenotypes as a risk factor for coronary artery disease in type 2 ... Recognition of diabetic individuals at greatest risk of developing coronary artery ... CAD, Group II: 48 type 2DM patients with developed CAD, Group III: 40 age and ...

Marked induction of IL-6, haptoglobin and IFN gamma following experimental BRSV infection in young calves

DEFF Research Database (Denmark)

Grell, Susanne Nedergaard; Tjørnehøj, Kirsten; Larsen, Lars Erik

2005-01-01

Bovine respiratory syncytial virus (BRSV) has been identified worldwide as an important pathogen associated with acute respiratory disease in calves. An infection model has been developed reflecting accurately the clinical course and die, development of pathological signs during a natural BRSV-infection....... In the experiments described in the present study, calves were infected at 13-21 weeks of age and reinfected 14 weeks later. Blood samples front the entire infection period were analysed for acute phase protein (haptoglobin) by ELISA and for expression (mRNA level in peripheral blood mononuclear cells...... to the first infection with BRSV The IFNgamma response was biphasic. with an early peak at day 1-3 post infection (p.i.) and a later increase between day 5 and 8 p.i. Reinfection also resulted in an induction of IFNgamma. but without induction of clinical signs, IL-6 and haptoglobin. These results indicate...

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

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Harris Nathan

2008-12-01

Full Text Available Abstract Background Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63 were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS for biomarker finding. Initial results were validated by analysis of sample set II (n = 371, using one-dimensional gel-electrophoresis. Results In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity ≤ 20 or > 20, identified as haptoglobin (Hp alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014. Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2, of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 – 1.34, p = 0.5221 and 1.03 (95% CI: 0.65 – 1.64, p = 0.8966 for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. Conclusion In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive

Determination of Haptoglobin Genotype in an Iranian Population with Idiopathic Generalized Epilepsy

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Sukaina Al-balaghee

2015-05-01

Full Text Available Background: Haptoglobin (Hp is a plasma α2-sialoglycoprotein that contains alpha and beta chains. It displays in three common phenotypes, Hp1-1, Hp2-1, and Hp2-2. Proteins expressed by polymorphic genes have grossly different molecular sizes resulting in different diffusion rates in the brain. Haptoglobin expressed by the Hp2-2 genotype has lower hemoglobin-binding capacity than Hp1-1 or Hp2-1 and is associated with idiopathic generalized epilepsy. Methods: To determine polymorphism in haptoglobin genes in patients with idiopathic generalized tonic-clonic seizures, 42 men, 42 women, and 50 controls were selected for this study. Genomic DNA was extracted from blood and studied by polymerase chain reactions (PCR. Results: The amplified fragments for the Hp1-1 and Hp2-2 genotypes were 1757 and 3481 base pairs (bp respectively, and the Hp2-1 genotype had both fragments, in addition to a 349-bp fragment. The distribution of the three major Hp phenotypes in epilepsy patients was 28.6 (1-1, 38.1 (2-1, and 33.3% (2-2 in the men, and 31 (1-1, 40.5 (2-1, and 28.6% (2-2 in the women. The distribution of Hp genotypes in controls was 22 (1-1, 40 (2-1, and 38% (2-2. Conclusion: We show that all Hp genotypes participate in idiopathic generalized epilepsy.

Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein

DEFF Research Database (Denmark)

Nielsen, Marianne Jensby; Petersen, Steen Vang; Jacobsen, Christian

2006-01-01

Haptoglobin-related protein (Hpr) is a primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL) particles shown to be a part of the innate immune defense. Despite the assumption hitherto that Hpr does not bind to hemoglobin, the present...

L'haptoglobine chez les enfants atteints de paludisme grave a ...

African Journals Online (AJOL)

SARAH

30 avr. 2014 ... 1- Professeur Titulaire d'Immunologie, UFR Sciences Médicales UFHB Cocody, Chef du Service d'Immunologie et d'Hématologie, CHU Cocody. 2- Attaché de ... milliers d'enfants de moins de 5 ans par an, l'haptoglobine pourrait être un excellent marqueur pour le suivi des états inflammatoires et de la ...

The haptoglobin-CD163-heme oxygenase-1 pathway for hemoglobin scavenging

DEFF Research Database (Denmark)

Thomsen, Jens Haugbølle; Etzerodt, Anders; Svendsen, Pia

2013-01-01

The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex...

Effect of Multiple Mutations in the Hemoglobin- and Hemoglobin-Haptoglobin-Binding Proteins, HgpA, HgpB, and HgpC, of Haemophilus influenzae Type b

OpenAIRE

Morton, Daniel J.; Whitby, Paul W.; Jin, Hongfan; Ren, Zhen; Stull, Terrence L.

1999-01-01

Haemophilus influenzae requires heme for growth and can utilize hemoglobin and hemoglobin-haptoglobin as heme sources. We previously identified two hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA and HgpB, in H. influenzae HI689. Insertional mutation of hgpA and hgpB, either singly or together, did not abrogate the ability to utilize or bind either hemoglobin or the hemoglobin-haptoglobin complex. A hemoglobin affinity purification method was used to isolate a protein of approxi...

Identification of a haptoglobin-hemoglobin complex in the Alaskan Least Cisco (Coregonus sardinella).

Science.gov (United States)

Wahl, S M; Boger, J K; Michael, V; Duffy, L K

1992-01-01

The hemoglobin and a hemoglobin binding protein have been characterized in the Arctic fish (Coregonus sardinella). The evolutionary significance of the hemoglobin and plasma protein differences between fish and mammals is still unresolved. Blood samples from the Alaskan Least Cisco were separated into plasma and hemoglobin fractions and the proteins in these fractions were analyzed both by alkaline agarose gel electrophoresis, by isolelectric focusing, and by capillary electrophoresis. Staining the plasma proteins gels with o-dianisidine revealed hemoglobin containing protein complexes. A hemoglobin-containing band was observed in hemolyzed plasma which did not migrate with free hemoglobin, and is believed to be hemoglobin-haptoglobin complex. Size exclusion chromatography further characterized the hemoglobin as disassociating freely into dimers, and hemoglobin-haptoglobin complex having a molecular weight greater then 200,000 daltons.

Development of monoclonal antibodies to pre-haptoglobin 2 and their use in an enzyme-linked immunosorbent assay (ELISA).

Science.gov (United States)

Flanagan, J J; Arjomandi, A; Delanoy, M L; Du Paty, E; Galea, P; Laune, D; Rieunier, F; Walker, R P; Binder, S R

2014-04-01

Haptoglobins (HPs) are alpha 2-globulin proteins that bind free hemoglobin in plasma to prevent oxidative damage. HPs are produced as preproteins that are proteolytically cleaved in the ER into alpha and beta chains prior to forming mature, functional tetramers. Two alleles exist in humans (HP1 and HP2), therefore three genotypes are present in the population, i.e., HP1-1, HP2-1, and HP2-2. A biochemical role for nascent haptoglobin 2 (pre-haptoglobin 2 or pre-HP2) as the only known modulator of intestinal permeability has been established. In addition, elevated levels of serum pre-HP2 have been detected in multiple conditions including celiac disease and type I diabetes, which are believed to result in part through dysregulation of the intestinal barrier. In this study, we report the development of a monoclonal antibody that is specific for pre-HP2 with a binding affinity in the nanomolar range. Additional antibodies with specificities for preHP but not mature haptoglobin were also characterized. A sandwich enzyme-linked immunosorbent assay (ELISA) was established and validated. The ELISA showed high specificity for pre-HP2 even in the presence of excess pre-HP1 or mature haptoglobins, and has excellent linearity and inter- and intra-assay reproducibility with a working range from 3.1ng/mL to 200ng/mL. Testing of sera from 76 healthy patients revealed a non-Gaussian distribution of pre-HP2 levels with a mean concentration of 221.2ng/mL (95% CI: 106.5-335.9ng/mL) and a median value of 23.9ng/mL. Compared to current approaches, this ELISA offers a validated, monoclonal-based method with high sensitivity and specificity for measuring pre-HP2 in human serum. Copyright © 2014 Elsevier B.V. All rights reserved.

The acute phase response of haptoglobin and serum amyloid A (SAA) in cattle undergoing experimental infection with bovine respiratory syncytial virus

DEFF Research Database (Denmark)

Heegaard, Peter M. H.; Godson, D.L.; Toussaint, M.J.M.

2000-01-01

respiratory syncytial virus (BRSV), analysing the induction of the two most dominant bovine acute phase proteins haptoglobin and serum amyloid A (SAA). Strong and reproducible acute phase responses were detected for both proteins, peaking at around 7-8 days after inoculation of BRSV, while no response...... was seen in mock-inoculated control animals. The serum concentrations reached for SAA and haptoglobin during the BRSV-induced acute phase response were generally the same or higher than previously reported for bacterial infections in calves. The magnitude and the duration of the haptoglobin response...... was found to correlate well with the severity of clinical signs (fever) and with the extent of lung consolidation while SAA responded most rapidly to infection....

Haptoglobin concentrations in free-range and temporarily captive juvenile steller sea lions.

Science.gov (United States)

Thomton, Jamie D; Mellish, Jo-Ann E

2007-04-01

Haptoglobin (Hp) is an acute-phase protein synthesized in the liver that circulates at elevated concentrations in response to tissue damage caused by inflammation, infection, and trauma. As part of a larger study, sera Hp concentrations were measured in temporarily captive (n = 21) and free-range (n = 38) western stock juvenile Steller sea lions (Eumetopias jubatus) sampled from 2003 to 2006. Baseline Hp concentration at time of capture was 133.3 +/- 17.4 mg/dl. Temporarily captive animals exhibited a 3.2-fold increase in Hp concentrations during the first 4 wk of captivity, followed by a return to entry levels by week 5. Haptoglobin levels were not influenced by age, season, or parasite load. There was a significant positive correlation between Hp concentrations and white blood cell count (P < 0.001) and globulin levels (P < 0.001) and a negative correlation to red blood cell count and hematocrit (P < 0.001 for both). There was no correlation between Hp levels and platelet count (P = 0.095) or hemoglobin (P = 0.457). Routine blubber biopsies collected under gas anesthesia did not produce a measurable Hp response. One animal with a large abscess had an Hp spike of 1,006.0 mg/dl that returned to entry levels after treatment. In conclusion, serum Hp levels correlate to the stable clinical health status observed during captivity, with moderate Hp response during capture and initial acclimation to captivity and acute response to inflammation and infection.

The Influence of Cigarette Smoking on Gingival Bleeding and Serum Concentrations of Haptoglobin and Alpha 1-Antitrypsin

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Fouad H. Al-Bayaty

2013-01-01

Full Text Available The objectives of this study were to evaluate the influence of cigarette smoking on gingival bleeding and serum concentrations of cotinine, haptoglobin, and alpha 1-antitrypsin in Malaysian smokers. A total of 197 male smokers and nonsmokers were recruited for this study. Plaque index, bleeding on probing (BOP, and levels of serum cotinine, haptoglobin, and alpha 1-antitrypsin were evaluated. The data were analyzed using SPSS version 20.0, with the significance level set at α≤0.05. Linear regression analyses were performed. The mean cigarette consumption per day was 13.39±5.75 cigarettes; the mean duration was 16.03±8.78 years. Relatively low BOP values (26.05±1.48 and moderate plaque indexes (51.35±11.27 were found. The levels of serum cotinine (106.9±30.71 ng/dL, haptoglobin (76.04±52.48 mg/dL, and alpha 1-antitrypsin (141.90±18.40 mg/dL were significantly higher in smokers compared to non-smokers. Multiple logistic regression models for all variables and smokers demonstrated observed differences between BOP, the number of cigarettes per day, and duration of smoking, while serum cotinine, haptoglobin and alpha-1 antitrypsin levels showed no significant differences. Duration of smoking (years and the cotinine level in serum showed a significant correlation with plaque index. The present analysis demonstrated that the duration of smoking in years, but not the number of cigarettes smoked per day, was associated with reduced gingival bleeding in smokers.

Re-evaluation of the haptoglobin reference values with the radial immunodiffusion technique

NARCIS (Netherlands)

Rijn, H.J.M. van; Schreurs, W.H.P.; Schrijver, J.

1984-01-01

The reference values of the three main types of serum haptoglobin Hp 1-1, Hp 2-1, and Hp 2-2, as determined by radial immunodiffusion and with phenotype determination on polyacrylamide gel electrophoresis have been re-evaluated for both sexes. For that purpose about 500 serum samples were collected

Determinação sérica de haptoglobina, ceruloplasmina e alfa-glicoproteína ácida em cães com gastrenterite hemorrágica Determination of serum haptoglobin, ceruloplasmin and acid alpha-glycoprotein in dogs with haemorrhagic gastroenteritis

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Márcia Mery Kogika

2003-06-01

Full Text Available As proteínas de fase aguda (PFA são proteínas plasmáticas, cujo estímulo à síntese ocorre de forma rápida e marcante em resposta à injúria tecidual. Estas proteínas permitem o diagnóstico de processos inflamatórios em animais com supressão ou depressão medular. Além disso, são úteis na monitorização da resolução tecidual de traumas ou inflamação e também na avaliação da resposta orgânica ao tratamento. Uma vez que a leucopenia é observada nos estádios iniciais da parvovirose canina, a dosagem das PFA pode permitir a avaliação do processo inflamatório sob estas condições. Considerando-se estas hipóteses, foram determinados os níveis séricos das PFA (haptoglobina, ceruloplasmina e alfa-glicoproteína ácida em 11 cães saudáveis e 11 cães leucopênicos com gastrenterite hemorrágica, com suspeita clínica de parvovirose canina. A avaliação estatística mostrou diferença significativa, com intervalo de confiabilidade de 99% (PAcute phase proteins (APP are serum proteins whose stimulus for the synthesis happens in a quick and intense manner in response to tissue injury. Those proteins allow the diagnosis of inflammatory process in animals with bone marrow depression and, also, they are useful in the follow up of tissue resolution of traumas or inflammation, as well as in the evaluation of the organic response of the treatment. As leukopenia is observed in the initial stage of the canine parvovirus infection, the dosage of APP can allow the evaluation of the inflammatory process under these conditions. According to these hypothesis, serum APP levels (haptoglobin, ceruloplasm and a-acid-glycoprotein in 11 healthy dogs and 11 leukopenic dogs with haemorrhagic gastroenteritis, clinically suspected of canine parvovirus infection, were measured. There was a significant difference, with confidence interval of 99% (P <0.01 for the haptoglobin (p <0.0064 and the acid alpha-glycoprotein (p <0.0042 and 95% (P <0.05 of

The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease.

Science.gov (United States)

Vanuytsel, Tim; Vermeire, Séverine; Cleynen, Isabelle

2013-12-01

Crohn's disease (CD) and ulcerative colitis (UC), collectively called inflammatory bowel disease (IBD), are immune-mediated conditions characterized by a chronic inflammation of the gut. Their precise etiology is unknown, although an increased intestinal permeability has been shown to play a central role in the pathogenesis of IBD. The intestinal epithelium provides the largest interface between the external environment and the host, and is thus a crucial regulation site of innate and adaptive immunity. Zonulin is one of the few known physiological mediators of paracellular intestinal permeability. It was found upregulated in different immune diseases like Celiac disease and Type 1 Diabetes (T1D). Recently, human zonulin was identified as prehaptoglobin-2 (pre-HP2) which before only had been regarded as the inactive precursor for HP2. Haptoglobin (HP) is a hemoglobin-binding protein with immunomodulatory properties. Its gene harbors a common polymorphism with 2 different alleles: HP1 and HP2. Allele HP2 and genotype HP22 has been shown to be overrepresented in different immune diseases like Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and T1D, and has also been found to be more frequent in patients with IBD (UC and CD) than in healthy controls.   In order to get some clues about the mechanism of action of HP(2) in IBD pathogenesis, we here review the current state of knowledge about zonulin and haptoglobin structure and function, and their plausible role in immune mediated diseases with an emphasis on IBD.

Effects of obesity, total fasting and re-alimentation on L-thyroxine (T4), 3,5,3'-L-triiodothyronine (T3), 3,3',5'-L-triiodothyronine (rT3), thyroxine binding globulin (TBG), cortisol, thyrotrophin, cortisol binding globulin (CBG), transferrin, alpha 2-haptoglobin and complement C'3 in serum.

Science.gov (United States)

Scriba, P C; Bauer, M; Emmert, D; Fateh-Moghadam, A; Hofmann, G G; Horn, K; Pickardt, C R

1979-08-01

The effects of total fasting for 31 +/- 10 days followed by re-alimentation with an 800 calorie diet on thyroid function, i.e. T4,T3,rT3,RT3U (resin T3 uptake), and TSH, and on TBG levels in serum were studied sequentially in obese hospitalized patients (N=18). Additionally, cortisol, growth hormone, prolactin, parathyrin and free fatty acids were followed as hormonal and metabolic parameters, respectively. Further, CBG, transferrin, alpha 2-haptoglobin and complement C'3 were measured as representatives of other serum proteins. Results before fasting: T4, T3, TBG, cortisol, CBG, alpha 2-haptoglobin and complement C'3 of the obese patients were elevated when compared with healthy normal weight controls, whereas rT3, T4/TBG ratio, T3/TBG ratio, TSH, coritsol/cbg ratio, growth hormone, prolactin, parathyrin and transferrin of the obese group were normal. RT3U and fT4 index were decreased in the obese patients. Results during fasting: Significant decreases were observed during fasting for the following parameters -- T3, TBG, T3/TBG ratio, transferrin, alpha 2-haptoglobin complement C'3. rT3, T4/TBG ratio, RT3U, fT4 index and FFA increased. T4, tsh response to TRH stimulation, cortisol, CBG, cortisol/cbg ratio, parathyrin, growth hormone and prolactin did not change. Results during re-alimentation: T3, TBG, T3/TBG ratio, TSH response to TRH, transferrin, alpha 2-haptoglobin and complement C'3 increased. Conversely, fT3, RT3U, FFA, cortisol and cortisol/cbg ratio decreased whereas the other parameters did not change. 1) There is no evidence for primary hypothyroidism in obese patients during prolonged fasting and re-alimentation. 2) The rapid decrease of T3 and increase of RT3U after initiation of fasting are not fully explained by the observed slower decreases in TBG. 3) The alterations of T3, rT3 and RT3U resemble in their kinetics the changes in FFA levels. 4) Fasting reduced the levels of only certain serum proteins, interestingly TBG, transferrin, alpha 2

Distribution of haptoglobin types and their significance for changes in biochemical and immunological parameters of people irradiated at small doses

International Nuclear Information System (INIS)

Tel'nov, V.I.; Vologodskaya, I.A.; Zhuntova, G.V.

1995-01-01

Haptoglobin (Hp) polymorphism and its significance for changes in biochemical and immunological parameters was analyzed in personnel of a nuclear plant receiving doses of external and internal irradiation close to maximum permissible levels. The distribution of Hp types and frequencies of alleles Hp in the group of probands as a whole (1-1, 14.1; 2-1, 49.2%; and 2-2, 36.7%) and in probands subjected to different types and doses of irradiation (1-1, 13.6 - 16.0%; 2-1, 47.8 - 50.5%; and 2-2, 35.8 - 38.2%) did not differ from those expected or from corresponding parameters of the control group and population. An increase in the frequency of allele Hp 1 was observed for persons over 60 years of age. It was found that the levels of uric acid, the activities of acid phosphatase, lactate dehydrogenase, alkaline phosphatase and its isozymes, and the content of certain lymphocyte classes and immune complexes are initially higher in carriers of Hp type 1-1. In these probands, changes in certain parameters related to irradiation were observed less frequently. In some cases, opposite changes in immunological parameters were observed in persons with different Hp types after internal irradiation. 23 refs., 6 tabs

Serum iron, ferritin, transferrin and haptoglobin concentration variations during repeated show jumping competition in horse

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Anna Assenza

2016-01-01

Full Text Available Modifications of the iron profile in athlete horses during two international three star (*** show jumping competitions performed in two consecutive weekends were evaluated. Serum iron, ferritin, transferrin, and haptoglobin were assessed in 12 well-trained Italian Saddle horses. Blood samplings were performed before the first day of competition (R1, within 10 min from the end of each competition (J1, J2 and on the day after competition (R2. The same plan was followed during the second weekend (J3, J4 and R3. One-way repeated measures analysis of variance (ANOVA was applied on obtained data, and a significant effect of exercise (P < 0.05 on all studied indices was found. These results suggest that serum iron, transferrin, ferritin and haptoglobin are responsive to intense exercise and could be considered important indicators that may give important information about the horse’s performance.

Thrombotic microangiopathy associated with Valproic acid toxicity.

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Hebert, Sean A; Bohan, Timothy P; Erikson, Christian L; Swinford, Rita D

2017-08-03

Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA. We present the first case of a patient meeting clinical criteria for DI-TMA following admission for valproic acid toxicity. An adolescent male with difficult to control epilepsy was admitted for impaired hepatic function while on valproic acid therapy. On the third hospital day, he developed severe metabolic lactic acidosis and multiorgan failure, prompting transfer to the pediatric intensive care unit. Progressive anemia and thrombocytopenia instigated an evaluation for thrombotic microangiopathy, where confirmed by concomitant hemolysis, elevated lactate dehydrogenase (LDH), low haptoglobin, and concurrent oliguric acute kidney injury. Thrombotic thrombocytopenic purpura was less likely with adequate ADAMTS13. Discontinuing valproic acid reversed the anemia, thrombocytopenia, and normalized the LDH and haptoglobin, supporting a drug-induced cause for the TMA. To the best of our knowledge, this is the first report of drug-induced TMA from valproic acid toxicity.

Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI as biomarkers of recovery.

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Valentina Peta

Full Text Available There is a clear need for better biomarkers of drug-induced-liver-injury (DILI.We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI.We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC of ActiTest components as predictors of recovery outcome defined as an ALT <2x the upper limit of normal (ULN, and BILI <2x ULN.After adjudication, 154 patients were considered to have DILI and 22 were considered to have acute liver injury without DILI. A multivariate regression analysis (ActiTest-DILI patent pending combining the ActiTest components without BILI and ALT (used as references, apolipoprotein-A1, haptoglobin, alpha-2-macroglobulin and GGT, age and gender, resulted in a significant prediction of recovery with 67.0% accuracy (77/115 and an AUROC of 0.724 (P<0.001 vs. no prediction 0.500. Repeated apolipoprotein-A1 and haptoglobin remained significantly higher in the DILI cases that recovered (n = 65 versus those that did not (n = 16, at inclusion, at 4-8 weeks and at 8-12 weeks. The same results were observed after stratification on APAP cases and non-APAP cases.We identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated.

High fat diet and inflammation - modulation of Haptoglobin level in rat brain

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Maria Stefania eSpagnuolo

2015-12-01

Full Text Available Obesity and dietary fats are well known risk factors for the pathogenesis of neurodegenerative diseases. The analysis of specific markers, whose brain level can be affected by diet, might contribute to unveil the intersection between inflammation/obesity and neurodegeneration. Haptoglobin (Hpt is an acute phase protein, which acts as antioxidant by binding free Haemoglobin (Hb, thus neutralizing its pro-oxidative action. We previously demonstrated that Hpt plays critical functions in brain, modulating cholesterol trafficking in neuroblastoma cell lines, beta-amyloid (Aβ uptake by astrocyte, and limiting Aβ toxicity on these cells. A major aim of this study was to evaluate whether a long term (12 or 24 weeks high-fat diet (HFD influences Hpt and Hb expression in rat hippocampus. We also assessed the development of obesity-induced inflammation by measuring hippocampal level of TNF-alpha, and the extent of protein oxidation by titrating nitro-tyrosine (N-Tyr. Hpt concentration was lower (p<0.001 in hippocampus of HFD rats than in control animals, both in the 12 and in the 24 weeks fed groups. HFD was also associated in hippocampus with the increase of Hb level (p<0.01, inflammation and protein oxidative modification, as evidenced by the increase in the concentration of TNF-alpha and nitro-tyrosine. In fact, TNF-alpha concentration was higher in rats receiving HFD for 12 (p<0.01 or 24 weeks (p<0.001 compared to those receiving the control diet. N-Tyr concentration was more elevated in hippocampus of HFD than in control rats in both 12 weeks (p=0.04 and 24 weeks groups (p=0.01, and a positive correlation between Hb and N-Tyr concentration was found in each group. Finally, we found that the treatment of the human glioblastoma-astrocytoma cell line U-87 MG with cholesterol and fatty acids, such as palmitic and linoleic acid, significantly impairs (p<0.001 Hpt secretion in the extracellular compartment.We hypothesize that the HFD-dependent decrease of

Association between haptoglobin gene and insulin resistance in Arab-Americans.

Science.gov (United States)

Burghardt, Kyle J; Masri, Dana El; Dass, Sabrina E; Shikwana, Sara S; Jaber, Linda A

2017-11-01

To analyze associations between variation in the HP gene and lipid and glucose-related measures in Arab-Americans. Secondary analyses were performed based on sex. Genomic DNA was extracted from samples obtained from a previous epidemiological study of diabetes in Arab-Americans. The HP 1 and 2 alleles were analyzed by polymerase chain reaction and gel electrophoresis. Associations were analyzed by linear regression. Associations were identified between the heterozygous haptoglobin 2-1 genotype and insulin resistance, fasting insulin and fasting c-peptide. The effect of sex did not remain significant after adjustment for relevant variables. HP genetic variation may have utility as a biomarker of insulin resistance and diabetes risk in Arab-Americans, however, future prospective studies are needed.

Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

DEFF Research Database (Denmark)

Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

2004-01-01

CD163 is the macrophage receptor for endocytosis of haptoglobin.hemoglobin complexes. The extracellular region consisting of nine scavenger receptor cysteine rich (SRCR) domains also circulates in plasma as a soluble protein. By ligand binding analysis of a broad spectrum of soluble CD163...... truncation variants, the amino-terminal third of the SRCR region was shown to be crucial for the binding of haptoglobin.hemoglobin complexes. By Western blotting of the CD163 variants, a panel of ten monoclonal antibodies was mapped to SRCR domains 1, 3, 4, 6, 7, and 9, respectively. Only the two antibodies...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...

Clinical Relevance of Transforming Growth Factor-β1, Interleukin-6 and Haptoglobin for Prediction of Obesity Complications in Prepubertal Egyptian Children

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Inas R. El-Alameey

2015-03-01

CONCLUSIONS: Obesity is associated with chronic low-grade inflammation. High levels of interleukin-6 and haptoglobin are considered to be early biomarkers of inflammation associated with severe obesity with subsequent cardiovascular and type 2 diabetes risk.

Increasing intake of essential fatty acids from milk replacer benefits performance, immune responses, and health of preweaned Holstein calves.

Science.gov (United States)

Garcia, M; Shin, J H; Schlaefli, A; Greco, L F; Maunsell, F P; Thatcher, W W; Santos, J E P; Staples, C R

2015-01-01

The objective was to evaluate the effect of feeding increasing amounts of essential fatty acids (FA) in milk replacer (MR) during the first 60 d of life on growth, health, and immunity of Holstein calves. Calves were born from dams fed low concentrations of total and essential FA during the lasT2 mo of pregnancy. Newborn calves were blocked by sex and parity of the dam and assigned randomly to receive 1 of 4 MR treatments (T). Hydrogenated coconut oil and soybean oil were mixed with emulsifier and commercial MR powder to prepare the following 4 MR containing 0.119 and 0.007 (T1), 0.187 and 0.017 (T2), 0.321 and 0.036 (T3), and 0.593 and 0.076 (T4) g of intake per kg of metabolic body weight (BW(0.75)) of linoleic acid and α-linolenic acid, respectively. At 30 d of life, concentrations of essential FA (linoleic acid and α-linolenic acid) in liver increased, whereas concentrations of C12:0, C14:0, C16:0, and C20:3n-9 decreased linearly with increasing intake of essential FA. Body weight gain and feed efficiency were optimized when male calves consumed T2, whereas gain by female calves tended to increase linearly with increasing intake of essential FA during the first 30 d of age. However, these responses to treatment were not maintained after initiation of concentrate feeding at 31 d of life. Over the 60-d preweaning period, wither and hip heights were improved in both sexes as intake of essential FA increased up to T3. Some measures of health and immunity were affected by replacing some coconut oil with soybean oil. Severity of diarrhea tended to decrease linearly; plasma concentrations of haptoglobin during diarrhea were lower in T2, T3, and T4; phagocytosis by blood neutrophils tended to peak for calves fed T2; in vitro proliferation of stimulated blood lymphocytes was greater for calves fed T2; in vitro stimulated blood cells produced more IFN-γ (up to T3 for males and T2 for females), concentrations of serum IgG against ovalbumin injections were increased in

Study of chaperone-like activity of human haptoglobin: conformational changes under heat shock conditions and localization of interaction sites

Czech Academy of Sciences Publication Activity Database

Ettrich, R.; Brandt, W.; Kopecký ml., V.; Baumruk, V.; Hofbauerová, Kateřina; Pavlíček, Z.

2002-01-01

Roč. 383, č. 10 (2002), s. 1667-1676 ISSN 1431-6730 Grant - others:GA UK(CZ) 220/2000/B-CH; Volkswagen Foundation(DE) I/74679 Institutional research plan: CEZ:AV0Z5011922; CEZ:MSM 113100001 Keywords : chaperone * haptoglobin * molecular modeling Subject RIV: BO - Biophysics Impact factor: 2.548, year: 2002

Modeling hemoglobin and hemoglobin:haptoglobin complex clearance in a non-rodent species–pharmacokinetic and therapeutic implications

OpenAIRE

Boretti, Felicitas S.; Baek, Jin Hyen; Palmer, Andre F.; Schaer, Dominik J.; Buehler, Paul W.

2014-01-01

Background: Haptoglobin (Hp) prevents hemoglobin (Hb) extravasation and attenuates Hb induced tissue oxidation and vasoconstriction. Small animal models such as mouse, rat and guinea pig appear to demonstrate proof-of-concept for Hb neutralization by Hp in diverse pre-clinical conditions. However, these species differ significantly from humans in the clearance of Hb:Hp and demonstrate long persistence of circulating Hb:Hp complexes. Objective: The focus of this study is to understand Hb:Hp...

Haplotype association between haptoglobin (Hp2 and Hp promoter SNP (A-61C may explain previous controversy of haptoglobin and malaria protection.

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Sharon E Cox

2007-04-01

Full Text Available Malaria is one of the strongest recent selective pressures on the human genome, as evidenced by the high levels of varying haemoglobinopathies in human populations-despite the increased risk of mortality in the homozygous states. Previously, functional polymorphisms of Hp, coded by the co-dominant alleles Hp1 and Hp2, have been variously associated with several infectious diseases, including malaria susceptibility.Risk of a clinical malarial episode over the course of a malarial transmission season was assessed using active surveillance in a cohort of Gambian children aged 10-72 months. We report for the first time that the major haplotype for the A-61C mutant allele in the promoter of haptoglobin (Hp-an acute phase protein that clears haemoglobin released from haemolysis of red cells-is associated with protection from malarial infection in older children, (children aged >or=36 months, >500 parasites/ul and temperature >37.5 degrees C; OR = 0.42; [95% CI 0.24-0.73] p = 0.002 (lr test for interaction, or=36 months, p = 0.014. Protection was also observed using two other definitions, including temperature >37.5 degrees C, dipstick positive, plus clinical judgement of malaria blinded to dipstick result (all ages, OR = 0.48, [95% CI 0.30-0.78] p = 0.003; >or=36 months, OR = 0.31, [95% CI 0.15-0.62] p = 0.001. A similar level of protection was observed for the known protective genetic variant, sickle cell trait (HbAS.We propose that previous conflicting results between Hp phenotypes/genotypes and malaria susceptibility may be explained by differing prevalence of the A-61C SNP in the populations studied, which we found to be highly associated with the Hp2 allele. We report the -61C allele to be associated with decreased Hp protein levels (independent of Hp phenotype, confirming in vitro studies. Decreased Hp expression may lead to increased oxidant stress and increased red cell turnover, and facilitate the development of acquired immunity, similar to

The porcine acute phase response to infection with Actinobacillus pleuropneumoniae. Haptoglobin, C-reactive protein, major acute phase protein and serum amyloid a protein are sensitive indicators of infection

DEFF Research Database (Denmark)

Heegaard, Peter M. H.; Klausen, Joan; Nielsen, J.P.

1998-01-01

response peaking at around 2 days after infection. Haptoglobin, C-reactive protein (CRP), and major acute phase protein (MAP) responded with large increases in serum levels, preceding the development of specific antibodies by 4-5 days. Serum amyloid A protein (SAA) was also strongly induced. The increase......, kinetics of induction and normalization were different between these proteins. It is concluded that experimental Ap-infection by the aerosol route induces a typical acute phase reaction in the pig, and that pig Hp, CRP, MAP, and SAA are major acute phase reactants. These findings indicate the possibility...

Aspirin increases mitochondrial fatty acid oxidation

International Nuclear Information System (INIS)

Uppala, Radha; Dudiak, Brianne; Beck, Megan E.; Bharathi, Sivakama S.; Zhang, Yuxun; Stolz, Donna B.; Goetzman, Eric S.

2017-01-01

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. - Highlights: • Aspirin increases mitochondrial—but inhibits peroxisomal—fatty acid oxidation. • Aspirin acetylates mitochondrial proteins including fatty acid oxidation enzymes. • SIRT3 does not influence the effect of aspirin on fatty acid oxidation. • Increased fatty acid oxidation is likely due to altered mitochondrial morphology and respiration.

Meta-analysis of the association of the haptoglobin genotype with cardiovascular outcomes and the pharmacogenomic interactions with vitamin E supplementation

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Asleh R

2018-04-01

Full Text Available Rabea Asleh,1,2 Alexandros Briasoulis,3 Elliot M Berinstein,1 Joshua B Wiener,1 Mohan Palla,4 Sudhir S Kushwaha,2 Andrew P Levy1 1Bruce and Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel; 2Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA; 3Division of Cardiovascular Diseases, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 4Department of Cardiology, Detroit Medical Center, Wayne State University, Detroit, MI, USA Objectives: The objectives of the study were to compile and summarize the data from all of the clinical trials designed to examine the association between haptoglobin (Hp genotype and incidence of cardiovascular (CV events in patients with diabetes mellitus (DM and to assess the impact of vitamin E treatment on CV outcomes according to the Hp genotype.Background: The Hp genotype could serve as a predictive biomarker to DM patients who may benefit from vitamin E therapy.Methods: The electronic databases MEDLINE, PubMed, EMBASE and the Cochrane Library for Central Register of Clinical Trials were searched systematically using the following MESH terms: “haptoglobin genotype”, “diabetes mellitus” and “cardiovascular events”.Results: Overall, 13 studies fit the inclusion criteria for this analysis, yielding a large study population that included 6,161 patients without Hp 2-2 and 4,684 patients with Hp 2-2. The analysis of these studies showed that the incidence of CV events in DM patients with the Hp 2-2 genotype was significantly increased as compared to non-Hp 2-2 patients in all three subgroups of case–control (OR: 2.2, 95% CI: 1.3–3.6; P=0.003, cohort (OR: 1.3, 95% CI: 1.2–1.5; P=0.001 and randomized controlled trials (OR: 1.6, 1.2–2.2; P=0.005. Among patients with the Hp 2-2 genotype, administration of vitamin E was associated with lower rates of CV events (OR: 0.66, 95% CI: 0.45–0.95; P=0.025. Further investigation into the association between Hp

Haptoglobin is required to prevent oxidative stress and muscle atrophy.

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Enrico Bertaggia

Full Text Available BACKGROUND: Oxidative stress (OS plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated. RESULTS: We used Hp knockout mice (Hp-/- to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD, OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced. CONCLUSIONS: Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges.

Proteomics mapping of cord blood identifies haptoglobin "switch-on" pattern as biomarker of early-onset neonatal sepsis in preterm newborns.

Science.gov (United States)

Buhimschi, Catalin S; Bhandari, Vineet; Dulay, Antonette T; Nayeri, Unzila A; Abdel-Razeq, Sonya S; Pettker, Christian M; Thung, Stephen; Zhao, Guomao; Han, Yiping W; Bizzarro, Matthew; Buhimschi, Irina A

2011-01-01

Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1(st)-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (PLCA) was further used for unbiased classification of all 180 cases based on probability of "antenatal IAI exposure" as latent variable. This was then subjected to 2(nd)-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage. Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth.

Proteomics Mapping of Cord Blood Identifies Haptoglobin “Switch-On” Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

Science.gov (United States)

Buhimschi, Catalin S.; Bhandari, Vineet; Dulay, Antonette T.; Nayeri, Unzila A.; Abdel-Razeq, Sonya S.; Pettker, Christian M.; Thung, Stephen; Zhao, Guomao; Han, Yiping W.; Bizzarro, Matthew; Buhimschi, Irina A.

2011-01-01

Background Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. Methodology/Principal Findings We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1st-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (PLCA) was further used for unbiased classification of all 180 cases based on probability of “antenatal IAI exposure” as latent variable. This was then subjected to 2nd-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage. Conclusions/Significance Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the

Meat juice: An alternative matrix for assessing animal health by measuring acute phase proteins. Correlations of pig-MAP and haptoglobin concentrations in pig meat juice and plasma.

Science.gov (United States)

Piñeiro, M; Gymnich, S; Knura, S; Piñeiro, C; Petersen, B

2009-10-01

Quantification of acute phase proteins (APPs) in blood can be used for monitoring animal health and welfare on farms, and could be also of interest for the detection of diseased animals during the meat inspection process. However serum or plasma is not always available for end-point analysis at slaughter. Meat juice might provide an adequate, alternative matrix that can be easily obtained for post-mortem analysis at abattoirs. The concentrations of pig Major Acute phase Protein (pig-MAP) and haptoglobin, two of the main APPs in pigs, were determined in approximately 300 paired samples of plasma and meat juice from the diaphragm (pars costalis), obtained after freezing and thawing the muscle. APPs concentrations in meat juice were closely correlated to those in plasma (r=0.695 for haptoglobin, r=0.858 for pig-MAP, panimal health in pig production, with implications for food safety and meat quality.

The haptoglobin promoter polymorphism rs5471 is the most definitive genetic determinant of serum haptoglobin level in a Ghanaian population.

Science.gov (United States)

Soejima, Mikiko; Teye, Kwesi; Koda, Yoshiro

2018-08-01

The serum haptoglobin (HP) level varies in various clinical conditions and among individuals. Recently, the common HP alleles, rs5472, and rs2000999 have been reported to associate with serum HP level, but no studies have been done on Africans. Here, we explored the relationship of not only these polymorphisms but also rs5470 and rs5471 to the serum HP level in 121 Ghanaians. Genotyping of rs2000999 was performed by PCR using hydrolysis probes, while the other polymorphisms have been already genotyped. Serum HP level was measured by a sandwich ELISA. We observed a significant association between rs5471 and the serum HP level (p = 0.026). It was also observed within the subgroups of HP 2 /HP 2 and HP 2 /HP 1 . In addition, we detected a trend toward lower HP levels for individuals with the A allele of rs2000999 than those without A, but it was not statistically significant (p = 0.156). However, we did not observe the clear associations between other polymorphisms and serum HP level that were observed for Europeans and Asians because of the small sample size and the complexity of SNPs affecting the HP level. We suggest that rs5471 is a strong genetic determinant of HP levels in Ghanaians, and this seems to be characteristic of Africans. Further investigation using large scale samples will help in understanding the genetic background of individual variability of the serum HP level. Copyright © 2018 Elsevier B.V. All rights reserved.

Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.

Science.gov (United States)

Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

2015-01-01

The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Increased Bile Acid Synthesis and Impaired Bile Acid Transport in Human Obesity

OpenAIRE

Haeusler, Rebecca A.; Camastra, Stefania; Nannipieri, Monica; Astiarraga, Brenno; Castro-Perez, Jose; Xie, Dan; Wang, Liangsu; Chakravarthy, Manu; Ferrannini, Ele

2015-01-01

We measured plasma bile acids, markers of bile acid synthesis, and expression of bile acid transporters in obese and nonobese subjects. We found that obesity was associated with increased bile acid synthesis and 12-hydroxylation, blunted response of plasma bile acids to insulin infusion or a mixed meal, and decreased expression of liver bile acid transporters.

The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

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Jens Haugbølle Thomsen

2013-01-01

Full Text Available The haptoglobin- (Hp- CD163-heme oxygenase-1 (HO-1 pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex in macrophages followed by lysosomal Hp-Hb breakdown and HO-1-catalyzed conversion of heme into the metabolites carbon monoxide (CO, biliverdin, and iron. The plasma concentration of Hp is a limiting factor as evident during accelerated hemolysis, where the Hp depletion may cause serious Hb-induced toxicity and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6, but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway in the anti-inflammatory response.

Increased levels of proteins of the acute inflammatory phase in the peritoneal fluid of women with advanced stages of endometriosis.

Science.gov (United States)

Polak, Grzegorz; Barczyński, Bartłomiej; Bednarek, Wiesława; Kwaśniewski, Wojciech; Wertell, Iwona; Derewianka-Polak, Magdalena; Makara-Studzińska, Marta; Kotarski, Jan

2015-06-01

Most investigators agree that endometriosis is associated with a state of subclinical, non-infectious peritoneal inflammation. The objective of the study was to assess concentrations of two markers of the acute inflammatory phase proteins, haptoglobin and ceruloplasmin, in peritoneal fluid of endometriotic women. 229 women who underwent diagnostic or therapeutic laparoscopy were included in the study Minimal, mild, moderate and severe endometriosis according to ASRM was confirmed in 119 women (study groups), whereas 110 patients suffered from simple serous or dermoid ovarian cysts (reference groups). Haptoglobin and ceruloplasmin concentrations in the peritoneal fluid samples aspirated during laparoscopy were measured using commercially available radial immunodiffusion kits. The concentration of haptoglobin in the peritoneal fluid of women with endometriosis was significantly higher as compared to patients with serous and dermoid ovarian cysts. Significantly higher haptoglobin level was observed in patients with severe and moderate endometriosis as compared to women from both reference groups. No significant difference in the peritoneal fluid ceruloplasmin levels was found between patients with endometriosis and women from reference groups. However, it was noted that ceruloplasmin levels are higher in the subgroup of patients with severe endometriosis as compared to both reference groups and women with mild disease. Our results support the hypothesis that endometriosis is associated with subclinical inflammation within the peritoneal cavity It may be speculated that pro-inflammatory stimuli strong enough to cause an increase in acute inflammatory phase proteins peritoneal fluid concentrations are observed only in the advanced stages of the disease.

Serum n-3 Tetracosapentaenoic Acid and Tetracosahexaenoic Acid Increase Following Higher Dietary α-Linolenic Acid but not Docosahexaenoic Acid.

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Metherel, Adam H; Domenichiello, Anthony F; Kitson, Alex P; Lin, Yu-Hong; Bazinet, Richard P

2017-02-01

n-3 Tetracosapentaenoic acid (24:5n-3, TPAn-3) and tetracosahexaenoic acid (24:6n-3, THA) are believed to be important intermediates to docosahexaenoic acid (DHA, 22:6n-3) synthesis. The purpose of this study is to report for the first time serum concentrations of TPAn-3 and THA and their response to changing dietary α-linolenic acid (18:3n-3, ALA) and DHA. The responses will then be used in an attempt to predict the location of these fatty acids in relation to DHA in the biosynthetic pathway. Male Long Evans rats (n = 6 per group) were fed either a low (0.1% of total fatty acids), medium (3%) or high (10%) ALA diet with no added DHA, or a low (0%), medium (0.2%) or high (2%) DHA diet with a background of 2% ALA for 8 weeks post-weaning. Serum n-3 and n-6 polyunsaturated fatty acid (PUFA) concentrations (nmol/mL ± SEM) were determined by gas chromatography-mass spectrometry. Serum THA increases from low (0.3 ± 0.1) to medium (5.8 ± 0.7) but not from medium to high (4.6 ± 0.9) dietary ALA, while serum TPAn-3 increases with increasing dietary ALA from 0.09 ± 0.04 to 0.70 ± 0.09 to 1.23 ± 0.14 nmol/mL. Following DHA feeding, neither TPAn-3 or THA change across all dietary DHA intake levels. Serum TPAn-3 demonstrates a similar response to dietary DHA. In conclusion, this is the first study to demonstrate that increases in dietary ALA but not DHA increase serum TPAn-3 and THA in rats, suggesting that both fatty acids are precursors to DHA in the biosynthetic pathway.

Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

DEFF Research Database (Denmark)

Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

2004-01-01

binding to SRCR domain 3 exhibited effective inhibition of ligand binding. Furthermore, analysis of purified native CD163 revealed that proteolytic cleavage in SRCR domain 3 inactivates ligand binding. Calcium protects against cleavage in this domain. Analysis of the calcium sensitivity of ligand binding...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...... for the calcium-sensitive coupling of haptoglobin.hemoglobin complexes....

Human haptoglobin phenotypes and concentration determination by nanogold-enhanced electrochemical impedance spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Cheng, Tsai-Mu; Lee, Tzu-Cheng; Tseng, Shin-Hua; Chu, Hsueh-Liang; Chang, Chia-Ching [Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30050, Taiwan (China); Pan, Ju-Pin, E-mail: ccchang01@faculty.nctu.edu.tw [Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan (China)

2011-06-17

Haptoglobin (Hp) is an acute phase protein that binds free hemoglobin (Hb), preventing Hb-induced oxidative damage in the vascular system. There are three phenotypes in human Hp, whose heterogeneous polymorphic structures and varying concentrations in plasma have been attributed to the cause of diseases and outcome of clinical treatments. Different phenotypes of Hp may be composed of the same subunits but different copy numbers, rendering their determination difficult by a single procedure. In this study, we have developed a simple, fast, reliable and sensitive method, using label-free nanogold-modified bioprobes coupled with self-development electrochemical impedance spectroscopy (EIS). By this method, probe surface charge transfer resistance is detected. The relative charge transfer resistance ratios for Hp 1-1, Hp 2-1 and Hp 2-2 were characterized. We were able to determine protein size difference within 3 nm, and the linear region of the calibration curve for Hp levels in the range of 90 pg ml{sup -1} and 90 {mu}g ml{sup -1} ({approx}1 fM to 1 pM). We surmise that similar approaches can be used to investigate protein polymorphism and altered protein-protein interaction associated with diseases.

Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine.

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Eckersall, P D; Bell, R

2010-07-01

Acute phase proteins (APPs) have been used as biomarkers of inflammation, infection and trauma for decades in human medicine but have been relatively under-utilised in the context of veterinary medicine. However, significant progress has been made in the detection, measurement and application of APPs as biomarkers in both companion and farm animal medicine over recent years. In the dog, C-reactive protein, haptoglobin and serum amyloid A have been identified as significant diagnostic 'markers' of steroid-responsive meningitis-arteritis, while in cats and cattle haptoglobin and alpha(1) acid glycoprotein and haptoglobin and serum amyloid A have proved valuable biomarkers of disease, respectively. In dairy cattle, haptoglobin and a mammary-associated serum amyloid A3 isoform, produced by the inflamed mammary gland during episodes of mastitis, have great potential as biomarkers of this economically important disease. Understanding the use of APP as biomarkers of inflammatory conditions of domestic animals has expanded significantly over recent years, and, with the insights provided by ongoing research, it is likely that these compounds will be increasingly used in the future in the diagnosis and prognosis of both companion and farm animal disease. Copyright 2010 Elsevier Ltd. All rights reserved.

An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

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Simopoulos, Artemis P.

2016-01-01

In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity. PMID:26950145

An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

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Artemis P. Simopoulos

2016-03-01

Full Text Available In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.

Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India.

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Bapat, Prachi R; Satav, Ashish R; Husain, Aliabbas A; Shekhawat, Seema D; Kawle, Anuja P; Chu, Justin J; Purohit, Hemant J; Daginawala, Hatim F; Taori, Girdhar M; Kashyap, Rajpal S

2015-01-01

Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

Spin trapping combined with quantitative mass spectrometry defines free radical redistribution within the oxidized hemoglobin:haptoglobin complex.

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Vallelian, Florence; Garcia-Rubio, Ines; Puglia, Michele; Kahraman, Abdullah; Deuel, Jeremy W; Engelsberger, Wolfgang R; Mason, Ronald P; Buehler, Paul W; Schaer, Dominik J

2015-08-01

Extracellular or free hemoglobin (Hb) accumulates during hemolysis, tissue damage, and inflammation. Heme-triggered oxidative reactions can lead to diverse structural modifications of lipids and proteins, which contribute to the propagation of tissue damage. One important target of Hb׳s peroxidase reactivity is its own globin structure. Amino acid oxidation and crosslinking events destabilize the protein and ultimately cause accumulation of proinflammatory and cytotoxic Hb degradation products. The Hb scavenger haptoglobin (Hp) attenuates oxidation-induced Hb degradation. In this study we show that in the presence of hydrogen peroxide (H2O2), Hb and the Hb:Hp complex share comparable peroxidative reactivity and free radical generation. While oxidation of both free Hb and Hb:Hp complex generates a common tyrosine-based free radical, the spin-trapping reaction with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) yields dissimilar paramagnetic products in Hb and Hb:Hp, suggesting that radicals are differently redistributed within the complex before reacting with the spin trap. With LC-MS(2) mass spectrometry we assigned multiple known and novel DMPO adduct sites. Quantification of these adducts suggested that the Hb:Hp complex formation causes extensive delocalization of accessible free radicals with drastic reduction of the major tryptophan and cysteine modifications in the β-globin chain of the Hb:Hp complex, including decreased βCys93 DMPO adduction. In contrast, the quantitative changes in DMPO adduct formation on Hb:Hp complex formation were less pronounced in the Hb α-globin chain. In contrast to earlier speculations, we found no evidence that free Hb radicals are delocalized to the Hp chain of the complex. The observation that Hb:Hp complex formation alters free radical distribution in Hb may help to better understand the structural basis for Hp as an antioxidant protein. Copyright © 2015 Elsevier Inc. All rights reserved.

Wheat aleurone polyphenols increase plasma eicosapentaenoic acid in rats

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Fayçal Ounnas

2014-08-01

Full Text Available Methods: These studies were designed to assess whether wheat polyphenols (mainly ferulic acid [FA] increased the very-long-chain omega-3 fatty acids (VLC n-3 [eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA] in rats. Wheat aleurone (WA was used as a dietary source of wheat polyphenols. Two experiments were performed; in the first one, the rats were fed WA or control pellets (CP in presence of linseed oil (LO to provide alpha-linolenic acid (ALA, the precursor of VLC n-3. In the second one, the rats were fed WA or CP in presence of control oil (CO without ALA. The concentrations of phenolic acid metabolites in urine were also investigated. Results: The urinary concentration of conjugated FA increased with WA ingestion (p<0.05. Plasma EPA increased by 25% (p<0.05 with WA in the CO group but not in the LO group. In contrast, there was no effect of WA on plasma DHA and omega-6 fatty acids (n-6. Finally, both n-3 and n-6 in the liver remained unchanged by the WA. Conclusion: These results suggest that WA consumption has a significant effect on EPA in plasma without affecting n-6. Subsequent studies are required to examine whether these effects may explain partly the health benefits associated with whole wheat consumption.

Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity*

Science.gov (United States)

Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro

2013-01-01

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681

Effects of fractionated colostrum replacer and vitamins A, D, and E on haptoglobin and clinical health in neonatal Holstein calves challenged with Mycobacterium avium ssp. paratuberculosis.

Science.gov (United States)

Krueger, L A; Reinhardt, T A; Beitz, D C; Stuart, R L; Stabel, J R

2016-04-01

Thirty Holstein calves were obtained from 2 dairy farms in central Iowa at birth and randomly assigned to 1 of 6 treatment groups: (1) colostrum deprived (CD), no vitamins; (2) colostrum replacer (CR), no vitamins; (3) CR, vitamin A; (4) CR, vitamin D3; (5) CR, vitamin E; and (6) CR, vitamins A, D3, E, with 5 calves per treatment in a 14-d study. Calves were fed pasteurized whole milk (CD) or fractionated colostrum replacer (CR) at birth (d 0) and injected with vitamins according to treatment group. From d 1 through d 14 of the study, all calves were fed pasteurized whole milk (PWM) supplemented with vitamins as assigned. All calves were inoculated with Mycobacterium avium ssp. paratuberculosis on d 1 and 3 of age. Calves fed CR acquired IgG1 and haptoglobin in serum within 24 h of birth, whereas CD calves did not. The CR-fed calves were 2.5 times less likely to develop scours, and CR calves supplemented with vitamins D3 and E also demonstrated a decreased incidence of scours. Serum vitamin levels of A, D, and E increased within treatment group by d 7 and 14 of the study. Interestingly, synergistic effects of supplemental vitamins A, D3, and E on serum 25-(OH)-vitamin D were observed at d 7, resulting in higher levels than in calves administered vitamin D only. Further, vitamin D3 deficiency was observed in CD and CR calves fed a basal diet of pasteurized whole milk and no supplemental vitamins. Colonization of tissues with Mycobacterium avium ssp. paratuberculosis was negligible and was not affected by colostrum feeding or vitamin supplementation. Results demonstrated passive transfer of haptoglobin to neonatal calves, and potential health benefits of supplemental vitamins D3 and E to calves fed pasteurized whole milk. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Pre-cold stress increases acid stress resistance and induces amino ...

African Journals Online (AJOL)

Pre-cold stress increases acid stress resistance and induces amino acid homeostasis in Lactococcus lactis NZ9000. ... Purpose: To investigate the effects of pre-cold stress treatments on subsequent acid stress resistance ... from 32 Countries:.

Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders.

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Ann eSmith

2015-06-01

Full Text Available The goal here is to describe our current understanding of heme metabolism and the deleterious effects of free heme on immunological processes, endothelial function, systemic inflammation, and various end-organ tissues (e.g. kidney, lung, liver, etc., with particular attention paid to the role of hemopexin (HPX. Because heme toxicity is the impetus for much of the pathology in sepsis, sickle cell disease, and other hemolytic conditions, the biological importance and clinical relevance of HPX, the predominant heme binding protein, is reinforced. A perspective on the function of HPX and haptoglobin (Hp is presented, updating how these two proteins and their respective receptors act simultaneously to protect the body in clinical conditions that entail hemolysis and/or systemic intravascular inflammation. Evidence from longitudinal studies in patients supports that HPX plays a Hp-independent role in genetic and non-genetic hemolytic diseases without the need for global Hp depletion. Evidence also supports that HPX has an important role in the prognosis of complex illnesses characterized predominantly by the presence of hemolysis, such as sickle cell disease, sepsis, hemolytic-uremic syndrome, and conditions involving intravascular and extravascular hemolysis, such as that generated by extracorporeal circulation during cardiopulmonary bypass and from blood transfusions. We propose that quantitating the amounts of plasma heme, HPX, Hb-Hp, heme-HPX and heme-albumin levels in various disease states may aid in the diagnosis and treatment of the above-mentioned conditions, which is crucial to developing targeted plasma protein supplementation (i.e. replenishment therapies for patients with heme toxicity due to HPX depletion.

Clofibric acid increases the formation of oleic acid in endoplasmic reticulum of the liver of rats.

Science.gov (United States)

Hirose, Akihiko; Yamazaki, Tohru; Sakamoto, Takeshi; Sunaga, Katsuyoshi; Tsuda, Tadashi; Mitsumoto, Atsushi; Kudo, Naomi; Kawashima, Yoichi

2011-01-01

The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [¹⁴C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty acids present in microsomes were significantly increased by the treatment of rats with clofibric acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [¹⁴C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to clofibric acid. The [¹⁴C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by clofibric acid. These results obtained from the in vivo experiments directly link the findings that clofibric acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.

Serum concentrations of haptoglobin and serum amyloid A in water buffaloes (Bubalus bubalis with abomasal ulcer

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Javad Tajik

2012-09-01

Full Text Available To evaluate the serum concentrations of haptoglobin (Hp and serum amyloid A (SAA in water buffaloes with abomasal ulcers, the abomasums of 100 randomly selected water buffaloes were examined after slaughter. Type I abomasal ulcers were found in 56 out of 100 buffaloes. Serum concentrations of Hp and SAA were measured. There was no significant difference between affected and non-affected buffaloes in the serum concentrations of Hp and SAA. The serum concentrations of Hp and SAA had no significant correlation with age and the serum SAA revealed no significant correlation with the number of abomasal ulcers. A significant correlation was found between the serum Hp and the number of abomasal ulcers (r =0.29, p = 0.04. There was no significant difference in the serum concentrations of Hp and SAA between buffaloes with different ulcer locations in the abomasums. Although more work on a larger number of animals is required in this area, it seems that the measurement of the serum Hp can be used to predict the abundance of type I abomasal ulcers.

Haptoglobin and serum amyloid A in bulk tank milk in relation to raw milk quality.

Science.gov (United States)

Akerstedt, Maria; Waller, Karin Persson; Sternesjö, Ase

2009-11-01

The aim of the present study was to evaluate relationships between the presence of the two major bovine acute phase proteins haptoglobin (Hp) and serum amyloid A (SAA) and raw milk quality parameters in bulk tank milk samples. Hp and SAA have been suggested as specific markers of mastitis but recently also as markers for raw milk quality. Since mastitis has detrimental effects on milk quality, it is important to investigate whether the presence of Hp or SAA indicates such changes in the composition and properties of the milk. Bulk tank milk samples (n=91) were analysed for Hp, SAA, total protein, casein, whey protein, proteolysis, fat, lactose, somatic cell count and coagulating properties. Samples with detectable levels of Hp had lower casein content, casein number and lactose content, but higher proteolysis than samples without Hp. Samples with detectable levels of SAA had lower casein number and lactose content, but higher whey protein content than samples without SAA. The presence of acute phase proteins in bulk tank milk is suggested as an indicator for unfavourable changes in the milk composition, e.g. protein quality, due to udder health disturbances, with economical implications for the dairy industry.

Serum amyloid A and haptoglobin levels in crossbred cows with endometritis following different therapy

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S. S. Biswal

2014-12-01

Full Text Available Aim: To determine the serum variations of two major acute phase proteins, serum amyloid A (SAA and haptoglobin (Hp levels in crossbred endometritis cows following pre and post immunomodulation therapy. Materials and Methods: 21 endometritis cows were randomly assigned to three groups (n=7 and treated with three different immunomodulators while seven healthy cows served as control. Uterine flushing collected from all animals was subjected to bacteriological study and serum samples were analyzed for SAA and Hp by sandwich ELISA method. Results: Escherichia coli was most prevalent Gram-negative bacteria (6.02 × 106 CFU/ml while Staphylococcus (0.86 × 106 CFU/ml and Streptococcus (0.52 × 106 CFU/ml were most predominant Gram-positive species isolated from uterine flushing. The pre-treatment SAA values (μg/ml varied significantly (p<0.01 between the treatment groups whereas no difference was observed in post-treatment groups. No significant difference (p<0.01 was observed for Hp values between the treatment groups, but the mean SAA (μg/ml and Hp (μg/ml levels were significantly (p<0.01 higher in pre-treatment when compared to post-treatment within the groups. Conclusion: In the diagnosis and monitoring of bovine endometritis, both SAA and Hp might serve as reliable biomarkers.

Acute phase proteins in cattle after exposure to complex stress

DEFF Research Database (Denmark)

Lomborg, S. R.; Nielsen, L. R.; Heegaard, Peter M. H.

2008-01-01

Abstract Stressors such as weaning, mixing and transportation have been shown to lead to increased blood concentrations of acute phase proteins (APP), including serum amyloid A (SAA) and haptoglobin, in calves. This study was therefore undertaken to assess whether SAA and haptoglobin levels...... concentrations of SAA and haptoglobin increased significantly in response to the stressors (P...... in blood mirror stress in adult cattle. Six clinically healthy Holstein cows and two Holstein heifers were transported for four to six hours to a research facility, where each animal was housed in solitary tie stalls. Blood samples for evaluation of leukocyte counts and serum SAA and haptoglobin...

Generation of a haptoglobin-hemoglobin complex-specific Fab antibody blocking the binding of the complex to CD163

DEFF Research Database (Denmark)

Horn, Ivo R; Nielsen, Marianne Jensby; Madsen, Mette

2003-01-01

During intravascular hemolysis hemoglobin (Hb) binds to haptoglobin (Hp) leading to endocytosis of the complex by the macrophage receptor, CD163. In the present study, we used a phage-display Fab antibody strategy to explore if the complex formation between Hp and Hb leads to exposure of antigenic...... epitopes specific for the complex. By Hp-Hb-affinity screening of a phage-Fab library, we isolated a phage clone against the ligand complex. Surface plasmon resonance analyses of the Fab part expressed as a recombinant protein revealed a high affinity binding (KD = 3.9 nm) to Hp-Hb, whereas no binding...... was measured for non-complexed Hp or Hb. The Fab antibody completely inhibited the binding of 125I-labeled Hp-Hb complexes to CD163 and blocked their uptake in CD163-transfected cells. In conclusion, we have raised a receptor-blocking antibody specifically recognizing the Hp-Hb complex. In addition to provide...

Effects of intramammary infection on whey proteinograms of sheep during lactation

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Vânia F. Lemos

2015-03-01

Full Text Available The study aimed to identify potential biomarkers of mammary gland infection in Santa Inês sheep. Commercial flocks of sheep provided the same hygiene, sanitary, and nutritional management under semi-intensive production systems were monitored during the lactation stage-and assessed 15, 30, 60, and 90 days after delivery (through the end of lactation and weaning. The California Mastitis Test (CMT was performed on the mammary glands. Milk was collected for bacterial examination and protein analysis. Bacterial culture and biochemical characterization of the samples were performed. Forty-two milk samples from healthy glands (negative CMT and bacterial testing and 43 milk samples from infected glands (positive CMT and bacterial testing taken at the predefined time points were assessed. A rennin solution was used to obtain the whey. The proteins analysis was performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE, which allowed for the quantification of nine whey proteins produced in healthy glands: serum albumin, lactoferrin, IgA, IgG heavy-chain (IgG HC, IgG light-chain (IgG LC, total IgG (IgG HC + IgG LC, α-lactalbumin, β-lactoglobulin, protein with MW 15.000 Da, protein with MW 29.000 Da and eleven whey proteins secreted by infected glands, including haptoglobin and α-1-acid glycoprotein. A comparison of whey proteins between healthy and infected glands showed increases (P<0.05 in the secreted and total contents of all proteins, except for IgG LC and α-lactoalbumin. The most significant changes were observed in α-1-acid glycoprotein, lactoferrin and haptoglobin, which showed three-, five-, and seven-fold increases in secretion, respectively. This study showed that haptoglobin, α-1-acid glycoprotein, lactoferrin, albumin, and the IgA and IgG immunoglobulins may serve as potential biomarkers for mammary gland infection in sheep.

Serum amyloid A and haptoglobin concentrations in serum and peritoneal fluid of healthy horses and horses with acute abdominal pain

DEFF Research Database (Denmark)

Pihl, Tina Holberg; Andersen, Pia Haubro; Kjelgaard-Hansen, Mads

2013-01-01

BACKGROUND: Peritoneal fluid (PF) analysis is a valuable diagnostic tool in equine medicine. Markers such as serum amyloid A (SAA) and haptoglobin (Hp) could facilitate the diagnosis of inflammatory abdominal conditions. OBJECTIVES: The objectives were to (1) establish reference intervals (RI......) for SAA and Hp in serum and PF in healthy horses, (2) compare SAA and Hp concentrations between healthy horses and horses with colic, and (3) to assess the correlation between serum and PF concentrations. METHODS: Serum amyloid A and Hp concentrations were determined by automated assays in prospectively...... enrolled healthy reference horses and horses with colic. RIs were calculated, group concentrations were compared by Student's t-test, and Pearson's correlation for serum and PF concentrations were determined. RESULTS: In healthy horses (n = 62) the measurements for SAA were below the detection limit (0...

Modelling hemoglobin and hemoglobin:haptoglobin complex clearance in a non-rodent species– pharmacokinetic and therapeutic implications

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Felicitas S Boretti

2014-10-01

Full Text Available Preclinical studies suggest that haptoglobin (Hp supplementation could be an effective therapeutic modality during acute or chronic hemolytic diseases. Hp prevents Hb extravasation and neutralizes Hb’s oxidative and NO scavenging activity in the vasculature. Small animal models such as mouse, rat and guinea pig appear to be valuable to provide proof-of-concept for Hb neutralization by Hp in diverse pre-clinical conditions. However, these species differ significantly from human in the clearance of Hb:Hp complexes, which leads to long persistence of circulating Hb:Hp complexes after administration of human plasma derived Hp. Alternative animal models must therefore be explored to guide pre-clinical development of these potential therapeutics. In contrast to rodents, dogs have high Hp plasma concentrations comparable to human. In this study we show that like human macrophages, dog peripheral blood monocyte derived macrophages express a glucocorticoid inducible endocytic clearance pathways with a high specificity for the Hb:Hp complex. Evaluating the Beagle dog as a non-rodent model species we provide the first pharmacokinetic parameter estimates of free Hb and Hb:Hp phenotype complexes. The data reflect a drastically reduced volume of distribution (Vc of the complex compared to free Hb, increased exposures (Cmax and AUC and significantly reduced total body clearance (CL with a terminal half-life (t1/2 of approximately 12 hours. Distribution and clearance was identical for dog and human Hb (± glucocorticoid stimulation and for dimeric and multimeric Hp preparations bound to Hb. Collectively, our study supports the dog as a non-rodent animal model to study pharmacological and pharmacokinetic aspects of Hb clearance systems and apply the model to studying Hp therapeutics.

Role of porcine serum haptoglobin in the host-parasite relationship of Taenia solium cysticercosis.

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Navarrete-Perea, José; Toledano-Magaña, Yanis; De la Torre, Patricia; Sciutto, Edda; Bobes, Raúl José; Soberón, Xavier; Laclette, Juan Pedro

2016-06-01

Human and porcine cysticercosis is a parasitic disease caused by the larval stage (cysts) of the tapeworm Taenia solium. Cysts may live in several host tissues such as skeletal muscle or brain. We have previously described the presence of host haptoglobin (Hp) and hemoglobin (Hb) in different protein extracts of the T. solium cysts. Here, we report the binding of host Hp and Hb to a number of cyst proteins, evaluated through measuring electrophoretic and light absorbance changes. In the sera obtained from 18 cysticercotic pigs, Hp-Hb complexes were abundant, whereas free Hp was undetectable. In contrast, in the sera from non 18 cysticercotic pigs, Hp-Hb and free Hp were found. In the soluble protein fraction of cysts tissue, free Hp was detected showing a considerable Hb-binding ability, whereas in the vesicular fluid, Hp is mainly bound to Hb. Interestingly, assays carried out with the insoluble fraction of T. solium cysts tissue, showed binding of Hp and Hp-Hb in a saturable way, suggesting the existence of specific interactions. Our results suggested that the parasite can take advantage of the uptaken host Hp and Hb, either free or in complexes, as a source of iron or as a way to modulate the inflammatory response surrounding the T. solium cysts. Copyright © 2016 Elsevier B.V. All rights reserved.

Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools

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Taha, Ameer Y.; Cheon, Yewon; Faurot, Keturah F.; MacIntosh, Beth; Majchrzak-Hong, Sharon F.; Mann, J. Douglas; Hibbeln, Joseph R.; Ringel, Amit; Ramsden, Christopher E.

2014-01-01

Background Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. Objective To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, change unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Design Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to: (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Results Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Conclusion Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFA for 12 weeks further increases n-3 PUFA plasma concentrations, but also reduces AA. PMID:24675168

Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

Science.gov (United States)

Taha, Ameer Y; Cheon, Yewon; Faurot, Keturah F; Macintosh, Beth; Majchrzak-Hong, Sharon F; Mann, J Douglas; Hibbeln, Joseph R; Ringel, Amit; Ramsden, Christopher E

2014-05-01

Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA. Published by Elsevier Ltd.

In Women with Previous Pregnancy Hypertension, Levels of Cardiovascular Risk Biomarkers May Be Modulated by Haptoglobin Polymorphism

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Andreia Matos

2014-01-01

Full Text Available Preeclampsia (PE may affect the risk for future cardiovascular disease. Haptoglobin (Hp, an acute phase protein with functional genetic polymorphism, synthesized in the hepatocyte and in many peripheral tissues secondary of oxidative stress of PE, may modulate that risk through the antioxidant, angiogenic, and anti-inflammatory differential effects of their genotypes. We performed a prospective study in 352 women aged 35±5.48 years, which 165 had previous PE, 2 to 16 years ago. We studied demographic, anthropometric, and haemodynamic biomarkers such as C-reactive protein (CRP, myeloperoxidase (MPO, and nitric oxide metabolites (total and nitrites, and others associated with liver function (AST and ALT and lipid profile (total LDL and cholesterol HDL, non-HDL, and apolipoproteins A and B. Finally, we study the influence of Hp genetic polymorphism on all these biomarkers and as a predisposing factor for PE and its remote cardiovascular disease prognosis. Previously preeclamptic women either hypertensive or normotensive presented significant differences in those risk biomarkers (MPO, nitrites, and ALT, whose variation may be modulated by Hp 1/2 functional genetic polymorphism. The history of PE may be relevant, in association with these biomarkers to the cardiovascular risk in premenopausal women.

Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.

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Ramzi J Khairallah

Full Text Available Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP. We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA docosahexaenoic acid (DHA; 22:6n3 and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6 in mitochondrial membranes is associated with a greater Ca(2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6. Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca(2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

Enhanced itaconic acid production in Aspergillus with increased LaeA expression

Science.gov (United States)

Dai, Ziyu; Baker, Scott E.

2018-03-06

Fungi, such as Aspergillus niger, having a dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase (Alg3) gene genetic inactivation, increased expression of a loss of aflR expression A (LaeA), or both, are described. In some examples, such mutants have several phenotypes, including an increased production of citric acid relative to the parental strain. Methods of using the disclosed fungi to make citric acid are also described, as are compositions and kits including the disclosed fungi. Further described are Aspergillus terreus fungi overexpressing the LaeA gene and the use of such fungi for the production of itaconic acid.

Microwave Energy Increases Fatty Acid Methyl Ester Yield in Human Whole Blood Due to Increased Sphingomyelin Transesterification.

Science.gov (United States)

Metherel, Adam H; Aristizabal Henao, Juan J; Ciobanu, Flaviu; Taha, Ameer Y; Stark, Ken D

2015-09-01

Dried blood spots (DBS) by fingertip prick collection for fatty acid profiling are becoming increasingly popular due to ease of collection, minimal invasiveness and its amenability to high-throughput analyses. Herein, we assess a microwave-assisted direct transesterification method for the production of fatty acid methyl esters (FAME) from DBS. Technical replicates of human whole blood were collected and 25-μL aliquots were applied to chromatography strips prior to analysis by a standard 3-h transesterification method or microwave-assisted direct transesterification method under various power (variable vs constant), time (1-5 min) and reagent (1-10% H2SO4 in methanol) conditions. In addition, a standard method was compared to a 5-min, 30-W power microwave in 1% H2SO4 method for FAME yield from whole blood sphingomyelin, and sphingomyelin standards alone and spiked in whole blood. Microwave-assisted direct transesterification yielded no significant differences in both quantitative (nmol/100 µL) and qualitative (mol%) fatty acid assessments after as little as 1.5- and 1-min reaction times, respectively, using the variable power method and 5% H2SO4 in methanol. However, 30-W power for 5 min increased total FAME yield of the technical replicates by 14%. This increase appears largely due to higher sphingomyelin-derived FAME yield of up to 109 and 399% compared to the standard method when determined from whole blood or pure standards, respectively. In conclusion, microwave-assisted direct transesterification of DBS achieved in as little as 1-min, and 5-min reaction times increase total fatty acids primarily by significantly improving sphingomyelin-derived fatty acid yield.

Organic acid excretion in Penicillium ochrochloron increases with ambient pH

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Pamela eVrabl

2012-04-01

Full Text Available Despite being of high biotechnological relevance, many aspects of organic acid excretion in filamentous fungi like the influence of ambient pH are still insufficiently understood. While the excretion of an individual organic acid may peak at a certain pH value, the few available studies investigating a broader range of organic acids indicate that total organic acid excretion rises with increasing external pH.We hypothesized that this phenomenon might be a general response of filamentous fungi to increased ambient pH. If this is the case, the observation should be widely independent of the organism, growth conditions or experimental design and might therefore be a crucial key point in understanding the function and mechanisms of organic acid excretion in filamentous fungi.In this study we explored this hypothesis using ammonium limited chemostat cultivations (pH 2-7, and ammonium or phosphate limited bioreactor batch cultivations (pH 5 and 7. Two strains of Penicillium ochrochloron were investigated differing in the spectrum of excreted organic acids.Confirming our hypothesis, the main result demonstrated that organic acid excretion in P. ochrochloron was enhanced at high external pH levels compared to low pH levels independent of the tested strain, nutrient limitation and cultivation method. We discuss these findings against the background of three hypotheses explaining organic acid excretion in filamentous fungi, i.e. overflow metabolism, charge balance and aggressive acidification hypothesis.

Mutant E. coli strain with increased succinic acid production

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Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

2001-09-25

A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

Mutant E. coli strain with increased succinic acid production

Science.gov (United States)

Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

1998-01-01

A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

Evaluation of C-reactive protein, Haptoglobin and cardiac troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome

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Planellas Marta

2012-08-01

Full Text Available Abstract Background Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS. The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI, in dogs with brachycephalic upper airway obstructive syndrome (BAOS. Results Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88% had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%, stenotic nares (96%, everted laryngeal saccules (32% and tracheal hypoplasia (29.1%. Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50 had values of CRP > 20 mg/L, 22.9% (11/48 had values of Hp > 3 g/L and 47.8% (22/46 had levels of cTnI > 0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p Conclusions According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration.

Evaluation of Fucosylated Haptoglobin and Mac-2 Binding Protein as Serum Biomarkers to Estimate Liver Fibrosis in Patients with Chronic Hepatitis C.

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Seiichi Tawara

Full Text Available Fucosylated haptoglobin (Fuc-Hpt and Mac-2 binding protein (Mac-2 bp are identified as cancer biomarkers, based on the results from a glyco-proteomic analysis. Recently, we reported that these glyco-biomarkers were associated with liver fibrosis and/or ballooning hepatocytes in patients with nonalcoholic fatty liver disease (NAFLD. We evaluated the ability of these glycoproteins to estimate liver fibrosis in 317 patients with chronic hepatitis C. We measured the serum Fuc-Hpt and Mac-2 bp levels using a lectin-antibody ELISA and ELISA, respectively. The serum levels of both Fuc-Hpt and Mac-2 bp increased with the progression of liver fibrosis. The multivariate analysis revealed that Mac-2 bp was an independent factor associated with moderate liver fibrosis (F ≥ 2. In contrast, Fuc-Hpt was an independent factor associated with advanced liver fibrosis (F ≥ 3. In terms of evaluating liver fibrosis, the serum levels of these glycomarkers were correlated with well-known liver fibrosis indexes, such as the aspartate aminotransferase to platelet ratio index (APRI and Fibrosis-4 (FIB4 index. An assay that combined the APRI or FIB4 index and the Fuc-Hpt or Mac-2 bp levels increased the AUC value for diagnosing hepatic fibrosis. Interestingly, the cumulative incidence of hepatocellular carcinoma (HCC was significantly higher in the patients with elevated serum levels of Fuc-Hpt and Mac-2 bp. In conclusion, both Fuc-Hpt and Mac-2 bp could be useful glyco-biomarkers of liver fibrosis and predictors of HCC in patients with chronic hepatitis C.

A study on the radiation and environment safety -Development of technology for biological dosimetry-

International Nuclear Information System (INIS)

Lee, Kang Suk; Kim, Kook Chan; Kim, In Kyoo; Kim, Jin Kyoo; Chun Kee Jung; Park, Hyo Kook; Kim, Sang Bok; Park Sun Yung

1995-07-01

Adult rats were treated a single, whole body exposure to a dose of 0.1, 0.5, 1.0, 2.0, 3.0 Gy. The animals were sacrificed 6, 24, 48, 72, 96 hours following exposure. The amount of serum acute phase proteins(haptoglobin, ceruloplasmin, C-reactive protein, alpha-1 antitrypsin, alpha-1 acid glycoprotein, transferrin) were measured by competitive ELISA. In the 0.1 Gy irradiated rats, serum haptoglobin, C-reactive protein and alpha-1 antitrypsin were 400% higher and serum transferrin was 50% lower as compared to controls, 96 hours after irradiation. Ceruloplasmin increased by 400%, 24 hours after irradiation, but 96 hours after irradiation, the concentration of this protein in rat returned to normal level. On the other hand, no changes were observed in the case of alpha-1 acid glycoprotein. In the group of the 3.0 Gy irradiated rats, transferrin increased by 200%, 96 hours after irradiation. These biochemical responses to radiation did not show dose-dependent relation, but the sensitivity of the indicators was high enough to detect absorbed dose of 0.1 Gy. The above results can be applied to the measurements of acute phase reactants in human serum for the assessment of exposure doses in radiation workers and patients under radiation therapy. 39 figs, 72 refs. (Author)

A study on the radiation and environment safety -Development of technology for biological dosimetry-

Energy Technology Data Exchange (ETDEWEB)

Lee, Kang Suk; Kim, Kook Chan; Kim, In Kyoo; Kim, Jin Kyoo; Jung, Chun Kee; Park, Hyo Kook; Kim, Sang Bok; Yung, Park Sun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1995-07-01

Adult rats were treated a single, whole body exposure to a dose of 0.1, 0.5, 1.0, 2.0, 3.0 Gy. The animals were sacrificed 6, 24, 48, 72, 96 hours following exposure. The amount of serum acute phase proteins(haptoglobin, ceruloplasmin, C-reactive protein, alpha-1 antitrypsin, alpha-1 acid glycoprotein, transferrin) were measured by competitive ELISA. In the 0.1 Gy irradiated rats, serum haptoglobin, C-reactive protein and alpha-1 antitrypsin were 400% higher and serum transferrin was 50% lower as compared to controls, 96 hours after irradiation. Ceruloplasmin increased by 400%, 24 hours after irradiation, but 96 hours after irradiation, the concentration of this protein in rat returned to normal level. On the other hand, no changes were observed in the case of alpha-1 acid glycoprotein. In the group of the 3.0 Gy irradiated rats, transferrin increased by 200%, 96 hours after irradiation. These biochemical responses to radiation did not show dose-dependent relation, but the sensitivity of the indicators was high enough to detect absorbed dose of 0.1 Gy. The above results can be applied to the measurements of acute phase reactants in human serum for the assessment of exposure doses in radiation workers and patients under radiation therapy. 39 figs, 72 refs. (Author).

Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells

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Vaughan Roger A

2012-10-01

Full Text Available Abstract Background Polyunsaturated fatty acids are popular dietary supplements advertised to contribute to weight loss by increasing fat metabolism in liver, but the effects on overall muscle metabolism are less established. We evaluated the effects of conjugated linoleic acid (CLA or combination omega 3 on metabolic characteristics in muscle cells. Methods Human rhabdomyosarcoma cells were treated with either DMSO control, or CLA or combination omega 3 for 24 or 48 hours. RNA was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Mitochondrial content was determined using flow cytometry and immunohistochemistry. Metabolism was quantified by measuring extracellular acidification and oxygen consumption rates. Results Omega 3 significantly induced metabolic genes as well as oxidative metabolism (oxygen consumption, glycolytic capacity (extracellular acidification, and metabolic rate compared with control. Both treatments significantly increased mitochondrial content. Conclusion Omega 3 fatty acids appear to enhance glycolytic, oxidative, and total metabolism. Moreover, both omega 3 and CLA treatment significantly increase mitochondrial content compared with control.

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

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

2015-02-01

Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Correlation of geographic distributions of haptoglobin alleles with prevalence of multiple sclerosis (MS) - a narrative literature review.

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Bamm, Vladimir V; Geist, Arielle M; Harauz, George

2017-02-01

We have proposed that the myelin damage observed in multiple sclerosis (MS) may be partly mediated through the long-term release and degradation of extracellular hemoglobin (Hb) and the products of its oxidative degradation [Cellular and Molecular Life Sciences, 71, 1789-1798, 2014]. The protein haptoglobin (Hpt) binds extracellular Hb as a first line of defense, and can serve as a vascular antioxidant. Humans have two different Hpt alleles: Hpt1 and Hpt2, giving either homozygous Hpt1-1 or Hpt2-2 phenotypes, or a heterozygous Hpt1-2 phenotype. We questioned whether those geographic regions with higher frequency of the Hpt2 allele (conversely, lower frequency of Hpt1 allele) would correlate with an increased incidence of MS, because different Hpt phenotypes will have variable anti-oxidative potentials in protecting myelin from damage inflicted by extracellular Hb and its degradation products. To test this hypothesis, we undertook a systematic analysis of the literature on reported geographic distributions of Hpt alleles to compare them with data reported in the World Health Organization Atlas of worldwide MS prevalence. We found the frequency of the Hpt1 allele to be low in European and North American countries with a high prevalence of MS, consistent with our hypothesis. However, this correlation was not observed in China and India, countries with the lowest Hpt1 frequencies, yet low reported prevalence of MS. Nevertheless, this work shows the need for continued refinement of geographic patterns of MS prevalence, including data on ethnic or racial origin, and for new clinical studies to probe the observed correlation and evaluate Hpt phenotype as a predictor of disease variability and progression, severity, and/or comorbidity with cardiovascular disorders.

Interleukin-2 stimulates osteoclastic activity: Increased acid production and radioactive calcium release

International Nuclear Information System (INIS)

Ries, W.L.; Seeds, M.C.; Key, L.L.

1989-01-01

Recombinant human interleukin-2 (IL-2) was studied to determine effects on acid production by individual osteoclasts in situ on mouse calvarial bones. This analysis was performed using a microspectrofluorimetric technique to quantify acid production in individual cells. Radioactive calcium release was determined using calvarial bones in a standard tissue culture system. This allowed us to correlate changes in acid production with a measure of bone resorption. IL-2 stimulated acid production and bone resorbing activity. Both effects were inhibited by calcitonin. No stimulation of bone resorption occurred when IL-2-containing test media was incubated with a specific anti-IL-2 antibody and ultrafiltered. Our data demonstrated a correlation between acid production and bone resorbing activity in mouse calvaria exposed to parathyroid hormone (PTH). The data obtained from cultured mouse calvaria exposed to IL-2 demonstrated similar stimulatory effects to those seen during PTH exposure. These data suggest that calvaria exposed to IL-2 in vitro have increased osteoclastic acid production corresponding with increased bone resorption. (author)

Pig major acute-phase protein and haptoglobin serum concentrations correlate with PCV2 viremia and the clinical course of postweaning multisystemic wasting syndrome

DEFF Research Database (Denmark)

Grau-Roma, Llorenc; Heegaard, Peter M. H.; Hjulsager, Charlotte Kristiane

2009-01-01

-PMWS affected pigs. In addition, evidence of infection with other pathogens and its relation with variations in APP's concentrations was also assessed. Fourteen independent batches of 100 to 154 pigs were monitored from birth to PMWS outbreak occurrence in 11 PMWS affected farms. Pigs displaying PMWS-like signs......The aim of the present longitudinal study was to assess the evolution of two acute phase proteins (APPs), pig-major acute phase protein (pig-MAP) and haptoglobin (HPT), in serum from pigs that developed postweaning multisystemic wasting syndrome (PMWS) in comparison to healthy and wasted non...... and age-matched healthy controls were euthanized during the clinical outbreak. PMWS was diagnosed according to internationally accepted creteria and pigs were classified as: i)PMWS cases, ii) wasted non-PMWS cases and iii) healthy pigs. At the moment of PMWS occurrence, pig-MAP and HPT concentration...

Free fatty acids increase hepatic glycogen content in obese males

NARCIS (Netherlands)

Allick, G.; Sprangers, F.; Weverling, G. J.; Ackermans, M. T.; Meijer, A. J.; Romijn, J. A.; Endert, E.; Bisschop, P. H.; Sauerwein, H. P.

2004-01-01

Obesity is associated with increased hepatic glycogen content. In vivo and in vitro data suggest that plasma free fatty acids (FFA) may cause this increase. In this study we investigated the effect of physiological plasma FFA levels on hepatic glycogen metabolism by studying intrahepatic glucose

Elevated carbon dioxide increases salicylic acid in Glycine max.

Science.gov (United States)

Casteel, Clare L; Segal, Lauren M; Niziolek, Olivia K; Berenbaum, May R; DeLucia, Evan H

2012-12-01

Concentrations of carbon dioxide (CO(2)) are increasing in the atmosphere, affecting soybean (Glycine max L.) phytohormone signaling and herbivore resistance. Whether the impact of elevated CO(2) on phytohormones and induced defenses is a generalized response within this species is an open question. We examined jasmonic acid (JA) and salicylic acid (SA) under ambient and elevated CO(2) concentrations with and without Japanese beetle (Popillia japonica Newman) damage and artificial damage across six soybean cultivars (HS93-4118, Pana, IA 3010, Loda, LN97-15076, and Dwight). Elevated CO(2) reduced constitutive levels of JA and related transcripts in some but not all soybean cultivars. In contrast to the variation in JA, constitutive levels of salicylic were increased universally among soybean cultivars grown under elevated CO(2). Variation in hormonal signaling may underpin observed variation in the response of insect herbivores and pathogens to plants grown under elevated CO(2).

Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

Science.gov (United States)

Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

2013-01-01

The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

Oleic, linoleic and linolenic acids increase ros production by fibroblasts via NADPH oxidase activation.

Directory of Open Access Journals (Sweden)

Elaine Hatanaka

Full Text Available The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47 (phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47 (phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts.

Increased proximal acid reflux is associated with early readmission following lung transplantation.

Science.gov (United States)

Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

2016-02-01

Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post-transplant readmission, an indicator of early clinical outcome, has not been previously assessed. This was a retrospective cohort study of lung transplant recipients undergoing pretransplant multichannel intraluminal impedance and pH (MII-pH) study off acid suppression at a tertiary care center since 2007. Subjects with pretransplant fundoplication were excluded. Time to readmission was defined as duration from post-transplant discharge to next hospital admission for any reason. Subgroup analysis was performed to exclude elective readmissions. Time-to-event analysis was performed using Cox proportional hazards model, with appropriate censoring. Forty-three subjects (60% men, mean age: 57, median follow-up: 1.7 years) met inclusion criteria for the study. Patient demographics and pretransplant cardiopulmonary function were similar between readmission cohorts. Time to all-cause readmission was associated with increased distal acid episodes (HR: 3.15, p = 0.04) and proximal acid episodes (HR: 3.61, p = 0.008) on impedance, increased acid exposure on pH (HR: 2.22, p = 0.04), and elevated Demeester score (HR: 2.26, p = 0.03). When elective readmissions were excluded, early readmission remained significantly associated with increased proximal acid reflux episodes (HR: 2.49, p = 0.04). All findings were confirmed on Kaplan-Meier analysis. Elevated proximal acid reflux on pretransplant MII-pH testing was associated with early readmission following lung transplantation, even after excluding elective readmissions. Exposure to severe acid reflux has measurable effects on early postoperative outcomes such as readmission, and aggressive early antireflux therapy should be considered. © 2015 John Wiley & Sons Ltd.

Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

Energy Technology Data Exchange (ETDEWEB)

Fu, Zidong Donna [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160 (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, 66160 (United States)

2013-12-15

Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.

Uric Acid or 1-Methyl Uric Acid in the Urinary Bladder Increases Serum Glucose, Insulin, True Triglyceride, and Total Cholesterol Levels in Wistar Rats

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T. Balasubramanian

2003-01-01

Full Text Available In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs, can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels.

Dynamics of biochemical and immunological blood markers in patients with pseudoarthrosis of the femoral neck after total hip arthroplasty

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S. E. Bondarenko

2017-08-01

Full Text Available The importance of biomarkers to predict recovery following total hip arthroplasty (THA is still unclear to clinicians. To assess the preoperative biomarkers of patients with pseudoarthrosis of the femoral neck and their dynamics in the early postoperative period after THA, 50 patients aged 33 to 82 years old, 18 males and 32 females diagnosed with pseudoarthrosis of the femoral neck after failed internal fixation and failed conservative management were studied. The control group consisted of 30 healthy people aged 27 to 50 years, 13 males, 17 females. Patients’ blood was examined for biochemical markers upon admission, and then on the 7th and 14th days after surgery. Their blood serum content of total protein, albumin, glycoproteins, sialic acids, chondroitin sulfates, haptoglobin, glucose, cholesterol, triglycerides, ALT, AST, alkaline phosphatase, GGT, acid phosphatase, thymol index; interleukins (IL-1, IL-4 and IL-6. and C-reactive protein was measured. The content of glycoproteins in the blood exceeded the norm by 2.3 times, chondroitin sulfate by 4.7 times, sialic acids by 1.5 times, haptoglobin by 55.8%, fibrinogen by 19.1%, globulin by 19,6%, alkaline phosphatase activity by 72.3%, IL-1 by 94.7 and IL-6 by 3 times, C-reactive protein by 2.6 times. After THA there was a gradual decrease in blood biochemical and immunological markers. The most informative laboratory markers were glycoproteins, chondroitin sulfates, sialic acids, haptoglobin, activity of alkaline phosphatase, IL-1, IL-6 and IL-4, and C-reactive protein. Subsequent research is required to validate these dynamics.

Radiation-induced increase in the release of amino acids by isolated, perfused skeletal muscle

International Nuclear Information System (INIS)

Schwenen, M.

1989-01-01

Local exposure of the hindquarter of the rat to 15Gy of gamma-radiation resulted, 4-6h after irradiation, in increased release of amino acids by the isolated, perfused hindquarter preparation, 70% of which is skeletal muscle. This increase in release involves not only alanine and glutamine, but also those amino acids not metabolized by muscle and, therefore, released in proportion to their occurrence in muscle proteins. Because metabolic parameters and content of energy-rich phosphate compounds in muscle remain unchanged, it is unlikely that general cellular damage is the underlying cause of the radiation-induced increase in amino acid release. The findings strongly favour the hypothesis that increased availability of amino acids results from enhanced protein break-down in skeletal muscle which has its onset shortly after irradiation. This radiation-induced disturbance in protein metabolism might be one of the pathogenetic factors in the aetiology of radiation myopathy. (author)

Studying titanium-molybdenum-zirconium alloys of increased corrosion resistance in acid solutions

International Nuclear Information System (INIS)

Tomashov, N.D.; Kazarin, V.I.; Mikheev, V.S.; Goncharenko, B.A.; Sigalovskaya, T.M.; Kalyanova, M.P.

1977-01-01

New promising Ti-Mo-Nb-Zr system alloys, possessing good workability and a high corrosion resistance in non-oxidizing solutions of acids, have been developed. The alloys may be recommended as structural materials for equipment operating in severely agressive acid media, such as hydrochloric, sulphuric and phosphoric acids. The corrosion resistance of alloys of the above system in solutions of H 2 SO 4 , HCl and H 3 PO 4 acids may be maximized by increasing the overall alloying to 42% (keeping the ratio of the alloying components Mo/Nb/Zr=4/1/1 unchanged), while retaining sufficiently good plasticity and workability

The potential role of omega-3 fatty acids supplements in increasing athletic performance

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Șerban GLIGOR

2017-03-01

Full Text Available Polyunsaturated omega-3 and omega-6 fatty acids are essential fatty acids that cannot be produced by the body itself and therefore must be provided through nutrition. Omega-6 and particularly omega-3 fatty acids have important roles in the organism, contributing to the maintenance and promotion of health. The optimal proportion of omega-6/omega-3 fatty acids is 2:1, or even better 1:1. They are involved in normal growth and development, play a role in the prevention of coronary and cardiovascular diseases, of diabetes mellitus, of arterial hypertension, arthritis and cancer. Omega-3 fatty acids mainly have an anti-inflammatory effect, but also act as hypolipidemic and antithrombotic agents. A potential role of omega-3 fatty acids is that of increasing physical performance. Their role in the physical activity refers on one side to the global health of athletes and on the other side to their anti-inflammatory effect, as high intensity physical exercise induces increased free-radical production and microtraumas, with the induction of an inflammatory status. The anti-inflammatory effect of these fatty acids manifests through an increased production of endogenous antioxidant enzymes, through decreasing the production of prostaglandins metabolites, decreasing the production of leukotriene B4, etc. They are also effective on reducing muscle pain post eccentric exercise and on decreasing the severity of bronchoconstriction induced by exercise, as well as improving pulmonary function variables. In conclusion it seems that supplementing diets with omega-3 fatty acids, apart from having benefic effects on health and on the prevention and management of certain affections, proves to be a beneficial for physical activity and athletic performance.

Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei

International Nuclear Information System (INIS)

Beetstra, Sasja; Thomas, Philip; Salisbury, Carolyn; Turner, Julie; Fenech, Michael

2005-01-01

Folic acid deficiency can lead to uracil incorporation into DNA, hypomethylation of DNA, inefficient DNA repair and increase chromosome malsegregation and breakage. Because ionising radiation increases demand for efficient DNA repair and also causes chromosome breaks we hypothesised that folic acid deficiency may increase sensitivity to radiation-induced chromosome breakage. We tested this hypothesis by using the cytokinesis-block micronucleus assay in 10 day WIL2-NS cell cultures at four different folic acid concentrations (0.2, 2, 20, and 200 nM) that span the 'normal' physiological range in humans. The study showed a significant dose-dependent increase in frequency of binucleated cells with micronuclei and/or nucleoplasmic bridges with decreasing folic acid concentration (P < 0.0001, P = 0.028, respectively). These biomarkers of chromosomal instability were also increased in cells irradiated (1.5 Gy γ-rays) on day 9 relative to un-irradiated controls (P < 0.05). Folic acid deficiency and γ-irradiation were shown to have a significant interactive effect on frequency of cells containing micronuclei (two-way ANOVA, interaction P 0.0039) such that the frequency of radiation-induced micronucleated cells (i.e. after subtracting base-line frequency of un-irradiated controls) increased with decreasing folic acid concentration (P-trend < 0.0001). Aneuploidy of chromosome 21, apoptosis and necrosis were increased by folic acid deficiency but not by ionising radiation. The results of this study show that folate status has an important impact on chromosomal stability and is an important modifying factor of cellular sensitivity to radiation-induced genome damage

Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

International Nuclear Information System (INIS)

Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A.

1990-01-01

Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. [3H] gamma-aminobutyric acid, [14C] butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of [3H] gamma-aminobutyric acid and [113mIn] transferrin were calculated using [14C] butanol as the highly extracted reference compound. The [113mIn] transferrin data were also used to correct the brain uptake index of [3H] gamma-aminobutyric acid for intravascular retention of [3H] gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid [3H] gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy

All-trans retinoic acid increases oxidative metabolism in mature adipocytes

DEFF Research Database (Denmark)

Mercader, Josep; Madsen, Lise; Felipe, Francisco

2007-01-01

BACKGROUND/AIMS: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. METHODS: Parameters of lipid......), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were...

Exploration of two-dimensional bio-functionalized phosphorene nanosheets (black phosphorous) for label free haptoglobin electro-immunosensing applications

Science.gov (United States)

Tuteja, Satish K.; Neethirajan, Suresh

2018-04-01

We report on the development of an antibody-functionalized interface based on electrochemically active liquid-exfoliated two-dimensional phosphorene (Ph) nanosheets—also known as black phosphorous nanosheets—for the label-free electrochemical immunosensing of a haptoglobin (Hp) biomarker, a clinical marker of severe inflammation. The electrodeposition has been achieved over the screen-printed electrode (SPE) using liquid-assisted ultrasonically exfoliated black phosphorus nanosheets. Subsequently, Ph-SPEs bioconjugated with Hp antibodies (Ab), using electrostatic interactions via a poly-L-lysine linker for biointerface development. Electrochemical analysis demonstrates that the Ab-modified Ph-SPEs (Ab@Ph-SPE) exhibit enhanced electroconducting behavior as compared to the pristine electrodes. This Ab-functionalized phosphorene-based electrochemical immunosensor platform has demonstrated remarkable sensitivity and specificity, having a dynamic linear response range from 0.01-10 mg ml-1 for Hp in standard and serum samples with a low detection limit (˜0.011 mg ml-1) using the label-free electrochemical technique. The sensor electrodes were also studied with other closely relative interferents to investigate cross reactivity and specificity. This strategy opens up avenues to POC (point-of-care) and on-farm livestock disease monitoring technologies for multiplexed diagnosis in complex biological samples such as serum. The technique is simple in fabrication and provides an analytical response in less than 60 s.

N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain.

Science.gov (United States)

Lavandera, Jimena Verónica; Saín, Juliana; Fariña, Ana Clara; Bernal, Claudio Adrián; González, Marcela Aída

2017-09-01

The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated. Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography. TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets. Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.

All-trans retinoic acid increases oxidative metabolism in mature adipocytes

DEFF Research Database (Denmark)

Mercader, Josep; Madsen, Lise; Felipe, Francisco

2007-01-01

), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were...

Fed levels of amino acids are required for the somatotropin-induced increase in muscle protein synthesis.

Science.gov (United States)

Wilson, Fiona A; Suryawan, Agus; Orellana, Renán A; Nguyen, Hanh V; Jeyapalan, Asumthia S; Gazzaneo, Maria C; Davis, Teresa A

2008-10-01

Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were maintained at fasting levels. This study aimed to determine whether the pST-induced increase in insulin promotes skeletal muscle protein synthesis when amino acids are provided at fed levels and whether the response is associated with enhanced translation initiation factor activation. Growing pigs were treated with pST (0 or 180 microg x kg(-1) x day(-1)) for 7 days, and then pancreatic-glucose-amino acid clamps were performed. Amino acids were raised to fed levels in the presence of either fasted or fed insulin concentrations; glucose was maintained at fasting throughout. Muscle protein synthesis was increased by pST treatment and by amino acids (with or without insulin) (P<0.001). In pST-treated pigs, fed, but not fasting, amino acid concentrations further increased muscle protein synthesis rates irrespective of insulin level (P<0.02). Fed amino acids, with or without raised insulin concentrations, increased the phosphorylation of S6 kinase (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1), decreased inactive 4EBP1.eIF4E complex association, and increased active eIF4E.eIF4G complex formation (P<0.02). pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of muscle protein synthesis requires fed amino acid levels, but not fed insulin levels. However, under the current conditions, the response to amino acids is not mediated by the activation of translation initiation factors that regulate mRNA binding to the ribosomal complex.

Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells

International Nuclear Information System (INIS)

Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.; Stillwell, W.

1991-01-01

Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication

Lactic Acid Bacteria from Kefir Increase Cytotoxicity of Natural Killer Cells to Tumor Cells.

Science.gov (United States)

Yamane, Takuya; Sakamoto, Tatsuji; Nakagaki, Takenori; Nakano, Yoshihisa

2018-03-27

The Japanese fermented beverage, homemade kefir, contains six lactic acid bacteria: Lactococcus. lactis subsp. Lactis , Lactococcus . lactis subsp. Cremoris , Lactococcus. Lactis subsp. Lactis biovar diacetylactis , Lactobacillus plantarum , Leuconostoc meseuteroides subsp. Cremoris and Lactobacillus casei . In this study, we found that a mixture of the six lactic acid bacteria from kefir increased the cytotoxicity of human natural killer KHYG-1 cells to human chronic myelogenous leukemia K562 cells and colorectal tumor HCT116 cells. Furthermore, levels of mRNA expression and secretion of IFN-γ (interferon gamma) increased in KHYG-1 cells that had been treated with the six lactic acid bacteria mixture from kefir. The results suggest that the six lactic acid bacteria mixture from kefir has strong effects on natural immunity and tumor cell cytotoxicity.

Pathogenicity of Cryptosporidium parvum - evaluation of an animal infection model

DEFF Research Database (Denmark)

Enemark, Heidi L.; Bille-Hansen, Vivi; Lind, Peter

2003-01-01

and rectum. The unintended presence of rotavirus in some of the experimental animals revealed an additive or synergistic effect between rotavirus and C. parvum as indicated by prolonged diarrhoea, increased oocyst shedding, decreased weight gain and elevated levels of serum haptoglobin and serum amyloid...... A (SAA) in piglets infected simultaneously with both pathogens. The difference in daily weight gain between infected and control animals was significant only for piglets co-infected with rotavirus. The acute phase response of haptoglobin and SAA was characterised by a large individual variation....... In piglets, co-infected with rotavirus, the levels of serum haptoglobin were 3.5 and 4.6 times higher in the infected versus the controls 6 and 9 dpi, respectively (mean values: 2411 mug/ml +/- S.D. 2023 and 1840 mug/ml +/- S.D. 1697). In the controls infected with rotavirus, peak haptoglobin concentration...

Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia

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Stephen A Brose

2016-11-01

Full Text Available Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA biosynthesis (FAS followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FAS maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FAS inhibition on NADH2+/NAD+ and NADPH2+/NADP+ ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FAS inhibitors, TOFA (inhibits Acetyl-CoA carboxylase and cerulenin (inhibits FA synthase, increased NADH2+/NAD+ and NADPH2+/NADP+ ratios under hypoxia. Further, FAS inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke.

Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia.

Science.gov (United States)

Brose, Stephen A; Golovko, Svetlana A; Golovko, Mikhail Y

2016-01-01

Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA) biosynthesis followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FA synthesis maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FA synthesis inhibition on [Formula: see text]/NAD + and [Formula: see text]/NADP + ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FA synthesis inhibitors, TOFA (inhibits Acetyl-CoA carboxylase) and cerulenin (inhibits FA synthase), increased [Formula: see text]/NAD + and [Formula: see text]/NADP + ratios under hypoxia. Further, FA synthesis inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke.

Lactic Acid Bacteria from Kefir Increase Cytotoxicity of Natural Killer Cells to Tumor Cells

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Takuya Yamane

2018-03-01

Full Text Available The Japanese fermented beverage, homemade kefir, contains six lactic acid bacteria: Lactococcus. lactis subsp. Lactis, Lactococcus. lactis subsp. Cremoris, Lactococcus. Lactis subsp. Lactis biovar diacetylactis, Lactobacillus plantarum, Leuconostoc meseuteroides subsp. Cremoris and Lactobacillus casei. In this study, we found that a mixture of the six lactic acid bacteria from kefir increased the cytotoxicity of human natural killer KHYG-1 cells to human chronic myelogenous leukemia K562 cells and colorectal tumor HCT116 cells. Furthermore, levels of mRNA expression and secretion of IFN-γ (interferon gamma increased in KHYG-1 cells that had been treated with the six lactic acid bacteria mixture from kefir. The results suggest that the six lactic acid bacteria mixture from kefir has strong effects on natural immunity and tumor cell cytotoxicity.

Peripartum cardiomyopathy is associated with increased uric acid concentrations: A population based study.

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Sagy, Iftach; Salman, Amjad Abu; Kezerle, Louise; Erez, Offer; Yoel, Idan; Barski, Leonid

Peri-partum cardiomyopathy (PPCM) is a clinical heart failure that usually develops during the final stage of pregnancy or the first months following delivery. High maternal serum uric acid concentrations have been previous associated with heart failure and preeclampsia. 1) To explored the clinical characteristics of PPCM patients; and 2) to determine the association between maternal serum uric acid concentrations and PPCM. This is a retrospective population based case control study. Cases and controls were matched 1:4 (for gestational age, medical history of cardiac conditions and creatinine); conditional logistic regression was used to identify clinical parameters that were associated with PPCM. The prevalence of peripartum cardiomyopathy at our institution was 1-3832 deliveries (42/160,964). In a matched multivariate analysis high maternal serum uric acid concentrations were associated with PPCM (O.R 1.336, 95% C.I 1.003-1.778). Uric acid concentrations were higher within the Non-Jewish patients and mothers of male infant with PPCM in compare to those without PPCM (p value 0.003 and 0.01 respectively). PPCM patients had increased maternal serum uric acid concentrations. This observation aligns with previous report regarding the increased uric acid concentration in women with preeclampsia and congestive heart failure, suggestive of a common underlying mechanism that mediates the myocardial damage. Copyright © 2017 Elsevier Inc. All rights reserved.

Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

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Manuela Oraldi

2009-01-01

Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids.

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Peng, Sui; Huo, Xiaofang; Rezaei, Davood; Zhang, Qiuyang; Zhang, Xi; Yu, Chunhua; Asanuma, Kiyotaka; Cheng, Edaire; Pham, Thai H; Wang, David H; Chen, Minhu; Souza, Rhonda F; Spechler, Stuart Jon

2014-07-15

Hydrophobic bile acids like deoxycholic acid (DCA), which cause oxidative DNA damage and activate NF-κB in Barrett's metaplasia, might contribute to carcinogenesis in Barrett's esophagus. We have explored mechanisms whereby ursodeoxycholic acid (UDCA, a hydrophilic bile acid) protects against DCA-induced injury in vivo in patients and in vitro using nonneoplastic, telomerase-immortalized Barrett's cell lines. We took biopsies of Barrett's esophagus from 21 patients before and after esophageal perfusion with DCA (250 μM) at baseline and after 8 wk of oral UDCA treatment. DNA damage was assessed by phospho-H2AX expression, neutral CometAssay, and phospho-H2AX nuclear foci formation. Quantitative PCR was performed for antioxidants including catalase and GPX1. Nrf2, catalase, and GPX1 were knocked down with siRNAs. Reporter assays were performed using a plasmid construct containing antioxidant responsive element. In patients, baseline esophageal perfusion with DCA significantly increased phospho-H2AX and phospho-p65 in Barrett's metaplasia. Oral UDCA increased GPX1 and catalase levels in Barrett's metaplasia and prevented DCA perfusion from inducing DNA damage and NF-κB activation. In cells, DCA-induced DNA damage and NF-κB activation was prevented by 24-h pretreatment with UDCA, but not by mixing UDCA with DCA. UDCA activated Nrf2 signaling to increase GPX1 and catalase expression, and protective effects of UDCA pretreatment were blocked by siRNA knockdown of these antioxidants. UDCA increases expression of antioxidants that prevent toxic bile acids from causing DNA damage and NF-κB activation in Barrett's metaplasia. Elucidation of this molecular pathway for UDCA protection provides rationale for clinical trials on UDCA for chemoprevention in Barrett's esophagus. Copyright © 2014 the American Physiological Society.

CPT1α over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

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Jambor de Sousa, Ulrike L.; Koss, Michael D.; Fillies, Marion; Gahl, Anja; Scheeder, Martin R.L.; Cardoso, M. Cristina; Leonhardt, Heinrich; Geary, Nori; Langhans, Wolfgang; Leonhardt, Monika

2005-01-01

To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1α (CPT1α). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1α transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1α over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1α over-expressing cells in a concentration-dependent manner. Both, PA and CPT1α over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1α, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo

Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

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Steven D Kunkel

Full Text Available Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II, blood vessel recruitment (Vegfa and autocrine/paracrine IGF-I signaling (Igf1. As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

Endomorphins potentiate acid-sensing ion channel currents and enhance the lactic acid-mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia.

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Farrag, Mohamed; Drobish, Julie K; Puhl, Henry L; Kim, Joyce S; Herold, Paul B; Kaufman, Marc P; Ruiz-Velasco, Victor

2017-12-01

Chronic limb ischaemia, characterized by inflammatory mediator release and a low extracellular pH, leads to acid-sensing ion channel (ASIC) activation and reflexively increases mean arterial pressure; endomorphin release is also increased under inflammatory conditions. We examined the modulation of ASIC currents by endomorphins in sensory neurons from rats with freely perfused and ligated femoral arteries: peripheral artery disease (PAD) model. Endomorphins potentiated sustained ASIC currents in both groups of dorsal root ganglion neurons, independent of mu opioid receptor stimulation or G protein activation. Intra-arterial administration of lactic acid (to simulate exercising muscle and evoke a pressor reflex), endomorphin-2 and naloxone resulted in a significantly greater pressor response than lactic acid alone, while administration of APETx2 inhibited endomorphin's enhancing effect in both groups. These results suggest a novel role for endomorphins in modulating ASIC function to effect lactic acid-mediated reflex increase in arterial pressure in patients with PAD. Chronic muscle ischaemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone. The potentiation was significantly greater in DRG neurons isolated from rats whose femoral arteries were ligated for 72 h. Sustained ASIC current potentiation was also observed

Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

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De Capite, Annette; Lancaster, Tyler; Puthoff, David

2016-01-01

Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.

Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

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Bridget M. Stroup

2017-01-01

Full Text Available Background. Skeletal fragility is a complication of phenylketonuria (PKU. A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF. Design. In a crossover design, 8 participants with PKU (16–35 y provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL of AA-MF and GMP-MF and determined bone mineral density (BMD measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p=0.002. Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p=0.012 and magnesium by 30% (p=0.029. Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258.

STUDY OF SERUM HAPTOGLOBIN LEVEL AND ITS RELATION TO ERYTHROPOIETIC ACTIVITY IN BETA THALASSEMIA CHILDREN .

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Seham Ragab

2015-02-01

Full Text Available Background  :Serum haptoglobin (Hp is a reliable marker for hemolysis regardless the inflammatory state.  Objective: We investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV infection and iron load in β-thalassemia children. Methods: Twenty  two β-thalassemia major (TM ,20 β-thalassemia  intermedia (TI children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered . Serum ferritin , Hp  and transferrin receptor  levels (sTfR  (by ELISA , alanine aminotransferase (ALT and  aspartate aminotransferase (AST  (by colorimetric method were assayed. Markers of hepatitis C virus  (HCV  were done by PCR. Results:  The mean Hp levels among the studied groups were as follows; 8.02 ± 0.93 (mg/dl , 8.6 ±0.72 (mg/dl  and 122  ± 18.5(mg/dl   for TM ,TI and the controls respectively . Both patient groups had significantly lower Hp level compared to the controls (P<0.0001  with significant lower level in TM compared to TI  children ( P= 0.034  .Significant inverse correlations were  found between serum Hp and sTfR levels in thalassemia children combined and in each group (TM and TI as well as among HCV infected children. STfR   was the only significant independent predictor for  serum Hp level (t= -5.585 , P<0.0001 . Among  HCV infected patients , no significant correlation was found between serum Hp and serum transaminases  .Conclusion:  Serum Hp depletion in thalassemia had significant relation to disease severity and correlated   well with their erythropoietic activity, as assessed by the measurement of  sTfR without significant relation  HCV infection . Large sample  multicenter studies are  recommended.

Development of marker-free transgenic Jatropha plants with increased levels of seed oleic acid

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Qu Jing

2012-02-01

Full Text Available Abstract Background Jatropha curcas is recognized as a new energy crop due to the presence of the high amount of oil in its seeds that can be converted into biodiesel. The quality and performance of the biodiesel depends on the chemical composition of the fatty acids present in the oil. The fatty acids profile of the oil has a direct impact on ignition quality, heat of combustion and oxidative stability. An ideal biodiesel composition should have more monounsaturated fatty acids and less polyunsaturated acids. Jatropha seed oil contains 30% to 50% polyunsaturated fatty acids (mainly linoleic acid which negatively impacts the oxidative stability and causes high rate of nitrogen oxides emission. Results The enzyme 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine delta 12-desaturase (FAD2 is the key enzyme responsible for the production of linoleic acid in plants. We identified three putative delta 12 fatty acid desaturase genes in Jatropha (JcFAD2s through genome-wide analysis and downregulated the expression of one of these genes, JcFAD2-1, in a seed-specific manner by RNA interference technology. The resulting JcFAD2-1 RNA interference transgenic plants showed a dramatic increase of oleic acid (> 78% and a corresponding reduction in polyunsaturated fatty acids (Jatropha had around 37% oleic acid and 41% polyunsaturated fatty acids. This indicates that FAD2-1 is the major enzyme responsible for converting oleic acid to linoleic acid in Jatropha. Due to the changes in the fatty acids profile, the oil of the JcFAD2-1 RNA interference seed was estimated to yield a cetane number as high as 60.2, which is similar to the required cetane number for conventional premium diesel fuels (60 in Europe. The presence of high seed oleic acid did not have a negative impact on other Jatropha agronomic traits based on our preliminary data of the original plants under greenhouse conditions. Further, we developed a marker-free system to generate the transgenic Jatropha

Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men

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Ribel-Madsen, Amalie; Ribel-Madsen, Rasmus; Brøns, Charlotte

2016-01-01

We hypothesized that an increased, incomplete fatty acid beta‐oxidation in mitochondria could be part of the metabolic events leading to insulin resistance and thereby an increased type 2 diabetes risk in low birth weight (LBW) compared with normal birth weight (NBW) individuals. Therefore, we...... measured fasting plasma levels of 45 acylcarnitine species in 18 LBW and 25 NBW men after an isocaloric control diet and a 5‐day high‐fat, high‐calorie diet. We demonstrated that LBW men had higher C2 and C4‐OH levels after the control diet compared with NBW men, indicating an increased fatty acid beta...

Increased saccharification yields from aspen biomass upon treatment with enzymatically generated peracetic acid.

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Duncan, Shona; Jing, Qing; Katona, Adrian; Kazlauskas, Romas J; Schilling, Jonathan; Tschirner, Ulrike; Aldajani, Waleed Wafa

2010-03-01

The recalcitrance of lignocellulosic biomass to enzymatic release of sugars (saccharification) currently limits its use as feedstock for biofuels. Enzymatic hydrolysis of untreated aspen wood releases only 21.8% of the available sugars due primarily to the lignin barrier. Nature uses oxidative enzymes to selectively degrade lignin in lignocellulosic biomass, but thus far, natural enzymes have been too slow for industrial use. In this study, oxidative pretreatment with commercial peracetic acid (470 mM) removed 40% of the lignin (from 19.9 to 12.0 wt.% lignin) from aspen and enhanced the sugar yields in subsequent enzymatic hydrolysis to about 90%. Increasing the amount of lignin removed correlated with increasing yields of sugar release. Unfortunately, peracetic acid is expensive, and concentrated forms can be hazardous. To reduce costs and hazards associated with using commercial peracetic acid, we used a hydrolase to catalyze the perhydrolysis of ethyl acetate generating 60-70 mM peracetic acid in situ as a pretreatment to remove lignin from aspen wood. A single pretreatment was insufficient, but multiple cycles (up to eight) removed up to 61.7% of the lignin enabling release of >90% of the sugars during saccharification. This value corresponds to a predicted 581 g of fermentable sugars from 1 kg of aspen wood. Improvements in the enzyme stability are needed before the enzymatically generated peracetic acid is a commercially viable alternative.

Oleic acid and docosahexaenoic acid cause an increase in the paracellular absorption of hydrophilic compounds in an experimental model of human absorptive enterocytes

International Nuclear Information System (INIS)

Aspenstroem-Fagerlund, Bitte; Ring, Linda; Aspenstroem, Pontus; Tallkvist, Jonas; Ilbaeck, Nils-Gunnar; Glynn, Anders W.

2007-01-01

Surface active compounds present in food possibly have the ability to enhance the absorption of water soluble toxic agents. Therefore, we investigated whether fatty acids such as oleic acid and docosahexaenoic acid (DHA), both commonly present in food, negatively affect the integrity of tight junctions (TJ) in the intestinal epithelium and thereby increase the absorption of poorly absorbed hydrophilic substances. Caco-2 cells, which are derived from human absorptive enterocytes, were grown on permeable filters for 20-25 days. Differentiated cell monolayers were apically exposed for 90 min to mannitol in emulsions of oleic acid (5, 15 or 30 mM) or DHA (5, 15 or 30 mM) in an experimental medium with or without Ca 2+ and Mg 2+ . Absorption of 14 C-mannitol increased and trans-epithelial electrical resistance (TEER) decreased in cell monolayers exposed to oleic acid and DHA, compared to controls. Cytotoxicity, measured as leakage of LDH, was higher in groups exposed to 30 mM oleic acid and all concentrations of DHA. Morphology of the cell monolayers was studied by using fluorescence microscopy. Exposure of cell monolayers to 5 mM DHA for 90 min resulted in a profound alteration of the cell-cell contacts as detected by staining the cells for β-catenin. Oleic acid (30 mM) treatment also induced dissolution of the cell-cell contacts but the effect was not as pronounced as with DHA. Cell monolayers were also exposed for 180 min to 250 nM cadmium (Cd) in emulsions of oleic acid (5 or 30 mM) or DHA (1 or 5 mM), in an experimental medium with Ca 2+ and Mg 2+ . Retention of Cd in Caco-2 cells was higher after exposure to 5 mM oleic acid but lower after exposure to 30 mM oleic acid and DHA. Absorption of Cd through the monolayers increased after DHA exposure but not after exposure to oleic acid. Our results indicate that fatty acids may compromise the integrity of the intestinal epithelium and that certain lipids in food may enhance the paracellular absorption of poorly

Increased dietary long-chain polyunsaturated fatty acids alter serum fatty acid concentrations and lower risk of urine stone formation in cats.

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Jean A Hall

Full Text Available The lifespan of cats with non-obstructive kidney stones is shortened compared with healthy cats indicating a need to reduce stone formation and minimize chronic kidney disease. The purpose of this study was to investigate the effects of increasing dietary polyunsaturated fatty acids (PUFA on urine characteristics. Domestic-short-hair cats (n = 12; mean age 5.6 years were randomized into two groups and fed one of two dry-cat foods in a cross-over study design. For one week before study initiation, all cats consumed control food that contained 0.07% arachidonic acid (AA, but no eicosapentaenoic acid (EPA or docosahexaenoic acid (DHA. Group 1 continued eating control food for 56 days. Group 2 was fed test food for 56 days, which was control food plus fish oil and high-AA oil. Test food contained 0.17% AA, 0.09% EPA and 0.18% DHA. After 56 days, cats were fed the opposite food for another 56 days. At baseline and after each feeding period, serum was analyzed for fatty acid concentrations, and urine for specific gravity, calcium concentration, relative-super-saturation for struvite crystals, and a calcium-oxalate-titrimetric test was performed. After consuming test food, cats had increased (all P<0.001 serum concentrations of EPA (173%, DHA (61%, and AA (35%; decreased urine specific gravity (P = 0.02; decreased urine calcium concentration (P = 0.06; decreased relative-super-saturation for struvite crystals (P = 0.03; and increased resistance to oxalate crystal formation (P = 0.06 compared with cats consuming control food. Oxalate crystal formation was correlated with serum calcium concentration (r = 0.41; P<0.01. These data show benefits for reducing urine stone formation in cats by increasing dietary PUFA.

Haptoglobin phenotype, preeclampsia risk and the efficacy of vitamin C and E supplementation to prevent preeclampsia in a racially diverse population.

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Tracey L Weissgerber

Full Text Available Haptoglobin's (Hp antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH. This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393 and a case-control cohort (703 cases, 1,406 controls. The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01 in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia.

Serum proteomic changes after randomized prolonged erythropoietin treatment and/or endurance training: detection of novel biomarkers.

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Britt Christensen

Full Text Available Despite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA exposure (Darbepoietin-α and/or aerobic training.Thirty-six healthy young males were randomly assigned to the following groups: Sedentary-placebo (n = 9, Sedentary-ESA (n = 9, Training-placebo (n = 10, or Training-ESA (n = 8. They were treated with placebo/Darbepoietin-α subcutaneously once/week for 10 weeks followed by a 3-week washout period. Training consisted of supervised biking 3/week for 13 weeks at the highest possible intensity. Serum was collected at baseline, week 3 (high dose Darbepoietin-α, week 10 (reduced dose Darbepoietin-α, and after a 3-week washout period.Serum proteins were separated according to charge and molecular mass (2D-gel electrophoresis. The identity of proteins from spots exhibiting altered intensity was determined by mass spectrometry.Six protein spots changed in response to Darbepoietin-α treatment. Comparing all 4 experimental groups, two protein spots (serotransferrin and haptoglobin/haptoglobin related protein showed a significant response to Darbepoietin-α treatment. The haptoglobin/haptoglobin related protein spot showed a significantly lower intensity in all subjects in the training-ESA group during the treatment period and increased during the washout period.An isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research.ClinicalTrials.gov NCT01320449.

Agents that increase phosphatidic acid inhibit the LH-induced testosterone production

DEFF Research Database (Denmark)

Lauritzen, L.; Nielsen, L.-L.A.; Vinggaard, Anne Marie

1994-01-01

The results of the present study point to phosphatidic acid (PtdOH) as a possible intracellular messenger, which might be involved in local modulation of testicular testosterone production in vivo. Propranolol (27-266 µM) induced an increased level of [H]PtdOH in isolated rat Leydig cells...

The degree of acceptability of swine blood values at increasing levels of hemolysis evaluated through visual inspection versus automated quantification.

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Di Martino, Guido; Stefani, Anna Lisa; Lippi, Giuseppe; Gagliazzo, Laura; McCormick, Wanda; Gabai, Gianfranco; Bonfanti, Lebana

2015-05-01

The pronounced fragility that characterizes swine erythrocytes is likely to produce a variable degree of hemolysis during blood sampling, and the free hemoglobin may then unpredictably bias the quantification of several analytes. The aim of this study was to evaluate the degree of acceptability of values obtained for several biochemical parameters at different levels of hemolysis. Progressively increased degrees of physical hemolysis were induced in 3 aliquots of 30 nonhemolytic sera, and the relative effects on the test results were assessed. To define the level of hemolysis, we used both visual estimation (on a scale of 0 to 3+) and analytical assessment (hemolytic index) and identified the best analytical cutoff values for discriminating the visual levels of hemolysis. Hemolysis led to a variable and dose-dependent effect on the test results that was specific for each analyte tested. In mildly hemolyzed specimens, C-reactive protein, haptoglobin, β1-globulin, β2-globulin, α1-globulin, γ-globulin, sodium, calcium, and alkaline phosphatase were not significantly biased, whereas α2-globulin, albumin, urea, creatinine, glucose, total cholesterol, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, nonesterified fatty acids, bilirubin, phosphorus, magnesium, iron, zinc, copper, lipase, triglycerides, lactate dehydrogenase, unbound iron-binding capacity, and uric acid were significantly biased. Chloride and total protein were unbiased even in markedly hemolyzed samples. Analytical interference was hypothesized to be the main source of this bias, leading to a nonlinear trend that confirmed the difficulty in establishing reliable coefficients of correction for adjusting the test results. © 2015 The Author(s).

Increased production of free fatty acids in Aspergillus oryzae by disruption of a predicted acyl-CoA synthetase gene.

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Tamano, Koichi; Bruno, Kenneth S; Koike, Hideaki; Ishii, Tomoko; Miura, Ai; Umemura, Myco; Culley, David E; Baker, Scott E; Machida, Masayuki

2015-04-01

Fatty acids are attractive molecules as source materials for the production of biodiesel fuel. Previously, we attained a 2.4-fold increase in fatty acid production by increasing the expression of fatty acid synthesis-related genes in Aspergillus oryzae. In this study, we achieved an additional increase in the production of fatty acids by disrupting a predicted acyl-CoA synthetase gene in A. oryzae. The A. oryzae genome is predicted to encode six acyl-CoA synthetase genes and disruption of AO090011000642, one of the six genes, resulted in a 9.2-fold higher accumulation (corresponding to an increased production of 0.23 mmol/g dry cell weight) of intracellular fatty acid in comparison to the wild-type strain. Furthermore, by introducing a niaD marker from Aspergillus nidulans to the disruptant, as well as changing the concentration of nitrogen in the culture medium from 10 to 350 mM, fatty acid productivity reached 0.54 mmol/g dry cell weight. Analysis of the relative composition of the major intracellular free fatty acids caused by disruption of AO090011000642 in comparison to the wild-type strain showed an increase in stearic acid (7 to 26 %), decrease in linoleic acid (50 to 27 %), and no significant changes in palmitic or oleic acid (each around 20-25 %).

Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals

DEFF Research Database (Denmark)

van Hall, Gerrit; Steensberg, Adam; Fischer, Christian

2008-01-01

CONTEXT: IL-6 is a key modulator of immune function and suggested to be involved in skeletal muscle wasting as seen in sepsis. OBJECTIVE: Our objective was to determine the role of IL-6 in human in vivo systemic and skeletal muscle amino acid metabolism and protein turnover. SUBJECTS AND METHODS...... synthesis was more suppressed than breakdown, causing a small increase in net muscle protein breakdown. Furthermore, rhIL-6 decreased arterial amino acid concentration with 20-40%, despite the increase net release from muscle. CONCLUSIONS: We demonstrated that IL-6 profoundly alters amino acid turnover....... A substantial decrease in plasma amino acids was observed with a concomitant 50% decrease in muscle protein turnover, however, modest increase in net muscle degradation. We hypothesize that the profound reduction in muscle protein turnover and modest increase in net degradation are primarily caused...

Increased ophthalmic acid production is supported by amino acid catabolism under fasting conditions in mice.

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Kobayashi, Sho; Lee, Jaeyong; Takao, Toshifumi; Fujii, Junichi

2017-09-23

Glutathione (GSH) plays pivotal roles in antioxidation and detoxification. The transsulfuration pathway, in conjunction with methionine metabolism, produces equimolar amounts of cysteine (Cys) and 2-oxobutyric acid (2OB). The resulting 2OB is then converted into 2-aminobutyric acid (2AB) by a transaminase and is utilized as a substitute for Cys by the GSH-synthesizing machinery to produce ophthalmic acid (OPT). By establishing a method for simultaneously measuring Cys, GSH, and OPT by liquid chromatography-mass spectrometry, we found that fasting causes an elevation in OPT levels in the liver and blood plasma, even though the levels of Cys and GSH are decreased. Autophagy was activated, but the levels of GSH/OPT-synthesizing enzymes remained unchanged. After 6 h of fasting, the mice were given 1% 2AB and/or 5% glucose in the drinking water for an additional 24 h and the above metabolites analyzed. 2AB administration caused an increase in OPT levels, and, when glucose was co-administered with 2AB, the levels of OPT were elevated further but GSH levels were decreased somewhat. These results suggest that, while Cys is utilized for glyconeogenesis under fasting conditions, reaching levels that were insufficient for the synthesis of GSH, 2OB was preferentially converted to 2AB via amino acid catabolism and was utilized as a building block for OPT. Thus the consumption of Cys and the parallel elevation of 2AB under fasting conditions appeared to force γ-glutamylcysteine synthetase to form γ-glutamyl-2AB, despite the fact that the enzyme has a higher Km value for 2AB than Cys. Copyright © 2017 Elsevier Inc. All rights reserved.

Interaction between the Haptoglobin 2 Phenotype and Diabetes Mellitus on Systolic Pulmonary Arterial Pressure and Nitric Oxide Bioavailability in Hemodialysis Patients

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Inbal Dahan

2015-01-01

Full Text Available Elevated systolic pulmonary artery pressure (s-PAP, ≥35 mmHg serves as an independent predictor of mortality in hemodialysis (HD and diabetic (DM patients. A polymorphism in the antioxidant Haptoglobin (Hp gene has been shown to regulate the bioavailability of nitric oxide (NO, a major mediator of pulmonary vascular tone. We therefore set out to test the hypothesis that the Hp polymorphism may be a determinant of developing elevated s-PAP specifically in the DM state due to a decreased bioavailability of NO. To test our hypothesis we Hp typed and performed transthoracic echocardiography on a series of HD patients and stratified them into elevated and normal s-PAP groups and then evaluated whether there was a significant association between the Hp type, elevated s-PAP, and decreased NO bioavailability as defined by low plasma nitrite. We found a statistically significant interaction between the Hp type and DM on the prevalence of elevated s-PAP and lower mean nitrite levels with the combination of elevated s-PAP and low nitrite levels being significantly more prevalent in Hp 2-2 DM individuals. We conclude that the Hp 2 type is associated with elevated s-PAP levels and low plasma nitrite levels in HD patients specifically in the DM state.

A composite model including visfatin, tissue polypeptide-specific antigen, hyaluronic acid, and hematological variables for the diagnosis of moderate-to-severe fibrosis in nonalcoholic fatty liver disease: a preliminary study.

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Chwist, Alina; Hartleb, Marek; Lekstan, Andrzej; Kukla, Michał; Gutkowski, Krzysztof; Kajor, Maciej

2014-01-01

Histopathological risk factors for end-stage liver failure in patients with nonalcoholic fatty liver disease (NAFLD) include nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis. There is a need for noninvasive diagnostic methods for these 2 conditions. The aim of this study was to investigate new laboratory variables with a predictive potential to detect advanced fibrosis (stages 2 and 3) in NAFLD. The study involved 70 patients with histologically proven NAFLD of varied severity. Additional laboratory variables included zonulin, haptoglobin, visfatin, adiponectin, leptin, tissue polypeptide-specific antigen (TPSA), hyaluronic acid, and interleukin 6. Patients with NASH (NAFLD activity score of ≥5) had significantly higher HOMA-IR values and serum levels of visfatin, haptoglobin, and zonulin as compared with those without NASH on histological examination. Advanced fibrosis was found in 16 patients (22.9%) and the risk factors associated with its prevalence were age, the ratio of erythrocyte count to red blood cell distribution width, platelet count, and serum levels of visfatin and TPSA. Based on these variables, we constructed a scoring system that differentiated between NAFLD patients with and without advanced fibrosis with a sensitivity of 75% and specificity of 100% (area under the receiver operating characteristic curve, 0.93). The scoring system based on the above variables allows to predict advanced fibrosis with high sensitivity and specificity. However, its clinical utility should be verified in further studies involving a larger number of patients.

Cardiomyocyte Triglyceride Accumulation and Reduced Ventricular Function in Mice with Obesity Reflect Increased Long Chain Fatty Acid Uptake and De Novo Fatty Acid Synthesis

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Fengxia Ge

2012-01-01

Full Text Available A nonarteriosclerotic cardiomyopathy is increasingly seen in obese patients. Seeking a rodent model, we studied cardiac histology, function, cardiomyocyte fatty acid uptake, and transporter gene expression in male C57BL/6J control mice and three obesity groups: similar mice fed a high-fat diet (HFD and db/db and ob/ob mice. At sacrifice, all obesity groups had increased body and heart weights and fatty livers. By echocardiography, ejection fraction (EF and fractional shortening (FS of left ventricular diameter during systole were significantly reduced. The Vmax for saturable fatty acid uptake was increased and significantly correlated with cardiac triglycerides and insulin concentrations. Vmax also correlated with expression of genes for the cardiac fatty acid transporters Cd36 and Slc27a1. Genes for de novo fatty acid synthesis (Fasn, Scd1 were also upregulated. Ten oxidative phosphorylation pathway genes were downregulated, suggesting that a decrease in cardiomyocyte ATP synthesis might explain the decreased contractile function in obese hearts.

Increased Toxicity of Chemotherapeutic Drugs by All-Trans Retinoic Acid in Cd44 Cells

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A Abbasi

2016-03-01

Full Text Available BACKGROUND AND OBJECTIVE: In recent studies, undifferentiated CD44 cells have been introduced as the major cause of chemotherapeutic drug resistance in esophageal cancer. In this study, we aimed to evaluate the effects of all-trans retinoic acid on reducing chemotherapeutic drug resistance and improving the associated toxic effects. METHODS: In this clinical study, CD44+ and CD44- cells were separated from KYSE-30 cell line, using magnetic-activated cell sorting (MACS method. The cytotoxic effects of retinoic acid treatment, combined with cisplatin and 5-fluorouracil, were separately evaluated in two cell groups, i.e., CD44+ and CD44-. Cytotoxicity was determined by identifying cellular metabolic activity, acridine orange/ethidium bromide staining, and flow cytometry. FINDINGS: In this study, CD44 marker was expressed in 6.25% of the cell population in KYSE-30 cell line. The results of flow cytometry revealed that treatment with a combination of retinoic acid and chemotherapeutic drugs could improve cell cycle arrest in CD44+ cells (p<0.05, unlike CD44- cells. Determination of cellular metabolic activity, increased cell apoptosis along with decreased half maximal inhibitory concentration (IC50, and acridine orange/ethidium bromide staining were indicative of the increased percentage of primary and secondary apoptotic CD44+ cells. However, in CD44- cells, these effects were only observed by using a combination of retinoic acid and cisplatin (p<0.05. CONCLUSION: The present results showed that all-trans retinoic acid could increase the toxicity of cisplatin and 5-fluorouracil in CD44+ cells.

Haptoglobin preferentially binds β but not α subunits cross-linked hemoglobin tetramers with minimal effects on ligand and redox reactions.

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Jia, Yiping; Wood, Francine; Buehler, Paul W; Alayash, Abdu I

2013-01-01

Human hemoglobin (Hb) and haptoglobin (Hp) exhibit an extremely high affinity for each other, and the dissociation of Hb tetramers into dimers is generally believed to be a prerequisite for complex formation. We have investigated Hp interactions with native Hb, αα, and ββ cross-linked Hb (ααXLHb and ββXLHb, respectively), and rapid kinetics of Hb ligand binding as well as the redox reactivity in the presence of and absence of Hp. The quaternary conformation of ββ subunit cross-linking results in a higher binding affinity than that of αα subunit cross-linked Hb. However, ββ cross-linked Hb exhibits a four fold slower association rate constant than the reaction rate of unmodified Hb with Hp. The Hp contact regions in the Hb dimer interfaces appear to be more readily exposed in ββXLHb than ααXLHb. In addition, apart from the functional changes caused by chemical modifications, Hp binding does not induce appreciable effects on the ligand binding and redox reactions of ββXLHb. Our findings may therefore be relevant to the design of safer Hb-based oxygen therapeutics by utilizing this preferential binding of ββXLHb to Hp. This may ultimately provide a safe oxidative inactivation and clearance pathway for chemically modified Hbs in circulation.

Changes of some serum proteins in rats continuously irradiated with daily dose rate of 0. 0258 C/kg

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Chlebovska, K; Chlebovsky, O; Praslicka, M [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie

1976-01-01

Changes of serum albumin, haptoglobin, hemopexin and IgG in rats during chronic /sup 60/Co gamma irradiation with a daily dose rate of 0.0258 C/kg within 44 days were investigated by the method of two-dimensional quantitative immunoelectrophoresis. In comparison with normal levels, the values of albumin and IgG in rats during irradiation decreased until the death of animals to 50%, the values of haptoglobin increased till the 39th day of irradiation to 250% and hemopexin values increased to 150%.

Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis

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Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung [Department of Pharmacology and Pharmacogenomics Research Center, Inje University, College of Medicine, Bokjiro 75, Busanjin-Gu, Busan 614-735 (Korea, Republic of); Park, Se-Myo; Oh, Jung-Hwa; Kim, Yong-Bum; Moon, Kyoung-Sik [Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343 (Korea, Republic of); Choi, Hyung-Kyoon [College of Pharmacy, Chung-Ang University, Seoul (Korea, Republic of); Jeong, Jayoung [Ministry of Food and Drug Safety, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do 361-951 (Korea, Republic of); Shin, Jae-Gook [Department of Pharmacology and Pharmacogenomics Research Center, Inje University, College of Medicine, Bokjiro 75, Busanjin-Gu, Busan 614-735 (Korea, Republic of); Kim, Dong Hyun, E-mail: dhkim@inje.ac.kr [Department of Pharmacology and Pharmacogenomics Research Center, Inje University, College of Medicine, Bokjiro 75, Busanjin-Gu, Busan 614-735 (Korea, Republic of)

2015-10-15

A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30 mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague–Dawley (SD) rats for 28 days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence of compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. - Highlights: • Endogenous metabolic profiles were assessed in rat after treatment of thioacetamide. • It significantly increased the levels of bile acids in serum but not in the liver. • Expression of the genes related to bile acid secretion and reuptake was decreased. • Increased serum bile acids result from block of enterohepatic circulation of bile acids.

Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis

International Nuclear Information System (INIS)

Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung; Park, Se-Myo; Oh, Jung-Hwa; Kim, Yong-Bum; Moon, Kyoung-Sik; Choi, Hyung-Kyoon; Jeong, Jayoung; Shin, Jae-Gook; Kim, Dong Hyun

2015-01-01

A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30 mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague–Dawley (SD) rats for 28 days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence of compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. - Highlights: • Endogenous metabolic profiles were assessed in rat after treatment of thioacetamide. • It significantly increased the levels of bile acids in serum but not in the liver. • Expression of the genes related to bile acid secretion and reuptake was decreased. • Increased serum bile acids result from block of enterohepatic circulation of bile acids.

D-tagatose, a stereoisomer of D-fructose, increases blood uric acid concentration.

Science.gov (United States)

Buemann, B; Toubro, S; Holst, J J; Rehfeld, J F; Bibby, B M; Astrup, A

2000-08-01

D-Fructose has been found to increase uric acid production by accelerating the degradation of purine nucleotides, probably due to hepatocellular depletion of inorganic phosphate (Pi) by an accumulation of ketohexose-1-phosphate. The hyperuricemic effect of D-tagatose, a stereoisomer of D-fructose, may be greater than that of D-fructose, as the subsequent degradation of D-tagatose-1-phosphate is slower than the degradation of D-fructose-1-phosphate. We tested the effect of 30 g oral D-tagatose versus D-fructose on plasma uric acid and other metabolic parameters in 8 male subjects by a double-blind crossover design. Both the peak concentration and 4-hour area under the curve (AUC) of serum uric acid were significantly higher after D-tagatose compared with either 30 g D-fructose or plain water. The decline in serum Pi concentration was greater at 50 minutes after D-tagatose versus D-fructose. The thermogenic and lactacidemic responses to D-tagatose were blunted compared with D-fructose. D-Tagatose attenuated the glycemic and insulinemic responses to a meal that was consumed 255 minutes after its administration. Moreover, both fructose and D-tagatose increased plasma concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The metabolic effects of D-tagatose occurred despite its putative poor absorption.

Role of Changes in Cell Fatty Acids Composition in the Increasing of Frost Resistance of Winter Wheat Suspension Culture

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I.V. Lyubushkina

2013-11-01

Full Text Available Influences of low temperatures (4 and 8 ° С on the frost tolerance and fatty acid compositions of cells in a winter wheat suspension culture have been studied. It has been found that treatment of the culture with 4 °C (7 days did not protect cells from subsequent freezing temperature action (-8 °С, 6 h and was not accompanied significant changes in the fatty acid composition. On the contrary, the treatment of the culture with the temperature 8 °C (7 days prevented the death caused by freezing temperature and the content of saturated fatty acids decreased: pentadecanoic acid (by 35,0%, palmitic acid (by 19,9% and stearic acid (by 65,4%, and the content of α-linolenic acid increased by 94%. That was the cause of the double bond index (DBI increase by 16%. The role of fatty acids composition changes in the process of increasing frost tolerance in plants are discussed.

Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

International Nuclear Information System (INIS)

Powell, Ashley A; Akare, Sandeep; Qi, Wenqing; Herzer, Pascal; Jean-Louis, Samira; Feldman, Rebecca A; Martinez, Jesse D

2006-01-01

There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype

Acute-phase responses in healthy and diseased rhesus macaques (Macaca mulatta)

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Krogh, Anne Kirstine Havnsøe; Lundsgaard, Jo F. H.; Bakker, Jaco

2014-01-01

Five acute-phase reactants—serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin, albumin, and iron—were measured using commercially available assays in 110 healthy rhesus macaques (Macaca mulatta), and reference intervals were established for future use in health monitoring of this species....... Reference intervals established were as follows: SAA, 29.5–87.7 mg/L; CRP, 0–17.5 mg/L; haptoglobin, 354.3–2,414.7 mg/L; albumin, 36.1–53.0 g/L; and iron, 13.3–40.2 lmol/L. Furthermore, changes in the acute-phase reactants were studied in two additional groups of animals: eight rhesus macaques suffering...... from acute traumatic injuries and nine rhesus macaques experimentally infected with Mycobacterium tuberculosis reflecting a chronic active inflammation. In animals with inflammation, SAA and haptoglobin concentrations were moderately increased, while CRP increased more than 200-fold. In addition, marked...

Dietary guanidinoacetic acid increases brain creatine levels in healthy men

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Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik

2017-01-01

OBJECTIVE: Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA......, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. RESULTS: Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation......, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8...

Some putative prebiotics increase the severity of Salmonella enterica serovar Typhimurium infection in mice

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Lahtinen Sampo

2009-01-01

Full Text Available Abstract Background Prebiotics are non-digestible food ingredients believed to beneficially affect host health by selectively stimulating the growth of the beneficial bacteria residing in the gut. Such beneficial bacteria have been reported to protect against pathogenic infections. However, contradicting results on prevention of Salmonella infections with prebiotics have been published. The aim of the present study was to examine whether S. Typhimurium SL1344 infection in mice could be prevented by administration of dietary carbohydrates with different structures and digestibility profiles. BALB/c mice were fed a diet containing 10% of either of the following carbohydrates: inulin, fructo-oligosaccharide, xylo-oligosaccharide, galacto-oligosaccharide, apple pectin, polydextrose or beta-glucan for three weeks prior to oral Salmonella challenge (107 CFU and compared to mice fed a cornstarch-based control diet. Results The mice fed with diets containing fructo-oligosaccharide (FOS or xylo-oligosaccharide (XOS had significantly higher (P < 0.01 and P < 0.05 numbers of S. Typhimurium SL1344 in liver, spleen and mesenteric lymph nodes when compared to the mice fed with the cornstarch-based control diet. Significantly increased amounts (P < 0.01 of Salmonella were detected in ileal and fecal contents of mice fed with diets supplemented with apple pectin, however these mice did not show significantly higher numbers of S. Typhimyrium in liver, spleen and lymph nodes than animals from the control group (P < 0.20. The acute-phase protein haptoglobin was a good marker for translocation of S. Typhimurium in mice. In accordance with the increased counts of Salmonella in the organs, serum concentrations of haptoglobin were significantly increased in the mice fed with FOS or XOS (P < 0.001. Caecum weight was increased in the mice fed with FOS (P < 0.01, XOS (P < 0.01, or polydextrose (P < 0.001, and caecal pH was reduced in the mice fed with polydextrose (P < 0

Acute exercise does not induce an acute phase response (APR) in Standardbred trotters

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Kristensen, Lena; Buhl, Rikke; Nostell, Katarina

2014-01-01

), and iron], muscle enzymes [creatinine kinase (CK) and aspartate transaminase (AST)], and hemoglobin were assessed in 58 Standardbred trotters before and after racing. Hemoglobin levels increased and iron levels decreased 12 to 14 h after racing and haptoglobin concentrations, white blood cell counts......, and iron levels were decreased 2 and/or 7 d after racing. Concentrations of CK, AST, SAA, and fibrinogen were unaltered in response to racing. Acute strenuous exercise did not elicit an acute phase reaction. The observed acute increase in hemoglobin levels and decreases in haptoglobin and iron levels may...

Fatty acid amide hydrolase (FAAH) regulates hypercapnia/ischemia-induced increases in n-acylethanolamines in mouse brain.

Science.gov (United States)

Lin, Lin; Metherel, Adam H; Jones, Peter J; Bazinet, Richard P

2017-09-01

N-acylethanolamines (NAEs) are endogenous lipid ligands for several receptors including cannabinoid receptors and peroxisome proliferator-activated receptor-alpha (PPAR-α), which regulate numerous physiological functions. Fatty acid amide hydrolase (FAAH) is largely responsible for the degradation of NAEs. However, at high concentrations of ethanolamines and unesterified fatty acids, FAAH can also catalyze the reverse reaction, producing NAEs. Several brain insults such as ischemia and hypoxia increase brain unesterified fatty acids. Because FAAH can catalyze the synthesis of NAE, we aimed to test whether FAAH was necessary for CO 2 -induced hypercapnia/ischemia increases in NAE. To test this, we examined levels of NAEs, 1- and 2-arachidonoylglycerols as well as their corresponding fatty acid precursors in wild-type and mice lacking FAAH (FAAH-KO) with three Kill methods: (i) head-focused, high-energy microwave irradiation (microwave), (ii) 5 min CO 2 followed by microwave irradiation (CO 2 + microwave), and (iii) 5 min CO 2 only (CO 2 ). Both CO 2 -induced groups increased, to a similar extent, brain levels of unesterified oleic, arachidonic, and docosahexaenoic acid and 1- and 2-arachidonoylglycerols compared to the microwave group in both wild-type and FAAH-KO mice. Oleoylethanolamide (OEA), arachidonoylethanolamide (AEA), and docosahexaenoylethanolamide (DHEA) levels were about 8-, 7-, and 2.5-fold higher, respectively, in the FAAH-KO mice compared with the wild-type mice. Interestingly, the concentrations of OEA, AEA, and DHEA increased 2.5- to 4-fold in response to both CO 2 -induced groups in wild-type mice, but DHEA increased only in the CO 2 group in FAAH-KO mice. Our study demonstrates that FAAH is necessary for CO 2 - induced increases in OEA and AEA but not DHEA. Targeting brain FAAH could impair the production of NAEs in response to brain injuries. © 2017 International Society for Neurochemistry.

Increased brain fatty acid uptake in metabolic syndrome

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Karmi, Anna; Iozzo, Patricia; Viljanen, Antti

2010-01-01

To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

Haptoglobin study in myasthenia gravis Estudo sobre a haptoglobina na miastenia grave

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Leonardo H. Mendonça Oliveira

2008-06-01

Full Text Available OBJECTIVE: A cross-sectional study of haptoglobin (Hp in myasthenia gravis (MG was designed, with the objective to identify its values and correlate them with different disease status. METHOD: 46 patients were enrolled in the study, all having disease severity established according to the quantitative myasthenia gravis strength scores (QMGSS. Based on the functional scale determined by Myasthenia Gravis Foundation of America (MGFA recommendations, patients were classified as having: complete stable remission (CSR; n=10; minimal manifestations-0 (MM0; n=6, minimal manifestations-1 (MM1; n=4; pharmacological remission (PR; n=6. Two other groups participated: thymomatous patients (T; n=10 and patients without imunosuppression or thymectomy, until the assessment for Hp (WIT; n=10. Hp dosage was done by immunonephelometry, blindly to clinical data. Student's t-test, Anova test and linear regression were employed for statistical analyses. RESULTS: Statistically significant differences occurred between CSR+MM0xWIT groups (86.62x157.57, pOBJECTIVO: Desenhou-se estudo transversal sobre a haptoglobina (Hp na miastenia grave (MG com o objetivo de identificar seus valores e correlacioná-los a diferentes condições na doença. MÉTODO: 46 pacientes foram incluídos, todos tendo a gravidade da doença estabelecida segundo escores internacionais (QMGSS. Os pacientes tiveram seu estado funcional determinado de acordo com a Myasthenia Gravis Foundation of América (MGFA e classificados em: remissão completa estável (CSR; n=10; mínima manifestação-0 (MM0; n=6, mínima manifestação-1 (MM1; n=4; remissão farmacológica (PR; n=6. Dois outros grupos participaram: pacientes timomatosos (T; n=10 e pacientes sem imunossupressão ou timectomia, até o momento da inclusão no estudo (WIT; n=10. A dosagem de Hp foi realizada por imunonefelometria, de modo cego quanto à clínica. As análises estatísticas incluíram o teste de Student, Anova e regressão linear

Amino acids fortification of low-protein diet for broilers under tropical climate. 2. Nonessential amino acids and increasing essential amino acids

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Elmutaz Atta Awad

2014-08-01

Full Text Available A three-week trial was carried out to evaluate the effect of nonessential amino acids (NEAA supplementation to a low-crude protein (CP diet with adequate essential amino acids (EAA level on growth performance, blood metabolites, and relative weights of abdominal fat, breast yield, and internal organs in broiler chickens raised under tropical hot and humid environment. Five isocaloric (3000 metabolisable energy/kg corn-soybean diets were administered (1 to 21 days to 5 groups of broilers (60 birds/group as follows: i 22.2% CP (positive control; PC; ii 16.2% CP+all EAA to meet or exceed the National Research Council (1994 recommendations (negative control; NC; iii NC+further EAA to equal the levels in the PC diet; iv NC+NEAA to equal the levels in the PC; v NC+EAA and NEAA to equal the amino acids levels in the PC diet. The results showed that the fortification of EAA alone, only improved feed intake (FI, whereas, addition of NEAA or EAA+NEAA significantly enhanced body weight, daily weight gain, and FI and decreased the feed conversion ratio to the same levels as in PC. Serum uric acid was significantly reduced and serum triglyceride increased in NC group. Dietary treatments had no significant effect on relative weights of heart, liver, abdominal fat, breast meat yield, serum albumin, and serum total protein. In conclusion, these results suggest that NEAA fortification may improve the growth performance of broilers fed an excessive low-CP diet under tropical hot and humid condition.

Lactic Acid Bacteria from Kefir Increase Cytotoxicity of Natural Killer Cells to Tumor Cells

OpenAIRE

Takuya Yamane; Tatsuji Sakamoto; Takenori Nakagaki; Yoshihisa Nakano

2018-01-01

The Japanese fermented beverage, homemade kefir, contains six lactic acid bacteria: Lactococcus. lactis subsp. Lactis, Lactococcus. lactis subsp. Cremoris, Lactococcus. Lactis subsp. Lactis biovar diacetylactis, Lactobacillus plantarum, Leuconostoc meseuteroides subsp. Cremoris and Lactobacillus casei. In this study, we found that a mixture of the six lactic acid bacteria from kefir increased the cytotoxicity of human natural killer KHYG-1 cells to human chronic myelogenous leukemia K562 cell...

Development of technology for biological dosimetry -A study on the radiation and environmental safety-

International Nuclear Information System (INIS)

Lee, Kang Suk; Cheon, Ki Jeong; Kim, Kook Chan; Kim, Jin Kyu; Kim, Sang Bok; Kim, In Kyu; Park, Hyo Kook

1994-07-01

α-amylase showed a significant increase in its activity when exposed to radiation of 0.1 Gy. However it had no relationship with radiation dose. Enzyme activities in liver tissue showed similar changes to those in serum. Among others, changes in acid phosphatase activity were highly related to radiation dose. Of acute phase proteins in serum, CRP, ceruloplasmin and haptoglobin positively responded to radiation while albumin did negatively. ELISA proved to be an efficient method to detect changes in serum protein level. Finally the measurements of changes in APRs using ELISA could provide an useful tools for biological dosimetry. (Author)

Uric acid stones increase the risk of chronic kidney disease.

Science.gov (United States)

Li, Ching-Chia; Chien, Tsu-Ming; Wu, Wen-Jeng; Huang, Chun-Nung; Chou, Yii-Her

2018-02-28

The aim of this study was to compare the clinical characteristics of uric acid stones and their potential risk for chronic kidney disease (CKD). A total of 401 patients (196 with uric acid stone and 205 without) were enrolled from our database of patients with urolithiasis. We analyzed the clinical demographic features, stone location, urine chemistries, and renal function. There was a significant difference (p uric acid group. Patients with uric acid stones had much lower pH of urine (p uric acid level (p = 0.002). Notably, those with uric acid stones had worse eGFR than those with non-uric acid stones. Multivariate analysis confirmed that age over 60 years (ORs = 9.19; 95% CI 3.5-24.3), female sex (ORs = 4.01; 95% CI 1.8-9.0), hyperuricemia (ORs = 8.47; 95% CI 1.6-43.5), and uric acid stone (OR = 2.86; 95% CI 1.2-6.7) were the independent predictors of poor prognoses in CKD. Therefore, an association exists between uric acid stones and higher prevalence of CKD. Patients with uric acid stones may need close monitoring of renal function during follow-up.

Studies on ’Macaca mulatta’ Infected with Rocky Mountain Spotted Fever

Science.gov (United States)

1976-09-10

Mountain spotted fever (RMSF) rickettsiae. The LD50 in monkeys of the yolk-sac-grown seed stock was 10 to the 1.35th power plaque-forming units. Blood...acid glycoprotein, haptoglobin and albumin) were measured during a study in 16 male rhesus monkeys to determine the median lethal dose (LD50) of Rocky

Amelioration of acidic soil increases the toxicity of the weak base carbendazim to the earthworm Eisenia fetida.

Science.gov (United States)

Liu, Kailin; Wang, Shaoyun; Luo, Kun; Liu, Xiangying; Yu, Yunlong

2013-12-01

Ameliorating acidic soils is a common practice and may affect the bioavailability of an ionizable organic pollutant to organisms. The toxicity of the weak base carbendazim to the earthworm (Eisenia fetida) was studied in an acidic soil (pH-H₂O, 4.6) and in the ameliorated soil (pH-H₂O, 7.5). The results indicated that the median lethal concentration of carbendazim for E. fetida decreased from 21.8 mg/kg in acidic soil to 7.35 mg/kg in the ameliorated soil. To understand why the amelioration increased carbendazim toxicity to the earthworm, the authors measured the carbendazim concentrations in the soil porewater. The authors found increased carbendazim concentrations in porewater, resulting in increased toxicity of carbendazim to earthworms. The increased pore concentrations result from decreased adsorption because of the effects of pH and calcium ions. © 2013 SETAC.

Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.

Directory of Open Access Journals (Sweden)

Joseph W McFadden

Full Text Available Modification of hypothalamic fatty acid (FA metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1 and fatty acid oxidation (FAOx, exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS, and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism.

Clofibric Acid Increases the Formation of Oleic Acid in Endoplasmic Reticulum of the Liver of Rats

OpenAIRE

広瀬, 明彦; 山崎, 研; 坂本, 武史; 須永, 克佳; 津田, 整; 光本, 篤史; 工藤, なをみ; 川嶋, 洋一

2011-01-01

The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [14C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellul...

Haptoglobin

DEFF Research Database (Denmark)

Andersen, Christian Brix Folsted; Stødkilde, Kristian; Sæderup, Kirstine Lindhardt

2017-01-01

Hpr, by acting as an Hp-lookalike, can sneak a lethal toxin into trypanosome parasites that cause mammalian sleeping sickness. Critical Issues and Future Directions: The new structural insight may facilitate ongoing attempts of developing Hp derivatives for prevention of Hb toxicity in hemolytic...

Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression

DEFF Research Database (Denmark)

Wang, Qian; Bailey, Charles G; Ng, Cynthia

2011-01-01

was sufficient to decrease cell growth and mTORC1 signaling in prostate cancer cells. These cells maintained levels of amino acid influx through androgen receptor-mediated regulation of LAT3 expression and ATF4 regulation of LAT1 expression after amino acid deprivation. These responses remained intact in primary......L-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential amino acids. Here, we report that prostate cancer cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 signaling and cell growth. Inhibiting LAT function...... prostate cancer, as indicated by high levels of LAT3 in primary disease, and by increased levels of LAT1 after hormone ablation and in metastatic lesions. Taken together, our results show how prostate cancer cells respond to demands for increased essential amino acids by coordinately activating amino acid...

Iodine application increased ascorbic acid content and modified the vascular tissue in opuntia ficus-indica

International Nuclear Information System (INIS)

Osuna, H.T.G.; Morales, R.; Rubio, E.M.; Mendoza, A.B.; Ruvalcaba, R.M

2014-01-01

The objective of this study was to discern the effect of applying both iodide and iodate to Opuntia ficus indica irrigation. The effect of iodate (KIO/sub 3/, 10-4 M) and iodide (KI, 10-4 M) on plant growth, yield and morphology was studied. Experiments were carried in three samples under tunnel conditions. In the last sampling, iodine species (KIO/sub 3/, KI) caused a negative effect in biomass. The amount of ascorbic acid, however, was increased over 51% in both iodine treatments. Phosphorus (0.26%), iron (50 ppm), and magnesium (1402 ppm) increases were also observed with iodate treatment in the first sampling, and increases in potassium (46.8 ppm) were apparent in the second. Iodide treatment increased the amounts of copper (1.02 ppm) and manganese (32.80 ppm) in the first sampling. Iodate treatment modified the number of xylem vessels and increased both the mucilage area and amount of druses. In general this study shows that iodate increases the amount of ascorbic acid and the morphology of the vascular tissue. (author)

Dietary Crude Lecithin Increases Systemic Availability of Dietary Docosahexaenoic Acid with Combined Intake in Rats.

Science.gov (United States)

van Wijk, Nick; Balvers, Martin; Cansev, Mehmet; Maher, Timothy J; Sijben, John W C; Broersen, Laus M

2016-07-01

Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined.

Oxidation in fish oil enriched mayonnaise : Ascorbic acid and low pH increase oxidative deterioration

DEFF Research Database (Denmark)

Jacobsen, Charlotte; Timm Heinrich, Maike; Meyer, Anne S.

2001-01-01

The effect of ascorbic acid (0-4000 ppm) and pH (3.8-6.2) on oxidation and levels of iron and copper in various fractions of mayonnaise enriched with 16% fish oil was investigated. Ascorbic acid induced release of iron from the assumed oil- water interface into the aqueous phase at all pH levels......, but this effect of ascorbic acid was strongest at low pH (pH 3.8- 4.2). Ascorbic acid generally promoted formation of volatile oxidation compounds and reduced the peroxide value in mayonnaises. Peroxide values and total volatiles generally increased with decreasing pH values, suggesting that low pH promoted...... oxidation. It is proposed that iron bridges between the egg yolk proteins low-density lipoproteins, lipovitellin, and phosvitin at the oil-water interface are broken at low pH values, whereby iron ions become accessible as oxidation initiators. In the presence of ascorbic acid, oxidation is further enhanced...

Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

DEFF Research Database (Denmark)

Penkowa, M; Molinero, A; Carrasco, J

2001-01-01

and were killed six days later. Morphological damage to the hippocampal field CA1-CA3 was seen after kainic acid treatment. Reactive astrogliosis and microgliosis were prominent in kainic acid-injected normal mice hippocampus, and clear signs of increased oxidative stress were evident. Thus......The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice......, and caused a significant mortality (62%) only in the latter mice, indicating that interleukin-6 deficiency increased the susceptibility to kainic acid-induced brain damage. To compare the histopathological damage caused to the brain, control and interleukin-6 null mice were administered 8.75mg/kg kainic acid...

Early increase of amino acid transport in stimulated lymphocytes

NARCIS (Netherlands)

Berg, K.J. van den; Betel, I.

1971-01-01

Chemicals/CAS: 2 amino 2 methylpropionic acid, 62-57-7; carbon, 7440-44-0; thymidine, 50-89-5; tritium, 10028-17-8; Aminoisobutyric Acids; Carbon Isotopes; Lectins; Thymidine, 50-89-5; Tritium, 10028-17-8

Method of increasing efficiency of uranium sorption from acid pulp

International Nuclear Information System (INIS)

Parobek, P.; Hinterholzinger, O.; Baloun, S.; Homolka, V.; Vanek, J.; Vebr, Z.

1989-01-01

Acid pulp containing uranium is adjusted to pH 2.5 to 4 with alkaline agents, such as alkaline pulp, lime milk, finely ground limestone or soda, or a combination thereof. The treated pulp is put into contact with an ion exchanger whose pH has been adjuste to a range of 2.5 to 4. Partial pulp neutralization causes the hydrolysis of the iron present and an overall reduction in salt contents and a significant increase in the ion exchanger sorptio capacity and thus the overall sorption efficiency. The quality o the eluate and of the uranium concentrate improves. (B.S.)

Development and validation of a SYBR Green I-based real-time polymerase chain reaction method for detection of haptoglobin gene deletion in clinical materials.

Science.gov (United States)

Soejima, Mikiko; Tsuchiya, Yuji; Egashira, Kouichi; Kawano, Hiroyuki; Sagawa, Kimitaka; Koda, Yoshiro

2010-06-01

Anhaptoglobinemic patients run the risk of severe anaphylactic transfusion reaction because they produce serum haptoglobin (Hp) antibodies. Being homozygous for the Hp gene deletion (HP(del)) is the only known cause of congenital anhaptoglobinemia, and clinical diagnosis of HP(del) before transfusion is important to prevent anaphylactic shock. We recently developed a 5'-nuclease (TaqMan) real-time polymerase chain reaction (PCR) method. A SYBR Green I-based duplex real-time PCR assay using two forward primers and a common reverse primer followed by melting curve analysis was developed to determine HP(del) zygosity in a single tube. In addition, to obviate initial DNA extraction, we examined serially diluted blood samples as PCR templates. Allelic discrimination of HP(del) yielded optimal results at blood sample dilutions of 1:64 to 1:1024. The results from 2231 blood samples were fully concordant with those obtained by the TaqMan-based real-time PCR method. The detection rate of the HP(del) allele by the SYBR Green I-based method is comparable with that using the TaqMan-based method. This method is readily applicable due to its low initial cost and analyzability using economical real-time PCR machines and is suitable for high-throughput analysis as an alternative method for allelic discrimination of HP(del).

17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

Science.gov (United States)

Mason, Julie K; Kharotia, Shikhil; Wiggins, Ashleigh K A; Kitson, Alex P; Chen, Jianmin; Bazinet, Richard P; Thompson, Lilian U

2014-08-01

Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

International Nuclear Information System (INIS)

Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-01-01

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

A sulfur amino acid-free meal increases plasma lipids in humans.

Science.gov (United States)

Park, Youngja; Le, Ngoc-Anh; Yu, Tianwei; Strobel, Fred; Gletsu-Miller, Nana; Accardi, Carolyn J; Lee, Kichun S; Wu, Shaoxiong; Ziegler, Thomas R; Jones, Dean P

2011-08-01

The content of sulfur amino acid (SAA) in a meal affects postprandial plasma cysteine concentrations and the redox potential of cysteine/cystine. Because such changes can affect enzyme, transporter, and receptor activities, meal content of SAA could have unrecognized effects on metabolism during the postprandial period. This pilot study used proton NMR ((1)H-NMR) spectroscopy of human plasma to test the hypothesis that dietary SAA content changes macronutrient metabolism. Healthy participants (18-36 y, 5 males and 3 females) were equilibrated for 3 d to adequate SAA, fed chemically defined meals without SAA for 5 d (depletion), and then fed isoenergetic, isonitrogenous meals containing 56 mg·kg(-1)·d(-1) SAA for 4.5 d (repletion). On the first and last day of consuming the chemically defined meals, a morning meal containing 60% of the daily food intake was given and plasma samples were collected over an 8-h postprandial time course for characterization of metabolic changes by (1)H-NMR spectroscopy. SAA-free food increased peak intensity in the plasma (1)H-NMR spectra in the postprandial period. Orthogonal signal correction/partial least squares-discriminant analysis showed changes in signals associated with lipids, some amino acids, and lactate, with notable increases in plasma lipid signals (TG, unsaturated lipid, cholesterol). Conventional lipid analyses confirmed higher plasma TG and showed an increase in plasma concentration of the lipoprotein lipase inhibitor, apoC-III. The results show that plasma (1)H-NMR spectra can provide useful macronutrient profiling following a meal challenge protocol and that a single meal with imbalanced SAA content alters postprandial lipid metabolism.

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun, E-mail: lijunzhou@tju.edu.cn

2015-12-25

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

Running speed in mammals increases with muscle n-6 polyunsaturated fatty acid content.

Directory of Open Access Journals (Sweden)

Thomas Ruf

Full Text Available Polyunsaturated fatty acids (PUFAs are important dietary components that mammals cannot synthesize de novo. Beneficial effects of PUFAs, in particular of the n-3 class, for certain aspects of animal and human health (e.g., cardiovascular function are well known. Several observations suggest, however, that PUFAs may also affect the performance of skeletal muscles in vertebrates. For instance, it has been shown that experimentally n-6 PUFA-enriched diets increase the maximum swimming speed in salmon. Also, we recently found that the proportion of PUFAs in the muscle phospholipids of an extremely fast runner, the brown hare (Lepus europaeus, are very high compared to other mammals. Therefore, we predicted that locomotor performance, namely running speed, should be associated with differences in muscle fatty acid profiles. To test this hypothesis, we determined phospholipid fatty acid profiles in skeletal muscles of 36 mammalian species ranging from shrews to elephants. We found that there is indeed a general positive, surprisingly strong relation between the n-6 PUFAs content in muscle phospholipids and maximum running speed of mammals. This finding suggests that muscle fatty acid composition directly affects a highly fitness-relevant trait, which may be decisive for the ability of animals to escape from predators or catch prey.

Does tranexamic acid increase the risk of thromboembolism after bilateral simultaneous total knee arthroplasties in Asian Population?

Science.gov (United States)

Kim, Young-Hoo; Park, Jang-Won; Kim, Jun-Shik; Seo, Dong-Hyuk

2018-01-01

To ascertain whether tranexamic acid reduces the blood loss and transfusion rate and volumes; increase the prevalence of deep vein thrombosis (DVT); and investigate factors associated with DVT in patients undergoing primary bilateral total knee arthroplasties (TKAs) without use of chemical thromboprophylaxis. There were 874 patients (1748 knees) in the control group who did not receive tranexamic acid and 871 patients (1742 knees) in the study group who received tranexamic acid. Mechanical compression device was applied without any chemical thromboprophylaxis. Transfusion rates and volumes were recorded. DVT was diagnosed using both sonogram and venogram at 7 or 8 day post-operatively. Intra- and post-operative blood loss and transfusion volumes were significantly lower in the tranexamic acid group. The prevalence of DVT was 14% (245 of 1748 knees) in the control group and 18% (314 of 1742 knees) in the tranexamic acid group. Pre- and post-operative perfusion lung scans revealed no evidence of PE in any patients in either group. Coagulation or thrombophilic data or molecular genetic testing was not significantly different between the two groups. The use of tranexamic acid reduces the volume of blood transfusion and does not increase the prevalence of DVT or PE in the patients who did not receive routine chemical thromboprophylaxis after primary bilateral simultaneous sequential TKAs in Asian patients.

The influence of thermal processing on the fatty acid profile of pork and lamb meat fed diet with increased levels of unsaturated fatty acids.

Science.gov (United States)

Janiszewski, Piotr; Grześkowiak, Eugenia; Lisiak, Dariusz; Borys, Bronisław; Borzuta, Karol; Pospiech, Edward; Poławska, Ewa

2016-01-01

The research was carried out on 32 crossbred pigs of Polish Large White × Danish Landrace with Duroc and 80 rams, crossbreds of the Prolific-Dairy Koludzka Sheep with the Ile de France, a meat sheep. The fodder for the animals was enriched with the unsaturated fatty acids originated mainly from linseed and rapeseed oils. The fatty acid profile was determined in cooked longissimus lumborum, roasted triceps brachii and raw ripened rump from pigs as well as in grilled lambs' legs and their corresponding raw materials. Roasting caused the most pronounced increase of the saturated fatty acids and decrease in the polyunsaturated fatty acids of heated pork muscles. The smallest changes were observed in grilled lamb legs. The heating processes applied in this study, in most cases, did not cause essential changes in the indices of pro-health properties of fatty acid, therefore meat in the majority fulfil the latest recommendations of EFSA and FAO/WHO according to human health.

Increased Erythrocyte Eicosapentaenoic Acid and Docosahexaenoic Acid Are Associated With Improved Attention and Behavior in Children With ADHD in a Randomized Controlled Three-Way Crossover Trial.

Science.gov (United States)

Milte, Catherine M; Parletta, Natalie; Buckley, Jonathan D; Coates, Alison M; Young, Ross M; Howe, Peter R C

2015-11-01

To investigate effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on attention, literacy, and behavior in children with ADHD. Ninety children were randomized to consume supplements high in EPA, DHA, or linoleic acid (control) for 4 months each in a crossover design. Erythrocyte fatty acids, attention, cognition, literacy, and Conners' Parent Rating Scales (CPRS) were measured at 0, 4, 8, 12 months. Fifty-three children completed the treatment. Outcome measures showed no significant differences between the three treatments. However, in children with blood samples (n = 76-46), increased erythrocyte EPA + DHA was associated with improved spelling (r = .365, p attention (r = -.540, p improve behavior, attention, and literacy in children with ADHD. © The Author(s) 2013.

Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians.

Science.gov (United States)

Gälman, Cecilia; Miquel, Juan Francisco; Pérez, Rosa Maria; Einarsson, Curt; Ståhle, Lars; Marshall, Guillermo; Nervi, Flavio; Rudling, Mats

2004-03-01

Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation. A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively. Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P or =100% (P Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women. The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.

Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

International Nuclear Information System (INIS)

Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V.

1990-01-01

Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3

Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

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Zheng, Liufeng; Zuo, Fangrui; Zhao, Shengjun; He, Pingli; Wei, Hongkui; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

2017-04-01

Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

Krill protein hydrolysate reduces plasma triacylglycerol level with concurrent increase in plasma bile acid level and hepatic fatty acid catabolism in high-fat fed mice

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Marie S. Ramsvik

2013-11-01

Full Text Available Background: Krill powder, consisting of both lipids and proteins, has been reported to modulate hepatic lipid catabolism in animals. Fish protein hydrolysate diets have also been reported to affect lipid metabolism and to elevate bile acid (BA level in plasma. BA interacts with a number of nuclear receptors and thus affects a variety of signaling pathways, including very low density lipoprotein (VLDL secretion. The aim of the present study was to investigate whether a krill protein hydrolysate (KPH could affect lipid and BA metabolism in mice. Method: C57BL/6 mice were fed a high-fat (21%, w/w diet containing 20% crude protein (w/w as casein (control group or KPH for 6 weeks. Lipids and fatty acid composition were measured from plasma, enzyme activity and gene expression were analyzed from liver samples, and BA was measured from plasma. Results: The effect of dietary treatment with KPH resulted in reduced levels of plasma triacylglycerols (TAG and non-esterified fatty acids (NEFAs. The KPH treated mice had also a marked increased plasma BA concentration. The increased plasma BA level was associated with induction of genes related to membrane canalicular exporter proteins (Abcc2, Abcb4 and to BA exporters to blood (Abcc3 and Abcc4. Of note, we observed a 2-fold increased nuclear farnesoid X receptor (Fxr mRNA levels in the liver of mice fed KPH. We also observed increased activity of the nuclear peroxiosme proliferator-activated receptor alpha (PPARα target gene carnitine plamitoyltransferase 2 (CPT-2. Conclusion: The KPH diet showed to influence lipid and BA metabolism in high-fat fed mice. Moreover, increased mitochondrial fatty acid oxidation and elevation of BA concentration may regulate the plasma level of TAGs and NEFAs.

ρ0 Cells Feature De-Ubiquitination of SLC Transporters and Increased Levels and Fluxes of Amino Acids

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André Bordinassi Medina

2017-04-01

Full Text Available Solute carrier (SLC transporters are a diverse group of membrane transporter proteins that regulate the cellular flux and distribution of endogenous and xenobiotic compounds. Post-translational modifications (PTMs, such as ubiquitination, have recently emerged as one of the major regulatory mechanisms in protein function and localization. Previously, we showed that SLC amino acid transporters were on average 6-fold de-ubiquitinated and increased amino acid levels were detected in ρ0 cells (lacking mitochondrial DNA, mtDNA compared to parental cells. Here, we elucidated the altered functionality of SLC transporters and their dynamic ubiquitination status by measuring the uptake of several isotopically labeled amino acids in both human osteosarcoma 143B.TK- and ρ0 cells. Our pulse chase analysis indicated that de-ubiquitinated amino acid transporters in ρ0 cells were accompanied by an increased transport rate, which leads to higher levels of amino acids in the cell. Finding SLC transport enhancers is an aim of the pharmaceutical industry in order to compensate for loss of function mutations in these genes. Thus, the ubiquitination status of SLC transporters could be an indicator for their functionality, but evidence for a direct connection between de-ubiquitination and transporter activity has to be further elucidated.

[Evaluation of the possibilities to increase the content of conjugated linoleic acid (CLA) in meat and meat product].

Science.gov (United States)

Piotrowska, Anna; Swiader, Katarzyna; Waszkiewicz-Robak, Bozena; Swiderski, Franciszek

2012-01-01

The paper characterizes pro-health properties of conjugated linoleic acid (CLA) and assesses the possibility of increasing their content in pork and pork meat products. Studies conducted on animals indicate antitumor, antiatherosclerotic and antiinflammatory effect ofCLA, also find impact on reducing body fat and increasing muscle growth. However, the number of observations concerning human populations is insufficient to fully evaluate the relationship between CLA intake and reducing the risk of lifestyle diseases. Therefore, it is necessary to conduct further research. Literature data indicate that the use in pigs feed suplementation with CLA preparations, can increase the content of these compounds in the meat and also show, that isomer cis-9, trans-11 is accumulated at significantly higher level. However, these changes were accompanied by increased the share of saturated fatty acids at the expense of monounsaturated which is unfavorable for human health. A better way to increase the CLA content in pork meat appears to be the addition of CLA preparation during the production process, because it does not affect the level of saturated fats. Pork and pork meat products enriched in CLA are characterized by low susceptibility to oxidation, which may result from the coupling of double bonds, antioxidantive properties of conjugated linoleic acid and the increased content of saturated fatty acids. The issue of beneficial effects on human health of pork and pork products with a higher content of CLA, requires further studies conducted on humans. Only then these products can be classified as a functional foods.

Acceptability and storage stability of pork products with increased levels of polyunsaturated fatty acids

NARCIS (Netherlands)

Houben, J.H.; Krol, B.

1980-01-01

Several batches of back bacon, belly bacon, Dutch-style cervelat sausage, pork loin roll, shoulder with fat, Bologna, Guelders ring sausage, Saxon liver sausage and luncheon meat were produced with increasing PUFA-levels using raw materials containing up to 30% linoleic acid in their fats. Only

Human milk arachidonic acid and docosahexaenoic acid contents increase following supplementation during pregnancy and lactation

NARCIS (Netherlands)

van Goor, Saskia A.; Dijick-Brouwer, D. A. Janneke; Hadders-Algra, Mijna; Doornbos, Bennard; Erwich, Jan Jaap H. M.; Schaafsma, Anne; Muskiet, Frits A. J.; Djick-Brouwer, D.A.J.

Introduction: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. Maternal diet influences milk DHA, whereas milk AA seems rather constant. We investigated milk AA, DHA and DHA/AA after supplementation of AA plus DHA, or DHA alone during pregnancy and lactation.

Effects of Organic Acids Treatments with or without Ultra-Sonic Treatment on Increasing the Shelf Life of Fresh Cut Kiwifruit

Directory of Open Access Journals (Sweden)

A. Mansoory

2016-02-01

Full Text Available The market sales of ready to use fresh cut fruits have grown rapidly in recent decades. Kiwi fruit is an important fruit that its marketing as fresh cut has increased in recent years. The main limiting factors in shelf life of fresh cut fruits are microbial spoilage, drastic softening and browning. In this study, the effects of oxalic and citric acids, both at 0, 2, 4 and 6 mM concentrations, with or without ultra-sonic treatment were investigated on the increasing the shelf life of fresh cut kiwi fruit. After treatments, the fresh slices were stored at 2°C for 7 or 14 days and assessed for several traits and analyzed. Results showed that, oxalic and citric acid treated slices, in comparison to the control, had greater marketability, as well as higher flesh firmness, titrable acidity, ascorbic acid content, total phenol content and antioxidant capacity and smaller bacterial forming colony unit (CFU. Among the treatments, 2, 4 and 6 mM oxalic acid and 6 mM citric acid treatments were found more appropriate than the reaming treatments. Application of ultra-sonic treatment, despite the reduction of microbial load and maintaining antioxidant capacity, had no effects on marketability of fresh cut kiwi fruit. Hence, application of organic acid treatments as dipping can be used to increase the shelf life of fresh cut kiwi fruit.

SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

Science.gov (United States)

Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

2014-01-01

Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits

Science.gov (United States)

Gruse, Jeannine; Kanitz, Ellen; Weitzel, Joachim M.; Tuchscherer, Armin; Stefaniak, Tadeusz; Jawor, Paulina; Wolffram, Siegfried; Hammon, Harald M.

2016-01-01

Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in

Increases in Phenolic, Fatty Acid, and Phytosterol Contents and Anticancer Activities of Sweet Potato after Fermentation by Lactobacillus acidophilus.

Science.gov (United States)

Shen, Yixiao; Sun, Haiyan; Zeng, Haiying; Prinyawiwatukul, Witoon; Xu, Wenqing; Xu, Zhimin

2018-03-21

Phenolic, fatty acid, and phytosterol contents in sweet potato (SP) fermented by Lactobacillus acidophilus were evaluated and compared with those of raw and boiled SPs. The differences in the profiles and levels of phenolics between the raw and boiled SPs were not as significant as the differences between those and the fermented SP. The levels of caffeic acid and 3,5-dicaffeoylquinic acid in fermented SP were more than 4 times higher than those in raw and boiled SPs. Two phenolics, p-coumaric acid and ferulic acid, which were not detected in either raw or boiled SP, were found in fermented SP. The level of each fatty acid or phytosterol increased in fermented SP and decreased in boiled SP. Among the hydrophilic and lipophilic extracts obtained from raw and fermented SPs, the hydrophilic extract of fermented SP exhibited the highest capability of inhibiting cancer-cell PC-12 proliferation. However, each of the extracts had very low cytotoxicities to normal-monkey-kidney-cell growth. The results indicated that SP fermented by L. acidophilus significantly increased free antioxidant-rich phenolics and inhibited cancer-cell-proliferation activity without cytotoxicity to normal cells.

Intraocular Pressure Increases After Intraarticular Knee Injection With Triamcinolone but Not Hyaluronic Acid.

Science.gov (United States)

Taliaferro, Kevin; Crawford, Alexander; Jabara, Justin; Lynch, Jonathan; Jung, Edward; Zvirbulis, Raimonds; Banka, Trevor

2018-03-09

Intraarticular steroid injections are a common first-line therapy for severe osteoarthritis, which affects an estimated 27 million people in the United States. Although topical, oral, intranasal, and inhalational steroids are known to increase intraocular pressure in some patients, the effect of intraarticular steroid injections on intraocular pressure has not been investigated, to the best of our knowledge. If elevated intraocular pressure is sustained for long periods of time or is of sufficient magnitude acutely, permanent loss of the visual field can occur. How does intraocular pressure change 1 week after an intraarticular knee injection either with triamcinolone acetonide or hyaluronic acid? A nonrandomized, nonblinded prospective cohort study was conducted at an outpatient, ambulatory orthopaedic clinic. This study compared intraocular pressure elevation before and 1 week after intraarticular knee injection of triamcinolone acetonide versus hyaluronic acid for management of primary osteoarthritis of the knee. Patients self-selected to be injected in their knee with either triamcinolone acetonide or hyaluronic acid before being informed of the study. The primary endpoint was intraocular pressure elevation of ≥ 7 mm Hg 1 week after injection. This cutoff is determined as the minimum significant pressure change in the ophthalmology literature recognized as an intermediate responder to steroids. Intraocular pressure was measured using a handheld Tono-Pen® applanation device. This device is frequently used in intraocular pressure measurement in clinical and research settings; 10 sequential measurements are obtained and averaged with a confidence interval. Only measurements with a 95% confidence interval were used. Over a 6-month period, a total of 96 patients were approached to enroll in the study. Sixty-two patients out of 96 approached (65%) agreed. Thirty-one (50%) were injected with triamcinolone and 31 (50%) were injected with hyaluronic acid. Patients

Pretreating dogwood seedlings with simulated acidic precipitation increases dogwood anthracnose symptoms in greenhouse-laboratory trials

Energy Technology Data Exchange (ETDEWEB)

Anderson, R.L.; Knighten, J. (USDA Forest Service, Resistance Screening Center, Asheville, NC (United States)); Berrange, P.; Lawton, K.A. (USDA Forest Service, Center for Forest Environmental Studies, Dry Branch, GA (United States)); Britton, K.O. (USDA Forest Service, Southeastern Forest Experiment Station, Athens, GA (United States))

1993-01-01

Dogwood anthracnose is the most damaging disease of flowering dogwood (Cornus florida L.) in a large part of the tree's natural range. It is caused by Discula destructiva infection. Previous attempts to inoculate C. florida to produce anthracnose symptoms have met with limited success except when the leaves were pretreated with acidic water, suggesting that acidic precipitation may predispose dogwoods to the disease. This hypothesis was tested in two greenhouse-laboratory studies in which year-old C. florida seedlings were randomly assigned to four treatments of simulated rain (pH 2.5, 3.5, 4.5, and 5.5) in 1989 and 1990. After 10 applications over a 42-d period, the seedlings were moved to a temperature-controlled laboratory, placed in plastic bags, humidified, and sprayed with a spore suspension of five D. destructiva isolates. About 30 d layter, the seedlings were examined for the percentage of leaves exhibiting anthracnose symptoms and disease severity on affected leaves. Both trials showed that as the acidity of the simulated rain increased, the incidence and severity of anthracnose leaf symptoms increased. The 1989 study included a soil lime treatment that showed the same trend but the overall occurrence and severity of symptoms was higher. 17 refs., 5 tabs.

Role of hemolysis in potassium release by iodinated contrast medium

Energy Technology Data Exchange (ETDEWEB)

Hayakawa, K.; Nakamura, T.; Shimizu, Y. [Department of Radiology, Kyoto City Hospital (Japan)

1999-09-01

It has been demonstrated that an iodinated contrast medium (CM) causes release of potassium into blood vessel lumina, resulting in an increase in serum potassium. The purpose of the present study was to assess whether this potassium release is due to hemolysis. Fresh human blood was mixed in vitro with CM at a ratio of 10:2. Potassium release rates were determined, and serum haptoglobin and free hemoglobin were measured after 30 min of exposure to CM. To compare the potassium release curve between CM exposure and true hemolysis induced by distilled water, fresh human blood was also mixed with distilled water. The level of serum haptoglobin decreased due to hemodilution. Changes in haptoglobin were not correlated with potassium release rates. The serum free hemoglobin level did not increase significantly, and there was no correlation between changes in the free hemoglobin level and the rate of potassium release. Hemolysis caused by water occurred instantaneously, whereas potassium release caused by CM was a slow response, which was linearly correlated with exposure time. Potassium release from blood cannot be explained by hemolysis. (orig.) With 4 figs., 4 tabs., 3 refs.

Hypercholesterolemia increases plasma saturated and n-6 fatty acids altering prostaglandin homeostasis and promotes endothelial dysfunction in rabbits.

Science.gov (United States)

Medina, M; Alberto, M R; Sierra, L; Van Nieuwenhove, C; Saad, S; Isla, M I; Jerez, S

2014-07-01

The present study evaluated the plasma fatty acid levels and the vascular prostaglandin (PG) release in a rabbit model of early hypercholesterolemia with endothelial dysfunction. Rabbits were fed either a control diet (CD) or a diet containing 1 % cholesterol (HD) for 5-6 weeks. The level of fatty acids was measured in plasma. The levels of PG and nitric oxide (NO) released from the aorta were also determined. Vascular morphology of the aorta was characterized by intima and media thickness measurements. The rabbits fed with HD had higher levels of arachidonic acid (ARA) and lower levels of oleic acid. The linoleic acid level was unchanged. PGI(2) and NO were diminished and PGF(2α) levels, the PGI(2)/TXA(2) ratio and the intima/media ratio were increased in rabbits fed with HD. In conclusion, feeding HD for a short period increased ARA plasma levels and unbalanced release of vasodilator/vasoconstrictor PG redirected the pathway to vasoconstrictor metabolite release. These lipid metabolism alterations in addition to the reduced NO levels and the moderate changes in the vascular morphology contributed to the endothelial dysfunction in this animal model. Therefore, the present findings support the importance of early correction or prevention of high cholesterol levels to disrupt the endothelial dysfunction process that leads to cardiovascular disease.

Temperature Increase Negatively Affects the Fatty Acid Bioconversion Capacity of Rainbow Trout (Oncorhynchus mykiss) Fed a Linseed Oil-Based Diet.

Science.gov (United States)

Mellery, Julie; Geay, Florian; Tocher, Douglas R; Kestemont, Patrick; Debier, Cathy; Rollin, Xavier; Larondelle, Yvan

2016-01-01

Aquaculture is meant to provide fish rich in omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA). This objective must be reached despite (1) the necessity to replace the finite and limited fish oil in feed production and (2) the increased temperature of the supply water induced by the global warming. The objective of the present paper was to determine to what extent increased water temperature influences the fatty acid bioconversion capacity of rainbow trout (Oncorhynchus mykiss) fed a plant-derived diet. Fish were fed two diets formulated with fish oil (FO) or linseed oil (LO) as only added lipid source at the optimal water temperature of 15°C or at the increased water temperature of 19°C for 60 days. We observed that a temperature increase close to the upper limit of the species temperature tolerance range negatively affected the feed efficiency of rainbow trout fed LO despite a higher feed intake. The negative impact of increased water temperature on fatty acid bioconversion capacity appeared also to be quite clear considering the reduced expression of fatty acid desaturase 2 in liver and intestine and the reduced Δ6 desaturase enzymatic activity in intestinal microsomes. The present results also highlighted a negative impact of increased temperature on the apparent in vivo enzymatic activity of Δ5 and Δ6 desaturases of fish fed LO. Interestingly, this last parameter appeared less affected than those mentioned above. This study highlights that the increased temperature that rainbow trout may face due to global warming could reduce their fatty acid bioconversion capacity. The unavoidable replacement of finite fish oil by more sustainable, readily available and economically viable alternative lipid sources in aquaculture feeds should take this undeniable environmental issue on aquaculture productivity into account.

Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans.

Science.gov (United States)

Herbel, B K; McGuire, M K; McGuire, M A; Shultz, T D

1998-02-01

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid (LA) with conjugated double bonds. CLA has anticarcinogenic properties and has been identified in human tissues, dairy products, meats, and certain vegetable oils. A variety of animal products are good sources of CLA, but plant oils contain much less. However, plant oils are a rich source of LA, which may be isomerized to CLA by intestinal microorganisms in humans. To investigate the effect of triacylglycerol-esterified LA consumption on plasma concentrations of esterified CLA in total lipids, a dietary intervention (6 wk) was conducted with six men and six women. During the intervention period a salad dressing containing 21 g safflower oil providing 16 g LA/d was added to the subjects' daily diets. Three-day diet records and fasting blood were obtained initially and during dietary and postdietary intervention periods. Although LA intake increased significantly during the dietary intervention, plasma CLA concentrations were not affected. Plasma total cholesterol and LDL-cholesterol concentrations were significantly lower after addition of safflower oil to the diet. In summary, consumption of triacylglycerol-esterified LA in safflower oil did not increase plasma concentrations of esterified CLA in total lipids.

Haptoglobin is a serological biomarker for adenocarcinoma lung cancer by using the ProteomeLab PF2D combined with mass spectrometry.

Science.gov (United States)

Chang, You-Kang; Lai, Yu-Heng; Chu, Yen; Lee, Ming-Cheng; Huang, Chun-Yao; Wu, Semon

2016-01-01

Identification of serological biomarker is urgently needed for cancer screening, monitoring cancer progression, treatment response, and surveillance for recurrence in lung cancer. Therefore, we try to find new serological biomarker that has more specificity and sensitivity for lung cancer diagnostics. In this study, the 2-D liquid phase fractionation system (PF2D) and mass spectrometry approach has been used for comparison the serum profiles between lung cancer patients and healthy individuals. Eight proteins were identified form PF2D and subsequently by mass spectrometry. Among these proteins, haptoglobin (HP) and apolipoprotein AI (APOA1) were chosen and validated with turbidimetric assay. We found that HP levels were significantly higher and APOA1 levels were significantly lower in lung cancer patients. However, after the participants were stratified by gender, the expression trends of HP and APOA1 in lung cancer patients existed only in men, which is gender specific phenomenon. HP, APOA1 and carcinoembryonic antigen (CEA), used for distinguishing lung adenocarcinoma, had a sensitivity of 64%, 64% and 79%, respectively. Area under the ROC curve (AUC) of HP, APOA1 and CEA were 0.768, 0.761 and 0.884, respectively. When restricted to male subjects, HP, APOA1 and CEA showed sensitivity of 89%, 73% and 100%, respectively. AUC of HP, APOA1 and CEA were 0.929, 0.840 and 0.877, respectively. Therefore, our results showed that combined with PF2D system and mass spectrometry, this is a promising novel approach to identify new serological biomarkers for lung cancer research. In addition, HP may be a potential serological biomarker for lung adenocarcinoma diagnostics, especially in male subjects.

Retroconversion is a minor contributor to increases in eicosapentaenoic acid following docosahexaenoic acid feeding as determined by compound specific isotope analysis in rat liver.

Science.gov (United States)

Metherel, Adam H; Chouinard-Watkins, Raphaël; Trépanier, Marc-Olivier; Lacombe, R J Scott; Bazinet, Richard P

2017-01-01

Dietary docosahexaenoic acid (DHA, 22:6n-3) not only increases blood and tissue levels of DHA, but also eicosapentaenoic acid (EPA, 20:5n-3). It is generally believed that this increase is due to DHA retroconversion to EPA, however, a slower conversion of α-linolenic acid (ALA, 18:3n-3) derived EPA to downstream metabolic products (i.e. slower turnover of EPA) is equally plausible. In this study, 21-day old Long Evans rats were weaned onto an ALA only or DHA + ALA diet for 12 weeks. Afterwards, livers were collected and the natural abundance 13 C-enrichment was determined by compound specific isotope analysis (CSIA) of liver EPA by isotope ratio mass-spectrometry and compared to dietary ALA and DHA 13 C-enrichment. Isotopic signatures (per mil, ‰) for liver EPA were not different ( p  > 0.05) between the ALA only diet (-25.89 ± 0.39 ‰, mean ± SEM) and the DHA + ALA diet (-26.26 ± 0.40 ‰), suggesting the relative contribution from dietary ALA and DHA to liver EPA did not change. However, with DHA feeding estimates of absolute EPA contribution from ALA increased 4.4-fold (147 ± 22 to 788 ± 153 nmol/g) compared to 3.2-fold from DHA (91 ± 14 to 382 ± 13 nmol/g), respectively. In conclusion, CSIA of liver EPA in rats following 12-weeks of dietary DHA suggests that retroconversion of DHA to EPA is a relatively small contributor to increases in EPA, and that this increase in EPA is largely coming from elongation/desaturation of ALA.

An Increase in Healthcare-Associated Clostridium difficile Infection Associated with Use of a Defective Peracetic Acid-Based Surface Disinfectant.

Science.gov (United States)

Cadnum, Jennifer L; Jencson, Annette L; O'Donnell, Marguerite C; Flannery, Elizabeth R; Nerandzic, Michelle M; Donskey, Curtis J

2017-03-01

BACKGROUND We investigated an increase in the incidence of healthcare-associated Clostridium difficile infection (CDI) that occurred following a change from a bleach disinfectant to a peracetic acid-based disinfectant. OBJECTIVE To evaluate the efficacy of the peracetic acid-based disinfectant. DESIGN Laboratory-based product evaluation. METHODS The commercial peracetic acid-based product is activated on site by mixing a small volume of concentrated hydrogen peroxide and peracetic acid present in a "SmartCap" reservoir with the remaining contents of the container. We measured concentrations of peracetic acid in newly activated and in-use product and determined the stability of nonactivated and activated product. We tested the efficacy of the product against C. difficile spores using the American Society for Testing and Materials standard quantitative carrier disk test method. RESULTS Measured concentrations of peracetic acid (50-800 parts per million [ppm]) were significantly lower than the level stated on the product label (1,500 ppm), and similar results were obtained for containers from multiple lot numbers and from another hospital. Product with peracetic acid levels below 600 ppm had significantly reduced activity against C. difficile spores. Peracetic acid concentrations were reduced markedly after storage of either activated or nonactivated product for several weeks. The Environmental Protection Agency confirmed the finding of low disinfectant levels and ordered discontinuation of sale of the product. CONCLUSION Use of a defective peracetic acid-based surface disinfectant may have contributed to an increase in healthcare-associated CDI. Our findings highlight the importance of evaluating the efficacy of liquid disinfectants in healthcare settings. Infect Control Hosp Epidemiol 2017;38:300-305.

Increasing the Analytical Sensitivity by Oligonucleotides Modified with Para- and Ortho-Twisted Intercalating Nucleic Acids - TINA

DEFF Research Database (Denmark)

Schneider, Uffe V; Géci, Imrich; Jøhnk, Nina

2011-01-01

-TINA molecules increased the melting point (Tm) of Watson-Crick based antiparallel DNA duplexes. The increase in Tm was greatest when the intercalators were placed at the 5' and 3' termini (preferable) or, if placed internally, for each half or whole helix turn. Terminally positioned TINA molecules improved......The sensitivity and specificity of clinical diagnostic assays using DNA hybridization techniques are limited by the dissociation of double-stranded DNA (dsDNA) antiparallel duplex helices. This situation can be improved by addition of DNA stabilizing molecules such as nucleic acid intercalators....... Here, we report the synthesis of a novel ortho-Twisted Intercalating Nucleic Acid (TINA) amidite utilizing the phosphoramidite approach, and examine the stabilizing effect of ortho- and para-TINA molecules in antiparallel DNA duplex formation. In a thermal stability assay, ortho- and para...

Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms in dilutional pseudoanemia (sports anemia).

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Miranda-Vilela, Ana L; Akimoto, Arthur K; Alves, Penha C Z; Pereira, Luiz C S; Klautau-Guimarães, Maria N; Grisolia, Cesar K

2010-04-01

Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb.) is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration) and RDW (red cell distribution width), the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects.

Increase in protoporphyrin IX after 5-aminolevulinic acid based photodynamic therapy is due to local re-synthesis

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de Bruijn, Henriëtte S.; Kruijt, Bastiaan; van der Ploeg-van den Heuvel, Angélique; Sterenborg, Henricus J. C. M.; Robinson, Dominic J.

2007-01-01

Protoporphyrin IX (PpIX) fluorescence that is bleached during aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) increases again in time after treatment. In the present study we investigated if this increase in PpIX fluorescence after illumination is the result of local re-synthesis or of

Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

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Samman S

2014-06-01

Full Text Available Samir Samman,1 Ben Crossett,2 Miles Somers,1 Kirstine J Bell,1 Nicole T Lai,1,3 David R Sullivan,3 Peter Petocz4 1Discipline of Nutrition and Metabolism, 2Discipline of Proteomics and Biotechnology, School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia; 3Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 4Department of Statistics, Macquarie University, Sydney, NSW, Australia Abstract: Amino acid (AA status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM or chicken (CM, and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014, with consistently higher changes observed after 60 minutes (P<0.001. Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the

Increased urinary imidazolepropionic acid, n-acetylhistamine and other imidazole compounds in patients with intestinal disorders

NARCIS (Netherlands)

Heiden, C. van der; Wadman, S.K.; Bree, P.K. de; Wauters, E.A.K.

In 26 out of a large group of patients with gastrointestinal disorders abnormal urinary imidazole excretion patterns were found. Most frequently excessive or increased amounts of imidazolepropionic acid (ImPA) occurred, and as next N-acetylhistamine was excreted in excess. In a number of cases the

THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

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Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

2013-06-07

Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

Acetic acid increases the phage-encoded enterotoxin A expression in Staphylococcus aureus

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da Silva Ayla

2010-05-01

Full Text Available Abstract Background The effects of acetic acid, a common food preservative, on the bacteriophage-encoded enterotoxin A (SEA expression and production in Staphylococcus aureus was investigated in pH-controlled batch cultures carried out at pH 7.0, 6.5, 6.0, 5.5, 5.0, and 4.5. Also, genomic analysis of S. aureus strains carrying sea was performed to map differences within the gene and in the temperate phage carrying sea. Results The sea expression profile was similar from pH 7.0 to 5.5, with the relative expression peaking in the transition between exponential and stationary growth phase and falling during stationary phase. The levels of sea mRNA were below the detection limit at pH 5.0 and 4.5, confirmed by very low SEA levels at these pH values. The level of relative sea expression at pH 6.0 and 5.5 were nine and four times higher, respectively, in the transitional phase than in the exponential growth phase, compared to pH 7.0 and pH 6.5, where only a slight increase in relative expression in the transitional phase was observed. Furthermore, the increase in sea expression levels at pH 6.0 and 5.5 were observed to be linked to increased intracellular sea gene copy numbers and extracellular sea-containing phage copy numbers. The extracellular SEA levels increased over time, with highest levels produced at pH 6.0 in the four growth phases investigated. Using mitomycin C, it was verified that SEA was at least partially produced as a consequence of prophage induction of the sea-phage in the three S. aureus strains tested. Finally, genetic analysis of six S. aureus strains carrying the sea gene showed specific sea phage-groups and two versions of the sea gene that may explain the different sea expression and production levels observed in this study. Conclusions Our findings suggest that the increased sea expression in S. aureus caused by acetic acid induced the sea-encoding prophage, linking SEA production to the lifecycle of the phage.

Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity.

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Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M; Park, Jin-Byung

The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3 Leads to Increase of the Fatty Acid Biotransformation Activity.

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Ji-Min Woo

Full Text Available The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid-induced stress. The metabolic and genomic responses of E. coli BL21(DE3 and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3. Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3 expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1 into n-heptanoic acid (5 and 11-hydroxyundec-9-enoic acid (4. This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

Topiramate increases the risk of valproic acid-induced encephalopathy.

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Noh, Young; Kim, Dong Wook; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Moon, Hye-Jin; Lee, Sang Kun

2013-01-01

Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice.

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Meissner, Maxi; Lombardo, Elisa; Havinga, Rick; Tietge, Uwe J F; Kuipers, Folkert; Groen, Albert K

2011-10-01

Regular physical activity decreases the risk for atherosclerosis but underlying mechanisms are not fully understood. We questioned whether voluntary wheel running provokes specific modulations in cholesterol turnover that translate into a decreased atherosclerotic burden in hypercholesterolemic mice. Male LDLR-deficient mice (8 weeks old) had either access to a voluntary running wheel for 12 weeks (RUN) or remained sedentary (CONTROL). Both groups were fed a western-type/high cholesterol diet. Running activity and food intake were recorded. At 12 weeks of intervention, feces, bile and plasma were collected to determine fecal, biliary and plasma parameters of cholesterol metabolism and plasma cytokines. Atherosclerotic lesion size was determined in the aortic root. RUN weighed less (∼13%) while food consumption was increased by 17% (p=0.004). Plasma cholesterol levels were decreased by 12% (p=0.035) and plasma levels of pro-atherogenic lipoproteins decreased in RUN compared to control. Running modulated cholesterol catabolism by enhancing cholesterol turnover: RUN displayed an increased biliary bile acid secretion (68%, p=0.007) and increased fecal bile acid (93%, p=0.009) and neutral sterol (33%, p=0.002) outputs compared to control indicating that reverse cholesterol transport was increased in RUN. Importantly, aortic lesion size was decreased by ∼33% in RUN (p=0.033). Voluntary wheel running reduces atherosclerotic burden in hypercholesterolemic mice. An increased cholesterol turnover, specifically its conversion into bile acids, may underlie the beneficial effect of voluntary exercise in mice. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Role of a single amino acid substitution of VP3 H142D for increased acid resistance of foot-and-mouth disease virus serotype A.

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Biswal, Jitendra K; Das, Biswajit; Sharma, Gaurav K; Khulape, Sagar A; Pattnaik, Bramhadev

2016-04-01

Foot-and-mouth disease virus (FMDV) particles lose infectivity due to their dissociation into pentamers at pH value below 6.5. After the uptake of FMDV by receptor-mediated endocytosis, the acid-dependent dissociation process is required for the release of FMDV genome inside endosomes. Nevertheless, dissociation of FMDV particles in mildly acidic conditions renders the inactivated FMD vaccine less effective. To improve the acid stability of inactivated FMD vaccine during the manufacturing process, a serotype A IND 40/2000 (in-use vaccine strain) mutant with increased resistance to acid inactivation was generated through reverse genetics approach. Based upon the earlier reports, the crucial amino acid residue, H142 of VP3 capsid protein was substituted separately to various amino acid residues Arg (R), Phe (F), Ala (A), and Asp (D) on the full-genome length cDNA clone. While the H142 → R or H142 → F or H142 → A substitutions resulted in non-infectious FMDV, H142 → D mutation on VP3 protein (H3142D) resulted in the generation of mutant virus with enhanced resistance to acid-induced inactivation. In addition, H3142D substitution did not alter the replication ability and antigenicity of mutant as compared to the parental virus. However, the virus competition experiments revealed that the H3142D substitution conferred a loss of fitness for the mutant virus. Results from this study demonstrate that the H3142D substitution is the molecular determinant of acid-resistant phenotype in FMDV serotype A.

Milk production and nutrient digestibility responses to increasing levels of stearic acid supplementation of dairy cows.

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Boerman, J P; de Souza, J; Lock, A L

2017-04-01

The objective of our study was to evaluate the dose-response effects of a stearic acid (C18:0)-enriched supplement on nutrient digestibility, production responses, and the maximum amount of C18:0 that can be incorporated into the milk fat of dairy cows. Multiparous Holstein cows (n = 32; 145 ± 66 d in milk) with a wide range in milk yield (30 to 70 kg/d) were blocked by milk yield and assigned to replicated 4 × 4 Latin squares. Treatments were diets supplemented with a C18:0-enriched supplement (SA; 93% C18:0) at 0, 0.80, 1.50, or 2.30% of diet dry matter (DM). Periods were 21 d with the final 5 d used for data and sample collection. Dry matter intake increased linearly as SA supplementation increased. Supplementation of SA had no effect on the yield of milk or milk components. Due to the increase in DM intake, SA linearly reduced the ratio of energy-corrected milk to DM intake. Supplementation of SA did not affect body weight. Increasing SA reduced digestibility of 16-carbon, 18-carbon, and total fatty acids (FA), with the reduction in digestibility of 18-carbon FA being approximately 30 percentage units from the 0.0 to 2.30% SA supplemented diets. Supplementation of SA linearly increased concentrations of preformed milk fatty acids (FA) but did not affect the yield of preformed milk FA. Yields of C18:0 plus cis-9 C18:1 were increased by SA supplementation; however, the increase from 0 to 2.3% SA was only 16 g/d. The concentration and yield of de novo and 16-carbon milk FA were unaffected by SA supplementation. In conclusion, increasing doses of SA decreased FA digestibility and had little effect on production parameters. Although SA increased the yield of C18:0 and cis-9 C18:1 in milk fat, it had no overall effect on milk fat yield. The lack of production responses to a C18:0-enriched fat supplement was most likely associated with the marked decrease in FA digestibility. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights

Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss.

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Donatella Granchi

Full Text Available The extracellular acidic milieu in bones results in activation of osteoclasts (OC and inhibition of osteoblasts (OB causing a net loss of calcium from the skeleton and the deterioration of bone microarchitecture. Alkalinization through supplementation with potassium citrate (K citrate has been proposed to limit the osteopenia progression, even though its pharmacological activity in bone microenvironment is not well defined. We evaluated if K citrate was able to prevent the adverse effects that acidic milieu induces on bone cells. OC and OB were maintained in neutral (pH 7.4 versus acidic (pH 6.9 culture medium, and treated with different K citrate concentrations. We evaluated the OC differentiation at seven days, by counting of multinucleated cells expressing tartrate-resistant acid phosphatase, and the activity of mature OC at 14 days, by quantifying of collagen degradation. To evaluate the effects on OB, we analyzed proliferation, mineralization, and expression of bone-related genes. We found that the low pH increased OC differentiation and activity and decreased OB function. The osteoclastogenesis was also promoted by RANKL concentrations ineffective at pH 7.4. Non-cytotoxic K citrate concentrations were not sufficient to steadily neutralize the acidic medium, but a inhibited the osteoclastogenesis, the collagen degradation, and the expression of genes involved in RANKL-mediated OC differentiation, b enhanced OB proliferation and alkaline phosphatase expression, whereas it did not affect the in vitro mineralization, and c were effective also in OC cultures resistant to alendronate, i.e. the positive control of osteoclastogenesis inhibition. In conclusion, K citrate prevents the increase in OC activity induced by the acidic microenvironment, and the effect does not depend exclusively on its alkalizing capacity. These data provide the biological basis for the use of K citrate in preventing the osteopenia progression resulting from low

Non-invasive Oil-Based Method to Increase Topical Delivery of Nucleic Acids to Skin.

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Vij, Manika; Alam, Shamshad; Gupta, Nidhi; Gotherwal, Vishvabandhu; Gautam, Hemlata; Ansari, Kausar M; Santhiya, Deenan; Natarajan, Vivek T; Ganguli, Munia

2017-06-07

Topical delivery of nucleic acids to skin has huge prospects in developing therapeutic interventions for cutaneous disorders. In spite of initial success, clinical translation is vastly impeded by the constraints of bioavailability as well as stability in metabolically active environment of skin. Various physical and chemical methods used to overcome these limitations involve invasive procedures or compounds that compromise skin integrity. Hence, there is an increasing demand for developing safe skin penetration enhancers for efficient nucleic acid delivery to skin. Here, we demonstrate that pretreatment of skin with silicone oil can increase the transfection efficiency of non-covalently associated peptide-plasmid DNA nanocomplexes in skin ex vivo and in vivo. The method does not compromise skin integrity, as indicated by microscopic evaluation of cellular differentiation, tissue architecture, enzyme activity assessment, dye penetration tests using Franz assay, and cytotoxicity and immunogenicity analyses. Stability of nanocomplexes is not hampered on pretreatment, thereby avoiding nuclease-mediated degradation. The mechanistic insights through Fourier transform infrared (FTIR) spectroscopy reveal some alterations in the skin hydration status owing to possible occlusion effects of the enhancer. Overall, we describe a topical, non-invasive, efficient, and safe method that can be used to increase the penetration and delivery of plasmid DNA to skin for possible therapeutic applications. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degenerations⃞

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Tanito, Masaki; Brush, Richard S.; Elliott, Michael H.; Wicker, Lea D.; Henry, Kimberly R.; Anderson, Robert E.

2009-01-01

The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 to n-3 PUFA. Mice carrying the fat-1 transgene and wild-type controls were fed an n-3-deficient/n-6-enriched diet [fat-1- safflower oil (SFO) and wt-SFO, respectively]. Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver demonstrated significantly lower n-6/n-3 ratios and higher docosahexaenoic acid (DHA) levels in fat-1-SFO compared with wt-SFO. When mice were exposed to light stress: 1) the outer nuclear layer (ONL) thickness was reduced; 2) amplitudes of the electroretinogram (ERG) were lower; 3) the number of apoptotic photoreceptor cells was greater; and 4) modification of retinal proteins by 4-hydroxyhexenal (4-HHE), an end-product of n-3 PUFA oxidation was increased in both fat-1-SFO and wt mice fed a regular lab chow diet compared with wt-SFO. The results indicate a positive correlation between the level of DHA, the degree of n-3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. In mice not exposed to intense light, the reduction in DHA resulted in reduced efficacy in phototransduction gain steps, while no differences in the retinal morphology or retinal biochemistry. These results highlight the dual roles of DHA in cellular physiology and pathology. PMID:19023138

Dietary fatty acid enrichment increases egg size and quality of yellow seahorse Hippocampus kuda.

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Saavedra, M; Masdeu, M; Hale, P; Sibbons, C M; Holt, W V

2014-02-01

Seahorses populations in the wild have been declining and to restore them a better knowledge of seahorse reproduction is required. This study examines the effect of dietary quality on seahorse fecundity and egg quality. Two different diets were tested with Hippocampus kuda females: frozen mysis (control) and frozen mysis enriched with a liposome spray containing essential fatty acids. Diets were given to females (two groups of five) over a seven week period. After this period, males (fed the control diet) and females were paired and the eggs dropped by the females were collected. Fatty acid profile were analysed and eggs were counted and measured. Results showed that females fed on enriched mysis had larger eggs and that these had a higher content of total polyunsaturated fatty acids. The size of the egg was especially affected in the first spawn, where egg size for females fed the enriched diet was significantly higher than the egg size from control females. This effect was reduced in the following spawning where no significant differences were found. Egg size is an important quality descriptor as seahorse juveniles originating from smaller eggs and/or eggs of poor quality will have less chances of overcoming adverse conditions in the wild and consequently have lower survival and growth rates. This study shows that enriching frozen mysis with polyunsaturated fatty acids increases egg size and egg quality of H. kuda. Copyright © 2013 Elsevier B.V. All rights reserved.

Overexpression of NtWRKY50 Increases Resistance to Ralstonia solanacearum and Alters Salicylic Acid and Jasmonic Acid Production in Tobacco.

Science.gov (United States)

Liu, Qiuping; Liu, Ying; Tang, Yuanman; Chen, Juanni; Ding, Wei

2017-01-01

WRKY transcription factors (TFs) modulate plant responses to biotic and abiotic stresses. Here, we characterized a WRKY IIc TF, NtWRKY50, isolated from tobacco ( Nicotiana tabacum ) plants. The results showed that NtWRKY50 is a nuclear-localized protein and that its gene transcript is induced in tobacco when inoculated with the pathogenic bacterium Ralstonia solanacearum . Overexpression of NtWRKY50 enhanced bacterial resistance, which correlated with enhanced SA and JA/ET signaling genes. However, silencing of the NtWRKY50 gene had no obvious effects on plant disease resistance, implying functional redundancy of NtWRKY50 with other TFs. In addition, it was found that NtWRKY50 can be induced by various biotic or abiotic stresses, such as Potato virus Y, Rhizoctonia solani, Phytophthora parasitica , hydrogen peroxide, heat, cold, and wounding as well as the hormones salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). Importantly, additional analysis suggests that NtWRKY50 overexpression markedly promotes SA levels but prevents pathogen-induced JA production. These data indicate that NtWRKY50 overexpression leads to altered SA and JA content, increased expression of defense-related genes and enhanced plant resistance to R. solanacearum. These probably due to increased activity of endogenous NtWRKY50 gene or could be gain-of-function phenotypes by altering the profile of genes affected by NtWRKY50 .

Soy-dairy protein blend and whey protein ingestion after resistance exercise increases amino acid transport and transporter expression in human skeletal muscle

Science.gov (United States)

Reidy, P. T.; Walker, D. K.; Dickinson, J. M.; Gundermann, D. M.; Drummond, M. J.; Timmerman, K. L.; Cope, M. B.; Mukherjea, R.; Jennings, K.; Volpi, E.

2014-01-01

Increasing amino acid availability (via infusion or ingestion) at rest or postexercise enhances amino acid transport into human skeletal muscle. It is unknown whether alterations in amino acid availability, from ingesting different dietary proteins, can enhance amino acid transport rates and amino acid transporter (AAT) mRNA expression. We hypothesized that the prolonged hyperaminoacidemia from ingesting a blend of proteins with different digestion rates postexercise would enhance amino acid transport into muscle and AAT expression compared with the ingestion of a rapidly digested protein. In a double-blind, randomized clinical trial, we studied 16 young adults at rest and after acute resistance exercise coupled with postexercise (1 h) ingestion of either a (soy-dairy) protein blend or whey protein. Phenylalanine net balance and transport rate into skeletal muscle were measured using stable isotopic methods in combination with femoral arteriovenous blood sampling and muscle biopsies obtained at rest and 3 and 5 h postexercise. Phenylalanine transport into muscle and mRNA expression of select AATs [system L amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, system A amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, cationic amino acid transporter 1/SLC7A1] increased to a similar extent in both groups (P protein blend resulted in a prolonged and positive net phenylalanine balance during postexercise recovery compared with whey protein (P protein synthesis increased similarly between groups. We conclude that, while both protein sources enhanced postexercise AAT expression, transport into muscle, and myofibrillar protein synthesis, postexercise ingestion of a protein blend results in a slightly prolonged net amino acid balance across the leg compared with whey protein. PMID:24699854

Analysis of proteomic changes of the serum of irradiated mice

International Nuclear Information System (INIS)

Wang Zhidong; Chen Xiaohua; Dong Bo; Zhang Junquan; Rao Yalan; Gao Ronglian; Hou Lili; Mao Bingzhi

2005-01-01

To explore the early diagnostic factors, new therapeutic targets and mechanisms of acute radiation disease. Proteomic changes of the serum of irradiated mice were studied using 2-DE and Q-TOF-MS approaches. One higher level expressed protein after the irradiation was found, and it was identified as α chain of haptoglobin by Q-TOF-MS. The authors confirmed the result by Western blotting with anti-haptoglobin antibody. Haptoglobin may involve in the process of acute radiation injury. (authors)

Serum proteinogram in sheep with acute ruminal lactic acidosis

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Amanda F. Sabes

2017-06-01

Full Text Available The electrophoretic fractionation represents one of the most reliable methods for the identification of blood proteins in ruminants. The aim of this study was to evaluate the serum proteinogram of sheep with acute ruminal lactic acidosis (ARA using the SDS-PAGE electrophoresis technique. Ten Santa Inês ewes were used and blood was collected to establish the basal values for induction of ARA. Sucrose was administered orally in a single dose of 15 g/kg body mass. After the administration, blood samples were obtained at the following moments: 4, 8, 12, 16, 20, 24, 28, 32, 36, 48, 72, 96, 120 and 144 h. Subsequently, samples were obtained every seven days for three further weeks, until complete one month. The total of 13 proteins were identified: immunoglobulins A and G, ceruloplasmin, transferrin, albumin, α1-antitrypsin, haptoglobin, α1-acid glycoprotein, proteins of molecular weight 95, 46, 36 and 31 kDa. The increase of haptoglobin from 08 h coincides with the ruminal pH decrease, possibly due to the death of Gram negative bacteria and also the inflammatory process on the rumen. Fibrinogen was presented on highest mean at 48 h and returned to normal with 144 h. We can conclude that changes in serum levels of acute phase proteins can assist the clinical evaluation and diagnosis of ARA in sheep.

Determination of dissociation constants or propionic acid and lactic acid (2-hydroxypropionic acid) by potentiometry and conductometry

International Nuclear Information System (INIS)

Saeeduddin; Khanzada, A.W.K.

2004-01-01

Dissociation constants of propionic acid and 2-hydroxypropionic acid (lactic acid) have been studied at different temperatures between 25 to 50 deg. C interval. Propionic acid is analyzed by conductometry while 2-hydroxypropionic acid is analyzed by potentiometry. Both investigated compounds are symmetrical carboxylic acids having same length of carbon chain but are markedly different in ionic behavior. We were interested to see how the hydroxyl group (-OH) induction in propionic acid affects on pKa values of 2-hydroxypropionic acid. We observed that as temperature increases pKa values increase. The increase is observed for both the investigated compounds. PKa values of 2-hydroxypropionic acid are lower as compared to propionic acid because of electron withdrawing (-OH). (author)

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

Directory of Open Access Journals (Sweden)

Stephanie K Venn-Watson

Full Text Available 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.

Military training elicits marked increases in plasma metabolomic signatures of energy metabolism, lipolysis, fatty acid oxidation, and ketogenesis.

Science.gov (United States)

Karl, J Philip; Margolis, Lee M; Murphy, Nancy E; Carrigan, Christopher T; Castellani, John W; Madslien, Elisabeth H; Teien, Hilde-Kristin; Martini, Svein; Montain, Scott J; Pasiakos, Stefan M

2017-09-01

Military training studies provide unique insight into metabolic responses to extreme physiologic stress induced by multiple stressor environments, and the impacts of nutrition in mediating these responses. Advances in metabolomics have provided new approaches for extending current understanding of factors modulating dynamic metabolic responses in these environments. In this study, whole-body metabolic responses to strenuous military training were explored in relation to energy balance and macronutrient intake by performing nontargeted global metabolite profiling on plasma collected from 25 male soldiers before and after completing a 4-day, 51-km cross-country ski march that produced high total daily energy expenditures (25.4 MJ/day [SD 2.3]) and severe energy deficits (13.6 MJ/day [SD 2.5]). Of 737 identified metabolites, 478 changed during the training. Increases in 88% of the free fatty acids and 91% of the acylcarnitines, and decreases in 88% of the mono- and diacylglycerols detected within lipid metabolism pathways were observed. Smaller increases in 75% of the tricarboxylic acid cycle intermediates, and 50% of the branched-chain amino acid metabolites detected were also observed. Changes in multiple metabolites related to lipid metabolism were correlated with body mass loss and energy balance, but not with energy and macronutrient intakes or energy expenditure. These findings are consistent with an increase in energy metabolism, lipolysis, fatty acid oxidation, ketogenesis, and branched-chain amino acid catabolism during strenuous military training. The magnitude of the energy deficit induced by undereating relative to high energy expenditure, rather than macronutrient intake, appeared to drive these changes, particularly within lipid metabolism pathways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Increased missense mutation burden of Fatty Acid metabolism related genes in nunavik inuit population.

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Zhou, Sirui; Xiong, Lan; Xie, Pingxing; Ambalavanan, Amirthagowri; Bourassa, Cynthia V; Dionne-Laporte, Alexandre; Spiegelman, Dan; Turcotte Gauthier, Maude; Henrion, Edouard; Diallo, Ousmane; Dion, Patrick A; Rouleau, Guy A

2015-01-01

Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism. Exome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals. Altogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians. The increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit.

Selection of protease for increased solubilization of protein-derived thiols during mashing with limited release of free amino acids in beer

DEFF Research Database (Denmark)

Murmann, Anne Nordmark; Lunde, Christina; Lund, Marianne Nissen

2016-01-01

Extraction of protein-derived thiols by protease treatment during mashing for improvement of flavor stability in beer has previously been shown to cause concomitant increase in free amino acid concentrations and thereby increased levels of unwanted Maillard reaction products during aging. The pre......Extraction of protein-derived thiols by protease treatment during mashing for improvement of flavor stability in beer has previously been shown to cause concomitant increase in free amino acid concentrations and thereby increased levels of unwanted Maillard reaction products during aging...... of a protease with a higher temperature optimum dosed at only 3 mg of enzyme/kg of malt, it is possible to increase thiol concentrations in wort by 30% and with only a maximum 10% increase in amino acid concentration compared with a control. Pilot brewing showed that beer brewed with addition of protease...... stability during storage could not be evaluated. Overall, similar brewing and sensory characteristics were obtained compared with a control beer brewed without addition of protease. Foam stability was decreased by protease treatment, and formation of haze was reduced by protease treatment....

Salicylate prevents virus-induced type 1 diabetes in the BBDR rat.

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Chaoxing Yang

Full Text Available Epidemiologic and clinical evidence suggests that virus infection plays an important role in human type 1 diabetes pathogenesis. We used the virus-inducible BioBreeding Diabetes Resistant (BBDR rat to investigate the ability of sodium salicylate, a non-steroidal anti-inflammatory drug (NSAID, to modulate development of type 1 diabetes. BBDR rats treated with Kilham rat virus (KRV and polyinosinic:polycytidylic acid (pIC, a TLR3 agonist develop diabetes at nearly 100% incidence by ~2 weeks. We found distinct temporal profiles of the proinflammatory serum cytokines, IL-1β, IL-6, IFN-γ, IL-12, and haptoglobin (an acute phase protein in KRV+pIC treated rats. Significant elevations of IL-1β and IL-12, coupled with sustained elevations of haptoglobin, were specific to KRV+pIC and not found in rats co-treated with pIC and H1, a non-diabetogenic virus. Salicylate administered concurrently with KRV+pIC inhibited the elevations in IL-1β, IL-6, IFN-γ and haptoglobin almost completely, and reduced IL-12 levels significantly. Salicylate prevented diabetes in a dose-dependent manner, and diabetes-free animals had no evidence of insulitis. Our data support an important role for innate immunity in virus-induced type 1 diabetes pathogenesis. The ability of salicylate to prevent diabetes in this robust animal model demonstrates its potential use to prevent or attenuate human autoimmune diabetes.

Dairy fat blends high in α-linolenic acid are superior to n-3 fatty-acid-enriched palm oil blends for increasing DHA levels in the brains of young rats.

Science.gov (United States)

Du, Qin; Martin, Jean-Charles; Agnani, Genevieve; Pages, Nicole; Leruyet, Pascale; Carayon, Pierre; Delplanque, Bernadette

2012-12-01

Achieving an appropriate docosahexaenoic acid (DHA) status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how different dietary fat matrices improved DHA content in the brains of both male and female rats. Forty rats of each gender were born from dams fed over gestation and lactation with a low α-linolenic acid (ALA) diet (0.4% of fatty acids) and subjected for 6 weeks after weaning to a palm oil blend-based diet (10% by weight) that provided either 1.5% ALA or 1.5% ALA and 0.12% DHA with 0.4% arachidonic acid or to an anhydrous dairy fat blend that provided 1.5% or 2.3% ALA. Fatty acids in the plasma, red blood cells (RBCs) and whole brain were determined by gas chromatography. The 1.5% ALA dairy fat was superior to both the 1.5% ALA palm oil blends for increasing brain DHA (14.4% increase, PDHA due to a gender-to-diet interaction, with dairy fats attenuating the gender effect. Brain DHA was predicted with a better accuracy by some plasma and RBC fatty acids when used in combination (R(2) of 0.6) than when used individually (R(2)=0.47 for RBC n-3 docosapentaenoic acid at best). In conclusion, dairy fat blends enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of postweaning rats. Human applications are worth considering. Copyright © 2012 Elsevier Inc. All rights reserved.

Nutrient digestibility and milk production responses to increasing levels of palmitic acid supplementation vary in cows receiving diets with or without whole cottonseed.

Science.gov (United States)

Rico, J E; de Souza, J; Allen, M S; Lock, A L

2017-01-01

Our study evaluated the dose-dependent effects of a palmitic acid-enriched supplement in basal diets with or without the inclusion of whole cottonseed on nutrient digestibility and production responses of dairy cows. Sixteen Holstein cows (149 ± 56 days in milk) were used in a split plot Latin square design experiment. Cows were blocked by 3.5% fat-corrected milk (FCM) and allocated to a main plot receiving either a basal diet with soyhulls (SH, = 8) or a basal diet with whole cottonseed (CS, = 8) that was fed throughout the experiment. A palmitic acid-enriched supplement (PA 88.5% C16:0) was fed at 0, 0.75, 1.50, or 2.25% of ration DM in a replicated 4 × 4 Latin Square design within each basal diet group. Periods were 14 d with the final 4 d used for data collection. PA dose increased milk fat content linearly, and cubically affected yields of milk fat and 3.5% FCM. The PA dose did not affect milk protein and lactose contents, BW, and BCS, but tended to increase yields of milk, milk protein, and milk lactose. Also, PA dose reduced DMI and 16-carbon fatty acid digestibility quadratically, and increased 18-carbon fatty acid digestibility quadratically. There were no effects of basal diet on the yield of milk or milk components, but DMI tended to decrease in CS compared with SH, increasing feed efficiency (3.5% FCM/DMI). Compared with SH, CS diets increased yield of preformed milk fatty acids and 16-carbon fatty acid digestibility, and tended to decrease 18-carbon fatty acid digestibility. We observed basal diet × PA dose interactions for yields of milk and milk protein and for 16-carbon and total fatty acid digestibility, as well as tendency for yields of milk fat and 3.5% FCM. Also, there was a tendency for an interaction between basal diet and PA dose for NDF digestibility, which increased more for CS with increasing PA than for SH. PA dose linearly decreased digestibility of total fatty acids in SH diets but did not affect it in CS diets Results demonstrate

The acidic functional groups of humic acid

Energy Technology Data Exchange (ETDEWEB)

Shanxiang, Li; Shuhe, Sun; Zhai Zongxi, Wu Qihu

1983-09-01

The acidic functional groups content, pK value, DELTAH and DELTAS of humic acid (HA) and nitro-humic acid (NHA) were determined by potentiometry, conductometry and calorimetric titration. The thermodynamic parameters of carboxylic groups and phenolic hydroxyl groups of humic acid are similar to that of simple hydroxy-benzoic acid. The configuration sites of acidic functional groups in humic acid from different coals are different. The carbonyl groups on aromatic rings are probably ortho to phenolic -OH for HA and NHA extracted from Huangxian's brown coal and Japanese lignite, while those from Lingshi's weathered coal are not. The weak -COOH groups of the latter possess higher chemical activity. The -COOH content in HA increases, phenolic -OH group decreases and the chemical acidity of acidic functional groups increases when HA is oxidized by nitric acid. (14 refs.)

Ethnicity/culture modulates the relationships of the haptoglobin (Hp) 1-1 phenotype with cognitive function in older individuals with type 2 diabetes.

Science.gov (United States)

Guerrero-Berroa, Elizabeth; Ravona-Springer, Ramit; Heymann, Anthony; Schmeidler, James; Hoffman, Hadas; Preiss, Rachel; Koifmann, Keren; Greenbaum, Lior; Levy, Andrew; Silverman, Jeremy M; Leroith, Derek; Sano, Mary; Schnaider-Beeri, Michal

2016-05-01

The haptoglobin (Hp) genotype has been associated with cognitive function in type 2 diabetes. Because ethnicity/culture has been associated with both cognitive function and Hp genotype frequencies, we examined whether it modulates the association of Hp with cognitive function. This cross-sectional study evaluated 787 cognitively normal older individuals (>65 years of age) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline study. Interactions in two-way analyses of covariance compared Group (Non-Ashkenazi versus Ashkenazi Jews) on the associations of Hp phenotype (Hp 1-1 versus non- Hp 1-1) with five cognitive outcome measures. The primary control variables were age, gender, and education. Compared with Ashkenazi Jews, non-Ashkenazi Jews with the Hp 1-1 phenotype had significantly poorer cognitive function than non-Hp 1-1 in the domains of Attention/Working Memory (p = 0.035) and Executive Function (p = 0.023), but not in Language/Semantic Categorization (p = 0.432), Episodic Memory (p = 0.268), or Overall Cognition (p = 0.082). After controlling for additional covariates (type 2 diabetes-related characteristics, cardiovascular risk factors, Mini-mental State Examination, and extent of depressive symptoms), Attention/Working Memory (p = 0.038) and Executive Function (p = 0.013) remained significant. Older individuals from specific ethnic/cultural backgrounds with the Hp 1-1 phenotype may benefit more from treatment targeted at decreasing or halting the detrimental effects of Hp 1-1 on the brain. Future studies should examine differential associations of Hp 1-1 and cognitive impairment, especially for groups with high prevalence of both, such as African-Americans and Hispanics. Copyright © 2015 John Wiley & Sons, Ltd.

Increasing the fidelity of noncanonical amino acid incorporation in cell-free protein synthesis.

Science.gov (United States)

Gan, Qinglei; Fan, Chenguang

2017-11-01

Cell-free protein synthesis provides a robust platform for co-translational incorporation of noncanonical amino acid (ncAA) into proteins to facilitate biological studies and biotechnological applications. Recently, eliminating the activity of release factor 1 has been shown to increase ncAA incorporation in response to amber codons. However, this approach could promote mis-incorporation of canonical amino acids by near cognate suppression. We performed a facile protocol to remove near cognate tRNA isoacceptors of the amber codon from total tRNAs, and used the phosphoserine (Sep) incorporation system as validation. By manipulating codon usage of target genes and tRNA species introduced into the cell-free protein synthesis system, we increased the fidelity of Sep incorporation at a specific position. By removing three near cognate tRNA isoacceptors of the amber stop codon [tRNA Lys , tRNA Tyr , and tRNA Gln (CUG)] from the total tRNA, the near cognate suppression decreased by 5-fold without impairing normal protein synthesis in the cell-free protein synthesis system. Mass spectrometry analyses indicated that the fidelity of ncAA incorporation was improved. Removal of near cognate tRNA isoacceptors of the amber codon could increase ncAA incorporation fidelity towards the amber stop codon in release factor deficiency systems. We provide a general strategy to improve fidelity of ncAA incorporation towards stop, quadruplet and sense codons in cell-free protein synthesis systems. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2016 Elsevier B.V. All rights reserved.

Co-expression of bacterial aspartate kinase and adenylylsulfate reductase genes substantially increases sulfur amino acid levels in transgenic alfalfa (Medicago sativa L.).

Science.gov (United States)

Tong, Zongyong; Xie, Can; Ma, Lei; Liu, Liping; Jin, Yongsheng; Dong, Jiangli; Wang, Tao

2014-01-01

Alfalfa (Medicago sativa L.) is one of the most important forage crops used to feed livestock, such as cattle and sheep, and the sulfur amino acid (SAA) content of alfalfa is used as an index of its nutritional value. Aspartate kinase (AK) catalyzes the phosphorylation of aspartate to Asp-phosphate, the first step in the aspartate family biosynthesis pathway, and adenylylsulfate reductase (APR) catalyzes the conversion of activated sulfate to sulfite, providing reduced sulfur for the synthesis of cysteine, methionine, and other essential metabolites and secondary compounds. To reduce the feedback inhibition of other metabolites, we cloned bacterial AK and APR genes, modified AK, and introduced them into alfalfa. Compared to the wild-type alfalfa, the content of cysteine increased by 30% and that of methionine increased substantially by 60%. In addition, a substantial increase in the abundance of essential amino acids (EAAs), such as aspartate and lysine, was found. The results also indicated a close connection between amino acid metabolism and the tricarboxylic acid (TCA) cycle. The total amino acid content and the forage biomass tested showed no significant changes in the transgenic plants. This approach provides a new method for increasing SAAs and allows for the development of new genetically modified crops with enhanced nutritional value.

Fatty Acid Metabolism in the Digestive Tract of Lactating Cows Fed Tallow in Increasing Amounts at Two Feed Levels

DEFF Research Database (Denmark)

Weisbjerg, Martin Riis; Børsting, Christian Friis; Hvelplund, Torben

1992-01-01

Long-chain fatty acid metabolism in the digestive tract was studied in lactating cows fed at two levels of dry matter intake (L, 8.6 kg DM and H, 12.6 kg DM), with 0, 4 and 6% added tallow at low feed level (L0, L4 and L6), and 0, 2, 4 and 6% fat at high feed level (H0, H2, H4 and H6). Mean fatty...... in the diet. As a mean 68% of the unsaturated C18 fatty acids were hydrogenated in the rumen. Fatty acid and crude fat true digestibilities decreased with increasing fat intakes owing to a decrease in stearic acid (C18:0) digestibility....

Overexpression of an alfalfa GDP-mannose 3, 5-epimerase gene enhances acid, drought and salt tolerance in transgenic Arabidopsis by increasing ascorbate accumulation.

Science.gov (United States)

Ma, Lichao; Wang, Yanrong; Liu, Wenxian; Liu, Zhipeng

2014-11-01

GDP-mannose 3', 5'-epimerase (GME) catalyses the conversion of GDP-D-mannose to GDP-L-galactose, an important step in the ascorbic acid (ascorbic acid) biosynthetic pathway in higher plants. In this study, a novel cDNA fragment (MsGME) encoding a GME protein was isolated and characterised from alfalfa (Medicago sativa). An expression analysis confirmed that MsGME expression was induced by salinity, PEG and acidity stresses. MsGME overexpression in Arabidopsis enhanced tolerance of the transgenic plants to salt, drought and acid. Real-time PCR analysis revealed that the transcript levels of GDP-D-mannose pyrophosphorylase (GMP), L-galactose-phosphate 1-P phosphatase (GP) and GDP-L-galactose phosphorylase (GGP) were increased in transgenic Arabidopsis (T3 generation). Moreover, the ascorbate content was increased in transgenic Arabidopsis. Our results suggest that MsGME can effectively enhance tolerance of transgenic Arabidopsis to acid, drought and salt by increasing ascorbate accumulation.

Overexpression of a 9-cis-epoxycarotenoid dioxygenase gene in Nicotiana plumbaginifolia increases abscisic acid and phaseic acid levels and enhances drought tolerance.

Science.gov (United States)

Qin, Xiaoqiong; Zeevaart, Jan A D

2002-02-01

The plant hormone abscisic acid (ABA) plays important roles in seed maturation and dormancy and in adaptation to a variety of environmental stresses. An effort to engineer plants with elevated ABA levels and subsequent stress tolerance is focused on the genetic manipulation of the cleavage reaction. It has been shown in bean (Phaseolus vulgaris) that the gene encoding the cleavage enzyme (PvNCED1) is up-regulated by water stress, preceding accumulation of ABA. Transgenic wild tobacco (Nicotiana plumbaginifolia Viv.) plants were produced that overexpress the PvNCED1 gene either constitutively or in an inducible manner. The constitutive expression of PvNCED1 resulted in an increase in ABA and its catabolite, phaseic acid (PA). When the PvNCED1 gene was driven by the dexamethasone (DEX)-inducible promoter, a transient induction of PvNCED1 message and accumulation of ABA and PA were observed in different lines after application of DEX. Accumulation of ABA started to level off after 6 h, whereas the PA level continued to increase. In the presence of DEX, seeds from homozygous transgenic line TN1 showed a 4-d delay in germination. After spraying with DEX, the detached leaves from line TN1 had a drastic decrease in their water loss relative to control leaves. These plants also showed a marked increase in their tolerance to drought stress. These results indicate that it is possible to manipulate ABA levels in plants by overexpressing the key regulatory gene in ABA biosynthesis and that stress tolerance can be improved by increasing ABA levels.

Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.

Science.gov (United States)

Thyrion, Lisa; Raedt, Robrecht; Portelli, Jeanelle; Van Loo, Pieter; Wadman, Wytse J; Glorieux, Griet; Lambrecht, Bart N; Janssens, Sophie; Vonck, Kristl; Boon, Paul

2016-03-01

Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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 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

Increased concentration of vasopressin in plasma of essential fatty acid-deficient rats

DEFF Research Database (Denmark)

Hansen, Harald S.; Jensen, B.; Warberg, J.

1985-01-01

The effect of essential fatty acid deficiency (EFA-D) on the plasma concentration of arginine-vasopressin (AVP) and the urinary AVP excretion was investigated. Weanling rats were fed a fat-free diet (FF-rats). Control rats received the same diet in which 6% by wt. of sucrose was replaced by arachis...... oil. After 4-6 weeks of feeding, urine and plasma were analysed for AVP, osmolality, sodium and potassium. When compared to control rats FF-rats had decreased urine volume (6.0 ± 1.6 ml/24 hr versus 11.7 ± 3.2 ml/24 hr), increased urine osmolality (2409 ± 691 mOsm/kg versus 1260 ± 434 m...

Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing-induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors.

Science.gov (United States)

Kawamura, O; Shimoyama, Y; Hosaka, H; Kuribayashi, S; Maeda, M; Nagoshi, A; Zai, H; Kusano, M

2011-05-01

Gastro-esophageal reflux disease (GERD)-related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro-esophageal reflux (GER), we studied patients with CC clearly responding to full-dose proton pump inhibitor (PPI) therapy (CC patients). Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24-h ambulatory pharyngo-esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire. Weakly acidic gas EPR and swallowing-induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P pump inhibitor therapy abolished swallowing-induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P gas EPR and swallowing-induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago-vagal reflex in some patients. © 2011 Blackwell Publishing Ltd.

Reduction of dietary saturated fatty acids correlates with increased plasma lecithin cholesterol acyltransferase activity in humans.

Science.gov (United States)

Bérard, A M; Dabadie, H; Palos-Pinto, A; Dumon, M-F; Darmon, M

2004-06-01

Increased HDL-cholesterol (HDL-C) concentrations have been associated with lower coronary heart disease risk. On the other hand, dietary fats are known to influence the fatty acid profile of plasma lipids, including phospholipids that are substrates of lecithin cholesterol acyltransferase (LCAT), an important enzyme in HDL metabolism. The purpose of this study was to examine the association between the saturated fatty acid (SFA) intake and LCAT activity. An interventional study was performed in a monk community of 25 men. A French monk community, South West of France. The basal diet of the study cohort contained SFA in a proportion of 13.5% of their total energy intake (TEI). They were submitted to two experimental isocaloric diets containing either 8.4% of the TEI in SFA (diet A) or 11% (diet B), each lasting 5 weeks. The elevation of SFA in diet B was mainly obtained by decreasing carbohydrates. The only significant difference among total fats between diets A and B was the myristic acid content (0.6 and 1.2% of TEI, respectively). The elevation in SFA in diet B resulted in a significant increase of HDL-C (P<0.04), while plasma apo A-I concentration and LCAT activity both decreased (P<0.02). Altogether, these results are consistent with a negative effect of SFA on reverse cholesterol transport.

Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class.

Directory of Open Access Journals (Sweden)

Monica Vera-Lise Tulstrup

Full Text Available Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group were dosed by oral gavage with either amoxicillin (AMX, cefotaxime (CTX, vancomycin (VAN, metronidazole (MTZ, or water (CON daily for 10-11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in

A single amino acid substitution in the core protein of West Nile virus increases resistance to acidotropic compounds.

Directory of Open Access Journals (Sweden)

Miguel A Martín-Acebes

Full Text Available West Nile virus (WNV is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu on the highly basic internal capsid or core (C protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses.

A single amino acid substitution in the core protein of West Nile virus increases resistance to acidotropic compounds.

Science.gov (United States)

Martín-Acebes, Miguel A; Blázquez, Ana-Belén; de Oya, Nereida Jiménez; Escribano-Romero, Estela; Shi, Pei-Yong; Saiz, Juan-Carlos

2013-01-01

West Nile virus (WNV) is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu) on the highly basic internal capsid or core (C) protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A) and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses.

Rehabilitating acid soils for increasing crop productivity through low-cost liming material.

Science.gov (United States)

Bhat, Javid Ahmad; Kundu, Manik Chandra; Hazra, Gora Chand; Santra, Gour Hari; Mandal, Biswapati

2010-09-15

Productivity of red and lateritic soils is low because of their acidity and deficiencies in few essential nutrients viz., nitrogen, phosphorus, calcium, zinc, boron, molybdenum etc. We compared the effectiveness of basic slag, a low-cost liming material, with that of calcite as an ameliorant for these soils using mustard followed by rice as test crops. Experiments were conducted with three levels of each of basic slag and calcite along with a control on farmers' fields at 14 different locations. Influence of farmyard manure (FYM) and poultry manure (PM) on the effectiveness of the slag was also tested. On an average, basic slag performed better than calcite in increasing yields of both mustard and rice and left over higher amounts of available Ca, Si and Zn in residual soils. The slag also improved N, P, K and Ca nutrition of mustard and Si and Zn nutrition of rice with a favorable benefit:cost (B:C) ratio over the calcite (4.82 vs. 1.44). Effectiveness of the basic slag improved when it was applied in combination with FYM or PM (B:C, 5.83 and 6.27). Basic slag can, therefore, be advocated for use in the acidic red and lateritic soils for economically improving their productivity. Copyright 2010 Elsevier B.V. All rights reserved.

Rehabilitating acid soils for increasing crop productivity through low-cost liming material

International Nuclear Information System (INIS)

Bhat, Javid Ahmad; Kundu, Manik Chandra; Hazra, Gora Chand; Santra, Gour Hari; Mandal, Biswapati

2010-01-01

Productivity of red and lateritic soils is low because of their acidity and deficiencies in few essential nutrients viz., nitrogen, phosphorus, calcium, zinc, boron, molybdenum etc. We compared the effectiveness of basic slag, a low-cost liming material, with that of calcite as an ameliorant for these soils using mustard followed by rice as test crops. Experiments were conducted with three levels of each of basic slag and calcite along with a control on farmers' fields at 14 different locations. Influence of farmyard manure (FYM) and poultry manure (PM) on the effectiveness of the slag was also tested. On an average, basic slag performed better than calcite in increasing yields of both mustard and rice and left over higher amounts of available Ca, Si and Zn in residual soils. The slag also improved N, P, K and Ca nutrition of mustard and Si and Zn nutrition of rice with a favorable benefit:cost (B:C) ratio over the calcite (4.82 vs. 1.44). Effectiveness of the basic slag improved when it was applied in combination with FYM or PM (B:C, 5.83 and 6.27). Basic slag can, therefore, be advocated for use in the acidic red and lateritic soils for economically improving their productivity.

Rehabilitating acid soils for increasing crop productivity through low-cost liming material

Energy Technology Data Exchange (ETDEWEB)

Bhat, Javid Ahmad [Directorate of Research, Bidhan Chandra Krishi Viswavidyalaya, Kalyani - 741 235, West Bengal (India); Kundu, Manik Chandra, E-mail: mckundu@rediffmail.com [Directorate of Research, Bidhan Chandra Krishi Viswavidyalaya, Kalyani - 741 235, West Bengal (India); Hazra, Gora Chand [Directorate of Research, Bidhan Chandra Krishi Viswavidyalaya, Kalyani - 741 235, West Bengal (India); Santra, Gour Hari [Department of Soil Science and Agril. Chemistry, Orissa University of Agriculture and Technology, Bhubaneswar - 751003, Orissa (India); Mandal, Biswapati [Directorate of Research, Bidhan Chandra Krishi Viswavidyalaya, Kalyani - 741 235, West Bengal (India)

2010-09-15

Productivity of red and lateritic soils is low because of their acidity and deficiencies in few essential nutrients viz., nitrogen, phosphorus, calcium, zinc, boron, molybdenum etc. We compared the effectiveness of basic slag, a low-cost liming material, with that of calcite as an ameliorant for these soils using mustard followed by rice as test crops. Experiments were conducted with three levels of each of basic slag and calcite along with a control on farmers' fields at 14 different locations. Influence of farmyard manure (FYM) and poultry manure (PM) on the effectiveness of the slag was also tested. On an average, basic slag performed better than calcite in increasing yields of both mustard and rice and left over higher amounts of available Ca, Si and Zn in residual soils. The slag also improved N, P, K and Ca nutrition of mustard and Si and Zn nutrition of rice with a favorable benefit:cost (B:C) ratio over the calcite (4.82 vs. 1.44). Effectiveness of the basic slag improved when it was applied in combination with FYM or PM (B:C, 5.83 and 6.27). Basic slag can, therefore, be advocated for use in the acidic red and lateritic soils for economically improving their productivity.

Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala, CAT (21A/T and GPX1 (Pro198Leu gene polymorphisms in dilutional pseudoanemia ("sports anemia"

Directory of Open Access Journals (Sweden)

Ana L. Miranda-Vilela

2010-01-01

Full Text Available Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb. is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala, CAT (21A/T and GPX1 (Pro198Leu gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration and RDW (red cell distribution width, the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects.

Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

International Nuclear Information System (INIS)

Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

1986-01-01

EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using 14 C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD

Further increased production of free fatty acids by overexpressing a predicted transketolase gene of the pentose phosphate pathway in Aspergillus oryzae faaA disruptant.

Science.gov (United States)

Tamano, Koichi; Miura, Ai

2016-09-01

Free fatty acids are useful as source materials for the production of biodiesel fuel and various chemicals such as pharmaceuticals and dietary supplements. Previously, we attained a 9.2-fold increase in free fatty acid productivity by disrupting a predicted acyl-CoA synthetase gene (faaA, AO090011000642) in Aspergillus oryzae. In this study, we achieved further increase in the productivity by overexpressing a predicted transketolase gene of the pentose phosphate pathway in the faaA disruptant. The A. oryzae genome is predicted to have three transketolase genes and overexpression of AO090023000345, one of the three genes, resulted in phenotypic change and further increase (corresponding to an increased production of 0.38 mmol/g dry cell weight) in free fatty acids at 1.4-fold compared to the faaA disruptant. Additionally, the biomass of hyphae increased at 1.2-fold by the overexpression. As a result, free fatty acid production yield per liter of liquid culture increased at 1.7-fold by the overexpression.

Increased formic acid excretion and the development of kidney toxicity in rats following chronic dosing with trichloroethanol, a major metabolite of trichloroethylene

International Nuclear Information System (INIS)

Green, Trevor; Dow, Jacky; Foster, John

2003-01-01

The chronic toxicity of trichloroethanol, a major metabolite of trichloroethylene, has been assessed in male Fischer rats (60 per group) given trichloroethanol in drinking water at concentrations of 0, 0.5 and 1.0 g/l for 52 weeks. The rats excreted large amounts of formic acid in urine reaching a maximum after 12 weeks (∼65 mg/24 h at 1 g/l) and thereafter declining to reach an apparent steady state at 40 weeks (15-20 mg/24 h). Urine from treated rats was more acidic throughout the study and urinary methylmalonic acid and plasma N-methyltetrahydrofolate concentrations were increased, indicating an acidosis, vitamin B12 deficiency and impaired folate metabolism, respectively. The rats treated with trichloroethanol developed kidney damage over the duration of the study which was characterised by increased urinary NAG activity, protein excretion (from 4 weeks), increased basophilia, protein accumulation and tubular damage (from 12 to 40 weeks), increased cell replication (at week 28) and evidence in some rats of focal proliferation of abnormal tubules at 52 weeks. It was concluded that trichloroethanol, the major metabolite of trichloroethylene, induced nephrotoxicity in rats as a result of formic acid excretion and acidosis

Increased cartilage volume after injection of hyaluronic acid in osteoarthritis knee patients who underwent high tibial osteotomy.

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Chareancholvanich, Keerati; Pornrattanamaneewong, Chaturong; Narkbunnam, Rapeepat

2014-06-01

High tibial osteotomy (HTO) is a surgical procedure used to correct abnormal mechanical loading of the knee joint; additionally, intra-articular hyaluronic acid injections have been shown to restore the viscoelastic properties of synovial fluid and balance abnormal biochemical processes. It was hypothesized that combining HTO with intra-articular hyaluronic acid injections would have benefit to improve the cartilage volume of knee joints. Forty patients with medial compartment knee osteoarthritis (OA) were randomly placed into 1 of 2 groups. The study group (n = 20) received 2 cycles (at 6-month intervals) of 5 weekly intra-articular hyaluronic acid injections after HTO operation. The control group (n = 20) did not receive any intra-articular injections after HTO surgery. Cartilage volume (primary outcome) was assessed by magnetic resonance imaging (MRI) pre-operatively and 1 year post-operatively. Treatment efficacy (secondary outcomes) was evaluated with the Western Ontario and McMaster Universities OA Index (WOMAC) and by the comparison of the total rescue medication (paracetamol/diclofenac) used (weeks 6, 12, 24, 48). MRI studies showed a significant increase in total cartilage volume (p = 0.033), lateral femoral cartilage volume (p = 0.044) and lateral tibial cartilage volume (p = 0.027) in the study group. Cartilage volume loss was detected at the lateral tibial plateau in the control group. There were significant improvements after surgery in both groups for all subscales of WOMAC scores (p hyaluronic acid injections may be beneficial for increasing total cartilage volume and preventing the loss of lateral tibiofemoral joint cartilage after HTO. Therapeutic study, Level I.

Investigation of inflammatory markers in horses with acute abdominal pain

DEFF Research Database (Denmark)

Pihl, Tina Holberg; Kjelgaard-Hansen, Mads; Andersen, Pia Haubro

of colic horses in a referral hospital have not been reported earlier. Objectives Evaluation of serum and peritoneal fluid (PF) levels of serum amyloid A (SAA) and haptoglobin in horses with colic. Methods Blood and PF samples were collected from 75 colic horses at admission to a referral hospital and from...... 19 healthy control horses. SAA and haptoglobin were measured in both serum and PF. Colic cases were classified according to diagnosis, treatment and outcome based on the clinical records. Protein concentrations were compared between groups with student´s t-test and ANOVA. Results Colic horses had...... significantly higher mean concentrations of serum SAA, PF SAA and PF haptoglobin compared to controls. PF SAA was significantly higher in horses with infectious conditions compared to both simple and strangulating obstructions, where as PF haptoglobin was higher in both strangulating and infectious conditions...

Overexpression of a 9-cis-Epoxycarotenoid Dioxygenase Gene in Nicotiana plumbaginifolia Increases Abscisic Acid and Phaseic Acid Levels and Enhances Drought Tolerance1

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Qin, Xiaoqiong; Zeevaart, Jan A.D.

2002-01-01

The plant hormone abscisic acid (ABA) plays important roles in seed maturation and dormancy and in adaptation to a variety of environmental stresses. An effort to engineer plants with elevated ABA levels and subsequent stress tolerance is focused on the genetic manipulation of the cleavage reaction. It has been shown in bean (Phaseolus vulgaris) that the gene encoding the cleavage enzyme (PvNCED1) is up-regulated by water stress, preceding accumulation of ABA. Transgenic wild tobacco (Nicotiana plumbaginifolia Viv.) plants were produced that overexpress the PvNCED1 gene either constitutively or in an inducible manner. The constitutive expression of PvNCED1 resulted in an increase in ABA and its catabolite, phaseic acid (PA). When the PvNCED1 gene was driven by the dexamethasone (DEX)-inducible promoter, a transient induction of PvNCED1 message and accumulation of ABA and PA were observed in different lines after application of DEX. Accumulation of ABA started to level off after 6 h, whereas the PA level continued to increase. In the presence of DEX, seeds from homozygous transgenic line TN1 showed a 4-d delay in germination. After spraying with DEX, the detached leaves from line TN1 had a drastic decrease in their water loss relative to control leaves. These plants also showed a marked increase in their tolerance to drought stress. These results indicate that it is possible to manipulate ABA levels in plants by overexpressing the key regulatory gene in ABA biosynthesis and that stress tolerance can be improved by increasing ABA levels. PMID:11842158

An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance.

OpenAIRE

Baier, L J; Sacchettini, J C; Knowler, W C; Eads, J; Paolisso, G; Tataranni, P A; Mochizuki, H; Bennett, P H; Bogardus, C; Prochazka, M

1995-01-01

The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimu...

Improvement of pea biomass and seed productivity by simultaneous increase of phloem and embryo loading with amino acids.

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Zhang, Lizhi; Garneau, Matthew G; Majumdar, Rajtilak; Grant, Jan; Tegeder, Mechthild

2015-01-01

The development of sink organs such as fruits and seeds strongly depends on the amount of nitrogen that is moved within the phloem from photosynthetic-active source leaves to the reproductive sinks. In many plant species nitrogen is transported as amino acids. In pea (Pisum sativum L.), source to sink partitioning of amino acids requires at least two active transport events mediated by plasma membrane-localized proteins, and these are: (i) amino acid phloem loading; and (ii) import of amino acids into the seed cotyledons via epidermal transfer cells. As each of these transport steps might potentially be limiting to efficient nitrogen delivery to the pea embryo, we manipulated both simultaneously. Additional copies of the pea amino acid permease PsAAP1 were introduced into the pea genome and expression of the transporter was targeted to the sieve element-companion cell complexes of the leaf phloem and to the epidermis of the seed cotyledons. The transgenic pea plants showed increased phloem loading and embryo loading of amino acids resulting in improved long distance transport of nitrogen, sink development and seed protein accumulation. Analyses of root and leaf tissues further revealed that genetic manipulation positively affected root nitrogen uptake, as well as primary source and sink metabolism. Overall, the results suggest that amino acid phloem loading exerts regulatory control over pea biomass production and seed yield, and that import of amino acids into the cotyledons limits seed protein levels. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Enhanced citric acid production in aspergillus with inactivated asparagine-linked glycosylation protein 3 (ALG3), and/or increased laeA expression

Science.gov (United States)

Dai, Ziyu; Baker, Scott E.

2015-12-08

Provided herein are fungi, such as Aspergillus niger, having a dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase (Alg3) gene genetic inactivation, increased expression of a loss of aflR expression A (Lae), or both. In some examples, such mutants have several phenotypes, including an increased production of citric acid relative to the parental strain. Methods of using the disclosed fungi to make citric acid are also provided, as are compositions and kits including the disclosed fungi.

Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids

DEFF Research Database (Denmark)

Golovko, Mikhail Y; Rosenberger, Thad A; Feddersen, Søren

2007-01-01

Previously, we demonstrated that ablation of alpha-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca ablation on docosahexaenoic acid (22:6n-3) metabolism is unknown...... and turnover in ethanolamine glycerophospholipid, phosphatidylserine, and phosphatidylinositol pools. Increased 22:6n-3-CoA mass was not the result of altered Acsl activity, which was unaffected by the absence of Snca. While Snca bound 22:6n-3, Kd = 1.0 +/- 0.5 micromol/L, it did not bind 22:6n-3-Co...

Acid suppression increases rates of Barrett's esophagus and esophageal injury in the presence of duodenal reflux.

LENUS (Irish Health Repository)

2012-01-31

BACKGROUND: The contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. This study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (PPI), or absent. METHODS: We randomized 136 Sprague-Dawley rats into 4 groups: group 1 (n = 33) were controls; group 2 (n = 34) underwent esophagoduodenostomy promoting "combined reflux"; group 3 (n = 34) underwent esophagoduodenostomy and PPI treatment to decrease acid reflux; and group 4, the \\'gastrectomy\\' group (n = 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. Esophaguses were examined for inflammatory, Barrett\\'s, and other histologic changes, and expression of proliferative markers Ki-67, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR). RESULTS: In all reflux groups, the incidence of Barrett\\'s mucosa was greater when acid was suppressed (group C, 62%; group D, 71%) than when not suppressed (group B, 27%; P = 0.004 and P < .001). Erosions were more frequent in the PPI and gastrectomy groups than in the combined reflux group. Edema (wet weight) and ulceration was more frequent in the gastrectomy than in the combined reflux group. Acute inflammatory changes were infrequent in the PPI group (8%) compared with the combined reflux (94%) or gastrectomy (100%) groups, but chronic inflammation persisted in 100% of the PPI group. EGFR levels were greater in the PPI compared with the combined reflux group (P = .04). Ki-67, PCNA, and combined marker scores were greater in the gastrectomy compared with the combined reflux group (P = .006, P = .14, and P < .001). CONCLUSION: Gastric acid suppression in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia, and molecular proliferative activity. PPIs suppressed acute inflammatory changes only, whereas chronic inflammatory changes persisted.

Increased production of pyruvic acid by Escherichia coli RNase G mutants in combination with cra mutations.

Science.gov (United States)

Sakai, Taro; Nakamura, Naoko; Umitsuki, Genryou; Nagai, Kazuo; Wachi, Masaaki

2007-08-01

The Escherichia coli RNase G is known as an endoribonuclease responsible for the 5'-end maturation of 16S rRNA and degradation of several specific mRNAs such as adhE and eno mRNAs. In this study, we found that an RNase G mutant derived from the MC1061 strain did not grow on a glucose minimal medium. Genetic analysis revealed that simultaneous defects of cra and ilvIH, encoding a transcriptional regulator of glycolysis/gluconeogenesis and one of isozymes of acetohydroxy acid synthase, respectively, were required for this phenomenon to occur. The results of additional experiments presented here indicate that the RNase G mutation, in combination with cra mutation, caused the increased production of pyruvic acid from glucose, which was then preferentially converted to valine due to the ilvIH mutation, resulting in depletion of isoleucine. In fact, the rng cra double mutant produced increased amount of pyruvate in the medium. These results suggest that the RNase G mutation could be applied in the breeding of producer strains of pyruvate and its derivatives such as valine.

Effects of the Soil Incorporation of Increasing Amounts of Non-Fermented Wet Pomace on the Oil Yield and Acid Profile of Sunflower Seeds

Directory of Open Access Journals (Sweden)

Giovanna Cucci

2007-12-01

Full Text Available The agricultural use of olive processing waste is a strategic resource in the integrated management of the agricultural system as it satisfies the two objectives of evacuating the olive-processing residue and using it beneficially for agricultural purposes. For such aims, a research was conducted in Bari (South of Italy to study the effects of the incorporation into the soil of increasing amounts of non-fermented wet pomace (WP (0, 17.5, 35, 70, 105, 140, 175, 210 Mg ha-1 on the oil yield and acid profile of sunflower seeds. The results obtained point out that the seed yield was negatively affected by the application of WP starting from 70 Mg ha-1; an opposite trend was observed for the seed oil yield. The incorporation of WP has also affected the oil fatty acids’ composition. Oleic and linoleic acids, the principal fatty acids (beyond 90% of total fatty acids, showed significant variations: from the control treatment to the one receiving the maximum application of waste, oleic acid decreased (-5.4%, linoleic acid increased (+ 6.6%, and the saturated fatty acids fraction decreased (-7.6%.

Randomized controlled trial of tranexamic acid among parturients at increased risk for postpartum hemorrhage undergoing cesarean delivery.

Science.gov (United States)

Sujata, Nambiath; Tobin, Raj; Kaur, Ranjeet; Aneja, Anjila; Khanna, Mona; Hanjoora, Vijay M

2016-06-01

To assess the effects of tranexamic acid among patients undergoing cesarean delivery who were at high risk of postpartum hemorrhage. Between August 1, 2012, and April 30, 2013, a randomized controlled trial was performed at a tertiary care center in India. Women undergoing an elective or emergency cesarean delivery who were at high risk for postpartum hemorrhage were enrolled. They were randomly assigned using sealed, opaque envelopes to receive 10mg/kg tranexamic acid or normal saline 10min before skin incision. Anesthesiologists were not masked to group assignment, but patients and obstetricians were. The primary outcome was need for additional uterotonic drugs within 24h after delivery. Analyses were by intention to treat. Thirty patients were assigned to each group. Additional uterotonic drugs were required in 7 (23%) patients assigned to tranexamic acid and 25 (83%) patients in the control group (Ptranexamic acid, administered before skin incision, significantly reduced the requirement for additional uterotonics among women at increased risk for postpartum hemorrhage. Clinical Trials Registry India: CTRI/2015/05/005752. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

MDMA Decreases Gluatamic Acid Decarboxylase (GAD) 67-Immunoreactive Neurons in the Hippocampus and Increases Seizure Susceptibility: Role for Glutamate

Science.gov (United States)

Huff, Courtney L.; Morano, Rachel L.; Herman, James P.; Yamamoto, Bryan K.; Gudelsky, Gary A.

2016-01-01

3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37–58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30 days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. PMID:27773601

MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

Science.gov (United States)

Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

2016-12-01

3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. Copyright © 2016 Elsevier B.V. All rights reserved.

Increase of essential amino acids in the bovine uterine lumen during preimplantation development.

Science.gov (United States)

Groebner, Anna E; Rubio-Aliaga, Isabel; Schulke, Katy; Reichenbach, Horst D; Daniel, Hannelore; Wolf, Eckhard; Meyer, Heinrich H D; Ulbrich, Susanne E

2011-05-01

Amino acids (AAs) are crucial for the developing conceptus prior to implantation. To provide insights into the requirements of the bovine embryo, we determined the AA composition of the uterine fluid. At days 12, 15, and 18 post-estrus, the uteri of synchronized pregnant and non-pregnant Simmental heifers were flushed for the analysis of 41 AAs and their derivatives by liquid chromatography-tandem mass spectrometry. The ipsilateral endometrium was sampled for quantitative PCR. In addition to a pregnancy-dependent increase of the essential AAs (P<0.01), we detected elevated concentrations for most non-essential proteinogenic AAs. Histidine (His) and the expression of the His/peptide transporter solute carrier 15A3 (SLC15A3) were significantly increased at day 18 of pregnancy in vivo. In addition, SLC15A3 was predominantly stimulated by trophoblast-derived interferon-τ in stroma cells of an in vitro co-culture model of endometrial cells. Our results show an increased concentration of AAs most likely to optimally provide the elongating pre-attachment conceptus with nutrients.

Wounding stimulates ALLENE OXIDE SYNTHASE gene and increases the level of jasmonic acid in Ipomoea nil cotyledons

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Emilia Wilmowicz

2016-03-01

Full Text Available Allene oxide synthase (AOS encodes the first enzyme in the lipoxygenase pathway, which is responsible for jasmonic acid (JA formation. In this study we report the molecular cloning and characterization of InAOS from Ipomoea nil. The full-length gene is composed of 1662 bp and encodes for 519 amino acids. The predicted InAOS contains PLN02648 motif, which is evolutionarily conserved and characteristic for functional enzymatic proteins. We have shown that wounding led to a strong stimulation of the examined gene activity in cotyledons and an increase in JA level, which suggest that this compound may be a modulator of stress responses in I. nil.

Bile Acids Increase Independently From Hypocaloric Restriction After Bariatric Surgery.

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Jahansouz, Cyrus; Xu, Hongliang; Hertzel, Ann V; Serrot, Federico J; Kvalheim, Nicholas; Cole, Abigail; Abraham, Anasooya; Luthra, Girish; Ewing, Kristin; Leslie, Daniel B; Bernlohr, David A; Ikramuddin, Sayeed

2016-12-01

To measure changes in the composition of serum bile acids (BA) and the expression of Takeda G-protein-coupled receptor 5 (TGR5) acutely after bariatric surgery or caloric restriction. Metabolic improvement after bariatric surgery occurs before substantial weight loss. BA are important metabolic regulators acting through the farnesoid X receptor and TGR5 receptor. The acute effects of surgery on BA and the TGR5 receptor in subcutaneous white adipose tissue (WAT) are unknown. A total of 27 obese patients with type 2 diabetes mellitus were randomized to Roux-en-Y gastric bypass (RYGB) or to hypocaloric diet (HC diet) restriction (NCT 1882036). A cohort of obese patients with and without type 2 diabetes mellitus undergoing vertical sleeve gastrectomy was also recruited (n = 12) as a comparison. After vertical sleeve gastrectomy, the level of BA increased [total: 1.17 ± 1.56 μmol/L to 4.42 ± 3.92 μmol/L (P = 0.005); conjugated BA levels increased from 0.99 ± 1.42 μmol/L to 3.59 ± 3.70 μmol/L (P = 0.01) and unconjugated BA levels increased from 0.18 ± 0.24 μmol/L to 0.83 ± 0.70 μmol/L (P = 0.009)]. With RYGB, there was a trend toward increased BA [total: 1.37 ± 0.97 μmol/L to 3.26 ± 3.01 μmol/L (P = 0.07); conjugated: 1.06 ± 0.81 μmol/L to 2.99 ± 3.02 μmol/L (P = 0.06)]. After HC diet, the level of unconjugated BA decreased [0.92 ± 0.55 μmol/L to 0.32 ± 0.43 μmol/L (P = 0.05)]. The level of WAT TGR5 gene expression decreased after surgery, but not in HC diet. Protein levels did not change. The levels of serum BA increase after bariatric surgery independently from caloric restriction, whereas the level of WAT TGR5 protein is unaffected.

Increase in tartrate-resistant acid phosphatase of bone at the early stage of ascorbic acid deficiency in the ascorbate-requiring Osteogenic Disorder Shionogi (ODS) rat.

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Goto, A; Tsukamoto, I

2003-08-01

The effect of ascorbic acid deficiency on bone metabolism was evaluated using the ascorbate-requiring Osteogenic Disorder Shionogi (ODS) rat model. Ascorbic acid (Asc)-deficient rats gained body weight in a manner similar to Asc-supplemented rats (control) during 3 weeks, but began to lose weight during the 4th week of Asc deficiency. The tartrate-resistant acid phosphatase (TRAP) activity in serum increased to about 2-fold the control value in the rats fed the Asc-free diet for 2, 3, and 4 weeks (AscD2, AscD3, and AscD4), while a decrease in the alkaline phosphatase (ALP) activity was observed only in AscD4 rats. The serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) level significantly increased to 1.3-, 1.4-, and 1.9-fold of that in the controls in AscD2, D3, and D4, respectively. The ALP activity in the distal femur was unchanged in AscD1, D2, and D3, but decreased to 50% of the control level in AscD4 rats. The TRAP activity in the distal femur increased to about 2-fold of that in the controls in the AscD2 and D3 and decreased to the control level in the AscD4 rats. The amount of hydroxyproline in the distal femur significantly decreased to about 80%, 70%, and 60% of the control in AscD2, D3, and D4 rats, respectively. These decreases were associated with a similar reduction in the calcium content of the distal femur. Histochemical analysis of the distal femur showed an increase in TRAP-positive cells in AscD2 and AscD3 rats and a decrease in the trabecular bone in AscD2, D3, and D4 rats. These results suggested that a deficiency of Asc stimulated bone resorption at an early stage, followed by a decrease in bone formation in mature ODS rats which already had a well-developed collagen matrix and fully differentiated osteoblasts.

The oleic acid esterification of policosanol increases its bioavailability and hypocholesterolemic action in rats

Energy Technology Data Exchange (ETDEWEB)

Hain, D.; Valenzuela, A.; Branes, M. C.; Fuenzalida, M.; Videla, L. A.

2012-07-01

Policosanol comprises a mixture of long-chain aliphatic alcohols from sugarcane wax. More than 50 studies indicate that policosanol decreases serum cholesterol, while others failed to reproduce this effect. The objective of this investigation was to assess the bioavailability of esterified policosanol and non-esterified policosanol (NEP), in relation to their hypocholesterolemic effects. Sprague Dawley rats were given a daily oral dose of 100 mg/kg of NEP, 117 mg kg1 of butyric acid esterified policosanol (BAEP), or 164 mg kg1 of oleic acid esterified policosanol (OAEP). Policosanol absorption was evaluated in plasma between 0 and 3 hours after ingestion. To assess changes in total cholesterol, LDL-cholesterol, HDLcholesterol and triacylglycerols in plasma and liver 3-hydroxy- 3-methylglutaryl coenzyme A reductase (HMG- CoA red) phosphorylation, the rats were supplemented with nonesterified or esterified policosanol for 5 weeks. The results indicate that policosanol absorption was significantly greater in OAEP-treated rats than in those subjected to NEP or BAEP administration. OAEP significantly reduced plasma total and LDL-cholesterol in rats, in addition to a 5.6-fold increase (P < 0.05) in the hepatic content of phosphorylated HMG-CoA red over the control values. In conclusion, esterification of policosanol with oleic acid enhances policosanol bioavailability, and significantly improves the serum lipid profile in normocholesterolemic rats in association with the inactivation of HMG-CoA red controlling cholesterogenesis. (Author) 49 refs.

Exogenous ascorbic acid increases resistance to salt of Silybum ...

African Journals Online (AJOL)

However, irrigation with salt water enhanced carotenoids and antioxidant enzyme activities. The detrimental effects of salt water were ameliorated by application of 100 ppm ascorbic acid (vitamin C). The inductive role of vitamin was associated with the improvement of seed germination, growth, plant water status, ...

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans.

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Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-12-25

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Acidic Food pH Increases Palatability and Consumption and Extends Drosophila Lifespan.

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Deshpande, Sonali A; Yamada, Ryuichi; Mak, Christine M; Hunter, Brooke; Soto Obando, Alina; Hoxha, Sany; Ja, William W

2015-12-01

Despite the prevalent use of Drosophila as a model in studies of nutrition, the effects of fundamental food properties, such as pH, on animal health and behavior are not well known. We examined the effect of food pH on adult Drosophila lifespan, feeding behavior, and microbiota composition and tested the hypothesis that pH-mediated changes in palatability and total consumption are required for modulating longevity. We measured the effect of buffered food (pH 5, 7, or 9) on male gustatory responses (proboscis extension), total food intake, and male and female lifespan. The effect of food pH on germfree male lifespan was also assessed. Changes in fly-associated microbial composition as a result of food pH were determined by 16S ribosomal RNA gene sequencing. Male gustatory responses, total consumption, and male and female longevity were additionally measured in the taste-defective Pox neuro (Poxn) mutant and its transgenic rescue control. An acidic diet increased Drosophila gustatory responses (40-230%) and food intake (5-50%) and extended survival (10-160% longer median lifespan) compared with flies on either neutral or alkaline pH food. Alkaline food pH shifted the composition of fly-associated bacteria and resulted in greater lifespan extension (260% longer median survival) after microbes were eliminated compared with flies on an acidic (50%) or neutral (130%) diet. However, germfree flies lived longer on an acidic diet (5-20% longer median lifespan) compared with those on either neutral or alkaline pH food. Gustatory responses, total consumption, and longevity were unaffected by food pH in Poxn mutant flies. Food pH can directly influence palatability and feeding behavior and affect parameters such as microbial growth to ultimately affect Drosophila lifespan. Fundamental food properties altered by dietary or drug interventions may therefore contribute to changes in animal physiology, metabolism, and survival. © 2015 American Society for Nutrition.

Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells

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Nataša Nikolić

2012-01-01

Full Text Available We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.

Directing vanillin production from ferulic acid by increased acetyl-CoA consumption in recombinant Escherichia coli.

Science.gov (United States)

Lee, Eun-Gyeong; Yoon, Sang-Hwal; Das, Amitabha; Lee, Sook-Hee; Li, Cui; Kim, Jae-Yean; Choi, Myung-Suk; Oh, Deok-Kun; Kim, Seon-Won

2009-01-01

The amplification of gltA gene encoding citrate synthase of TCA cycle was required for the efficient conversion of acetyl-CoA, generated during vanillin production from ferulic acid, to CoA, which is essential for vanillin production. Vanillin of 1.98 g/L was produced from the E. coli DH5alpha (pTAHEF-gltA) with gltA amplification in 48 h of culture at 3.0 g/L of ferulic acid, which was about twofold higher than the vanillin production of 0.91 g/L obtained by the E. coli DH5alpha (pTAHEF) without gltA amplification. The icdA gene encoding isocitrate dehydrogenase of TCA cycle was deleted to make the vanillin producing E. coli utilize glyoxylate bypass which enables more efficient conversion of acetyl-CoA to CoA in comparison with TCA cycle. The production of vanillin by the icdA null mutant of E. coli BW25113 harboring pTAHEF was enhanced by 2.6 times. The gltA amplification of the glyoxylate bypass in the icdA null mutant remarkably increased the production rate of vanillin with a little increase in the amount of vanillin production. The real synergistic effect of gltA amplification and icdA deletion was observed with use of XAD-2 resin reducing the toxicity of vanillin produced during culture. Vanillin of 5.14 g/L was produced in 24 h of the culture with molar conversion yield of 86.6%, which is the highest so far in vanillin production from ferulic acid using recombinant E. coli.

Effects of dietary conjugated linoleic acid and linoleic:linolenic acid ratio on polyunsaturated fatty acid status in laying hens.

Science.gov (United States)

Du, M; Ahn, D U; Sell, J L

2000-12-01

A study was conducted to determine the effects of dietary conjugated linoleic acid (CLA) and the ratio of linoleic:linolenic acid on long-chain polyunsaturated fatty acid status. Thirty-two 31-wk-old White Leghorn hens were randomly assigned to four diets containing 8.2% soy oil, 4.1% soy oil + 2.5% CLA (4.1% CLA source), 4.1% flax oil + 2.5% CLA, or 4.1% soy oil + 4.1% flax oil. Hens were fed the diets for 3 wk before eggs and tissues were collected for the study. Lipids were extracted from egg yolk and tissues, classes of egg yolk lipids were separated, and fatty acid concentrations of total lipids, triglyceride, phosphatidylethanolamine, and phosphatidylcholine were analyzed by gas chromatography. The concentrations of monounsaturated fatty acids and non-CLA polyunsaturated fatty acids were reduced after CLA feeding. The amount of arachidonic acid was decreased after CLA feeding in linoleic acid- and linolenic acid-rich diets, but amounts of eicosapentaenoic acid and docosahexaenoic acid were increased in the linolenic-rich diet, indicating that the synthesis or deposition of long-chain n-3 fatty acids was accelerated after CLA feeding. The increased docosahexaenoic acid and eicosapentaenoic acid contents in lipid may be compensation for the decreased arachidonic acid content. Dietary supplementation of linoleic acid increased n-6 fatty acid levels in lipids, whereas linolenic acid increased n-3 fatty acid levels. Results also suggest that CLA might not be elongated to synthesize long-chain fatty acids in significant amounts. The effect of CLA in reducing the level of n-6 fatty acids and promoting the level of n-3 fatty acids could be related to the biological effects of CLA.

Intraileal casein infusion increases plasma concentrations of amino acids in humans: A randomized cross over trial.

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Ripken, Dina; van Avesaat, Mark; Troost, Freddy J; Masclee, Ad A; Witkamp, Renger F; Hendriks, Henk F

2017-02-01

Activation of the ileal brake by casein induces satiety signals and reduces energy intake. However, adverse effects of intraileal casein administration have not been studied before. These adverse effects may include impaired amino acid digestion, absorption and immune activation. To investigate the effects of intraileal infusion of native casein on plasma amino acid appearance, immune activation and gastrointestinal (GI) symptoms. A randomized single-blind cross over study was performed in 13 healthy subjects (6 male; mean age 26 ± 2.9 years; mean body mass index 22.8 ± 0.4 kg/m -2 ), who were intubated with a naso-ileal feeding catheter. Thirty minutes after intake of a standardized breakfast, participants received an ileal infusion, containing either control (C) consisting of saline, a low-dose (17.2 kcal) casein (LP) or a high-dose (51.7 kcal) of casein (HP) over a period of 90 min. Blood samples were collected for analysis of amino acids (AAs), C-reactive protein (CRP), pro-inflammatory cytokines and oxylipins at regular intervals. Furthermore, GI symptom questionnaires were collected before, during and after ileal infusion. None of the subjects reported any GI symptoms before, during or after ileal infusion of C, LP and HP. Plasma concentrations of all AAs analyzed were significantly increased after infusion of HP as compared to C (p casein, respectively. Ileal casein infusion did not affect plasma concentrations of CRP, IL-6, IL-8, IL-1β and TNF-α. Infusion of HP resulted in a decreased concentration of 11,12-dihydroxyeicosatrienoic acid whereas none of the other oxylipins analyzed were affected. A single intraileal infusion of native casein results in a concentration and time dependent increase of AAs in plasma, suggesting an effective digestion and absorption of AAs present in casein. Also, ileal infusion did not result in immune activation nor in GI symptoms. CLINICALTRIALS.GOV: NCT01509469. Copyright © 2016 The Authors. Published by Elsevier

Maternal Docosahexaenoic Acid Increases Adiponectin and Normalizes IUGR-Induced Changes in Rat Adipose Deposition

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Heidi N. Bagley

2013-01-01

Full Text Available Intrauterine growth restriction (IUGR predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor-γ2 (PPARγ2 in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPARγ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA, a PPARγ agonist, would normalize IUGR adipose deposition in association with increased PPARγ, adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI- induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1 normalizes IUGR-induced changes in adipose deposition and visceral PPARγ expression in male rats and (2 increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced changes in rat adipose deposition.

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Bagley, Heidi N; Wang, Yan; Campbell, Michael S; Yu, Xing; Lane, Robert H; Joss-Moore, Lisa A

2013-01-01

Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor- γ 2 (PPAR γ 2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPAR γ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPAR γ agonist, would normalize IUGR adipose deposition in association with increased PPAR γ , adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPAR γ expression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

Induction of resistance to gray mold with benzothiadiazole modifies amino acid profile and increases proanthocyanidins in grape: primary versus secondary metabolism.

Science.gov (United States)

Iriti, Marcello; Rossoni, Mara; Borgo, Michele; Ferrara, Luigia; Faoro, Franco

2005-11-16

Field treatments of grapevine (cv. Merlot) with the plant activator benzothiadiazole (BTH, 0.3 mM) induced resistance against gray mold caused by Botrytis cinerea. Both incidence and severity of the disease were reduced. The resistance was associated with an increase of total polyphenols in berry skins, in particular, the proanthocyanidin fraction, that increased up to 36%. The amino acid profile of leaves was also modified by treatments, particularly lysine, that augmented 4-fold. Other amino acids involved in resistance mechanisms to either biotic or abiotic stress increased as well. These results indicate that BTH treatments can be used to control gray mold, thereby limiting an excessive use of fungicides, and could be exploited to increase the content of micronutrients of high nutritional value, arising from both primary and secondary metabolisms.

Tall oil fatty acid inclusion in the diet improves performance and increases ileal density of lactobacilli in broiler chickens.

Science.gov (United States)

Vienola, K; Jurgens, G; Vuorenmaa, J; Apajalahti, J

2018-04-20

1. Studies were conducted with tall oil fatty acids (TOFA) to determine their effect on broiler chicken performance and ileal microbiota. TOFA, a product originating from coniferous trees and recovered by fractional distillation of side-streams from pulp production, mainly comprises free long-chain fatty acids (~90%) and resin acids (~8%). Conjugated linolenic acids and pinolenic acid are characteristic fatty acid components of TOFA. 2. TOFA products at 750 mg/kg feed were tested in two 35-day broiler chicken trials, each using a wheat soya-based diet and with 12 replicate pens per treatment. In both trials, TOFA improved body weight gain at all time points (P TOFA formulations (silica carrier and palm oil coating) were tested and showed performance effects similar to liquid TOFA. 3. Ileal digesta of the broiler chickens was analysed for total eubacteria, Lactobacillus spp., Enterococcus spp., Escherichia coli and Clostridium perfringens on days 14 and 35. TOFA significantly increased total eubacteria and lactobacilli density on day 14 (P TOFA (P 250 mg/l. The in vitro results were thus in line with in vivo observations. 5. The mechanisms behind the bacterial shifts and their role in performance improvement are unknown. Further purification of TOFA components is needed to identify the effective agents.

Effect of propionic acid on citric acid fermentation in an integrated citric acid-methane fermentation process.

Science.gov (United States)

Xu, Jian; Bao, Jia-Wei; Su, Xian-Feng; Zhang, Hong-Jian; Zeng, Xin; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui

2016-03-01

In this study, an integrated citric acid-methane fermentation process was established to solve the problem of wastewater treatment in citric acid production. Citric acid wastewater was treated through anaerobic digestion and then the anaerobic digestion effluent (ADE) was further treated and recycled for the next batch citric acid fermentation. This process could eliminate wastewater discharge and reduce water resource consumption. Propionic acid was found in the ADE and its concentration continually increased in recycling. Effect of propionic acid on citric acid fermentation was investigated, and results indicated that influence of propionic acid on citric acid fermentation was contributed to the undissociated form. Citric acid fermentation was inhibited when the concentration of propionic acid was above 2, 4, and 6 mM in initial pH 4.0, 4.5 and, 5.0, respectively. However, low concentration of propionic acid could promote isomaltase activity which converted more isomaltose to available sugar, thereby increasing citric acid production. High concentration of propionic acid could influence the vitality of cell and prolong the lag phase, causing large amount of glucose still remaining in medium at the end of fermentation and decreasing citric acid production.

Exposure to TBT increases accumulation of lipids and alters fatty acid homeostasis in the ramshorn snail Marisa cornuarietis.

Science.gov (United States)

Janer, Gemma; Navarro, Juan Carlos; Porte, Cinta

2007-09-01

Recent studies have shown that organotin compounds affect lipid homeostasis in vertebrates, probably through interaction with RXR and/or PPARgamma receptors. Molluscs are sensitive species to the toxic effects of tributyltin (TBT), particularly to masculinization, and TBT has been recently shown to bind to molluscs RXR. Thus, we hypothesized that exposure to TBT could affect lipid homeostasis in the ramshorn snail Marisa cornuarietis. For comparative purposes, the synthetic androgen methyl-testosterone (MT) was included in the study due to its masculinization effects, but its lack of binding to the RXR receptor. M. cornuarietis was exposed to different concentrations of TBT (30, 125, 500 ng/L as Sn) and MT (30, 300 ng/L) for 100 days. Females exposed to 500 ng/L TBT showed increased percentage of lipids and increased levels of fatty acids in the digestive gland/gonad complex (2- to 3-fold). In addition, fatty acid profiles were altered in both males and females exposed to 125 and 500 ng/L TBT. These effects were not observed in females exposed to MT. Overall, this work suggest that TBT acts as a potent inducer of lipid and fatty acid accumulation in M. cornuarietis as shown in vertebrate studies earlier, and that sex differences in sensitivity do exist.

Folic acid treatment increases homocysteine remethylation and methionine transmethylation in healthy subjects

NARCIS (Netherlands)

Stam, F.; Smulders, Y.M.; van Guldener, C.; Jakobs, C.A.J.M.; Stehouwer, C.D.A.; van der Meer, K.

2005-01-01

Folic acid treatment decreases plasma total homocysteine concentrations in healthy subjects, but the effects on homocysteine metabolism are unknown. In the present study, we investigated the effect of 3 weeks of oral treatment with 5 mg of folic acid on one-carbon flux rates in 12 healthy subjects,

Increasing CO2 differentially affects essential and non-essential amino acid concentration of rice grains grown in cadmium-contaminated soils.

Science.gov (United States)

Wu, Huibin; Song, Zhengguo; Wang, Xiao; Liu, Zhongqi; Tang, Shirong

2016-09-01

Environmental pollution by both ambient CO2 and heavy metals has been steadily increasing, but we do not know how fluctuating CO2 concentrations influence plant nutrients under high Cd pollution, especially in crops. Here, we studied the effects of elevated CO2 and Cd accumulation on proteins and amino acids in rice under Cd stress. In this pot experiment, we analyzed the amino-acid profile of 20 rice cultivars that accumulate Cd differently; the plants were grown in Cd-containing soils under ambient conditions and elevated CO2 levels. We found that although Cd concentrations appeared to be higher in most cultivars under elevated CO2 than under ambient CO2, the effect was significant only in seven cultivars. Combined exposure to Cd and elevated CO2 strongly decreased rice protein and amino acid profiles, including essential and non-essential amino acids. Under elevated CO2, the ratios of specific amino acids were either higher or lower than the optimal ratios provided by FAO/WHO, suggesting that CO2 may flatten the overall amino-acid profile, leading to an excess in some amino acids and deficiencies in others when the rice is consumed. Thus, Cd-tainted rice limits the concentration of essential amino acids in rice-based diets, and the combination with elevated CO2 further exacerbates the problem. Copyright © 2016 Elsevier Ltd. All rights reserved.

Allelopathic interactions of linoleic acid and nitric oxide increase the competitive ability of Microcystis aeruginosa.

Science.gov (United States)

Song, Hao; Lavoie, Michel; Fan, Xiaoji; Tan, Hana; Liu, Guangfu; Xu, Pengfei; Fu, Zhengwei; Paerl, Hans W; Qian, Haifeng

2017-08-01

The frequency and intensity of cyanobacterial blooms are increasing worldwide with major societal and economic costs. Interactions between toxic cyanobacteria and eukaryotic algal competitors can affect toxic bloom formation, but the exact mechanisms of interspecies interactions remain unknown. Using metabolomic and proteomic profiling of co-cultures of the toxic cyanobacterium Microcystis aeruginosa with a green alga as well as of microorganisms collected in a Microcystis spp. bloom in Lake Taihu (China), we disentangle novel interspecies allelopathic interactions. We describe an interspecies molecular network in which M. aeruginosa inhibits growth of Chlorella vulgaris, a model green algal competitor, via the release of linoleic acid. In addition, we demonstrate how M. aeruginosa takes advantage of the cell signaling compound nitric oxide produced by C. vulgaris, which stimulates a positive feedback mechanism of linoleic acid release by M. aeruginosa and its toxicity. Our high-throughput system-biology approach highlights the importance of previously unrecognized allelopathic interactions between a broadly distributed toxic cyanobacterial bloom former and one of its algal competitors.

Specific serum protein changes associated with primary and secondary Strongylus vulgaris infections in pony yearlings.

Science.gov (United States)

Kent, J E

1987-03-01

The concentrations of haptoglobin, immunoglobin (Ig)G(T) and IgG were measured in the serum of four previously parasite-free pony yearlings following a single dose of 700 (Group H) or 200 (Group L) stage three Strongylus vulgaris larvae (L3) and following a reinfection with the same doses 34 weeks later. The results are compared with an uninfected control pony. The haptoglobin concentration increased during Weeks 1 to 6 and 14 to 17 after infection in the serum of the ponies receiving 200 L3, but in only one pony dosed with 700 L3 (during Weeks 1 to 16). The serum haptoglobin also increased during the first seven weeks after the second infection, in three of the four ponies following the second dose of larvae. The serum IgG(T) concentration started to increase from Week 6 or 9 in the ponies given 700 L3, reaching peaks of 44 and 32 g/litre respectively, eight to nine weeks later, compared with a peak of 16 g/litre 20 to 22 weeks after infection in ponies dosed with 200 L3. The IgG(T) concentration increased to a maximum of 25 g/litre in the serum of only one of the four ponies after the reinfection. The serum IgG concentration in all ponies increased nearly twofold during the first eight weeks after both the primary and secondary dose of larvae. It is concluded that the measurement of specific proteins is more reliable and quicker than the electrophoretic separation and quantitation of protein bands, in tracing changes in serum proteins following the artificial infection of ponies with S vulgaris larvae.

Diabetes-induced increases in 131I-albumin permeation are unaffected by essential fatty acid depletion

International Nuclear Information System (INIS)

Williamson, J.R.; Lefkowith, J.B.; Chang, K.; Tilton, R.G.

1990-01-01

The authors assessed effects of essential fatty acid deficiency (EFAD) on regional 131 I-albumin permeation in diabetic and age-matched control rats. Male, Sprague-Dawley rats (50-75 g) were randomized into EFAD diet or normal diet groups. Three months later, diabetes was induced in one half of the rats in each group by injecting i.v. 35-45 mg/kg b.w. streptozotocin. One month later, 131 I-albumin clearance (μ g plasma/g tissue/minute) was assessed as described previously (Circ Res 64;890, 1989). Within controls, EFAD decreased body weight gain 28% but did not affect control values for plasma glucose (118±8 (SD) mg/dl) or glycosylated hemoglobin (1.33±0.22 % of total hemoglobin). In normal diet and EFAD diabetics, plasma glucose (535±64 and 419±161, respectively) and glycosylated hemoglobin (4.38±0.97 and 2.97±1.69) were increased significantly versus controls. Diabetes increased 131 I-albumin clearance in retinal (5.1x controls), choroid (3.4x), anterior uvea (2.7x), aorta (3.5x), and sciatic nerve (2.2x). No differences were evident in tissue 131 I-albumin clearances between both control groups or both diabetic groups. These results suggest that essential fatty acids do not modulate diabetes-induced changes in endothelial cell barrier function

Boronic acid recognition of non-interacting carbohydrates for biomedical applications: increasing fluorescence signals of minimally interacting aldoses and sucralose.

Science.gov (United States)

Resendez, Angel; Halim, Md Abdul; Singh, Jasmeet; Webb, Dominic-Luc; Singaram, Bakthan

2017-11-22

To address carbohydrates that are commonly used in biomedical applications with low binding affinities for boronic acid based detection systems, two chemical modification methods were utilized to increase sensitivity. Modified carbohydrates were analyzed using a two component fluorescent probe based on boronic acid-appended viologen-HPTS (4,4'-o-BBV). Carbohydrates normally giving poor signals (fucose, l-rhamnose, xylose) were subjected to sodium borohydride (NaBH 4 ) reduction in ambient conditions for 1 h yielding the corresponding sugar alcohols from fucose, l-rhamnose and xylose in essentially quantitative yields. Compared to original aldoses, apparent binding affinities were increased 4-25-fold. The chlorinated sweetener and colon permeability marker sucralose (Splenda), otherwise undetectable by boronic acids, was dechlorinated to a detectable derivative by reactive oxygen and hydroxide intermediates by the Fenton reaction or by H 2 O 2 and UV light. This method is specific to sucralose as other common sugars, such as sucrose, do not contain any carbon-chlorine bonds. Significant fluorescence response was obtained for chemically modified sucralose with the 4,4'-o-BBV-HPTS probe system. This proof of principle can be applied to biomedical applications, such as gut permeability, malabsorption, etc.

Red Blood Cell Docosapentaenoic Acid (DPA n-3) is Inversely Associated with Triglycerides and C-reactive Protein (CRP) in Healthy Adults and Dose-Dependently Increases Following n-3 Fatty Acid Supplementation

Science.gov (United States)

Skulas-Ray, Ann C.; Flock, Michael R.; Richter, Chesney K.; Harris, William S.; West, Sheila G.; Kris-Etherton, Penny M.

2015-01-01

The role of the long-chain omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in lipid metabolism and inflammation has been extensively studied; however, little is known about the relationship between docosapentaenoic acid (DPA, 22:5 n-3) and inflammation and triglycerides (TG). We evaluated whether n-3 DPA content of red blood cells (RBC) was associated with markers of inflammation (interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CRP) and fasting TG prior to n-3 supplementation in two studies (Study 1: n = 115, aged 20–44 years, body mass index (BMI) 20–30 kg/m2, TG = 34–176 mg/dL; Study 2: n = 28, aged 22–65 years, BMI 24–37 kg/m2, TG = 141–339 mg/dL). We also characterized the dose-response effects of n-3 fatty acid supplementation on RBC n-3 DPA after five months of supplementation with fish oil (Study 1: 0, 300, 600, 900, and 1800 mg/day EPA + DHA) and eight weeks of prescription n-3 ethyl esters (Study 2: 0, 850, and 3400 mg/day EPA + DHA). In Study 1, RBC n-3 DPA was inversely correlated with CRP (R2 = 36%, p < 0.001) and with fasting TG (r = −0.30, p = 0.001). The latter finding was replicated in Study 2 (r = −0.33, p = 0.04). In both studies, n-3 supplementation significantly increased RBC n-3 DPA dose-dependently. Relative increases were greater for Study 1, with increases of 29%–61% vs. 14%–26% for Study 2. The associations between RBC n-3 DPA, CRP, and fasting TG may have important implications for the prevention of atherosclerosis and chronic inflammatory diseases and warrant further study. PMID:26247967

Increased intestinal mucosal turnover and radiosensitivity to supralethal whole-body irradiation resulting from cholic acid-induced alterations of the intestinal microecology of germfree CFW mice

International Nuclear Information System (INIS)

Mastromarino, A.J.; Wilson, R.

1976-01-01

The prolonged mean survival time of germfree mice, compared to conventional mice, after exposure to 1000-10,000 rad whole-body irradiation has been postulated to be a function of an increased turnover time of the intestinal mucosal cells caused by the absence of free bile acids. To test this hypothesis, the diet of germ-free CFW mice was supplemented with 0.15 percent cholic acid for 2 weeks. The turnover of thymidine-labeled intestinal mucosal cells and the radiosensitivity to supralethal whole-body irradiation were significantly increased compared to germfree controls. There was a positive correlation between increased survivial time after supralethal whole-body irradiation and slower intestinal mucosal turnover time. Germfree mice supplemented with cholic acid had intestinal mucosal turnover times comparable to those of conventionalized controls. Although cholic acid reduces the mean survival time of germfree mice after suppralethal whole-body irradiation, the mean survival value is significantly greater than the conventionalized controls. Supplementing the diet of conventionalized CFW mice with cholic acid did not significantly decrease the intestinal mucosal turnover time nor did it significantly alter their radiosensitivity to supralethal whole-body irradiation. The data suggest that cholic acid is one of the microecological factors responsible for controlling the mucosal renewal rate and the mean survival time after whole-body irradiation

Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome.

Science.gov (United States)

Barrett, Eoin; Fitzgerald, Patrick; Dinan, Timothy G; Cryan, John F; Ross, R Paul; Quigley, Eamonn M; Shanahan, Fergus; Kiely, Barry; Fitzgerald, Gerald F; O'Toole, Paul W; Stanton, Catherine

2012-01-01

The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (10(9) microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (pbreve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (pbreve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (pbreve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (pbreve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (pbreve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.

Mixed cultures of Kimchi lactic acid bacteria show increased cell ...

African Journals Online (AJOL)

ufuoma

production and amino acid release among the tested bacteria. W. koreensis 521 ... production of fermented food products, such as yogurt, cheese, sauerkraut and ... habits, stress and excessive dieting (Kapka-Skrzypczak et al., 2012). Mixed ...

Saturated fatty acid intake can influence increase in plasminogen activator inhibitor-1 in obese adolescents.

Science.gov (United States)

Masquio, D C L; de Piano, A; Campos, R M S; Sanches, P L; Corgosinho, F C; Carnier, J; Oyama, L M; do Nascimento, C M P O; de Mello, M T; Tufik, S; Dâmaso, A R

2014-04-01

The aim of this study was to verify if saturated fatty acid intake adjusted by tertiles can influence metabolic, inflammation, and plasminogen activator inhibitor-1 (PAI-1) in obese adolescents. Body mass, height, body mass index, waist circumference, blood pressure, and body composition of 108 obese adolescents were obtained. Fasting glucose, insulin, PAI-1, and CRP were determined. Insulin resistance was assessed by Homeostasis Model Assessment (HOMA-IR) and insulin sensitivity by Quantitative Insulin Sensitivity Check Index (QUICKI). Dietetic intake was estimated by a 3-day dietary record, and volunteers were divided according to consumption of saturated fatty acids: tertile 1 [Low Saturated Fatty Acid Intake (Low-SFA): ≤12.14 g], tertile 2 [Moderate Saturated Fatty Intake (Moderate SFA intake): 12.15-20.48 g], and tertile 3 [High Saturated Fatty Acid Intake (High-SFA Intake); >20.48 g]. Statistical analysis was performed using STATISTICA 7.0 software and the significance level was set at pstudy is that Moderate and High-SFA intakes presented significantly higher values of PAI-1 than Low-SFA Intake. PAI-1 was positively associated with saturated fatty intake, waist circumference, mean blood pressure, and HOMA-IR. SFA intake was predictor of PAI-1 independent of body fat, HOMA-IR and total-cholesterol. In addition, PAI-1 was an independent predictor of blood pressure. HOMA-IR and QUICKI presented significantly higher and lower, respectively, in High-SFA compared to Moderate-SFA intake. High-SFA influenced cardiovascular disease risks, since it increased PAI-1 and insulin resistance, and decreased insulin sensibility, leading to vicious cycle among food ingestion, pro-thrombotic state, and cardiovascular risks in obese adolescents. © Georg Thieme Verlag KG Stuttgart · New York.

Pre-cold stress increases acid stress resistance and induces amino ...

African Journals Online (AJOL)

pre-adapted to cold stress revealed induction of amino acid homeostasis and energy ... substrate, thereby reducing yeast and mould ..... spontaneous mutation of llmg_1816 (gdpp) induced by .... species to UV-B-induced damage in bacteria. J.

Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

Science.gov (United States)

Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

2015-09-01

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion

DEFF Research Database (Denmark)

Ferreira, Raphael; Teixeiraa, Paulo Goncalves; Siewers, Verena

2018-01-01

and tightly regulated metabolic network. Here we generated a Saccharomyces cerevisiae platform strain with a simplified lipid metabolism network with high-level production of free fatty acids (FFAs) due to redirected fatty acid metabolism and reduced feedback regulation. Deletion of the main fatty acid...

Uric Acid Excretion Predicts Increased Blood Pressure Among American Adolescents of African Descent.

Science.gov (United States)

Mrug, Sylvie; Mrug, Michal; Morris, Anjana Madan; Reynolds, Nina; Patel, Anita; Hill, Danielle C; Feig, Daniel I

2017-04-01

Hyperuricemia predicts the incidence of hypertension in adults and its treatment has blood pressure (BP)-lowering effects in adolescents. To date, no studies have examined the predictive usage of hyperuricemia or urinary uric acid excretion on BP changes in adolescents. Mechanistic models suggest that uric acid impairs both endothelial function and vascular compliance, which would potentially exacerbate a myriad of hypertensive mechanisms, yet little is known about interaction of uric acid and other hypertension risk factors. The primary study was aimed at the effects of stress on BP in adolescents. A community sample of 84 low-income, urban adolescents (50% male, 95% African American, mean age = 13.36 ± 1 years) was recruited from public schools. Youth completed a 12-hour (overnight) urine collection at home and their BP was measured during rest and in response to acute psychosocial stress. Seventy-six of the adolescents participated in a follow-up visit at 1.5 years when their resting BP was reassessed. In this substudy, we assessed the relationship of renal urate excretion and BP reactivity. After adjusting for resting BP levels at baseline and other covariates, higher levels of uric acid excretion predicted greater BP reactivity to acute psychosocial stress and higher resting BP at 18 months. Urinary excretion of uric acid can serve as an alternative, noninvasive measure of serum uric acid levels that are predictive of BP changes. As hyperuricemia-associated hypertension is treatable, urban adolescents may benefit from routine screening for hyperuricemia or high uric acid excretion. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Comparison of Buffer Effect of Different Acids During Sandstone Acidizing

International Nuclear Information System (INIS)

Shafiq, Mian Umer; Mahmud, Hisham Khaled Ben; Hamid, Mohamed Ali

2015-01-01

The most important concern of sandstone matrix acidizing is to increase the formation permeability by removing the silica particles. To accomplish this, the mud acid (HF: HCl) has been utilized successfully for many years to stimulate the sandstone formations, but still it has many complexities. This paper presents the results of laboratory investigations of different acid combinations (HF: HCl, HF: H 3 PO 4 and HF: HCOOH). Hydrofluoric acid and fluoboric acid are used to dissolve clays and feldspar. Phosphoric and formic acids are added as a buffer to maintain the pH of the solution; also it allows the maximum penetration of acid into the core sample. Different tests have been performed on the core samples before and after the acidizing to do the comparative study on the buffer effect of these acids. The analysis consists of permeability, porosity, color change and pH value tests. There is more increase in permeability and porosity while less change in pH when phosphoric and formic acids were used compared to mud acid. From these results it has been found that the buffer effect of phosphoric acid and formic acid is better than hydrochloric acid. (paper)

Root jasmonic acid synthesis and perception regulate folivore-induced shoot metabolites and increase Nicotiana attenuata resistance.

Science.gov (United States)

Fragoso, Variluska; Rothe, Eva; Baldwin, Ian T; Kim, Sang-Gyu

2014-06-01

While jasmonic acid (JA) signaling is widely accepted as mediating plant resistance to herbivores, and the importance of the roots in plant defenses is recently being recognized, the role of root JA in the defense of above-ground parts remains unstudied. To restrict JA impairment to the roots, we micrografted wildtype Nicotiana attenuata shoots to the roots of transgenic plants impaired in JA signaling and evaluated ecologically relevant traits in the glasshouse and in nature. Root JA synthesis and perception are involved in regulating nicotine production in roots. Strikingly, systemic root JA regulated local leaf JA and abscisic acid (ABA) concentrations, which were associated with differences in nicotine transport from roots to leaves via the transpiration stream. Root JA signaling also regulated the accumulation of other shoot metabolites; together these account for differences in resistance against a generalist, Spodoptera littoralis, and a specialist herbivore, Manduca sexta. In N. attenuata's native habitat, silencing root JA synthesis increased the shoot damage inflicted by Empoasca leafhoppers, which are able to select natural jasmonate mutants. Silencing JA perception in roots also increased damage by Tupiocoris notatus. We conclude that attack from above-ground herbivores recruits root JA signaling to launch the full complement of plant defense responses. © 2014 Max Planck Society. New Phytologist © 2014 New Phytologist Trust.

Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid

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Ryan C. Bates

2015-08-01

Full Text Available Neural tissue exposure to valproic acid (VPA increases several pro-survival phospho-proteins that can be used as biomarkers for indicating a beneficial drug response (pAktSer473, pGSK3βSer9, pErk1/2Thr202/Tyr204. Unfortunately, targeting VPA to neural tissue is a problem due to severe asymmetrical distribution, wherein the drug tends to remain in peripheral blood rather than localizing within the brain. Intracerebral delivery of an amide-linked VPA–PEG conjugate could address these issues by enhancing retention and promoting cerebro-global increases in pro-survival phospho-proteins. It is necessary to assay for the retained bioactivity of a PEGylated valproic acid molecule, along with locating an intracranial cannula placement that optimizes the increase of a known downstream biomarker for chronic VPA exposure. Here we show an acute injection of VPA–PEG conjugate within brain tissue increased virtually all of the assayed phospho-proteins, including well-known pro-survival factors. In contrast, an acute injection of VPA expectedly decreased signaling throughout the hour. Needle penetration into whole brain tissue is the intentional cause of trauma in this procedure. The trauma to brain tissue was observed to overcome known phospho-protein increases for unmodified VPA in the injected solution, while VPA–PEG conjugate appeared to induce significant increases in pro-survival phospho-proteins, despite the procedural trauma.

Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome.

Directory of Open Access Journals (Sweden)

Eoin Barrett

Full Text Available The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15 were orally gavaged with either B. breve DPC6330 (10(9 microorganisms/day alone or in combination with 0.5% (w/w linoleic acid & 0.5% (w/w α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11 in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05. Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11 in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05, whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05 compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01 and α-linolenic acid in adipose tissue (p<0.001, whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05, and α-linolenic acid in adipose tissue (p<0.001. B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated

Short-term increase of plasma free fatty acids does not interfere with intrinsic mitochondrial function in healthy young men

NARCIS (Netherlands)

Brands, Myrte; Hoeks, Joris; Sauerwein, Hans P.; Ackermans, Mariette T.; Ouwens, Margriet; Lammers, Nicolette M.; van der Plas, Mart N.; Schrauwen, Patrick; Groen, Albert K.; Serlie, Mireille J.

2011-01-01

Free fatty acid (FFA)- and obesity-induced insulin resistance has been associated with disturbed mitochondrial function. Elevated plasma FFA can impair insulin-induced increase of adenosine triphosphate synthesis and downregulate the expression of genes important in the biogenesis of mitochondria in

Increase in the penetration of tracer compounds into the rat brain during 2-methyl-4-chlorophenoxyacetic acid (MCPA) intoxication

International Nuclear Information System (INIS)

Elo, H.A.; Ylitalo, P.; Kyoettilae, J.; Hervonen, H.

1982-01-01

The penetration of different intravenous tracer molecules such as 14 C-labelled 2-methyl-4-chlorophenoxyacetic acid ( 14 C-MCPA), 14 C-p-aminobenzoic acid ( 14 C-PABA), 14 C-sucrose, 14 C-antipyrine and iodinated ( 125 I) human albumin ( 125 I-HA) into the brain and cerebrospinal fluid (CSF) was studied in MCPA-intoxicated and control rats. Toxic subcutaneous doses of sodium salt of MCPA (200-500 mg/kg) increased highly the brain/plasma and CSF/plasma ratios of 14 C-MCPA and 14 C-PABA, as compared to the muscle/plasma ratio. Probenecid (200 mg/kg) did not affect the cerebral MCPA concentration in the intoxicated animals. The tissue/plasma ratios of 14 C-sucrose, 14 C-antipyrine and 125 I-HA were also increased in the brain and CSF of intoxicated animals, but the increases were less pronounced than those of 14 C-MCPA or 14 C-PABA. The results indicate that MCPA intoxication caused a selective damage of the blood-brain barrier in the brain areas studied. (author)

Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

NARCIS (Netherlands)

Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

2004-01-01

Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized,

Allelopathic interactions of linoleic acid and nitric oxide increase the competitive ability of Microcystis aeruginosa

Science.gov (United States)

Song, Hao; Lavoie, Michel; Fan, Xiaoji; Tan, Hana; Liu, Guangfu; Xu, Pengfei; Fu, Zhengwei; Paerl, Hans W; Qian, Haifeng

2017-01-01

The frequency and intensity of cyanobacterial blooms are increasing worldwide with major societal and economic costs. Interactions between toxic cyanobacteria and eukaryotic algal competitors can affect toxic bloom formation, but the exact mechanisms of interspecies interactions remain unknown. Using metabolomic and proteomic profiling of co-cultures of the toxic cyanobacterium Microcystis aeruginosa with a green alga as well as of microorganisms collected in a Microcystis spp. bloom in Lake Taihu (China), we disentangle novel interspecies allelopathic interactions. We describe an interspecies molecular network in which M. aeruginosa inhibits growth of Chlorella vulgaris, a model green algal competitor, via the release of linoleic acid. In addition, we demonstrate how M. aeruginosa takes advantage of the cell signaling compound nitric oxide produced by C. vulgaris, which stimulates a positive feedback mechanism of linoleic acid release by M. aeruginosa and its toxicity. Our high-throughput system-biology approach highlights the importance of previously unrecognized allelopathic interactions between a broadly distributed toxic cyanobacterial bloom former and one of its algal competitors. PMID:28398349

Genomic and metabolic disposition of non-obese type 2 diabetic rats to increased myocardial fatty acid metabolism.

Directory of Open Access Journals (Sweden)

Sriram Devanathan

Full Text Available Lipotoxicity of the heart has been implicated as a leading cause of morbidity in Type 2 Diabetes Mellitus (T2DM. While numerous reports have demonstrated increased myocardial fatty acid (FA utilization in obese T2DM animal models, this diabetic phenotype has yet to be demonstrated in non-obese animal models of T2DM. Therefore, the present study investigates functional, metabolic, and genomic differences in myocardial FA metabolism in non-obese type 2 diabetic rats. The study utilized Goto-Kakizaki (GK rats at the age of 24 weeks. Each rat was imaged with small animal positron emission tomography (PET to estimate myocardial blood flow (MBF and myocardial FA metabolism. Echocardiograms (ECHOs were performed to assess cardiac function. Levels of triglycerides (TG and non-esterified fatty acids (NEFA were measured in both plasma and cardiac tissues. Finally, expression profiles for 168 genes that have been implicated in diabetes and FA metabolism were measured using quantitative PCR (qPCR arrays. GK rats exhibited increased NEFA and TG in both plasma and cardiac tissue. Quantitative PET imaging suggests that GK rats have increased FA metabolism. ECHO data indicates that GK rats have a significant increase in left ventricle mass index (LVMI and decrease in peak early diastolic mitral annular velocity (E' compared to Wistar rats, suggesting structural remodeling and impaired diastolic function. Of the 84 genes in each the diabetes and FA metabolism arrays, 17 genes in the diabetes array and 41 genes in the FA metabolism array were significantly up-regulated in GK rats. Our data suggest that GK rats' exhibit increased genomic disposition to FA and TG metabolism independent of obesity.

Increased serum levels of hyaluronic acid in pregnancies complicated by preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

Science.gov (United States)

Osmers, R G; Schütz, E; Diedrich, F; Wehry, B; Krauss, T; Oellerich, M; Kuhn, W

1998-02-01

Fifteen percent of patients who later have hemolysis, elevated liver enzymes, and low platelets syndrome develop initially have nonspecific symptoms. Early diagnosis could ensure adequate obstetric management; however, prognostic biochemical tests are lacking. We hypothesized that elevated hyaluronic acid serum levels might be an early indicator of hemolysis, elevated liver enzymes, and low platelets syndrome because it is known to be a sensitive marker of liver cell function. Hyaluronic acid in serum was measured in patients with normal pregnancies (n = 109) and in those patients with pregnancies complicated by preeclampsia (n = 14) or hemolysis, elevated liver enzymes, and low platelets syndrome (n = 11). A significant increase in hyaluronic acid serum concentrations was observed in patients with hemolysis, elevated liver enzymes, and low platelets syndrome or with preeclampsia (p hyaluronic acid serum levels in hemolysis, elevated liver enzymes, and low platelets syndrome correlated with the clinical severity of the individual course of disease as measured by intensive care unit time (r = 0.72; p hyaluronic acid in preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome are significantly elevated and might play an important diagnostic and prognostic role in patients with hemolysis, elevated liver enzymes, and low platelets syndrome.

Acetylsalicylic acid supplementation improves protein utilization efficiency while vitamin E supplementation reduces markers of the inflammatory response in weaned pigs challenged with enterotoxigenic E.coli

Institute of Scientific and Technical Information of China (English)

Jae Cheol Kim; Bruce P.Mullan; John L.Black; Robert J.E.Hewitt; Robert J.van Barneveld; John R.Pluske

2017-01-01

Background:This experiment was conducted to test the hypothesis that vitamin E (Vit E) and acetylsalicylic acid (ASA),a cyclooxygenase-2 (COX-2) inhibitor,will additively reduce the production of the immunosuppressive molecule prostaglandin E2 (PGE2) and hence reduce inflammatory responses in weaner pigs experimentally infected with an enterotoxigenic strain of E.coli.Methods:The experiment was conducted in a research facility with 192 individually-housed male weaner pigs (Landrace × Large White) weighing 6.6 ± 0.04 kg (mean ± SEM).The pigs were experimentally infected with an enterotoxigenic strain of E.coli and were allocated to a 2 × 3 factorial design with the respective factors being without and with 125 ppm ASA and three levels ofVit E supplementation (50,100 or 200 IU/kg diet,dl-α-tocopheryl acetate).Results:Acetylsalicylic acid supplementation improved average daily gain (P ＜ 0.05) and tended to improve feed:gain ratio (P ＜ 0.10) during the first 14 d after weaning.Acetylsalicylic acid supplementation also improved (P ＜ 0.001) amino acid utilization efficiency (as assessed by plasma urea level) and tended to decrease (P ＜ 0.10) PGE2 production in the liver without affecting small intestinal histology and tight junction protein mRNA expression in the jejunal epithelium.Vitamin E supplementation greater than 100 IU/kg diet sustained both the plasma Vit E concentration (P ＜ 0.001) and plasma haptoglobin content (P ＜ 0.001) after weaning.However,there was no additive effects of the combined supplementation of ASA and Vit E on performance,intestinal barrier function and inflammatory responses of weaned pigs.Conclusions:Although ASA and vitamin E improved amino acid utilization efficiency and reduced acute inflammatory responses,ASA and vitamin E did not additively reduce production of PGE2 and inflammatory responses in weaner pigs experimentally infected with an enterotoxigenic strain of E.coli.

Differences in serum protein 2D gel electrophoresis patterns of Przewalski's (Mongolian wild horse) and thoroughbred horses.

Science.gov (United States)

Barsuren, Enkhbolor; Namkhai, Bandi; Kong, Hong Sik

2015-04-01

The objective of this study was to assess differences in serum protein expression profiles of Przewalski's (Mongolian wild horse) and thoroughbred horses using proteome analysis. The serum proteins were separated by two-dimensional electrophoresis (2-DE) and five different gene products were identified. Proteins represented by the five spots were identified by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry (MS)/MS technology. The identities of all proteins were deduced based on their similarity to proteins in the human plasma protein database. Three proteins (a haptoglobin-2 alpha glycoprotein and two haptoglobin-2beta glycoproteins with different accession numbers) were downregulated in Przewalski's horse sera compared to thoroughbred horse sera. Moreover, two proteins (tetraspanin-18 and pM5) were upregulated in Przewalski's horses compared to thoroughbred horses. Haptoglobin-2 alpha and haptoglobin-2beta may serve as candidate molecules in future studies of inflammation, coagulation, immune modulation and pro-oxidant and antioxidant activity with consequential effects on the entire metabolism of the horse. © 2014 Japanese Society of Animal Science.

Methods of increasing the harshness of texture of old concrete pavements--acid etching.

Science.gov (United States)

1975-01-01

Of the four acids tested in the laboratory, the nitric and hydrochloric types were selected for field experiments. These two acids performed about equally well, the choice as to which to use is dictated by price and availability. In the field experim...

Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention.

Science.gov (United States)

Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D; Tuck, Michael L; Frautschy, Sally A; Cole, Greg M

2007-12-26

Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate beta-amyloid (Abeta). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential omega-3 fatty acid related to reduced AD risk and reduced Abeta accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Abeta production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD.

Butyrate and other short-chain fatty acids increase the rate of lipolysis in 3T3-L1 adipocytes

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John M. Rumberger

2014-10-01

Full Text Available We determined the effect of butyrate and other short-chain fatty acids (SCFA on rates of lipolysis in 3T3-L1 adipocytes. Prolonged treatment with butyrate (5 mM increased the rate of lipolysis approximately 2–3-fold. Aminobutyric acid and acetate had little or no effect on lipolysis, however propionate stimulated lipolysis, suggesting that butyrate and propionate act through their shared activity as histone deacetylase (HDAC inhibitors. Consistent with this, the HDAC inhibitor trichostatin A (1 µM also stimulated lipolysis to a similar extent as did butyrate. Western blot data suggested that neither mitogen-activated protein kinase (MAPK activation nor perilipin down-regulation are necessary for SCFA-induced lipolysis. Stimulation of lipolysis with butyrate and trichostatin A was glucose-dependent. Changes in AMP-activated protein kinase (AMPK phosphorylation mediated by glucose were independent of changes in rates of lipolysis. The glycolytic inhibitor iodoacetate prevented both butyrate- and tumor necrosis factor-alpha-(TNF-α mediated increases in rates of lipolysis indicating glucose metabolism is required. However, unlike TNF-α– , butyrate-stimulated lipolysis was not associated with increased lactate release or inhibited by activation of pyruvate dehydrogenase (PDH with dichloroacetate. These data demonstrate an important relationship between lipolytic activity and reported HDAC inhibitory activity of butyrate, other short-chain fatty acids and trichostatin A. Given that HDAC inhibitors are presently being evaluated for the treatment of diabetes and other disorders, more work will be essential to determine if these effects on lipolysis are due to inhibition of HDAC.

Replacing soybean oil with increasing levels of soybean acid oil in diets of coturnix quails (Coturnix coturnix coturnix) and the effects on egg quality.

Science.gov (United States)

Roll, Aline A P; Forgiarini, Juliana; Xavier, Eduardo G; Lopes, Débora C N; Roll, Victor F B; Rutz, Fernando

2018-01-01

The effects of increasing levels of soybean acid oil in diets of quails on the quality of eggs were evaluated over a period of 56 days. A completely randomized design with five treatment levels of soybean acid oil (0, 2, 4, 6, and 8%) as a replacer for soybean oil and eight replicates of two quails each were used. A total of 240 fresh eggs were used for quality analysis, and 400 eggs were stored at 23ºC over a period of 0, 7, 14, 21, and 28 days for analysis of shelf-life. Polynomial regression and ANOVA with repeated measurements and Tukey´s tests were used. Soybean acid oil linearly increased the intensity of red (a* = -5.26 + 0.14 x, R2 = 0.89, P = 0.01) and yellow (b* = 42.32 + 0.44 x, R2 = 0.88 P = 0.01). All other variables of egg quality were not affected by the treatments, with the exception of sensory attributes, such as odor and aftertaste, which were more pronounced with soybean acid oil. In conclusion, soybean acid oil affects the intensity of yellow and red color of the yolk. Trained assessors detected differences in odor and aftertaste of eggs when soybean acid oil was included in the quail diet.

Increased Glutamate and Homocysteine and Decreased Glutamine Levels in Autism: A Review and Strategies for Future Studies of Amino Acids in Autism

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Ahmad Ghanizadeh

2013-01-01

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

Increased Glutamate and Homocysteine and Decreased Glutamine Levels in Autism: A Review and Strategies for Future Studies of Amino Acids in Autism

Science.gov (United States)

Ghanizadeh, Ahmad

2013-01-01

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

Effects of alkali or acid treatment on the isomerization of amino acids.

Science.gov (United States)

Ohmori, Taketo; Mutaguchi, Yuta; Doi, Katsumi; Ohshima, Toshihisa

2012-10-01

The effect of alkali treatment on the isomerization of amino acids was investigated. The 100×D/(D+L) values of amino acids from peptide increased with increase in the number of constituent amino acid residues. Furthermore, the N-terminal amino acid of a dipeptide was isomerized to a greater extent than the C-terminal residue. Copyright © 2012. Published by Elsevier B.V.

Nocturnal weakly acidic reflux promotes aspiration of bile acids in lung transplant recipients.

Science.gov (United States)

Blondeau, Kathleen; Mertens, Veerle; Vanaudenaerde, Bart A; Verleden, Geert M; Van Raemdonck, Dirk E; Sifrim, Daniel; Dupont, Lieven J

2009-02-01

Gastroesophageal reflux (GER) and aspiration of bile acids have been implicated as non-alloimmune risk factors for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of our study was to investigate the association between GER and gastric aspiration of bile acids and to establish which reflux characteristics may promote aspiration of bile acids into the lungs and may feature as a potential diagnostic tool in identifying lung transplantation (LTx) patients at risk for aspiration. Twenty-four stable LTx recipients were studied 1 year after transplantation. All patients underwent 24-hour ambulatory impedance-pH recording for the detection of acid (pH acidic (pH 4 to 7) reflux. On the same day, bronchoalveolar lavage fluid (BALF) was collected and then analyzed for the presence of bile acids (Bioquant enzymatic assay). Increased GER was detected in 13 patients, of whom 9 had increased acid reflux and 4 had exclusively increased weakly acidic reflux. Sixteen patients had detectable bile acids in the BALF (0.6 [0.4 to 1.5] micromol/liter). The 24-hour esophageal volume exposure was significantly increased in patients with bile acids compared to patients without bile acids in the BALF. Acid exposure and the number of reflux events (total, acid and weakly acidic) were unrelated to the presence of bile acids in the BALF. However, both nocturnal volume exposure and the number of nocturnal weakly acidic reflux events were significantly higher in patients with bile acids in the BALF. Weakly acidic reflux events, especially during the night, are associated with the aspiration of bile acids in LTx recipients and may therefore feature as a potential risk factor for the development of BOS.

Serum uric acid concentration is associated with early changes of glomerular filtration rate in patients with diabetes type 1 without increased albumin excretion.

Science.gov (United States)

Spaleniak, Sebastian; Korzeniewska-Dyl, Irmina; Moczulski, Dariusz

2014-10-01

The early loss of renal function in patients with type 1 diabetes may begin before proteinuria. Only 30% of patients with diabetes manifest overt proteinuria. According to the previous studies, increased urinary albumin excretion, which is considered a classic marker of progression of diabetic kidney disease, can regress to normal urine albumin excretion. The current studies conducted in patients with type 1 diabetes without increased urine albumin excretion showed that the uric acid concentration was an independent factor for the development of diabetic kidney disease. The aim of study was to assess the impact of uric acid concentration and to identify risk factors of the early glomerular filtration loss in patients with type 1 diabetes and normal urinary albumin excretion. 147 patients (61 women and 86 men) with type 1 diabetes without increased urine albumin excretion were analysed. GFR (gromerular filtration rate) was estimated based on the serum cystatin C concentration. Centile charts were used to determine the variation of uric acid concentration depending on GFR and gender. The mean value of the filtration rate for the study group was 117 ml/min/m2. The uric acid level above 90th percentile in relation to GFR was diagnosed in 8.2% of women and 0% of men, between 90th and 50th percentile in 44.3 % of women and 5.8% of men and below 50th percentile in 47.5% of women and 94.2% of men. Contrary to men in women higher serum acid concentration was strongly associated with higher glomerular filtration rate. Hyperfiltraion was diagnosed in 15 of women and 19 of men. The high normal uric acid concentration in women with type 1 diabetes might play a crucial role in development of hyperfiltration.

Dietary Caprylic Acid (C8:0) Does Not Increase Plasma Acylated Ghrelin but Decreases Plasma Unacylated Ghrelin in the Rat

Science.gov (United States)

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

Non-lethal infection parameters in mice separate sheep Type II Toxoplasma gondii isolates by virulence

DEFF Research Database (Denmark)

Jungersen, Gregers; Jensen, L; Rask, M.R.

2002-01-01

. six sheep abortions, two pigs. one cat and one fox were examined for their virulence to young mice by less dramatic parameters. Clinical disease of inoculated mice, directly evidenced by reduced weight gain, was correlated to increase in serum level of haptoglobin and level of specific antibodies...

Gambogic Acid Lysinate Induces Apoptosis in Breast Cancer MCF-7 Cells by Increasing Reactive Oxygen Species

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Yong-Zhan Zhen

2015-01-01

Full Text Available Gambogic acid (GA inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of GA is limited. Objectives. To investigate the antitumor activity of gambogic acid lysinate (GAL and its mechanism. Methods. Inhibition of cell proliferation was determined by MTT assay; intracellular ROS level was detected by staining cells with DCFH-DA; cell apoptosis was determined by flow cytometer and the mechanism of GAL was investigated by Western blot. Results. GAL inhibited the proliferation of MCF-7 cells with IC50 values 1.46 μmol/L comparable with GA (IC50, 1.16 μmol/L. GAL promoted the production of ROS; however NAC could remove ROS and block the effect of GAL. GAL inhibited the expression of SIRT1 but increased the phosphorylation of FOXO3a and the expression of p27Kip1. At knockdown of FOXO3a, cell apoptosis induced by GAL can be partly blocked. In addition it also enhanced the cleavage of caspase-3. Conclusions. GAL inhibited MCF-7 cell proliferation and induced MCF-7 cell apoptosis by increasing ROS level which could induce cell apoptosis by both SIRT1/FOXO3a/p27Kip1 and caspase-3 signal pathway. These results suggested that GAL might be useful as a modulation agent in cancer chemotherapy.

Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

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Stengärde Lena

2008-08-01

Full Text Available Abstract Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations. Cows were examined and blood sampled every three weeks from four weeks ante partum (ap to nine weeks postpartum (pp. Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA, insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds.

Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

Science.gov (United States)

Stengärde, Lena; Tråvén, Madeleine; Emanuelson, Ulf; Holtenius, Kjell; Hultgren, Jan; Niskanen, Rauni

2008-01-01

Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations). Cows were examined and blood sampled every three weeks from four weeks ante partum (ap) to nine weeks postpartum (pp). Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA), insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds. PMID:18687108

Bioprocessing of wheat bran in whole wheat bread increases the bioavailability of phenolic acids in men and exerts antiinflammatory effects ex vivo.

Science.gov (United States)

Mateo Anson, Nuria; Aura, Anna-Marja; Selinheimo, Emilia; Mattila, Ismo; Poutanen, Kaisa; van den Berg, Robin; Havenaar, Robert; Bast, Aalt; Haenen, Guido R M M

2011-01-01

Whole grain consumption has been linked to a lower risk of metabolic syndrome, which is normally associated with a low-grade chronic inflammation. The benefits of whole grain are in part related to the inclusion of the bran, rich in phenolic acids and fiber. However, the phenols are poorly bioaccessible from the cereal matrix. The aim of the present study was to investigate the effect of bioprocessing of the bran in whole wheat bread on the bioavailability of phenolic acids, the postprandial plasma antioxidant capacity, and ex vivo antiinflammatory properties. After consumption of a low phenolic acid diet for 3 d and overnight fasting, 8 healthy men consumed 300 g of whole wheat bread containing native bran (control bread) or bioprocessed bran (bioprocessed bread) in a cross-over design. Urine and blood samples were collected for 24 h to analyze the phenolic acids and metabolites. Trolox equivalent antioxidant capacity was measured in plasma. Cytokines were measured in blood after ex vivo stimulation with LPS. The bioavailabilities of ferulic acid, vanillic acid, sinapic acid, and 3,4-dimethoxybenzoic acid from the bioprocessed bread were 2- to 3-fold those from the control bread. Phenylpropionic acid and 3-hydroxyphenylpropionic acid were the main colonic metabolites of the nonbioaccessible phenols. The ratios of pro-:antiinflammatory cytokines were significantly lower in LPS-stimulated blood after the consumption of the bioprocessed bread. In conclusion, bioprocessing can remarkably increase the bioavailability of phenolic acids and their circulating metabolites, compounds which have immunomodulatory effects ex vivo.

Efficient Enzymatic Synthesis of Phenolic Ester by Increasing Solubility of Phenolic Acids in Ionic Liquids

DEFF Research Database (Denmark)

Yang, Zhiyong; Guo, Zheng; Xu, Xuebing

Compounds from phenolic acid family are well known natural antioxidants, but the application of phenolic acids as antioxidants in industry is limited due to the relatively low solubility in oil-based media. The properties of phenolic acids can be modified through enzymatic lipophilization...... and modified phenolic acids will have amphiphilic property, therefore they can be localized at oil-water or water-oil phase where oxidation is considered to occur frequently. It had been reported that immobilized Candida Antarctica lipase B was the most effective biocatalyst for the various esterification...... reactions, and it had been widely used for esterification of various phenolic acids with fatty alcohol or triglycerides. However, the conversion of phenolic acids is low due to low solubility in hydrophobic solvents and hindrance effect of unsaturated side chain towards the enzyme. Our studies show...

Increasing the analytical sensitivity by oligonucleotides modified with para- and ortho-twisted intercalating nucleic acids--TINA.

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Uffe V Schneider

Full Text Available The sensitivity and specificity of clinical diagnostic assays using DNA hybridization techniques are limited by the dissociation of double-stranded DNA (dsDNA antiparallel duplex helices. This situation can be improved by addition of DNA stabilizing molecules such as nucleic acid intercalators. Here, we report the synthesis of a novel ortho-Twisted Intercalating Nucleic Acid (TINA amidite utilizing the phosphoramidite approach, and examine the stabilizing effect of ortho- and para-TINA molecules in antiparallel DNA duplex formation. In a thermal stability assay, ortho- and para-TINA molecules increased the melting point (Tm of Watson-Crick based antiparallel DNA duplexes. The increase in Tm was greatest when the intercalators were placed at the 5' and 3' termini (preferable or, if placed internally, for each half or whole helix turn. Terminally positioned TINA molecules improved analytical sensitivity in a DNA hybridization capture assay targeting the Escherichia coli rrs gene. The corresponding sequence from the Pseudomonas aeruginosa rrs gene was used as cross-reactivity control. At 150 mM ionic strength, analytical sensitivity was improved 27-fold by addition of ortho-TINA molecules and 7-fold by addition of para-TINA molecules (versus the unmodified DNA oligonucleotide, with a 4-fold increase retained at 1 M ionic strength. Both intercalators sustained the discrimination of mismatches in the dsDNA (indicated by ΔTm, unless placed directly adjacent to the mismatch--in which case they partly concealed ΔTm (most pronounced for para-TINA molecules. We anticipate that the presented rules for placement of TINA molecules will be broadly applicable in hybridization capture assays and target amplification systems.

Central pipecolic acid increases food intake under ad libitum feeding conditions in the neonatal chick.

Science.gov (United States)

Takagi, Tomo; Tachibana, Tetsuya; Saito, Ei-Suke; Tomonaga, Shouzou; Saito, Shin; Bungo, Takashi; Denbow, D Michael; Furuse, Mitsuhiro

2003-08-21

It has been demonstrated that L-pipecolic acid (L-PA) is a major metabolic intermediate of L-lysine in the mammalian and chicken brain. A previous study showed that intracerebroventricular (i.c.v.) injection of L-PA suppressed feeding in neonatal chicks, and the actions were associated with gamma-aminobutyric acid (GABA)-B receptor activation. It has been reported that endogenous L-PA in the brain fluctuated under different feeding conditions. In the present study, we investigated the effect of i.c.v. injection of L-PA on food intake in the neonatal chick under ad libitum feeding conditions. The food intake was increased by 0.5 or 1.0 mg L-PA under ad libitum feeding conditions contrary to previous studies using fasted birds. A hyperphagic effect of L-PA (0.5 mg) was attenuated by both GABA-A receptor antagonist (picrotoxin, 0.5 microg) and GABA-B receptor antagonist (CGP54626, 21.0 ng). These results indicate that a hyperphagic effect of L-PA is mediated by both GABA-A and GABA-B receptors and L-PA differentially affects food intake under different feeding conditions in the neonatal chick.

Postprandial PYY increase by resistant starch supplementation is independent of net portal appearance of short-chain fatty acids in pigs

DEFF Research Database (Denmark)

Ingerslev, Anne Krog; Jagalur Mutt, Shivaprakash; Lærke, Helle Nygaard

2017-01-01

Increased dietary fiber (DF) fermentation and short-chain fatty acid (SCFA) production may stimulate peptide tyrosine-tyrosine (PYY) secretion. In this study, the effects of hindgut SCFA production on postprandial PYY plasma levels were assessed using different experimental diets in a porto.......001), but similar among diets (P > 0.10). In conclusion, the increased postprandial PYY responses in pigs fed with different levels and sources of DF are not caused by an increased SCFA absorption and suggest that other mechanisms such as neural reflexes and possibly an increased flow of digesta in the small...

Rice straw incorporated just before soil flooding increases acetic acid formation and decreases available nitrogen

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Ronaldir Knoblauch

2014-02-01

before, the concentration of N-NH4+ in the soil was 28 and 54 mg kg-1, equivalent to an accumulation of 42 and 81 kg ha-1 of N-NH4+, respectively. There was formation of acetic acid in which toxic concentrations were reached (7.2 mmol L-1 on the 15th day of flooding only for the treatment with straw incorporated on the day of flooding. The pH of the soil solution of all the treatments increased after flooding and this increase was faster in the treatments with incorporation of straw, followed by the ash treatment and then the control. After 60 days of flooding, however, the pH values were around 6.5 for all treatments, except for the control, which reached a pH of 6.3. Rice straw should be incorporated into the soil at least 30 days before flooding; otherwise, it may immobilize part of the mineral N and produce acetic acid in concentrations toxic to rice seedlings.

Replacing soybean oil with increasing levels of soybean acid oil in diets of coturnix quails (Coturnix coturnix coturnix and the effects on egg quality

Directory of Open Access Journals (Sweden)

ALINE A.P. ROLL

2017-10-01

Full Text Available ABSTRACT The effects of increasing levels of soybean acid oil in diets of quails on the quality of eggs were evaluated over a period of 56 days. A completely randomized design with five treatment levels of soybean acid oil (0, 2, 4, 6, and 8% as a replacer for soybean oil and eight replicates of two quails each were used. A total of 240 fresh eggs were used for quality analysis, and 400 eggs were stored at 23ºC over a period of 0, 7, 14, 21, and 28 days for analysis of shelf-life. Polynomial regression and ANOVA with repeated measurements and Tukey´s tests were used. Soybean acid oil linearly increased the intensity of red (a* = -5.26 + 0.14 x, R2 = 0.89, P = 0.01 and yellow (b* = 42.32 + 0.44 x, R2 = 0.88 P = 0.01. All other variables of egg quality were not affected by the treatments, with the exception of sensory attributes, such as odor and aftertaste, which were more pronounced with soybean acid oil. In conclusion, soybean acid oil affects the intensity of yellow and red color of the yolk. Trained assessors detected differences in odor and aftertaste of eggs when soybean acid oil was included in the quail diet.

Investigation of a valuable biochemical indicator in radiotherapy. Pt. 2

International Nuclear Information System (INIS)

Horvath, M.; Geszti, O.; Benedek, E.; Farkas, J.; Reischl, G.

1979-01-01

The hemoglobin level of blood plasma is a sensitive tool in measuring radiation effects. Its value has increased in most of the cases during radiotherapy of cancer patients even applied at low doses. Haptoglobins behave similarly, the timedependent changes during radiotherapy are almost identical at both parameters. (orig.) [de

New Acid Combination for a Successful Sandstone Acidizing

Science.gov (United States)

Shafiq, M. U.; Mahmud, H. K. B.; Rezaee, R.

2017-05-01

With the development of new enhanced oil recovery techniques, sandstone acidizing has been introduced and played a pivotal role in the petroleum industry. Different acid combinations have been applied, which react with the formation, dissolve the soluble particles; thus increase the production of hydrocarbons. To solve the problems which occurred using current preflush sandstone acidizing technology (hydrochloric acid); a new acid combination has been developed. Core flooding experiments on sandstone core samples with dimensions 1.5 in. × 3 in. were conducted at a flow rate of 2 cm3/min. A series of hydrochloric-acetic acid mixtures with different ratios were tested under 150°F temperature. The core flooding experiments performed are aimed to dissolve carbonate, sodium, potassium and calcium particles from the core samples. These experiments are followed by few important tests which include, porosity-permeability, pH value, Inductively Coupled Plasma (ICP) analysis and Nuclear Magnetic Resonance (NMR measurements). All the results are compared with the results of conventional hydrochloric acid technology. NMR and porosity analysis concluded that the new acid combination is more effective in creating fresh pore spaces and thus increasing the reservoir permeability. It can be seen from the pore distribution before and after the acidizing. Prior applying acid; the large size of pores appears most frequently in the pore distribution while with the applied acid, it was found that the small pore size is most the predominant of the pore distribution. These results are validated using ICP analysis which shows the effective removal of calcium and other positive ions from the core sample. This study concludes that the combination of acetic-hydrochloric acid can be a potential candidate for the preflush stage of sandstone acidizing at high temperature reservoirs.

Humic Acid and Water Management to Decrease Ferro (Fe2+ Solution and Increase Productivity of Established New Rice Field

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Amrizal Saidi

2012-01-01

Full Text Available The purpose of this research was to gain a technological breakthrough in controlling Fe toxicity (Fe2+ on Ultisol ina new established rice field by using humic acid from rice straw compost and water management, so that optimalproduction of rice plants could be achieved. The experiment was designed using a 2 × 4 factorials with 3 replicationsin a split plot design. The main plot was water management consists of 2 levels: continuous and intermittentirrigation (2 weeks flooded and 2 weeks field capacity. Small plot was humic acid which was extracted from ricestraw compost by NaOH 0.5 N which consists of 4 levels: 0, 200, 400, and 600 mg kg-1. The results showed thatapplications of humic acid from 0 to 600 mg kg-1 that was followed by 2 weeks of intermittent irrigation decreasedFe2+ concentration. It was approaching levels that were not toxic to plants, with soil Fe2+ between 180-250 mg kg-1.The best treatment was found at the application of 600 mg kg-1 humic acid extracted from rice straw compostcombined with 2 week flooded – 2 weeks field capacity of water management. Those treatment decreased Fe2+concentration from 1,614 to 180 mg kg-1 and increased the dry weight of grain from 5.15 to 16.73 g pot-1 compared tocontinuous flooding and without humic acid application.

Plasma amino acids

Science.gov (United States)

Amino acids blood test ... types of methods used to determine the individual amino acid levels in the blood. ... test is done to measure the level of amino acids in the blood. An increased level of a ...

Uric acid nephrolithiasis: An update.

Science.gov (United States)

Cicerello, Elisa

2018-04-01

Uric acid nephrolithiasis appears to increase in prevalence. While a relationship between uric acid stones and low urinary pH has been for long known, additional association with various metabolic conditions and pathophysiological basis has recently been elucidated. Some conditions such as diabetes and metabolic syndrome disease, excessive dietary intake, and increased endogenous uric acid production and/or defect in ammoniagenesis are associated with low urinary pH. In addition, the phenomenon of global warming could result in an increase in areas with greater climate risk for uric acid stone formation. There are three therapeutic steps to be taken for management of uric acid stones: identification of urinary pH profiles, assessment of urinary volume status, and identification of disorders leading to excessive uric acid production. However, the most important factor for uric acid stone formation is acid urinary pH, which is a prerequisite for uric acid precipitation. This article reviews recent insights into the pathophysiology of uric acid stones and their management.

Weekly intra-amniotic IGF-1 treatment increases growth of growth-restricted ovine fetuses and up-regulates placental amino acid transporters.

Directory of Open Access Journals (Sweden)

Jibran A Wali

Full Text Available Frequent treatment of the growth-restricted (IUGR ovine fetus with intra-amniotic IGF-1 increases fetal growth. We aimed to determine whether increased growth was maintained with an extended dosing interval and to examine possible mechanisms. Pregnant ewes were allocated to three groups: Control, and two IUGR groups (induced by placental embolization treated with weekly intra-amniotic injections of either saline (IUGR or 360 µg IGF-1 (IGF1. IUGR fetuses were hypoxic, hyperuremic, hypoglycemic, and grew more slowly than controls. Placental glucose uptake and SLC2A1 (GLUT2 mRNA levels decreased in IUGR fetuses, but SLC2A3 (GLUT3 and SLC2A4 (GLUT4 levels were unaffected. IGF-1 treatment increased fetal growth rate, did not alter uterine blood flow or placental glucose uptake, and increased placental SLC2A1 and SLC2A4 (but not SLC2A3 mRNA levels compared with saline-treated IUGR animals. Following IGF-1 treatment, placental mRNA levels of isoforms of the system A, y(+, and L amino acid transporters increased 1.3 to 5.0 fold, while the ratio of phosphorylated-mTOR to total mTOR also tended to increase. Weekly intra-amniotic IGF-1 treatment provides a promising avenue for intra-uterine treatment of IUGR babies, and may act via increased fetal substrate supply, up-regulating placental transporters for neutral, cationic, and branched-chain amino acids, possibly via increased activation of the mTOR pathway.

Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.

Directory of Open Access Journals (Sweden)

Heidi O Nousiainen

Full Text Available Prostatic acid phosphatase (PAP, the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG, but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP in the brain by utilizing mice deficient in TMPAP (PAP-/- mice. Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype.

Serum proteomic analysis reveals potential serum biomarkers for occupational medicamentosa-like dermatitis caused by trichloroethylene.

Science.gov (United States)

Huang, Peiwu; Ren, Xiaohu; Huang, Zhijun; Yang, Xifei; Hong, Wenxu; Zhang, Yanfang; Zhang, Hang; Liu, Wei; Huang, Haiyan; Huang, Xinfeng; Wu, Desheng; Yang, Linqing; Tang, Haiyan; Zhou, Li; Li, Xuan; Liu, Jianjun

2014-08-17

Trichloroethylene (TCE) is an industrial solvent with widespread occupational exposure and also a major environmental contaminant. Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become one major hazard in China. In this study, sera from 3 healthy controls and 3 OMLDT patients at different disease stages were used for a screening study by 2D-DIGE and MALDI-TOF-MS/MS. Eight proteins including transthyretin (TTR), retinol binding protein 4 (RBP4), haptoglobin, clusterin, serum amyloid A protein (SAA), apolipoprotein A-I, apolipoprotein C-III and apolipoprotein C-II were found to be significantly altered among the healthy, acute-stage, healing-stage and healed-stage groups. Specifically, the altered expression of TTR, RBP4 and haptoglobin were further validated by Western blot analysis and ELISA. Our data not only suggested that TTR, RBP4 and haptoglobin could serve as potential serum biomarkers of OMLDT, but also indicated that measurement of TTR, RBP4 and haptoglobin or their combination could help aid in the diagnosis, monitoring the progression and therapy of the disease. Copyright © 2014. Published by Elsevier Ireland Ltd.

Polyunsaturated fatty acids acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increases postprandial insulin sensitivity

NARCIS (Netherlands)

Jans, Anneke; Konings, Ellen; Goossens, Gijs H.; Bouwman, Freek G.; Moors, Chantalle C.; Boekschoten, Mark; Afman, Lydia; Muller, Michael; Mariman, Edwin C.; Blaak, Ellen E.

2012-01-01

Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin

Does perinatal omega-3 polyunsaturated fatty acid deficiency increase appetite signaling?

Science.gov (United States)

Mathai, Michael L; Soueid, Mona; Chen, Nora; Jayasooriya, Anura P; Sinclair, Andrew J; Wlodek, Mary E; Weisinger, Harrison S; Weisinger, Richard S

2004-11-01

To investigate the effect of maternal dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling. Sprague-Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) omega-3 PUFA. All offspring were raised on the maternal diet until weaning. After weaning, two groups remained on the respective maternal diet (CON and DEF groups), whereas a third group, born of dams fed the DEF diet, were switched to the CON diet (REC). Experiments on food intake began when the male rats reached 16 weeks of age. Food intake was stimulated either by a period of food restriction, by blocking glucose utilization (by 2-deoxyglucose injection), or by blocking beta-oxidation of fatty acids (by beta-mercaptoacetate injection). DEF animals consumed more than CON animals in response to all stimuli, with the greatest difference (1.9-fold) demonstrated following administration of 2-deoxyglucose. REC animals also consumed more than CON animals in response to food restriction and 2-deoxyglucose but not to beta-mercaptoacetate. These findings indicate that supply of omega-3 PUFA, particularly during the perinatal period, plays a role in the normal development of mechanisms controlling food intake, especially glucoprivic (i.e. reduced glucose availability) appetite signaling. Dietary repletion of omega-3 PUFA from 3 weeks of age restored intake responses to fatty acid metabolite signaling but did not reverse those in response to food restriction or glucoprivic stimuli.

Unsaturated fatty acids protect trophoblast cells from saturated fatty acid-induced autophagy defects.

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Hong, Ye-Ji; Ahn, Hyo-Ju; Shin, Jongdae; Lee, Joon H; Kim, Jin-Hoi; Park, Hwan-Woo; Lee, Sung Ki

2018-02-01

Dysregulated serum fatty acids are associated with a lipotoxic placental environment, which contributes to increased pregnancy complications via altered trophoblast invasion. However, the role of saturated and unsaturated fatty acids in trophoblastic autophagy has yet to be explored. Here, we demonstrated that prolonged exposure of saturated fatty acids interferes with the invasiveness of human extravillous trophoblasts. Saturated fatty acids (but not unsaturated fatty acids) inhibited the fusion of autophagosomes and lysosomes, resulting in the formation of intracellular protein aggregates. Furthermore, when the trophoblast cells were exposed to saturated fatty acids, unsaturated fatty acids counteracted the effects of saturated fatty acids by increasing degradation of autophagic vacuoles. Saturated fatty acids reduced the levels of the matrix metalloproteinases (MMP)-2 and MMP-9, while unsaturated fatty acids maintained their levels. In conclusion, saturated fatty acids induced decreased trophoblast invasion, of which autophagy dysfunction plays a major role. Copyright © 2017 Elsevier B.V. All rights reserved.

Valproic Acid

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... acid is in a class of medications called anticonvulsants. It works by increasing the amount of a ... older (about 1 in 500 people) who took anticonvulsants such as valproic acid to treat various conditions ...

9-cis-retinoic acid increases apolipoprotein AI secretion and mRNA expression in HepG2 cells.

Science.gov (United States)

Haghpassand, M; Moberly, J B

1995-10-01

HepG2 cells were studied as a model for regulation of hepatic apolipoprotein AI (apo AI) secretion and gene expression by 9-cis-retinoic acid. HepG2 cells cultured on plastic dishes were exposed to 9-cis-retinoic acid (9-cis-RA) for 48 h with a complete media change at 24 h. Apo AI mass in cultured media was determined by ELISA, by quantitative immunoblotting and by steady-state 35S-methionine labeling. Messenger RNA levels were determined by RNase protection using probes for apo AI and the housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (G3PDH). 9-cis-RA increased secretion of apo AI by 52% at doses of 10 and 1 microM (6.3 +/- 0.6 vs. 4.2 +/- 0.3; P G3PDH mRNA was slightly decreased (14%, P < 0.05). Thus, 9-cis-RA stimulates apo AI expression in HepG2 cells, suggesting a role for retinoids in activating endogenous apo AI gene expression.

Transport of acidic amino acids by human jejunal brush-border membrane vesicles

International Nuclear Information System (INIS)

Rajendran, V.M.; Harig, J.M.; Adams, M.B.; Ramaswamy, K.

1987-01-01

This study characterizes the transport of radiolabeled acidic amino acids into brush-border membrane vesicles prepared from human jejunum. The uptakes of L-glutamic, L-aspartic, and D-aspartic acids were stimulated by a Na + gradient. Concentrative uptake (resulting in an overshoot phenomenon) of these dicarboxylic amino acids occurred when there was an outward K + gradient. In addition, increasing K + gradients resulted in enhanced uptake of L-glutamic acid. This K + requirement is somewhat specific as Rb + and Cs + could enhance uptake to a limited extent, whereas Li + and choline + showed no enhancement. The presence of a K + gradient did not affect the affinity of the carrier system for L-glutamic acid but it did increase the V/sub max/. The presence of extravesicular anions having differing membrane permeabilities did not altar L-glutamic acid uptake indicating an absence of an effect of membrane potential on the transport process. Finally, the human transport system for L-glutamic acid appears to be specific for acidic amino acids as demonstrated by inhibition studies. The studies demonstrate a transport system in human jejunum specific for acidic amino acids that is energized by an inward Na + gradient and an outward K + gradient

Peptide Nucleic Acids Having Amino Acid Side Chains

DEFF Research Database (Denmark)

1998-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than the corresponding DNA or RNA strands, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting...

Exposure to acute severe hypoxia leads to increased urea loss and disruptions in acid-base and ionoregulatory balance in dogfish sharks (Squalus acanthias).

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Zimmer, Alex M; Wood, Chris M

2014-01-01

The effects of acute moderate (20% air O2 saturation; 6-h exposure) and severe (5% air O2 saturation; 4-h exposure) hypoxia on N-waste, acid-base, and ion balance in dogfish sharks (Squalus acanthias suckleyi) were evaluated. We predicted that the synthesis and/or retention of urea, which are active processes, would be inhibited by hypoxia. Exposure to moderate hypoxia had negligible effects on N-waste fluxes or systemic physiology, except for a modest rise in plasma lactate. Exposure to severe hypoxia led to a significant increase in urea excretion (Jurea), while plasma, liver, and muscle urea concentrations were unchanged, suggesting a loss of urea retention. Ammonia excretion (Jamm) was elevated during normoxic recovery. Moreover, severe hypoxia led to disruptions in acid-base balance, indicated by a large increase in plasma [lactate] and substantial decreases in arterial pHa and plasma [Formula: see text], as well as loss of ionic homeostasis, indicated by increases in plasma [Mg(2+)], [Ca(2+)], and [Na(+)]. We suggest that severe hypoxia in dogfish sharks leads to a reduction in active gill homeostatic processes, such as urea retention, acid-base regulation and ionoregulation, and/or an osmoregulatory compromise due to increased functional gill surface area. Overall, the results provide a comprehensive picture of the physiological responses to a severe degree of hypoxia in an ancient fish species.

New food approaches to reduce and/or eliminate increased gastric acidity related to gastroesophageal pathologies.

Science.gov (United States)

Langella, Ciro; Naviglio, Daniele; Marino, Marina; Calogero, Armando; Gallo, Monica

2018-03-22

Gastroesophageal reflux disease is very common in industrialized countries and rapidly and significantly increasing even in developing countries. The approach in this study is one not commonly found to date in the scientific literature. To assess the ability of reduced-carbohydrate diets and foods that are enriched with acid potential of hydrogen (pH; lemon and tomato) to quickly and exponentially reduce symptoms that are related to conditions such as gastritis and gastroesophageal reflux and unrelated to Helicobacter pylori. After the administration of an anamnestic test, 130 patients were selected including 73 women and 57 men, 21 to 67 y, and with a gastritis diagnosis for 92 patients (56 women, 36 men) and reflux gastritis for 38 patients (17 women, 21 men). Study participants followed three dietary treatments in succession. Each treatment lasted 2 wk and treatments were separated by 2 wk of washout. The patients followed a diet that consisted primarily of proteins and fats and included the exponential reduction of glycides (simple and complex). In addition, the treatment provided for the daily intake of the juice of two lemons and approximately 100 g of fresh orange tomato without seeds eaten either raw or cooked and peeled. During treatment and at the end of 2 wk of treatment, the patients reported significant improvements including an almost total disappearance of symptoms that were related to the disease in question. This study shows that a carbohydrate-free diet and/or highly hypoglycidal diet that is enriched with acid pH foods appears to lead to a decrease in the pH of the gastric contents, thus inhibiting the further production of hydrochloric acid with a reduction or disappearance of heartburn symptoms that are typical of gastroesophageal diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Ion-exclusion chromatography with conductimetric detection of aliphatic carboxylic acids on a weakly acidic cation-exchange resin by elution with benzoic acid-beta-cyclodextrin.

Science.gov (United States)

Tanaka, Kazuhiko; Mori, Masanobu; Xu, Qun; Helaleh, Murad I H; Ikedo, Mikaru; Taoda, Hiroshi; Hu, Wenzhi; Hasebe, Kiyoshi; Fritz, James S; Haddad, Paul R

2003-05-16

In this study, an aqueous solution consisting of benzoic acid with low background conductivity and beta-cyclodextrin (beta-CD) of hydrophilic nature and the inclusion effect to benzoic acid were used as eluent for the ion-exclusion chromatographic separation of aliphatic carboxylic acids with different pKa values and hydrophobicity on a polymethacrylate-based weakly acidic cation-exchange resin in the H+ form. With increasing concentration of beta-cyclodextrin in the eluent, the retention times of the carboxylic acids decreased due to the increased hydrophilicity of the polymethacrylate-based cation-exchange resin surface from the adsorption of OH groups of beta-cyclodextrin. Moreover, the eluent background conductivity decreased with increasing concentration of beta-cyclodextrin in 1 mM benzoic acid, which could result in higher sensitivity for conductimetric detection. The ion-exclusion chromatographic separation of carboxylic acids with high resolution and sensitivity was accomplished successfully by elution with a 1 mM benzoic acid-10 mM cyclodextrin solution without chemical suppression.

Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD.

Science.gov (United States)

Jiao, Na; Baker, Susan S; Chapa-Rodriguez, Adrian; Liu, Wensheng; Nugent, Colleen A; Tsompana, Maria; Mastrandrea, Lucy; Buck, Michael J; Baker, Robert D; Genco, Robert J; Zhu, Ruixin; Zhu, Lixin

2017-08-03

Bile acids are regulators of lipid and glucose metabolism, and modulate inflammation in the liver and other tissues. Primary bile acids such as cholic acid and chenodeoxycholic acid (CDCA) are produced in the liver, and converted into secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by gut microbiota. Here we investigated the possible roles of bile acids in non-alcoholic fatty liver disease (NAFLD) pathogenesis and the impact of the gut microbiome on bile acid signalling in NAFLD. Serum bile acid levels and fibroblast growth factor 19 (FGF19), liver gene expression profiles and gut microbiome compositions were determined in patients with NAFLD, high-fat diet-fed rats and their controls. Serum concentrations of primary and secondary bile acids were increased in patients with NAFLD. In per cent, the farnesoid X receptor (FXR) antagonistic DCA was increased, while the agonistic CDCA was decreased in NAFLD. Increased mRNA expression for cytochrome P450 7A1, Na + -taurocholate cotransporting polypeptide and paraoxonase 1, no change in mRNA expression for small heterodimer partner and bile salt export pump, and reduced serum FGF19 were evidence of impaired FXR and fibroblast growth factor receptor 4 (FGFR4)-mediated signalling in NAFLD. Taurine and glycine metabolising bacteria were increased in the gut of patients with NAFLD, reflecting increased secondary bile acid production. Similar changes in liver gene expression and the gut microbiome were observed in high-fat diet-fed rats. The serum bile acid profile, the hepatic gene expression pattern and the gut microbiome composition consistently support an elevated bile acid production in NAFLD. The increased proportion of FXR antagonistic bile acid explains, at least in part, the suppression of hepatic FXR-mediated and FGFR4-mediated signalling. Our study suggests that future NAFLD intervention may target the components of FXR signalling, including the bile acid converting gut microbiome. © Article

Bioavailable Concentrations of Delphinidin and Its Metabolite, Gallic Acid, Induce Antioxidant Protection Associated with Increased Intracellular Glutathione in Cultured Endothelial Cells

Science.gov (United States)

Goszcz, Katarzyna; Deakin, Sherine J.; Duthie, Garry G.; Stewart, Derek

2017-01-01

Despite limited bioavailability and rapid degradation, dietary anthocyanins are antioxidants with cardiovascular benefits. This study tested the hypothesis that the antioxidant protection conferred by the anthocyanin, delphinidin, is mediated by modulation of endogenous antioxidant defences, driven by its degradation product, gallic acid. Delphinidin was found to degrade rapidly (t1/2 ~ 30 min), generating gallic acid as a major degradation product. Both delphinidin and gallic acid generated oxygen-centred radicals at high (100 μM) concentrations in vitro. In a cultured human umbilical vein endothelial cell model of oxidative stress, the antioxidant protective effects of both delphinidin and gallic acid displayed a hormesic profile; 100 μM concentrations of both were cytotoxic, but relatively low concentrations (100 nM–1 μM) protected the cells and were associated with increased intracellular glutathione. We conclude that delphinidin is intrinsically unstable and unlikely to confer any direct antioxidant activity in vivo yet it offered antioxidant protection to cells at low concentrations. This paradox might be explained by the ability of the degradation product, gallic acid, to confer benefit. The findings are important in understanding the mode of protection conferred by anthocyanins and reinforce the necessity to conduct in vitro experiments at biologically relevant concentrations. PMID:29081896

Individual bile acids have differential effects on bile acid signaling in mice

International Nuclear Information System (INIS)

Song, Peizhen; Rockwell, Cheryl E.; Cui, Julia Yue; Klaassen, Curtis D.

2015-01-01

Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In the liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and

Individual bile acids have differential effects on bile acid signaling in mice

Energy Technology Data Exchange (ETDEWEB)

Song, Peizhen, E-mail: songacad@gmail.com; Rockwell, Cheryl E., E-mail: rockwelc@msu.edu; Cui, Julia Yue, E-mail: juliacui@uw.edu; Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com

2015-02-15

Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In the liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and

Lipoprotein cholesterol uptake mediates upregulation of bile acid synthesis by increasing cholesterol 7a-hydroxylase but not sterol 27- hydroxylase gene expression in cultured rat hepatocytes.

NARCIS (Netherlands)

Post, S.M.; Twisk, J.W.R.; van der Fits, L.T.E.; Wit, E.C.M.; Hoekman, M.F.M.; Mager, W.H.; Princen, H.M.G.

1999-01-01

Lipoproteins may supply substrate for the formation of bile acids, and the amount of hepatic cholesterol can regulate bile-acid synthesis and increase cholesterol 7α-hydroxylase expression. However, the effect of lipoprotein cholesterol on sterol 27-hydroxylase expression and the role of different

Dependence of the metabolic fecal amino acids on the amino acid content of the feed. 2

International Nuclear Information System (INIS)

Krawielitzki, K.; Schadereit, R.; Voelker, T.; Reichel, K.

1982-01-01

In an experiment with 20 15 N-labelled growing rats the excretion of amino acids as well as of metabolic fecal amino acids were investigated after feeding of soybean oil meal as sole protein source. A low, yet statistically significant increase of the excretion of amino acids and metabolic fecal amino acids was ascertained in accordance with a growing quota of soybean oil meal in the ration. The true digestibility of amino acids ascertained according to conventional methods is above 90% and, under consideration of the increase of metabolic fecal amino acids, on the average increases by 3.5 digestibility units (1.4 to 6.2). (author)

Fatty acid composition of Swedish bakery products, with emphasis on trans-fatty acids.

Science.gov (United States)

Trattner, Sofia; Becker, Wulf; Wretling, Sören; Öhrvik, Veronica; Mattisson, Irene

2015-05-15

Trans-fatty acids (TFA) have been associated with increased risk of coronary heart disease, by affecting blood lipids and inflammation factors. Current nutrition recommendations emphasise a limitation of dietary TFA intake. The aim of this study was to investigate fatty acid composition in sweet bakery products, with emphasis on TFA, on the Swedish market and compare fatty acid composition over time. Products were sampled in 2001, 2006 and 2007 and analysed for fatty acid composition by using GC. Mean TFA levels were 0.7% in 2007 and 5.9% in 2001 of total fatty acids. In 1995-97, mean TFA level was 14.3%. In 2007, 3 of 41 products had TFA levels above 2% of total fatty acids. TFA content had decreased in this product category, while the proportion of saturated (SFA) and polyunsaturated (PUFA) fatty acids had increased, mostly through increased levels of 16:0 and 18:2 n-6, respectively. The total fat content remained largely unchanged. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

Energy Technology Data Exchange (ETDEWEB)

Dawson, Jennifer E [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Raymond, Angela M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Winn, Louise M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada)

2006-03-01

In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

Long-term administration of olanzapine induces adiposity and increases hepatic fatty acid desaturation protein in female C57BL/6J mice

Science.gov (United States)

Hou, Po-Hsun; Chang, Geng-Ruei; Chen, Chin-Pin; Lin, Yen-Ling; Chao, I-Shuan; Shen, Ting-Ting; Mao, Frank Chiahung

2018-01-01

Objective(s): Weight gain and metabolic disturbances such as dyslipidemia, are frequent side effects of second-generation antipsychotics, including olanzapine. This study examined the metabolic effects of chronic olanzapine exposure. In addition, we investigated the hepatic fatty acid effects of olanzapine in female C57BL/6J mice fed a normal diet. Materials and Methods: Female C57BL/6J mice orally received olanzapine or normal saline for 7 weeks. The effects of long-term olanzapine exposure on body weight changes, food efficiency, blood glucose, triglyceride (TG), insulin, and leptin levels were observed. Hepatic TG and abdominal fat mass were investigated, and fat cell morphology was analyzed through histopathological methods. The levels of protein markers of fatty acid regulation in the liver, namely fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), were measured. Results: Olanzapine treatment increased the food intake of the mice as well as their body weight. Biochemical analyses showed that olanzapine increased blood TG, insulin, leptin, and hepatic TG. The olanzapine group exhibited increased abdominal fat mass and fat cell enlargement in abdominal fat tissue. Western blotting of the mouse liver revealed significantly higher (1.6-fold) levels of SCD-1 in the olanzapine group relative to the control group; by contrast, FAS levels in the two groups did not differ significantly. Conclusion: Enhanced lipogenesis triggered by increased hepatic SCD-1 activity might be a probable peripheral mechanism of olanzapine-induced dyslipidemia. Some adverse metabolic effects of olanzapine may be related to the disturbance of lipid homeostasis in the liver. PMID:29922430

Perfluorodecanoic acid enhances the formation of oleic acid in rat liver.

Science.gov (United States)

Yamamoto, A; Kawashima, Y

1997-01-01

The feeding of perfluorodecanoic acid (PFDA) to male rats at a dietary concentration of 0.005% (w/w) for 7 days resulted in a marked increase in the activity of microsomal stearoyl-CoA desaturation in the liver. This increase in the overall desaturation activity was due to the induction of terminal desaturase among the components comprising the desaturation system. In contrast, PFDA inhibited desaturation in vitro, seemingly due to interference with electron transport through the desaturation system. Accordingly, PFDA can be an inducer and also an inhibitor of delta9-desaturation. PFDA feeding enhanced the conversion of radioactive stearic acid into oleic acid in the liver in vivo, indicating that the induction of delta9-desaturase by PFDA functions in vivo. PFDA feeding increased the mass of octadecenoic acid (C18:1) in the liver and the proportion of C18:1 in microsomal lipid. A highly significant linear correlation existed between the microsomal desaturase activity and the proportion of C18:1 in microsomal lipid when compared using rats in five different physiological states: control, PFDA-fed, p-chlorophenoxyisobutyric acid (clofibric acid)-fed, starved and starved/refed. These results suggest that the increase in the hepatic level of C18:1 caused by feeding of PFDA to rats can be explained by the common concept of regulation, i.e. the hepatic level of C18:1 is under the control of delta9-desaturase. The dietary administration of PFDA also increased the content of cytochrome P-450 and the activity of 7-ethoxycoumarin O-de-ethylase in the liver. PMID:9230124

Acidizing reservoirs while chelating iron with sulfosalicylic acid

Energy Technology Data Exchange (ETDEWEB)

McLaughlin, W A; Berkshire, D C

1980-09-30

A well treating process is described in which an aqueous solution of a strong acid capable of dissolving solids in a manner increasing the permeability of a subterranean earth formation is injected into a subterranean reservoir that contains an asphaltenic oil. At least the first injected portion of the aqueous acid and a solution or homogeneous dispersion of at least enough 5-sulfosalicylic acid to chelate with and prevent the formation of iron-asphaltene solids are included with substantially all of the ferric ions that become dissolved within the strong acid solution that enters the earth formation. 10 claims.

Temperature-dependent dynamic control of the TCA cycle increases volumetric productivity of itaconic acid production by Escherichia coli.

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Harder, Björn-Johannes; Bettenbrock, Katja; Klamt, Steffen

2018-01-01

Based on the recently constructed Escherichia coli itaconic acid production strain ita23, we aimed to improve the productivity by applying a two-stage process strategy with decoupled production of biomass and itaconic acid. We constructed a strain ita32 (MG1655 ΔaceA Δpta ΔpykF ΔpykA pCadCs), which, in contrast to ita23, has an active tricarboxylic acid (TCA) cycle and a fast growth rate of 0.52 hr -1 at 37°C, thus representing an ideal phenotype for the first stage, the growth phase. Subsequently we implemented a synthetic genetic control allowing the downregulation of the TCA cycle and thus the switch from growth to itaconic acid production in the second stage. The promoter of the isocitrate dehydrogenase was replaced by the Lambda promoter (p R ) and its expression was controlled by the temperature-sensitive repressor CI857 which is active at lower temperatures (30°C). With glucose as substrate, the respective strain ita36A grew with a fast growth rate at 37°C and switched to production of itaconic acid at 28°C. To study the impact of the process strategy on productivity, we performed one-stage and two-stage bioreactor cultivations. The two-stage process enabled fast formation of biomass resulting in improved peak productivity of 0.86 g/L/hr (+48%) and volumetric productivity of 0.39 g/L/hr (+22%) in comparison to the one-stage process. With our dynamic production strain, we also resolved the glutamate auxotrophy of ita23 and increased the itaconic acid titer to 47 g/L. The temperature-dependent activation of gene expression by the Lambda promoters (p R /p L ) has been frequently used to improve protein or, in a few cases, metabolite production in two-stage processes. Here we demonstrate that the system can be as well used in the opposite direction to selectively knock-down an essential gene (icd) in E. coli to design a two-stage process for improved volumetric productivity. The control by temperature avoids expensive inducers and has the

Intraperitoneal administration of docosahexaenoic acid for 14days increases serum unesterified DHA and seizure latency in the maximal pentylenetetrazol model.

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Trépanier, Marc-Olivier; Lim, Joonbum; Lai, Terence K Y; Cho, Hye Jin; Domenichiello, Anthony F; Chen, Chuck T; Taha, Ameer Y; Bazinet, Richard P; Burnham, W M

2014-04-01

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) which has been shown to raise seizure thresholds following acute administration in rats. The aims of the present experiment were the following: 1) to test whether subchronic DHA administration raises seizure threshold in the maximal pentylenetetrazol (PTZ) model 24h following the last injection and 2) to determine whether the increase in seizure threshold is correlated with an increase in serum and/or brain DHA. Animals received daily intraperitoneal (i.p.) injections of 50mg/kg of DHA, DHA ethyl ester (DHA EE), or volume-matched vehicle (albumin/saline) for 14days. On day 15, one subset of animals was seizure tested in the maximal PTZ model (Experiment 1). In a separate (non-seizure tested) subset of animals, blood was collected, and brains were excised following high-energy, head-focused microwave fixation. Lipid analysis was performed on serum and brain (Experiment 2). For data analysis, the DHA and DHA EE groups were combined since they did not differ significantly from each other. In the maximal PTZ model, DHA significantly increased seizure latency by approximately 3-fold as compared to vehicle-injected animals. This increase in seizure latency was associated with an increase in serum unesterified DHA. Total brain DHA and brain unesterified DHA concentrations, however, did not differ significantly in the treatment and control groups. An increase in serum unesterified DHA concentration reflecting increased flux of DHA to the brain appears to explain changes in seizure threshold, independent of changes in brain DHA concentrations. Copyright © 2014 Elsevier Inc. All rights reserved.

Flotation-nitric acid leach procedure for increasing uranium recovery from a refractory ore

International Nuclear Information System (INIS)

Carnahan, T.G.; Lei, K.P.V.

1979-01-01

The Bureau of Mines investigated a flotation-nitric acid leach procedure as part of the goal to maximize minerals and metals recovered from primary and secondary domestic resources. Studies were conducted on an ore that contained carbon-bearing and sulfide mineralization that rendered a portion of the ore refractory (resistant) to conventional leaching technology. The procedure investigated for treating the ore consisted of the following: (1) separation by flotation of the carbonaceous and sulfidic components from the ore, (2) leaching the flotation concentrate with nitric acid at 100 0 to 110 0 C, (3) leaching the flotation tailings with sulfuric acid, and (4) processing the combined leached slurries in a conventional manner to recover yellow cake. In step 2, HNO 3 is converted to gaseous products from which it is regenerated by reacting these products with air and water for further leaching. An overall uranium extraction of 96% was achieved by this procedure

Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.

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Young, Lindsay R; Kurzer, Mindy S; Thomas, William; Redmon, J Bruce; Raatz, Susan K

2013-07-01

The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in healthy individuals are not well defined. Three test diets-high-fat diet (40% energy as fat), low-fat diet (LF; 20% energy as fat), and a diet with low fat and high omega-3 fatty acid (LFn3; 23% energy as fat)--were tested in a randomized crossover designed controlled feeding trial in healthy postmenopausal women. Plasma IGF-I, IGF binding protein-3 (IGFBP-3), insulin, glucose, and ratio of IGF-I/IGFBP-3 concentrations were measured in response to diets. Insulin sensitivity was calculated using the homeostatic model assessment of insulin resistance We hypothesized that IGF-I, insulin, and glucose concentrations would decrease and IGFBP-3 concentration would increase in response to the low-fat diets. Eight weeks of the LFn3 diet increased circulating IGF-I (P diet increased IGFBP-3 (P = .04), resulting in trends toward an increased IGF-I/IGFBP-3 ratio with the LFn3 diet and a decreased IGF-I/IGFBP-3 ratio with the LF diet (P = .13 for both comparisons). No statistically significant differences were detected between treatments at baseline or 8 weeks for IGF-1, IGFBP-3, or the ratio of IGF-1/IGFBP-3. Insulin, glucose, and the homeostatic model assessment of insulin resistance were not altered by the interventions. Low-fat diet with high n-3 fatty acids may increase circulating IGF-I concentrations without adversely affecting insulin sensitivity in healthy individuals. Published by Elsevier Inc.

Waste fatty acid addition to black liquor to decrease tall oil soap solubility and increase skimming efficiency in kraft mills pulping mountain pine beetle-infested wood

Energy Technology Data Exchange (ETDEWEB)

Uloth, V.; Guy, E. [FPInnovations, Prince George, BC (Canada). PAPRICAN Div.; Shewchuk, D. [Cariboo Pulp and Paper, Quesnel, BC (Canada); Van Heek, R. [Aker Kvaerner, Vancouver, BC (Canada)

2009-07-01

This paper presented the results of tests conducted to determine if the addition of waste fatty acids from vegetable oil processing might decrease tall oil soap solubility in pine-beetle impacted wood from British Columbia (BC). The soap recovery and tall oil production at BC mills has fallen by 30 to 40 percent in recent years due to the pulping of high proportions of grey-stage beetle-impacted wood. Full-scale mill tests were conducted over a 4-day period. The study showed that the addition of tall oil fatty acids or waste fatty acids from vegetable oil processing could decrease tall oil soap solubility and increase the soup skimming efficiency in mills pulping a large percentage of grey stage beetle-infested wood. The addition of fatty acids increased tall oil soap skimming efficiency from 50.2 percent in the baseline tests to 71.8 percent based on the total soap available, and from 76.7 percent in the baseline tests to 87.5 percent based on insoluble soap only. The economic analyses indicated that waste fatty acid addition could be economical when natural gas and oil prices are high. 4 tabs., 9 figs.

Increased Pre- and Post-Meal Free Fatty Acid Levels in Black, Obese Adolescents.

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Cazeau, Rachel-Marie; Rauch, Lindsey; Huang, Hong; Bauer, John A; Hoffman, Robert P

2016-09-01

Black adolescents are at increased risk of cardiometabolic disease but have lower fasting triglyceride, which is usually associated with decreased risk. No one has studied racial differences in triglycerides or free fatty acids (FFAs) after a high-fat meal. Oral glucose tolerance testing was used to assess insulin secretion, sensitivity, and disposition index (DI). Endothelial function, triglycerides, FFA, c-reactive protein, interleukin 6 (IL6), and adiponectin were measured both pre- and 3 hr postprandially (McDonald's Big Breakfast(®) and 12 ounce Sprite(®)) in obese adolescents (10-13 years, 9 black and 7 white). Endothelial function was assessed using reactive hyperemic changes in forearm vascular resistance (FVR). Oral glucose tolerance test (OGTT) showed no difference in insulin sensitivity, but blacks tended to have (P = 0.08) higher insulin secretion and had increased DI (P = 0.003). After a high-fat meal, triglycerides increased in both groups (P < 0.001), tended to be lower in blacks compared with whites preprandially (64 ± 33 mg/dL vs 110 ± 80, P = 0.064), and was lower postprandially (112 ± 63 vs 188 ± 112, P = 0.039). Pre- and postprandial FFA (Black: 0.58 ± 0.15 and 0.39 ± 0.18 vs. white: 0.44 ± 0.14 and 0.26 ± 0.06, P = 0.020) and adiponectin (P = 0.002) were increased in blacks. FFA decreased in both groups postprandially (P = 0.002). IL6 increased after the meal (P = 0.022). Endothelial function decreased postprandially (P < 0.02), but this was due to a decrease in preocclusion FVR. These results indicate that differences in fat metabolism are present in both black and white obese adolescents. How these differences explain higher rates of cardiometabolic disease in blacks is unclear.

Increasing Thai Catfish's Immunity (Pangasius hypophthalmus Fowler Using Ascorbic Acid

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, Ilmiah

2007-08-01

Full Text Available ABSTRACTAn experiment to determine Thai catfish's (Pangasius hypophthalmus Fowler immunity was carried out using different levels of ascorbic acid (0, 1.000, 2.000 and 3.000 mg/kg feed.  Fish of 15-20 g in weight were kept in aquaria for 6 weeks with density of 15 fish/aquaria.  Feed was given at 5-10 % of total biomass with frequency of three times a day.  The blood sampling was taken every week and the challenge test with Aeromonas hydrophila (106cells/mm3 injection intramuscular was done on the 30th day.   The result of this experiment shown that feed with ascorbic acid of 2.000 mg/kg was elevated the cellular responses such as: leucocyte total (34.850 cels/mm3, differential of leucocyte (lymphocyte: 72,2%, monocyte: 8,0%, neutrophyl: 7,8%, phagocytic index (13% and humoral response (titre antibody: 0.829 serum aglutination unit, which at the same time proves high level of survival rate against the artificial injection using A. hydrophila. Key words :  Ascorbic acid, fish immunity, Thai catfish, Pangasius hypophthalmus.   ABSTRAK Suatu penelitian telah dilakukan di laboratorium dengan menggunakan ikan jambal Siam (Pangasius hypophthalmus Fowler untuk melihat tingkat kekebalan ikan dengan menambahkan vitamin C pada pakan (0, 1.000, 2.000 dan 3.000 mg/kg pakan.  Ikan jambal Siam ukuran 15-20 g dipelihara dalam aquarium selama 6 minggu dengan kepadatan 15 ekor/wadah.  Pemberian pakan dilakukan 3 kali sehari sebanyak 5-10% dari bobot biomasa, pengambilan contoh darah dilakukan setiap minggu dan uji tantang dilakukan pada hari ke-30 dengan bakteri Aeromonas hydrophila (106 sel/mm3 secara intramuskular.  Hasil penelitian menunjukkan bahwa penambahan vitamin C sebanyak 2.000 mg/kg pakan menyebabkan meningkatnya respon seluler antara lain: total lekosit (34.850 sel/mm3, jenis lekosit (limfosit: 72,2%, monosit: 8,0%, netrofil: 7,7% dan trombosit: 17,6% indeks fagositik 13% dan respon humoral (titer antibodi: 0,829 unit serum aglutinasi

Research and application of multi-hydrogen acidizing technology of low-permeability reservoirs for increasing water injection

Science.gov (United States)

Ning, Mengmeng; Che, Hang; Kong, Weizhong; Wang, Peng; Liu, Bingxiao; Xu, Zhengdong; Wang, Xiaochao; Long, Changjun; Zhang, Bin; Wu, Youmei

2017-12-01

The physical characteristics of Xiliu 10 Block reservoir is poor, it has strong reservoir inhomogeneity between layers and high kaolinite content of the reservoir, the scaling trend of fluid is serious, causing high block injection well pressure and difficulty in achieving injection requirements. In the past acidizing process, the reaction speed with mineral is fast, the effective distance is shorter and It is also easier to lead to secondary sedimentation in conventional mud acid system. On this point, we raised multi-hydrogen acid technology, multi-hydrogen acid release hydrogen ions by multistage ionization which could react with pore blockage, fillings and skeletal effects with less secondary pollution. Multi-hydrogen acid system has advantages as moderate speed, deep penetration, clay low corrosion rate, wet water and restrains precipitation, etc. It can reach the goal of plug removal in deep stratum. The field application result shows that multi-hydrogen acid plug removal method has good effects on application in low permeability reservoir in Block Xiliu 10.

Alkyl phosphonic acids and sulfonic acids in the Murchison meteorite

Science.gov (United States)

Cooper, George W.; Onwo, Wilfred M.; Cronin, John R.

1992-01-01

Homologous series of alkyl phosphonic acids and alkyl sulfonic acids, along with inorganic orthophosphate and sulfate, are identified in water extracts of the Murchison meteorite after conversion to their t-butyl dimethylsilyl derivatives. The methyl, ethyl, propyl, and butyl compounds are observed in both series. Five of the eight possible alkyl phosphonic acids and seven of the eight possible alkyl sulfonic acids through C4 are identified. Abundances decrease with increasing carbon number as observed of other homologous series indigenous to Murchison. Concentrations range downward from approximately 380 nmol/gram in the alkyl sulfonic acid series, and from 9 nmol/gram in the alkyl phosphonic acid series.

Exaggerated compensatory response to acute respiratory alkalosis in panic disorder is induced by increased lactic acid production.

Science.gov (United States)

Ueda, Yoshiyasu; Aizawa, Masayo; Takahashi, Atsushi; Fujii, Masamitsu; Isaka, Yoshitaka

2009-03-01

In acute respiratory alkalosis, the severity of alkalaemia is ameliorated by a decrease in plasma [HCO(3)(-)] of 0.2 mEq/L for each 1 mmHg decrease in PaCO(2). Although hyperventilation in panic disorder patients is frequently encountered in outpatients, the drop in plasma [HCO(3)(-)] sometimes surpasses the expectation calculated from the above formula. The quantitative relationship between reduced PaCO(2) and plasma [HCO(3)(-)] in acute respiratory alkalosis has not been studied in panic disorder patients. Our objective was to provide reference data for the compensatory metabolic changes in acute respiratory alkalosis in panic disorder patients. In 34 panic disorder patients with hyperventilation attacks, we measured arterial pH, PaCO(2), plasma [HCO(3)(-)] and lactate on arrival at the emergency room. For each decrease of 1 mmHg in PaCO(2), plasma [HCO(3)(-)] decreased by 0.41 mEq/L. During hypocapnia, panic disorder patients exhibited larger increases in serum lactate levels (mean +/- SD; 2.59 +/- 1.50 mmol/L, range; 0.78-7.78 mmol/L) than previously reported in non-panic disorder subjects. Plasma lactate accumulation was correlated with PaCO(2) (P respiratory alkalosis is exaggerated by increased lactic acid production in panic disorder patients. Here, we call attention to the diagnosis of acid-base derangements by means of plasma [HCO(3)(-)] and lactate concentration in panic disorder patients.

Demographic Responses to Oxidative Stress and Inflammation in the Wandering Albatross (Diomedea exulans.

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David Costantini

Full Text Available One of the major challenges in ecological research is the elucidation of physiological mechanisms that underlie the demographic traits of wild animals. We have assessed whether a marker of plasma oxidative stress (TBARS and plasma haptoglobin (protein of the acute inflammatory phase response measured at time t predict five demographic parameters (survival rate, return rate to the breeding colony, breeding probability, hatching and fledging success in sexually mature wandering albatrosses over the next four years (Diomedea exulans using a five-year individual-based dataset. Non-breeder males, but not females, having higher TBARS at time t had reduced future breeding probabilities; haptoglobin was not related to breeding probability. Neither TBARS nor haptoglobin predicted future hatching or fledging success. Haptoglobin had a marginally positive effect on female survival rate, while TBARS had a marginally negative effect on return rate. Our findings do not support the role for oxidative stress as a constraint of future reproductive success in the albatross. However, our data point to a potential mechanism underlying some aspects of reproductive senescence and survival. Our results also highlight that the study of the consequences of oxidative stress should consider the life-cycle stage of an individual and its reproductive history.

Noble Metal Decoration and Presulfation on TiO2: Increased Photocatalytic Activity and Efficient Esterification of n-Butanol with Citric Acid

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Yu Niu

2016-01-01

Full Text Available TiO2 has been widely used as a key catalyst in photocatalytic reactions; it also shows good catalytic activity for esterification reactions. Different sulfated M-TiO2 nanoparticles (M = Ag, Au, Rh, and Pt were prepared by photodeposition and ultrasonic methods. The results show that the noble metal nanoparticles, which were loaded onto a TiO2 surface, slightly affected the crystal phase and particle size of TiO2. Among all the catalysts, SO42-/Au-TiO2 exhibited the best catalytic activity in the esterification reaction for the synthesis of citric acid n-butyl acetate and in the decomposition of methyl orange, as confirmed by a high conversion rate of up to 98.2% and 100% degradation rate, respectively. This can be attributed to an increase in the Lewis acidity of the catalyst and increased separation efficiency of electron-hole pairs. This superior catalyst has great potential applications in esterification reactions and wastewater treatments.

High Normal Uric Acid Levels Are Associated with an Increased Risk of Diabetes in Lean, Normoglycemic Healthy Women.

Science.gov (United States)

Shani, Michal; Vinker, Shlomo; Dinour, Dganit; Leiba, Merav; Twig, Gilad; Holtzman, Eliezer J; Leiba, Adi

2016-10-01

The risk associated with serum uric acid (SUA) levels within the normal range is unknown, especially among lean and apparently healthy adults. Evaluating whether high-normal SUA levels, 6.8 mg/dL and below, are associated with an increased diabetes risk, compared with low-normal SUA. This was a cohort study with 10 years of followup involving all clinics of the largest nationally distributed Health Maintenance Organization in Israel. Participants included 469,947 examinees, 40-70 years old at baseline, who had their SUA measured during 2002. We excluded examinees who had hyperuricemia (SUA > 6.8 mg/dL), impaired fasting glucose, overweight or obesity and chronic cardiovascular or renal disorders. The final cohort was composed of 30 302 participants. Participants were followed up to a new diagnosis of diabetes during the study period. Odds ratio of developing diabetes among participants with high-normal baseline SUA were compared with low-normal (2 ≤ uric acid lean women when compared with those with low-normal values.

Retinoic acid-treated pluripotent stem cells undergoing neurogenesis present increased aneuploidy and micronuclei formation.

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Rafaela C Sartore

Full Text Available The existence of loss and gain of chromosomes, known as aneuploidy, has been previously described within the central nervous system. During development, at least one-third of neural progenitor cells (NPCs are aneuploid. Notably, aneuploid NPCs may survive and functionally integrate into the mature neural circuitry. Given the unanswered significance of this phenomenon, we tested the hypothesis that neural differentiation induced by all-trans retinoic acid (RA in pluripotent stem cells is accompanied by increased levels of aneuploidy, as previously described for cortical NPCs in vivo. In this work we used embryonal carcinoma (EC cells, embryonic stem (ES cells and induced pluripotent stem (iPS cells undergoing differentiation into NPCs. Ploidy analysis revealed a 2-fold increase in the rate of aneuploidy, with the prevalence of chromosome loss in RA primed stem cells when compared to naïve cells. In an attempt to understand the basis of neurogenic aneuploidy, micronuclei formation and survivin expression was assessed in pluripotent stem cells exposed to RA. RA increased micronuclei occurrence by almost 2-fold while decreased survivin expression by 50%, indicating possible mechanisms by which stem cells lose their chromosomes during neural differentiation. DNA fragmentation analysis demonstrated no increase in apoptosis on embryoid bodies treated with RA, indicating that cell death is not the mandatory fate of aneuploid NPCs derived from pluripotent cells. In order to exclude that the increase in aneuploidy was a spurious consequence of RA treatment, not related to neurogenesis, mouse embryonic fibroblasts were treated with RA under the same conditions and no alterations in chromosome gain or loss were observed. These findings indicate a correlation amongst neural differentiation, aneuploidy, micronuclei formation and survivin downregulation in pluripotent stem cells exposed to RA, providing evidence that somatically generated chromosomal

Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats

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Kusmiyati Tjahjono DK

2013-04-01

Full Text Available Background The prevalence of diabetes in Indonesia is increasing due to various factors, including life style changes such as trans fatty acid (TFA intake. High TFA intake is known to be related to blood lipid profile changes resulting in cardiovascular disorders. This study was to identify the effect of TFA on nitric oxide (NO production and on necrosis of pancreatic beta cells. Methods A study of randomized pre-test post–test design with control group. Thirty Sprague Dawley rats were divided into 3 groups, i.e. group K (control, group P1 receiving a diet with 5% TFA, and P2 receiving 10% TFA. The intervention was performed for 8 weeks. NO level and pancreatic beta-cell necrosis were analyzed using Pearson’s chi square test. Results After 4 weeks of treatment there was no change in NO levels in group K, but increased NO in P2 (2.6-3.8 ìM. At 8 weeks after treatment, NO levels in groups P1 and P2 increased to 2.6-3.4 ìM and 4.2-14.3 ìM, respectively, while in group K only 2 rats had increased NO levels of 2.8-2.9 ìM. With Pearson’s chi-square test, there was a signifant difference in the proportions of necrotic pancreatic beta cells after 4 weeks and 8 weeks (p=0.000. No necrosis of beta cells was found in group K, mild necrosis in group P1 (1-25% and moderate necrosis in group P2 (26-50%. Conclusion TFA consumption significantly increases NO levels in Sprague Dawley rats and also results in moderate grades of necrosis of pancreatic beta cells.

Trans fatty acids increase nitric oxide levels and pancreatic beta-cell necrosis in rats

Directory of Open Access Journals (Sweden)

Kusmiyati Tjahjono DK

2015-12-01

Full Text Available BACKGROUND The prevalence of diabetes in Indonesia is increasing due to various factors, including life style changes such as trans fatty acid (TFA intake. High TFA intake is known to be related to blood lipid profile changes resulting in cardiovascular disorders. This study was to identify the effect of TFA on nitric oxide (NO production and on necrosis of pancreatic beta cells. METHODS A study of randomized pre-test post–test design with control group. Thirty Sprague Dawley rats were divided into 3 groups, i.e. group K (control, group P1 receiving a diet with 5% TFA, and P2 receiving 10% TFA. The intervention was performed for 8 weeks. NO level and pancreatic beta-cell necrosis were analyzed using Pearson’s chi square test. RESULTS After 4 weeks of treatment there was no change in NO levels in group K, but increased NO in P2 (2.6-3.8 ìM. At 8 weeks after treatment, NO levels in groups P1 and P2 increased to 2.6-3.4 ìM and 4.2-14.3 ìM, respectively, while in group K only 2 rats had increased NO levels of 2.8-2.9 ìM. With Pearson’s chi-square test, there was a signifant difference in the proportions of necrotic pancreatic beta cells after 4 weeks and 8 weeks (p= 0.000. No necrosis of beta cells was found in group K, mild necrosis in group P1 (1-25% and moderate necrosis in group P2 (26-50%. CONCLUSION TFA consumption significantly increases NO levels in Sprague Dawley rats and also results in moderate grades of necrosis of pancreatic beta cells

Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women.

Science.gov (United States)

Marini, A; Grether-Beck, S; Jaenicke, T; Weber, M; Burki, C; Formann, P; Brenden, H; Schönlau, F; Krutmann, J

2012-01-01

In recent years there has been an increasing interest in the use of nutritional supplements to benefit human skin. Molecular evidence substantiating such effects, however, is scarce. In the present study we investigated whether nutritional supplementation of women with the standardized pine bark extract Pycnogenol® will improve their cosmetic appearance and relate these effects to expression of corresponding molecular markers of their skin. For this purpose 20 healthy postmenopausal women were supplemented with Pycnogenol for 12 weeks. Before, during and after supplementation, their skin condition was assessed (i) by employing non-invasive, biophysical methods including corneometry, cutometry, visioscan and ultrasound analyses and (ii) by taking biopsies and subsequent PCR for gene expression analyses related to extracellular matrix homeostasis. Pycnogenol supplementation was well tolerated in all volunteers. Pycnogenol significantly improved hydration and elasticity of skin. These effects were most pronounced in women presenting with dry skin conditions prior to the start of supplementation. The skin-physiological improvement was accompanied by a significant increase in the mRNA expression of hyaluronic acid synthase-1 (HAS-1), an enzyme critically involved in the synthesis of hyaluronic acid, and a noticeable increase in gene expression involved in collagen de novo synthesis. This study provides skin-physiological and for the first time molecular evidence that Pycnogenol supplementation benefits human skin by increasing skin hydration and skin elasticity. These effects are most likely due to an increased synthesis of extracellular matrix molecules such as hyaluronic acid and possibly collagen. Pycnogenol supplementation may thus be useful to counteract the clinical signs of skin aging. Copyright © 2012 S. Karger AG, Basel.

Ultraviolet B irradiation induces changes in the distribution and release of arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture

International Nuclear Information System (INIS)

Punnonen, K.; Puustinen, T.; Jansen, C.T.

1987-01-01

There is increasing evidence that derivatives of 20-carbon polyunsaturated fatty acids, the eicosanoids, play an important role in the inflammatory responses of the human skin. To better understand the metabolic fate of fatty acids in the skin, the effect of ultraviolet B (UVB) irradiation (280-320 nm) on the distribution and release of 14 C-labeled arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture was investigated. Ultraviolet B irradiation induced the release of all three 14 C-labeled fatty acids from the phospholipids, especially from phosphatidylethanolamine, and this was accompanied by increased labeling of the nonphosphorus lipids. This finding suggests that UVB induces a significant liberation of eicosanoid precursor fatty acids from cellular phospholipids, but the liberated fatty acids are largely reincorporated into the nonphosphorus lipids. In conclusion, the present study suggests that not only arachidonic acid but also dihomo-gamma-linolenic acid, and eicosapentaenoic acid might be involved in the UVB irradiation-induced inflammatory reactions of human skin

Corrosion of stainless steels and nickel-base alloys in solutions of nitric acid and hydrofluoric acid

International Nuclear Information System (INIS)

Horn, E.M.; Renner, M.

1992-01-01

Reactions involving nitric acid may always result in the contamination of this acid with fluorides. In highly concentrted nitric acid, the presence of small amounts of HF will substantially reduce the corrosion of metallic materials. Mixtures consisting of hydrofluoric acid and hypo-azeotropic nitric acid on the other hand will strongly attack: the metal loss will markedly increase with increasing HNO 3 and HF concentrations as well as with rising temperatures. The investigation covered 12 stainless steel grades and nickel-base alloys. With constant HNO 3 content, corrosion rates will rise linearly when increasing the HF concentration. With constant HF concentration (0,25 M), corrosion rates will increase rapidly with increasing nitric acid concentration (from 0.3 M to 14.8 M). This can best be described by superimposing a linear function and a hyperbolic function that is reflecting the change in the HNO 3 content. Alloys containing as much chromium as possible (up to 46 wt.%) will exhibit the best corrosion resistance. Alloy NiCr30FeMo (Hastelloy alloy G-30) proved to be well suitable in this investigation. (orig.) [de

Dependence of the metabolic fecal amino acids on the amino acid content of the feed. 1

International Nuclear Information System (INIS)

Krawielitzki, K.; Schadereit, R.; Voelker, T.; Reichel, K.

1981-01-01

The amount of metabolic fecal amino acids (MFAA) in dependence on the amino acid intake was determined for graded maize rations in 15 N-labelled rats and the part of labelled endogenous amino acids in feces was calculated by the isotope dilution method. The excretion of amino acids and MFAA in feces are described as functions of the amino acid intake for 17 amino acids and calculated regressively. For all 17 amino acids investigated, there was a more or less steep increase of MFAA according to an increasing amino acid intake. In contrast to N-free feeding, the MFAA increase to the 2- to 4.5-fold value in feeding with pure maize (16.5% crude protein). The thesis of the constancy of the excretion of MFAA can consequently be no longer maintained. The true digestibility according to the conventional method is, on an average of all amino acids, 7.3 units below ascertained according to the 15 N method. The limiting amino acids lysine and threonine revealed the greatest difference. Tryptophane as first limiting amino acid could not be determined. The true digestibility of nearly all amino acids ascertained for maize by the isotope method is above 90%. (author)

Biopropionic acid production via molybdenumcatalyzed deoxygenation of lactic acid

NARCIS (Netherlands)

Korstanje, T.J.; Kleijn, H.; Jastrzebski, J.T.B.H.; Klein Gebbink, R.J.M.

2013-01-01

As the search for non-fossil based building blocks for the chemical industry increases, new methods for the deoxygenation of biomass-derived substrates are required. Here we present the deoxygenation of lactic acid to propionic acid, using a catalyst based on the non-noble and abundant metal

Effect of acetic acid on citric acid fermentation in an integrated citric acid-methane fermentation process.

Science.gov (United States)

Xu, Jian; Chen, Yang-Qiu; Zhang, Hong-Jian; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui

2014-09-01

An integrated citric acid-methane fermentation process was proposed to solve the problem of extraction wastewater in citric acid fermentation process. Extraction wastewater was treated by anaerobic digestion and then recycled for the next batch of citric acid fermentation to eliminate wastewater discharge and reduce water resource consumption. Acetic acid as an intermediate product of methane fermentation was present in anaerobic digestion effluent. In this study, the effect of acetic acid on citric acid fermentation was investigated and results showed that lower concentration of acetic acid could promote Aspergillus niger growth and citric acid production. 5-Cyano-2,3-ditolyl tetrazolium chloride (CTC) staining was used to quantify the activity of A. niger cells, and the results suggested that when acetic acid concentration was above 8 mM at initial pH 4.5, the morphology of A. niger became uneven and the part of the cells' activity was significantly reduced, thereby resulting in deceasing of citric acid production. Effects of acetic acid on citric acid fermentation, as influenced by initial pH and cell number in inocula, were also examined. The result indicated that inhibition by acetic acid increased as initial pH declined and was rarely influenced by cell number in inocula.

Modification of cassava starch using combination process lactic acid hydrolysis and micro wave heating to increase coated peanut expansion quality

Science.gov (United States)

Sumardiono, Siswo; Pudjihastuti, Isti; Jos, Bakti; Taufani, Muhammad; Yahya, Faad

2017-05-01

Modified cassava starch is very prospective products in the food industry. The main consideration of this study is the increasing volume of imported wheat and the demand for modified cassava starch industry. The purpose of this study is the assessing of lactic acid hydrolysis and microwave heating impact to the physicochemical and rheological properties of modified cassava starch, and test applications of modified cassava starch to coated peanut expansion quality. Experimental variables include the concentration of lactic acid (0.5% w/w, 1% w/w; 2% w/w), a time of hydrolysis (15, 30, 45 minutes), a time of microwave heating (1, 2, 3 hours). The research step is by dissolving lactic acid using aquadest in the stirred tank reactor, then added cassava starch. Hydrolysed cassava starch was then heated by microwave. Physicochemical properties and rheology of the modified cassava starch is determined by the solubility, swelling power, and test congestion. The optimum obtained results indicate that solubility, swelling power, congestion test, respectively for 19.75%; 24.25% and 826.10% in the hydrolysis treatment for 15 minutes, 1% w lactic acid and microwave heating 3 hours. The physicochemical and rheological properties of modified cassava starch have changed significantly when compared to the native cassava starch. Furthermore, these modified cassava starch are expected to be used for the substitution of food products.

Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes.

Science.gov (United States)

Lee, Bonggi; Kwon, Misung; Choi, Jae Sue; Jeong, Hyoung Oh; Chung, Hae Young; Kim, Hyeung-Rak

2015-12-01

Stamens of Nelumbo nucifera Gaertn have been used as a Chinese medicine due to its antioxidant, hypoglycemic, and antiatherogenic activity. However, the effects of kaempferol, a main component of N. nucifera, on obesity are not fully understood. We examined the effect of kaempferol on adipogenesis and fatty acid oxidation signaling pathways in 3T3-L1 adipocytes. Kaempferol reduced cytoplasmic triglyceride (TG) accumulation in dose and time-dependent manners during adipocyte differentiation. Accumulation of TG was rapidly reversed by retrieving kaempferol treatment. Kaempferol broadly decreased mRNA or protein levels of adipogenic transcription factors and their target genes related to lipid accumulation. Kaempferol also suppressed glucose uptake and glucose transporter GLUT4 mRNA expression in adipocytes. Furthermore, protein docking simulation suggests that Kaempferol can directly bind to and activate peroxisome proliferator-activated receptor (PPAR)-α by forming hydrophobic interactions with VAL324, THR279, and LEU321 residues of PPARα. The binding affinity was higher than a well-known PPARα agonist fenofibrate. Consistently, mRNA expression levels of PPARα target genes were increased. Our study indicates while kaempferol inhibits lipogenic transcription factors and lipid accumulation, it may bind to PPARα and stimulate fatty acid oxidation signaling in adipocytes.

Phytanic acid-an overlooked bioactive fatty acid in dairy fat?

DEFF Research Database (Denmark)

Hellgren, Lars

2010-01-01

dissipation in skeletal muscles. Phytanic acid levels in serum are associated with an increased risk of developing prostate cancer, but the available data do not support a general causal link between circulating phytanic acid and prostate cancer risk. However, certain individuals, with specific single......Phytanic acid is a multibranched fatty acid with reported retinoid X receptor (RXR) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist activity, which have been suggested to have preventive effects on metabolic dysfunctions. Serum level in man is strongly correlated...

Increasing the efficiency of sulphur dioxide in wine by using of saturated higher fatty acids

Directory of Open Access Journals (Sweden)

Petra Bábíková

2012-01-01

Full Text Available This work is aimed on stopping of alcoholic fermentation to leave residual sugar and the possibility of sulfur dioxide reduction in wine technology and storage. As a very good opportunity showed mixture of higher saturated fatty acids with a reduced dose of sulfur dioxide. Experiments have confirmed that the concentration of viable yeasts in 1 ml of wine for variants treated with a mixture of fatty acids is significantly lower than in variants treated with sulfur dioxide alone. Then was monitored the influence of fatty acids on stored wine with residual sugar. At this point a dramatically prolongation of interval to secondary fermentation (depreciation of wine in the bottle was confirmed. Finally, attention was paid to influence on the organoleptic characteristics of wine treated this way. In this case, it is possible to consider the recommended concentration of fatty acid below the threshold of susceptibility.

Periplasmic Acid Stress Increases Cell Division Asymmetry (Polar Aging of Escherichia coli.

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Michelle W Clark

Full Text Available Under certain kinds of cytoplasmic stress, Escherichia coli selectively reproduce by distributing the newer cytoplasmic components to new-pole cells while sequestering older, damaged components in cells inheriting the old pole. This phenomenon is termed polar aging or cell division asymmetry. It is unknown whether cell division asymmetry can arise from a periplasmic stress, such as the stress of extracellular acid, which is mediated by the periplasm. We tested the effect of periplasmic acid stress on growth and division of adherent single cells. We tracked individual cell lineages over five or more generations, using fluorescence microscopy with ratiometric pHluorin to measure cytoplasmic pH. Adherent colonies were perfused continually with LBK medium buffered at pH 6.00 or at pH 7.50; the external pH determines periplasmic pH. In each experiment, cell lineages were mapped to correlate division time, pole age and cell generation number. In colonies perfused at pH 6.0, the cells inheriting the oldest pole divided significantly more slowly than the cells inheriting the newest pole. In colonies perfused at pH 7.50 (near or above cytoplasmic pH, no significant cell division asymmetry was observed. Under both conditions (periplasmic pH 6.0 or pH 7.5 the cells maintained cytoplasmic pH values at 7.2-7.3. No evidence of cytoplasmic protein aggregation was seen. Thus, periplasmic acid stress leads to cell division asymmetry with minimal cytoplasmic stress.

[Lipid synthesis by an acidic acid tolerant Rhodotorula glutinis].

Science.gov (United States)

Lin, Zhangnan; Liu, Hongjuan; Zhang, Jian'an; Wang, Gehua

2016-03-01

Acetic acid, as a main by-product generated in the pretreatment process of lignocellulose hydrolysis, significantly affects cell growth and lipid synthesis of oleaginous microorganisms. Therefore, we studied the tolerance of Rhodotorula glutinis to acetic acid and its lipid synthesis from substrate containing acetic acid. In the mixed sugar medium containing 6 g/L glucose and 44 g/L xylose, and supplemented with acetic acid, the cell growth was not:inhibited when the acetic acid concentration was below 10 g/L. Compared with the control, the biomass, lipid concentration and lipid content of R. glutinis increased 21.5%, 171% and 122% respectively when acetic acid concentration was 10 g/L. Furthermore, R. glutinis could accumulate lipid with acetate as the sole carbon source. Lipid concentration and lipid yield reached 3.20 g/L and 13% respectively with the initial acetic acid concentration of 25 g/L. The lipid composition was analyzed by gas chromatograph. The main composition of lipid produced with acetic acid was palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, including 40.9% saturated fatty acids and 59.1% unsaturated fatty acids. The lipid composition was similar to that of plant oil, indicating that lipid from oleaginous yeast R. glutinis had potential as the feedstock of biodiesel production. These results demonstrated that a certain concentration of acetic acid need not to be removed in the detoxification process when using lignocelluloses hydrolysate to produce microbial lipid by R. glutinis.

Unsaturated free fatty acids increase benzodiazepine receptor agonist binding depending on the subunit composition of the GABAA receptor complex.

Science.gov (United States)

Witt, M R; Westh-Hansen, S E; Rasmussen, P B; Hastrup, S; Nielsen, M

1996-11-01

It has been shown previously that unsaturated free fatty acids (FFAs) strongly enhance the binding of agonist benzodiazepine receptor ligands and GABAA receptor ligands in the CNS in vitro. To investigate the selectivity of this effect, recombinant human GABAA/benzodiazepine receptor complexes formed by different subunit compositions (alpha x beta y gamma 2, x = 1, 2, 3, and 5; y = 1, 2, and 3) were expressed using the baculovirus-transfected Sf9 insect cell system. At 10(-4) M, unsaturated FFAs, particularly arachidonic (20:4) and docosahexaenoic (22:6) acids, strongly stimulated (> 200% of control values) the binding of [3H]flunitrazepam ([3H]FNM) to the alpha 3 beta 2 gamma 2 receptor combination in whole cell preparations. No effect or small increases in levels of unsaturated FFAs on [3H]FNM binding to alpha 1 beta x gamma 2 and alpha 2 beta x gamma 2 receptor combinations were observed, and weak effects (130% of control values) were detected using the alpha 5 beta 2 gamma 2 receptor combination. The saturated FFAs, stearic and palmitic acids, were without effect on [3H]FNM binding to any combination of receptor complexes. The hydroxylated unsaturated FFAs, ricinoleic and ricinelaidic acids, were shown to decrease the binding of [3H]FNM only if an alpha 1 beta 2 gamma 2 receptor combination was used. Given the heterogeneity of the GABAA/ benzodiazepine receptor subunit distribution in the CNS, the effects of FFAs on the benzodiazepine receptor can be assumed to vary at both cellular and regional levels.

Increased sensitivity of the respiratory system of plants grown in Gibberellic acid toward fluoride

Energy Technology Data Exchange (ETDEWEB)

Lustinec, J; Pokorna, V; Ruzicka, J

1962-01-01

Gibberellic acid in concentrations between 2 and 80 mg/l does not affect the ratio of radioactivities of /sup 14/CO/sub 2/ liberated from glucose-6-/sup 14/C and -1-/sup 14/C(C/sub 6//C/sub 1/) when acting for several hours on sliced wheat leaves, and that at a concentration of 10 mg/l it does not alter the degree of inhibition of respiration due to fluoride, iodoacetate and malonate or the consumption of oxygen. A linear relationship was established between the decrease in /sup 14/CO/sub 2/ liberation from glucose-/sup 14/C and the concentration of gibberellic acid. The C/sub 6//C/sub 1/ ratio as well as the absolute values of radioactivity decrease more rapidly in the course of several days after the germination of plants grown in a solution of gibberellic acid (10-20 mg/l) than in the water-grown controls. Fluoride inhibits the respiration of plants grown in gibberellic acid more than of those grown in water, its tissue concentration being either equal or less in the gibberellic -grown plants; the effect of iodoacetate and malonate is the same with plants of equal age (4 days) in both variants. 11 references, 1 figure, 4 tables.

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

Science.gov (United States)

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 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. Copyright © 2016 the American Physiological Society.

Nicotinic Acid Increases Adiponectin Secretion from Differentiated Bovine Preadipocytes through G-Protein Coupled Receptor Signaling

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Christina Kopp

2014-11-01

Full Text Available The transition period in dairy cows (3 weeks prepartum until 3 weeks postpartum is associated with substantial mobilization of energy stores, which is often associated with metabolic diseases. Nicotinic acid (NA is an antilipolytic and lipid-lowering compound used to treat dyslipidaemia in humans, and it also reduces non-esterified fatty acids in cattle. In mice the G-protein coupled receptor 109A (GPR109A ligand NA positively affects the secretion of adiponectin, an important modulator of glucose and fat metabolism. In cattle, the corresponding data linking NA to adiponectin are missing. Our objective was to examine the effects of NA on adiponectin and AMPK protein abundance and the expression of mRNAs of related genes such as chemerin, an adipokine that enhances adiponectin secretion in vitro. Differentiated bovine adipocytes were incubated with pertussis toxin (PTX to verify the involvement of GPR signaling, and treated with 10 or 15 µM NA for 12 or 24 h. NA increased adiponectin concentrations (p ≤ 0.001 and the mRNA abundances of GPR109A (p ≤ 0.05 and chemerin (p ≤ 0.01. Pre-incubation with PTX reduced the adiponectin response to NA (p ≤ 0.001. The NA-stimulated secretion of adiponectin and the mRNA expression of chemerin in the bovine adipocytes were suggestive of GPR signaling-dependent improved insulin sensitivity and/or adipocyte metabolism in dairy cows.

Aryl hydrocarbon receptor–ligand axis mediates pulmonary fibroblast migration and differentiation through increased arachidonic acid metabolism

International Nuclear Information System (INIS)

Su, Hsiang-Han; Lin, Hsin-Ting; Suen, Jau-Ling; Sheu, Chau Chyun; Yokoyama, Kazunari K.; Huang, Shau-Ku; Cheng, Chih Mei

2016-01-01

Pulmonary fibroblast migration and differentiation are critical events in fibrogenesis; meanwhile, fibrosis characterizes the pathology of many respiratory diseases. The role of aryl hydrocarbon receptor (AhR), a unique cellular chemical sensor, has been suggested in tissue fibrosis, but the mechanisms through which the AhR-ligand axis influences the fibrotic process remain undefined. In this study, the potential impact of the AhR-ligand axis on pulmonary fibroblast migration and differentiation was analyzed using human primary lung fibroblasts HFL-1 and CCL-202 cells. Boyden chamber-based cell migration assay showed that activated AhR in HFL-1cells significantly enhanced cell migration in response to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), and a known AhR antagonist, CH223191, inhibited its migratory activity. Furthermore, the calcium mobilization and subsequent upregulated expression of arachidonic acid metabolizing enzymes, including cyclooxygenase2 (COX-2) and 5-lipoxygenase (5-LOX), were observed in TCDD-treated HFL-1 cells, concomitant with elevated levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) secretion. Also, significantly increased expression of α-smooth muscle actin α-SMA), a fibroblast differentiation marker, was also noted in TCDD-treated HFL-1 cells (p < 0.05), resulting in a dynamic change in cytoskeleton protein levels and an increase in the nuclear translocation of the myocardin-related transcription factor. Moreover, the enhanced levels of α-SMA expression and fibroblast migration induced by TCDD, PGE2 and LTB4 were abrogated by selective inhibitors for COX-2 and 5-LOX. Knockdown of AhR by siRNA Completely diminished intracellular calcium uptake and reduced α-SMA protein verified by promoter-reporter assays and chromatin immunoprecipitation. Taken together, our results suggested the importance of the AhR-ligand axis in fibroblast migration and differentiation through its capacity in enhancing arachidonic acid metabolism.

Lead–acid batteries coupled with photovoltaics for increased electricity self-sufficiency in households

International Nuclear Information System (INIS)

Oliveira e Silva de, Guilherme; Hendrick, Patrick

2016-01-01

Highlights: • Grid parity is reached for PV installations up to nearly 40% self-sufficiency. • Reaching beyond 40% self-sufficiency requires storage and support policies. • Peak consumption remains constant but load variability rises with self-sufficiency. • Changes in power plants portfolio and wholesale electricity prices are expected. • Limiting feed-in power is a promising solution for reducing load variability. - Abstract: With distributed generation of electricity growing in importance (especially with photovoltaics) and buildings being one of the main consumers of energy in modern societies, distributed storage of energy in buildings is expected to become increasingly present. This paper analyses the use of residential lead–acid energy storage coupled with photovoltaics and its possible interaction with the grid for different limits of feed-in power without any support policies. In the literature, these subjects are often treated independently and for very specific, non-optimised cases, thus motivating further research. Results show that reaching self-sufficiency values up to 40% is possible, close to grid parity values, and only with photovoltaics. Beyond 40%, energy storage must be used, strongly raising the cost of the electricity consumed and therefore the need for support policies for widespread adoption. Also, peak power consumption from the grid remains constant and load variability rises, suggesting that an increase in self-sufficiency would be accompanied by lower utilisation factors of power plants and, consequently, higher wholesale electricity prices during no sunshine hours. Limiting feed-in power attenuates the increased load variability and only slightly affects the economic viability of such installations. These results present a novel optimisation tool for developers and should be considered in future studies of distributed photovoltaics and energy storage as well as in energy policy.