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Sample records for acid excretion increased

  1. Uric acid excretion predicts increased aggression in urban adolescents.

    PubMed

    Mrug, Sylvie; Mrug, Michal

    2016-09-01

    Elevated levels of uric acid have been linked with impulsive and disinhibited behavior in clinical and community populations of adults, but no studies have examined uric acid in relation to adolescent aggression. This study examined the prospective role of uric acid in aggressive behavior among urban, low income adolescents, and whether this relationship varies by gender. A total of 84 adolescents (M age 13.36years; 50% male; 95% African American) self-reported on their physical aggression at baseline and 1.5years later. At baseline, the youth also completed a 12-h (overnight) urine collection at home which was used to measure uric acid excretion. After adjusting for baseline aggression and age, greater uric acid excretion predicted more frequent aggressive behavior at follow up, with no significant gender differences. The results suggest that lowering uric acid levels may help reduce youth aggression. PMID:27180134

  2. Organic Acid Excretion in Penicillium ochrochloron Increases with Ambient pH

    PubMed Central

    Vrabl, Pamela; Fuchs, Viktoria; Pichler, Barbara; Schinagl, Christoph W.; Burgstaller, Wolfgang

    2012-01-01

    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. PMID:22493592

  3. Nod2 deficiency protects mice from cholestatic liver disease by increasing renal excretion of bile acids

    PubMed Central

    Wang, Lirui; Hartmann, Phillipp; Haimerl, Michael; Bathena, Sai P.; Sjöwall, Christopher; Almer, Sven; Alnouti, Yazen; Hofmann, Alan F.; Schnabl, Bernd

    2014-01-01

    Background & aims Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis. Methods We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2−/− mice. Results Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2−/− mice than wild type mice following bile duct ligation for 3 weeks. In contrast to wild type mice, Nod2−/− mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1β in a Nod2 dependent fashion. Conclusions Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte. PMID:24560660

  4. Amaranth oil increased fecal excretion of bile Acid but had no effect in reducing plasma cholesterol in hamsters.

    PubMed

    de Castro, Luíla Ivini Andrade; Soares, Rosana Aparecida Manólio; Saldiva, Paulo H N; Ferrari, Roseli A; Miguel, Ana M R O; Almeida, Claudia A S; Arêas, José Alfredo Gomes

    2013-06-01

    Hamsters were fed for 4 weeks on four different diets: control (C) (balanced diet containing 20 % corn oil as the lipid source), hypercholesterolemic (H) (identical to C but containing 12 % coconut oil, 8 % corn oil and 0.1 % cholesterol as the lipid source), amaranth oil (A) (identical to H without corn oil but with amaranth oil), and squalene (S) (identical to H but admixed with squalene in the ratio found in amaranth oil). There were no significant differences in lipid profile, and in the cholesterol excreted in the animals' feces from amaranth oil (A) and squalene (S) groups. Fecal excretion of bile acids was greater in the amaranth oil (A) and squalene groups (S) as compared to the other groups. The scores of steatosis and parenchymal inflammation observed in the amaranth oil (A) and squalene groups (S) were superior to the ones observed in the other groups. Our findings demonstrated that amaranth oil, and its component squalene, increased the excretion of bile acids but did not have a hypocholesterolemic effect in hamsters fed on a diet containing high amounts of saturated fat and cholesterol. PMID:23456975

  5. SALT LOADING INCREASES URINARY EXCRETION OF LINOLEIC ACID DIOLS AND TRIOLS IN HEALTHY HUMAN SUBJECTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Urinary linoleate (LA) metabolite excretion was investigated in subjects exposed to a salt loading/salt depletion regimen. Twelve healthy subjects were recruited from the New Orleans population (pre-Katrina) and admitted to Tulane-LSU Charity Hospital GCRC after a 5-day outpatient lead in phase on a...

  6. Relation between creatinine and uric acid excretion.

    PubMed Central

    Nishida, Y

    1992-01-01

    The relation between creatinine and uric acid metabolism was analysed in 77 male patients with primary gout and 62 healthy male subjects. Significant positive correlations between 24 hour urinary creatinine and uric acid excretion were shown in both groups. The mean urinary creatinine and uric acid excretions in the patients with gout were significantly increased as compared with those of normal male controls. These results suggest that there is a close correlation between creatinine and uric acid synthesis. In addition, it seems that accelerated uric acid synthesis seen in some patients with gout is due to increased creatinine synthesis. PMID:1540011

  7. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats

    PubMed Central

    Hosomi, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-01-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

  8. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats.

    PubMed

    Hosomi, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-03-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

  9. A poorly fermented gel from psyllium seed husk increases excreta moisture and bile acid excretion in rats.

    PubMed

    Marlett, Judith A; Fischer, Milton H

    2002-09-01

    Psyllium seed husk (PSH) increases stool output and lowers blood cholesterol levels in humans. PSH and three fractions isolated from it were meal-fed to colectomized rats and fermented in vitro to test the hypothesis that viscous, gel-forming fraction B was responsible for these physiological actions. Control rats were fed 50 g/kg cellulose. The concentration of each PSH fraction in the test meals was equivalent to its concentration in PSH. Yields of the fractions were: A, 171; B, 575; and C, 129 g/kg of PSH. The wet weight and moisture content of ileal excreta (IE) from rats fed test meals containing PSH or fraction B were greater than those measured in excreta from rats fed meals containing cellulose or the other two PSH fractions. Total bile acids in IE did not differ between rats fed PSH or fraction B and were greater in these groups than in the other groups. Fraction A was not fermented during 3 d of incubation; fraction B was poorly fermented, with approximately 30% of the constituent sugars disappearing; and fraction C was rapidly and nearly completely fermented. These results indicate that the gel-forming fraction we isolated from PSH is the physiologically active component of the husks. PMID:12221223

  10. Hippuric acid excretion after benzylamine ingestion in man.

    PubMed Central

    Wood, S G; Al-Ani, M R; Lawson, A

    1978-01-01

    The fate of 14C-benzylamine after oral administration as the hydrochloride has been investigated in two male volunteers. Over 98% of the administered radiolabel was excreted in the urine as 14C-hippuric acid within 24 hours. The rate of urinary hippuric acid excretion was extremely rapid, with more than 90% of the dose excreted after three hours. PMID:698137

  11. Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

    SciTech Connect

    Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A. )

    1990-04-01

    Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients.

  12. Increased Salivary Nitrite and Nitrate Excretion in Rats with Cirrhosis.

    PubMed

    Mahmoodi, Somayeh; Rahmatollahi, Mahdieh; Shahsavari, Fatemeh; Shafaroodi, Hamed; Grayesh-Nejad, Siyavash; Dehpour, Ahmad R

    2015-11-01

    Increased nitric oxide (NO) formation is mechanistically linked to pathophysiology of the extrahepatic complications of cirrhosis. NO is formed by either enzymatic or non-enzymatic pathways. Enzymatic production is catalyzed by NO synthase (NOS) while entero-salivary circulation of nitrate and nitrite is linked to non-enzymatic formation of NO under acidic pH in the stomach. There is no data on salivary excretion of nitrate and nitrite in cirrhosis. This study was aimed to investigate salivary levels of nitrate and nitrite in a rat model of biliary cirrhosis. Cirrhosis was induced by bile duct ligation (BDL). Four weeks after the operation, submandibular ducts of anesthetized BDL and control rats were cannulated with polyethylene microtube for saliva collection. Assessment of pH, nitrite and nitrate levels was performed in our research. We also investigated NOS expression by real time RT-PCR to estimate eNOS, nNOS and iNOS mRNA levels in the submandibular glands. Salivary pH was significantly lower in BDL rats in comparison to control animals. We also observed a statistically significant increase in salivary levels of nitrite as well as nitrate in BDL rats while there was no elevation in the mRNA expression of nNOS, eNOS, and iNOS in submandibular glands of cirrhotic groups. This indicates that an increased salivary level of nitrite/nitrate is less likely to be linked to increased enzymatic production of NO in the salivary epithelium. It appears that nitrate/nitrite can be transported from the blood stream by submandibular glands and excreted into saliva as entero-salivary circulation, and this mechanism may have been exaggerated during cirrhosis. PMID:26786986

  13. Regulation of uric acid metabolism and excretion.

    PubMed

    Maiuolo, Jessica; Oppedisano, Francesca; Gratteri, Santo; Muscoli, Carolina; Mollace, Vincenzo

    2016-06-15

    Purines perform many important functions in the cell, being the formation of the monomeric precursors of nucleic acids DNA and RNA the most relevant one. Purines which also contribute to modulate energy metabolism and signal transduction, are structural components of some coenzymes and have been shown to play important roles in the physiology of platelets, muscles and neurotransmission. All cells require a balanced quantity of purines for growth, proliferation and survival. Under physiological conditions the enzymes involved in the purine metabolism maintain in the cell a balanced ratio between their synthesis and degradation. In humans the final compound of purines catabolism is uric acid. All other mammals possess the enzyme uricase that converts uric acid to allantoin that is easily eliminated through urine. Overproduction of uric acid, generated from the metabolism of purines, has been proven to play emerging roles in human disease. In fact the increase of serum uric acid is inversely associated with disease severity and especially with cardiovascular disease states. This review describes the enzymatic pathways involved in the degradation of purines, getting into their structure and biochemistry until the uric acid formation. PMID:26316329

  14. Increased Renal Solute Excretion in Rats Following Space Flight

    NASA Technical Reports Server (NTRS)

    Wade, Charles E.; Moore, A. L.; Morey-Holton, E.

    1995-01-01

    Following space flight a diuresis, due to an increase in free water clearance, has been suggested in humans. To assess the effects of space flight on renal function, rats were flown in space for 14 days. Rats were divided into three groups; vivarium controls (V;n=6; housed 2/shoe box cage), flight controls (FC;n=6; group housed in a flight cage), and flight animals (F;n=6). Upon landing all animals were placed into individual metabolic cages. Urine was collected daily for 7 days and every other day for 14 days. Urine output was increased (p less than 0.05; ANOVA) following flight for 3 days. On postflight day 1, flow rates were, V=6.8 plus or minus 0.9, FC=8.711.8 and F=16.6 plus or minus 2.7 microliter/min. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate (V=7.9 plus or minus 0.9, FC=6.1 plus or minus 0.7 and F=13.5 plus or minus 0.7 uOsm/min). Creatinine excretion rate was increased over the first two postflight days. In the absence of changes in plasma creatinine, Na+, or K+ (samples obtained immediately post flight from similar rats compared to Day 14), GFR was increased following space flight. The increased excretion of solute was thus the result of increased delivery and decreased reabsorption. Osmotic clearance was increased (V=28, FC=27 and F=51 microliter/min), while free water clearance was decreased post flight (V=-21,FC=-18 and F=-34 microliter/min). In rats, the postflight diuresis is the result of an increase in solute (osmotic) excretion with an accompanying reduction in free water clearance.

  15. Acid glycosaminoglycan (aGAG) excretion is increased in children with autism spectrum disorder, and it can be controlled by diet.

    PubMed

    Endreffy, Ildikó; Bjørklund, Geir; Dicső, Ferenc; Urbina, Mauricio A; Endreffy, Emőke

    2016-04-01

    Autism research continues to receive considerable attention as the options for successful management are limited. The understanding of the autism spectrum disorder (ASD) etiology has now progressed to encompass genetic, epigenetic, neurological, hormonal, and environmental factors that affect outcomes for patients with ASD. Glycosaminoglycans (GAGs) are a family of linear, sulfated polysaccharides that are associated with central nervous system (CNS) development, maintenance, and disorders. Proteoglycans (PG) regulate diverse functions in the central nervous system. Heparan sulfate (HS) and chondroitin sulfate (CS) are two major GAGs present in the PGs of the CNS. As neuroscience advances, biochemical treatments to correct brain chemistry become better defined. Nutrient therapy can be very potent and has minimal to no side effects, since no molecules foreign to the body are needed. Given GAGs are involved in several neurological functions, and that its level can be somewhat modulated by the diet, the present study aimed to evaluate the role of GAGs levels in ASD symptoms. Both tGAG and its different fractions were evaluated in the urine of ASD and healthy control childrens. As levels differed between groups, a second trial was conduted evaluating if diet could reduce tGAG levels and if this in turn decrease ASD symptoms. The present study found that tGAG concentration was significantly higher in the urine of children with ASD compared to healthy control children and this was also evident in all GAG fractions. Within groups (controls and ASD), no gender differences in GAG excretion were found. The use of a 90 days elimination diet (casein-free, special carbohydrates, multivitamin/mineral supplement), had major effects in reducing urinary tGAG excretion in children with ASD. PMID:26464064

  16. Urinary 3-methylhistidine excretion increases with repeated weight training exercise.

    PubMed

    Pivarnik, J M; Hickson, J F; Wolinsky, I

    1989-06-01

    This investigation examines the effect of progressive resistance weight training exercise on urinary 3-methylhistidine (3-MH) excretions in untrained subjects. For 19 consecutive days, 11 males were fed a weight maintenance, lactovegetarian diet which contained the Recommended Dietary Allowance (0.8g.kg-1.d-1) for protein. No exercise was performed for the first 7 d of the study. Subjects were strength tested on day 8 and performed upper and lower body weight training exercises from days 9-19. Complete, 24-h urine collections were obtained from each subject on a daily basis. Samples were assayed for creatinine and 3-MH. Stable baseline 3-MH values were present during the pre-exercise control period. Significant increases in 3-MH occurred by study day 11, which was the third day of weight training exercise. This was true regardless of whether the data were expressed by daily excretions (microM.d-1; P less than 0.01), per unit of body weight (microM.kg-1.d-1; P less than 0.005), or per unit of creatinine excretion (microM.g Creat-1.d-1; P less than 0.001). Since urinary 3-MH is an index of actin and myosin catabolism, these data support the hypothesis that the rate of skeletal muscle degradation is increased during strength building exercises. PMID:2733577

  17. Effect of iron poly (sorbitolgluconic acid) complex on urinary cellular excretion.

    PubMed

    Elliott, H L; Lawrence, J R; Campbell, B C; Goldberg, A; Smart, L E

    1981-01-01

    The intramuscular injection of 250 mg iron poly (sorbitol-gluconic acid) complex caused no increase in urinary cellular or bacterial excretion in 8 patients with chronic pyelonephritis, 4 patients with non-infective renal disease, and 4 controls. However, in 4 patients with chronic infective disease of the renal tract given 500 g there was a significant increase in cellular excretion. This response was not seen in 2 control patients, nor in 2 patients with non-infective renal disease. Using a differential staining technique, this increase in urinary cellular excretion was found to be due, not to leucocytes, but to renal tubular cells. The precise significance of this is unclear, but there would be concern that the high concentration of excreted iron was providing a 'toxic' insult to susceptible, infection-damaged cells. PMID:7226874

  18. Urinary glucaric acid excretion in rheumatoid arthritis: influence of disease activity and disease modifying drugs.

    PubMed Central

    Addyman, R; Beyeler, C; Astbury, C; Bird, H A

    1996-01-01

    OBJECTIVE: To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arthritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism. METHODS: Patients with RA were treated with sulphasalazine, sodium aurothiomalate, or D-penicillamine in standard dose regimens, for 24 weeks. Patients with ankylosing spondylitis (AS) or non-inflammatory arthritis (NIA) acted as controls. The urinary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatment. RESULTS: Patients with RA had a slightly greater urinary GA:creatinine ratio than patients with AS or NIA at baseline; this increased during treatment with disease modifying antirheumatic drugs (DMARDs). Sulphasalazine treatment had a greater effect on GA excretion than sodium aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspeptidase concentration showed a weak correlation with GA excretion between weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, and articular index) were found not to correlate with GA excretion between weeks 0-12 or 0-24. CONCLUSION: The increased excretion of GA in patients with RA receiving DMARD treatment is probably the result of an indirect effect on hepatic metabolism bearing no relationship to disease activity. PMID:8774168

  19. Pyridoxic acid excretion during low vitamin B-6 intake, total fasting, and bed rest

    NASA Technical Reports Server (NTRS)

    Coburn, S. P.; Thampy, K. G.; Lane, H. W.; Conn, P. S.; Ziegler, P. J.; Costill, D. L.; Mahuren, J. D.; Fink, W. J.; Pearson, D. R.; Schaltenbrand, W. E.

    1995-01-01

    Vitamin B-6 metabolism in 10 volunteers during 21 d of total fasting was compared with results from 10 men consuming a diet low only in vitamin B-6 (1.76 mumol/d) and with men consuming a normal diet during bed rest. At the end of the fast mean plasma concentrations of vitamin B-6 metabolites and urinary excretion of 4-pyridoxic acid tended to be higher in the fasting subjects than in the low-vitamin B-6 group. The fasting subjects lost approximately 10% of their total vitamin B-6 pool and approximately 13% of their body weight. The low-vitamin B-6 group lost only approximately 4% of their vitamin B-6 pool. Compared with baseline, urinary excretion of pyridoxic acid was significantly increased during 17 wk of bed rest. There was no increase in pyridoxic acid excretion during a second 15-d bed rest study. These data suggest the possibility of complex interactions between diet and muscle metabolism that may influence indexes that are frequently used to assess vitamin B-6 status.

  20. Roles of urea production, ammonium excretion, and amino acid oxidation in acid-base balance.

    PubMed

    Mackenzie, W

    1986-02-01

    Atkinson and colleagues recently proposed several concepts that contrast with traditional views: first, that acid-base balance is regulated chiefly by the reactions leading to urea production in the liver; second, that ammonium excretion by the kidney plays no role in acid-base homeostasis; and third, that ammonium does not stimulate ureagenesis (except indirectly). To examine these concepts, plasma ions other than bicarbonate are categorized as 1) fixed cations (Na+, K+, Ca2+, and Mg2+, symbolized M+) and anions (Cl-), 2) buffer anions (A-), 3) other anions (X-), and 4) ammonium plus charged amino groups (N+). Since electroneutrality dictates that M+ + N+ = Cl- + HCO3- + A- + X-, it follows that delta HCO3- = delta(M+ - Cl-) - delta A- - delta X- + delta N+. Therefore acid-base disturbances (changes in HCO3-) can be categorized as to how they affect bodily content and hence plasma concentration of each of these four types of ions. The stoichiometry of ureagenesis, glutamine hydrolysis, ammonium and titratable acid excretion, oxidation of neutral, acidic, and basic amino acids, and oxidation of methionine, phosphoserine, and protein are examined to see how they alter these quantities. It is concluded that 1) although ureagenesis is pH dependent and also counteracts a tendency of amino acid oxidation to cause alkalosis, this tendency is inherently limited by the hyperammonemia (delta N+) that necessarily accompanies it, 2) ammonium excretion is equivalent to hydrogen excretion in its effects on acid-base balance if, and only if, it occurs in exchange for sodium or is accompanied by chloride excretion and only when the glutamate generated by glutamine hydrolysis is oxidized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3511732

  1. Testosterone urinary excretion rate increases during hypergravity in male monkeys

    NASA Technical Reports Server (NTRS)

    Strollo, F.; Barger, L.; Fuller, C.

    2000-01-01

    Real and simulated microgravity impairs T secretion both in animals and in the human. To verify whether hypergravity might enhance T secretion as a consequence of an opposite mechanical effect, 6 male monkeys were centrifuged at 2 G for 3 weeks after a 1 G stabilization period lasting 3 weeks and then taken back to 1 G for 1 week and urine were collected daily for T excretion measurement. Significantly higher level were observed during the initial 2 G phase as compared to pre- and post centrifugation periods and the trend was the same during the remaining 2 G period. This may reflect changes in testicular perfusion rather than endocrine adaptation per se.

  2. Purine derivative excretion in dairy cows: endogenous excretion and the effect of exogenous nucleic acid supply.

    PubMed

    Gonzalez-Ronquillo, M; Balcells, J; Guada, J A; Vicente, F

    2003-04-01

    An experiment was conducted with dairy cows to study the partitioning of excreted purine derivatives between urine and milk and to quantify the endogenous contribution following the isotopic labeling of microbial purine bases. Three lactating cows in their second lactation that had been cannulated in the rumen and the duodenum were fed a mixed diet (48:52, roughage/concentrate ratio) distributed in equal fractions every 2 h, and duodenal flow of purine bases was determined by the dual-phase marker system. Nitrogen-15 was infused continuously into the rumen to label microbial purine bases, and the endogenous fraction was determined from the isotopic dilution in urinary purine derivatives. Urinary and milk recovery of duodenal purine bases were estimated at early (wk 10) and late (wk 33) lactation by the duodenal infusion of incremental doses (75 and 150 mmol purine bases/d) of RNA from Torula yeast. Each period was 6 d, with RNA being infused during the last 4 d, followed by measurement of the flow of purine bases to the duodenum. The isotope dilution of purine derivatives in urine samples confirmed the presence of an endogenous fraction (512 +/- 36.43 micromol/W0.75 or 56.86 mmol/d) amounting to 26 +/- 3.8% of total renal excretion. Total excretion of purine derivatives in urine plus milk was linearly related to the duodenal input of purine bases, but the slopes differed (P < 0.005) between lactation stages resulting in a lower equimolar recovery in early (y = 58.86 (+/-3.89) +0.56 (+/-0.0164) x; r = 0.90) than late lactation (y = 58.86 (+/-3.89) + 0.70 (+/-0.046) x; r = 0.80). Excretion of purine derivatives through milk represented a minimum fraction of total excretion but responded significantly to the duodenal input of purine bases. No differences between lactation stages were detected, and variations in milk yield did modify significantly the amount of purine derivatives excreted through the milk. PMID:12741553

  3. Urinary excretion of phenolic acids in rats fed cranberry, blueberry, or black raspberry powder.

    PubMed

    Khanal, Ramesh; Howard, Luke R; Prior, Ronald L

    2014-05-01

    Dietary polyphenolics can be converted into smaller phenolic acids (PA) by microorganisms in the colon and may contribute to health benefits associated with the parent polyphenolics. Urinary excretion of 18 PA and their conjugates was studied, using HPLC-MS/MS, in rats fed AIN93G-based diets containing 5% (dry weight basis) of either cranberry (CB), blueberry (BB), or black raspberry (BRB). Hippuric, 4-hydroxyphenylacetic, 3-methoxy-4-hydroxyphenylacetic, and 4-hydroxybenzoic acids were excreted in greatest quantity in the urine over a 24 h period in all diets. Primary PA excreted in the berry diets were 4-hydroxycinnamic acid for CB; chlorogenic, ferulic, and 3,4-dihydroxycinnamic acids for BB; and 3-hydroxyphenylpropionic, 3-hydroxybenzoic, and 3-hydroxycinnamic acids for BRB. PA were present in conjugated form with cinnamic acid derivatives being 50-70% and phenylacetic acid derivatives conjugated <10%. Conjugated, and not just the free, PA are significant contributors to total urinary excretion. PMID:24180593

  4. Effect of penicillin on fatty acid synthesis and excretion in Streptococcus mutans BHT

    SciTech Connect

    Brissette, J.L.; Pieringer, R.A.

    1985-03-01

    Treatment of exponentially growing cultures of Streptococcus mutans BHT with growth-inhibitory concentrations (0.2 microgram/ml) of benzylpenicillin stimulates the incorporation of (2-/sup 14/C) acetate into lipids excreted by the cells by as much as 69-fold, but does not change the amount of /sup 14/C incorporated into intracellular lipids. At this concentration of penicillin cellular lysis does not occur. The radioactive label is incorporated exclusively into the fatty acid moieties of the glycerolipids. During a 4-hr incubation in the presence of penicillin, the extracellular fatty acid ester concentration increases 1.5 fold, even though there is no growth or cellular lysis. An indication of the relative rate of fatty acid synthesis was most readily obtained by placing S. mutans BHT in a buffer containing /sup 14/C-acetate. Under these nongrowing conditions free fatty acids are the only lipids labeled, a factor which simplifies the assay. The addition of glycerol to the buffer causes all of the nonesterified fatty acids to be incorporated into glycerolipid. The cells excrete much of the lipid whether glycerol is present or not. Addition of penicillin to the nongrowth supporting buffer system does not stimulate the incorporation of (/sup 14/C)-acetate into fatty acids.

  5. The association of bile acid excretion and atherosclerotic coronary artery disease

    PubMed Central

    Charach, Gideon; Grosskopf, Itamar; Rabinovich, Alexander; Shochat, Michael; Weintraub, Moshe; Rabinovich, Pavel

    2011-01-01

    Background: Excess cholesterol is usually eliminated from the body by conversion to bile acids excreted in feces as bile salts. The excretion of large amounts of bile protects against atherosclerosis, while diminished excretion may lead to coronary artery disease (CAD). Objective: To investigate a relationship between CAD and bile acid excretion. Methods: Bile acid excretion was compared between 36 patients with proven CAD and 37 CAD-free individuals (controls). The groups were comparable for demographics and selected risk factors. All subjects received a 4-day standard diet that included ∼500 mg of cholesterol. Fecal bile acids from 24-hour stool collections were measured by gas liquid chromatography. Results: CAD patients excreted lower amounts of total bile acids (358 ± 156 mg) than controls (617 ± 293 mg; p < 0.01) and less deoxycholic acid (188.29 ± 98.12 mg versus 325.96 ± 198.57 mg; p < 0.0001) and less lithocholic acid (115.43 ± 71.89 mg versus 197.27 ± 126.87 mg; p < 0.01). Advanced age, male gender, left ventricular ejection fraction and total bile acid levels were significant independent factors that predicted CAD (p < 0.05). Mortality, CAD and cerebrovascular accident development rates were significantly lower for the controls at the 13-year follow up. Conclusion: CAD patients have significantly decreased bile acid excretion levels than non-CAD patients. An impaired ability to excrete cholesterol may be an additional risk factor for CAD development. PMID:21694811

  6. Urinary Excretion of Phenolic Acids by Infants and Children: A Randomised Double-Blind Clinical Assay

    PubMed Central

    Uberos, J.; Fernández-Puentes, V.; Molina-Oya, M.; Rodríguez-Belmonte, R.; Ruíz-López, A.; Tortosa-Pinto, P.; Molina-Carballo, A.; Muñoz-Hoyos, A.

    2012-01-01

    Objectives: The present study, which is part of the ISRCTN16968287 clinical assay, is aimed at determining the effects of cranberry syrup or trimethoprim treatment for UTI. Methods: This Phase III randomised clinical trial was conducted at the San Cecilio Clinical Hospital (Granada, Spain) with a study population of 192 patients, aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI, associated or otherwise with vesico-ureteral reflux of any degree, or renal pelvic dilatation associated with urinary infection. Each child was randomly given 0.2 mL/Kg/day of either cranberry syrup or trimethoprim (8 mg/mL). The primary and secondary objectives, respectively, were to determine the risk of UTI and the levels of phenolic acids in urine associated with each intervention. Results: With respect to UTI, the cranberry treatment was non-inferior to trimethoprim. Increased urinary excretion of ferulic acid was associated with a greater risk of UTI developing in infants aged under 1 year (RR 1.06; CI 95% 1.024–1.1; P = 0.001). Conclusions: The results obtained show the excretion of ferulic acid is higher in infants aged under 1 year, giving rise to an increased risk of UTI, for both treatment options. PMID:23641168

  7. Genetic variation in GPBAR1 predisposes to quantitative changes in colonic transit and bile acid excretion

    PubMed Central

    Shin, Andrea; Busciglio, Irene; Carlson, Paula; Acosta, Andres; Bharucha, Adil E.; Burton, Duane; Lamsam, Jesse; Lueke, Alan; Donato, Leslie J.; Zinsmeister, Alan R.

    2014-01-01

    The pathobiology of irritable bowel syndrome (IBS) is multifaceted. We aimed to identify candidate genes predisposing to quantitative traits in IBS. In 30 healthy volunteers, 30 IBS-constipation, and 64 IBS-diarrhea patients, we measured bowel symptoms, bile acid (BA) synthesis (serum 7α-hydroxy-4-cholesten-3-one and FGF19), fecal BA and fat, colonic transit (CT by scintigraphy), and intestinal permeability (IP by 2-sugar excretion). We assessed associations of candidate genes controlling BA metabolism (KLB rs17618244 and FGFR4 rs351855), BA receptor (GPBAR1 rs11554825), serotonin (5-HT) reuptake (SLC6A4 through rs4795541 which encodes for the 44-bp insert in 5HTTLPR), or immune activation (TNFSF15 rs4263839) with three primary quantitative traits of interest: colonic transit, BA synthesis, and fecal BA excretion. There were significant associations between fecal BA and CT at 48 h (r = 0.43; P < 0.001) and IP (r = 0.23; P = 0.015). GPBAR1 genotype was associated with CT48 (P = 0.003) and total fecal BA [P = 0.030, false detection rate (FDR) P = 0.033]. Faster CT48 observed with both CC and TT GPBAR1 genotypes was due to significant interaction with G allele of KLB, which increases BA synthesis and excretion. Other univariate associations (P < 0.05, without FDR correction) observed between GPBAR1 and symptom phenotype and gas sensation ratings support the role of GPBAR1 receptor. Associations between SLC6A4 and stool consistency, ease of passage, postprandial colonic tone, and total fecal BA excretion provide data in support of future hypothesis-testing studies. Genetic control of GPBAR1 receptor predisposing to pathobiological mechanisms in IBS provides evidence from humans in support of the importance of GPBAR1 to colonic motor and secretory functions demonstrated in animal studies. PMID:25012842

  8. Renal Regulation of Acid-Base Balance: Ammonia Excretion.

    ERIC Educational Resources Information Center

    Tanner, George A.

    1984-01-01

    Describes an experiment which demonstrates changes in ammonia excretion and urine pH that occur in response to metabolic acidosis (induced by ammonium chloride ingestion) or metabolic alkalosis (produced by sodium bicarbonate ingestion). List of materials needed and background information are included. Typical results are provided and discussed.…

  9. Urinary excretion of mutagens, thioethers and D-glucaric acid in workers exposed to bitumen fumes.

    PubMed

    Pasquini, R; Monarca, S; Scassellati Sforzolini, G; Savino, A; Bauleo, F A; Angeli, G

    1989-01-01

    The authors carried out biological monitoring of the mutagenic/carcinogenic hazards associated with exposure to bitumen fumes during paving operations, analysing some biological parameters in the urine of a group of exposed workers. The urine samples were studied for mutagenicity by the Ames test and for thioethers concentration. D-Glucaric acid urine excretion was also determined to investigate the enzymatic induction potential of bitumens. Even though, in a previous environmental monitoring phase, a low content of mutagenic/carcinogenic compounds was found in bitumen and air samples, urinary mutagenicity data of exposed workers were statistically higher than those of a group of unexposed subjects. The urinary mutagenicity increased further if exposure to bitumens was associated with cigarette smoking. Thioethers were higher only in subjects exposed simultaneously to bitumens and cigarettes. D-Glucaric acid excretion did not increase significantly. The authors think that this type of coupled environmental and biological monitoring is a valid tool for a better evaluation of the mutagenic/carcinogenic exposure to bitumens or similar complex mixtures. PMID:2707871

  10. Increased urinary excretion of analogs of Krebs cycle metabolites and arabinose in two brothers with autistic features.

    PubMed

    Shaw, W; Kassen, E; Chaves, E

    1995-08-01

    A marked increase in analogs of Krebs cycle metabolites was found in the urine of two brothers with autistic features. These metabolites included citramalic, tartaric (3-OH-malic), and 3-oxoglutaric acids and compounds tentatively identified as a citric acid analog and partially identified as a phenylcarboxylic acid by the fragmentation pattern of the trimethylsilyl (TMS) derivatives of the compounds and mass shifts of the same compounds derivatized with perdeuterated N,O-bis(trimethylsilyl)trifluoroacetamide. The molecular mass of the TMS derivative of the tentatively identified citric acid analog was 596 Da, based on a finding of a significant M - 15 ion at m/z 581. The citric acid analog was excreted in quantities as high as 137 mmol/mol creatinine, based on the response factor of citric acid as a surrogate calibrator. A carbohydrate with a retention time and mass spectrum identical to arabinose was also found in high concentrations in the urine of these brothers. PMID:7628083

  11. Psyllium husk fibre supplementation to soybean and coconut oil diets of humans: effect on fat digestibility and faecal fatty acid excretion.

    PubMed

    Ganji, V; Kies, C V

    1994-08-01

    The effects of psyllium fibre supplementation to polyunsaturated fatty acid rich soybean oil and saturated fatty acid rich coconut oil diets on fat digestibility and faecal fatty acid excretion were investigated in healthy humans. The study consisted of four 7-day experimental periods. Participants consumed soybean oil (SO), soybean oil plus psyllium fibre (20 g/day) (SO+PF), coconut oil (CO) and coconut oil plus psyllium fibre (20 g/day) (CO+PF) diets. Laboratory diet provided 30% calories from fat (20% from test oils and 10% from basal diet), 15% calories from protein and 55% calories from carbohydrate. Fat digestibility was significantly lower and faecal fat excretion was significantly higher with SO+PF diet than SO diet and with CO+PF diet than CO diet. Faecal excretion of myristic and lauric acids was not affected by test diets. Percent faecal palmitic acid excretion was significantly higher during psyllium supplementation periods. Higher faecal linoleic acid excretion was observed with soybean oil diets compared with coconut oil diets. Increased faecal fat loss, decreased fat digestibility and increased faecal palmitic acid excretion with psyllium supplementation may partly explain the hypocholesterolaemic action of psyllium fibre. PMID:7957006

  12. Serum uric acid levels in normal pregnancy with observations on the renal excretion of urate in pregnancy

    PubMed Central

    Boyle, James A.; Campbell, Stuart; Duncan, Anne M.; Greig, William R.; Buchanan, W. Watson

    1966-01-01

    Serum uric acid estimations were performed in 106 healthy pregnant women during early, middle, and late pregnancy, using an automated colorimetric method. The mean serum uric acid level was significantly lower during early and middle pregnancy than that of 64 age-matched female controls. The serum uric acid level was not significantly different in late pregnancy from the control group. Studies of the daily urinary urate excretion in 31 pregnant women showed normal urinary urate excretion in early pregnancy and enhanced renal loss of urate in middle and late pregnancy. It appears that the renal clearance of urate in pregnancy is high, especially in the middle period when the serum level is low in spite of the increased production of uric acid by the foetus. PMID:5919366

  13. Urine sodium excretion increased slightly among U.S. adults between 1988 and 2010.

    PubMed

    Pfeiffer, Christine M; Hughes, Jeffery P; Cogswell, Mary E; Burt, Vicki L; Lacher, David A; Lavoie, Donna J; Rabinowitz, Daniel J; Johnson, Clifford L; Pirkle, James L

    2014-05-01

    Little information is available on temporal trends in sodium intake in the U.S. population using urine sodium excretion as a biomarker. Our aim was to assess 1988-2010 trends in estimated 24-h urine sodium (24hUNa) excretion among U.S. adults (age 20-59 y) participating in the cross-sectional NHANES. We used subsamples from a 1988-1994 convenience sample, a 2003-2006 one-third random sample, and a 2010 one-third random sample to comply with resource constraints. We estimated 24hUNa excretion from measured sodium concentrations in spot urine samples by use of calibration equations (for men and women) derived from the International Cooperative Study on Salt, Other Factors, and Blood Pressure study. Estimated 24hUNa excretion increased over the 20-y period [1988-1994, 2003-2006, and 2010; means ± SEMs (n): 3160 ± 38.4 mg/d (1249), 3290 ± 29.4 mg/d (1235), and 3290 ± 44.4 mg/d (525), respectively; P-trend = 0.022]. We observed significantly higher mean estimated 24hUNa excretion in each survey period (P < 0.001) for men compared with women (31-33%) and for persons with a higher body mass index (BMI; 32-35% for obese vs. normal weight) or blood pressure (17-26% for hypertensive vs. normal blood pressure). After adjusting for age, sex, and race-ethnicity, temporal trends in mean estimated 24hUNa excretion remained significant (P-trend = 0.004). We observed no temporal trends in mean estimated 24hUNa excretion among BMI subgroups, nor after adjusting for BMI. Although several limitations apply to this analysis (the use of a convenience sample in 1988-1994 and using estimated 24hUNa excretion as a biomarker of sodium intake), these first NHANES data suggest that mean estimated 24hUNa excretion increased slightly in U.S. adults over the past 2 decades, and this increase may be explained by a shift in the distribution of BMI. PMID:24623847

  14. Urinary excretion of guanidinoacetic acid in rats with diabetic nephropathy.

    PubMed

    Kiyatake, I; Nakamura, T; Koide, H

    2006-01-01

    Urinary guanidinoacetic acid (GAA) is a sensitive marker for gentamicin nephrotoxicity in rats. This study assesses the usefulness of GAA concentrations in the diagnosis of renal tubular injury in diabetic nephropathy. Serum, urine, and renal cortex samples were obtained from rats 1, 2, and 3 weeks after streptozotocin injection (65 mg/kg body weight). Guanidinoacetic acid levels were measured by high-performance liquid chromatography. N-acetyl-beta-D-glucosaminidase (NAG) activity in urine was determined by an enzymatic method. GAA levels in serum, urine, and renal cortex were significantly decreased in diabetic rats compared with those in control rats. In contrast, urinary NAG activity was significantly increased in diabetic rats. Decreases in serum, urine, and renal cortical GAA levels were attenuated by insulin treatment. These results indicate that a high serum glucose level may affect GAA synthesis in the renal cortex and that urinary GAA may be a clinically useful indicator of renal tubular injury in diabetic nephropathy. PMID:16538977

  15. Association between serum uric acid, urinary albumin excretion, and glycated hemoglobin in Type 2 diabetic patient

    PubMed Central

    Neupane, Sunita; Dubey, Raju Kumar; Gautam, Narayan; Agrawal, Krishna Kumar; Jayan, Archana; Shrestha, Sujata; Jha, Amit Chandra

    2016-01-01

    Background: Diabetes mellitus (DM) is a chronic disease characterized by insulin deficiency or peripheral resistance resulting in hyperglycemia. Poor glycemic control leads to diabetic complications. Hyperuricemia has been reported with increased risk of renal insufficiency. The aim of this study was to evaluate the relationship between serum uric acid concentration, degree of urinary albumin excretion (UAE) and glycated hemoglobin (HbA1c) in Type 2 DM (T2DM) patients. Materials and Methods: Serum uric acid concentrations, urine microalbumin, and HbA1c were measured in fifty T2DM patients. We then evaluated relationship between uric acid concentrations, degree of UAE and glycemic control as well as other confounding variables. Results: Serum uric acid concentration correlated positively with UAE (r = 0.323, P < 0.05), age (r = 0.337, P < 0.05), age at onset (r = 0.341, P < 0.05), and duration of DM (r = 0.312, P < 0.05). Multiple regression analysis demonstrated that serum uric acid concentration (β = 0.293, P < 0.0001), duration of DM (β = 0.261, P < 0.0001), HbA1c (β = 0.173, P < 0.005), and systolic blood pressure (β = 0.268, P < 0.005) were independent determinants of UAE. Conclusions: Serum uric acid concentration is associated with microalbuminuria and HbA1c in T2DM patients. PMID:27226687

  16. Increased Feeding and Nutrient Excretion of Adult Antarctic Krill, Euphausia superba, Exposed to Enhanced Carbon Dioxide (CO2)

    PubMed Central

    Saba, Grace K.; Schofield, Oscar; Torres, Joseph J.; Ombres, Erica H.; Steinberg, Deborah K.

    2012-01-01

    Ocean acidification has a wide-ranging potential for impacting the physiology and metabolism of zooplankton. Sufficiently elevated CO2 concentrations can alter internal acid-base balance, compromising homeostatic regulation and disrupting internal systems ranging from oxygen transport to ion balance. We assessed feeding and nutrient excretion rates in natural populations of the keystone species Euphausia superba (Antarctic krill) by conducting a CO2 perturbation experiment at ambient and elevated atmospheric CO2 levels in January 2011 along the West Antarctic Peninsula (WAP). Under elevated CO2 conditions (∼672 ppm), ingestion rates of krill averaged 78 µg C individual−1 d−1 and were 3.5 times higher than krill ingestion rates at ambient, present day CO2 concentrations. Additionally, rates of ammonium, phosphate, and dissolved organic carbon (DOC) excretion by krill were 1.5, 1.5, and 3.0 times higher, respectively, in the high CO2 treatment than at ambient CO2 concentrations. Excretion of urea, however, was ∼17% lower in the high CO2 treatment, suggesting differences in catabolic processes of krill between treatments. Activities of key metabolic enzymes, malate dehydrogenase (MDH) and lactate dehydrogenase (LDH), were consistently higher in the high CO2 treatment. The observed shifts in metabolism are consistent with increased physiological costs associated with regulating internal acid-base equilibria. This represents an additional stress that may hamper growth and reproduction, which would negatively impact an already declining krill population along the WAP. PMID:23300621

  17. A Case of Hypophosphatemia with Increased Urinary Excretion of Phosphorus Associated with Ibrutinib

    PubMed Central

    Wysokinska, Ewa M.; Thompson, Amanda M.; Franco Palacios, Carlos R.

    2016-01-01

    Ibrutinib, an irreversible oral inhibitor of Bruton's tyrosine kinase, has been used in the treatment of patients with multiple hematologic malignancies. A 59-year-old male with chronic lymphocytic leukemia was treated with 420 mg/day of ibrutinib. No evidence of bruising or diarrhea was noted. The treatment was complicated by a transient increase in creatinine (from a baseline of 1.2 to 1.5 mg/dl) and potassium (reaching a peak of 6.5 mEq/l). Uric acid and calcium levels were normal. The patient developed hypophosphatemia (prior to initiation of therapy the serum phosphorus was 2.9 mg/dl). No metabolic acidosis was noted. Urinalysis showed no glucosuria or proteinuria. Urinary fraction of excretion of phosphate was found to be 345% (normal <5%). Because of these changes, ibrutinib was held, and the patient was given kayexalate. Serum potassium normalized. Serum phosphorus was checked a couple of weeks later and also normalized. A lower dose of ibrutinib (140 mg/day) was restarted. Upon follow-up, the phosphorus level has been between 2.9 and 3.2 mg/dl. No further evidence of hyperkalemia has been noted. Renal function has remained at baseline. To the best of our knowledge, this is the first case report describing the mechanism of hypophosphatemia in a patient treated with ibrutinib. PMID:27194982

  18. A Case of Hypophosphatemia with Increased Urinary Excretion of Phosphorus Associated with Ibrutinib.

    PubMed

    Wysokinska, Ewa M; Thompson, Amanda M; Franco Palacios, Carlos R

    2016-01-01

    Ibrutinib, an irreversible oral inhibitor of Bruton's tyrosine kinase, has been used in the treatment of patients with multiple hematologic malignancies. A 59-year-old male with chronic lymphocytic leukemia was treated with 420 mg/day of ibrutinib. No evidence of bruising or diarrhea was noted. The treatment was complicated by a transient increase in creatinine (from a baseline of 1.2 to 1.5 mg/dl) and potassium (reaching a peak of 6.5 mEq/l). Uric acid and calcium levels were normal. The patient developed hypophosphatemia (prior to initiation of therapy the serum phosphorus was 2.9 mg/dl). No metabolic acidosis was noted. Urinalysis showed no glucosuria or proteinuria. Urinary fraction of excretion of phosphate was found to be 345% (normal <5%). Because of these changes, ibrutinib was held, and the patient was given kayexalate. Serum potassium normalized. Serum phosphorus was checked a couple of weeks later and also normalized. A lower dose of ibrutinib (140 mg/day) was restarted. Upon follow-up, the phosphorus level has been between 2.9 and 3.2 mg/dl. No further evidence of hyperkalemia has been noted. Renal function has remained at baseline. To the best of our knowledge, this is the first case report describing the mechanism of hypophosphatemia in a patient treated with ibrutinib. PMID:27194982

  19. Increased urinary excretion of platelet activating factor in mice with lupus nephritis

    SciTech Connect

    Macconi, D.; Noris, M.; Benfenati, E.; Quaglia, R.; Pagliarino, G. ); Remuzzi, G. Ospedali Riuniti di Bergamo )

    1991-01-01

    Platelet activating factor (PAF) is present in urine from humans and experimental animals in normal conditions. Very little is known about changes in PAF urinary excretion under pathologic conditions and no data are available about the origin of PAF in the urine. In the present study we explored the possibility that immunologic renal disease is associated with an increase in PAF urinary excretion using gas chromatography-mass spectrometry technique. To clarify the renal or extrarenal origin of urinary PAF we evaluated whether exogenously administered PAF (1-(1{prime},2{prime}-{sup 3}H)alkyl) is filtered through the glomerulus and excreted in the urine. The results show that: (1) urine from mice with lupus nephritis in the early phase of the disease contained amounts of PAF comparable to those excreted in normal mouse urine, (2) PAF levels increased when animals started to develop high grade proteinuria, (3) after intravenous injection of ({sup 3}H) PAF In nephritic mice, a negligible amount of ({sup 3}H) ether lipid, corresponding to ({sup 3}H)1-alkyl -2-acyl-3-phosphocholine (alkyl-2-acyl-GPC), was recovered from the 24 h urine extract.

  20. Urinary excretion of mevalonic acid as an indicator of cholesterol synthesis.

    PubMed

    Lindenthal, B; Simatupang, A; Dotti, M T; Federico, A; Lütjohann, D; von Bergmann, K

    1996-10-01

    Urinary excretion of mevalonic acid was investigated as an indicator of cholesterol synthesis. In normolipemic volunteers, excretion of mevalonic acid averaged 3.51 +/- 0.59 (SD) micrograms/kg x day1; (n = 24) and was not different from patients with hypercholesterolemia (3.30 +/- 0.92 micrograms/kg x day1; n = 24). In patients with cerebrotendineous xanthomatosis, the excretion was significantly higher (8.55 +/- 1.92 micrograms/kg x day1; n = 6, P < 0.001) but comparable to volunteers treated with cholestyramine (6.69 +/- 2.6 micrograms/kg x day1; n = 5). A significant correlation was found between 24-h excretion of mevalonic acid and cholesterol synthesis (r = 0.835; n = 35; P < 0.001). The coefficient of variation of excretion of mevalonic acid during 3 consecutive days was small (9.8%; n = 7). However, urinary output of mevalonic acid was significantly higher during the night (164 +/- 14 micrograms/12-h) than during the day (129 +/- 9 micrograms/12-h; n = 11; P < 0.05). In patients treated with simvastatin (40 mg/day) for 6 weeks, the ratio of mevalonic acid to creatinine in a morning urine sample decreased significantly compared to pretreatment values (110 +/- 25 micrograms/g vs. 66 +/- 25 micrograms/g; P < 0.001). Furthermore, the ratio of mevalonic acid to creatinine in a morning urine sample correlated with the ratio from the 24-h collection period (r = 0.714; n = 34; P < 0.001). The results indicate that the analysis of urinary mevalonic acid, either in 24-h collection or in a single morning sample, is an attractive method for evaluation of long and very short term changes of the rates of cholesterol synthesis. PMID:8906596

  1. Urinary excretion of phenolic acids in rats fed cranberry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary flavonoids can be converted into phenolic acids by colonic microflora and be absorbed into the circulation and may contribute to the health-promoting effects of the parent compounds. The phenolic acids can be further metabolized in other tissues via methylation and conjugation with glucuroni...

  2. EFFECT OF DOSE ON THE EXCRETION AND METABOLISM OF MONOMETHYLARSONIC ACID IN THE MOUSE

    EPA Science Inventory

    EFFECT OF DOSE ON THE EXCRETION AND METABOLISM OF MONOMETHYLARSONIC ACID IN THE MOUSE
    M F Hughes1, V Devesa2, B C Edwards1, C T Mitchell1, E M Kenyon1, and D J Thomas1. 1US EPA, ORD, NHEERL, ETD, Research Triangle Park, NC; 2UNC-CH, CEMALB, Chapel Hill, NC

    Monomethylar...

  3. Yoghurt impacts on the excretion of phenolic acids derived from colonic breakdown of orange juice flavanones in humans.

    PubMed

    Roowi, Suri; Mullen, William; Edwards, Christine A; Crozier, Alan

    2009-05-01

    Human urine was collected over a 24 h period after the consumption of 250 mL of (i) water, (ii) orange juice, and (iii) orange juice plus 150 mL of full fat natural yoghurt. The orange juice contained 168 micromol of hesperetin-7-O-rutinoside and 18 micromol of naringenin-7-O-rutinoside. GC-MS analysis of the urine identified nine phenolic acids, five of which, 3-hydroxyphenylacetic acid, 3-hydroxyphenylhydracrylic acid, dihydroferulic acid, 3-methoxy-4-hydroxyphenylhydracrylic acid and 3-hydroxyhippuric acid, were associated with orange juice consumption indicating that they were derived from colonic catabolism of hesperetin-7-O-rutinoside. The overall 0-24 h excretion of the five phenolic acids was 6.7 +/- 1.8 micromol after drinking water and this increased significantly (p < 0.05) to 62 +/- 18 micromol, equivalent to 37% of the ingested flavanones, following orange juice consumption. When the orange juice was ingested with yoghurt excretion fell back markedly to 9.3 +/- 4.4 micromol. This was not due to a difference in mouth to caecum transit time, as measured with breath hydrogen production, though possibly there may have been a slowing of the bulk of the meal reaching the large intestine which may then have altered the catabolism of the flavanones to phenolic acids by the colonic microbiota. PMID:19415668

  4. Naloxone increases water and electrolyte excretion after water loading in patients with cirrhosis and ascites.

    PubMed

    Leehey, D J; Gollapudi, P; Deakin, A; Reid, R W

    1991-11-01

    Endogenous opioids may be involved in the pathogenesis of ascites and edema in patients with liver cirrhosis. We administered the opioid antagonist naloxone (5 mg bolus followed by a 0.06 mg/min infusion) to eight male patients with alcoholic cirrhosis and ascites and to five healthy age- and sex-matched control subjects and determined the effects of naloxone on water and electrolyte excretion after a nonsustained water load (20 ml/kg). In comparison with saline vehicle infusion carried out in the same subjects, naloxone administration resulted in a 50% increase in urine output and creatinine clearance and twofold increases in sodium and potassium excretion in patients with cirrhosis. Fractional sodium and potassium excretion, minimal urinary osmolality, plasma vasopressin and aldosterone levels, arterial blood pressure, and heart rate were not affected by naloxone treatment. The diuretic effect of naloxone was not observed in control subjects. Plasma naloxone levels were about six times higher in patients with cirrhosis than in control subjects (probably because of impaired metabolism of the drug) but only a weak correlation was found between drug levels and the degree of diuresis observed. The diuretic effect of naloxone may be related to an increase in glomerular filtration rate, possibly in conjunction with altered tubular reabsorption. PMID:1940589

  5. Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations

    PubMed Central

    Blázquez-Medela, Ana M.; García-Sánchez, Omar; Quirós, Yaremi; Blanco-Gozalo, Victor; Prieto-García, Laura; Sancho-Martínez, Sandra M.; Romero, Miguel; Duarte, Juan M.; López-Hernández, Francisco J.; López-Novoa, José M.; Martínez-Salgado, Carlos

    2015-01-01

    Abstract Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys. We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage. Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments. The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats. The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9. Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels. Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy. KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening. KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations. Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage. PMID:26469898

  6. A diet high in meat protein and potential renal acid load increases fractional Ca absorption and urinary Ca excretion, without affecting markers of bone resorption or formation in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: The objective was to determine the effects of high dietary protein (mostly meat) and high potential renal acid load (PRAL) on calcium (Ca) balance and markers of bone metabolism. Methods: In a randomized crossover design, sixteen healthy postmenopausal women consumed two diets: one with l...

  7. Plasma cholesterol-lowering activity of gingerol- and shogaol-enriched extract is mediated by increasing sterol excretion.

    PubMed

    Lei, Lin; Liu, Yuwei; Wang, Xiaobo; Jiao, Rui; Ma, Ka Ying; Li, Yuk Man; Wang, Lijun; Man, Sun Wa; Sang, Shengmin; Huang, Yu; Chen, Zhen-Yu

    2014-10-29

    The present study investigated the cholesterol-lowering activity of gingerol- and shogaol-enriched ginger extract (GSE). Thirty hamsters were divided into three groups and fed the control diet or one of the two experimental diets containing 0.5 and 1.0% GSE. Plasma total cholesterol, liver cholesterol, and aorta atherosclerotic plaque were dose-dependently decreased with increasing amounts of GSE added into diets. The fecal sterol analysis showed dietary GSE increased the excretion of both neutral and acidic sterols in a dose-dependent manner. GSE down-regulated the mRNA levels of intestinal Niemann-Pick C1-like 1 protein (NPC1L1), acyl CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP binding cassette transporter 5 (ABCG5), whereas it up-regulated hepatic cholesterol-7α-hydroxylase (CYP7A1). It was concluded that beneficial modification of the lipoprotein profile by dietary GSE was mediated by enhancing excretion of fecal cholesterol and bile acids via up-regulation of hepatic CYP7A1 and down-regulation of mRNA of intestinal NPC1L1, ACAT2, and MTP. PMID:25290252

  8. Oral intake of ranitidine increases urinary excretion of N-nitrosodimethylamine.

    PubMed

    Zeng, Teng; Mitch, William A

    2016-06-01

    The H2-receptor antagonist, ranitidine, is among the most widely used pharmaceuticals to treat gastroesophageal reflux disease and peptic ulcers. While previous studies have demonstrated that amines can form N-nitrosamines when exposed to nitrite at stomach-relevant pH, N-nitrosamine formation from ranitidine, an amine-based pharmaceutical, has not been demonstrated under these conditions. In this work, we confirmed the production of N-nitrosodimethylamine (NDMA), a potent carcinogen, by nitrosation of ranitidine under stomach-relevant pH conditions in vitro We also evaluated the urinary NDMA excretion attributable to ingestion of clinically used ranitidine doses. Urine samples collected from five female and five male, healthy adult volunteers over 24-h periods before and after consumption of 150mg ranitidine were analyzed for residual ranitidine, ranitidine metabolites, NDMA, total N-nitrosamines and dimethylamine. Following ranitidine intake, the urinary NDMA excreted over 24h increased 400-folds from 110 to 47 600ng, while total N-nitrosamines increased 5-folds. NDMA excretion rates after ranitidine intake equaled or exceeded those observed previously in patients with schistosomiasis, a disease wherein N-nitrosamines are implicated as the etiological agents for bladder cancer. Due to metabolism within the body, urinary NDMA measurements represent a lower-bound estimate of systemic NDMA exposure. Our results suggest a need to evaluate the risks attributable to NDMA associated with chronic consumption of ranitidine, and to identify alternative treatments that minimize exposure to N-nitrosamines. PMID:26992900

  9. Excretion of amino acids by humans during space flight

    NASA Technical Reports Server (NTRS)

    Stein, T. P.; Schluter, M. D.

    1998-01-01

    We measured the urine amino acid distribution patterns before, during and after space flight on the Space Shuttle. The urine samples were collected on two separate flights of the space shuttle. The first flight lasted 9.5 days and the second flight 15 days. Urine was collected continuously on 8 subjects for the period beginning 10 d before launch to 6 d after landing. Results: In contrast to the earlier Skylab missions where a pronounced amino aciduria was found, on shuttle the urinary amino acids showed little change with spaceflight except for a marked decrease in all of the amino acids on FD (flight day) 1 (p<0.05) and a reduction in isoleucine and valine on FD3 and FD4 (p<0.05). Conclusions: (i) Amino aciduria is not an inevitable consequence of space flight. (ii) The occurrence of amino aciduria, like muscle protein breakdown is a mission specific effect rather than part of the general human response to microgravity.

  10. Urinary nitrate excretion is increased in patients with rheumatoid arthritis and reduced by prednisolone.

    PubMed Central

    Stichtenoth, D O; Fauler, J; Zeidler, H; Frölich, J C

    1995-01-01

    OBJECTIVES--To determine daily production of nitric oxide (NO) measured as urinary nitrate excretion, and the effect of prednisolone in patients with rheumatoid arthritis (RA). METHODS--Twenty four hour urinary nitrate was measured by gas chromatography in 10 patients with RA, before and two to four weeks after commencement of prednisolone 0.5 mg/kg body weight, and in 18 healthy controls. RESULTS--Before the start of prednisolone treatment the urinary nitrate excretion in patients with RA was 2.7-fold greater (p < 0.001) than that in healthy volunteers. After prednisolone it decreased significantly, by 28%, at which time inflammatory activity (as indicated by C reactive protein, erythrocyte sedimentation rate, joint count, and early morning stiffness) was also reduced considerably. Despite this decrease, the urinary nitrate excretion in patients with RA remained twice that in the control group (p < 0.05). CONCLUSIONS--Our data suggest that the endogenous production of NO is enhanced in patients with RA. Furthermore, the results indicate that, in parallel with suppression of inflammation, this increased NO synthesis could be reduced by prednisolone treatment. PMID:7492221

  11. Recent advances in understanding trans-epithelial acid-base regulation and excretion mechanisms in cephalopods

    PubMed Central

    Hu, Marian Y; Hwang, Pung-Pung; Tseng, Yung-Che

    2015-01-01

    Cephalopods have evolved complex sensory systems and an active lifestyle to compete with fish for similar resources in the marine environment. Their highly active lifestyle and their extensive protein metabolism has led to substantial acid-base regulatory abilities enabling these organisms to cope with CO2 induced acid-base disturbances. In convergence to teleost, cephalopods possess an ontogeny-dependent shift in ion-regulatory epithelia with epidermal ionocytes being the major site of embryonic acid-base regulation and ammonia excretion, while gill epithelia take these functions in adults. Although the basic morphology and excretory function of gill epithelia in cephalopods were outlined almost half a century ago, modern immunohistological and molecular techniques are bringing new insights to the mechanistic basis of acid-base regulation and excretion of nitrogenous waste products (e.g. NH3/NH4+) across ion regulatory epithelia of cephalopods. Using cephalopods as an invertebrate model, recent findings reveal partly conserved mechanisms but also novel aspects of acid-base regulation and nitrogen excretion in these exclusively marine animals. Comparative studies using a range of marine invertebrates will create a novel and exciting research direction addressing the evolution of pH regulatory and excretory systems. PMID:26716070

  12. Recent advances in understanding trans-epithelial acid-base regulation and excretion mechanisms in cephalopods.

    PubMed

    Hu, Marian Y; Hwang, Pung-Pung; Tseng, Yung-Che

    2015-01-01

    Cephalopods have evolved complex sensory systems and an active lifestyle to compete with fish for similar resources in the marine environment. Their highly active lifestyle and their extensive protein metabolism has led to substantial acid-base regulatory abilities enabling these organisms to cope with CO2 induced acid-base disturbances. In convergence to teleost, cephalopods possess an ontogeny-dependent shift in ion-regulatory epithelia with epidermal ionocytes being the major site of embryonic acid-base regulation and ammonia excretion, while gill epithelia take these functions in adults. Although the basic morphology and excretory function of gill epithelia in cephalopods were outlined almost half a century ago, modern immunohistological and molecular techniques are bringing new insights to the mechanistic basis of acid-base regulation and excretion of nitrogenous waste products (e.g. NH3/NH4 (+)) across ion regulatory epithelia of cephalopods. Using cephalopods as an invertebrate model, recent findings reveal partly conserved mechanisms but also novel aspects of acid-base regulation and nitrogen excretion in these exclusively marine animals. Comparative studies using a range of marine invertebrates will create a novel and exciting research direction addressing the evolution of pH regulatory and excretory systems. PMID:26716070

  13. Potassium excretion in healthy Japanese women was increased by a dietary intervention utilizing home-parcel delivery of Okinawan vegetables.

    PubMed

    Tuekpe, Mallet K-N; Todoriki, Hidemi; Sasaki, Satoshi; Zheng, Kui-Cheng; Ariizumi, Makoto

    2006-06-01

    Potassium, which is abundant in vegetables, is inversely related to blood pressure. Although the situation has changed somewhat in recent years, the Okinawan diet has generally included a large amount of vegetables, and until recently Okinawans had the lowest rates of mortality due to stroke and coronary heart disease in Japan. Based on the hypothesis that these low mortality rates are partly attributable to increased potassium intake resulting from the high vegetable consumption, this study examined whether increasing the consumption of typical yellow-green Okinawan vegetables increases potassium intake. The purpose of this investigation was to determine whether increased consumption of these vegetables should be one of the dietary modifications recommended in public health promotion programs for Okinawans. The study employed 56 healthy, normotensive, free-living Japanese women aged 18-38 years living in Okinawa. They were randomized to a dietary intervention group (n=27) or a control group (n=29). Members of the dietary intervention group received an average weight of 371.4 g/day of a combination of the following vegetables twice weekly through an express home parcel deliver service for a period of 14 days: Goya (Momordica charantia), green papaya (Carica papaya), Handama (Gynura bicolor), Karashina (Brassica juncea), Njana (Crepidiastrum lanceolatium), Fuchiba (Artemisia vulgaris) and Fudanso (Beta vulgaris); and they consumed an average of 144.9 g/day, resulting in a 20.5% increase in their urinary potassium excretion over the baseline (p=0.045). The members of the control group were asked to avoid these vegetables, and the change in potassium excretion in this group was not significant (p=0.595). Urinary sodium and magnesium excretions, systolic and diastolic blood pressures, folic acid, triglycerides and serum high density lipoprotein cholesterol, low density lipoprotein cholesterol and total cholesterols changed non-significantly in both groups. Also, post

  14. Two Cases of Hypophosphatemia with Increased Renal Phosphate Excretion in Legionella Pneumonia

    PubMed Central

    Watanabe, Shuhei; Kono, Keiji; Fujii, Hideki; Nakai, Kentaro; Goto, Shunsuke; Nishi, Shinichi

    2016-01-01

    We encountered 2 cases of hypophosphatemia due to Legionella pneumonia. Both cases showed increased urinary phosphate excretion and renal tubular dysfunction, which ameliorated with recovery from Legionella pneumonia. Serum fibroblast growth factor-23 level was suppressed, whereas serum 1,25(OH)2 vitamin D and parathyroid hormone levels were normal. Delayed elevation of serum 1,25(OH)2 vitamin D levels was observed with improvement in renal tubular function. These findings suggested hypophosphatemia might be mediated by renal tubular dysfunction. PMID:27066493

  15. Plasma lipids, lipoproteins, and fecal excretion of neutral sterols and bile acids in rats fed various high fat diets or a low fat/high sucrose diet.

    PubMed

    Høstmark, A T; Lystad, E; Haug, A; Eilertsen, E

    1989-03-01

    The effect of feeding various diets on plasma lipids and lipoproteins and on fecal excretion of neutral sterols and bile acids was studied in rats fed for 7 wk diets containing 42% of energy as either coconut oil (CO), sunflower seed oil (SO), fish body oil (FBO), cod liver oil (CLO), or a low fat/high sucrose diet (SU). Triacylglycerols (TG) in whole plasma and VLDL + LDL were lower in rats fed high amounts of polyunsaturated fatty acids (PUFA) than in those fed the CO diet. Plasma HDL2 components in FBO and CLO groups were generally lower than in the other groups. Percentages of liver and heart linoleic and arachidonic acid were higher in the SO group, but lower in groups fed marine oils, than in the CO group. There was a high relative amount of eicosapentaenoic and docosahexaenoic acid in liver and heart of rats fed marine oils. Fecal excretion of bile acids was lower in the PUFA groups than in the CO group, whereas the sum of neutral sterols was similar in all groups. Plasma HDL2 (and VLDL + LDL) correlated positively, but HDL3 negatively, with fecal bile acid excretion. Accordingly, increased bile acid excretion does not seem to account for hypolipemia following intake of PUFA diets. PMID:2921639

  16. Comparison of postprandial phenolic acid excretions and glucose responses after ingestion of breads with bioprocessed or native rye bran.

    PubMed

    Lappi, Jenni; Aura, Anna-Marja; Katina, Kati; Nordlund, Emilia; Kolehmainen, Marjukka; Mykkänen, Hannu; Poutanen, Kaisa

    2013-06-01

    Rye bran contains a high amount of phenolic acids with potential health promoting effects. However, due to binding to dietary fibre, the phenolic acids are poorly absorbed in human body. We used bioprocessing with enzymes and yeast to release phenolic acids from the fibre complex and studied the effect of bioprocessing on absorption of phenolic acids in healthy humans. White wheat breads fortified with bioprocessed or native rye bran, and wholegrain rye bread and white wheat bread as controls were served to 15 subjects in a randomized order in the cross-over design. Urine was collected at the basal state and over 24 hours in four-, eight-, and twelve-hour periods and analyzed for phenolic acids and their metabolites with gas chromatography. A total of six blood samples were taken over four hours to study the effect of the bread ingestion on postprandial glucose and insulin responses. Bioprocessing of rye bran increased the proportion of free ferulic acid (FA) and soluble arabinoxylan in the bread. Ingestion of the white wheat bread fortified with bioprocessed rye bran increased (p < 0.001) urinary excretion of FA particularly during the first four hours, indicating increased absorption of FA from the small intestine. The postprandial glucose and insulin responses were similar between these breads. Bioprocessing of rye bran did not affect excretion of benzoic, phenylpropionic, and phenylacetic acid metabolites. As a conclusion, bioprocessed rye bran as compared with native rye bran increased absorption of FA from the small intestine, but did not improve postprandial glucose and insulin responses. PMID:23674066

  17. Excretion pathways and ruminal disappearance of glyphosate and its degradation product aminomethylphosphonic acid in dairy cows.

    PubMed

    von Soosten, D; Meyer, U; Hüther, L; Dänicke, S; Lahrssen-Wiederholt, M; Schafft, H; Spolders, M; Breves, G

    2016-07-01

    From 6 balance experiments with total collection of feces and urine, samples were obtained to investigate the excretion pathways of glyphosate (GLY) in lactating dairy cows. Each experiment lasted for 26d. The first 21d served for adaptation to the diet, and during the remaining 5d collection of total feces and urine was conducted. Dry matter intake and milk yield were recorded daily and milk and feed samples were taken during the sampling periods. In 2 of the 6 experiments, at the sampling period for feces and urine, duodenal contents were collected for 5d. Cows were equipped with cannulas at the dorsal sac of the rumen and the proximal duodenum. Duodenal contents were collected every 2h over 5 consecutive days. The daily duodenal dry matter flow was measured by using chromium oxide as a volume marker. All samples (feed, feces, urine, milk and duodenal contents were analyzed for GLY and aminomethylphosphonic acid (AMPA). Overall, across the 6 experiments (n=32) the range of GLY intake was 0.08 to 6.67mg/d. The main proportion (61±11%; ±SD) of consumed GLY was excreted with feces; whereas excretion by urine was 8±3% of GLY intake. Elimination via milk was negligible. The GLY concentrations above the limit of quantification were not detected in any of the milk samples. A potential ruminal degradation of GLY to AMPA was derived from daily duodenal GLY flow. The apparent ruminal disappearance of GLY intake was 36 and 6%. In conclusion, the results of the present study indicate that the gastrointestinal absorption of GLY is of minor importance and fecal excretion represents the major excretion pathway. A degradation of GLY to AMPA by rumen microbes or a possible retention in the body has to be taken into account. PMID:27108173

  18. Waste nitrogen excretion via amino acid acylation: benzoate and phenylacetate in lysinuric protein intolerance.

    PubMed

    Simell, O; Sipilä, I; Rajantie, J; Valle, D L; Brusilow, S W

    1986-11-01

    Benzoate and phenylacetate improve prognosis in inherited urea cycle enzyme deficiencies by increasing waste nitrogen excretion as amino acid acylation products. We studied metabolic changes caused by these substances and their pharmacokinetics in a biochemically different urea cycle disorder, lysinuric protein intolerance (LPI), under strictly standardized induction of hyperammonemia. Five patients with LPI received an intravenous infusion of 6.6 mmol/kg L-alanine alone and separately with 2.0 mmol/kg of benzoate or phenylacetate in 90 min. Blood for ammonia, serum urea and creatinine, plasma benzoate, hippurate, phenylacetate, phenylacetylglutamine, and amino acids was obtained at 0, 120, 180, and 270 min. Urine was collected in four consecutive 6-h periods. Alanine caused hyperammonemia: maximum increase 107, 28-411 microM (geometric mean, 95% confidence interval); ammonia increments were nearly identical after alanine + benzoate (60, 17-213 microM) and alanine + phenylacetate (79, 13-467 microM) (NS). Mean plasma benzoate was 6.0 mM when extrapolated to the end of alanine + benzoate infusions; phenylacetate was 4.9 mM at the end of alanine + phenylacetate. Transient toxicity (dizziness, nausea, vomiting) occurred in four patients at the end of combined infusions, and we suggest upper therapeutic plasma concentrations of 4.5 mM for benzoate and 3.5 mM for phenylacetate. Benzoate and phenylacetate then decreased following first-order kinetics with t1/2S of 273 and 254 min, respectively. Maximal plasma hippurate (0.24, 0.14-0.40 mM) was lower than maximal phenylacetylglutamine (0.48, 0.22-1.06 mM, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3099249

  19. Aspartame ingestion increases urinary calcium, but not oxalate excretion, in healthy subjects.

    PubMed

    Nguyen, U N; Dumoulin, G; Henriet, M T; Regnard, J

    1998-01-01

    Aspartame is the artificial sweetener most extensively used as a substitute for glucose or sucrose in the food industry, particularly in soft drinks. As glucose ingestion increases calciuria and oxaluria, the two main determinants of urinary calcium-oxalate saturation, we considered it worthwhile to determine whether aspartame ingestion also affects calcium-oxalate metabolism. Our study compares the effects of the ingestion of similarly sweet doses of aspartame (250 mg) and glucose (75 g) on calcium and oxalate metabolisms of seven healthy subjects. Urinary calcium excretion increased after the intake of both aspartame (+86%; P < 0.01) and glucose (+124%; P < 0.01). This may be due to the rise in calcemia observed after both aspartame (+2.2%; P < 0.05) and glucose ingestion (+1.8%; P < 0.05). The increased calcemia may be linked to the decrease in phosphatemia that occurred after both aspartame (P < 0.01) and glucose (P < 0.01) load. Aspartame did not alter glycemia or insulinemia, whereas glucose intake caused striking increases in both glycemia (+59%; P < 0.001) and insulinemia (+869%; P < 0.01). Although insulin was considered the main calciuria-induced factor after glucose load, it is unlikely that this mechanism played a role with aspartame. Urinary oxalate excretion did not change after aspartame, whereas it increased (+27%; P < 0.05) after glucose load. Thus, as aspartame induced a similar increase in calciuria as did glucose but, conversely, no change in oxaluria, substituting glucose by aspartame in soft drinks may appear to be of some potential benefit. PMID:9435435

  20. Breathing Assistance by the Iron Lung Increases Sympathetic Tone and Modifies Fluid Excretion

    NASA Astrophysics Data System (ADS)

    Baisch, F. J.; Gerzer, R.

    Adaptation to weightlessness is not accompanied by an increase in sodium- and urine- excretion in humans in contrast to the expectations and the bed rest model in use to simulate effects of weightlessness on earth. On earth the thorax remains compressed by gravity in the horizontal body position while its unloading in weightlessness reduces transmural pressure in the mediastinal walls and membranes. Thus, wall stretching. or the Henry-Gauer mechanism, is reduced and may even result in a reduced water and sodium excretion. We have therefore lowered the transmural mediastinal pressure by the principle of the "Iron Lung" in a terrestrial model, and have studied whether or not this principle might reduce body fluid loss seen during onset of head down tilt bed rest. Methods: Two experiment runs were performed in a cross over design: one run pure 6° head down tilt body position (HDT) and the other with iron lung assistance. Six male subjects (26.5 +/- 8.1 years old; 187+/- 5 cm tall; 84.0 +/- 6.6 kg body weight) participated. Lung pressure was modified by the iron lung where the whole body except the head is enclosed in a box. The air pressure inside the box was 5 cm H2O lower than ambient during activation of the iron lung. For inspiration negative pressure increased up to 15 cm H2O, roughly doubling resting breath tide. The counteracting lung pressure was 8.1 +/- 0.6 cm H2O for 4 hours in mean. Breathing rate was reduced under iron lung to avoid hyperventilation (10.2 +/- 0.6 bpm [iron lung] versus 14.0 +/- 1.2 Bpm [spontaneously]). The relationship between expiration and inspiration remained at 2:1 in both runs. End expiratory CO2 was measured breath by breath via a nose clip. Heart rate, peripheral oxygen saturation, and sphygmomanometric blood pressure were determined every half hour. Urine volume was measured hourly. sodium excretion and pH was determined. Ambient conditions were kept constant at thermoneutral conditions. Evaporative fluid loss was evaluated by a

  1. Urinary guanidinoacetic acid excretion as an indicator of gentamicin nephrotoxicity in rats.

    PubMed

    Kiyatake, Ikuo; Nakamura, Tsukasa; Koide, Hikaru

    2004-07-01

    The kidney is the main site of guanidinoacetic acid synthesis and excretion. The aim of this study was to examine whether urinary guanidinoacetic acid is a sensitive indicator for diagnosis of early-stage gentamicin nephrotoxicity. Early-stage renal injury was induced in rats by a single intravenous injection of 5, 10, or 30 mg/kg body weight gentamicin. Twenty-four hours after injection all rats were killed. Blood, urine and tissue guanidino compound concentrations were determined by high performance liquid chromatography. Glycine amidinotransferase activity in tissues was assayed according to the method of Pilsum. Urinary guanidinoacetic acid excretion was decreased in 5 mg/kg gentamicin-treated rats in comparison to that in control rats, whereas urine N-acetyl-beta-D-glucosaminidase activity and beta2-microglobulin were unchanged. Guanidinoacetic acid concentration and glycine amidinotransferase activity in the kidney were significantly decreased in 5, 10, and 30 mg/kg gentamicin-treated rats; the decreases were dose-dependent. These results suggest that the urine guanidinoacetic acid concentration is a more sensitive indicator of renal injury than conventional indicators such as urine N-acetyl-beta-D-glucosaminidase and beta2-microglobulin. PMID:15462098

  2. The urinary excretion of orally administered pteroyl-l-glutamic acid by the rat

    PubMed Central

    Blair, J. A.; Dransfield, E.

    1971-01-01

    1. The urinary excretion of folates after oral administration of [2-14C]pteroyl-l-glutamic acid was studied by assaying the radioactivity in the urine and in materials purified and characterized by t.l.c. 2. Radioactivity excreted was 6.8, 5.9 and 30.7% of the oral dose in the first 24h after doses of 3.1, 32 and 320μg/kg respectively. 3. Extensive decomposition of urinary folates to pteroyl-l-glutamic acid was prevented by antioxidants or collection of urine frozen. 4. At the three dosages, two major and one minor radioactive compounds were isolated. One of the major metabolites was 5-methyltetrahydropteroylglutamic acid. The others were unidentified but were not pteroylglutamic acid, 7,8-dihydro-, 5,6,7,8-tetrahydro-, 5- or 10-formyl-tetrahydro-, 5,10-methylidyne-tetrahydro-, 5-formimidoyl-tetrahydro-, 5,10-methylene-tetrahydro-, 5-methyltetrahydro-pteroylglutamic acid, nor any decomposition products of these compounds formed during isolation. Labelled unconjugated pteridines were absent. 5. Labelled pteroyl-l-glutamic acid was displaced by oral administration of unlabelled pteroyl-l-glutamic acid (1.6mg/kg) when given 3.5h after, but not when given 24h after the labelled dose. 6. The results show that orally administered [2-14C]pteroyl-l-glutamic acid is absorbed without metabolism and is then metabolized into naturally occurring tetrahydro-folates. 7. These findings are discussed with reference to previous work. PMID:5124394

  3. SN2-Palmitate Reduces Fatty Acid Excretion in Chinese Formula-fed Infants

    PubMed Central

    Bar-Yoseph, Fabiana; Lifshitz, Yael; Cohen, Tzafra; Malard, Patrice; Xu, Chungdi

    2016-01-01

    ABSTRACT Objectives: Palmitic acid (PA) comprises 17% to 25% of human milk fatty acids, of which 70% to 75% are esterified to the SN2 position of the triglyceride (SN2-palmitate). In vegetable oils, which are commonly used in infant formulas, palmitate is primarily esterified to other positions, resulting in reduced calcium and fat absorption and hard stools. The aim of this study was to elucidate the effects of SN2-palmitate on nutrient excretion. Methods: In total, 171 Chinese infants were included (within 14 days of birth) in this multicenter study. Formula-fed infants were randomly assigned to receive either SN2-palmitate formula (INFAT, n = 57) or control formula (n = 57). The formulas (Biostime, China) differed only in their SN2 PA proportions. Stool was collected at 6 postnatal weeks. Results: The stool dry weight and fat content of the SN2-palmitate group were lower compared with the control group (dry weight 4.25 g vs 7.28 g, P < 0.05; fat 0.8 g vs 1.2 g, P < 0.05). The lipid component was also significantly lower for the SN2-palmitate group (0.79 g vs 1.19 g, P < 0.05). PA, representing ∼50% of the saponified fatty acids, was significantly lower in the SN2-palmitate group compared with the control group (0.3 g vs 0.7 g, P < 0.01). Breast-fed infants had a significantly lower stool dry weight, fat content, and saponified fat excretion compared with formula-fed infants (P < 0.01). Conclusions: Similar to breast milk, the SN2-palmitate infant formula primarily reduced calcium-saponified fat excretion. The results of this study further emphasize the nutritional importance of SN2-palmitate structured fat for infants. PMID:26334255

  4. Urinary excretion of LH and testosterone from male rats during exposure to increased gravity: post-spaceflight and centrifugation

    NASA Technical Reports Server (NTRS)

    Ortiz, R. M.; Wade, C. E.; Morey-Holton, E.

    2000-01-01

    A dissociation between plasma luteinizing hormone (LH) and testosterone (T) appears to exist during exposure to altered gravity. The pulsatile nature of LH release and the diurnal variability of T secretion may mask or bias the effects of altered gravity on the pituitary-gonadal axis when analyzing plasma concentrations. Therefore, we examined the relationship between the excretion of urinary LH and T in male Sprague-Dawley rats during exposure to increased gravity upon return to Earth following a 14-day spaceflight (n = 6) and by 12 days of centrifugation at 2g (n = 8). Excreted LH and T were elevated on the first 3 days postflight. Excreted T was elevated between Days 1 and 8 of centrifugation; however, excreted LH was reduced on Days 2 and 3 compared with control animals. Excreted LH and T were significantly correlated (R = 0.731 and 0.706, respectively) in postspaceflight and centrifuged animals. Correlation curves had similar slopes (0.0213 and 0.023, respectively), but different y-intercepts (-1.43 and 3.32, respectively). The sustained increase in excreted T during centrifugation suggests that the pituitary-gonadal axis in postspaceflight animals may adapt quicker to increased gravity. The upward shift in the correlation curve exhibited by the centrifuged animals suggests that the sensitivity of LH-induced T release is increased in these animals. The previous dissociation between plasma LH and T during altered gravity was not observed in the present study in which excreted LH and T were measured.

  5. Impact of beta-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters.

    PubMed

    Trautwein, E A; Forgbert, K; Rieckhoff, D; Erbersdobler, H F

    1999-01-29

    To examine the impact on bile acid metabolism and fecal steroid excretion as a mechanism involved in the lipid-lowering action of beta-cyclodextrin and resistant starch in comparison to cholestyramine, male golden Syrian hamsters were fed 0% (control), 8% or 12% of beta-cyclodextrin or resistant starch or 1% cholestyramine. Resistant starch, beta-cyclodextrin and cholestyramine significantly lowered plasma total cholesterol and triacylglycerol concentrations compared to control. Distinct changes in the bile acid profile of gallbladder bile were caused by resistant starch, beta-cyclodextrin and cholestyramine. While cholestyramine significantly reduced chenodeoxycholate independently of its taurine-glycine conjugation, beta-cyclodextrin and resistant starch decreased especially the percentage of taurochenodeoxycholate by -75% and -44%, respectively. As a result, the cholate:chenodeoxycholate ratio was significantly increased by 100% with beta-cyclodextrin and by 550% with cholestyramine while resistant starch revealed no effect on this ratio. beta-Cyclodextrin and resistant starch, not cholestyramine, significantly increased the glycine:taurine conjugation ratio demonstrating the predominance of glycine conjugated bile acids. Daily fecal excretion of bile acids was 4-times higher with 8% beta-cyclodextrin and 19-times with 1% cholestyramine compared to control. beta-Cyclodextrin and cholestyramine also induced a 2-fold increase in fecal neutral sterol excretion, demonstrating the sterol binding capacity of these two compounds. Resistant starch had only a modest effect on fecal bile acid excretion (80% increase) and no effect on excretion of neutral sterols, suggesting a weak interaction with intestinal steroid absorption. These data demonstrate the lipid-lowering potential of beta-cyclodextrin and resistant starch. An impaired reabsorption of circulating bile acids and intestinal cholesterol absorption leading to an increase in fecal bile acid and neutral sterol

  6. Biotransformation of acrolein in rat: excretion of mercapturic acids after inhalation and intraperitoneal injection.

    PubMed

    Linhart, I; Frantík, E; Vodicková, L; Vosmanská, M; Smejkal, J; Mitera, J

    1996-01-01

    Biotransformation of acrolein (ACR) was studied in vivo in the rat following inhalation and ip administration. The major and minor urinary metabolites were 3-hydroxypropylmercapturic acid (HPMA) and 2-carboxyethylmercapturic acid (CEMA), respectively. Male Wistar rats were exposed to ACR, 23, 42, 77 and 126 mg/m3, for 1 hr. The sum of mercapturic acids HPMA and CEMA excreted within 24 hr after the exposure amounted to 0.87 +/- 0.12, 1.34 +/- 0.5, 2.81 +/- 1.15, and 7.13 +/- 1.56 mumol/kg, i.e., 10.9 +/- 1.5, 13.3 +/- 5.0, 16.7 +/- 6.9, and 21.5 +/- 4.8% of the estimated absorbed dose, respectively. The dose estimate was based on reported values of minute respiratory volume and respiratory tract retention and was corrected for the ACR-induced changes in minute respiratory volume. In the relevant dose range (8.9 to 35.7 mumol/kg) the portion of mercapturic acids excreted was nearly constant for ip exposed rats. The sum of HPMA and CEMA amounted to 29.1 +/- 6.5% of the dose. These results indicate that the deficiency in rat lung metabolism of ACR to acrylic acid previously observed is not compensated by the other detoxication pathway in vivo, mercapturic acid formation. The health hazard arising from inhalation of ACR is likely to be higher than that from other routes of exposure. PMID:8560469

  7. Subpressor doses of angiotensin II do not increase albumin excretion in humans.

    PubMed

    Erley, C M; Grau, C; Furian, T C; Wolf, S; Braun, N; Risler, T

    1996-11-01

    The objective of our study was to evaluate the effects of subpressor doses of angiotensin II and mild physical stress on renal hemodynamics and urinary albumin excretion (UAE) in a group of young patients with essential hypertension compared to normotensive subjects. Eleven patients (26 +/- 6 years) and ten healthy control persons (25 +/- 2 years) were enrolled in the study. Secondary forms of hypertension had been excluded. Angiotensin II was infused at a dose of 0.3 and 1.0 ng/kg/min and physical stress testing was done with a cycle ergometer (50 W at 10 min for hypertensives, 100 W at 10 min for normotensives). Renal hemodynamics were assessed by clearance techniques (continuous insulin and p-aminohippurate clearance). Mean arterial pressure (MAP) and UAE were significantly higher in the hypertensive group than in normotensive control persons at any time of measurement. There was no significant increase in MAP or UAE under angiotensin II infusion either in the hypertensive group or in the normotensive group. MAP increased significantly under physical stress in the normotensive group only (83 +/- 7 mmHg baseline vs. 108 +/- mmHg during physical stress, p < 0.05). Angiotensin II infusion resulted in a significant change concerning renal hemodynamics in the hypertensive group only. The filtration fraction increased (18 +/- 3% baseline vs. 25 +/- 7% under infusion of 1.0 ng/kg/min angiotensin II, p < 0.05) due to a decline in ERPF and an increase in GFR in the hypertensive group. The amount of UAE correlated with the magnitude of the MAP in both groups. No correlation was found between renal hemodynamic parameters and the UAE. A significant correlation was found between the norepinephrine levels and the UAE in the control group. We could not demonstrate an albuminuric effect of subpressor doses of angiotensin II in normotensive or hypertensive subjects despite its well known effects on renal hemodynamics with an increase of the filtration fraction. These data

  8. Association between consumption of cruciferous vegetables and condiments and excretion in urine of isothiocyanate mercapturic acids.

    PubMed

    Vermeulen, Martijn; van den Berg, Robin; Freidig, Andreas P; van Bladeren, Peter J; Vaes, Wouter H J

    2006-07-26

    A high intake of cruciferous vegetables is associated with a reduced risk of cancer and cardiovascular diseases. This protective effect has been linked to isothiocyanates, enzymatic hydrolysis products of glucosinolates. In this study, the metabolic fate of glucosinolates and isothiocyanates after ingestion of 19 different cruciferous vegetables was studied in three male subjects. After the consumption of 13 cruciferous vegetables (glucosinolate content, 0.01-0.94 mmol/kg) and six condiments (isothiocyanate content, 0.06-49.3 mmol/kg), eight different isothiocyanate mercapturic acids were determined in urine samples. Excretion levels after the consumption of raw vegetables and condiments were higher (bioavailability, 8.2-113%) as compared to cooked vegetables (bioavailability, 1.8-43%), but the excretion rate was similar (t1/2=2.1-3.9 h). Isothiocyanates in urine remain longer at a nonzero level after the consumption of glucosinolates from cooked vegetables, as compared to raw vegetables and condiments, and maximal levels in urine were reached about 4 h later. Isothiocyanate mercapturic acids can be used as a biomarker to reflect the active dose of isothiocyanates absorbed. PMID:16848516

  9. Colonic mucosal gene expression and genotype in irritable bowel syndrome patients with normal or elevated fecal bile acid excretion

    PubMed Central

    Carlson, Paula; Acosta, Andres; Busciglio, Irene

    2015-01-01

    The mucosal gene expression in rectosigmoid mucosa (RSM) in irritable bowel syndrome with diarrhea (IBS-D) is unknown. Our objectives were, first, to study mRNA expression [by RT2 PCR of 19 genes pertaining to tight junctions, immune activation, intestinal ion transport and bile acid (BA) homeostasis] in RSM in IBS-D patients (n = 47) and healthy controls (n = 17) and study expression of a selected protein (PDZD3) in 10 IBS-D patients and 4 healthy controls; second, to assess RSM mRNA expression according to genotype and fecal BA excretion (high ≥2,337 μmol/48 h); and third, to determine whether genotype or mucosal mRNA expression is associated with colonic transit or BA parameters. Fold changes were corrected for false detection rate for 19 genes studied (P < 0.00263). In RSM in IBS-D patients compared with controls, mRNA expression of GUC2AB, PDZD3, and PR2Y4 was increased, whereas CLDN1 and FN1 were decreased. One immune-related gene was upregulated (C4BP4) and one downregulated (CCL20). There was increased expression of a selected ion transport protein (PDZD3) on immunohistochemistry and Western blot in IBS-D compared with controls (P = 0.02). There were no significant differences in mucosal mRNA in 20 IBS-D patients with high compared with 27 IBS-D patients with normal BA excretion. GPBAR1 (P < 0.05) was associated with colonic transit. We concluded that mucosal ion transport mRNA (for several genes and PDZD3 protein) is upregulated and barrier protein mRNA downregulated in IBS-D compared with healthy controls, independent of genotype. There are no differences in gene expression in IBS-D with high compared with normal fecal BA excretion. PMID:25930081

  10. Colonic mucosal gene expression and genotype in irritable bowel syndrome patients with normal or elevated fecal bile acid excretion.

    PubMed

    Camilleri, Michael; Carlson, Paula; Acosta, Andres; Busciglio, Irene

    2015-07-01

    The mucosal gene expression in rectosigmoid mucosa (RSM) in irritable bowel syndrome with diarrhea (IBS-D) is unknown. Our objectives were, first, to study mRNA expression [by RT(2) PCR of 19 genes pertaining to tight junctions, immune activation, intestinal ion transport and bile acid (BA) homeostasis] in RSM in IBS-D patients (n = 47) and healthy controls (n = 17) and study expression of a selected protein (PDZD3) in 10 IBS-D patients and 4 healthy controls; second, to assess RSM mRNA expression according to genotype and fecal BA excretion (high ≥ 2,337 μmol/48 h); and third, to determine whether genotype or mucosal mRNA expression is associated with colonic transit or BA parameters. Fold changes were corrected for false detection rate for 19 genes studied (P < 0.00263). In RSM in IBS-D patients compared with controls, mRNA expression of GUC2AB, PDZD3, and PR2Y4 was increased, whereas CLDN1 and FN1 were decreased. One immune-related gene was upregulated (C4BP4) and one downregulated (CCL20). There was increased expression of a selected ion transport protein (PDZD3) on immunohistochemistry and Western blot in IBS-D compared with controls (P = 0.02). There were no significant differences in mucosal mRNA in 20 IBS-D patients with high compared with 27 IBS-D patients with normal BA excretion. GPBAR1 (P < 0.05) was associated with colonic transit. We concluded that mucosal ion transport mRNA (for several genes and PDZD3 protein) is upregulated and barrier protein mRNA downregulated in IBS-D compared with healthy controls, independent of genotype. There are no differences in gene expression in IBS-D with high compared with normal fecal BA excretion. PMID:25930081

  11. Effect of milk on the urinary excretion of microbial phenolic acids after cocoa powder consumption in humans.

    PubMed

    Urpi-Sarda, Mireia; Llorach, Rafael; Khan, Nasiruddin; Monagas, Maria; Rotches-Ribalta, Maria; Lamuela-Raventos, Rosa; Estruch, Ramon; Tinahones, Francisco J; Andres-Lacueva, Cristina

    2010-04-28

    Health effects of cocoa flavonols depend on their bioavailability, which is strongly influenced by the food matrix and the degree of flavanol polymerization. The effect of milk on the bioavailability of cocoa flavanoids considering phase II metabolites of epicatechin has been the subject of considerable debate. This work studies the effect of milk at the colonic microbial metabolism level of the nonabsorbed flavanol fraction that reaches the colon and is metabolized by the colonic microbiota into various phenolic acids. Twenty-one human volunteers followed a diet low in polyphenols for at least 48 h before taking, in a random order, 40 g of cocoa powder dissolved either in 250 mL of whole milk or in 250 mL of water. Urine samples were collected before the intake and during three different periods (0-6, 6-12, and 12-24 h). Phenolic acids were analyzed by LC-MS/MS after solid-phase extraction. Of the 15 metabolites assessed, the excretion of 9 phenolic acids was affected by the intake of milk. The urinary concentration of 3,4-dihydroxyphenylacetic, protocatechuic, 4-hydroxybenzoic, 4-hydroxyhippuric, hippuric, caffeic, and ferulic acids diminished after the intake of cocoa with milk, whereas urinary concentrations of vanillic and phenylacetic acids increased. In conclusion, milk partially affects the formation of microbial phenolic acids derived from the colonic degradation of procyanidins and other compounds present in cocoa powder. PMID:20222713

  12. Breastfeeding: A Potential Excretion Route for Mothers and Implications for Infant Exposure to Perfluoroalkyl Acids

    PubMed Central

    Mondal, Debapriya; Weldon, Rosana Hernandez; Armstrong, Ben G.; Gibson, Lorna J.; Lopez-Espinosa, Maria-Jose; Shin, Hyeong-Moo

    2013-01-01

    Background: The presence of perfluoroalkyl acids (PFAAs) in breast milk has been documented, but their lactational transfer has been rarely studied. Determination of the elimination rates of these chemicals during breastfeeding is important and critical for assessing exposure in mothers and infants. Objectives: We aimed to investigate the association between breastfeeding and maternal serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS). For a subset of the population, for whom we also have their infants’ measurements, we investigated associations of breastfeeding with infant serum PFAA concentrations. Methods: The present analysis included 633 women from the C8 Science Panel Study who had a child < 3.5 years of age and who provided blood samples and reported detailed information on breastfeeding at the time of survey. PFAA serum concentrations were available for all mothers and 8% (n = 49) of the infants. Maternal and infant serum concentrations were regressed on duration of breastfeeding. Results: Each month of breastfeeding was associated with lower maternal serum concentrations of PFOA (–3%; 95% CI: –5, –2%), PFOS (–3%; 95% CI: –3, –2%), PFNA (–2%; 95% CI: –2, –1%), and PFHxS (–1%; 95% CI: –2, 0%). The infant PFOA and PFOS serum concentrations were 6% (95% CI: 1, 10%) and 4% (95% CI: 1, 7%) higher per month of breastfeeding. Conclusions: Breast milk is the optimal food for infants, but is also a PFAA excretion route for lactating mothers and exposure route for nursing infants. Citation: Mondal D, Weldon RH, Armstrong BG, Gibson LJ, Lopez-Espinosa MJ, Shin HM, Fletcher T. 2014. Breastfeeding: a potential excretion route for mothers and implications for infant exposure to perfluoroalkyl acids. Environ Health Perspect 122:187–192; http://dx.doi.org/10.1289/ehp.1306613 PMID:24280536

  13. ABCA1 overexpression leads to hyperalphalipoproteinemia and increased biliary cholesterol excretion in transgenic mice

    PubMed Central

    Vaisman, Boris L.; Lambert, Gilles; Amar, Marcelo; Joyce, Charles; Ito, Toshimitsu; Shamburek, Robert D.; Cain, William J.; Fruchart-Najib, Jamila; Neufeld, Edward D.; Remaley, Alan T.; Brewer, H. Bryan; Santamarina-Fojo, Silvia

    2001-01-01

    The discovery of the ABCA1 lipid transporter has generated interest in modulating human plasma HDL levels and atherogenic risk by enhancing ABCA1 gene expression. To determine if increased ABCA1 expression modulates HDL metabolism in vivo, we generated transgenic mice that overexpress human ABCA1 (hABCA1-Tg). Hepatic and macrophage expression of hABCA1 enhanced macrophage cholesterol efflux to apoA-I; increased plasma cholesterol, cholesteryl esters (CEs), free cholesterol, phospholipids, HDL cholesterol, and apoA-I and apoB levels; and led to the accumulation of apoE-rich HDL1. ABCA1 transgene expression delayed 125I-apoA-I catabolism in both liver and kidney, leading to increased plasma apoA-I levels, but had no effect on apoB secretion after infusion of Triton WR1339. Although the plasma clearance of HDL-CE was not significantly altered in hABCA1-Tg mice, the net hepatic delivery of exogenous 3H-CEt-HDL, which is dependent on the HDL pool size, was increased 1.5-fold. In addition, the cholesterol and phospholipid concentrations in hABCA1-Tg bile were increased 1.8-fold. These studies show that steady-state overexpression of ABCA1 in vivo (a) raises plasma apoB levels without altering apoB secretion and (b) raises plasma HDL-C and apoA-I levels, facilitating hepatic reverse cholesterol transport and biliary cholesterol excretion. Similar metabolic changes may modify atherogenic risk in humans. PMID:11457883

  14. Increased urinary excretion of hydroxyproline in runners training in urban areas.

    PubMed

    Perdelli, F; Gallelli, G; Cristina, M L; Sartini, M; Panatto, D; Reggiani, E; Orlando, P

    2000-01-01

    In this study, the authors investigated urinary excretion of hydroxyproline in 120 subjects to test the hypothesis that physical activity is associated with increased exposure to pollution derived from traffic exhaust. The study population comprised active noncompetitive runners (i.e., 21.1% trained < 2.5 hr/wk, 20% trained for 2.5-5.0 hr/wk, and 54.4% trained > 5 hr/wk) who lived in Genoa, an urban area of Northern Italy. The mean hydroxyproline value (24.39 +/- 8.38 standard deviation] mg/24 hr x m2) in a group of 69 runners who trained in tracks and streets located in downtown Genoa was higher (p < .05) than the mean value recorded in a group of 21 runners (13.33 +/- 2.51 mg/24 hr x m2) who trained mainly in a rural environment of Genoa. The difference was even greater (p < .01) when a third comparable group of 30 nonrunners was considered (mean = 12.54 +/- 3.41 [standard deviation] mg/24 hr x m2). In the urban environment, urinary levels of hydroxyproline were correlated significantly with intensity and frequency of running, but they were unrelated to smoking status. PMID:11128874

  15. Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase.

    PubMed

    Vicente-Vicente, Laura; Sánchez-Juanes, Fernando; García-Sánchez, Omar; Blanco-Gozalo, Víctor; Pescador, Moisés; Sevilla, María A; González-Buitrago, José Manuel; López-Hernández, Francisco J; López-Novoa, José Miguel; Morales, Ana Isabel

    2015-04-16

    Nephrotoxicity limits the therapeutic efficacy of the antineoplastic drug cisplatin. Due to dosage adjustment and appropriate monitoring, most therapeutic courses with cisplatin produce no or minimal kidney damage. However, we studied whether even sub-nephrotoxic dosage of cisplatin poses a potential risk for the kidneys by predisposing to acute kidney injury (AKI), specifically by lowering the toxicity threshold for a second nephrotoxin. With this purpose rats were treated with a single sub-nephrotoxic dosage of cisplatin (3mg/kg, i.p.) and after two days, with a sub-nephrotoxic regime of gentamicin (50mg/kg/day, during 6 days, i.p.). Control groups received only one of the drugs or the vehicle. Renal function and renal histology were monitored throughout the experiment. Cisplatin treatment did not cause any relevant functional or histological alterations in the kidneys. Rats treated with cisplatin and gentamicin, but not those under single treatments, developed an overt renal failure characterized by both renal dysfunction and massive tubular necrosis. In addition, the urinary excretion of fumarylacetoacetase was increased in cisplatin-treated animals at subtoxic doses, which might be exploited as a cisplatin-induced predisposition marker. In fact, the urinary level of fumarylacetoacetase prior to the second nephrotoxin correlated with the level of AKI triggered by gentamicin in predisposed animals. PMID:25677510

  16. Fecal bile acid excretion and messenger RNA expression levels of ileal transporters in high risk gallstone patients

    PubMed Central

    2009-01-01

    Background Cholesterol gallstone disease (GS) is highly prevalent among Hispanics and American Indians. In GS, the pool of bile acids (BA) is decreased, suggesting that BA absorption is impaired. In Caucasian GS patients, mRNA levels for ileal BA transporters are decreased. We aimed to determine fecal BA excretion rates, mRNA levels for ileal BA transporter genes and of regulatory genes of BA synthesis in Hispanic GS patients. Results Excretion of fecal BA was measured in seven GS females and in ten GS-free individuals, all with a body mass index < 29. Participants ingested the stool marker Cr2O3 (300 mg/day) for 10 days, and fecal specimens were collected on the last 3 days. Chromium was measured by a colorimetric method, and BA was quantitated by gas chromatography/mass spectroscopy. Intake of calories, nutrients, fiber and cholesterol were similar in the GS and GS-free subjects. Mean BA excretion levels were 520 ± 80 mg/day for the GS-free group, and 461 ± 105 mg/day for the GS group. Messenger RNA expression levels were determined by RT-PCR on biopsy samples obtained from ileum during diagnostic colonoscopy (14 GS-free controls and 16 GS patients) and from liver during surgery performed at 8 and 10 AM (12 GS and 10 GS-free patients operated on for gastrointestinal malignancies), all with a body mass index < 29. Messenger RNA level of the BA transporter genes for ileal lipid binding protein, multidrug resistance-associated protein 3, organic solute transporter alpha, and organic solute transporter beta were similar in GS and GS-free subjects. Messenger RNA level of Cyp27A1, encoding the enzyme 27α-hydroxylase, the short heterodimer partner and farnesoid X receptor remained unchanged, whereas the mRNA level of Cyp7A1, the rate limiting step of BA synthesis, was increased more than 400% (p < 0.01) in the liver of GS compared to GS-free subjects. Conclusion Hispanics with GS have fecal BA excretion rates and mRNA levels of genes for ileal BA transporters that

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

    PubMed

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

    2016-06-01

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

  18. Effect of dietary supplementation of gallic acid on nitrogen balance, nitrogen excretion pattern and urinary nitrogenous constituents in beef cattle.

    PubMed

    Wei, Chen; Yang, Kai; Zhao, Guangyong; Lin, Shixin; Xu, Zhiwei

    2016-10-01

    The objective of the trial was to study the effects of dietary supplementation of gallic acid (GA) on nitrogen (N) balance, N excretion pattern and urinary N constituents in beef cattle. In a 4 × 4 Latin square design, four male 30-month-old Simmental cattle (443 ± 22 kg live weight) received four levels of GA (purity ≥ 98.5%), i.e. 0, 5.3, 10.5, 21.1 g/kg DM, added to a basal ration. Each experimental period lasted 17 d, consisting of 12 d adaptation and 5 d sampling. The results showed that supplementation of GA at 5.3, 10.5 or 21.1 g/kg DM did not affect the N balance but regulated the N excretion pattern by increasing the ratio of faecal N/urinary N and decreasing the ratio of urinary urea N/total urinary N in beef cattle fed at maintenance level. PMID:27494638

  19. A Grape Seed Procyanidin Extract Ameliorates Fructose-Induced Hypertriglyceridemia in Rats via Enhanced Fecal Bile Acid and Cholesterol Excretion and Inhibition of Hepatic Lipogenesis.

    PubMed

    Downing, Laura E; Heidker, Rebecca M; Caiozzi, Gianella C; Wong, Brian S; Rodriguez, Kelvin; Del Rey, Fernando; Ricketts, Marie-Louise

    2015-01-01

    The objective of this study was to determine whether a grape seed procyanidin extract (GSPE) exerts a triglyceride-lowering effect in a hyperlipidemic state using the fructose-fed rat model and to elucidate the underlying molecular mechanisms. Rats were fed either a starch control diet or a diet containing 65% fructose for 8 weeks to induce hypertriglyceridemia. During the 9th week of the study, rats were maintained on their respective diet and administered vehicle or GSPE via oral gavage for 7 days. Fructose increased serum triglyceride levels by 171% after 9 weeks, compared to control, while GSPE administration attenuated this effect, resulting in a 41% decrease. GSPE inhibited hepatic lipogenesis via down-regulation of sterol regulatory element binding protein 1c and stearoyl-CoA desaturase 1 in the fructose-fed animals. GSPE increased fecal bile acid and total lipid excretion, decreased serum bile acid levels and increased the expression of genes involved in cholesterol synthesis. However, bile acid biosynthetic gene expression was not increased in the presence of GSPE and fructose. Serum cholesterol levels remained constant, while hepatic cholesterol levels decreased. GSPE did not modulate expression of genes responsible for esterification or biliary export of the newly synthesized cholesterol, but did increase fecal cholesterol excretion, suggesting that in the presence of GSPE and fructose, the liver may secrete more free cholesterol into the plasma which may then be shunted to the proximal small intestine for direct basolateral to apical secretion and subsequent fecal excretion. Our results demonstrate that GSPE effectively lowers serum triglyceride levels in fructose-fed rats after one week administration. This study provides novel insight into the mechanistic actions of GSPE in treating hypertriglyceridemia and demonstrates that it targets hepatic de novo lipogenesis, bile acid homeostasis and non-biliary cholesterol excretion as important mechanisms for

  20. A Grape Seed Procyanidin Extract Ameliorates Fructose-Induced Hypertriglyceridemia in Rats via Enhanced Fecal Bile Acid and Cholesterol Excretion and Inhibition of Hepatic Lipogenesis

    PubMed Central

    Wong, Brian S.; Rodriguez, Kelvin; Del Rey, Fernando; Ricketts, Marie-Louise

    2015-01-01

    The objective of this study was to determine whether a grape seed procyanidin extract (GSPE) exerts a triglyceride-lowering effect in a hyperlipidemic state using the fructose-fed rat model and to elucidate the underlying molecular mechanisms. Rats were fed either a starch control diet or a diet containing 65% fructose for 8 weeks to induce hypertriglyceridemia. During the 9th week of the study, rats were maintained on their respective diet and administered vehicle or GSPE via oral gavage for 7 days. Fructose increased serum triglyceride levels by 171% after 9 weeks, compared to control, while GSPE administration attenuated this effect, resulting in a 41% decrease. GSPE inhibited hepatic lipogenesis via down-regulation of sterol regulatory element binding protein 1c and stearoyl-CoA desaturase 1 in the fructose-fed animals. GSPE increased fecal bile acid and total lipid excretion, decreased serum bile acid levels and increased the expression of genes involved in cholesterol synthesis. However, bile acid biosynthetic gene expression was not increased in the presence of GSPE and fructose. Serum cholesterol levels remained constant, while hepatic cholesterol levels decreased. GSPE did not modulate expression of genes responsible for esterification or biliary export of the newly synthesized cholesterol, but did increase fecal cholesterol excretion, suggesting that in the presence of GSPE and fructose, the liver may secrete more free cholesterol into the plasma which may then be shunted to the proximal small intestine for direct basolateral to apical secretion and subsequent fecal excretion. Our results demonstrate that GSPE effectively lowers serum triglyceride levels in fructose-fed rats after one week administration. This study provides novel insight into the mechanistic actions of GSPE in treating hypertriglyceridemia and demonstrates that it targets hepatic de novo lipogenesis, bile acid homeostasis and non-biliary cholesterol excretion as important mechanisms for

  1. Purine and pyrimidine excretion in psoriasis

    PubMed Central

    Simmonds, H. A.; Bowyer, A.

    1974-01-01

    1 Urinary purine excretion has been investigated in two healthy controls and two patients with psoriasis, one a hyperuricaemic, one a normouricaemic. No difference was detected between the patients and controls. Therapy with allopurinol effectively lowered blood and urinary uric acid levels and produced a deficit in total urinary oxypurine excretion in both controls and patients with psoriasis. The concomitant increase in xanthine excretion was greater than the increase in hypoxanthine excretion and xanthine/hypoxanthine ratios (average 0.70 and 1.0 prior to therapy) were increased by allopurinol to an average of 3.0 and 3.8 respectively in the two groups. Allopurinol also reduced the excretion of 8-hydroxy-7-methyl guanine but no effect on the excretion levels of other minor purine bases was noted. 2 Allopurinol was metabolized similarly by both patients and controls, 84% of the administered allopurinol being accounted for as urinary metabolites. 74% of the drug in the urine was excreted as oxipurinol, 26% as unchanged allopurinol plus allopurinol riboside, the remainder being oxipurinol riboside. 3 Pseudouridine excretion in 25 healthy controls was 86.5 ± 17.8 mg/24 hours. Pseudouridine excretion was not excessive in the patients with psoriasis and was not altered by allopurinol therapy. 4 No abnormality or difference in purine or pyrimidine excretion in either patient was detected prior to or during therapy which could be related to the epidermal lesion. PMID:22454896

  2. Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but magnitude of effect depend on food type

    PubMed Central

    2012-01-01

    Background Dietary fibers have been proposed to play a role in cardiovascular risk as well as body weight management. Flaxseeds are a good source of dietary fibers, and a large proportion of these are water-soluble viscous fibers. Method Here, we examine the effect of flaxseed dietary fibers in different food matrices on blood lipids and fecal excretion of fat and energy in a double-blind randomized crossover study with 17 subjects. Three different 7-d diets were tested: a low-fiber control diet (Control), a diet with flaxseed fiber drink (3/day) (Flax drink), and a diet with flaxseed fiber bread (3/day) (Flax bread). Total fat and energy excretion was measured in feces, blood samples were collected before and after each period, and appetite sensation registered 3 times daily before main meals. Results Compared to control, Flax drink lowered fasting total-cholesterol and LDL-cholesterol by 12 and 15%, respectively, (p < 0.01), whereas Flax bread only produced a reduction of 7 and 9%, respectively (p < 0.05). Fecal fat and energy excretion increased by 50 and 23% with Flax drink consumption compared to control (p < 0.05), but only fecal fat excretion was increased with Flax bread compared to control (p < 0.05). Conclusion Both Flax drink and Flax bread resulted in decreased plasma total and LDL-cholesterol and increased fat excretion, but the food matrix and/or processing may be of importance. Viscous flaxseed dietary fibers may be a useful tool for lowering blood cholesterol and potentially play a role in energy balance. Trial Registration ClinicalTrials.gov: NCT00953004 PMID:22305169

  3. Biomonitoring the intake of garlic via urinary excretion of allyl mercapturic acid.

    PubMed

    Verhagen, H; Hageman, G J; Rauma, A L; Versluis-de Haan, G; van Herwijnen, M H; de Groot, J; Törrönen, R; Mykkänen, H

    2001-08-01

    Allium vegetables (onions, leeks, chives) and in particular garlic have been claimed to have health-promoting potential. This study was conducted to get insight into the perspectives for monitoring the intake of garlic by a biomarker approach. Chemically, the biomarker results from exposure to gamma-glutamyl-S-allyl-l-cysteine, which is first hydrolysed by gamma-glutamine-transpeptidase resulting in the formation of S-allyl-l-cysteine. The latter compound is subsequently N-acetylated by N-acetyltransferase into S-allyl-mercapturic acid (ALMA) and excreted into urine. The mercapturic acid was measured in urine using gaschromatography with mass spectrometry. Thus the intake of garlic was determined to check the compliance of garlic intake in a placebo-controlled intervention study. Results indicate that S-allyl-mercapturic acid could be detected in 15 out of 16 urine samples of garlic supplement takers, indicating good compliance. In addition, the intake of garlic was also monitored in a cross-section study of vegans versus controls in Finland, in which no differences in garlic consumption nor in ALMA output were recorded between vegans and controls. These data indicate good possibilities for further studies in the field of biomarkers to investigate the putative chemopreventive effects of garlic and garlic-containing products. PMID:11520428

  4. Increasing levels of dietary crystalline methionine affect plasma methionine profiles, ammonia excretion, and the expression of genes related to the hepatic intermediary metabolism in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Rolland, Marine; Skov, Peter V; Larsen, Bodil K; Holm, Jørgen; Gómez-Requeni, Pedro; Dalsgaard, Johanne

    2016-08-01

    Strictly carnivorous fish with high requirements for dietary protein, such as rainbow trout (Oncorhynchus mykiss) are interesting models for studying the role of amino acids as key regulators of intermediary metabolism. Methionine is an essential amino acid for rainbow trout, and works as a signalling factor in different metabolic pathways. The study investigated the effect of increasing dietary methionine intake on the intermediary metabolism in the liver of juvenile rainbow trout. For this purpose, five diets were formulated with increasing methionine levels from 0.60 to 1.29% dry matter. The diets were fed in excess for six weeks before three sampling campaigns carried out successively to elucidate (i) the hepatic expression of selected genes involved in lipid, glucose and amino acid metabolism; (ii) the postprandial ammonia excretion; and (iii) the postprandial plasma methionine concentrations. The transcript levels of enzymes involved in lipid metabolism (fatty acid synthase, glucose 6 phosphate dehydrogenase and carnitine palmitoyl transferase 1 a), gluconeogenesis (fructose-1,6-biphosphatase) and amino acid catabolism (alanine amino transferase and glutamate dehydrogenase) were significantly affected by the increase in dietary methionine. Changes in gene expression reflected to some extent the decrease in ammonia excretion (P=0.022) and in the hepatosomatic index (HSI; P<0.001) when dietary methionine increased. Postprandial plasma methionine concentrations correlated positively with the dietary level (P<0.001) at the different sampling points. The study shows that the expression of several genes related to the hepatic intermediary metabolism in rainbow trout responded in a dose-dependent manner to increasing levels of dietary methionine. PMID:27105833

  5. D-penicillamine does not increase urinary bismuth excretion in patients treated with tripotassium dicitrato bismuthate.

    PubMed Central

    Nwokolo, C U; Pounder, R E

    1990-01-01

    Twenty-four urinary bismuth excretion was measured in five patients who had been treated with tripotassium dicitrato bismuthate, before and after single 1 g oral dose of D-penicillamine. Before dosing with D-penicillamine, the median 24 h urinary bismuth output was 55 micrograms 24 h-1 (range 17-156 micrograms 24 h-1) and following dosing with D-penicillamine the median 24 h urinary bismuth output was 53 micrograms 24 h-1 (range 12-156 micrograms 24 h-1). D-penicillamine does not facilitate the urinary excretion of bismuth, hence it is unsuitable for use as an oral chelator in patients with bismuth intoxication. PMID:2291879

  6. Urinary Acid Excretion Can Predict Changes in Bone Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Zwart, Sara R.; Smith, Scott M.

    2011-01-01

    Mitigating space flight-induced bone loss is critical for space exploration, and a dietary countermeasure would be ideal. We present here preliminary data from a study where we examined the role of dietary intake patterns as one factor that can influence bone mineral loss in astronauts during space flight. Crewmembers (n=5) were asked to consume a prescribed diet with either a low (0.3-0.6) or high (1.0-1.3) ratio of animal protein to potassium (APro:K) before and during space flight for 4-d periods. Diets were controlled for energy, total protein, calcium, and sodium. 24-h urine samples were collected on the last day of each of the 4-d controlled diet sessions. 24-h urinary acid excretion, which was predicted by dietary potential renal acid load, was correlated with urinary n-telopeptide (NTX, Pearson R = 0.99 and 0.80 for the high and low APro:K sessions, respectively, p<0.001). The amount of protein when expressed as the percentage of total energy (but not as total grams) was also correlated with urinary NTX (R = 0.66, p<0.01). These results, from healthy individuals in a unique environment, will be important to better understand diet and bone interrelationships during space flight as well as on Earth. The study was funded by the NASA Human Research Program.

  7. Influence of diets high and low in animal fat on bowel habit, gastrointestinal transit time, fecal microflora, bile acid, and fat excretion.

    PubMed Central

    Cummings, J H; Wiggins, H S; Jenkins, D J; Houston, H; Jivraj, T; Drasar, B S; Hill, M J

    1978-01-01

    Epidemiological observations and animal experiments suggest that large bowel cancer is related to serveral factors. Among them, high dietary intakes of animal fat, the presence in the colon of relatively high levels of bile acids, specific patterns of intestinal microflora, slow transit through the gut, and low stool weights. Under metabolic conditions we have observed the effect on these variables of dietes containing 62 or 152 g/day of fat mainly of animal origin in six healthy young men over 4-wk periods. No change attributable to the diet was observed in the subjects' bowel habit, fecal weight, mean transit time through the gut, or in the excretion of dry matter. Total fecal bile acid excretion was significantly higher on the high fat diet (320 +/- 120 mg/day) than on the low fat diet (139.7) +/- 63 mg/day) t test = 7.78 P less than 0.001 as also was the total fecal fatty acid excretion, 3.1+/-0.71 and 1.14+/-0.35 g/day, respectively t test = 11.4 P less than 0.001). The fecal microflora including the nuclear dehydrogenating clostridia were unaltered by the dietary changes as was fecal beta-glucuronidase activity. Dietary changes which increase animal fat intake clearly influence fecal bile acid excretion in a way that would favor the development of large bowel cancer if current theories prove to be true. Dietary fat however has no effect on overall colonic function so other components of the diet must be responsible for the observed associations of bowel cancer with slow transit and reduced fecal bulk. PMID:659584

  8. Hepatic drug-oxidizing enzyme systems and urinary D-glucaric acid excretion in patients with congestive heart failure.

    PubMed Central

    Tokola, O; Pelkonen, O; Karki, N T; Luoma, P

    1975-01-01

    Drug-oxidizing enzyme systems in liver biopsy samples and the urinary excretion of D-glucaric acid were studied in two different groups of patients with cardiac insufficiency. 2. In one group of six patients, the activities of drug-metabolizing enzymes had decreased considerably as compared with the control values, but in four liver samples from patients treated with oral hypoglycaemic agents for their diabetes, activities were higher than in control samples from ten patients. 3. In the other group of seven patients, the urinary excretion of D-glucaric acid (isolated by ion-exchange chromatography) was 60% lower than in the control group of nine humans, whereas in four patients taking antiepileptic agents excretion rate was higher than control values. 4. Because the age distribution was markedly different between cardiac insufficiency and control groups, it is difficult to conclude, if the impairment of drug metabolism was a consequence of the old age or of the disease process. However, drug-oxidizing enzyme systems seem to be inducible also in old age. 5. The results support further the opinion that the urinary excretion of D-glucaric acid may be one useful index in assessing an individual's capacity to metabolize foreign compounds especially in the patients with lowered drug metabolizing capacity. PMID:786355

  9. Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome

    PubMed Central

    Acosta, Andrés; Camilleri, Michael; Shin, Andrea; Linker Nord, Sara; O'Neill, Jessica; Gray, Amber V; Lueke, Alan J; Donato, Leslie J; Burton, Duane D; Szarka, Lawrence A; Zinsmeister, Alan R; Golden, Pamela L; Fodor, Anthony

    2016-01-01

    Objectives: Rifaximin relieves irritable bowel syndrome (IBS) symptoms, bloating, abdominal pain, and loose or watery stools. Our objective was to investigate digestive functions in rifaximin-treated IBS patients. Methods: In a randomized, double-blind, placebo-controlled, parallel-group study, we compared the effects of rifaximin, 550 mg t.i.d., and placebo for 14 days in nonconstipated IBS and no evidence of small intestinal bacterial overgrowth (SIBO). All subjects completed baseline and on-treatment evaluation of colonic transit by scintigraphy, mucosal permeability by lactulose–mannitol excretion, and fecal microbiome, bile acids, and short chain fatty acids measured on random stool sample. Overall comparison of primary response measures between treatment groups was assessed using intention-to-treat analysis of covariance (ANCOVA, with baseline value as covariate). Results: There were no significant effects of treatment on bowel symptoms, small bowel or colonic permeability, or colonic transit at 24 h. Rifaximin was associated with acceleration of ascending colon emptying (14.9±2.6 h placebo; 6.9±0.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.0±0.3 h placebo; 4.7±0.2 h rifaximin; P=0.046); however, rifaximin did not significantly alter total fecal bile acids per g of stool or proportion of individual bile acids or acetate, propionate, or butyrate in stool. Microbiome studies showed strong associations within subjects, modest associations with time across subjects, and a small but significant association of microbial richness with treatment arm (rifaximin vs. treatment). Conclusions: In nonconstipated IBS without documented SIBO, rifaximin treatment is associated with acceleration of colonic transit and changes in microbial richness; the mechanism for reported symptomatic benefit requires further investigation. PMID:27228404

  10. Renal clearance of uric acid is linked to insulin resistance and lower excretion of sodium in gout patients.

    PubMed

    Perez-Ruiz, Fernando; Aniel-Quiroga, Maria Angeles; Herrero-Beites, Ana María; Chinchilla, Sandra Pamela; Erauskin, Gorka Garcia; Merriman, Toni

    2015-09-01

    Inefficient renal excretion of uric acid is the main pathophysiological mechanism for hyperuricemia in gout patients. Polymorphisms of renal tubular transporters linked with sodium and monosaccharide transport have yet to be demonstrated. We intended to evaluate the impact of insulin resistance, evaluated with the homeostasis model assessment (HOMA), through a transversal study of non-diabetic patients with gout, with normal renal function, not treated with any medication but colchicine as prophylaxis. One hundred and thirty-three patients were evaluated. Clearance of uric acid was inversely correlated with insulin resistance and directly correlated with fractional excretion of sodium. In multivariate analysis, hypertension and hyperlipidemia, in addition to insulin resistance and fractional excretion of sodium, were associated with renal clearance of uric acid. HOMA cutoff for efficient versus inefficient renal handling of uric acid was 2.72, close to that observed in studies of reference population. The impact of insulin resistance and renal handling of sodium on renal clearance of uric acid may help to explain why hyperuricemia is more commonly associated with diabetes and hypertension. PMID:25763991

  11. Comparison of isotope dilution and excretion methods for determining the half-life of ascorbic acid in the guinea pig

    SciTech Connect

    Kipp, D.E.; Rivers, J.M.

    1984-08-01

    The half-life of ascorbic acid (AA) in guinea pigs was investigated by the isotope dilution and excretion methods. The dilution method measures (1-14C)AA disappearance from the plasma, whereas the excretion method measures the elimination of (1-14C)AA and the metabolites from the body. Two groups of animals underwent both isotope studies in reverse order. Animals were conditioned to the experimental procedures and fed 2.5 mg AA/100 g body weight orally to maintain a daily intake of the vitamin independent of food consumption. The two isotope procedures imposed similar stress on the animals, as determined by plasma cortisol levels and body weight changes. The AA half-life calculations of the rapidly exchangeable pool by the isotope dilution method yielded values of 1.23 and 0.34 hours for the two groups, respectively. The half-life of the slowly exchangeable pool for the two groups was 60.2 and 65.8 hours, respectively. The half-life of AA in the rapidly exchangeable pool, as measured by the excretion studies, was 4.57-8.75 hours. For the slowly exchangeable pool, it was 146-149 hours. The longer half-life of both pools obtained with the excretion method indicates that the isotope is disappearing from the plasma more rapidly than it is being excreted. This suggests that a portion of the (1-14C)AA leaving the plasma is removed to a body pool that is not sampled by the isotope excretion method.

  12. Comparative effects of oral aromatic and branched-chain amino acids on urine calcium and excretion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aromatic amino acids (AAAs) bind to the calcium sensor receptor (CaR) but branched-chain amino acids (B-CAAs) do not; by binding to this receptor, AAAs have an increased potential to affect calcium homeostasis. This study was conducted to determine and compare the effects of AAAs and B-CAAs on calci...

  13. A severe phenotype of Gitelman syndrome with increased prostaglandin excretion and favorable response to indomethacin

    PubMed Central

    Larkins, Nicholas; Wallis, Mathew; McGillivray, Barbara; Mammen, Cherry

    2014-01-01

    Our understanding of Gitelman syndrome (GS) and Bartter syndrome has continued to evolve with the use of genetic testing to more precisely define the tubular defects responsible. GS is caused by mutations in the SLC12A3 gene encoding the Na+–Cl− co-transporter of the distal convoluted tubule (NCCT) and tends to be associated with a milder salt-losing phenotype. We describe two female siblings presenting in infancy with a severe salt-losing tubulopathy and failure to thrive due to compound heterozygous mutations in the SLC12A3 gene encoding the NCCT. Both children were treated with indomethacin resulting in improved linear growth and polyuria. Some atypical biochemical findings in our cases are discussed including raised urinary prostaglandin (PGE2) excretion that normalized with intravenous fluid repletion. PMID:25852896

  14. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting

    PubMed Central

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Alshahrani, Saeed; Brooks, Marybeth; McCormack, Francis X.; Smith, Roger D.; Zahedi, Kamyar

    2016-01-01

    Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2) and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE) levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2) in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR) reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of sodium and

  15. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting.

    PubMed

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Alshahrani, Saeed; Brooks, Marybeth; McCormack, Francis X; Smith, Roger D; Zahedi, Kamyar

    2016-01-01

    Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2) and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE) levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2) in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR) reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of sodium and

  16. Dietary hydroxypropyl methylcellulose increases excretion of saturated and trans fats by hamsters fed fast food diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The hypocholesterolemic and hypoglycemic effects of hydroxypropyl methylcellulose (HPMC), a semisynthetic nonfermentable soluble dietary fiber, are well established. However, effects of HPMC on dietary saturated fatty acids and trans fatty acids are largely unknown. This study investigated the eff...

  17. Ascorbic Acid may Exacerbate Aspirin-Induced Increase in Intestinal Permeability.

    PubMed

    Sequeira, Ivana R; Kruger, Marlena C; Hurst, Roger D; Lentle, Roger G

    2015-09-01

    Ascorbic acid in combination with aspirin has been used to prevent aspirin-induced oxidative GI damage. We aimed to determine whether ascorbic acid reduces or prevents aspirin-induced changes in intestinal permeability over a 6-hr period using saccharidic probes mannitol and lactulose. The effects of administration of 600 mg aspirin alone, 500 mg ascorbic acid alone and simultaneous dosage of both agents were compared in a cross-over study in 28 healthy female volunteers. These effects were also compared with that of a placebo. The ability of ascorbic acid to mitigate the effects of aspirin when administered either half an hour before or after dosage with aspirin was also assessed in 19 healthy female volunteers. The excretion of lactulose over the 6-hr period was augmented after consumption of either aspirin or ascorbic acid compared with that after consumption of placebo. Dosage with ascorbic acid alone augmented the excretion of lactulose more than did aspirin alone. Simultaneous dosage with both agents augmented the excretion of lactulose in an additive manner. The timing of dosage with ascorbic acid in relation to that with aspirin had no significant effect on the excretion of the two sugars. These findings indicate that ascorbic acid does not prevent aspirin-induced increase in gut permeability rather that both agents augment it to a similar extent. The additive effect on simultaneous dosage with both agents in augmenting the absorption of lactulose suggests that each influences paracellular permeability by different pathways. PMID:25641731

  18. Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats

    SciTech Connect

    Fuhrman-Lane, C.; Fujimoto, J.M.

    1982-09-01

    The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

  19. Effects of lunar soil, Zagami meteorite, and ocean ridge basalt on the excretion of itoic acid, a siderophore, and coproporphyrin by Bacillus subtilis

    NASA Technical Reports Server (NTRS)

    Ito, T.

    1986-01-01

    Samples of lunar soil (10084,151), Zagami meteorite, postulated to be ejected from Mars, and ocean ridge basalt, the most abundant volcanic rock on earth, all completely inhibited the excretion of itoic acid and of coproporphyrin by Bacillus subtilis, a common airborne bacterium. Since such inhibition has been known to occur only under iron rich growth conditions(the excretion of these compounds occurs under iron deficient growth conditions), the result indicated that the organism was capable of extracting iron quite readily from these materials. A sample of synthetic ilmenite completely failed to inhibit the excretion of coproporphyrin, and inhibited the excretion of itoic acid only slightly. The result suggested that much of the iron extracted by the organism must have come from iron sources other than ilmenite,such as pyroxenes and olivines,in these natural materials tested.

  20. Urinary excretion of 5-hydroxy-3-indoleacetic acid in dystimic/depressed, adult obese women: what correlations to hepatic steatosis?

    PubMed

    Tarantino, Giovanni; Savastano, S; Colao, A; Polichetti, G; Capone, D

    2011-01-01

    The synthesis of serotonin at CNS level is influenced by diet. Moreover, insulin resistance is associated with lower serotonin levels. Visceral obesity, strictly linked to hepatic steatosis is specifically associated with mild to severe somatic affective-depressive symptom clusters. Previous data support the view that depression involves serotonergic systems, reflecting low levels of urinary 5- hydroxy-3-indoleacetic acid (5-HIAA). The 24-h urinary excretion of 5-HIAA was evaluated in 76 dystimic/depressed, obese/overweight females, divided into two groups, i.e., on a hyper-caloric diet, associated with a life style characterized by leisure time sedentary behavior (LTSB, 35 women), or on a normo-caloric diet, assisted by program-based strategies aimed at promoting physical activity participation (PAP, 41 women). Beck Depression Inventory (BDI) was carried out to score the severity of dystimia/depression. Anthropometric measures, metabolic indices, severity of hepatic steatosis at sonography and HOMA were studied. Urinary levels of 5-HIAA in controls and PAP groups were comparable with a great overlap, while in the LTSB group the urinary excretion of 5-HIAA was significantly reduced in respect to that of the PAP group and obviously compared to that of the control group, 3.4±1.4 mg/L versus 6.2±2.7 mg/L and 6.4±2.6 mg/L, respectively, ANOVA test, P= 0.001. Among metabolic indices, cholesterol, HDL-cholesterol, triglycerides and uric acid were not able to predict urinary concentrations of 5-HIAA, which were not associated with hepatic steatosis; vice versa, ferritin levels, and mainly HOMA values, were independent predictors of the urinary excretion of 5-HIAA (β=0.235 and 0.45, respectively). Dystimia/depression severity was negatively predicted by urinary 5-HIAA levels in the sense that the highest BDI values were forecast by the lowest values of urinary 5-HIAA (β= -0.72).The importance of measuring the 24-h urinary excretion of 5-HIAA in follow-ups could rely

  1. Low urine pH and acid excretion do not predict bone fractures or the loss of bone mineral density: a prospective cohort study

    PubMed Central

    2010-01-01

    Background The acid-ash hypothesis, the alkaline diet, and related products are marketed to the general public. Websites, lay literature, and direct mail marketing encourage people to measure their urine pH to assess their health status and their risk of osteoporosis. The objectives of this study were to determine whether 1) low urine pH, or 2) acid excretion in urine [sulfate + chloride + 1.8x phosphate + organic acids] minus [sodium + potassium + 2x calcium + 2x magnesium mEq] in fasting morning urine predict: a) fragility fractures; and b) five-year change of bone mineral density (BMD) in adults. Methods Design: Cohort study: the prospective population-based Canadian Multicentre Osteoporosis Study. Multiple logistic regression was used to examine associations between acid excretion (urine pH and urine acid excretion) in fasting morning with the incidence of fractures (6804 person years). Multiple linear regression was used to examine associations between acid excretion with changes in BMD over 5-years at three sites: lumbar spine, femoral neck, and total hip (n = 651). Potential confounders controlled included: age, gender, family history of osteoporosis, physical activity, smoking, calcium intake, vitamin D status, estrogen status, medications, renal function, urine creatinine, body mass index, and change of body mass index. Results There were no associations between either urine pH or acid excretion and either the incidence of fractures or change of BMD after adjustment for confounders. Conclusion Urine pH and urine acid excretion do not predict osteoporosis risk. PMID:20459740

  2. Increased urinary excretion of toxic hydrazino metabolites of isoniazid by slow acetylators. Effect of a slow-release preparation of isoniazid.

    PubMed

    Peretti, E; Karlaganis, G; Lauterburg, B H

    1987-01-01

    To test the hypothesis that slow acetylators, who may have a greater risk of developing isoniazid hepatitis than rapid acetylators, are exposed to more acetylhydrazine and hydrazine, two toxic metabolites of isoniazid, the urinary excretion of hydrazino metabolites of isoniazid was measured following the ingestion of 300 mg isoniazid. Slow acetylators (n = 7) excreted significantly more isoniazid (32.4 vs 9.2% dose), acetylhydrazine (3.1 vs 1.6% dose), and hydrazine (1.0 vs 0.4% dose) in 24 h than rapid acetylators (n = 5), whereas the excretion of acetylisoniazid and diacetylhydrazine was significantly lower. As the acetylation (i.e. detoxification) of acetylhydrazine is inhibited in the presence of high concentrations of isoniazid, a study was also made of the effect of a slow-release preparation that results in lower plasma concentrations of isoniazid on the production of hydrazino metabolites. The ratio of acetylisoniazid to isoniazid in urine was significantly increased in slow acetylators from 0.84 to 1.02 following administration of the slow release preparation, indicating increased acetylation of isoniazid. However, the excretion of diacetylhydrazine relative to the excretion of acetylhydrazine and hydrazine did not change. It is concluded that exposure to toxic metabolites of isoniazid is increased in slow acetylators. Detoxification of the toxic metabolites was not enhanced by a slow-release preparation of isoniazid. PMID:3691615

  3. Activation of the Ca2+-sensing receptor increases renal claudin-14 expression and urinary Ca2+ excretion

    PubMed Central

    Dimke, Henrik; Desai, Prajakta; Borovac, Jelena; Lau, Alyssa; Pan, Wanling; Alexander, R. Todd

    2016-01-01

    Kidney stones are a prevalent clinical condition imposing a large economic burden on the health-care system. Hypercalciuria remains the major risk factor for development of a Ca2+-containing stone. The kidney’s ability to alter Ca2+ excretion in response to changes in serum Ca2+ is in part mediated by the Ca2+-sensing receptor (CaSR). Recent studies revealed renal claudin-14 (Cldn14) expression localized to the thick ascending limb (TAL) and its expression to be regulated via the CaSR. We find that Cldn14 expression is increased by high dietary Ca2+ intake and by elevated serum Ca2+ levels induced by prolonged 1,25-dihydroxyvitamin D3 administration. Consistent with this, activation of the CaSR in vivo via administration of the calcimimetic cinacalcet hydrochloride led to a 40-fold increase in Cldn14 mRNA. Moreover, overexpression of Cldn14 in two separate cell culture models decreased paracellular Ca2+ flux by preferentially decreasing cation permeability, thereby increasing transepithelial resistance. These data support the existence of a mechanism whereby activation of the CaSR in the TAL increases Cldn14 expression, which in turn blocks the paracellular reabsorption of Ca2+. This molecular mechanism likely facilitates renal Ca2+ losses in response to elevated serum Ca2+. Moreover, dys-regulation of the newly described CaSR-Cldn14 axis likely contributes to the development of hypercalciuria and kidney stones. PMID:23283989

  4. Hyaluronic acid is increased in the skin and urine in patients with amyotrophic lateral sclerosis

    NASA Technical Reports Server (NTRS)

    Ono, S.; Imai, T.; Yamauchi, M.; Nagao, K.

    1996-01-01

    We performed morphological studies of skin and measured glycosaminoglycans in the urine from patients with sporadic amyotrophic lateral sclerosis (ALS) and control subjects. The wide spaces separating collagen bundles reacted strongly with alcian blue stain in ALS patients and stained more markedly as ALS progressed. Staining with alcian blue was virtually eliminated by Streptomyces hyaluronidase. The urinary excretion of hyaluronic acid (HA) (mg/day) was significantly increased (P < 0.01) in ALS patients compared with that of control subjects, and there was a significant positive correlation between the excreted amount of HA and the duration of illness in advanced ALS patients with a duration of more than 2 years from clinical onset (r = 0.72, P < 0.02). We suggest that sporadic ALS includes a metabolic disorder of HA in which an accumulation of HA in the skin is linked to an increased urinary excretion of HA.

  5. Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats

    PubMed Central

    Paßlack, Nadine; Schmiedchen, Bettina; Raila, Jens; Schweigert, Florian J.; Stumpff, Friederike; Kohn, Barbara; Neumann, Konrad; Zentek, Jürgen

    2016-01-01

    Background Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. Results Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D2 and 25(OH)D3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). Conclusions In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P. PMID:26870965

  6. A Rosemary Extract Rich in Carnosic Acid Selectively Modulates Caecum Microbiota and Inhibits β-Glucosidase Activity, Altering Fiber and Short Chain Fatty Acids Fecal Excretion in Lean and Obese Female Rats

    PubMed Central

    Larrosa, Mar; Obiol, María; García-Villalba, Rocío; González-Barrio, Rocío; Issaly, Nicolas; Flanagan, John; Roller, Marc; Tomás-Barberán, Francisco A.; García-Conesa, María-Teresa

    2014-01-01

    Background Carnosic acid (CA) and rosemary extracts (RE) show body-weight, energy metabolism and inflammation regulatory properties in animal models but the mechanisms are not yet understood. Gut microbiota plays an important role in the host metabolism and inflammatory status and is modulated by the diet. The aim of this research was to investigate whether a RE enriched in CA affected caecum microbiota composition and activity in a rat model of genetic obesity. Methods and Principal Findings A RE (40% CA) was administered with the diet (0.5% w/w) to lean (fa/+) and obese (fa/fa) female Zucker rats for 64 days. Changes in the microbiota composition and β-glucosidase activity in the caecum and in the levels of macronutrients and short chain fatty acids (SCFA) in feces were examined. The RE increased the Blautia coccoides and Bacteroides/Prevotella groups and reduced the Lactobacillus/Leuconostoc/Pediococccus group in both types of animals. Clostridium leptum was significantly decreased and Bifidobacterium increased only in the lean rats. β-Glucosidase activity was significantly reduced and fecal fiber excretion increased in the two genotypes. The RE also increased the main SCFA excreted in the feces of the obese rats but decreased them in the lean rats reflecting important differences in the uptake and metabolism of these molecules between the two genotypes. Conclusions Our results indicate that the consumption of a RE enriched in CA modifies microbiota composition and decreases β-glucosidase activity in the caecum of female Zucker rats while it increases fiber fecal elimination. These results may contribute to explain the body weight gain reducing effects of the RE. The mutated leptin receptor of the obese animals significantly affects the microbiota composition, the SCFA fecal excretion and the host response to the RE intake. PMID:24733124

  7. Effect of cisplatin treatment on the urinary excretion of guanidinoacetic acid, creatinine and creatine in patients with urinary tract neoplasm, and on superoxide generation in human neutrophils.

    PubMed

    Yasuda, M; Sugahara, K; Zhang, J; Shuin, T; Kodama, H

    2000-01-01

    Production of guanidinoacetic acid, a precursor of creatinine is known to be reduced by metabolic disturbance when kidney function is damaged, and thus it may be a sensitive marker of renal damage. Therefore, the urinary levels of guanidinoacetic acid, creatinine and creatine from patients with urinary tract neoplasm who received cisplatin treatment were measured by liquid chromatography-mass spectrometry. Following the administration of cisplatin, the urinary excretion of guanidinoacetic acid decreased significantly, and the low concentration was maintained for at least five days. The concentrations of creatinine and creatine gradually decreased until the third day after cisplatin administration, and slightly increased on the fifth day. As superoxide might be concerned in renal damage by cisplatin, the effect of cisplatin on superoxide generation was also investigated using human neutrophils. Cisplatin significantly enhanced phorbol 12-myristate 13-acetate-induced superoxide generation in a concentration-dependent manner, but had no effect on the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine and arachidonic acid. The superoxide generation increased by cisplatin was inhibited by staurosporine, an inhibitor of protein kinase C, but was rather enhanced by genistein, an inhibitor of protein tyrosine kinase. PMID:11383133

  8. The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats.

    PubMed

    Ma, Feng-Wei; Deng, Qing-Fang; Zhou, Xin; Gong, Xiao-Jian; Zhao, Yang; Chen, Hua-Guo; Zhao, Chao

    2016-01-01

    In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study. PMID:27023501

  9. Urine albumin excretion, within normal range, reflects increasing prevalence of metabolic syndrome in patients with essential hypertension.

    PubMed

    Vyssoulis, Gregory; Karpanou, Eva; Spanos, Pangiotis; Kyvelou, Stella-Maria; Adamopoulos, Dionysios; Stefanadis, Christodoulos

    2010-08-01

    Microalbuminuria is a prognostic marker of cardiovascular disease and is related to metabolic syndrome (MetS). For this purpose, the authors examined the relationship of low grade albuminuria to MetS, using 4 current definitions and a MetS score. They studied 6650 consecutive, nondiabetic, hypertensive patients with normal microalbumin excretion. MetS was defined by Adult Treatment Panel III, American Heart Association, World Heart Organization, International Diabetes Federation criteria, and MetS Gruppo Italiano per lo Studio della Streptochinasi nell'Infarcto Miocardico (GISSI) score. Urine microalbumin concentration was measured after a 24-hour urine collection by immunonephelometry. By all definitions, hypertensive patients with MetS had higher microalbumin levels. Significantly higher microalbumin levels were observed as the number of metabolic components rose. After adjustment for systolic blood pressure, the strength of this association was reduced to a nonsignificant level. Microalbumin levels, within normal range, are increased in patients with MetS, irrespective of the definition criteria. PMID:20695936

  10. Elevated cholinesterase activity and increased urinary excretion of inorganic fluorides in the workers producing fluorine-containing plastic (polytetrafluoroethylene)

    SciTech Connect

    Baohui Xu |; Jiusun Zhang; Guaogeng Mao; Guifen Yang; Aini Chen; Aoyama, Kohji; Matsushita, Toshio; Ueda, Atsushi

    1992-07-01

    Fluoropolymers are widely used in thermal and electrical industries. Polytetrafluoroethylene (PTFE) plastic is a typical one. During its production, workers are occupationally exposed to many organic fluorides, especially tetrafluoroethylene, chlorodifluoromethane, PTFE and its thermal decomposition products. Of these compounds, it has been documented that following inhalation of combustion products of PTFE the focal hemorrhages, edema, fibrin deposition in lungs and renal infarcts were observed in rats. Odum and Green have demonstrated a marked damage to proximal tubule of kidney with no effects on the liver in rats exposed to 6000 ppm tetrafluoroethylene for 6 hr. The investigations of the hazards of these compounds to workers have been mainly focused on acute toxicity. There have been some reports that polymers and its pyrolysis caused polymer fume fever and pulmonary edema. In practice, workers engaged in PTFE manufacture are chronically exposed to the above-mentioned chemicals, but little was known about the hazards ascribed to these chemicals. To clarify the influences of the exposed chemicals on health in PTFE production we conducted a mass survey investigation in a PTFE production factory. As a result, in addition to the nephrotoxicity characterized by elevated ALP and NAG activities in urine, more interestingly, we have also found a reversible increase in cholinesterase (ChE) activity and enhanced urinary excretion of inorganic fluorides in workers engaged in PTFE production. We report here these findings and discuss their physiological significance. 18 refs., 4 tabs.

  11. Bile acid production in human subjects: rate of oxidation of (24,25-/sup 3/H)cholesterol compared to fecal bile acid excretion

    SciTech Connect

    Davidson, N.O.; Bradlow, H.L.; Ahrens, E.H. Jr.; Rosenfeld, R.S.; Schwartz, C.C.

    1986-02-01

    Bile acid production has been quantitated in seven subjects by methods that compare the results of two independent approaches, namely, quantitation of cholesterol side-chain oxidation and fecal bile acid excretion. Six hypertriglyceridemic (HT) subjects and one normolipidemic control were studied by both techniques. A further control subject was studied by the cholesterol side-chain oxidation method alone. Cholesterol side-chain oxidation was quantitated by measuring the appearance of /sup 3/H/sub 2/O after intravenous administration of (24,25-/sup 3/H)cholesterol, using multicompartmental analysis of plasma cholesterol and (/sup 3/H)water specific activity. Body water kinetics were independently defined by use of oral D/sub 2/O. Two HT subjects were restudied while they were taking cholestyramine, 16 g/day. In all ten studies, multicompartmental analysis closely simulated the observed appearance of /sup 3/H/sub 2/O. Values obtained for bile acid production suggest that cholesterol oxidation, or bile acid input, was significantly greater than fecal bile acid output in the HT subjects (P less than 0.05). Cholesterol side-chain oxidation rates in the two normal subjects were lower than those encountered in HT subjects, being similar to published values for normal subjects both for bile acid synthesis as determined by isotope dilution kinetics and fecal bile acid excretion. Studies conducted with two, synthetically different, preparations of (24,25-/sup 3/H)cholesterol indicated that, in one of the two preparations, approximately 20% of the tritium label was at positions proximal to C24. In the other preparation examined, all of the tritium was located at, or distal to, C24. Further studies revealed that 0.055-0.24% of the dose was present as labile tritium by virtue of its appearance as /sup 3/H/sub 2/O following in vitro incubation with human plasma. (Abstract Truncated)

  12. Assessing accumulation and biliary excretion of naphthenic acids in yellow perch exposed to oil sands-affected waters.

    PubMed

    van den Heuvel, Michael R; Hogan, Natacha S; MacDonald, Gillian Z; Berrue, Fabrice; Young, Rozlyn F; Arens, Collin J; Kerr, Russell G; Fedorak, Phillip M

    2014-01-01

    Naphthenic acids are known to be the most prevalent group of organic compounds in oil sands tailings-associated waters. Yellow perch (Perca flavescens) were exposed for four months to oil sands-influenced waters in two experimental systems located on an oil sands lease 30 km north of Fort McMurray Alberta: the Demonstration Pond, containing oil sands tailings capped with natural surface water, and the South Bison Pond, integrating lean oil sands. Yellow perch were also sampled from three lakes: Mildred Lake that receives water from the Athabasca River, Sucker Lake, at the edge of oil sands extraction activity, and Kimowin Lake, a distant reference site. Naphthenic acids were measured in perch muscle tissue using gas chromatography-mass spectrometry (GC-MS). Bile metabolites were measured by GC-MS techniques and by high performance liquid chromatography (HPLC) with fluorescence detection at phenanthrene wavelengths. A method was developed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) to evaluate naphthenic acids in bile. Tissue analysis did not show a pattern of naphthenic acids accumulation in muscle tissue consistent with known concentrations in exposed waters. Bile fluorescence and LC-HRMS methods were capable of statistically distinguishing samples originating from oil sands-influenced waters versus reference lakes. Although the GC-MS and HPLC fluorescence methods were correlated, there were no significant correlations of these methods and the LC-HRMS method. In yellow perch, naphthenic acids from oil sands sources do not concentrate in tissue at a measurable amount and are excreted through a biliary route. LC-HRMS was shown to be a highly sensitive, selective and promising technique as an indicator of exposure of biota to oil sands-derived naphthenic acids. PMID:24182406

  13. B vitamin supplementation reduces excretion of urinary dicarboxylic acids in autistic children.

    PubMed

    Kałużna-Czaplińska, Joanna; Socha, Ewa; Rynkowski, Jacek

    2011-07-01

    Urinary dicarboxylic acids are an important source of information about metabolism and potential problems especially connected with energy production, intestinal dysbiosis, and nutritional individuality in autistic children. A diet rich in vitamins and macroelements is a new idea of intervention in autism. The objective of the present study was to test the hypothesis that vitamin B2, vitamin B6, and magnesium supplementation is effective in reducing the level of dicarboxylic acids in the urine of autistic children. We examined the levels of succinic, adipic, and suberic acids in the urine of autistic children before and after vitamin supplementation. Thirty children with autism received magnesium (daily dose, 200 mg), vitamin B6 (pyridoxine; daily dose, 500 mg), and vitamin B2 (riboflavin; daily dose, 20 mg). The treatment was provided for a period of 3 months. Organic acids were determined using gas chromatography/mass spectrometry. Before supplementation, the levels of succinic, adipic, and suberic acids in the urine of autistic children were 41.47 ± 50.40 μmol/mmol creatinine, 15.61 ± 15.31 μmol/mmol creatinine, 8.02 ± 6.08 μmol/mmol creatinine; and after supplementation, the levels were 9.90 ± 8.26 μmol/mmol creatinine, 2.92 ± 2.41 μmol/mmol creatinine, and 2.57 ± 3.53 μmol/mmol creatinine, respectively. The results suggest that the supplementation reduces the level of dicarboxylic acid in the urine of autistic children. PMID:21840465

  14. Absorption and excretion of 14C-perfluorooctanoic acid (PFOA)in angus cattle (Bos taurus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perfluorinated chemicals (PFCs), such as perfluorooctanoic acid (PFOA), are environmentally persistent industrial chemicals often found in biosolids. Application of these biosolids to pastures raises concern about accumulation of PFOA in the edible tissues of food animals. Because data on the absorp...

  15. Absorption and excretion of 14C- perfluorooctanoic acid (PFOA) in beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are industrial chemicals that are environmentally persistent. PFOS has recently been classified as a persistent organic pollutant under the Stockholm Convention. Both PFOS and PFOA can be found in biosolids, and the application of c...

  16. Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats.

    PubMed

    Shao, Weijian; Miyata, Kayoko; Katsurada, Akemi; Satou, Ryousuke; Seth, Dale M; Rosales, Carla B; Prieto, Minolfa C; Mitchell, Kenneth D; Navar, L Gabriel

    2016-08-01

    In angiotensin II (ANG II)-dependent hypertension, there is an angiotensin type 1 receptor-dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion in the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of two-kidney, one-clip Sprague-Dawley hypertensive rats subjected to left renal arterial clipping (0.25-mm gap). By 18-21 days, systolic arterial pressure increased to 180 ± 3 mmHg, and uAGT increased. Water intake, body weights, 24-h urine volumes, and sodium excretion were similar. In separate measurements of renal function in anesthetized rats, renal plasma flow and glomerular filtration rate were similar in clipped and nonclipped kidneys and not different from those in sham rats, indicating that the perfusion pressure to the clipped kidneys remained within the autoregulatory range. The nonclipped kidneys exhibited increased urine flow and sodium excretion. The uAGT excretion was significantly greater in nonclipped kidneys compared with clipped and sham kidneys. AGT mRNA was 2.15-fold greater in the nonclipped kidneys compared with sham (1.0 ± 0.1) or clipped (0.98 ± 0.15) kidneys. AGT protein levels were also greater in the nonclipped kidneys. The nonclipped kidneys exhibited greater glomerular expansion and immune cell infiltration, medullary fibrosis, and cellular proliferation than the clipped kidneys. Because both kidneys have elevated ANG II levels, the greater tissue injury in the nonclipped kidneys indicates that an increased arterial pressure synergizes with increased intrarenal ANG II to stimulate AGT production and exert greater renal injury. PMID:27194718

  17. Bilirubin conjugates of human bile. The excretion of bilirubin as the acyl glycosides of aldobiouronic acid, pseudoaldobiouronic acid and hexuronosylhexuronic acid, with a branched-chain hexuronic acid as one of the components of hexuronosylhexuronide

    PubMed Central

    Kuenzle, Clive C.

    1970-01-01

    Structure elucidations have been performed on the bilirubin conjugates isolated from human hepatic bile as the phenylazo derivatives. The major bilirubin conjugates are excreted, not as was formerly thought in the form of glucuronides, but as the acyl glycosides of aldobiouronic acid, pseudoaldobiouronic acid and hexuronosylhexuronic acid. The isolated aldobiouronides are proposed to have the structures of an acyl 6-O-hexopyranosyluronic acid-hexopyranoside, an acyl 4-O-hexofuranosyluronic acid-d-glucopyranoside, and an acyl 4-O-β-d-glucofuranosyluronic acid-d-glucopyranoside respectively, with the acyl radicals being those of the phenylazo derivative of bilirubin. The pseudoaldobiouronide is suggested to be the acyl 4-O-α-d-glucofuranosyl-β-d -glucopyranosiduronic acid, with the acyl radical being that of the phenylazo derivative of vinylneoxanthobilirubinic acid. The hexuronosylhexuronide presumably is the acyl 4-O-(3-C-hydroxymethylribofuranosyluronic acid)-β-d-glucopyranosiduronic acid, with the acyl radical being that of the phenylazo derivative of bilirubin. The 3-C-hydroxymethylriburonic acid, isolated as one of the components of the hexuronosylhexuronide, is the first natural branched-chain hexuronic acid to be detected, and the first branched-chain sugar ever detected in humans. PMID:5500303

  18. Polychlorinated Biphenyl Congeners that Increase the Glucuronidation and Biliary Excretion of Thyroxine Are Distinct from the Congeners that Enhance the Serum Disappearance of Thyroxine

    PubMed Central

    Martin, L. A.; Wilson, D. T.; Reuhl, K. R.; Gallo, M. A.

    2012-01-01

    Polychlorinated biphenyl (PCB) congeners differentially reduce serum thyroxine (T4) in rats, but little is known about their ability to affect biliary excretion of T4. Thus, male Sprague-Dawley rats were orally administered Aroclor-1254, Aroclor-1242 (32 mg/kg per day), PCB-95, PCB-99, PCB-118 (16 mg/kg per day), PCB-126 (40 μg/kg per day), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (3.9 μg/kg per day), or corn oil for 7 days. Twenty-four hours after the last dose, [125I]T4 was administered intravenously, and blood, bile, and urine samples were collected for quantifying [125I]T4 and in bile [125I]T4 metabolites. Serum T4 concentrations were reduced by all treatments, but dramatic reductions occurred in response to Aroclor-1254, PCB-99 [phenobarbital (PB)-type congener], and PCB-118 (mixed-type congener). None of the treatments increased urinary excretion of [125I]T4. Aroclor-1254, PCB-118, TCDD, and PCB-126 (TCDD-type congener) increased biliary excretion of T4-glucuronide by 850, 756, 710, and 573%, respectively, corresponding to marked induction of hepatic UDP-glucuronosyltransferase (UGT) activity toward T4. PCB-95 and PCB-99 did not induce UGT activity; therefore, the increased biliary excretion of T4-glucuronide was related to the affinity of congeners for the aryl hydrocarbon receptor. The disappearance of [125I]T4 from serum was rapid (within 15-min) and was increased by Aroclor-1254, PCB-99 and PCB-118. Thus, reductions in serum T4 in response to PCBs did not always correspond with UGT activity toward T4 or with increased biliary excretion of T4-glucuronide. The rapid disappearance of [125I]T4 from the serum of rats treated with PB-like PCBs suggests that increased tissue uptake of T4 is an additional mechanism by which PCBs may reduce serum T4. PMID:22187485

  19. A model to produce pure zinc deficiency in rats and its use to demonstrate that dietary phytate increases the excretion of endogenous zinc.

    PubMed

    Flanagan, P R

    1984-03-01

    An early effect of zinc deficiency in rats is loss of appetite with consequent malnourishment. To obviate the need for pair-feeding, rats were fed liquid semipurified diets by gastric tube feeding. Rats tube fed a zinc-deficient diet at a daily rate of 90-110 g/kg thrived for 6-7 days and then rapidly became seriously ill. In contrast rats fed the deficient diet ad libitum stopped growing after 3 days but remained relatively healthy. Animals tube fed a zinc-replete diet or the deficient diet with subcutaneous injections of zinc grew normally and suffered no ill effects. Rats tube fed the deficient diet and supplemented parenterally with zinc excreted significantly more endogenous zinc into small intestinal luminal washings and into feces than unsupplemented rats. Sodium phytate, added to the tube feed in three groups of rats fed the deficient diet and supplemented daily with 0, 0.33 and 3.3 mg Zn/kg, significantly increased the zinc content of luminal washings in all three groups, increased fecal zinc excretion in two groups and lowered body zinc levels, estimated by femur zinc, in two groups. Tube feeding provides a means to study: 1) pure zinc deficiency without malnourishment of other nutrients; and 2) the excretion of endogenous zinc into the gastrointestinal tract. PMID:6422015

  20. Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers.

    PubMed

    Corsetti, Roberto; Barassi, Alessandra; Perego, Silvia; Sansoni, Veronica; Rossi, Alessandra; Damele, Clara Anna Linda; Melzi D'Eril, Gianlodovico; Banfi, Giuseppe; Lombardi, Giovanni

    2016-01-01

    The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis. PMID:26306846

  1. INCREASED LEVELS OF MEDIAN URINARY IODINE EXCRETION OF PRIMARY SCHOOL CHILDREN IN THE SUBURBAN AREA, KHON KAEN, THAILAND.

    PubMed

    Apirajkamol, Nahatai; Panamonta, Ouyporn; Panamonta, Manat

    2016-01-01

    Iodine deficiency disorder (IDD) is associated with a low IQ in children and is an important public health problem in northeastern Thailand. Despite campaigns to reduce IDD in northeastern Thailand, studies showed people in this region continue to have the lowest median urinary iodine (UI) excretion and Intelligence Quotient scores. We conducted a cross sectional study of median urinary iodine excretion among primary school children in suburban Khon Kaen Province, in northeastern Thailand, during December 2012 to evaluate the current status of IDD in this population. We studied 377 school children. Urine samples were collected and measured for UI using a simple microplate method. The median UI level was 229.0 μg/l (range 15.0-1,124.1). Forty school children (10.6%) had UI levels less than 100 μg/l and 10 children (2.7%) had UI levels less than 50 μg/l. One hundred nine children (28.9%) had UI levels greater than 300 μg/l. Our study shows that there are still children in the study population and study area with inadequate UI levels. Programs to prevent IDD need to include this population in this area. PMID:27086431

  2. Exercise and a High Fat Diet Synergistically Increase the Pantothenic Acid Requirement in Rats.

    PubMed

    Takahashi, Kei; Fukuwatari, Tsutomu; Shibata, Katsumi

    2015-01-01

    It is thought that both exercise and dietary composition increase the utilization of, and thus the requirement for, certain water-soluble vitamins. However, there have been no studies evaluating the combined impacts of exercise and dietary composition on vitamin utilization. In this experiment, rats were fed a pantothenic acid (PaA)-restricted (0.004 g PaA-Ca/kg diet) diet containing 5% (ordinary amount of dietary fat) or 20% fat (high fat), and were forced to swim until exhaustion every other day for 22 d. PaA status was assessed by urinary excretion, which reflects body stores of water-soluble vitamins. The urinary excretion of PaA in rats fed a 5% fat diet was not affected by swimming (5% fat + non-swimming vs. 5% fat + swim; p>0.05). Excretion of PaA was decreased by the high-fat diet (5% fat + non-swim vs. 20% fat + non-swim; p<0.05) and synergistically decreased by exercise (20% fat + non-swim vs. 20% fat + swim; p<0.05). There was a significant interaction between exercise and a high-fat diet. Plasma PaA concentrations showed changes similar to those seen for urinary excretion. The experiment was then repeated using rats fed a PaA-sufficient (0.016 g PaA-Ca/kg diet) diet, and PaA excretion was again synergistically decreased by the combination of exercise and a high-fat diet (p<0.05). These results suggest that the combination of exercise and a high-fat diet synergistically increases the requirement for PaA. PMID:26226957

  3. Mineral phosphate solubilization by Streptomyces sp. CTM396 involves the excretion of gluconic acid and is stimulated by humic acids.

    PubMed

    Farhat, Mounira Ben; Boukhris, Ines; Chouayekh, Hichem

    2015-03-01

    The actinomycetes isolates (128) which were taken from agricultural soil samples and collected near a rock phosphate processing unit were screened for mineral phosphate-solubilizing (MPS) ability. A significant MPS activity was observed for 30 isolates on various phosphate sources when grown in the National Botanical Research Institute's phosphate broth. CTM396 and CTM397 strains which showed the highest MPS abilities were identified by 16S rDNA sequencing as members of the genus Streptomyces. Their MPS activity was proved to be concomitant with a drop in pH due to the secretion of gluconic acid (GA). This was correlated with the simultaneous detection by PCR of genes gdh [encoding the glucose dehydrogenase (GDH) responsible for GA production from glucose] and pqq (involved in biosynthesis of the pyrroloquinoline quinone cofactor of GDH), as well as the highlighting of GHD enzyme activity, for the first time in a Streptomyces sp. strain producing GA. Furthermore, the 0.05% of humic acids proved to have a stimulatory effect on the growth and the ability of CTM396 to solubilize Gafsa rock phosphate. According to this study, it is possible to use humic acids and Gafsa rock phosphate in association with spores of ad hoc Streptomyces strains as natural and efficient amendments to improve plant growth with no need of costly and pollutant transformation of Gafsa rock phosphate. PMID:25743071

  4. A Polysaccharide from Ganoderma atrum Improves Liver Function in Type 2 Diabetic Rats via Antioxidant Action and Short-Chain Fatty Acids Excretion.

    PubMed

    Zhu, Ke-Xue; Nie, Shao-Ping; Tan, Le-He; Li, Chuan; Gong, De-Ming; Xie, Ming-Yong

    2016-03-01

    The present study was to evaluate the beneficial effect of polysaccharide isolated from Ganoderma atrum (PSG-1) on liver function in type 2 diabetic rats. Results showed that PSG-1 decreased the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), while increasing hepatic glycogen levels. PSG-1 also exerted strong antioxidant activities, together with upregulated mRNA expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), glucose transporter-4 (GLUT4), phosphoinositide 3-kinase (PI3K), and phosphorylated-Akt (p-Akt) in the liver of diabetic rats. Moreover, the concentrations of short-chain fatty acids (SCFA) were significantly higher in the liver, serum, and faeces of diabetic rats after treating with PSG-1 for 4 weeks. These results suggest that the improvement of PSG-1 on liver function in type 2 diabetic rats may be due to its antioxidant effects, SCFA excretion in the colon from PSG-1, and regulation of hepatic glucose uptake by inducing GLUT4 translocation through PI3K/Akt signaling pathways. PMID:26898215

  5. [Effect of a diet containing calcium pantothenate on urinary vitamin excretion and on the liver and kidney total pantothenic acid level in rats].

    PubMed

    Lhuissier, M; Bringer, M

    1988-01-01

    Four groups of five adult rats weighing 310 g received during 20 days a diet containing 0, 1.68, 16.8 or 168 mumol of pantothenic acid per kg of diet. The daily urinary vitamin excretion was, in nmol per day: 32 +/- 8, 32 +/- 4, 180 +/- 23 and 2,100 +/- 91, respectively (mean +/- SEM). Liver and kidney pantothenic acid content was the same in all groups, in nmol per g of fresh tissue: 300 +/- 36 and 190 +/- 6, respectively (mean +/- SEM, n = 20). PMID:2978017

  6. Established dietary estimates of net acid production do not predict measured net acid excretion in patients with Type 2 diabetes on Paleolithic-Hunter-Gatherer-type diets

    PubMed Central

    Frassetto, Lynda A; Shi, Lijie; Schloetter, Monique; Sebastian, Anthony; Remer, Thomas

    2014-01-01

    Background Formulas developed to estimate diet-dependent net acid excretion (NAE) generally agree with measured values for typical Western diets. Whether they can also appropriately predict NAE for "Paleolithic-type" (Paleo) diets – which contain very high amounts of fruits and vegetables (F&V) and concurrent high amounts of protein is unknown. Here we compare measured NAEs with established NAE-estimates in subjects with Type 2 diabetes (T2D). Methods Thirteen subjects with well controlled T2D were randomized to either a Paleo or American Diabetes Association (ADA) diet for 14 days. 24-hour urine collections were performed at baseline and end of the diet period, and analyzed for titratable acid, bicarbonate, and ammonium to calculate measured NAE. Three formulas for estimating NAE from dietary intake were used; two (NAE_diet R or L) that include dietary mineral intake and sulfate- and organic acid (OA) production, and one that is empirically-derived (NAE_diet F) only considering potassium and protein intake. Results Measured NAE on the Paleo diet was significantly lower than on the ADA diet (+31±22 vs. 112±52 mEq/day, p=0.002). Although all formula estimates showed similar and reasonable correlations (r=0.52–0.76) with measured NAE, each one underestimated measured values. The formula with the best correlation did not contain an estimate of dietary organic acid production. Conclusions Paleo diets are lower in NAE than typical Western diets. However, commonly used formulas clearly underestimate NAE, especially for diets with very high F&V (as the Paleo diet), and in subjects with T2D. This may be due to an inappropriate estimation of proton loads stemming from OAs, underlining the necessity for improved measures of OA-related proton sources. PMID:23859996

  7. Pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) in the beagle dog and rhesus monkey: perspective on the reduced capacity of dogs to excrete this organic acid relative to the rat, monkey, and human.

    PubMed

    Timchalk, C; Nolan, R J

    1997-06-01

    The pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) were measured in the beagle dog and rhesus monkey and compared with the kinetics observed in rats and humans. In addition, studies were conducted in anesthetized dogs to better understand the mechanism by which [14C]triclopyr is eliminated in this species. Triclopyr was dissolved in distilled water, and administered as a single oral dose of 0.5, 5, or 20 mg/kg to three male dogs. A single male rhesus monkey was given an intravenous dose of 30 mg [14C]triclopyr/kg body wt on two occasions separated by 10 days. Anesthetized male dogs, were implanted with venous, arterial, and urethral catheters and given increasing amounts of triclopyr to produce plasma triclopyr levels ranging from 0.3 to 27 microg eq/mL. In the monkey, triclopyr was rapidly eliminated from the plasma (t1/2 = 6.3 hr) with >95% of the urinary 14C activity excreted within 24 hr postdosing. In the dog, orally administered triclopyr was rapidly and effectively absorbed at every dose level with virtually all of it excreted in the urine by 72 hr postdosing. However, the kinetics were slightly nonlinear, and the fraction of the dose excreted in the urine decreased with increasing dose. Several nonlinear processes may collectively contribute to the modest nonlinear pharmacokinetics in the dog. Plasma protein binding of triclopyr in the dog ranged from 94 to 99%, was nonlinear, and was an important determinant in the renal clearance of triclopyr. The nonlinear plasma protein binding indicates that glomerular filtration became disproportionately more important as plasma triclopyr concentration increased. There was good evidence for a high-affinity low-capacity active-secretory process that was saturated by low plasma triclopyr concentrations. As plasma triclopyr concentrations increased, tubular reabsorption begins to exceed secretion, resulting in decreased renal clearance. The volume of distribution, normalized for body weight

  8. Studies on the increase in serum concentrations of urea cycle amino acids among subjects exposed to cadmium

    SciTech Connect

    Nishino, H.; Shiroishi, K. ); Kagamimori, S.; Naruse, Y. ); Watanabe, M. )

    1988-05-01

    Itai-itai disease (I disease) is a combination of renal tubular damage and osteomalacia accompanied by osteoporosis among subjects exposed to cadmium (Cd). When the renal tubular damage progresses, the excretion of amino acids, especially, threonine, hydroxyproline, proline, citrulline, ornithine, arginine, etc. increase in urine. It was reported that the increase in urinary excretion of citrulline, arginine and ornithine may be associated with an inhibition of urea synthesis in the urea cycle. The authors have found that serum citrulline, arginine and ornithine also increased in I disease patients. In order to investigate the mechanism of the increase in these serum amino acids, comparative studies were performed using both healthy subjects and patients with renal disease as control groups.

  9. Studies on the increase in serum concentrations of urea cycle amino acids among subjects exposed to cadmium

    SciTech Connect

    Nishino, H.; Shiroishi, K.; Kagamimori, S.; Naruse, Y.; Watanabe, M.

    1988-04-01

    Itai-itai disease (I disease) is a combination of renal tubular damage and osteomalacia accompanied by osteoporosis among subjects exposed to cadmium (Cd). When the renal tubular damage progresses, the excretion of amino acids, especially, threonine, hydroxyproline, proline, citrulline, ornithine, arginine increased in urine. It has been reported that the increase in urinary excretion of citrulline, arginine and ornithine may be associated with an inhibition of urea synthesis in the urea cycle. The authors have found that serum citrulline, arginine and ornithine also increased in I disease patients. In order to investigate the mechanism of the increase in these serum amino acids, comparative studies were performed using both healthy subjects and patients with renal disease as control groups.

  10. Urinary excretion of the acrylonitrile metabolite 2-cyanoethylmercapturic acid is correlated with a variety of biomarkers of tobacco smoke exposure and consumption

    PubMed Central

    Minet, Emmanuel; Cheung, Francis; Errington, Graham; Sterz, Katharina; Scherer, Gerhard

    2011-01-01

    Acrylonitrile is an IARC class 2B carcinogen present in cigarette smoke. Urinary 2-cyanoethylmercapturic acid (CEMA) is an acrylonitrile metabolite and a potential biomarker for acrylonitrile exposure. The objective of this work was to study the dose response of CEMA in urine of non-smokers and smokers of different ISO tar yield cigarettes. We observed that smokers excreted >100-fold higher amounts of urinary CEMA than non-smokers. The CEMA levels in smokers were significantly correlated with ISO tar yield, daily cigarette consumption, and urinary biomarkers of smoke exposure. In conclusion, urinary CEMA is a suitable biomarker for assessing smoking-related exposure to acrylonitrile. PMID:21108560

  11. A New Episomic Element Controlling Fermentative Metabolism and Excretion of Amino Acids by Citrobacter intermedium C3

    PubMed Central

    Pares, R.; Guinea, J.; Hernandez, S.; Valoix, Josefina; Jofre, J.

    1974-01-01

    Glutamate excretion by colonies of Citrobacter intermedium C3 was detected by using the auxotrophic strain Leuconostoc mesenteroides P-60. A constant ratio of strain C3 colonies did not excrete glutamate. These colonies were subcultured, and colonial analysis of their descendants established that the change from non-excretor to excretor (Sg− → Sg+) is a spontaneous and random process with occurs at a high rate, and that an equilibrium state results from the back-transition Sg+ → Sg− in large populations. Acridine orange, ethidium bromide, and shaking have a strong influence on Sg+-to-Sg− interconversion, which suggests that a genetic element like an episome is implicated (S factor). Various auxotrophic mutants of bacterial strain C3 have been cured of the S factor. Strains lacking the S factor (S− strains) do not excrete glutamate and lose their fermentative metabolism completely. Consequently, the S factor is different from other extrachromosomal genetic factors whose elimination does not modify central metabolism. The gain of the S factor by infectious transfer has been shown with different C3 auxotrophic mutant strains. Also, the S factor has been transferred to Paracolobactrum intermedium ATCC 11606. These findings suggest that phenotypic changes observed are a consequence of elimination or infectious gain of the S factor, with its autonomous or integrated multiplication. PMID:4600693

  12. Potassium bicarbonate attenuates the urinary nitrogen excretion that accompanies an increase in dietary protein and may promote calcium absorption

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protein is an essential component of muscle and bone. However, the acidic byproducts of protein metabolism may have a negative impact on the musculoskeletal system particularly in older individuals with declining renal function. We sought to determine whether adding an alkaline salt, potassium bicar...

  13. Pentahaloethane-based chlorofluorocarbon substitutes and halothane: Correlation of in vivo hepatic protein trifluoroacetylation and urinary trifluoroacetic acid excretion with calculated enthalpies of activation

    SciTech Connect

    Harris, J.W.; Jones, J.P.; Martin, J.L.; LaRosa, A.C.; Olson, M.J.; Pohl, L.R.; Anders, M.W. )

    1992-09-01

    The hydrochlorofluorocarbons (HCFCs) 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) and 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124) and the hydrofluorocarbon (HFC) pentafluoroethane (HFC-125) are being developed as substitutes for chlorofluorocarbons that deplete stratospheric ozone. The structural similarity of these HCFCs and HFCs to halothane, which is hepatotoxic under certain circumstances, indicates that the metabolism and cellular interactions of HCFCs and HFCs must be explored. In a previous study [Harris et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1407], similar patterns of trifluoroacetylated proteins (TFA-proteins) were detected by immunoblotting with anti-TFA-protein antibodies in livers of rats exposed to halothane or HCFC-123. The present study extends these results and demonstrates that in vivo TFA-protein formation resulting from a 6-h exposure to a 1% atmosphere of these compounds follows the trend: halothane approximately HCFC-123 much greater than HFC-124, greater than HFC-125. The calculated enthalpies of activation of halothane, HCFC-123, HCFC-124, and HFC-125 paralleled the observed rate of trifluoroacetic acid excretion in HCFC- or HFC-exposed rats. Exposure of rats to a range of HCFC-123 concentrations indicated that TFA-protein formation was saturated at an exposure concentration between 0.01% and 0.1% HCFC-123. Deuteration of HCFC-123 decreased TFA-protein formation in vivo. Urinary trifluoroacetic acid excretion by treated rats correlated with the levels of TFA-proteins found after each of these treatments.

  14. Multiple functions of the crustacean gill: osmotic/ionic regulation, acid-base balance, ammonia excretion, and bioaccumulation of toxic metals

    PubMed Central

    Henry, Raymond P.; Lucu, Čedomil; Onken, Horst; Weihrauch, Dirk

    2012-01-01

    The crustacean gill is a multi-functional organ, and it is the site of a number of physiological processes, including ion transport, which is the basis for hemolymph osmoregulation; acid-base balance; and ammonia excretion. The gill is also the site by which many toxic metals are taken up by aquatic crustaceans, and thus it plays an important role in the toxicology of these species. This review provides a comprehensive overview of the ecology, physiology, biochemistry, and molecular biology of the mechanisms of osmotic and ionic regulation performed by the gill. The current concepts of the mechanisms of ion transport, the structural, biochemical, and molecular bases of systemic physiology, and the history of their development are discussed. The relationship between branchial ion transport and hemolymph acid-base regulation is also treated. In addition, the mechanisms of ammonia transport and excretion across the gill are discussed. And finally, the toxicology of heavy metal accumulation via the gill is reviewed in detail. PMID:23162474

  15. Urinary Adiponectin Excretion

    PubMed Central

    von Eynatten, Maximilian; Liu, Dan; Hock, Cornelia; Oikonomou, Dimitrios; Baumann, Marcus; Allolio, Bruno; Korosoglou, Grigorios; Morcos, Michael; Campean, Valentina; Amann, Kerstin; Lutz, Jens; Heemann, Uwe; Nawroth, Peter P.; Bierhaus, Angelika; Humpert, Per M.

    2009-01-01

    OBJECTIVE Markers reliably identifying vascular damage and risk in diabetic patients are rare, and reports on associations of serum adiponectin with macrovascular disease have been inconsistent. In contrast to existing data on serum adiponectin, this study assesses whether urinary adiponectin excretion might represent a more consistent vascular damage marker in type 2 diabetes. RESEARCH DESIGN AND METHODS Adiponectin distribution in human kidney biopsies was assessed by immunohistochemistry, and urinary adiponectin isoforms were characterized by Western blot analysis. Total urinary adiponectin excretion rate was measured in 156 patients with type 2 diabetes who had a history of diabetic nephropathy and 40 healthy control subjects using enzyme-linked immunosorbent assay. Atherosclerotic burden was assessed by common carotid artery intima-media-thickness (IMT). RESULTS A homogenous staining of adiponectin was found on the endothelial surface of glomerular capillaries and intrarenal arterioles in nondiabetic kidneys, whereas staining was decreased in diabetic nephropathy. Low-molecular adiponectin isoforms (∼30–70 kDa) were detected in urine by Western blot analysis. Urinary adiponectin was significantly increased in type 2 diabetes (7.68 ± 14.26 vs. control subjects: 2.91 ± 3.85 μg/g creatinine, P = 0.008). Among type 2 diabetic patients, adiponectinuria was associated with IMT (r = 0.479, P < 0.001) and proved to be a powerful independent predictor of IMT (β = 0.360, P < 0.001) in multivariable regression analyses. In a risk prediction model including variables of the UK Prospective Diabetes Study coronary heart disease risk engine urinary adiponectin, but not the albumin excretion rate, added significant value for the prediction of increased IMT (P = 0.007). CONCLUSIONS Quantification of urinary adiponectin excretion appears to be an independent indicator of vascular damage potentially identifying an increased risk for vascular events. PMID:19509019

  16. Studies on the excretion of ascorbic acid 2-sulfate and total vitamin C into human urine after oral administration of ascorbic acid 2-sulfate.

    PubMed

    Tsujimura, M; Fukuda, T; Kasai, T

    1982-10-01

    The excretion of AsS and total vitamin C into urine after oral administration of AsS to humans was investigated. When 10 mmol of AsS was administered to the subjects, the excretion of AsS into urine continued for 60 hr in males and 48 hr in females. The average amount excreted per hour was less than 5 mg. These results differed from those for AsA and DAsA orally administered to humans. The determination of vitamin C after oral administration of AsS to the subjects consisting of ten males and six females showed no vitamin C effect in humans, similarly to the case with the guinea pig and the rhesus monkey. PMID:7161646

  17. Screening for diets that reduce urinary nitrogen excretion and methane emissions while maintaining or increasing production by dairy cows.

    PubMed

    Gregorini, Pablo; Beukes, Pierre C; Dalley, Dawn; Romera, Alvaro J

    2016-05-01

    Farmers face complex decisions at the time to feed animals, trying to achieve production goals while contemplating social and environmental constraints. Our purpose was to facilitate such decision making for pastoral dairy farmers, aiming to reduce urinary N (UN) and methane emissions (CH4), while maintaining or increasing milk production (MP). There is a number of feeds the farmers can choose from and combine. We used 50 feeds (forages and grains) combined systematically in different proportions producing 11,526 binary diets. Diets were screened, using an a posteriori approach and a Pareto front (PF) analysis of model (Molly) outputs. The objective was to identify combinations with the best possible compromise (i.e. frontier) between UN, CH4, and MP. Using high MP and low UN as objective functions, PF included 10, 14, 12 and 50 diets, for non-lactating, early-, mid- and late-lactation periods, with cereals and beets featuring strongly. Using the same objective functions, but including ryegrass as dietary base PF included 2, 4, 8 and 4 diets for those periods. Therefore, from a wide range of diets, farmers could choose from few feeds combined into binary diets to reduce UN while maintaining or increasing MP. If the intention is maintaining pasture-based systems, there are fewer suitable options. Reducing UN will simply require dilution of N supplied by pasture by supplementing low N conserved forages. The results also evidence the risk of pollution swapping, reaching the frontier means arriving at a point where trade-off decisions need to be made. Any further reduction in UN implies an increment in CH4, or reduction in CH4 emissions increases UN. There is no perfect diet to optimize all objectives simultaneously; but if the current diet is not in the frontier some options can offset pollution swapping. The choice is with the farmers and conditioned by their context. PMID:26874758

  18. Ferrioxamine excretion in iron-loaded man

    SciTech Connect

    Pippard, M.J.; Callender, S.T.; Finch, C.A.

    1982-08-01

    Factors affecting iron excretion after subcutaneous desferrioxamine infusion were evaluated in individuals with iron overload. Urinary iron varied directly, whereas stool iron varied inversely with the level of erythropoiesis. Ascorbic acid greatly enhanced urinary iron excretion but had a less constant effect on stool iron. Stool iron losses contributed a greater proportion of total iron excretion at higher chelator dosage. These studies indicate the importance of biliary iron excretion in monitoring the effectiveness of desferrioxamine. They also suggest that large chelator doses may remove established iron overload much more rapidly than has previously been realized.

  19. Use of a cloned multidrug resistance gene for coamplification and overproduction of major excreted protein, a transformation-regulated secreted acid protease

    SciTech Connect

    Kane, S.E.; Troen, B.R.; Gal, S.; Ueda, K.; Pastan, I.; Gottesman, M.M.

    1988-08-01

    Malignantly transformed mouse fibroblasts synthesize and secrete large amounts of major excreted protein (MEP), a 39,000-dalton precursor to an acid protease (cathepsin L). To evaluate the possible role of this protease in the transformed phenotype, the authors transfected cloned genes for mouse or human MEP into mouse MIH 3T3 cells with an expression vector for the dominant, selectable human multidrug resistance (MDR1) gene. The cotransfected MEP sequences were efficiently coamplified and transcribed during stepwise selection for multidrug resistance in colchicine. The transfected NIH 3T3 cell lines containing amplified MEP sequences synthesized as much MEP as did Kirsten sarcoma virus-transformed NIH 3T3 cells. The MEP synthesized by cells transfected with the cloned mouse and human MEP genes were also secreted. Elevated synthesis and secretion of MEP by NIH 3T3 cells did not change the nontransformed phenotype of these cells.

  20. Increased formation of ursodeoxycholic acid in patients treated with chenodeoxycholic acid.

    PubMed Central

    Salen, G; Tint, G S; Eliav, B; Deering, N; Mosbach, E H

    1974-01-01

    The formation of ursodeoxycholic acid, the 7 beta-hydroxy epimer of chenodeoxycholic acid, was investigated in three subjects with cerebrotendinous xanthomatosis and in four subjects with gallstones. Total biliary bile acid composition was analyzed by gas-liquid chromatography before and after 4 months of treatment with 0.75 g/day of chenodeoxycholic acid. Individual bile acids were identified by mass spectrometry. Before treatment, bile from cerebrotendinous xanthomatosis (CTX) subjects contained cholic acid, 85%; chenodeoxycholic acid, 7%; deoxycholic acid, 3%; allocholic acid, 3%; and unidentified steroids, 2%; while bile from gallstone subjects contained cholic acid, 45%; chenodeoxycholic acid, 43%; deoxycholic acid, 11%, and lithocholic acid, 1%. In all subjects, 4 months of chenodeoxycholic acid therapy increased the proportion of this bile acid to approximately 80% and decreased cholic acid to 3% of the total biliary bile acids, the remaining 17% of bile acids were identified as ursodeoxycholic acid. After the intravenous injection of [3H]chenodeoxycholic acid, the specific activity of biliary ursodeoxycholic acid exceeded the specific activity of chenodeoxycholic acid, and the resulting specific activity decay curves suggested precursor-product relationships. When [3H]7-ketolithocholic acid was administrated to another patient treated with chenodeoxycholic acid, radioactivity was detected in both the ursodeoxycholic acid and chenodeoxycholic acid fractions. These results indicate that substantial amounts of ursodeoxycholic acid are formed in patients treated with chenodeoxycholic acid. The ursodeoxycholic acid was synthesized from chenodeoxycholic acid presumably via 7-ketolithocholic acid. Images PMID:11344576

  1. Effects of supplemental dietary calcium on quantitative and qualitative fecal fat excretion in man.

    PubMed

    Welberg, J W; Monkelbaan, J F; de Vries, E G; Muskiet, F A; Cats, A; Oremus, E T; Boersma-van Ek, W; van Rijsbergen, H; van der Meer, R; Mulder, N H

    1994-01-01

    Oral calcium supplementation is thought to be a useful interventional agent to decrease colon cancer risk. This is supposedly due, at least in part, to the binding of bile acids and fatty acids by calcium in the colon, thus prohibiting the damaging effects of these substances to the epithelium. To determine the effects of calcium supplementation on fecal fat excretion, 24 subjects kept a fat and calcium constant diet for one week and were supplemented with either 0, 2 or 4 g elemental calcium as calcium carbonate in a double-blind fashion. At the end of the week 72-hour feces was collected, and total fat, neutral fat, fatty acids and the ratio of polyunsaturated and saturated fatty acids (P/S ratio) were measured. Calcium dose-dependently increased the percentual excretion of total fat as related to fat intake: 6.8 +/- 0.9% during 0 g, 7.4 +/- 1.0% during 2 g and 10.2 +/- 1.4% during 4 g, r = 0.44, p = 0.03. This was due to increased fatty acid excretion, excretion of neutral fat was not affected, nor was the P/S ratio. It is concluded that calcium supplementation modestly increases fecal fatty acid excretion. No adverse metabolic effects are to be expected from this in case of long-term calcium supplementation in subjects at increased risk for colon cancer. PMID:7832578

  2. Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in Wistar rats.

    PubMed

    Balasubramanian, T

    2003-10-01

    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. PMID:15241498

  3. Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats

    SciTech Connect

    Adair, Blakely M.; Moore, Tanya; Conklin, Sean D.; Creed, John T.; Wolf, Douglas C.; Thomas, David J. . E-mail: thomas.david@epa.gov

    2007-07-15

    Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethylated and trimethylated arsenicals; urines were analyzed for these arsenicals and their thiolated derivatives. In dimethylarsinic acid-treated rats, highest concentrations of dimethylated arsenic were found in blood. In lung, liver, and kidney, concentrations of dimethylated arsenic exceeded those of trimethylated species; in urinary bladder and urine, trimethylated arsenic predominated. Dimethylthioarsinic acid and trimethylarsine sulfide were present in urine of dimethylarsinic acid-treated rats. Concentrations of dimethylated arsenicals were similar in most tissues of dimethylarsinic acid- and arsenate-treated rats, including urinary bladder which is the target for dimethylarsinic acid-induced carcinogenesis in the rat. Mean concentration of dimethylated arsenic was significantly higher (P < 0.05) in urine of dimethylarsinic acid-treated rats than in arsenate-treated rats, suggesting a difference between treatment groups in the flux of dimethylated arsenic through urinary bladder. Concentrations of trimethylated arsenic concentrations were consistently higher in dimethylarsinic acid-treated rats than in arsenate-treated rats; these differences were significant (P < 0.05) in liver, urinary bladder, and urine. Concentrations of dimethylthioarsinic acid and trimethylarsine sulfide were higher in urine from dimethylarsinic acid-treated rats than from arsenate-treated rats. Dimethylarsinic acid is extensively metabolized in the rat, yielding significant concentrations of trimethylated species and of thiolated derivatives. One or more of these metabolites could be the species causing alterations of cellular function that lead to tumors in the urinary bladder.

  4. Urinary Calcium and Oxalate Excretion in Healthy Adult Cats Are Not Affected by Increasing Dietary Levels of Bone Meal in a Canned Diet

    PubMed Central

    Passlack, Nadine; Zentek, Jürgen

    2013-01-01

    This study aimed to investigate the impact of dietary calcium (Ca) and phosphorus (P), derived from bone meal, on the feline urine composition and the urinary pH, allowing a risk assessment for the formation of calcium oxalate (CaOx) uroliths in cats. Eight healthy adult cats received 3 canned diets, containing 12.2 (A), 18.5 (B) and 27.0 g Ca/kg dry matter (C) and 16.1 (A), 17.6 (B) and 21.1 g P/kg dry matter (C). Each diet was fed over 17 days. After a 7 dayś adaptation period, urine and faeces were collected over 2×4 days (with a two-day rest between), and blood samples were taken. Urinary and faecal minerals, urinary oxalate (Ox), the urinary pH and the concentrations of serum Ca, phosphate and parathyroid hormone (PTH) were analyzed. Moreover, the urine was microscopically examined for CaOx uroliths. The results demonstrated that increasing levels of dietary Ca led to decreased serum PTH and Ca and increased faecal Ca and P concentrations, but did not affect the urinary Ca or Ox concentrations or the urinary fasting pH. The urinary postprandial pH slightly increased when the diet C was compared to the diet B. No CaOx crystals were detected in the urine of the cats. In conclusion, urinary Ca excretion in cats seems to be widely independent of the dietary Ca levels when Ca is added as bone meal to a typical canned diet, implicating that raw materials with higher contents of bones are of subordinate importance as risk factors for the formation of urinary CaOx crystals. PMID:23940588

  5. Urinary angiotensinogen excretion is associated with blood pressure in obese young adults.

    PubMed

    Sato, Emiko; Mori, Takefumi; Satoh, Michihiro; Fujiwara, Mutsuko; Nakamichi, Yoshimi; Oba, Ikuko; Ogawa, Susumu; Kinouchi, Yoshitaka; Sato, Hiroshi; Ito, Sadayoshi; Hida, Wataru

    2016-01-01

    Intrarenal RAS has been suggested to be involved in the pathogenesis of hypertension. It was recently reported that urinary angiotensinogen excretion levels are associated with intrarenal RAS. However, few markers predicting intrarenal RAS have been investigated in obese young subjects. The present study evaluated the association between blood pressure and intrarenal RAS activity, inflammation and oxidative stress in obese young adults. Urinary angiotensinogen excretion and urinary monocyte chemotactic protein (MCP)-1, and urinary thiobarbituric acid reaction substance (TBARS) as markers of intrarenal RAS activity, inflammation, and oxidative stress, respectively, were determined from morning urine of 111 young male adults. Participants were divided into two groups based on the body mass index (BMI). Natural log-transformed urinary angiotensinogen excretion level was significantly associated with blood pressure, MCP-1 excretion, and TBARS excretion elevation in the obese group (BMI ≥25 kg/m(2)). Multivariable analyses showed that every 1 standard deviation increase in natural-log transformed urinary angiotensinogen and MCP-1 excretion, but not TBARS excretion level was associated with elevated blood pressure in the obese group. These results indicate that urinary angiotensinogen and MCP-1 excretion were associated with blood pressure elevation in this population of obese young adults. It suggested that inappropriate RAS activity and inflammation precedes hypertension in obese young subjects and urinary angiotensinogen could be a screening maker for hypertension in young obese subjects. PMID:26825581

  6. Absorption and excretion of 14C-perfluorooctanoic acid (PFOA) and perfluorooctane aulfonate (PFOS) in beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perfluoroalkyl compounds such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are industrial chemicals that are environmentally persistent. Both PFOS and PFOA are found in biosolids, and the application of these contaminated biosolids to pastures has raised concerns about possi...

  7. Absorption and excretion of 14C-perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perfluoroalkyl compounds such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are industrial chemicals that are environmentally persistent. Both PFOS and PFOA are found in biosolids, and the application of these contaminated biosolids to pastures has raised concerns about possi...

  8. Relation of impaired coronary microcirculation to increased urine albumin excretion in patients with systemic hypertension and no epicardial coronary arterial narrowing.

    PubMed

    Tsiachris, Dimitris; Tsioufis, Costas; Dimitriadis, Kyriakos; Syrseloudis, Dimitris; Rousos, Dimitris; Kasiakogias, Alexandros; Papademetriou, Vasilios; Tousoulis, Dimitris; Stefanadis, Christodoulos

    2012-04-01

    Coronary flow reserve (CFR) is impaired and urinary albumin excretion is increased in patients with essential hypertension. Our aim was to investigate the associations between CFR and cardiac and renal damage in hypertensives. For this purpose we studied 37 never-treated hypertensives (57.9 years old, 16 men) without chest pain but with a positive ischemia stress test result and normal coronary arteries on coronary angiogram. CFR was calculated by a 0.014-inch Doppler guidewire (Flowire, Volcano, San Diego) in the left anterior descending artery in response to bolus intracoronary administration of adenosine (60 μg) as the ratio of hyperemic to basal average peak velocity of the distal vessel. All participants underwent complete echocardiographic study including left ventricular diastolic function evaluation by tissue Doppler imaging (peak early diastolic velocity/peak atrial systolic velocity) and determination of the albumin-to-creatinine ratio (ACR). Hypertensives with low CFR (<2.5, n = 22) compared to those with high CFR (n = 15) exhibited a larger left ventricular mass index by 10.9 g/m(2) (p = 0.045) and ACR values by 10 mg/g (p <0.001). CFR was negatively correlated with logACR (r = -0.511, p = 0.001). LogACR (beta -0.792, p <0.001), male gender (beta 0.313, p = 0.005), left ventricular mass index (beta -0.329, p = 0.007), and peak early diastolic velocity/peak atrial systolic velocity (beta 0.443, p <0.001) were the only independent predictors of CFR in linear regression analysis (adjusted R(2) = 0.672). In conclusion, never-treated asymptomatic hypertensives who exhibit impaired CFR and angiographically normal epicardial arteries are characterized by intrarenal vascular damage as reflected by increased ACR. These findings suggest a plausible role of ACR estimation in the identification of hypertensive subjects with early coronary microvascular dysfunction. PMID:22221953

  9. Tissue Distribution and Urinary Excretion of Dimethylated Arsenic and Its Metabolites in Dimethylarsinic acid- or Arsenate-treated Rats - MCEARD

    EPA Science Inventory

    Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethy...

  10. Energetics of end product excretion in anaerboic bacteria and the metabolism of fatty acids by Syntrophomonas wolfei

    SciTech Connect

    McInerney, M.J.

    1989-10-01

    Anaerobic syntrophic bacteria degrade fatty acids which are important intermediates in anaerobic degradation and methanogenesis. These bacteria grow very slowly and require the presence of a hydrogen/formate-using organism to degrade fatty acids. Thus, these bacteria serve as models to study the biochemical aspects of mutualism and the energetics of slow growing organisms. We developed methods to physically separate cells of the anaerobic, fatty acid degrader, Syntrophomonas wolfei, from cells of the hydrogen user by Percoll gradient centrifugation and to selectively lyse S. wolfei cells using lysozyme. These methods allowed the study of the physiology of S. wolfei without significant contamination by cellular components of the hydrogen user. We also obtained pure cultures of S. wolfei by adapting the organism to grow on crotonate. Fatty acids were degraded by the {beta}-oxidation pathway using a coenzyme A (CoA) transferase activity to activate the fatty acid and substrate-level phosphorylation reactions to synthesize adenosine-5{prime}-triphosphate (ATP). The substrate specificity of the CoA transferase activity in the pure culture of S. wolfei differed from that found in the coculture suggesting that the ability to use crotonate resulted from an alteration of this enzyme. S. wolfei grown alone degraded crotonate in a manner similar to that of other crotonate-fermenting anaerobes, but the molar growth yields of S. wolfei were 2 to 3 times higher than those organisms. This suggests that the reduction of crotonyl-CoA to butyryl-CoA is energy yielding. S. wolfei contained a c-type cytochrome which may be involved in this reaction. S. wolfei synthesized large amounts of the storage polymer, poly-{beta}-hydroxybutyrate (PHB). Radioisotopic incorporation experiments showed that PHB was synthesized directly from the {beta}-oxidation intermediate rather than from the condensation of two acetyl-CoA molecules.

  11. Method of increasing conversion of a fatty acid to its corresponding dicarboxylic acid

    DOEpatents

    Craft, David L.; Wilson, C. Ron; Eirich, Dudley; Zhang, Yeyan

    2004-09-14

    A nucleic acid sequence including a CYP promoter operably linked to nucleic acid encoding a heterologous protein is provided to increase transcription of the nucleic acid. Expression vectors and host cells containing the nucleic acid sequence are also provided. The methods and compositions described herein are especially useful in the production of polycarboxylic acids by yeast cells.

  12. Effects of methylxanthines on urinary prostaglandin E excretion in rats.

    PubMed

    Takeuchi, K; Kogo, H; Aizawa, Y

    1981-04-01

    Effect of methylxanthines (theophylline, theobromine and caffeine) on urinary prostaglandin E (PGE) excretion in male rats was studied. Oral administration of xanthines significantly increased the urinary excretion of PGE. Dose-response studies showed that the maximal excretion of urinary PGE and water was obtained by administration of theophylline (50 mg/kg), where the increase in PGE was about 20 times that of the control. The excretion of urinary sodium, potassium and chloride was also markedly increased by xanthines, particularly, theophylline. Increases in urinary PGE excretion, urine volume and electrolytes excretion were inhibited by 10 mg/kg of indomethacin administered prior to theophylline. The increase of urinary PGE excretion after theophylline administration (50 mg/kg) preceded increases in water and sodium excretion. These results suggest that renal PGE mediates, at least in part, the diuretic effect of theophylline. PMID:7311144

  13. Evidence that auxin-induced growth of soybean hypocotyls involves proton excretion

    SciTech Connect

    Rayle, D.L.; Cleland, R.E.

    1980-09-01

    The role of H/sup +/ excretion in auxin-induced growth of soybean hypocotyl tissues has been investigated, using tissues whose cuticle was rendered permeable to protons or buffers by scarification (scrubbing). Indoleacetic acid induces both elongation and H/sup +/ excretion after a lag of 10 to 12 minutes. Cycloheximide inhibits growth and causes the tissues to remove protons from the medium. Neutral buffers (pH 7.0) inhibit auxin-induced growth of scrubbed but not intact sections; the inhibition increases as the buffers strength is increased. Both live and frozen-thawed sections, in the absence of auxin, extend in response to exogenously supplied protons. Fusicoccin induces both elongation and H/sup +/ excretion at rates greater than does auxin. These results indicate that H/sup +/ excretion is involved in the initiation of auxin-induced elongation in soybean hypocotyl tissue.

  14. Breeding Vegetables with Increased Content in Bioactive Phenolic Acids.

    PubMed

    Kaushik, Prashant; Andújar, Isabel; Vilanova, Santiago; Plazas, Mariola; Gramazio, Pietro; Herraiz, Francisco Javier; Brar, Navjot Singh; Prohens, Jaime

    2015-01-01

    Vegetables represent a major source of phenolic acids, powerful antioxidants characterized by an organic carboxylic acid function and which present multiple properties beneficial for human health. In consequence, developing new varieties with enhanced content in phenolic acids is an increasingly important breeding objective. Major phenolic acids present in vegetables are derivatives of cinnamic acid and to a lesser extent of benzoic acid. A large diversity in phenolic acids content has been found among cultivars and wild relatives of many vegetable crops. Identification of sources of variation for phenolic acids content can be accomplished by screening germplasm collections, but also through morphological characteristics and origin, as well as by evaluating mutations in key genes. Gene action estimates together with relatively high values for heritability indicate that selection for enhanced phenolic acids content will be efficient. Modern genomics and biotechnological strategies, such as QTL detection, candidate genes approaches and genetic transformation, are powerful tools for identification of genomic regions and genes with a key role in accumulation of phenolic acids in vegetables. However, genetically increasing the content in phenolic acids may also affect other traits important for the success of a variety. We anticipate that the combination of conventional and modern strategies will facilitate the development of a new generation of vegetable varieties with enhanced content in phenolic acids. PMID:26473812

  15. Influence of feeding increasing levels of dry corn distillers grains plus solubles in whole corn grain-based finishing diets on total tract digestion, nutrient balance, and excretion in beef steers.

    PubMed

    Salim, H; Wood, K M; Abo-Ismail, M K; McEwen, P L; Mandell, I B; Miller, S P; Cant, J P; Swanson, K C

    2012-12-01

    Four crossbred steers (average BW = 478 ± 33 kg) were used in a 4 × 4 Latin square design to determine the effects of dietary concentration of dry corn distillers grains plus solubles (DDGS) in whole corn-based finishing diets on total tract digestion and nutrient balance and excretion. The DDGS were fed at 0% (control), 16.7%, 33.3%, and 50% of dietary DM. All diets contained 10% (DM basis) alfalfa/grass haylage and were formulated to meet or exceed the estimated requirements for CP. Steers were fed the experimental diets ad libitum for a 14-d adaptation period followed by a 5-d period for fecal and urine collection. Increasing concentration of DDGS in diets from 0 to 50% of DM linearly decreased (P < 0.05) total tract DM and starch digestibility (from 77.8 to 72.9%, and 89.2 to 81.5%, respectively). Daily N and P intakes linearly increased (P = 0.06 and P = 0.01, respectively) with increasing DDGS concentration. Fecal and urinary N, P, S, Mg, and K excretion linearly increased (P < 0.05) with increasing DDGS concentration; however, Se and Na excretion did not differ (P > 0.38) among treatments. Retention (g/d; intake minus urinary and fecal excretion) of N did not differ (P > 0.16) among treatments. Retention of P tended (P = 0.07) to linearly increase and retention of S (g/d) linearly increased (P = 0.004), with increasing DDGS concentration. There were no effects (P > 0.16) of dietary treatment on digestion and retention of Se, Mg, K, and Na. Plasma P and S concentrations increased (P = 0.03 and 0.01, respectively) with increasing DDGS concentration. These data indicate that feeding DDGS up to 50% of dietary DM in whole corn grain-based finishing diets does not have a negative effect on nutrient retention but decreases digestibility. Total excretion of N, P, Ca, Mg, S, and K increased as DDGS concentration increased. PMID:22952356

  16. Vasopressin regulates renal calcium excretion in humans

    PubMed Central

    Hanouna, Guillaume; Haymann, Jean-Philippe; Baud, Laurent; Letavernier, Emmanuel

    2015-01-01

    Antidiuretic hormone or arginine vasopressin (AVP) increases water reabsorption in the collecting ducts of the kidney. Three decades ago, experimental models have shown that AVP may increase calcium reabsorption in rat kidney. The objective of this study was to assess whether AVP modulates renal calcium excretion in humans. We analyzed calcium, potassium, and sodium fractional excretion in eight patients affected by insipidus diabetes (nephrogenic or central) under acute vasopressin receptor agonist action and in 10 patients undergoing oral water load test affected or not by inappropriate antidiuretic hormone secretion (SIADH). Synthetic V2 receptor agonist (dDAVP) reduced significantly calcium fractional excretion from 1.71% to 0.58% (P < 0.05) in patients with central diabetes insipidus. In patients with nephrogenic diabetes insipidus (resistant to AVP), calcium fractional excretion did not change significantly after injection (0.48–0.68%, P = NS). In normal subjects undergoing oral water load test, calcium fractional excretion increased significantly from 1.02% to 2.54% (P < 0.05). Patients affected by SIADH had a high calcium fractional excretion at baseline that remained stable during test from 3.30% to 3.33% (P = NS), possibly resulting from a reduced calcium absorption in renal proximal tubule. In both groups, there was a significant correlation between urine output and calcium renal excretion. In humans, dDAVP decreases calcium fractional excretion in the short term. Conversely, water intake, which lowers AVP concentration, increases calcium fractional excretion. The correlation between urine output and calcium excretion suggests that AVP-related antidiuresis increases calcium reabsorption in collecting ducts. PMID:26620256

  17. A mechanism for branchial acid excretion in marine fish: identification of multiple Na+/H+ antiporter (NHE) isoforms in gills of two seawater teleosts.

    PubMed

    Claiborne, J B; Blackston, C R; Choe, K P; Dawson, D C; Harris, S P; Mackenzie, L A; Morrison-Shetlar, A I

    1999-02-01

    Both Na+/H+ exchange and the electrogenic extrusion of H+ via an H+-ATPase have been postulated to drive acid excretion across the branchial epithelium of fishes. While the H+-ATPase/Na+ channel system appears to be the predominant mechanism in some freshwater species, it may play a reduced role in seawater and brackish-water animals, where high external Na+ concentrations may thermodynamically favor Na+/H+ exchange driven by a Na+/H+ antiporter (NHE). In this study, we used molecular and immunological methods to assess the role of NHE isoforms in the branchial epithelium of the marine long-horned sculpin (Myoxocephalus octodecimspinosus) and the euryhaline killifish (Fundulus heteroclitus). Northern blot analysis of RNA probed with the human NHE-1 BamHI fragment suggested the presence of homologous gill NHE mRNA in sculpin. RT-PCR on gill RNA isolated from sculpin recovering from metabolic acidosis provided evidence for two distinct NHE isoforms; one with 76 % amino acid homology to mammalian NHE-2, and another 92 % homologous to trout erythrocytic beta-NHE. Killifish also have transcripts with 91 % homology to beta-NHE. Immunological detection using monoclonal antibodies for mammalian NHE-1 revealed a protein antigenically similar to this isoform in the gills of both species. Metabolic acidosis caused an approximately 30-fold decrease in expression of the NHE-1-like protein in sculpin. We speculate that beta-NHE in the gills plays the intracellular 'housekeeping' roles described for mammalian NHE-1. During systemic acidosis, apical gill NHE-2 (which is sensitive to external amiloride and low [Na+]) in parallel with a dramatic suppression of basolateral NHE-1 activity enhances net capdelta H+ transfers to the water. PMID:9882643

  18. Increasing the Oleic Acid in Soybean Oil with Plant Breeding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing the oleic acid content along with decrease in linolenic acid can improve the oxidative stability of soybean oil. Genetic changes in soybean using standard plant breeding practices has resulted in a publicly released a mid-oleic breeding line, N98-4445A, with oil that averages 57% oleic ac...

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

    PubMed

    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

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

    PubMed Central

    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

  1. Increase of α1-acid glycoprotein after treatment with amitriptyline

    PubMed Central

    Baumann, P.; Tinguely, D.; Schöpf, J.

    1982-01-01

    Sixteen primary depressive patients were treated for 3 weeks with amitriptyline 150 mg daily. In thirteen patients the plasma level of α1-acid glycoprotein (AAG) significantly increased after the treatment but the albumin levels did not change. PMID:7104160

  2. Effect of metal chelators on excretion and tissue levels of essential trace elements

    SciTech Connect

    Tandon, S.K.; Jain, V.K.; Mathur, A.K.

    1984-10-01

    The influence of one, three, and six doses of ethylenediaminetetraacetic acid (EDTA) diethylenetriaminepentaacetic acid (DTPA), and triethylenetetramine (TETA) on the urinary excretion of Ca, Cu, Fe, and Zn, and on their levels in liver, kidneys, heart, and serum in rats, was investigated to ascertain their suitability in amelioration of metal intoxication. While excretion of all the essential trace metals examined was enhanced significantly, the tissue and serum levels of some of them either increased or decreased after administration of the chelators. The results suggest depletion of some of the endogenous trace metals from the body and their intertissue redistribution following treatment with these chelating agents.

  3. Acid mine drainage and subsidence: effects of increased coal utilization.

    PubMed Central

    Hill, R D; Bates, E R

    1979-01-01

    The increases above 1975 levels for acid mine drainage and subsidence for the years 1985 and 2000 based on projections of current mining trends and the National Energy Plan are presented. No increases are projected for acid mine drainage from surface mines or waste since enforcement under present laws should control this problem. The increase in acid mine drainage from underground mines is projected to be 16 percent by 1985 and 10 percent by 2000. The smaller increase in 2000 over 1985 reflects the impact of the PL 95-87 abandoned mine program. Mine subsidence is projected to increase by 34 and 115 percent respectively for 1985 and 2000. This estimate assumes that subsidence will parallel the rate of underground coal production and that no new subsidence control measures are adopted to mitigate subsidence occurrence. PMID:540617

  4. Cinnamic acid increases lignin production and inhibits soybean root growth.

    PubMed

    Salvador, Victor Hugo; Lima, Rogério Barbosa; dos Santos, Wanderley Dantas; Soares, Anderson Ricardo; Böhm, Paulo Alfredo Feitoza; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth. PMID:23922685

  5. Predicting nitrogen excretion from cattle.

    PubMed

    Reed, K F; Moraes, L E; Casper, D P; Kebreab, E

    2015-05-01

    Manure nitrogen (N) from cattle production facilities can lead to negative environmental effects, such as contribution to greenhouse gas emissions, leaching and runoff to aqueous ecosystems leading to eutrophication, and acid rain. To mitigate these effects and to improve the efficiency of N use, accurate prediction of N excretion and secretions are required. A genetic algorithm was implemented to select models to predict fecal, urinary, and total manure N excretions, and milk N secretions from 3 classes of animals: lactating dairy cows, heifers and dry cows, and steers. Two tiers of model classes were developed for each category of animals based on model input requirements. A total of 6 models for heifers and dry cows and steers and an additional 2 models for lactating dairy cattle were developed. Evaluation of the models using K-fold cross validation based on all data and using the most recent 6 yr of data showed better prediction for total manure N and fecal N compared with urinary N excretion, which was the most variable response in the database. Compared with extant models from the literature, the models developed in this study resulted in a significant improvement in prediction error for fecal and urinary N excretions from lactating cows. For total manure production by lactating cows, extant and new models were comparable in their prediction ability. Both proposed and extant models performed better than the prediction methods used by the US Environmental Protection Agency for the national inventory of greenhouse gases. Therefore, the proposed models are recommended for use in estimation of manure N from various classes of animals. PMID:25747829

  6. Hyperuricemia in acute gastroenteritis is caused by decreased urate excretion via ABCG2.

    PubMed

    Matsuo, Hirotaka; Tsunoda, Tomoyuki; Ooyama, Keiko; Sakiyama, Masayuki; Sogo, Tsuyoshi; Takada, Tappei; Nakashima, Akio; Nakayama, Akiyoshi; Kawaguchi, Makoto; Higashino, Toshihide; Wakai, Kenji; Ooyama, Hiroshi; Hokari, Ryota; Suzuki, Hiroshi; Ichida, Kimiyoshi; Inui, Ayano; Fujimori, Shin; Shinomiya, Nariyoshi

    2016-01-01

    To clarify the physiological and pathophysiological roles of intestinal urate excretion via ABCG2 in humans, we genotyped ABCG2 dysfunctional common variants, Q126X (rs72552713) and Q141K (rs2231142), in end-stage renal disease (hemodialysis) and acute gastroenteritis patients, respectively. ABCG2 dysfunction markedly increased serum uric acid (SUA) levels in 106 hemodialysis patients (P = 1.1 × 10(-4)), which demonstrated the physiological role of ABCG2 for intestinal urate excretion because their urate excretion almost depends on intestinal excretion via ABCG2. Also, ABCG2 dysfunction significantly elevated SUA in 67 acute gastroenteritis patients (P = 6.3 × 10(-3)) regardless of the degree of dehydration, which demonstrated the pathophysiological role of ABCG2 in acute gastroenteritis. These findings for the first time show ABCG2-mediated intestinal urate excretion in humans, and indicates the physiological and pathophysiological importance of intestinal epithelium as an excretion pathway besides an absorption pathway. Furthermore, increased SUA could be a useful marker not only for dehydration but also epithelial impairment of intestine. PMID:27571712

  7. Hyperuricemia in acute gastroenteritis is caused by decreased urate excretion via ABCG2

    PubMed Central

    Matsuo, Hirotaka; Tsunoda, Tomoyuki; Ooyama, Keiko; Sakiyama, Masayuki; Sogo, Tsuyoshi; Takada, Tappei; Nakashima, Akio; Nakayama, Akiyoshi; Kawaguchi, Makoto; Higashino, Toshihide; Wakai, Kenji; Ooyama, Hiroshi; Hokari, Ryota; Suzuki, Hiroshi; Ichida, Kimiyoshi; Inui, Ayano; Fujimori, Shin; Shinomiya, Nariyoshi

    2016-01-01

    To clarify the physiological and pathophysiological roles of intestinal urate excretion via ABCG2 in humans, we genotyped ABCG2 dysfunctional common variants, Q126X (rs72552713) and Q141K (rs2231142), in end-stage renal disease (hemodialysis) and acute gastroenteritis patients, respectively. ABCG2 dysfunction markedly increased serum uric acid (SUA) levels in 106 hemodialysis patients (P = 1.1 × 10−4), which demonstrated the physiological role of ABCG2 for intestinal urate excretion because their urate excretion almost depends on intestinal excretion via ABCG2. Also, ABCG2 dysfunction significantly elevated SUA in 67 acute gastroenteritis patients (P = 6.3 × 10−3) regardless of the degree of dehydration, which demonstrated the pathophysiological role of ABCG2 in acute gastroenteritis. These findings for the first time show ABCG2-mediated intestinal urate excretion in humans, and indicates the physiological and pathophysiological importance of intestinal epithelium as an excretion pathway besides an absorption pathway. Furthermore, increased SUA could be a useful marker not only for dehydration but also epithelial impairment of intestine. PMID:27571712

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

    SciTech Connect

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

    2009-10-16

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

  9. Vitamin C modulates lead excretion in rats

    PubMed Central

    Lihm, Hoseob; Kim, Hyun; Chang, Heekyung; Yoon, Myunghee; Lee, Kayoung

    2013-01-01

    Lead, one of the most toxic heavy metals, takes longer time to be excreted from the body than other heavy metals. The purpose of this study is, by measuring lead excretion via urine and feces, to find out the effect of vitamin C in lead chelation. Thirty-six rats were randomly assorted into four groups. All 33 rats except for the control group were administered with lead, before orally administered with different doses of vitamin C per kilogram of body weight. The lead excretion levels in urine and feces as well as the survival rate were then measured for each group. The rats with lead administrations (10/13, 76.9%) with lead administrations only, 10/11 rats (90.9%) with lead administrations and low dose of vitamin C, 9/9 rats (100%) with lead administrations and high dose of vitamin C survived. Among the 29 surviving rats, low vitamin C intake group exhibited higher urinary excretion than the lead only group. The urinary excretion level in high dose vitamin C intakegroup was significantly higher than the lead only group. In addition, fecal lead excretion seemed to be increased in the high dose vitamin C intake group, compared to the group with lead administrations only with statistical significance. Through animal experiment, it was found out that administrating high dose of vitamin C accelerated the excretion of lead in body compared to low dose of vitamin C. PMID:24386596

  10. Diel variation in ammonia excretion, glutamine levels, and hydration status in two species of terrestrial isopods.

    PubMed

    Wright, Jonathan C; Peña-Peralta, Mariasol

    2005-01-01

    Terrestrial isopods (suborder Oniscidea) excrete most nitrogen diurnally as volatile ammonia, and ammonia-loaded animals accumulate nonessential amino acids, which may constitute the major nocturnal nitrogen pool. This study explored the relationship between ammonia excretion, glutamine storage/mobilization, and water balance, in two sympatric species Ligidium lapetum (section Diplocheta), a hygric species; and Armadillidium vulgare (Section Crinocheta), a xeric species capable of water-vapor absorption (WVA). Ammonia excretion (12-h), tissue glutamine levels, and water contents were measured following field collection of animals at dusk and dawn. In both species, diurnal ammonia excretion exceeded nocturnal excretion four- to fivefold while glutamine levels increased four- to sevenfold during the night. Most glutamine was accumulated in the somatic tissues ("body wall"). While data support the role of glutamine in nocturnal nitrogen storage, potential nitrogen mobilization from glutamine breakdown (162 micromol g(-1) in A. vulgare) exceeds measured ammonia excretion (2.5 micromol g(-1)) over 60-fold. This may serve to generate the high hemolymph ammonia concentrations (and high P(NH3)) seen during volatilization. The energetic cost of ammonia volatilization is discussed in the light of these findings. Mean water contents were similar at dusk and dawn in both species, indicating that diel cycles of water depletion and replenishment were not occurring. PMID:15578188

  11. Effects of kaliuretic peptide on sodium and water excretion in persons with congestive heart failure.

    PubMed

    Nasser, A; Dietz, J R; Siddique, M; Patel, H; Khan, N; Antwi, E K; San Miguel, G I; McCormick, M T; Schocken, D D; Vesely, D L

    2001-07-01

    Kaliuretic peptide, a 20-amino acid peptide hormone synthesized in the heart, enhances urine flow twofold, whereas atrial natriuretic peptide (ANP) enhances urine flow four- to 11-fold in healthy persons. The present investigation was designed to (1) determine whether kaliuretic peptide may have beneficial diuretic effects in persons with congestive heart failure (CHF), and (2) compare its beneficial effects with ANP in the treatment of CHF. Kaliuretic peptide (100 ng/kg body weight/min) given intravenously for 60 minutes to subjects with New York Heart Association class III CHF increased urine flow fourfold (p <0.001), which was maximal 212 hours after its infusion was stopped. Kaliuretic peptide enhanced sodium excretion threefold in subjects with CHF (p <0.01). Kaliuretic peptide increased the urinary excretion rate of potassium ion and fractional excretion of potassium 3.5- and twofold (p <0.05), respectively. ANP (same concentration) did not significantly enhance urine flow. ANP enhanced sodium excretion two- to sixfold in half of the CHF subjects, whereas it had no effect on sodium excretion in the other half. ANP did not significantly increase fractional excretion of sodium but did increase fractional excretion of potassium (p <0.05) during the first 20 minutes of its infusion. ANP-infused patients with CHF became hypotensive. None became hypotensive secondary to kaliuretic peptide. These data indicate that the diuretic properties of kaliuretic peptide in persons with CHF, as opposed to those of ANP, are not diminished (but rather are increased) compared with their effects in healthy persons. In patients with CHF, kaliuretic peptide causes a natriuresis-a feature not observed in those without sodium retention. PMID:11423053

  12. Urinary porphyrin excretion in hepatitis C infection.

    PubMed

    Vogeser, M; Jacob, K; Zachoval, R

    1999-08-01

    A high prevalence of hepatitis C virus infection in porphyria cutanea tarda in some populations suggests a close link between viral hepatitis and alteration of porphyrin metabolism. Moreover, there is evidence of a role of porphyrinopathies in hepatocarcinogenesis. The aim of our study was to obtain data on the prevalence and patterns of heme metabolism alterations in patients with chronic hepatitis C virus infection. Urinary porphyrin excretion was prospectively studied in 100 consecutive outpatients with chronic hepatitis C infection without signs of photosensitivity, using an ion-pair high-performance liquid chromatography method. Increased total porphyrin excretion was found in 41 patients, with predominant excretion of coproporphyrins (whole study group: mean 146 microg/g creatinine, interquartile range 76-186; normal < 150), in 10 patients excretion exceeded 300 microg/g creatinine. In the majority of all patients studied (75/100) an increased ratio of the relatively hydrophobic coproporphyrin isomer I to isomer III was found. In just one case, urinary porphyrin pattern characteristic for chronic hepatic porphyria was present (uroporphyrin > coproporphyrin, heptacarboxyporphyrin III increased) but the total porphyrin excretion was only slightly elevated in this case. In the whole group, total urinary porphyrin excretion correlated well with serum bilirubin and was inversely correlated with albumin and thrombin time. In conclusion, secondary coproporphyrinuria occurs frequently in heptatitis C infection, whereas in Germany, preclinical porphyria cutanea tarda seems to be rare in these patients. PMID:10536928

  13. Fecapentaene excretion and fecal mutagenicity in relation to nutrient intake and fecal parameters in humans on omnivorous and vegetarian diets.

    PubMed

    de Kok, T M; van Faassen, A; Bausch-Goldbohm, R A; ten Hoor, F; Kleinjans, J C

    1992-02-14

    Fecapentaenes are strong fecal mutagenic compounds presumably occurring in the majority of Western human individuals, and are possibly essential initiators of colon carcinogenesis. Dietary factors have been shown to influence colorectal cancer risk and to modulate both fecal mutagenicity and fecapentaene concentrations. Therefore, in this study, excretion of fecapentaenes is determined in humans consuming either vegetarian or omnivorous diets. The results show that the most predominant fecapentaene forms are excreted in higher concentrations by vegetarians. Consumption of cereal fiber, calcium and carotene as well as fecal concentrations of iso-lithocholic acid were found to correlate positively with excreted concentrations of one or more fecapentaene analogues. On average, 22% of excreted fecapentaene concentrations was found to be related to nutrient intake in stepwise regression models. Dietary calcium intake was found to be the most significant factor positively correlating with excreted fecapentaene concentrations. Intake of mono-unsaturated fatty acids or fiber from vegetables and fruit could be shown to correlate with fecapentaene excretion to a lesser degree. Despite high fecapentaene concentrations in fecal dichloromethane extracts, only 1 out of 20 samples revealed significant mutagenic activity in Salmonella typhimurium TA 100. Further, aqueous extracts of feces from omnivores appeared to be equally mutagenic as feces from vegetarians and contained non-detectable concentrations of fecapentaenes. It is concluded that dietary factors do affect excreted fecapentaene levels, but only to a relatively minor extent. Since vegetarians at low risk for colorectal cancer excrete higher concentrations of fecapentaenes, it could be hypothesized that relatively increased fecapentaene excretion in combination with antimutagenic compounds in feces represents colon cancer prevention. PMID:1540928

  14. Mutant E. coli strain with increased succinic acid production

    DOEpatents

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

    2002-01-01

    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 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.

  15. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, M.; Millard, C.S.; Stols, L.

    1998-06-23

    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. 2 figs.

  16. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    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.

  17. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    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.

  18. The effects of repeated parenteral administration of chelating agents on the distribution and excretion of uranium

    SciTech Connect

    Domingo, J.L.; Ortega, A.; Llobet, J.M.; Paternain, J.L.; Corbella, J.

    1989-04-01

    The effects of repeated ip administration of gallic acid, 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) on the distribution and excretion of uranium were assessed in male Swiss mice. Only Tiron significantly increased the amount of uranium excreted into urine and feces. A significant decrease in the concentration of uranium in liver, spleen and bone was observed after administration of Tiron, whereas injection of gallic acid or DTPA resulted in a significant decrease in the concentration of the metal in the liver. The results show that Tiron was consistently the most effective chelator of those tested in the treatment of uranium poisoning after repeated daily administration of the metal.

  19. Increased acyclovir oral bioavailability via a bile acid conjugate.

    PubMed

    Tolle-Sander, Sanna; Lentz, Kimberley A; Maeda, Dean Y; Coop, Andrew; Polli, James E

    2004-01-12

    The objective of this work was to design an acyclovir prodrug that would utilize the human apical sodium-dependent bile acid transporter (hASBT) and enhance acyclovir oral bioavailability. Using each chenodeoxycholate, deoxycholate, cholate, and ursodeoxycholate, four bile acid prodrugs of acyclovir were synthesized, where acyclovir was conjugated to a bile acid via a valine linker. The affinity of the prodrug for hASBT was determined through inhibition of taurocholate uptake by COS-7 cells transfected with hASBT (hASBT-COS). The prodrug with the highest inhibitory affinity was further evaluated in vitro and in vivo. The prodrug acyclovir valylchenodeoxycholate yielded the highest affinity for hASBT (Ki = 35 microM), showing that chenodeoxycholate is the free bile acid with the greatest affinity for hASBT. Acyclovir valylchenodeoxycholate's affinity was similar to that of cholic acid (Ki = 25 microM). Further characterization showed that acyclovir was catalytically liberated from acyclovir valylchenode-oxycholate by esterase. Relative to cellular uptake studies of acyclovir alone, the cellular uptake from the prodrug resulted in a 16-fold greater acyclovir accumulation within hASBT-COS cells, indicating enhanced permeation properties of the prodrug. Enhanced permeability was due to hASBT-mediated uptake and increased passive permeability. The extent of acyclovir uptake in the presence of sodium was 1.4-fold greater than the extent of passive prodrug uptake in the absence of sodium (p = 0.02), indicating translocation of the prodrug by hASBT. The prodrug also exhibited an almost 12-fold enhanced passive permeability, relative to acyclovir's passive permeability. Oral administration of acyclovir valylchenodeoxycholate to rats resulted in a 2-fold increase in the bioavailability of acyclovir, compared to the bioavailability after administration of acyclovir alone. Results indicate that a bile acid prodrug strategy may be useful in improving the oral bioavailability of

  20. Clinical usefulness of urinary 3-methylhistidine excretion in indicating muscle protein breakdown.

    PubMed Central

    Elia, M; Carter, A; Bacon, S; Winearls, C G; Smith, R

    1981-01-01

    Urinary excretion of the post-translationally modified amino-acid 3-methylhistidine, derived from the contractile proteins actin and myosin, was measured in patients with conditions associated with nitrogen loss. The ratio of 3-methylhistidine:creatinine excretion, a measure of the fractional catabolic rate of myofibrillar protein was increased in severe injury, thyrotoxicosis, neoplastic disease, prednisolone administration, and sometimes Duchenne muscular dystrophy. In myxoedema, osteomalacia, and hypothermia the ratio was decreased; and starvation, elective operations, and rheumatoid arthritis had little effect. Provided that the diet is meat free, measurement of urinary 3-methylhistidine may provide useful information on the cause of protein loss. PMID:6780020

  1. The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity.

    PubMed

    Broeders, Evie P M; Nascimento, Emmani B M; Havekes, Bas; Brans, Boudewijn; Roumans, Kay H M; Tailleux, Anne; Schaart, Gert; Kouach, Mostafa; Charton, Julie; Deprez, Benoit; Bouvy, Nicole D; Mottaghy, Felix; Staels, Bart; van Marken Lichtenbelt, Wouter D; Schrauwen, Patrick

    2015-09-01

    The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans. PMID:26235421

  2. Factors Altering Pyruvate Excretion in a Glycogen Storage Mutant of the Cyanobacterium, Synechococcus PCC7942.

    PubMed

    Benson, Phoebe J; Purcell-Meyerink, Diane; Hocart, Charles H; Truong, Thy T; James, Gabriel O; Rourke, Loraine; Djordjevic, Michael A; Blackburn, Susan I; Price, G D

    2016-01-01

    Interest in the production of carbon commodities from photosynthetically fixed CO2 has focused attention on cyanobacteria as a target for metabolic engineering and pathway investigation. We investigated the redirection of carbon flux in the model cyanobacterial species, Synechococcus elongatus PCC 7942, under nitrogen deprivation, for optimized production of the industrially desirable compound, pyruvate. Under nitrogen limited conditions, excess carbon is naturally stored as the multi-branched polysaccharide, glycogen, but a block in glycogen synthesis, via knockout mutation in the gene encoding ADP-glucose pyrophosphorylase (glgC), results in the accumulation of the organic acids, pyruvate and 2-oxoglutarate, as overflow excretions into the extracellular media. The ΔglgC strain, under 48 h of N-deprivation was shown to excrete pyruvate for the first time in this strain. Additionally, by increasing culture pH, to pH 10, it was possible to substantially elevate excretion of pyruvate, suggesting the involvement of an unknown substrate/proton symporter for export. The ΔglgC mutant was also engineered to express foreign transporters for glucose and sucrose, and then grown photomixotrophically with exogenous organic carbon supply, as added 5 mM glucose or sucrose during N- deprivation. Under these conditions we observed a fourfold increase in extracellular pyruvate excretion when glucose was added, and a smaller increase with added sucrose. Although the magnitude of pyruvate excretion did not correlate with the capacity of the ΔglgC strain for bicarbonate-dependent photosynthetic O2 evolution, or with light intensity, there was, however, a positive correlation observed between the density of the starter culture prior to N-deprivation and the final extracellular pyruvate concentration. The factors that contribute to enhancement of pyruvate excretion are discussed, as well as consideration of whether the source of carbon for pyruvate excretion might be derived from

  3. Factors Altering Pyruvate Excretion in a Glycogen Storage Mutant of the Cyanobacterium, Synechococcus PCC7942

    PubMed Central

    Benson, Phoebe J.; Purcell-Meyerink, Diane; Hocart, Charles H.; Truong, Thy T.; James, Gabriel O.; Rourke, Loraine; Djordjevic, Michael A.; Blackburn, Susan I.; Price, G. D.

    2016-01-01

    Interest in the production of carbon commodities from photosynthetically fixed CO2 has focused attention on cyanobacteria as a target for metabolic engineering and pathway investigation. We investigated the redirection of carbon flux in the model cyanobacterial species, Synechococcus elongatus PCC 7942, under nitrogen deprivation, for optimized production of the industrially desirable compound, pyruvate. Under nitrogen limited conditions, excess carbon is naturally stored as the multi-branched polysaccharide, glycogen, but a block in glycogen synthesis, via knockout mutation in the gene encoding ADP-glucose pyrophosphorylase (glgC), results in the accumulation of the organic acids, pyruvate and 2-oxoglutarate, as overflow excretions into the extracellular media. The ΔglgC strain, under 48 h of N-deprivation was shown to excrete pyruvate for the first time in this strain. Additionally, by increasing culture pH, to pH 10, it was possible to substantially elevate excretion of pyruvate, suggesting the involvement of an unknown substrate/proton symporter for export. The ΔglgC mutant was also engineered to express foreign transporters for glucose and sucrose, and then grown photomixotrophically with exogenous organic carbon supply, as added 5 mM glucose or sucrose during N- deprivation. Under these conditions we observed a fourfold increase in extracellular pyruvate excretion when glucose was added, and a smaller increase with added sucrose. Although the magnitude of pyruvate excretion did not correlate with the capacity of the ΔglgC strain for bicarbonate-dependent photosynthetic O2 evolution, or with light intensity, there was, however, a positive correlation observed between the density of the starter culture prior to N-deprivation and the final extracellular pyruvate concentration. The factors that contribute to enhancement of pyruvate excretion are discussed, as well as consideration of whether the source of carbon for pyruvate excretion might be derived from

  4. Biliary excretion of iron and ferritin in idiopathic hemochromatosis

    SciTech Connect

    Hultcrantz, R.; Angelin, B.; Bjoern-Rasmussen, E.E.; Ewerth, S.; Einarsson, K.

    1989-06-01

    The role of biliary excretion of iron and ferritin in iron overload was studied and evaluated. Ten patients with idiopathic hemochromatosis and two groups of controls (14 gallstone patients and 16 healthy subjects) were included. Liver tissue (obtained by percutaneous or operative biopsy) was investigated with light microscopy and transmission electron microscopy in combination with x-ray microanalysis. Fasting bile samples were obtained through duodenal aspiration or at cholecystectomy. Iron was determined in liver tissue and bile using atomic absorption spectroscopy, and ferritin was determined in serum and bile with a radioimmunoassay technique. All patients with hemochromatosis had iron-positive staining as seen in light microscopy. Electron microscopy showed iron-containing proteins in the lysosomes and cytosol of liver parenchymal cells, and this observation was supported by x-ray microanalysis. Hepatic iron concentration was increased about eightfold in the patients with hemochromatosis (p less than 0.001). Biliary iron concentration, expressed per millimole of bile acid, was increased about twofold (p less than 0.05) and biliary ferritin concentration about fivefold (p less than 0.001) in hemochromatosis. Four of the patients with hemochromatosis were reexamined after completed treatment with venesection; this resulted in normalized biliary concentrations of iron and ferritin. We conclude that biliary secretion of ferritin occurs in humans and that both iron and ferritin excretion are enhanced in hepatic iron overload. The apparently limited capacity of biliary iron excretion may be of importance for the hepatic iron accumulation in hemochromatosis.

  5. Antidiuretic hormone excretion at high altitude.

    PubMed

    Harber, M J; Williams, J D; Morton, J J

    1981-01-01

    Urinary excretion of electrolytes, creatinine, urea, and antidiuretic hormone--measured as arginine vasopressin (AVP) by radioimmunoassay--was investigated in eight Himalayan mountaineers during ascent on foot from 1900- 5400 m. Specimens were collected from each individual whenever urine was voided, preserved with 1% boric acid, and subsequently pooled to give samples representative of 24-h collections. AVP was found to be reasonably stable under simulated conditions of storage. In all subjects, the observed AVP excretion rates were mostly in the lower region of the normal range and there was generally no correlation with altitude, urine osmolality, electrolyte excretion, or occurrence of AMS symptoms--even in a fatal case of cerebral oedema. It is concluded that AVP does not play a primary role in the changes in fluid balance which accompany either acclimatization to high altitude or the onset of AMS. PMID:7213286

  6. Exposure to acute severe hypoxia leads to increased urea loss and disruptions in acid-base and ionoregulatory balance in dogfish sharks (Squalus acanthias).

    PubMed

    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. PMID:25244375

  7. Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences

    PubMed Central

    Derr, Julien; Manapat, Michael L.; Rajamani, Sudha; Leu, Kevin; Xulvi-Brunet, Ramon; Joseph, Isaac; Nowak, Martin A.; Chen, Irene A.

    2012-01-01

    During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life. PMID:22319215

  8. Involvement of breast cancer resistance protein (ABCG2) in the biliary excretion mechanism of fluoroquinolones.

    PubMed

    Ando, Tomohiro; Kusuhara, Hiroyuki; Merino, Gracia; Alvarez, Ana I; Schinkel, Alfred H; Sugiyama, Yuichi

    2007-10-01

    Fluoroquinolones are effective antibiotics for the treatment of bile duct infections. It has been shown that the biliary excretion of grepafloxacin is partly accounted for by multidrug resistance-associated protein 2 (MRP2/ABCC2), whereas neither MRP2 nor P-glycoprotein is involved in the biliary excretion of ulifloxacin. In the present study, we examined the involvement of breast cancer resistance protein (BCRP/ABCG2) in the biliary excretion of fluoroquinolones (grepafloxacin, ulifloxacin, ciprofloxacin, and ofloxacin). In Madin-Darby canine kidney II cells expressing human BCRP or mouse Bcrp, the basal-to-apical transport of grepafloxacin and ulifloxacin was greater than that of the mock control, which was inhibited by a BCRP inhibitor, 3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[1',2':1,6]pyrido[3,4-b]indol-3-yl)-propionic acid tert-butyl ester (Ko143). Plasma and bile concentrations of fluoroquinolones were determined in wild-type and Bcrp(-/-) mice after i.v. bolus injection. The cumulative biliary excretion of fluoroquinolones was significantly reduced in Bcrp(-/-) mice, resulting in a reduction of the biliary excretion clearances to 86, 50, 40, and 16 of the control values, for ciprofloxacin, grepafloxacin, ofloxacin, and ulifloxacin, respectively. Preinfusion of sulfobromophthalein significantly inhibited the biliary excretion of grepafloxacin in Bcrp(-/-) mice. There was no change in the tissue/plasma concentration ratios of fluoroquinolones in the liver or brain, whereas those in the kidney were increased 3.6- and 1.5-fold for ciprofloxacin and grepafloxacin, respectively, in Bcrp(-/-) mice but were unchanged for ofloxacin and ulifloxacin. The present study shows that BCRP mediates the biliary excretion of fluoroquinolones and suggests that it is also involved in the tubular secretion of ciprofloxacin and grepafloxacin. PMID:17639028

  9. Renal dopamine excretion in healthy volunteers after oral ingestion of L-dopa.

    PubMed

    Barthelmebs, M; Mbou, P; Stephan, D; Grima, M; Imbs, J L

    1993-01-01

    L-Dopa is converted to dopamine by aromatic-L-amino acid decarboxylase (AADC). In the kidney, proximal tubular epithelial cells are rich in AADC and urinary free dopamine excretion is a marker for endorenal extraneuronal dopamine synthesis. The urinary free dopamine excretion was analysed in a double-blind cross-over study after oral ingestion of L-Dopa or a placebo in five healthy volunteers. The drug ingestions were separated by one week's wash-out. Since in a preliminary study, two volunteers ingesting a single L-Dopa dose of 500 mg with breakfast experienced nausea, the five volunteers of the present study were given 300 mg L-Dopa (50 mg at 9 am with breakfast, 100 mg before lunch and 150 mg before dinner) without any adverse effects. L-Dopa induced an increase in 24-h urinary dopamine excretion (HPLC with electrochemical detection). Free urinary dopamine (1900 micrograms/24 h) accounted for 0.8% of the daily oral L-Dopa dose and represented 10% of total urinary dopamine excretion. L-Dopa treatment had no significant effect on mean ambulatory arterial blood pressure and heart rate measured from 9 am to 6 pm (Spacelabs) or on 24 h urinary water and sodium excretion. PMID:8458598

  10. Biliary excretion of pravastatin and taurocholate in rats with bile salt export pump (Bsep) impairment.

    PubMed

    Cheng, Yaofeng; Freeden, Chris; Zhang, Yueping; Abraham, Pamela; Shen, Hong; Wescott, Debra; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2016-07-01

    The bile salt export pump (BSEP) is expressed on the canalicular membrane of hepatocytes regulating liver bile salt excretion, and impairment of BSEP function may lead to cholestasis in humans. This study explored drug biliary excretion, as well as serum chemistry, individual bile acid concentrations and liver transporter expressions, in the SAGE Bsep knockout (KO) rat model. It was observed that the Bsep protein in KO rats was decreased to 15% of that in the wild type (WT), as quantified using LC-MS/MS. While the levels of Ntcp and Mrp2 were not significantly altered, Mrp3 expression increased and Oatp1a1 decreased in KO animals. Compared with the WT rats, the KO rats had similar serum chemistry and showed normal liver transaminases. Although the total plasma bile salts and bile flow were not significantly changed in Bsep KO rats, individual bile acids in plasma and liver demonstrated variable changes, indicating the impact of Bsep KO. Following an intravenous dose of deuterium labeled taurocholic acid (D4-TCA, 2 mg/kg), the D4-TCA plasma exposure was higher and bile excretion was delayed by approximately 0.5 h in the KO rats. No differences were observed for the pravastatin plasma concentration-time profile or the biliary excretion after intravenous administration (1 mg/kg). Collectively, the results revealed that these rats have significantly lower Bsep expression, therefore affecting the biliary excretion of endogenous bile acids and Bsep substrates. However, these rats are able to maintain a relatively normal liver function through the remaining Bsep protein and via the regulation of other transporters. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27059119

  11. Sleep restriction increases free fatty acids in healthy men

    PubMed Central

    Broussard, Josiane L.; Chapotot, Florian; Abraham, Varghese; Day, Andrew; Delebecque, Fanny; Whitmore, Harry R.; Tasali, Esra

    2015-01-01

    Aims/hypothesis Sleep loss is associated with insulin resistance and an increased risk for type 2 diabetes, yet underlying mechanisms are not understood. Elevation of circulating non-esterified (i.e. free) fatty acid (NEFA) concentrations can lead to insulin resistance and plays a central role in the development of metabolic diseases. Circulating NEFA in healthy individuals shows a marked diurnal variation with maximum levels occurring at night, yet the impact of sleep loss on NEFA levels across the 24 h cycle remains unknown. We hypothesised that sleep restriction would alter hormones that are known to stimulate lipolysis and lead to an increase in NEFA levels. Methods We studied 19 healthy young men under controlled laboratory conditions with four consecutive nights of 8.5 h in bed (normal sleep) and 4.5 h in bed (sleep restriction) in randomised order. The 24 h blood profiles of NEFA, growth hormone (GH), noradrenaline (norepinephrine), cortisol, glucose and insulin were simultaneously assessed. Insulin sensitivity was estimated by a frequently sampled intravenous glucose tolerance test. Results Sleep restriction relative to normal sleep resulted in increased NEFA levels during the nocturnal and early-morning hours. The elevation in NEFA was related to prolonged nocturnal GH secretion and higher early-morning noradrenaline levels. Insulin sensitivity was decreased after sleep restriction and the reduction in insulin sensitivity was correlated with the increase in nocturnal NEFA levels. Conclusions/interpretation Sleep restriction in healthy men results in increased nocturnal and early-morning NEFA levels, which may partly contribute to insulin resistance and the elevated diabetes risk associated with sleep loss. PMID:25702040

  12. A high linoleic acid diet increases oxidative stress in vivo and affects nitric oxide metabolism in humans.

    PubMed

    Turpeinen, A M; Basu, S; Mutanen, M

    1998-09-01

    Evidence from in vitro studies shows that increased intake of polyunsaturated fatty acids leads to increased oxidative stress, which may be associated with endothelial damage. We measured the urinary levels of 8-iso-PGF2alpha and nitric oxide metabolites as well as plasma sICAM-1 levels from healthy subjects after strictly controlled diets rich in either linoleic acid (LA, C18:2 n-6) or oleic acid (OA, C18:1 n-9). Thirty-eight volunteers (20 women and 18 men, mean age 27 years) consumed a baseline diet rich in saturated fatty acids (SFA) for 4 weeks and were then switched to either a high LA diet (11.5 en%) or a high OA diet (18.0 en%) also for 4 weeks. During the LA and OA diets, nearly all food was provided for the whole day. A control group of 13 subjects consumed their habitual diet throughout the study. Urinary excretion of 8-iso-PGF2alpha was significantly increased after the LA diet (170 vs 241 ng/mmol creatinine, P=0.04), whereas the urinary concentration of nitric oxide metabolites decreased (4.2 vs 2.6 mg/mmol creatinine, P=0.03). No significant changes were seen in the OA group. Significant differences between the LA and control group were found for both 8-oxo-PGF2alpha (P=0.03) and NO (P=0.02), whereas the OA and LA groups did not differ with respect to any parameter. Also plasma sICAM-1 remained unchanged in both groups throughout the study. In conclusion, the high-LA diet increased oxidative stress and affected endothelial function in a way which may in the long-term predispose to endothelial dysfunction. PMID:9844997

  13. Dietary arachidonic acid dose-dependently increases the arachidonic acid concentration in human milk.

    PubMed

    Weseler, Antje R; Dirix, Chantal E H; Bruins, Maaike J; Hornstra, Gerard

    2008-11-01

    Lactation hampers normalization of the maternal arachidonic acid (AA) status, which is reduced after pregnancy and can further decline by the presently recommended increased consumption of (n-3) long-chain PUFA [(n-3) LCPUFA]. This may be unfavorable for breast-fed infants, because they also require an optimum supply of (n-6) LCPUFA. We therefore investigated the LCPUFA responses in nursing mothers upon increased consumption of AA and (n-3) LCPUFA. In a parallel, double-blind, controlled trial, lactating women received for 8 wk no extra LCPUFA (control group, n = 8), 200 (low AA group, n = 9), or 400 (high AA group, n = 8) mg/d AA in combination with (n-3) LCPUFA [320 mg/d docosahexaenoic acid (DHA), 80 mg/d eicosapentaenoic acid, and 80 mg/d other (n-3) fatty acids], or this dose of (n-3) LCPUFA alone [DHA + eicosapentaenoic acid group, n = 8]. Relative concentrations of AA, DHA, and sums of (n-6) and (n-3) LCPUFA were measured in milk total lipids (TL) and erythrocyte phospholipids (PL) after 2 and 8 wk and changes were compared by ANCOVA. The combined consumption of AA and (n-3) LCPUFA caused dose-dependent elevations of AA and total (n-6) LCPUFA concentrations in milk TL and did not significantly affect the DHA and total (n-3) LCPUFA increases caused by (n-3) LCPUFA supplementation only. This latter treatment did not significantly affect breast milk AA and total (n-6) LCPUFA concentrations. AA and DHA concentrations in milk TL and their changes were strongly and positively correlated with their corresponding values in erythrocyte PL (r(2) = 0.27-0.50; P increased the AA concentration of their milk TL. PMID:18936218

  14. The effect of surgery on the renal excretion of beta 2-microglobulin.

    PubMed

    Walenkamp, G H; Vree, T B; Guelen, P J; Jongman-Nix, B

    1983-03-28

    Surgical trauma causes an increase in the renal excretion rate of beta 2-microglobulin whilst creatinine excretion is not influenced. The increase in the renal excretion rate of beta 2-microglobulin is probably the result of an increased release of beta 2-microglobulin by the cells which exceeds a maximum in the active tubular reabsorption of the compound by the proximal tubule cell. The renal excretion of beta 2-microglobulin is proportional to the relative clinical trauma score. PMID:6189646

  15. Effect of intercalated cell-specific Rh C glycoprotein deletion on basal and metabolic acidosis-stimulated renal ammonia excretion

    PubMed Central

    Lee, Hyun-Wook; Verlander, Jill W.; Bishop, Jesse M.; Nelson, Raoul D.; Handlogten, Mary E.

    2010-01-01

    Rh C glycoprotein (Rhcg) is an NH3-specific transporter expressed in both intercalated cells (IC) and principal cells (PC) in the renal collecting duct. Recent studies show that deletion of Rhcg from both intercalated and principal cells inhibits both basal and acidosis-stimulated renal ammonia excretion. The purpose of the current studies was to better understand the specific role of Rhcg expression in intercalated cells in basal and metabolic acidosis-stimulated renal ammonia excretion. We generated mice with intercalated cell-specific Rhcg deletion (IC-Rhcg-KO) using Cre-loxP techniques; control (C) mice were floxed Rhcg but Cre negative. Under basal conditions, IC-Rhcg-KO and C mice excreted urine with similar ammonia content and pH. Mice were then acid loaded by adding HCl to their diet. Ammonia excretion after acid loading increased similarly in IC-Rhcg-KO and C mice during the first 2 days of acid loading but on day 3 was significantly less in IC-Rhcg-KO than in C mice. During the first 2 days of acid loading, urine was significantly more acidic in IC-Rhcg-KO mice than in C mice; there was no difference on day 3. In IC-Rhcg-KO mice, acid loading increased principal cell Rhcg expression in both the cortex and outer medulla as well as expression of another ammonia transporter, Rh glycoprotein B (Rhbg), in principal cells in the outer medulla. We conclude that 1) Rhcg expression in intercalated cells is necessary for the normal renal response to metabolic acidosis; 2) principal cell Rhcg contributes to both basal and acidosis-stimulated ammonia excretion; and 3) adaptations in Rhbg expression occur in response to acid-loading. PMID:20462967

  16. INTESTINAL EXCRETION OF ENDOGENOUS ZINC IN GUATEMALAN SCHOOL CHILDREN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The intestine is the major route of excretion of endogenous zinc and has a key role in maintaining zinc homeostasis. Phytate has been reported to increase these losses. Objective: To determine the rate of excretion of endogenous zinc in school-aged children in a poor rural community for ...

  17. Increased mutagenicity of chromium compounds by nitrilotriacetic acid

    SciTech Connect

    Loprieno, N.; Boncristiani, G.; Venier, P.; Montaldi, A.; Majone, F.; Bianchi, V.; Paglialunga, S.; Levis, A.G.

    1985-01-01

    Nitrilotriacetic acid trisodium salt (NTA), which is a substitute for polyphosphates in household laundry detergents, and N-nitrosoiminodiacetic acid (NIDA), a derivative of NTA produced by metabolism of soil microorganisms, were tested for in vitro mutagenicity in bacteria and yeasts. No gene reversions in five strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98, and TA100), no forward gene mutations in Schizosaccharomyces pombe P1, and no mitotic gene conversions at two loci in Saccharomyces cerevisiae D4 were induced by NTA and NIDA independently of the presence of rat liver metabolic activation. The influence of NTA on the mutagenic and clastogenic activity of several chromium compounds was examined in the Salmonella/microsome assay and in the sister chromatid exchange (SCE) assay in mammalian cell cultures (Chinese hamster ovary (CHO) line). NTA does not affect the genetic inactivity of water-soluble Cr(III) (Cr/sub 2/(SO/sub 4/)/sub 3/) and the direct mutagenicity of soluble Cr(VI) (Na/sub 2/CrO/sub 4/, K/sub 2/Cr/sub 2/O/sub 7/) compounds. The very insoluble Cr(VI) compounds PbCrO/sub 4/ and PbCrO/sub 4/ x PbO are instead clearly mutagenic in the Salmonella/microsome assay (TA100 strain) only in the presence of NTA or NaOH. The chromosome-damaging activity of PbCrO/sub 4/ is significantly increased by NTA but not by NaOH.

  18. Acid-activated biochar increased sulfamethazine retention in soils.

    PubMed

    Vithanage, Meththika; Rajapaksha, Anushka Upamali; Zhang, Ming; Thiele-Bruhn, Sören; Lee, Sang Soo; Ok, Yong Sik

    2015-02-01

    Sulfamethazine (SMZ) is an ionizable and highly mobile antibiotic which is frequently found in soil and water environments. We investigated the sorption of SMZ onto soils amended with biochars (BCs) at varying pH and contact time. Invasive plants were pyrolyzed at 700 °C and were further activated with 30 % sulfuric (SBBC) and oxalic (OBBC) acids. The sorption rate of SMZ onto SBBC and OBBC was pronouncedly pH dependent and was decreased significantly when the values of soil pH increased from 3 to 5. Modeled effective sorption coefficients (K D,eff) values indicated excellent sorption on SBBC-treated loamy sand and sandy loam soils for 229 and 183 L/kg, respectively. On the other hand, the low sorption values were determined for OBBC- and BBC700-treated loamy sand and sandy loam soils. Kinetic modeling demonstrated that the pseudo second order model was the best followed by intra-particle diffusion and the Elovich model, indicating that multiple processes govern SMZ sorption. These findings were also supported by sorption edge experiments based on BC characteristics. Chemisorption onto protonated and ligand containing functional groups of the BC surface, and diffusion in macro-, meso-, and micro-pores of the acid-activated BCs are the proposed mechanisms of SMZ retention in soils. Calculated and experimental q e (amount adsorbed per kg of the adsorbent at equilibrium) values were well fitted to the pseudo second order model, and the predicted maximum equilibrium concentration of SBBC for loamy sand soils was 182 mg/kg. Overall, SBBC represents a suitable soil amendment because of its high sorption rate of SMZ in soils. PMID:25172460

  19. Recombinant microorganisms for increased production of organic acids

    DOEpatents

    Yi, Jian; Kleff, Susanne; Guettler, Michael V.

    2012-02-21

    Disclosed are recombinant microorganisms for producing organic acids. The recombinant microorganisms express a polypeptide that has the enzymatic activity of an enzyme that is utilized in the pentose phosphate cycle. The recombinant microorganism may include recombinant Actinobacillus succinogenes that has been transformed to express a Zwischenferment (Zwf) gene. The recombinant microorganisms may be useful in fermentation processes for producing organic acids such as succinic acid and lactic acid. Also disclosed are novel plasmids that are useful for transforming microorganisms to produce recombinant microorganisms that express enzymes such as Zwf.

  20. Recombinant microorganisms for increased production of organic acids

    DOEpatents

    Yi, Jian; Kleff, Susanne; Guettler, Michael V

    2013-04-30

    Disclosed are recombinant microorganisms for producing organic acids. The recombinant microorganisms express a polypeptide that has the enzymatic activity of an enzyme that is utilized in the pentose phosphate cycle. The recombinant microorganism may include recombinant Actinobacillus succinogenes that has been transformed to express a Zwischenferment (Zwf) gene. The recombinant microorganisms may be useful in fermentation processes for producing organic acids such as succinic acid and lactic acid. Also disclosed are novel plasmids that are useful for transforming microorganisms to produce recombinant microorganisms that express enzymes such as Zwf.

  1. Acid-Base Homeostasis

    PubMed Central

    Nakhoul, Nazih; Hering-Smith, Kathleen S.

    2015-01-01

    Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. PMID:26597304

  2. Manipulation of dietary methionine+cysteine and threonine in broilers significantly decreases environmental nitrogen excretion.

    PubMed

    Donato, D C Z; Sakomura, N K; Silva, E P; Troni, A R; Vargas, L; Guagnoni, M A N; Meda, B

    2016-06-01

    The intensification of livestock have increased the emission of pollutants to the environment, leading to a growing interest in seeking strategies that minimise these emissions. Studies have shown that it is possible to manipulate diets by reducing CP levels and thus reducing nitrogen (N) excretion, without compromising performance. However, there is no knowledge of any study that has focused on reducing N excretion and relating this reduction to individual amino acids. This study investigated the effect of dietary methionine+cysteine (MC) and threonine (THR), the two most limiting amino acids for broiler production, on nitrogen excretion (NE) and nitrogen deposition (ND) and determined the efficiency of utilisation of both amino acids for protein deposition. Six trials were conducted to measure the NE and ND in broiler chickens during three rearing phases in response to dietary amino acid. The efficiency of utilisation of the amino acids was calculated by linear regression of body protein deposition and the amino acid intake. Despite the differences between sexes and phases, the efficiency of utilisation was the same, being 0.60 and 0.59 for MC and THR, respectively. The rate of NE behaved exponentially, increasing with amino acid intake, and can exceed 50% of N intake, being higher than ND. On average, for a reduction in intake of each unit of MC or THR (mg) there is a reduction of 0.5% of NE. Although this reduction seems low, considering that it corresponds to changes in one amino acid only, the impact on a large scale would be significant. Knowledge of how animals respond to NE and ND/protein deposition according to amino acid dietary content may represent new efforts towards reducing the impact on environment. PMID:27076031

  3. Biliary excretion of acetaminophen-glutathione as an index of toxic activation of acetaminophen: effect of chemicals that alter acetaminophen hepatotoxicity

    SciTech Connect

    Madhu, C.; Gregus, Z.; Klaassen, C.D.

    1989-03-01

    Acetaminophen (AA) is converted, presumably by cytochrome P-450, to an electrophile which is conjugated with glutathione (GS). AA-GS is excreted into bile, therefore the biliary excretion rate of AA-GS may reflect the rate of activation of AA in vivo. In order to test this hypothesis, the effect of agents capable of altering the activation of AA including cytochrome P-450 inducers and inhibitors, cobaltous chloride which decreases the amount of P-450, prostaglandin synthetase inhibitors (indomethacin and naproxen), antioxidants (butylated hydroxyanisole, alpha-tocopherol, ascorbic acid and ascorbic acid palmitate) and other chemicals known to decrease AA hepatotoxicity (dimethylsulfoxide and cysteamine), on the biliary excretion of AA-GS was studied in hamsters, the species most sensitive to AA-induced hepatotoxicity. The biliary excretion of AA-GS increased linearly up to 1 mmol/kg of AA i.v., but at higher dosages exhibited saturation kinetics. Dosages above 0.5 mmol/kg lowered hepatic GS concentration. Of the cytochrome P-450 inducers, 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin, increased the biliary excretion of AA-GS (2.9- and 3.2-fold, respectively) whereas ethanol and isoniazid did not affect it, and pregnenolone-16 alpha-carbonitrile tended to decrease it (43%). Phenobarbital tended to increase the biliary excretion of AA-GS, but not in a statistically significant manner. Several cytochrome P-450 inhibitors (metyrapone, 8-methoxypsoralen, 2-(4,6-dichloro-biphenyloxy) ethylamine, alpha-naphthoflavone and cimetidine) decreased the biliary excretion of AA-GS, although SKF 525-A and piperonyl butoxide did not. Cobaltous chloride decreased dramatically the biliary excretion of AA-GS.

  4. Hesperetin Modifies the Composition of Fecal Microbiota and Increases Cecal Levels of Short-Chain Fatty Acids in Rats.

    PubMed

    Unno, Tomonori; Hisada, Takayoshi; Takahashi, Shunsuke

    2015-09-16

    There has been particular interest in the prebiotic-like effects of commonly consumed polyphenols. This study aimed to evaluate the effects of hesperidin (HD) and its aglycone hesperetin (HT), major flavonoids in citrus fruits, on the structure and activity of gut microbiota in rats. Rats ingested an assigned diet (a control diet, a 0.5% HT diet, or a 1.0% HD diet) for 3 weeks. Terminal restriction fragment length polymorphism analysis revealed that the proportion of Clostridium subcluster XIVa in the feces collected at the third week of feeding was significantly reduced by the HT diet: 19.8 ± 4.3% for the control diet versus 5.3 ± 1.5% for the HT diet (P < 0.01). There was a significant difference in the cecal pool of short-chain fatty acids (SCFA), the sum of acetic, propionic, and butyric acids, between the control diet (212 ± 71 μmol) and the HT diet (310 ± 51 μmol) (P < 0.05), whereas the HD diet exhibited no effects (245 ± 51 μmol). Interestingly, dietary HT resulted in a significant increase in the excretion of starch in the feces. HT, but not HD, might reduce starch digestion, and parts of undigested starch were utilized to produce SCFA by microbial fermentation in the large intestine. PMID:26306898

  5. QSAR analysis of drug excretion into human breast milk.

    PubMed

    Meskin, M S; Lien, E J

    1985-09-01

    Breast feeding has increased by approximately 25% in the United States during the past decade and this trend appears to be continuing. The number of drugs available to lactating women is also growing at a rapid pace. The excretion of drugs into breast-milk presents a potential danger to infants. In spite of this, little is known about the excretion of drugs into breast-milk. The ability to predict which drugs are potential hazards would be very useful in the clinical setting. This study quantitatively correlates the human milk to plasma concentration ratio of various basic and acidic drugs (log M/P) with the square root of the molecular weight, the partition coefficient (log P) and the degree of dissociation (log U/D). For basic drugs there is a negative-dependence on both log P and log U/D. High lipophilicity favours protein binding and reduces the amount of drug available for diffusion into milk. Therefore, as log P increases, the log M/P decreases. The negative-dependence on log U/D indicates that the higher the degree of dissociation of the base in plasma, the greater the log M/P will be. This fits well with the concept of ion-trapping. A strong base is more likely to be transferred and then trapped in milk which has a lower pH than plasma. For acidic drugs there is a negative-dependence on both square root (MW) and log P. The negative-dependence on square root (MW) suggests that large molecules are less likely to be able to diffuse into the milk. A negative-dependence on log P appears to hold true for bases and acids. Log M/P decreases as log P increases. This is probably due to increased protein binding by lipophilic drugs through non-specific hydrophobic interaction with plasma protein. PMID:4066977

  6. An Increase Incidence in Uric Acid Nephrolithiasis: Changing Patterns

    PubMed Central

    Kumari, Asha; Mittal, Pawan; Kumar, Rajender; Goel, Richa; Bansal, Piyush; Kumar, Himanshu Devender; Bhutani, Jaikrit

    2016-01-01

    Introduction Nephrolithiasis is a complex disease affecting all age groups globally. As the causative factors for nephrolithiasis rises significantly, its incidence, prevalence and recurrence continues to baffle clinicians and patients. Aim To study the prevalence of different types of renal stones extracted by Percutaneous Nephrolithotomy (PCNL) and open surgical procedures. Materials and Methods Renal stones from 50 patients were retrieved by Percutaneous Nephrolithotomy (PCNL), Ureterorenoscopy (URS) and open surgical techniques for qualitative tests for detection of calcium, oxalate, uric acid, phosphate, ammonium ion, carbonate, cystine and xanthine. Results Three patients had stone removed by open surgery and rest had undergone PCNL. Nine of the stones were pure of calcium oxalate, 9 were of pure uric acid and 32 were mixed stones. Forty one stones had calcium. Among the mixed stones, oxalate was present in 25 samples (39 of total), uric acid was seen in 17 (25 of total stones), phosphate was present in 23 (23 of total) and carbonate was present in 4 stones (4 of total). Only 1 patient had triple phosphate stone. 12 were of staghorn appearance of which 6 were of struvite type, 6 were pure uric acid and remaining were mixed oxalate-phosphate stones. Conclusion Our study, though in a small number of hospital based patients, found much higher prevalence of uric acid stones and mixed stones than reported by previous hospital based studies in north India (oxalate stones~90%, uric acid~1% and mixed stones~3%). Biochemical analysis of renal stones is warranted in all cases.

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

    PubMed

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

    2016-07-01

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

  8. Transcript and metabolite alterations increase ganoderic acid content in Ganoderma lucidum using acetic acid as an inducer.

    PubMed

    Ren, Ang; Li, Xiong-Biao; Miao, Zhi-Gang; Shi, Liang; Jaing, Ai-Liang; Zhao, Ming-Wen

    2014-12-01

    Acetic acid at 5-8 mM increased ganoderic acid (GA) accumulation in Ganoderma lucidum. After optimization by the response surface methodology, the GA content reached 5.5/100 mg dry weight, an increase of 105% compared with the control. The intermediate metabolites of GA biosynthesis, lanosterol and squalene also increased to 47 and 15.8 μg/g dry weight, respectively, in response to acetic acid. Acetic acid significantly induced transcription levels of sqs, lano, hmgs and cyp51 in the GA biosynthesis pathway. An acetic acid-unregulated acetyl coenzyme A synthase (acs) gene was selected from ten candidate homologous acs genes. The results indicate that acetic acid alters the expression of genes related to acetic acid assimilation and increases GA biosynthesis and the metabolic levels of lanosterol, squalene and GA-a, thereby resulting in GA accumulation. PMID:25216642

  9. Urinary excretion of glycosaminoglycans in malignant diseases of the haemopoietic and lymphatic tissues.

    PubMed

    Friman, C; Juvani, M

    1975-01-01

    A study has been made of the urinary excretion of glycosaminoglycans (GAG) in 50 patients with malignancies, including 6 patients with acute myeloid leukaemia (AML), 11 with chronic myeloid leukaemia (CML), 10 with chronic lymphatic leukaemia (CLL), 10 with multiple myeloma (MM), 7 with Hodgkin's disease and 6 with mycosis fungoides (MF). The total urinary GAG were isolated by precipitation with cetyltrimethyl-ammoniumbromide (CTAB), and assayed in terms of their hexuronic acid content. A statistically highly significant increase in the excretion of total GAG was observed in all the disorders studied, except Hodgkin's disease, the highest value being seen in myeloid leukaemia (ML). Constant amounts of non-dialysable urinary GAG were electrophoresed in 0.5 M lithium acetate on cellulose acetate strips, and stained with alcian blue. The densitometric tracing derived from the electrophoresis strips were analysed with a Du Pont Curve Resolver. The electrophoretic data suggested the existence of a qualitative deviation in GAG excretion in CLL and in MF, in that patients with these diseases excreted on an average larger than normal amounts of slowly migrating GAG fractions. Pooled crude urinary GAG material from patients with CLL, MF, AML and CML and from control subjects was further purified and subjected to analytical studies. These indicated that a similar qualitative urinary GAG distribution exists in ML and in controls, whereas the urinary GAG in CLL and MF patients contained relatively more dermatan sulphate (DS, in terms of iduronate) than those of the controls. PMID:126635

  10. Urinary excretion of arsenic following rice consumption.

    PubMed

    Meharg, A A; Williams, P N; Deacon, C M; Norton, G J; Hossain, M; Louhing, D; Marwa, E; Lawgalwi, Y; Taggart, M; Cascio, C; Haris, P

    2014-11-01

    Patterns of arsenic excretion were followed in a cohort (n = 6) eating a defined rice diet, 300 g per day d.wt. where arsenic speciation was characterized in cooked rice, following a period of abstinence from rice, and other high arsenic containing foods. A control group who did not consume rice were also monitored. The rice consumed in the study contained inorganic arsenic and dimethylarsinic acid (DMA) at a ratio of 1:1, yet the urine speciation was dominated by DMA (90%). At steady state (rice consumption/urinary excretion) ∼40% of rice derived arsenic was excreted via urine. By monitoring of each urine pass throughout the day it was observed that there was considerable variation (up to 13-fold) for an individual's total arsenic urine content, and that there was a time dependent variation in urinary total arsenic content. This calls into question the robustness of routinely used first pass/spot check urine sampling for arsenic analysis. PMID:25145278

  11. Engineering Porous Organic Cage Crystals with Increased Acid Gas Resistance.

    PubMed

    Zhu, Guanghui; Hoffman, Christopher D; Liu, Yang; Bhattacharyya, Souryadeep; Tumuluri, Uma; Jue, Melinda L; Wu, Zili; Sholl, David S; Nair, Sankar; Jones, Christopher W; Lively, Ryan P

    2016-07-25

    Both known and new CC3-based porous organic cages are prepared and exposed to acidic SO2 in vapor and liquid conditions. Distinct differences in the stability of the CC3 cages exist depending on the chirality of the diamine linkers used. The acid catalyzed CC3 degradation mechanism is probed via in situ IR and a degradation pathway is proposed and supported with computational results. CC3 crystals synthesized with racemic mixtures of diaminocyclohexane exhibited enhanced stability compared to CC3-R and CC3-S. Confocal fluorescent microscope images reveal that the stability difference in CC3 species originates from an abundance of mesoporous grain boundaries in CC3-R and CC3-S, allowing facile access of aqueous SO2 throughout the crystal, promoting decomposition. These grain boundaries are absent from CC3 crystals made with racemic linkers. PMID:27253350

  12. Chylomicrons enhance endotoxin excretion in bile.

    PubMed Central

    Read, T E; Harris, H W; Grunfeld, C; Feingold, K R; Calhoun, M C; Kane, J P; Rapp, J H

    1993-01-01

    Chylomicrons prevent endotoxin toxicity and increase endotoxin uptake by hepatocytes. As a consequence, less endotoxin is available to activate macrophages, thereby reducing tumor necrosis factor secretion. To determine whether the chylomicron-mediated increase in hepatocellular uptake of endotoxin results in increased endotoxin excretion into bile, we examined bile after endotoxin administration. A sublethal dose (7 micrograms/kg) of 125I-endotoxin was incubated with either rat mesenteric lymph containing nascent chylomicrons (500 mg of chylomicron triglyceride per kg of body weight) or an equal volume of normal saline (controls) for 3 h and then infused into male Sprague-Dawley rats. Bile samples were collected via a common bile duct catheter for 24 h. Infusion of endotoxin incubated with chylomicrons increased biliary excretion of endotoxin by 67% at 3 h (P < or = 0.006) and by 20% at 24 h (P < or = 0.01) compared with infusion of endotoxin incubated in saline. Endotoxin activity, as measured by the Limulus assay, was not detected in the bile of test animals. However, endotoxin activity was detected after hot phenol-water extraction of bile, demonstrating that endotoxin is inactive in the presence of bile but retains bioactivity after hepatic processing. Since the majority of an intravenous endotoxin load has been shown to be cleared by the liver, acceleration of hepatocyte clearance and biliary excretion of endotoxin may represent a component of the mechanism by which chylomicrons protect against endotoxin-induced lethality. PMID:8335381

  13. Altered Nitrogen Balance and Decreased Urea Excretion in Male Rats Fed Cafeteria Diet Are Related to Arginine Availability

    PubMed Central

    Sabater, David; Arriarán, Sofía; Fernández-López, José-Antonio; Romero, María del Mar; Remesar, Xavier

    2014-01-01

    Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids. We analyzed whether reduced urea excretion was a consequence of higher NOx; (nitrite, nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion. There were no differences in plasma nitrate or nitrite. NOx and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithine when compared with controls, whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability. PMID:24707502

  14. Enhancement in fecal excretion of dioxin isomer in mice by several dietary fibers.

    PubMed

    Aozasa, O; Ohta, S; Nakao, T; Miyata, H; Nomura, T

    2001-10-01

    The effect of increased nutrients (protein, lipid, vitamins and minerals) on dioxin-induced toxic manifestations such as immune suppression, hepatic hypertrophy, splenic atrophy and enzyme induction was investigated in mice after oral administration of 1,2,3,4,7,8-HxCDD (HxCDD) as one of a representative compound of dioxin isomers. Consequently, it appeared that increased minerals and vitamins in the diet prevented immune suppression by HxCDD. In addition, to clarify the additive effect of nutrients and the ability to hasten the excretion of dioxins by dietary fiber, the adsorbing of dioxins by 16 dietary fibers was investigated by in vitro experiment. Among 16 dietary fibers, locust bean gum, pectin, alginic acid, guar gum, chitin and cellulose were effective in binding dioxin isomers. These dietary fibers also enhanced the fecal excretion of HxCDD in mice. PMID:11572611

  15. The effect of feeding diets containing permitted antibiotics on the faecal excretion of Salmonella typhimurium by experimentally infected chickens.

    PubMed Central

    Smith, H. W.; Tucker, J. F.

    1975-01-01

    Groups of 45 chickens were fed continuously on diets containing 10 or 100 mg./kg. of different 'growth-promoting' antibiotics and infected orally with a nalidixic acid-resistant mutant of Salmonella typhimurium. The amount of S. typhimurium organisms excreted in their faeces was estimated by culturing them at weekly intervals and in a standard manner on plates of brilliant green agar containing sodium nalidixate, both direct and after enrichment in selenite broth. All of four groups fed diets containing 100 mg./kg. of nitrovin in three different experiments excreted much larger amounts of S. typhimurium than did groups fed antibiotic-free diets. In some, but not all, experiments, larger amounts were also excreted by groups fed diets containing 10 mg./kg. of nitrovin or 10 or 100 mg./kg. of flavomycin or tylosin. Feeding diets containing 10 or 100 mg./kg. of virginiamycin or bacitracin either did not influence or slightly increased the amount of S. typhimiurium excreted. Two groups fed continuously on diets containing 100 or 500 mg./kg. of sulphaquinoxaline for 44 days excreted smaller amounts of the S. typhimurium organisms that did groups fed antibiotic-free diets; no sulphonamide-resistant organisms of the S. typhimurium strain were isolated from the faeces. PMID:1100715

  16. Hydrogen Sulfide Targets EGFR Cys797/Cys798 Residues to Induce Na+/K+-ATPase Endocytosis and Inhibition in Renal Tubular Epithelial Cells and Increase Sodium Excretion in Chronic Salt-Loaded Rats

    PubMed Central

    Ge, Shun-Na; Zhao, Man-Man; Wu, Dong-Dong; Chen, Ying; Wang, Yi; Zhu, Jian-Hua; Cai, Wen-Jie; Zhu, Yi-Zhun

    2014-01-01

    Abstract Aims: The role of hydrogen sulfide (H2S) in renal sodium and water homeostasis is unknown. We investigated whether H2S promoted Na+/K+-ATPase endocytosis via the H2S/EGFR/gab1/PI3K/Akt pathway in renal tubular epithelial cells. Results: H2S decreased Na+/K+-ATPase activity and induced its endocytosis in renal tubular epithelial cells, which was abrogated by small interfering RNA (siRNA) knockdown of epidermal growth factor receptor (EGFR) and gab1, a dominant-negative mutant of Akt and PI3K inhibitors. H2S increased EGFR, gab1, PI3K, and Akt phosphorylation in both renal tubular epithelial cells and kidneys of chronic salt-loaded rats. These increases were abrogated by siRNA knockdown of EGFR, but not of c-Src. Radiolabeled H2S exhibited transient, direct binding to EGFR and directly activated EGFR. Some disulfide bonds in EGFR intracellular kinase domain were susceptible to H2S-induced cleavage. Mutations of EGFR Cys797 (human) or Cys798 (rat) residues increased EGFR activity and prevented H2S-induced Na+/K+-ATPase endocytosis. H2S also inhibited sodium hydrogen exchanger-3 (NHE3) activity in renal tubular epithelial cells. H2S treatment increased sodium excretion in chronic and acute salt-loaded rats and decreased blood pressure in chronic salt-loaded rats. Innovation and Conclusion: H2S directly targets some disulfide bonds in EGFR, which activates the EGFR/gab1/PI3K/Akt pathway and subsequent Na+/K+-ATPase endocytosis and inhibition in renal tubular epithelial cells. EGFR Cys797/Cys798 residues are essential for an intrinsic inhibitory mechanism and for H2S actions in renal tubular epithelial cells. Other pathways, including NHE3, may be involved in mediating the renal effects of H2S. Our results reveal a new renal sodium homeostasis mechanism, which may provide for novel treatment approaches for diseases related to renal sodium homeostasis dysfunction. Antioxid. Redox Signal. 21, 2061–2082. PMID:24684506

  17. Increased Production of Fatty Acids and Triglycerides in Aspergillus oryzae by Enhancing Expressions of Fatty Acid Synthesis-Related Genes

    SciTech Connect

    Tamano, Koichi; Bruno, Kenneth S.; Karagiosis, Sue A.; Culley, David E.; Deng, Shuang; Collett, James R.; Umemura, Myco; Koike, Hideaki; Baker, Scott E.; Machida, Masa

    2013-01-01

    Microbial production of fats and oils is being developedas a means of converting biomass to biofuels. Here we investigate enhancing expression of enzymes involved in the production of fatty acids and triglycerides as a means to increase production of these compounds in Aspergillusoryzae. Examination of the A.oryzaegenome demonstrates that it contains twofatty acid synthases and several other genes that are predicted to be part of this biosynthetic pathway. We enhancedthe expressionof fatty acid synthesis-related genes by replacing their promoters with thepromoter fromthe constitutively highly expressedgene tef1. We demonstrate that by simply increasing the expression of the fatty acid synthasegenes we successfullyincreasedtheproduction of fatty acids and triglyceridesby more than two fold. Enhancement of expression of the fatty acid pathway genes ATP-citrate lyase and palmitoyl-ACP thioesteraseincreasedproductivity to a lesser extent.Increasing expression ofacetyl-CoA carboxylase caused no detectable change in fatty acid levels. Increases in message level for each gene were monitored usingquantitative real-time RT-PCR. Our data demonstrates that a simple increase in the abundance of fatty acid synthase genes can increase the detectable amount of fatty acids.

  18. Effects of dairy cow diet forage proportion on duodenal nutrient supply and urinary purine derivative excretion.

    PubMed

    Moorby, J M; Dewhurst, R J; Evans, R T; Danelón, J L

    2006-09-01

    Four mature Holstein-Friesian dairy cows were used in a 4 x 4 Latin square change-over design experiment made up of four 4-wk periods to investigate the relationship between microbial protein flow to the duodenum and excretion of purine derivatives (PD) in the urine. Four dietary treatments based on ad libitum access to ryegrass silage were offered, with a standard dairy concentrate included at different forage:concentrate (F:C) ratios, calculated on a dry matter basis: 80:20, 65:35, 50:50, and 35:65. Feed intakes increased as the proportion of concentrate in the diet increased, despite a concurrent decrease in silage intake. Increased feed intake led to increased nutrient flow to the duodenum. Milk yields increased as the diet F:C ratio decreased, with cows offered the 35:65 diet yielding nearly 8 kg/d more milk than cows offered the 80:20 diet; the concentrations of milk fat decreased and milk protein increased with a decreasing F:C ratio. Purine derivative excretion in the urine increased with an increasing proportion of concentrate in the diet, and there was a strong linear relationship between total PD excretion (allantoin and uric acid) and microbial N flow to the duodenum: microbial N (g/d) = 19.9 + 0.689 x total PD (mmol/d); R = 0.887. This strengthens the case for using PD excretion as a noninvasive marker of microbial protein flow from the rumen in dairy cows. PMID:16899691

  19. Urinary excretion of meperidine and its metabolites.

    PubMed

    Yeh, S Y; Krebs, H A; Changchit, A

    1981-08-01

    The urine of male and female mice, rats, guinea pigs, rabbits, cats, and dogs, given meperidine hydrochloride, 20--40 mg/kg ip, was analyzed by GLC for meperidine, normeperidine, p-hydroxymeperidine, and total (free and conjugated) meperidinic and normeperidinic acids. More than 90% of the excreted drugs was found in the 24-hr urine. Meperidine was observed in the urine of mice, rats, guinea pigs, and cats, but only a trace amount was observed in the urine of rabbits and dogs. Normeperidine, p-hydroxymeperidine (except in the mice), and total meperidinic and normeperidinic acids were observed in all species. All of the species studied have the capacity to N-demethylate meperidine to normeperidine and to hydrolyze meperidine and normeperidine to their respective acids. The male has a higher N-demethylating activity that the female with the exception of mice. Ester hydrolysis is a major metabolic pathway for meperidine metabolism. PMID:7310653

  20. Increase in the permeability of tonoplast of garlic (Allium sativum) by monocarboxylic acids.

    PubMed

    Bai, Bing; Li, Lei; Hu, Xiaosong; Wang, Zhengfu; Zhao, Guanghua

    2006-10-18

    Immersion of intact aged garlic (Allium sativum) cloves in a series of 5% weak organic monocarboxylate solutions (pH 2.0) resulted in green color formation. No color was formed upon treatment with other weak organic acids, such as citric and malic acids, and the inorganic hydrochloric acid under the same conditions. To understand the significance of monocarboxylic acids and their differing function from that of other acids, acetic acid was compared with organic acids citric and malic and the inorganic hydrochloric acid. The effects of these acids on the permeability of plasma and intracellular membrane of garlic cells were measured by conductivity, light microscopy, and transmission electron microscopy. Except for hydrochloric acid, treatment of garlic with all three organic acids greatly increased the relative conductivity of their respective pickling solutions, indicating that all tested organic acids increased the permeability of plasma membrane. Moreover, a pickling solution containing acetic acid exhibited 1.5-fold higher relative conductivity (approximately 90%) as compared to those (approximately 60%) of both citric and malic acids, implying that exposure of garlic cloves to acetic acid not only changed the permeability of the plasma membrane but also increased the permeability of intracellular membrane. Exposure of garlic to acetic acid led to the production of precipitate along the tonoplast, but no precipitate was formed by citric and malic acids. This indicates that the structure of the tonoplast was damaged by this treatment. Further support for this conclusion comes from results showing that the concentration of thiosulfinates [which are produced only by catalytic conversion of S-alk(en)yl-l-cysteine sulfoxides in cytosol by alliinase located in the vacuole] in the acetic acid pickling solution is 1.3 mg/mL, but almost no thiosulfinates were detected in the pickling solution of citric and malic acids. Thus, all present results suggest that damage of

  1. Absorption, biotransformation, and excretion of environmental chemicals.

    PubMed

    Oehme, F W

    1980-08-01

    Foreign chemicals are continually present in the environment of man and animals. Mammalian systems are in a constant state of balance-the intake compensated for by the outflow. The intake is largely determined by the route of exposure and the chemical characteristics of the environmental compound. Under normal conditions of exposure to small or moderate amounts of environmental chemicals, the system is capable of biotransforming and detoxifying such materials into compounds more easily handled by the mammalian system. These are largely converted to more water-soluble materials and excreted in the urine, bile, and less commonly through other excretory routes. In situations of massive exposure to foreign materials, or when repeated exposure to moderate amounts of chemicals results in accumulation in body systems, toxicoses may result. These are essentially an overwhelming of the biological mechanisms for detoxifying and excreting such materials. The hazard associated with environmental chemicals is greatly increased if a preexisting disease modifies the normal biological detoxification processes. Therapy to assist intoxicated individuals is largely aimed at increasing excretory processes and maintaining or restoring the physiological balance between the amount of environmental chemical absorbed and the level capable of being excreted. PMID:7408430

  2. Energetics of end product excretion in anaerobic bacteria and the metabolism of fatty acids by Syntrophomonas wolfei: Progress report, November 16, 1986-November 15, 1987

    SciTech Connect

    McInerney, M.J.

    1987-01-01

    We have studied the growth and metabolism of Syntrophomonas wolfei in pure culture with crotonate as the energy source. S. wolfei grows in crotonate mineral salts medium without rumen fluid with cobalamin, thymine, lipoic acid and biotin added. However, after four to six transfers in this medium, growth ceases, indicating that another vitamin is required. The chemically defined medium allows large batches of S. wolfei to be grown for enzyme purification. All the enzymes involved in the oxidation of crotonyl-CoA to acetate have been detected. The pure culture of S. wolfei or coculture of S. wolfei grown with crotonate contain high activities of a crotonate: acetyl-CoA CoA-transferase activity. This activity is not detected in cocultures grown with butyrate. Thus, we believe that the reason why S. wolfei can now grow with crotonate is that an alteration or mutation occurred which allows the organism to activate this crotonate. S. wolfei also makes small amounts of H/sub 2/ when grown in pure culture with crotonate. A methyl viologen-dependent hydrogenase activity was found. We have also demonstrated the production of H/sub 2/ from 3-hydroxybutyryl-CoA in cell-free extracts of S. wolfei by coupling H/sub 2/ production to CH/sub 4/ production with the addition of Methanobacterium bryantii and directly using a hydrogen electrode. These results clearly show that S. wolfei makes H/sub 2/. S. wolfei does not contain formate dehydrogenase or CO dehydrogenase activities.

  3. Increased Bile Acid Synthesis and Deconjugation After Biliopancreatic Diversion.

    PubMed

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

    2015-10-01

    Biliopancreatic diversion (BPD) improves insulin sensitivity and decreases serum cholesterol out of proportion with weight loss. Mechanisms of these effects are unknown. One set of proposed contributors to metabolic improvements after bariatric surgeries is bile acids (BAs). We investigated the early and late effects of BPD on plasma BA levels, composition, and markers of BA synthesis in 15 patients with type 2 diabetes (T2D). We compared these to the early and late effects of Roux-en-Y gastric bypass (RYGB) in 22 patients with T2D and 16 with normal glucose tolerance. Seven weeks after BPD, insulin sensitivity had doubled and serum cholesterol had halved. At this time, BA synthesis markers and total plasma BAs, particularly unconjugated BAs, had markedly risen; this effect could not be entirely explained by low FGF19. In contrast, after RYGB, insulin sensitivity improved gradually with weight loss and cholesterol levels declined marginally; BA synthesis markers were decreased at an early time point (2 weeks) after surgery and returned to the normal range 1 year later. These findings indicate that BA synthesis contributes to the decreased serum cholesterol after BPD. Moreover, they suggest a potential role for altered enterohepatic circulation of BAs in improving insulin sensitivity and cholesterol metabolism after BPD. PMID:26015549

  4. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

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

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  5. Effect of disulfiram pretreatment on the tissue distribution, macromolecular binding, and excretion of (U-1,2-14C)dichloroethane in the rat

    SciTech Connect

    Igwe, O.J.; Que Hee, S.S.; Wagner, W.D.

    1986-01-01

    The effect of disulfiram (DSF) pretreatment on the distribution of (14C)ethylene dichloride (EDC) in selected organs and/or tissues of control and EDC-pretreated rats was studied. The presence of EDC metabolites and their binding to an acid-insoluble extract of the tissues, as well as purified protein and DNA, were evaluated. Dietary DSF was found to modulate the distribution, excretion, and macromolecular binding of EDC and/or its metabolites at 4 and 24 hr following ip administration. The urinary excretion of (14C)EDC metabolites was not affected by subchronic inhalation exposure to nonradiolabeled EDC. However, DSF pretreatment increased the fat deposition of EDC and decreased the urinary excretion of its metabolites. DSF also increased the binding of EDC metabolites to DNA and decreased the binding to protein in the liver, kidneys, spleen, and testes. However, prior exposure to EDC alone increased the binding of its metabolites to DNA in the kidneys only.

  6. Increased universality of Lepidopteran elicitor compounds across insects: Identification of fatty acid amino acid conjugates (FACs)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acid amino acid conjugates (FACs) are known elicitors of induced release of volatile compounds in plants that, in turn, attract foraging parasitoids. Since the discovery of volicitin [N-(17-hydroxylinolenoyl)-L-glutamine] in the regurgitant of larval Spodoptera exigua1, a series of related FAC...

  7. Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance

    PubMed Central

    Ding, Jun; Holzwarth, Garrett; Penner, Michael H.; Patton-Vogt, Jana; Bakalinsky, Alan T.

    2015-01-01

    Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification. PMID:25673654

  8. Increase of betulinic acid production in Saccharomyces cerevisiae by balancing fatty acids and betulinic acid forming pathways.

    PubMed

    Li, Jing; Zhang, Yansheng

    2014-04-01

    Betulinic acid is a plant-based triterpenoid that has been recognized for its antitumor and anti-HIV activities. The level of betulinic acid in its natural hosts is extremely low. In the present study, we constructed betulinic acid biosynthetic pathway in Saccharomyces cerevisiae by metabolic engineering. Given the betulinic acid forming pathways sharing the common substrate acetyl-CoA with fatty acid synthesis, the metabolic fluxes between the two pathways were varied by changing gene expressions, and their effects on betulinic acid production were investigated. We constructed nine S. cerevisiae strains representing nine combinations of the flux distributions between betulinic acid and fatty acid pathways. Our results demonstrated that it was possible to improve the betulinic acid production in S. cerevisiae while keeping a desirable growth phenotype by optimally balancing the carbon fluxes of the two pathways. Through modulating the expressions of the key genes on betulinic acid and fatty acid pathways, the difference in betulinic acid yield varied largely in the range of 0.01-1.92 mg L(-1) OD(-1). The metabolic engineering approach used in this study could be extended for synthesizing other triterpenoids in S. cerevisiae. PMID:24389702

  9. Intravenous lipid and amino acids briskly increase plasma glucose concentrations in small premature infants.

    PubMed

    Savich, R D; Finley, S L; Ogata, E S

    1988-07-01

    We determined the glycemic response to intravenous lipid infusion alone, lipid with amino acids, or amino acids alone in 15 very small premature infants receiving constant glucose infusion during early life. Infants who received lipid or lipid and amino acids demonstrated significant increases in glucose compared with infants who received amino acids. The combination of lipid and amino acids resulted in an earlier increase than lipid alone. Although plasma insulin did not change in all three groups, infants who received amino acids alone demonstrated an appropriate increase in glucagon. These data suggest that lipid infusion, a commonly used means of providing nutrition to premature infants, may cause significant disturbances in glucoregulation, particularly when administered with amino acids. PMID:3132930

  10. Directed evolution increases desaturation of a cyanobacterial fatty acid desaturase in eukaryotic expression systems.

    PubMed

    Bai, Shuangyi; Wallis, James G; Denolf, Peter; Browse, John

    2016-07-01

    Directed evolution of a cyanobacterial Δ9 fatty acid desaturase (DSG) from Synechococcus elongatus, PCC6301 created new, more productive desaturases and revealed the importance of certain amino acid residues to increased desaturation. A codon-optimized DSG open reading frame with an endoplasmic-reticulum retention/retrieval signal appended was used as template for random mutagenesis. Increased desaturation was detected using a novel screen based on complementation of the unsaturated fatty acid auxotrophy of Saccharomyces cerevisiae mutant ole1Δ. Amino acid residues whose importance was discovered by the random processes were further examined by saturation mutation to determine the best amino acid at each identified location in the peptide chain and by combinatorial analysis. One frequently-detected single amino acid change, Q240R, yielded a nearly 25-fold increase in total desaturation in S. cerevisiae. Several other variants of the protein sequence with multiple amino acid changes increased total desaturation more than 60-fold. Many changes leading to increased desaturation were in the vicinity of the canonical histidine-rich regions known to be critical for electron transfer mediated by these di-iron proteins. Expression of these evolved proteins in the seed of Arabidopsis thaliana altered the fatty acid composition, increasing monounsaturated fatty acids and decreasing the level of saturated fatty acid, suggesting a potential application of these desaturases in oilseed crops. Biotechnol. Bioeng. 2016;113: 1522-1530. © 2016 Wiley Periodicals, Inc. PMID:26724425

  11. Cobalt excretion test for the assessment of body iron stores.

    PubMed

    Sorbie, J; Olatunbosun, D; Corbett, W E; Valberg, L S

    1971-05-01

    Iron absorption is under delicate control and the level of absorption is adjusted to comply with the body's need for iron. To measure the intestinal setting for iron absorption, and thereby indirectly assess body iron requirements, cobaltous chloride labelled with (57)Co or (60)Co was given by mouth and the percentage of the test dose excreted in the urine in 24 hours was measured in a gamma counter. Seventeen control subjects with normal iron stores excreted 18% (9-23%) of the dose. Increased excretion, 31% (23-42%), was found in 10 patients with iron deficiency anemia and in 15 patients with depleted iron stores in the absence of anemia. In contrast, 12 patients with anemia due to causes other than iron deficiency excreted amounts of radiocobalt within the normal control range. In patients with iron deficiency, replenishment of iron stores by either oral or parenteral iron caused the previously high results to return to normal.Excretion of the test dose was normal in portal cirrhosis with normal iron stores but it was markedly increased in patients with cirrhosis complicated by either iron deficiency or endogenous iron overload. It was also raised in primary hemochromatosis. Excretion of the dose was reduced in gluten-sensitive enteropathy. Gastrointestinal surgery and inflammatory disease of the lower small intestine had no effect on the results except that some patients with steatorrhea had diminished excretion.The cobalt excretion test provides the clinician with a tool for the assessment of iron absorption, the detection of a reduction in body iron stores below the level that is normal for the subject in question, the differentiation of iron deficiency anemia from anemia due to other causes, and the investigation of patients with iron-loading disorders. PMID:5578125

  12. Ammonia excretion in mytilid mussels is facilitated by ciliary beating.

    PubMed

    Thomsen, J; Himmerkus, N; Holland, N; Sartoris, F J; Bleich, M; Tresguerres, M

    2016-08-01

    The excretion of nitrogenous waste products in the form of ammonia (NH3) and ammonium (NH4 (+)) is a fundamental process in aquatic organisms. For mytilid bivalves, little is known about the mechanisms and sites of excretion. This study investigated the localization and the mechanisms of ammonia excretion in mytilid mussels. An Rh protein was found to be abundantly expressed in the apical cell membrane of the plicate organ, which was previously described as a solely respiratory organ. The Rh protein was also expressed in the gill, although at significantly lower concentrations, but was not detectable in mussel kidney. Furthermore, NH3/NH4 (+) was not enriched in the urine, suggesting that kidneys are not involved in active NH3/NH4 (+) excretion. Exposure to elevated seawater pH of 8.5 transiently reduced NH3/NH4 (+) excretion rates, but they returned to control values following 24 h acclimation. These mussels had increased abundance of V-type H(+)-ATPase in the apical membranes of plicate organ cells; however, NH3/NH4 (+) excretion rates were not affected by the V-type H(+)-ATPase specific inhibitor concanamycin A (100 nmol l(-1)). In contrast, inhibition of ciliary beating with dopamine and increased seawater viscosity significantly reduced NH3 excretion rates under control pH (8.0). These results suggest that NH3/NH4 (+) excretion in mytilid mussels takes place by passive NH3 diffusion across respiratory epithelia via the Rh protein, facilitated by the water current produced for filter feeding, which prevents accumulation of NH3 in the boundary layer. This mechanism would be energy efficient for sessile organisms, as they already generate water currents for filter feeding. PMID:27489216

  13. Effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol.

    PubMed Central

    Yamamoto, T; Moriwaki, Y; Takahashi, S; Suda, M; Higashino, K

    1991-01-01

    The effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol were investigated. Pyrazinamide decreased the mean (SEM) fractional clearance of oxypurinol from 19.2 (2.1) to 8.8 (1.5). Probenecid increased the fractional clearance of oxypurinol from 14.1 (3.5) to 24.8 (4.1). Benzbromarone increased the fractional clearance of oxypurinol from 15.6 (2.3) to 33.8 (2.8). These results suggest that oxypurinol may be secreted by 'an organic acid system' and that oxypurinol is reabsorbed at a putative postsecretory site of the renal tubules. PMID:1929586

  14. Chlorogenic acid increased 5-hydroxymethylfurfural formation when heating fructose alone or with aspartic acid at two pH levels.

    PubMed

    Zhang, Zhenhua; Zou, Yueyu; Wu, Taigang; Huang, Caihuan; Pei, Kehan; Zhang, Guangwen; Lin, Xiaohua; Bai, Weibin; Ou, Shiyi

    2016-01-01

    Chlorogenic acid (CGA) is a phenolic acid that ubiquitously exists in fruits. This work aims to investigate whether and how CGA influences HMF formation during heating fructose alone, or with an amino acid. The results showed that that CGA increased 5-hydroxymethylfurfural (HMF) formation. At pH 5.5 and 7.0, the addition of 5.0 μmol/ml CGA increased HMF formation by 49.4% and 25.2%, respectively when heating fructose alone, and by 9.0% and 16.7%, respectively when heating fructose with aspartic acid. CGA significantly increased HMF formation by promoting 3-deoxosone formation, and its conversion to HMF by inhibiting HMF elimination, especially in the Maillard reaction system. A comparison of the catalytic capacity of CGA with its six analogous compounds showed that both its di-hydroxyphenyl and carboxyl groups function in increasing HMF formation. PMID:26213045

  15. Ammonia excretion by Azobacter chroococcum

    SciTech Connect

    Narula, N.; Lakshminarayana, K.; Tauro, P.

    1981-02-01

    In recent years, research has focused attention on the development of biological systems for nitrogen fixation. In this report, two strains of Azotobacter chroococcum are identified which can excrete as much as 45 mg ammonia/ml of the culture broth in a sucrose supplemented synthetic medium.

  16. Phosphorus limitation strategy to increase propionic acid flux towards 3-hydroxyvaleric acid monomers in Cupriavidus necator.

    PubMed

    Grousseau, Estelle; Blanchet, Elise; Déléris, Stéphane; Albuquerque, Maria G E; Paul, Etienne; Uribelarrea, Jean-Louis

    2014-02-01

    Properties of polyhydroxybutyrate-co-hydroxyvalerate (P(3HB-co-3HV)) depend on their 3HV content. 3HV can be produced by Cupriavidus necator from propionic acid. Few studies explored carbon distribution and dynamics of 3HV and 3HB monomers production, and none of them have been done with phosphorus as limiting nutrient. In this study, fed-batch cultures of C. necator with propionic acid, as sole carbon source or mixed with butyric acid, were performed. Phosphorus deficiency allowed sustaining 3HV production rate and decreasing 3HB production rate, leading to an instant production of up to 100% of 3HV. When a residual growth is sustained by a phosphorus feeding, the maximum 3HV percentage produced from propionic acid is limited to 33% (Mole.Mole(-1)). The association of a second carbon source like butyric acid lead to higher conversion of propionic acid into 3HV. This study showed the importance of the limiting nutrient and of the culture strategy to get the appropriate product. PMID:24365742

  17. Anthocyanin excretion increases linearly with increasing strawberry dose.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A clinical study was conducted to investigate the dose response and metabolism of strawberry anthocyanins. In a crossover study design, twelve healthy adults consumed each of three strawberry treatments. The treatments were 100 g, 200 g, and 400 g of pureed strawberries, delivering 15 micromol, 30 m...

  18. The Chinese soft-shelled turtle, Pelodiscus sinensis, decreases nitrogenous excretion, reduces urea synthesis and suppresses ammonia production during emersion.

    PubMed

    Ip, Yuen K; Lee, Serene M L; Wong, Wai P; Chew, Shit F

    2013-05-01

    The objective of this study was to examine the effects of 6 days of emersion on nitrogen metabolism and excretion in the Chinese soft-shelled turtle, Pelodiscus sinensis. Despite having a soft shell with a cutaneous surface that is known to be water permeable, P. sinensis lost only ~2% of body mass and was able to maintain its hematocrit and plasma osmolality, [Na(+)] and [Cl(-)] during 6 days of emersion. During emersion, it ameliorated water loss by reducing urine output, which led to a reduction (by 29-76%) in ammonia excretion. In comparison, there was a more prominent reduction (by 82-99%) in urea excretion during emersion due to a lack of water to flush the buccopharyngeal epithelium, which is known to be the major route of urea excretion. Consequently, emersion resulted in an apparent shift from ureotely to ammonotely in P. sinensis. Although urea concentration increased in several tissues, the excess urea accumulated could only account for 13-22% of the deficit in urea excretion. Hence, it can be concluded that a decrease (~80%) in urea synthesis occurred in P. sinensis during the 6 days of emersion. Indeed, emersion led to significant decreases in the activity of some ornithine-urea cycle enzymes (argininosuccinate synthetase/argininosuccinate lyase and arginase) from the liver of P. sinensis. As a decrease in urea synthesis occurred without the accumulation of ammonia and total free amino acids, it can be deduced that ammonia production through amino acid catabolism was suppressed with a proportional reduction in proteolysis in P. sinensis during emersion. Indeed, calculated results revealed that there could be a prominent decrease (~88%) in ammonia production in turtles after 6 days of emersion. In summary, despite being ureogenic and ureotelic in water, P. sinensis adopted a reduction in ammonia production, instead of increased urea synthesis, as the major strategy to ameliorate ammonia toxicity and problems associated with dehydration during

  19. Contribution of dietary oxalate to urinary oxalate excretion

    NASA Technical Reports Server (NTRS)

    Holmes, R. P.; Goodman, H. O.; Assimos, D. G.

    2001-01-01

    BACKGROUND: The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and stone formation. Dietary oxalate is believed to make only a minor (10 to 20%) contribution to the amount of oxalate excreted in urine, but the validity of the experimental observations that support this conclusion can be questioned. An understanding of the actual contribution of dietary oxalate to urinary oxalate excretion is important, as it is potentially modifiable. METHODS: We varied the amount of dietary oxalate consumed by a group of adult individuals using formula diets and controlled, solid-food diets with a known oxalate content, determined by a recently developed analytical procedure. Controlled solid-food diets were consumed containing 10, 50, and 250 mg of oxalate/2500 kcal, as well as formula diets containing 0 and 180 mg oxalate/2500 kcal. Changes in the content of oxalate and other ions were assessed in 24-hour urine collections. RESULTS: Urinary oxalate excretion increased as dietary oxalate intake increased. With oxalate-containing diets, the mean contribution of dietary oxalate to urinary oxalate excretion ranged from 24.4 +/- 15.5% on the 10 mg/2500 kcal/day diet to 41.5 +/- 9.1% on the 250 mg/2500 kcal/day diet, much higher than previously estimated. When the calcium content of a diet containing 250 mg of oxalate was reduced from 1002 mg to 391 mg, urinary oxalate excretion increased by a mean of 28.2 +/- 4.8%, and the mean dietary contribution increased to 52.6 +/- 8.6%. CONCLUSIONS: These results suggest that dietary oxalate makes a much greater contribution to urinary oxalate excretion than previously recognized, that dietary calcium influences the bioavailability of ingested oxalate, and that the absorption of dietary oxalate may be an important factor in calcium oxalate stone formation.

  20. Quantitative immunological determination of 12 plasma proteins excreted in human urine collected before and after exercise

    PubMed Central

    Poortmans, Jacques; Jeanloz, Roger W.

    1968-01-01

    Urine was collected from 6 healthy male adults at rest and from 20 male adults after a marathon race (25 miles). The concentrated urines were quantitatively analyzed, by single radial immunodiffusion, for their content in 12 different plasma proteins: tryptophan-rich prealbumin, albumin, α1-acid glycoprotein, α1-antitrypsin, ceruloplasmin, haptoglobin, Gc-globulin, transferrin, hemopexin, β2-glycoprotein I, γA-globulin, and γG-globulin. Albumin, γA-globulin, and γG-globulin represent the major part of the plasma proteins detected in normal urine excreted by humans at rest (12, 0.5, and 2.5 mg respectively, out of a total excretion of 17.5 mg of plasma proteins per 24 hr). The other plasma proteins were excreted at a lower rate (< 0.4 mg/24 hr). The relative content of tryptophan-rich prealbumin, α1-antitrypsin, Gc-globulin, transferrin, and γG-globulin was lower in normal urine than in normal serum, whereas that of α1-acid glycoprotein, β2-glycoprotein I, and γA-globulin was higher. The ratio of γG-globulin to γA-globulin was 4.9:1. When plotted on a logarithmic scale, no direct relationship between the molecular weight of a protein and the value of its renal clearance could be observed. Strenuous exercise increased (up to 50-fold) the excretion of plasma proteins which represent 82% of the total proteins found in urine, instead of 57% in urine collected from humans at rest. There was particularly a significant rise of tryptophan-rich albumin, albumin, α1-acid glycoprotein, transferrin, γA-globulin, and γG-globulin (0.26, 127, 11.8, 3.3, 1.2, and 2.0 μg respectively, out of a total excretion of 167 μg of plasma proteins per min). The ratio of γG-globulin to γA-globulin was 16:1. After exercise, the renal clearance of proteins increased from 2 to 40 times, but, as for the urine of normal subjects at rest, no direct relationship between molecular weight and renal clearance could be observed. Images PMID:4170390

  1. [SKIERS URINARY CATECHOLAMINES EXCRETION AT REST AND BY COMPETITIVE LOADS LENGTH VARIETY].

    PubMed

    Chinkin, A S

    2015-11-01

    While night sleeps urinary noradrenaline excretion of skilled skiers less than their untrained peers, but the difference in excretion of adrenaline is not revealed. By increasing the distance and time to overcome it during skiing catecholamine excretion is increased both - totally and per minute. Most urinary catecholamines detected at a distance of 50 km in low sliding: increased excretion of adrenaline - 84 times, and noradrenaline -95 times. These results shows that high qualificated skier's functional reserve of the sympathoadrenal system, is mobilize at long competitions for ten times higher than in rest. PMID:26995960

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

    PubMed

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

    2015-02-01

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

  3. Increased Biomass Yield of Lactococcus lactis by Reduced Overconsumption of Amino Acids and Increased Catalytic Activities of Enzymes

    PubMed Central

    Adamberg, Kaarel; Seiman, Andrus; Vilu, Raivo

    2012-01-01

    Steady state cultivation and multidimensional data analysis (metabolic fluxes, absolute proteome, and transcriptome) are used to identify parameters that control the increase in biomass yield of Lactococcus lactis from 0.10 to 0.12 C-mol C-mol−1 with an increase in specific growth rate by 5 times from 0.1 to 0.5 h−1. Reorganization of amino acid consumption was expressed by the inactivation of the arginine deiminase pathway at a specific growth rate of 0.35 h−1 followed by reduced over-consumption of pyruvate directed amino acids (asparagine, serine, threonine, alanine and cysteine) until almost all consumed amino acids were used only for protein synthesis at maximal specific growth rate. This balanced growth was characterized by a high glycolytic flux carrying up to 87% of the carbon flow and only amino acids that relate to nucleotide synthesis (glutamine, serine and asparagine) were consumed in higher amounts than required for cellular protein synthesis. Changes in the proteome were minor (mainly increase in the translation apparatus). Instead, the apparent catalytic activities of enzymes and ribosomes increased by 3.5 times (0.1 vs 0.5 h−1). The apparent catalytic activities of glycolytic enzymes and ribosomal proteins were seen to follow this regulation pattern while those of enzymes involved in nucleotide metabolism increased more than the specific growth rate (over 5.5 times). Nucleotide synthesis formed the most abundant biomonomer synthetic pathway in the cells with an expenditure of 6% from the total ATP required for biosynthesis. Due to the increase in apparent catalytic activity, ribosome translation was more efficient at higher growth rates as evidenced by a decrease of protein to mRNA ratios. All these effects resulted in a 30% decrease of calculated ATP spilling (0.1 vs 0.5 h−1). Our results show that bioprocesses can be made more efficient (using a balanced metabolism) by varying the growth conditions. PMID:23133574

  4. Ammonia excretion in aquatic and terrestrial crabs.

    PubMed

    Weihrauch, Dirk; Morris, Steve; Towle, David W

    2004-12-01

    The excretory transport of toxic ammonia across epithelia is not fully understood. This review presents data combined with models of ammonia excretion derived from studies on decapod crabs, with a view to providing new impetus to investigation of this essential issue. The majority of crabs preserve ammonotely regardless of their habitat, which varies from extreme hypersaline to freshwater aquatic environments, and ranges from transient air exposure to obligate air breathing. Important components in the excretory process are the Na+/K+(NH4+)-ATPase and other membrane-bound transport proteins identified in many species, an exocytotic ammonia excretion mechanism thought to function in gills of aquatic crabs such as Carcinus maenas, and gaseous ammonia release found in terrestrial crabs, such as Geograpsus grayi and Ocypode quadrata. In addition, this review presents evidence for a crustacean Rhesus-like protein that shows high homology to the human Rhesus-like ammonia transporter both in its amino acid sequence and in its predicted secondary structure. PMID:15579545

  5. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions

    PubMed Central

    2010-01-01

    Background Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Methods Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. Results The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. Conclusions These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation. PMID:21092209

  6. Exogenous fatty acids affect CDP-choline pathway to increase phosphatidylcholine synthesis in granular pneumocytes

    SciTech Connect

    Chander, A.; Gullo, J.; Reicherter, J.; Fisher, A.

    1987-05-01

    Regulation of phosphatidylcholine (PC) synthesis in rat granular pneumocytes isolated by tryptic digestion of lungs and maintained in primary culture for 24 h was investigated by following effects of exogenous fatty acids on (/sup 3/H-methyl)choline incorporation into PC and disaturated PC (DSPC). At 0.1 mM choline, the rate of choline incorporation into PC and DSPC was 440 +/- and 380 +/- 50 pmol/h/ug Pi (mean +/- SE, n=3-5), respectively, and was linear for up to 3 h. PC synthesis was significantly increased by 0.1 mM each of palmitic, oleic, linoleic, or linolenic acid. However, synthesis of DSPC was increased only by palmitic acid and this increase was prevented by addition of oleic acid suggesting lack of effect on the remodeling pathway. Pulse-chase experiments with choline in absence or presence of palmitic or oleic acid showed that the label declined in choline phosphate and increased in PC more rapidly in presence of either of the fatty acids, suggesting rapid conversion of choline phosphate to PC. Microsomal choline phosphate cytidyltransferase activity in cells preincubated without or with palmitic acid for 3 h was 0.81 +/- 0.07 and 1.81 +/- 0.09 nmol choline phosphate converted/min/mg protein (n=4). These results suggest that in granular pneumocytes, exogenous fatty acids modulate PC synthesis by increasing choline phosphate cytidyltransferase activity.

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

    PubMed

    Fu, Zidong Donna; Klaassen, Curtis D

    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. PMID:24183703

  8. Uric acid secretion from adipose tissue and its increase in obesity.

    PubMed

    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

    2013-09-20

    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

  9. Dietary oleic acid increases M2 macrophages in the mesenteric adipose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several studies have implicated fatty-acids as inflammatory regulators, suggesting that there may be a direct role for common dietary fatty-acids in regulating innate immune cells. In humans, a single high-fat meal increases systemic cytokines and leukocytes. In mice, short term high-fat feeding in...

  10. Excretion of drugs in human breast milk

    SciTech Connect

    Welch, R.M.; Findlay, J.W.

    1981-01-01

    The present report briefly discusses some of the morphological, physiological, and compositional aspects of animal and human breast milk and how these characteristics might be important for the accumulation of drugs and foreign compounds. In addition, a study is described confirming the presence of caffeine, codeine, morphine, phenacetin, acetaminophen, and salicylic acid in the breast milk of a lactating mother following oral administration of a combination analgesic containing aspirin, phenacetin, caffeine, and codeine. Although the study is limited to one subject, it has provided critically needed data on the rates of appearance in, and elimination of these drugs from, breast milk. A similar amount of information is presented on phenacetin, also a component of the analgesic mixture, which has not been previously reported to enter human milk. The distribution of these drugs between the slightly more acidic breast milk and the relatively neutral plasma is consistent with their weakly basic, acidic, or relatively neutral properties. In general, the study shows that codeine and morphine milk concentrations are higher than, salicylic acid milk levels are much lower than, and phenacetin, caffeine, and acetaminophen milk concentrations are relatively similar to their respective plasma levels. It is projected, from estimated steady-state milk concentrations of the drugs and their metabolites studied, that very low percentages of the therapeutic dosages (less than 0.7%) would be excreted in mother's milk, too low an amount to be clinically significant to the infant.

  11. Endogenous flow of amino acids in the avian ileum as influenced by increasing dietary peptide concentrations.

    PubMed

    Ravindran, Velmurugu; Morel, Patrick C H; Rutherfurd, Shane M; Thomas, Donald V

    2009-03-01

    The aim of the present study was to establish whether feeding broiler chickens with diets containing increasing dietary peptide concentrations would cause increases in ileal endogenous amino acid flow. The flow of N and most amino acids increased quadratically (P < 0.05 to 0.001) with increasing dietary concentrations of peptides. The exceptions were the flow of threonine, serine, glycine, tyrosine and cystine, which increased linearly (P < 0.001) with dietary peptide levels. Another notable exception to the general trend was the flow of proline, which was significantly higher (P < 0.01) in birds fed the protein-free diet. The amino acid profile of endogenous protein, expressed as proportion of crude protein, indicated that the ratios of threonine, glutamic acid, proline, glycine, leucine, histidine, arginine and cystine were influenced (P < 0.05) with increasing dietary peptide concentrations. In general, compared with the protein-free diet, the ratios of threonine and arginine in endogenous protein were lower (P < 0.05) and those of glutamic acid, glycine and histidine were greater (P < 0.05) in diets with high concentrations of peptides. The ratio of proline was found to decrease (P < 0.05) with increasing dietary peptide concentrations. These changes in the amino acid profile of endogenous protein are probably reflective of changes in the output of one or more of the components of endogenous protein. Overall, the present results demonstrated that increasing dietary peptide concentrations increased the flow of endogenous amino acid flow at the terminal ileum of broiler chickens in a dose-dependent manner and also caused changes in the composition of endogenous protein. The observed changes in endogenous amino flow will influence the maintenance requirements for amino acids and also have implications for the calculation of true digestibility coefficient of feedstuffs. PMID:18662428

  12. Titratable acidity: a Pitts concept revisited.

    PubMed

    Mioni, Roberto; Mioni, Giuseppe

    2014-08-01

    Titratable Acidity (TA) in urine can be measured directly or calculated from actual and reference pH, by using the pKa₂ 6,8 for phosphate. In urine, H₂PO₄(-) represents the excretion of filtered H₂PO₄(-), filtrated HPO₄(2-) being completely reabsorbed by the proximal tubule (the Van Slyke approach). Since excretion of H₂PO₄(-) frequently exceeds its glomerular filtration, this approach is considered inadequate by Pitts. He claimed that it is the tubular H(+) secretion which converts filtered HPO₄(2-) to H₂PO₄(-), thereafter excreted in urine. This is only true under conditions of inorganic acid or neutral phosphate loading, when the maximum tubular phosphate reabsorption (TmPi) is overcharged. In controls, H₂PO₄(-) excretion is lower than its glomerular filtration, provided that acid-base status is normal and tubular phosphate reabsorption is below the TmPi. The TmPi is lower than its glomerular filtration, provided that acid-base status is normal and tubular phosphate reabsorption is below the TmPi. When the TmPi is exceeded, a portion of HPO₄(2-) escapes proximal reabsorption, reaching the distal tubule where its absorption is precluded, while tubular H(+) secretion converts HPO₄(2-) to H₂PO₄(-). In man and dog, the attainment of TmPi is evidenced by a FE% of 20%, and only beyond this limit H₂PO₄(-) excretion exceeds glomerular filtration. When FE% is lower than 20%, H₂PO₄(-) filtration exceeds excretion, HPO4(2-) being completely reabsorbed at the proximal tubule by NaPi-2a and 2c cotransporters. While Van Slyke's approach is always valid, Pitts' approach is only valid under loading conditions, when the two processes of H₂PO₄(-) excretion overlap each other. NH (+4) increases inversely to TA excretion in conditions of acidosis and tP restriction, but is independent of TA in Pi-replete dogs, independently of acidosis. PMID:24684475

  13. Increase in adipose tissue linoleic acid of US adults in the last half century.

    PubMed

    Guyenet, Stephan J; Carlson, Susan E

    2015-11-01

    Linoleic acid (LA) is a bioactive fatty acid with diverse effects on human physiology and pathophysiology. LA is a major dietary fatty acid, and also one of the most abundant fatty acids in adipose tissue, where its concentration reflects dietary intake. Over the last half century in the United States, dietary LA intake has greatly increased as dietary fat sources have shifted toward polyunsaturated seed oils such as soybean oil. We have conducted a systematic literature review of studies reporting the concentration of LA in subcutaneous adipose tissue of US cohorts. Our results indicate that adipose tissue LA has increased by 136% over the last half century and that this increase is highly correlated with an increase in dietary LA intake over the same period of time. PMID:26567191

  14. Dihydrolipoic acid activates oligomycin-sensitive thiol groups and increases ATP synthesis in mitochondria.

    PubMed

    Zimmer, G; Mainka, L; Krüger, E

    1991-08-01

    Investigations with dihydrolipoic acid in rat heart mitochondria and mitoplasts reveal an activation of ATP-synthase up to 45%, whereas ATPase activities decrease by 36%. In parallel with an increase in ATP synthesis oligomycin-sensitive mitochondrial -SH groups are activated at 2-4 nmol dihydrolipoic acid/mg protein. ATPase activation by the uncouplers carbonylcyanide-p-trifluoromethoxyphenylhydrazone and oleate is diminished by dihydrolipoic acid, and ATP synthesis depressed by oleate is partially restored. No such efficiency of dihydrolipoic acid is seen with palmitate-induced ATPase activation or decrease of ATP synthesis. This indicates different interference of oleate and palmitate with mitochondria. In addition to its known coenzymatic properties dihydrolipoic acid may act as a substitute for coenzyme A, thereby diminishing the uncoupling efficiency of oleate. Furthermore, dihydrolipoic acid is a very potent antioxidant, shifting the -SH-S-S- equilibrium in mitochondria to the reduced state and improving the energetic state of cells. PMID:1832845

  15. Strongyloides stercoralis larvae excretion patterns before and after treatment.

    PubMed

    Schär, F; Hattendorf, J; Khieu, V; Muth, S; Char, M C; Marti, H P; Odermatt, P

    2014-06-01

    The variability of larval excretion impedes the parasitological diagnosis of Strongyloides stercoralis in infected individuals. We assessed the number of larvae excreted per gram (LPG) stool in 219 samples from 38 infected individuals over 7 consecutive days before and in 470 samples from 44 persons for 21 consecutive days after ivermectin treatment (200 μg kg-1 BW). The diagnostic sensitivity of a single stool sample was about 75% for individuals with low-intensity infections (⩽1 LPG) and increased to 95% for those with high-intensity infections (⩾10 LPG). Doubling the number of samples examined per person increased sensitivity to more than 95%, even for low-intensity infections. There was no indication of a cyclic excretion of larvae. After treatment, all individuals stopped excreting larvae within 3 days. Larvae were not detected during any of the following 18 days (total 388 Baermann and 388 Koga Agar tests). Two stool samples, collected on consecutive days, are recommended in settings where low or heterogeneous infection intensities are likely. In this way, taking into account the possible biological variability in excretion, the efficacy of ivermectin treatment can be assessed as soon as 4 days after treatment. PMID:24534076

  16. Changes in parasite transmission stage excretion after pheasant release.

    PubMed

    Villanúa, D; Acevedo, P; Höfle, U; Rodríguez, O; Gortázar, C

    2006-09-01

    The production of parasite transmission stages was investigated in the faeces of 77 farm-bred ring-necked pheasants (Phasianus colchicus). Coccidian oocysts (Eimeria sp.), and nematode eggs (Heterakis sp., and Capillaria-like eggs) were recovered before and after release but all birds were treated prior to release. Treatment with fenbendazole significantly reduced the abundance of transmission-stage excretion for all parasites, and reduced the prevalence in the case of Eimeria sp. and Heterakis sp. Nonetheless, a significant increase in the excretion abundance for all parasites and in the prevalence of Eimeria sp. and Heterakis sp. was found after release. Eggs of Ascaridia sp. were found only after releasing, suggesting infection ocurred in the wild. A negative relationship was found between the pheasant body condition and Heterakis excretion abundance and a higher abundance of Capillaria sp. eggs in female birds. No significant relationship was found between parasite excretion abundance and pheasant survival. Despite this, results suggest that an increase in the excretion of parasite transmission stages follows the release of captive pheasants into the wild. This can in part explain restocking failures, but also means that autochtonous free-living birds may become exposed to new and potentially harmful pathogens. To avoid these risks it is proposed that improved prophylactic measures should be taken. PMID:16923277

  17. Homeostatic control of manganese excretion in the neonatal rat

    SciTech Connect

    Ballatori, N.; Miles, E.; Clarkson, T.W.

    1987-05-01

    Previous studies in neonatal and suckling animals showed that immature animals have a greatly diminished capacity to excrete manganese and therefore were considered to be unable to regulate tissue manganese concentrations. In contrast, the present studies indicate that suckling rats have the capacity to excrete excess manganese at rates nearly comparable to those of adults. Eight- to 10-day-old rats given a tracer dose of /sup 54/MnCl/sub 2/ (essentially carrier free), either via gavage or by intraperitoneal injection showed little elimination of the /sup 54/Mn until the 18-19th day of life, when there was an abrupt increase in the rate of the metal's excretion. However, when manganese was given in doses of 1 and 10 mg/kg, the young animals excreted from 30-70% of the dose in only 4 days, at which time a new rate of excretion was achieved. This enhanced rate of excretion remained constant until the 18-19th day of life, when it was again accelerated. Biliary excretion of manganese, the primary route for the elimination of the metal, was only 30-60% lower in 14-day-old rats compared with adults at doses ranging from tracer to 10 mg /sup 54/Mn/kg. For both the 14-day-old and adult rats, an apparent biliary transport maximum was reached at a dose of 10 mg Mn/kg. These studies indicate that the excretory pathways for manganese are well developed in the neonatal rat. The avid retention of tracer quantities of manganese by the neonate may be a consequence of the scarcity of this essential trace metal in its diet.

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

    SciTech Connect

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

    1990-03-01

    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.

  19. Fatty acids and glucose increase neutral endopeptidase activity in human microvascular endothelial cells.

    PubMed

    Muangman, Pornprom; Spenny, Michelle L; Tamura, Richard N; Gibran, Nicole S

    2003-06-01

    Neutral endopeptidase (NEP), a membrane-bound metallopeptidase enzyme that degrades neuropeptides, bradykinin, atrial natriuretic factor, enkephalins, and endothelin may regulate response to injury. We have previously demonstrated increased NEP localization and enzyme activity in diabetic wounds and skin compared with normal controls. We hypothesized that hyperlipidemia and hyperglycemia associated with type 2 diabetes mellitus may induce excessive NEP activity and thereby diminish normal response to injury. Human microvascular endothelial cells were treated with five different fatty acids (40 microM) with varying degrees of saturation, including oleic acid, linoleic acid, palmitic acid, stearic acid, and linolenic acid and/or glucose (40 mM) for 48 h. The effect of the antioxidative agents vitamin E and C on NEP enzyme activation was determined by treating the cultured cells with alpha-tocopherol succinate and/or L-ascorbic acid. Cell membrane preparations were assayed for NEP activity by incubation with glutaryl-Ala-Ala-Phe-4-methoxy-beta naphthylamide to generate a fluorescent degradation product methoxy 2 naphthylamine. High glucose or fatty acid concentration upregulated NEP activity. The highest NEP activity was observed with combined elevated glucose, linoleic acid, and oleic acid (P < 0.05). Antioxidant vitamin E and C treatment significantly reduced NEP enzyme activity after fatty acid exposure (P < 0.05). Thus, hyperglycemia and hyperlipidemia associated with type 2 diabetes mellitus may increase endothelial cell NEP activity and thereby decrease early pro-inflammatory responses. The modulator effect of vitamin E and C on NEP membrane enzyme activity after exposure to fatty acid stimulation suggests that lipid oxidation may activate NEP. PMID:12785004

  20. Skeletal muscle amino acid transporter expression is increased in young and older adults following resistance exercise

    PubMed Central

    Fry, Christopher S.; Glynn, Erin L.; Timmerman, Kyle L.; Dickinson, Jared M.; Walker, Dillon K.; Gundermann, David M.; Volpi, Elena; Rasmussen, Blake B.

    2011-01-01

    Amino acid transporters and mammalian target of rapamycin complex 1 (mTORC1) signaling are important contributors to muscle protein anabolism. Aging is associated with reduced mTORC1 signaling following resistance exercise, but the role of amino acid transporters is unknown. Young (n = 13; 28 ± 2 yr) and older (n = 13; 68 ± 2 yr) subjects performed a bout of resistance exercise. Skeletal muscle biopsies (vastus lateralis) were obtained at basal and 3, 6, and 24 h postexercise and were analyzed for amino acid transporter mRNA and protein expression and regulators of amino acid transporter transcription utilizing real-time PCR and Western blotting. We found that basal amino acid transporter expression was similar in young and older adults (P > 0.05). Exercise increased L-type amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, sodium-coupled neutral amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, and cationic amino acid transporter 1/SLC7A1 mRNA expression in both young and older adults (P < 0.05). L-type amino acid transporter 1 and CD98 protein increased only in younger adults (P < 0.05). eukaryotic initiation factor 2 α-subunit (S52) increased similarly in young and older adults postexercise (P < 0.05). Ribosomal protein S6 (S240/244) and activating transcription factor 4 nuclear protein expression tended to be higher in the young, while nuclear signal transducer and activator of transcription 3 (STAT3) (Y705) was higher in the older subjects postexercise (P < 0.05). These results suggest that the rapid upregulation of amino acid transporter expression following resistance exercise may be regulated differently between the age groups, but involves a combination of mTORC1, activating transcription factor 4, eukaryotic initiation factor 2 α-subunit, and STAT3. We propose an increase in amino acid transporter expression may contribute to enhanced amino acid sensitivity following exercise in young and older

  1. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    PubMed

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF. PMID:27144905

  2. Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli.

    PubMed

    Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M; Baerga-Ortiz, Abel

    2014-02-01

    Increasing the production of fatty acids by microbial fermentation remains an important step toward the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations toward accessible biodiesel precursors. PMID:24411456

  3. Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli

    PubMed Central

    Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M.; Baerga-Ortiz, Abel

    2014-01-01

    Increasing the production of fatty acids by microbial fermentation remains an important step towards the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations towards accessible biodiesel precursors. PMID:24411456

  4. Short term tolvaptan increases water intake and effectively decreases urinary calcium oxalate, calcium phosphate, and uric acid supersaturations

    PubMed Central

    Cheungpasitporn, Wisit; Erickson, Stephen B.; Rule, Andrew D.; Enders, Felicity; Lieske, John C.

    2016-01-01

    Purpose Many patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should reduce urinary supersaturation (SS) of stone forming solutes, but this has never been proven. Materials and Methods We conducted a double blind, randomized, placebo-controlled, crossover study in 21 adult calcium urinary stone formers stratified as majority calcium oxalate(CaOx, n=10) or calcium phosphate(CaP, n=11). Patients received tolvaptan 45 mg/day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24h urines was collected at the end of weeks 1 and 3. Results Tolvaptan vs. placebo decreased urinary osmolality (204±96 vs 529±213 mOsm/kg, P<0.001) and increased urinary volume (4.8±2.9 vs 1.8±0.9 L, P<0.001). The majority of urinary solute excretion rates including sodium and calcium did not significantly change, although oxalate secretion slightly increased (23±8 to 15±8 mg/24h, P = 0.009). Urinary CaOx SS (−0.01±1.14 vs 0.95±0.87 DG, P<0.001), CaP SS (−1.66±1.17 vs −0.13±1.02 DG, P<0.001) and Uric Acid SS (−2.05±4.05 vs −5.24±3.12 DG, P=0.04) all dramatically decreased. Effects did not differ between CaOx and CaP groups (P>0.05 for all interactions). Conclusions Tolvaptan increases urine volume and decreases urinary SS in calcium stone formers. Further study is needed to determine if long term use of V2 receptor antagonists results in fewer stone events. PMID:26598423

  5. Increased expression of SVCT2 in a new mouse model raises ascorbic acid in tissues and protects against paraquat-induced oxidative damage in lung.

    PubMed

    Harrison, Fiona Edith; Best, Jennifer Lee; Meredith, Martha Elizabeth; Gamlin, Clare Ruth; Borza, Dorin-Bogdan; May, James Marion; May, James Michael

    2012-01-01

    A new transgenic mouse model for global increases in the Sodium Dependent Vitamin C transporter 2 (SVCT2) has been generated. The SVCT2-Tg mouse shows increased SVCT2 mRNA levels in all organs tested and correspondingly increased ascorbic acid (ASC) levels in all organs except liver. The extent of the increase in transporter mRNA expression differed among mice and among organs. The increased ASC levels did not have any adverse effects on behavior in the SVCT2-Tg mice, which did not differ from wild-type mice on tests of locomotor activity, anxiety, sensorimotor or cognitive ability. High levels of SVCT2 and ASC were found in the kidneys of SVCT2-Tg mice and urinary albumin excretion was lower in these mice than in wild-types. No gross pathological changes were noted in kidneys from SVCT2-Tg mice. SVCT2 immunoreactivity was detected in both SVCT2 and wild-type mice, and a stronger signal was seen in tubules than in glomeruli. Six treatments with Paraquat (3x10 and 3x15 mg/kg i.p.) were used to induce oxidative stress in mice. SVCT2-Tg mice showed a clear attenuation of Paraquat-induced oxidative stress in lung, as measured by F(2)-isoprostanes. Paraquat also decreased SVCT2 mRNA signal in liver, lung and kidney in SVCT2-Tg mice. PMID:22558179

  6. Increased Expression of SVCT2 in a New Mouse Model Raises Ascorbic Acid in Tissues and Protects against Paraquat-Induced Oxidative Damage in Lung

    PubMed Central

    Harrison, Fiona Edith; Best, Jennifer Lee; Meredith, Martha Elizabeth; Gamlin, Clare Ruth; Borza, Dorin-Bogdan; May, James Michael

    2012-01-01

    A new transgenic mouse model for global increases in the Sodium Dependent Vitamin C transporter 2 (SVCT2) has been generated. The SVCT2-Tg mouse shows increased SVCT2 mRNA levels in all organs tested and correspondingly increased ascorbic acid (ASC) levels in all organs except liver. The extent of the increase in transporter mRNA expression differed among mice and among organs. The increased ASC levels did not have any adverse effects on behavior in the SVCT2-Tg mice, which did not differ from wild-type mice on tests of locomotor activity, anxiety, sensorimotor or cognitive ability. High levels of SVCT2 and ASC were found in the kidneys of SVCT2-Tg mice and urinary albumin excretion was lower in these mice than in wild-types. No gross pathological changes were noted in kidneys from SVCT2-Tg mice. SVCT2 immunoreactivity was detected in both SVCT2 and wild-type mice, and a stronger signal was seen in tubules than in glomeruli. Six treatments with Paraquat (3x10 and 3x15 mg/kg i.p.) were used to induce oxidative stress in mice. SVCT2-Tg mice showed a clear attenuation of Paraquat-induced oxidative stress in lung, as measured by F2-isoprostanes. Paraquat also decreased SVCT2 mRNA signal in liver, lung and kidney in SVCT2-Tg mice. PMID:22558179

  7. Dietary alpha-linolenic acid increases brain but not heart and liver docosahexaenoic acid levels.

    PubMed

    Barceló-Coblijn, Gwendolyn; Collison, Lauren W; Jolly, Christopher A; Murphy, Eric J

    2005-08-01

    Fish oil-enriched diets increase n-3 FA in tissue phospholipids; however, a similar effect by plant-derived n-3 FA is poorly defined. To address this question, we determined mass changes in phospholipid FA, individual phospholipid classes, and cholesterol in the liver, heart, and brain of rats fed diets enriched in flax oil (rich in 18:3n-3), fish oil (rich in 22:6n-3 and 20:5n-3), or safflower oil (rich in 18:2n-6) for 8 wk. In the heart and liver phospholipids, 22:6n-3 levels increased only in the fish oil group, although rats fed flax oil accumulated 20:5n-3 and 22:5n-3. However, in the brain, the flax and fish oil diets increased the phospholipid 22:6n-3 mass. In all tissues, these diets decreased the 20:4n-6 mass, although the effect was more marked in the fish oil than in the flax oil group. Although these data do not provide direct evidence for 18:3n-3 elongation and desaturation by the brain, they demonstrate that 18:3n-3-enriched diets reduced tissue 20:4n-6 levels and increased cellular n-3 levels in a tissue-dependent manner. We hypothesize, based on the lack of increased 22:6n-3 but increased 18:3n-3 in the liver and heart, that the flax oil diet increased circulating 18:3n-3, thereby presenting tissue with this EFA for further elongation and desaturation. PMID:16296397

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

    SciTech Connect

    Fu, Zidong Donna; Klaassen, Curtis D.

    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.

  9. Chemical Changes Associated with Increased Acid Resistance of Er:YAG Laser Irradiated Enamel

    PubMed Central

    Olea-Mejía, Oscar Fernando; García-Fabila, María Magdalena; Rodríguez-Vilchis, Laura Emma; Sánchez-Flores, Ignacio; Centeno-Pedraza, Claudia

    2014-01-01

    Background. An increase in the acid resistance of dental enamel, as well as morphological and structural changes produced by Er:YAG laser irradiation, has been reported. Purpose. To evaluate the chemical changes associated with acid resistance of enamel treated with Er:YAG laser. Methods. Forty-eight enamel samples were divided into 4 groups (n = 12). Group I (control); Groups II, III, and IV were irradiated with Er:YAG at 100 mJ (12.7 J/cm2), 200 mJ (25.5 J/cm2), and 300 mJ (38.2 J/cm2), respectively. Results. There were significant differences in composition of irradiated groups (with the exception of chlorine) and in the amount of calcium released. Conclusions. Chemical changes associated with an increase in acid resistance of enamel treated with Er:YAG laser showed a clear postirradiation pattern characterized by a decrease in C at.% and an increase in O, P, and Ca at.% and no changes in Cl at.%. An increased Ca/P ratio after Er:YAG laser irradiation was associated with the use of higher laser energy densities. Chemical changes produced by acid dissolution showed a similar trend among experimental groups. Stable or increased Ca/P ratio after acid dissolution was observed in the irradiated groups, with reduction of Ca released into the acid solution. PMID:24600327

  10. Acetic acid suppresses the increase in disaccharidase activity that occurs during culture of caco-2 cells.

    PubMed

    Ogawa, N; Satsu, H; Watanabe, H; Fukaya, M; Tsukamoto, Y; Miyamoto, Y; Shimizu, M

    2000-03-01

    To understand how blood glucose level is lowered by oral administration of vinegar, we examined effects of acetic acid on glucose transport and disaccharidase activity in Caco-2 cells. Cells were cultured for 15 d in a medium containing 5 mmol/L of acetic acid. This chronic treatment did not affect cell growth or viability, and furthermore, apoptotic cell death was not observed. Glucose transport, evaluated with a nonmetabolizable substrate, 3-O-methyl glucose, also was not affected. However, the increase of sucrase activity observed in control cells (no acetic acid) was significantly suppressed by acetic acid (P < 0.01). Acetic acid suppressed sucrase activity in concentration- and time-dependent manners. Similar treatments (5 mmol/L and 15 d) with other organic acids such as citric, succinic, L-maric, L-lactic, L-tartaric and itaconic acids, did not suppress the increase in sucrase activity. Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme, whereas the activities of other hydrolases (alkaline phosphatase, aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected. To understand mechanisms underlying the suppression of disaccharidase activity by acetic acid, Northern and Western analyses of the sucrase-isomaltase complex were performed. Acetic acid did not affect the de novo synthesis of this complex at either the transcriptional or translational levels. The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity. This suppression seems to occur during the post-translational processing. PMID:10702577

  11. Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling

    PubMed Central

    Alrob, Osama Abo; Sankaralingam, Sowndramalingam; Ma, Cary; Wagg, Cory S.; Fillmore, Natasha; Jaswal, Jagdip S.; Sack, Michael N.; Lehner, Richard; Gupta, Mahesh P.; Michelakis, Evangelos D.; Padwal, Raj S.; Johnstone, David E.; Sharma, Arya M.; Lopaschuk, Gary D.

    2014-01-01

    Aims Lysine acetylation is a novel post-translational pathway that regulates the activities of enzymes involved in both fatty acid and glucose metabolism. We examined whether lysine acetylation controls heart glucose and fatty acid oxidation in high-fat diet (HFD) obese and SIRT3 knockout (KO) mice. Methods and results C57BL/6 mice were placed on either a HFD (60% fat) or a low-fat diet (LFD; 4% fat) for 16 or 18 weeks. Cardiac fatty acid oxidation rates were significantly increased in HFD vs. LFD mice (845 ± 76 vs. 551 ± 87 nmol/g dry wt min, P < 0.05). Activities of the fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD), and β-hydroxyacyl-CoA dehydrogenase (β-HAD) were increased in hearts from HFD vs. LFD mice, and were associated with LCAD and β-HAD hyperacetylation. Cardiac protein hyperacetylation in HFD-fed mice was associated with a decrease in SIRT3 expression, while expression of the mitochondrial acetylase, general control of amino acid synthesis 5 (GCN5)-like 1 (GCN5L1), did not change. Interestingly, SIRT3 deletion in mice also led to an increase in cardiac fatty acid oxidation compared with wild-type (WT) mice (422 ± 29 vs. 291 ± 17 nmol/g dry wt min, P < 0.05). Cardiac lysine acetylation was increased in SIRT3 KO mice compared with WT mice, including increased acetylation and activity of LCAD and β-HAD. Although the HFD and SIRT3 deletion decreased glucose oxidation, pyruvate dehydrogenase acetylation was unaltered. However, the HFD did increase Akt acetylation, while decreasing its phosphorylation and activity. Conclusion We conclude that increased cardiac fatty acid oxidation in response to high-fat feeding is controlled, in part, via the down-regulation of SIRT3 and concomitant increased acetylation of mitochondrial β-oxidation enzymes. PMID:24966184

  12. High hydrostatic pressure increases amino acid requirements in the piezo-hyperthermophilic archaeon Thermococcus barophilus.

    PubMed

    Cario, Anaïs; Lormières, Florence; Xiang, Xiao; Oger, Philippe

    2015-11-01

    We have established a defined growth medium for the piezophilic hyperthermophilic archaeon Thermococcus barophilus, which allows growth yields of ca. 10(8) cells/ml under both atmospheric and high hydrostatic pressure. Our results demonstrate a major impact of hydrostatic pressure on amino acid metabolism, with increases from 3 amino acids required at atmospheric pressure to 17 at 40 MPa. We observe in T. barophilus and other Thermococcales a similar discrepancy between the presence/absence of amino acid synthesis pathways and amino acid requirements, which supports the existence of alternate, but yet unknown, amino acid synthesis pathways, and may explain the low number of essential amino acids observed in T. barophilus and other Thermococcales. T. barophilus displays a strong metabolic preference for organic polymers such as polypeptides and chitin, which may constitute a more readily available resource of carbon and energy in situ in deep-sea hydrothermal vents. We hypothesize that the low energy yields of fermentation of organic polymers, together with energetic constraints imposed by high hydrostatic pressure, may render de novo synthesis of amino acids ecologically unfavorable. Induction of this metabolic switch to amino acid recycling can explain the requirement for non-essential amino acids by Thermococcales for efficient growth in defined medium. PMID:26226334

  13. Electric field increases the phase transition temperature in the bilayer membrane of phosphatidic acid.

    PubMed

    Antonov, V F; Smirnova EYu; Shevchenko, E V

    1990-02-01

    The effect of the electric field on the phase transition temperature (Tc) of acidic 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA) and 1,2-dipalmitoyl-sn-glycero-3-thionphosphate (thion-DPPA) and zwitterion, i.e. 1,2-dipalmitoyl-rac-3-phosphocholine and 1,2-distearoyl-rac-glycero-3-phosphocholine (DPPC and DSPC), lipids has been investigated. The phase transition was detected using the jump-like increase effect in the conductance of the planar bilayer membrane. A voltage increase to 150 mV has been shown to increase the phase transition temperature in a bilayer lipid membrane (BLM) of phosphatidic acids (DPPA and thion-DPPA) by 8-12 degrees C while the transition temperature in the bilayer of zwitterion lipids (DPPC and DSPC) increases insignificantly. The increasing of Tt in BLM of acidic lipids is attributed to the voltage-induced changes in the molecule packing density. PMID:2340602

  14. Airborne arsenic exposure and excretion of methylated arsenic compounds.

    PubMed Central

    Smith, T J; Crecelius, E A; Reading, J C

    1977-01-01

    First void urine samples were collected from copper smelter workers exposed to inorganic arsenic and from unexposed controls. Arsenic compounds (As (III), As (V), methylarsonic acid and dimethylarsinic acid) in these samples were analyzed by selective volatilization as arsines with determination of arsenic by plasma excitation emission spectrometry. On the day preceding the urine sample collection a breathing zone measurement was made of respirable arsenic particulates for each subject. It was found that all of the subjects, including the controls excreted arsenic primarily as methylated species. Approximately 50% of the total arsenic was excreted as dimethylarsinic acid and 20% as methylarsonic acid. Slight differences in the proportion of various arsenic compounds were observed with varying levels of inorganic arsenic exposure. Amounts of arsenic species were all closely correlated with each other and with exposure. Irrespirable particulate exposures were measured on a subset of high exposure workers. Irrespirable arsenic was found to be more closely correlated with excretion of arsenic compounds than was respirable arsenic. PMID:908318

  15. Influence of dietary retrograded starch on the metabolism of neutral steroids and bile acids in rats.

    PubMed

    Verbeek, M J; De Deckere, E A; Tijburg, L B; Van Amelsvoort, J M; Beynen, A C

    1995-12-01

    Diets enriched in retrograded amylose (RS3) have been shown to lower serum cholesterol concentrations in rats. The possibility was tested that this hypocholesterolaemic effect of RS3 is caused by an increase in excretion of neutral steroids and/or bile acids. Six groups of ten rats were fed on purified diets containing either 12 or 140 g RS3/kg solid ingredients with and without added cholesterol (5g/kg). Low-RS3 diets, with and without added cholesterol, to which the bile-acid-binding resin cholestyramine (20 g/kg) was added, were used as reference. The high-RS3 diets v. the low-RS3 diets tended to reduce the increase in the total serum cholesterol concentration during the course of the experiment (P = 0.067), decreased serum triacylglycerol concentrations, raised total neutral steroids and total bile acids in caecal contents and faecal excretion of total bile acids, but lowered faecal excretion of neutral steroids. In addition, the serum concentration of total 3 alpha-bile acids was markedly raised by the high-RS3 diets. The high-RS3 diets raised the faecal excretion of lithocholic and muricholic acids, but lowered that of hyodeoxycholic acid, and increased the caecal amounts of lithocholic, ursodeoxycholic, beta-muricholic and omega-muricholic acids. Apart from the stimulation of faecal bile acids excretion, the effects of cholestyramine on bile acid metabolism differed at various points from those of RS3. Cholesterol feeding had predictable effects on cholesterol metabolism and led to greater elevating effects of RS3 on the faecal and caecal amounts of muricholic acids. The results suggest that the serum-cholesterol-lowering effect of high-RS3 diets may be explained by an increased influx of neutral steroids and bile acids into the caecum, and increased faecal excretion of bile acids, and/or by an altered intestinal bile acid profile. PMID:8562568

  16. [Predictors of bacterial excretion in patients with infiltrative pulmonary tuberculosis].

    PubMed

    Volchegorskiĭ, I A; Novoselov, P N; Bolotov, A A

    2009-01-01

    An association of bacterial excretion with the magnitude of the X-ray and clinical symptoms of infiltrative pulmonary tuberculosis, with the intensity of concomitant anxiety-depression disorders and the results of complex laboratory peripheral blood tests was studied in 100 patients with this condition. The fact that M. tuberculosis was present in the sputum was shown to be linked to the significant increase in the size of tuberculous infiltrates, the extent of decay in the latter, their connection with the root of the lung, the spread of excretion foci, and the intensity of cough and bloody expectoration. The similar trend was demonstrated in the degree of situational anxiety, depressive indecision, and pessimism, as well as in the values of leukocytosis and erythrocyte sedimentation rate. The predictive informative value of a set of findings is illustrated by the discriminant function equation that allows the correct prediction of bacterial excretion in 76.8% of cases. PMID:20095373

  17. Effects of feeding and confinement on nitrogen metabolism and excretion in the gulf toadfish Opsanus beta

    PubMed

    Walsh; Milligan

    1995-01-01

    In order to elucidate further the cues for, and the biochemical mechanisms of, the transition to ureogenesis in the gulf toadfish Opsanus beta, experiments on the effects of feeding (i.e. nitrogen loading) were carried out. Baseline nitrogen excretion rates were first measured on solitary toadfish in large water volumes (i.e. unconfined conditions). These nitrogen excretion rates were higher, and had a higher proportion as ammonia (61 %), than previously published 'control' measurements. Feeding of unconfined toadfish elevated total nitrogen excretion approximately threefold, with little change in the proportion of urea versus ammonia. During the first 24 h of confinement of unfed toadfish, absolute levels of urea excretion remained constant while ammonia excretion rates fell to near zero, so that toadfish became 90 % ureotelic. When fed prior to confinement, urea excretion rates remained constant for the first 24 h, and the bulk of the nitrogen was excreted as ammonia (80 %); excretion of the excess dietary nitrogen took up to 48 h to complete. If pre-adapted to confinement and then fed, toadfish excreted only about 55 % of their nitrogenous waste as ammonia, and excretion of excess dietary nitrogen was completed by 24 h. Elevations of hepatic glutamine synthetase (GNS) activities accompanied confinement and were shown to be almost exclusively in the cytosolic compartment and to be correlated with a decrease in the ratio of hepatic levels of glutamate:glutamine. These GNS activity increases also appear to account in part for the decrease in the percentage of ammoniotely in toadfish under conditions of nitrogen loading after confinement. However, additional means of regulating total nitrogen excretion (e.g. changes in protein turnover rates) and the degree of ureogenesis versus ammoniogenesis (e.g. N-acetylglutamate stimulation of carbamoylphosphate synthetase) must be postulated to account fully for changes in nitrogen excretion rates and activation of ureogenesis

  18. CONCENTRATION OF GLIAL FIBRILLARY ACIDIC PROTEIN INCREASES WITH AGE IN THE MOUSE AND RAT BRAIN

    EPA Science Inventory

    The role of aging in the expression of the astrocyte protein, glial fibrillary acidic protein (GFAP), was examined. n both mice and rats the concentration of GFAP increased throughout the brain as a function of aging. he largest increase (2-fold) was observed in striatum for both...

  19. Structural stability and prebiotic properties of resistant starch type 3 increase bile acid turnover and lower secondary bile acid formation.

    PubMed

    Dongowski, Gerhard; Jacobasch, Gisela; Schmiedl, Detlef

    2005-11-16

    Microbial metabolism is essential in maintaining a healthy mucosa in the large bowel, preferentially through butyrate specific mechanisms. This system depends on starch supply. Two structurally different resistant starches type 3 (RS3) have been investigated with respect to their resistance to digestion, fermentability, and their effects on the composition and turnover of bile acids in rats. RSA (a mixture of retrograded maltodextrins and branched high molecular weight polymers), which is more resistant than RSB (a retrograded potato starch), increased the rate of fermentation accompanied by a decrease of pH in cecum, colon, and feces. Because they were bound to RS3, less bile acids were reabsorbed, resulting in a higher turnover through the large bowel. Because of the rise of volume, the bile acid level was unchanged and the formation of secondary bile acids was partly suppressed. The results proved a strong relation between RS3, short chain fatty acid production, and microflora. However, butyrate specific benefits are only achieved by an intake of RS3 that result in good fermentation properties, which depend on the kind of the resistant starch structures. PMID:16277431

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

    PubMed Central

    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

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

    PubMed

    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 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. PMID:23579616

  2. Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron

    PubMed Central

    Cornelius, Ryan J.; Wen, Donghai; Hatcher, Lori I.

    2012-01-01

    Ca-activated K channels (BK), which are stimulated by high distal nephron flow, are utilized during high-K conditions to remove excess K. Because BK predominantly reside with BK-β4 in acid/base-transporting intercalated cells (IC), we determined whether BK-β4 knockout mice (β4KO) exhibit deficient K excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-β4 expression increased (Western blot). When WT and β4KO were placed on HK-Cl, plasma K concentration ([K]) was elevated compared with control K diets; however, K excretion was not different between WT and β4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with β4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and β4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in β-IC, comparing WT and β4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in β4KO, compared with WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to minimize Na reabsorption exaggerated the defective K handling of β4KO. When WT on LNaHK were given NH4Cl in the drinking water, K excretion was reduced to the magnitude of β4KO on LNaHK. These results show that WT, but not β4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-α/β4-mediated K secretion is promoted by bicarbonaturia. PMID:22993067

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

    PubMed

    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. PMID:26634573

  4. Increased acid responsiveness in vagal sensory neurons in a guinea pig model of eosinophilic esophagitis

    PubMed Central

    Hu, Youtian; Liu, Zhenyu; Yu, Xiaoyun; Pasricha, Pankaj J.; Undem, Bradley J.

    2014-01-01

    Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells predominated allergic inflammation in the esophagus and present with esophageal dysfunctions such as dysphagia, food impaction, and heartburn. However, the underlying mechanism of esophageal dysfunctions is unclear. This study aims to determine whether neurons in the vagal sensory ganglia are modulated in a guinea pig model of EoE. Animals were actively sensitized by ovalbumin (OVA) and then challenged with aerosol OVA inhalation for 2 wk. This results in a mild esophagitis with increases in mast cells and eosinophils in the esophageal wall. Vagal nodose and jugular neurons were disassociated, and their responses to acid, capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist AMG-9810 were studied by calcium imaging and whole cell patch-clamp recording. Compared with naïve animals, antigen challenge significantly increased acid responsiveness in both nodose and jugular neurons. Their responses to capsaicin were also increased after antigen challenge. AMG-9810, at a concentration that blocked capsaicin-evoked calcium influx, abolished the increase in acid-induced activation in both nodose and jugular neurons. Vagotomy strongly attenuated those increased responses of nodose and jugular neurons to both acid and capsaicin induced by antigen challenge. These data for the first time demonstrated that prolonged antigen challenge significantly increases acid responsiveness in vagal nodose and jugular ganglia neurons. This sensitization effect is mediated largely through TRPV1 and initiated at sensory nerve endings in the peripheral tissues. Allergen-induced enhancement of responsiveness to noxious stimulation by acid in sensory nerve may contribute to the development of esophageal dysfunctions such as heartburn in EoE. PMID:24875100

  5. Excretion of biliary compounds during intrauterine life

    PubMed Central

    Macias, Rocio IR; Marin, Jose JG; Serrano, Maria A

    2009-01-01

    In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem. PMID:19230042

  6. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

    PubMed

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

    2013-07-15

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. PMID:23673156

  7. Production of siderophores increases resistance to fusaric acid in Pseudomonas protegens Pf-5.

    PubMed

    Ruiz, Jimena A; Bernar, Evangelina M; Jung, Kirsten

    2015-01-01

    Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt diseases caused by these fungi. This study was undertaken to evaluate the effect of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the bacterium to survive in the presence of the mycotoxin. The results confirm that fusaric acid negatively affects growth and motility of P. protegens. Moreover, a notable increase in secretion of the siderophore pyoverdine was observed when P. protegens was grown in the presence of fusaric acid. Concomitantly, levels of enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the second siderophore encoded by P. protegens, increased markedly. Moreover, while similar levels of resistance to fusaric acid were observed for P. protegens mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild type strain, a double mutant unable to synthesize both kinds of siderophores showed a dramatically reduced resistance to this compound. This reduced resistance was not observed when this mutant was grown under conditions of iron excess. Spectrophotometric titrations revealed that fusaric acid binds not only Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results demonstrate that iron sequestration accounts at least in part for the deleterious effect of the mycotoxin on P. protegens. PMID:25569682

  8. Production of Siderophores Increases Resistance to Fusaric Acid in Pseudomonas protegens Pf-5

    PubMed Central

    Ruiz, Jimena A.; Bernar, Evangelina M.; Jung, Kirsten

    2015-01-01

    Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt diseases caused by these fungi. This study was undertaken to evaluate the effect of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the bacterium to survive in the presence of the mycotoxin. The results confirm that fusaric acid negatively affects growth and motility of P. protegens. Moreover, a notable increase in secretion of the siderophore pyoverdine was observed when P. protegens was grown in the presence of fusaric acid. Concomitantly, levels of enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the second siderophore encoded by P. protegens, increased markedly. Moreover, while similar levels of resistance to fusaric acid were observed for P. protegens mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild type strain, a double mutant unable to synthesize both kinds of siderophores showed a dramatically reduced resistance to this compound. This reduced resistance was not observed when this mutant was grown under conditions of iron excess. Spectrophotometric titrations revealed that fusaric acid binds not only Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results demonstrate that iron sequestration accounts at least in part for the deleterious effect of the mycotoxin on P. protegens. PMID:25569682

  9. Linoleic acid supplementation results in increased arachidonic acid and eicosanoid production in CF airway cells and in cftr−/− transgenic mice

    PubMed Central

    Zaman, Munir M.; Martin, Camilia R.; Andersson, Charlotte; Bhutta, Abdul Q.; Cluette-Brown, Joanne E.; Laposata, Michael

    2010-01-01

    Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o− sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr−/− transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage fluid from knockout mice following linoleic acid supplementation and exposure to aerosolized Pseudomonas LPS. Linoleic acid supplementation increased arachidonic acid levels in CF but not WT cells. IL-8, PGE2, and PGF2α secretion were increased in CF compared with WT cells, with a further increase following linoleic acid supplementation. cftr−/− Mice supplemented with 100 mg of linoleic acid had increased arachidonic acid levels in lung tissue associated with increased neutrophil infiltration into the airway compared with control mice. These findings support the hypothesis that increasing linoleic acid levels in the setting of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to increased arachidonic acid levels and proinflammatory mediators. PMID:20656894

  10. Biliary excretion of foreign compounds. Benzene and its derivatives in the rat

    PubMed Central

    Abou-El-Makarem, M. M.; Millburn, P.; Smith, R. L.; Williams, R. T.

    1967-01-01

    1. The extent of the excretion in the bile of the rat of benzene and 21 of its simple derivatives was studied. 2. Some 16 compounds of molecular weight less than 200, and including neutral molecules (benzene and toluene), aromatic acids, aromatic amines and phenols, were injected in solution intraperitoneally into biliary-cannulated rats. Metabolites in the bile were identified and estimated. The extent of biliary excretion of these compounds was low, i.e. 0–10% of the dose in 24hr., and most appeared in the bile mainly as conjugates. 3. The biliary excretion of six conjugates of molecular weight less than 300, including three glycine conjugates, one sulphate conjugate, one glucuronic acid conjugate and two acetyl derivatives, was low (less than 3% of the dose). 4. It is concluded that simple benzene derivatives of molecular weight less than about 300 are poorly excreted in rat bile. PMID:16742555

  11. Elevated urinary excretion of aluminium and iron in multiple sclerosis.

    PubMed

    Exley, Christopher; Mamutse, Godwin; Korchazhkina, Olga; Pye, Eleanor; Strekopytov, Stanislav; Polwart, Anthony; Hawkins, Clive

    2006-10-01

    Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system of as yet unknown aetiology. A consensus of opinion has suggested that the disorder is the result of an interplay between environmental factors and susceptibility genes. We have used a battery of analytical techniques to determine if the urinary excretion of i) markers of oxidative damage; ii) iron and iii) the environmental toxin aluminium and its antagonist, silicon, are altered in relapsing-remitting (RRMS) and secondary progressive MS (SPMS). Urinary concentrations of oxidative biomarkers, MDA and TBARS, were not found to be useful indicators of inflammatory disease in MS. However, urinary concentrations of another potential marker for inflammation and oxidative stress, iron, were significantly increased in SPMS (P<0.01) and insignificantly increased in RRMS (P>0.05). Urinary concentrations of aluminium were also significantly increased in RRMS (P<0.001) and SPMS (P <0.05) such that the levels of aluminium excretion in the former were similar to those observed in individuals undergoing metal chelation therapy. The excretion of silicon was lower in MS and significantly so in SPMS (P<0.05). Increased excretion of iron in urine supported a role for iron dysmetabolism in MS. Levels of urinary aluminium excretion similar to those seen in aluminium intoxication suggested that aluminium may be a hitherto unrecognized environmental factor associated with the aetiology of MS. If aluminium is involved in MS then an increased dietary intake of its natural antagonist, silicon, might be a therapeutic option. PMID:17086897

  12. Increased hepatic Fatty Acid uptake and esterification contribute to tetracycline-induced steatosis in mice.

    PubMed

    Choi, You-Jin; Lee, Chae-Hyeon; Lee, Kang-Yo; Jung, Seung-Hwan; Lee, Byung-Hoon

    2015-06-01

    Tetracycline induces microvesicular steatosis, which has a poor long-term prognosis and a higher risk of steatohepatitis development compared with macrovesicular steatosis. Recent gene expression studies indicated that tetracycline treatment affects the expression of many genes associated with fatty acid transport and esterification. In this study, we investigated the role of fatty acid transport and esterification in tetracycline-induced steatosis. Intracellular lipid accumulation and the protein expression of fatty acid translocase (FAT or CD36) and diacylglycerol acyltransferase (DGAT) 2 were increased in both mouse liver and HepG2 cells treated with tetracycline at 50 mg/kg (intraperitoneal injection, i.p.) and 100 μM, respectively. Tetracycline increased the cellular uptake of boron-dipyrromethene-labeled C16 fatty acid, which was abolished by CD36 RNA interference. Oleate-induced cellular lipid accumulation was further enhanced by co-incubation with tetracycline. Tetracycline downregulated extracellular signal-regulated kinase (ERK) phosphorylation, which negatively regulated DGAT2 expression. U0126, a specific ERK inhibitor, also increased DGAT2 expression and cellular lipid accumulation. DGAT1 and 2 knock-down with specific small interfering (si)-RNA completely abrogated the steatogenic effect of tetracycline in HepG2 cells. Taken together, our data showed that tetracycline induces lipid accumulation by facilitating fatty acid transport and triglyceride esterification by upregulating CD36 and DGAT2, respectively. PMID:25745068

  13. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    SciTech Connect

    Olson, Aaron; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly-Priddy, Colleen M.; Isern, Nancy G.; Portman, Michael A.

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained

  14. Ascorbic acid recycling by cultured beta cells: effects of increased glucose metabolism.

    PubMed

    Steffner, Robert J; Wu, Lan; Powers, Alvin C; May, James M

    2004-11-15

    Ascorbic acid is necessary for optimal insulin secretion from pancreatic islets. We evaluated ascorbate recycling and whether it is impaired by increased glucose metabolism in the rat beta-cell line INS-1. INS-1 cells, engineered with the potential for overexpression of glucokinase under the control of a tetracycline-inducible gene expression system, took up and reduced dehydroascorbic acid to ascorbate in a concentration-dependent manner that was optimal in the presence of physiologic D-glucose concentrations. Ascorbate uptake did not affect intracellular GSH concentrations. Whereas depletion of GSH in culture to levels about 25% of normal also did not affect the ability of the cells to reduce dehydroascorbic acid, more severe acute GSH depletion to less than 10% of normal levels did impair dehydroascorbic acid reduction. Culture of inducible cells in 11.8 mM D-glucose and doxycycline for 48 h enhanced glucokinase activity, increased glucose utilization, abolished D-glucose-dependent insulin secretion, and increased generation of reactive oxygen species. The latter may have contributed to subsequent decreases in the ability of the cells both to maintain intracellular ascorbate and to recycle it from dehydroascorbic acid. Cultured beta cells have a high capacity to recycle ascorbate, but this is sensitive to oxidant stress generated by increased glucose metabolism due to culture in high glucose concentrations and increased glucokinase expression. Impaired ascorbate recycling as a result of increased glucose metabolism may have implications for the role of ascorbate in insulin secretion in diabetes mellitus and may partially explain glucose toxicity in beta cells. PMID:15477012

  15. Metabolism and Excretion of Trichloroethylene after Inhalation by Human Subjects

    PubMed Central

    Bartoníček, V.

    1962-01-01

    Eight volunteers were exposed to trichloroethylene vapour (1,042 μg./l.) for five hours; 51 to 64% of the inhaled trichloroethylene was retained. The concentration of trichloroethanol and trichloroacetic acid in the urine was studied daily for a three-week period; on the third day both metabolites were determined in faeces, sweat, and saliva. The concentration of trichloroacetic acid in plasma and red blood cells was studied on alternate days. Of the trichloroethylene retained, 38·0 to 49·7% was excreted in the urine as trichloroethanol and 27·4 to 35·7% as trichloroacetic acid. Of both metabolites 8·4% was excreted in the faeces. Sweat collected on the third day of the experiment contained 0·10 to 1·92 mg./100 ml. trichloroethanol and 0·15 to 0·35 mg./100 ml. trichloroacetic acid. In saliva the concentrations were 0·09 to 0·32 mg./100 ml. trichloroethanol and 0·10 to 0·15 mg./100 ml. trichloroacetic acid. The value of the expression trichloroethanol/trichloroacetic acid calculated in the urine within 22 days was within the range 1·15 to 1·81. PMID:13865497

  16. INCREASE IN GLIAL FIBRILLARY ACIDIC PROTEIN FOLLOWS BRAIN HYPERTHERMIA IN RATS

    EPA Science Inventory

    Previously, the authors have demonstrated that an increase in the astrocyte-associated protein, glial fibrillary acidic protein (GFAP), accompanies brain injury induced by a variety of chemical insults. In the present study the authors examined the effects of microwave-induced hy...

  17. Polyunsaturated fatty acid content is increased in the milk of women with pregnancy associated breast cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Pregnancy associated breast cancer (PABC) is aggressive and difficult to diagnose. High intake of most types of dietary fat is thought to increase breast cancer risk, however results in humans supporting this premise remain equivocal. Fatty acid (FA) concentrations in the body comprise b...

  18. Variability of urinary salt excretion estimated by spot urine in treated hypertensive patients.

    PubMed

    Arakawa, Kimika; Sakaki, Minako; Sakata, Satoko; Oniki, Hideyuki; Tominaga, Mitsuhiro; Tsuchihashi, Takuya

    2015-01-01

    Among the several methods used to assess salt intake, estimating 24 h urinary salt excretion by spot urine seems appropriate for clinical practice. In this study, we investigated variability in urinary salt excretion using spot urine in hypertensive outpatients. Participants included 200 hypertensive patients who underwent spot urinary salt excretion at least three times during the observation period. Mean urinary salt excretion and the coefficient of the variation were 8.62 ± 1.96 g/day and 19.0 ± 10.2%, respectively. In the analysis of participants who underwent assessment of urinary salt excretion at least eight times (n = 54), a significant reduction in mean urinary salt excretion was found at the 5th measurement. On the contrary, the coefficient of the variation of urinary salt excretion continued to increase until the 5th measurement, and became stable thereafter. Mean urinary salt excretion was positively correlated with mean clinic diastolic blood pressure (r = 0.27, p < 0.05). Clinic diastolic blood pressure in the high urinary salt excretion group (≥ 10 g/day) was significantly higher than that of the low group (76.2 ± 7.5 vs 73.4 ± 8.3 mmHg, p < 0.05). Mean urinary salt excretion in summer was significantly lower than that of the other seasons (7.75 ± 1.94 vs 9.09 ± 2.68 (spring), 8.72 ± 2.12 (autumn), 8.92 ± 2.17 (winter) g/day, p < 0.01). In conclusion, repeated measurements of urinary salt excretion using spot urine are required to assess daily salt intake of hypertensive patients. PMID:26395949

  19. Increased muscle fatty acid oxidation in dairy cows with intensive body fat mobilization during early lactation.

    PubMed

    Schäff, C; Börner, S; Hacke, S; Kautzsch, U; Sauerwein, H; Spachmann, S K; Schweigel-Röntgen, M; Hammon, H M; Kuhla, B

    2013-10-01

    The beginning of lactation requires huge metabolic adaptations to meet increased energy demands for milk production of dairy cows. One of the adaptations is the mobilization of body reserves mainly from adipose tissue as reflected by increased plasma nonesterified fatty acid (NEFA) concentrations. The capacity of the liver for complete oxidation of NEFA is limited, leading to an increased formation of ketone bodies, reesterification, and accumulation of triglycerides in the liver. As the skeletal muscle also may oxidize fatty acids, it may help to decrease the fatty acid load on the liver. To test this hypothesis, 19 German Holstein cows were weekly blood sampled from 7 wk before until 5 wk after parturition to analyze plasma NEFA concentrations. Liver biopsies were obtained at d 3, 18, and 30 after parturition and, based on the mean liver fat content, cows were grouped to the 10 highest (HI) and 9 lowest (LO). In addition, muscle biopsies were obtained at d -17, 3, and 30 relative to parturition and used to quantify mRNA abundance of genes involved in fatty acid degradation. Plasma NEFA concentrations peaked after parturition and were 1.5-fold higher in HI than LO cows. Muscle carnitine palmitoyltransferase 1α and β mRNA was upregulated in early lactation. The mRNA abundance of muscle peroxisome proliferator-activated receptor γ (PPARG) increased in early lactation and was higher in HI than in LO cows, whereas the abundance of PPARA continuously decreased after parturition. The mRNA abundance of muscle PPARD, uncoupling protein 3, and the β-oxidative enzymes 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase, very long-chain acyl-CoA dehydrogenase, and 3-ketoacyl-CoA was greatest at d 3 after parturition, whereas the abundance of PPARγ coactivator 1α decreased after parturition. Our results indicate that around parturition, oxidation of fatty acids in skeletal muscle is highly activated, which may contribute to diminish the fatty acid load on the liver. The

  20. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide

    PubMed Central

    Yao, Chien-An; Chen, Chin-Chu; Wang, Nai-Phog; Chien, Chiang-Ting

    2016-01-01

    The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids’ oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis. PMID:27043621

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

    SciTech Connect

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

    1991-05-01

    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.

  2. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.

    PubMed

    Peliciari-Garcia, Rodrigo A; Goel, Mehak; Aristorenas, Jonathan A; Shah, Krishna; He, Lan; Yang, Qinglin; Shalev, Anath; Bailey, Shannon M; Prabhu, Sumanth D; Chatham, John C; Gamble, Karen L; Young, Martin E

    2016-10-01

    A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26721420

  3. Homologous electron transport components fail to increase fatty acid hydroxylation in transgenic Arabidopsis thaliana

    PubMed Central

    Wayne, Laura L.; Browse, John

    2013-01-01

    Ricinoleic acid, a hydroxylated fatty acid (HFA) present in castor ( Ricinus communis) seeds, is an important industrial commodity used in products ranging from inks and paints to polymers and fuels. However, due to the deadly toxin ricin and allergens also present in castor, it would be advantageous to produce ricinoleic acid in a different agricultural crop. Unfortunately, repeated efforts at heterologous expression of the castor fatty acid hydroxylase (RcFAH12) in the model plant Arabidopsis thaliana have produced only 17-19% HFA in the seed triacylglycerols (TAG), whereas castor seeds accumulate up to 90% ricinoleic acid in the endosperm TAG. RcFAH12 requires an electron supply from NADH:cytochrome b5 reductase (CBR1) and cytochrome b5 (Cb5) to synthesize ricinoleic acid. Previously, our laboratory found a mutation in the Arabidopsis CBR1 gene, cbr1-1, that caused an 85% decrease in HFA levels in the RcFAH12 Arabidopsis line. These results raise the possibility that electron supply to the heterologous RcFAH12 may limit the production of HFA. Therefore, we hypothesized that by heterologously expressing RcCb5, the reductant supply to RcFAH12 would be improved and lead to increased HFA accumulation in Arabidopsis seeds. Contrary to this proposal, heterologous expression of the top three RcCb5 candidates did not increase HFA accumulation. Furthermore, coexpression of RcCBR1 and RcCb5 in RcFAH12 Arabidopsis also did not increase in HFA levels compared to the parental lines. These results demonstrate that the Arabidopsis electron transfer system is supplying sufficient reductant to RcFAH12 and that there must be other bottlenecks limiting the accumulation of HFA. PMID:24555099

  4. Organic reactions increasing the absorption index of atmospheric sulfuric acid aerosols

    NASA Astrophysics Data System (ADS)

    Nozière, B.; Esteve, W.

    2005-02-01

    Unlike most environments present at Earth's surface atmospheric aerosols can be favorable to organic reactions. Among them, the acid-catalyzed aldol condensation of aldehydes and ketones produces light-absorbing compounds. In this work the increase of the absorption index of sulfuric acid solutions 50-96 wt. % resulting from the uptake of gas-phase acetaldehyde, acetone, and 2-butanone (methyl ethyl ketone), has been measured in the near UV and visible range. Our results indicate that the absorption index between 200 and 500 nm for stratospheric sulfuric aerosols exposed to 100 pptV of acetaldehyde (1 pptV = 10-12 v/v) would increase by four orders of magnitude over a two-year lifetime. Rough estimates based on previous radiative calculations suggest that this reaction could result in an increase of the radiative forcing of sulfate aerosols of the order of 0.01 W m-2, and that these processes are worth further investigation.

  5. 17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

    PubMed

    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. PMID:24913495

  6. Conjugated linoleic acid increases in milk from cows fed condensed corn distillers solubles and fish oil.

    PubMed

    Bharathan, M; Schingoethe, D J; Hippen, A R; Kalscheur, K F; Gibson, M L; Karges, K

    2008-07-01

    Twelve lactating Holstein cows were randomly assigned to 1 of 4 experimental diets in a replicated 4 x 4 Latin square design with 4-wk periods to ascertain the lactational response to feeding fish oil (FO), condensed corn distillers solubles (CDS) as a source of extra linoleic acid, or both. Diets contained either no FO or 0.5% FO and either no CDS or 10% CDS in a 2 x 2 factorial arrangement of treatments. Diets were fed as total mixed rations for ad libitum consumption. The forage to concentrate ratio was 55:45 on a dry matter basis for all diets and the diets contained 16.2% crude protein. The ether extract concentrations were 2.86, 3.22, 4.77, and 5.02% for control, FO, CDS, and FOCDS diets, respectively. Inclusion of FO or CDS or both had no effect on dry matter intake, feed efficiency, body weight, and body condition scores compared with diets without FO and CDS, respectively. Yields of milk (33.3 kg/d), energy-corrected milk, protein, lactose, and milk urea N were similar for all diets. Feeding FO and CDS decreased milk fat percentages (3.85, 3.39, 3.33, and 3.12%) and yields compared with diets without FO and CDS. Proportions of trans-11 C18:1 (vaccenic acid), cis-9 trans-11 conjugated linoleic acid (CLA; 0.52, 0.90, 1.11, and 1.52 g/100 g of fatty acids), and trans-10 cis-12 CLA (0.07, 0.14, 0.13, and 0.16 g/100 g of fatty acids) in milk fat were increased by FO and CDS. No interactions were observed between FO and CDS on cis-9 trans-11 CLA although vaccenic acid tended to be higher with the interaction. The addition of CDS to diets increased trans-10 C18:1. Greater ratios of vaccenic acid to cis-9 trans-11 CLA in plasma than in milk fat indicate tissue synthesis of cis-9 trans-11 CLA in the mammary gland from vaccenic acid in cows fed FO or CDS. Feeding fish oil at 0.5% of diet dry matter with a C18:2 n-6 rich source such as CDS increased the milk CLA content but decreased milk fat percentages. PMID:18565937

  7. Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid.

    PubMed

    D'Aniello, Enrico; Rydeen, Ariel B; Anderson, Jane L; Mandal, Amrita; Waxman, Joshua S

    2013-01-01

    Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA) signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1), a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM) specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA. PMID:23990796

  8. Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis

    PubMed Central

    2016-01-01

    Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients. PMID:26955238

  9. Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis.

    PubMed

    Pieringer, Herwig; Brummaier, Tobias; Piringer, Bettina; Auer-Hackenberg, Lorenz; Hartl, Andreas; Puchner, Rudolf; Pohanka, Erich; Schmid, Michael

    2016-03-01

    Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients. PMID:26955238

  10. Heparin, free fatty acids and an increased metabolic demand for oxygen.

    PubMed

    Jung, R T; Shetty, P S; James, W P

    1980-05-01

    Obese and lean subjects were given heparin with or without Intralipid in order to assess the effect of heparin on plasma concentration of free fatty acids (FFA) and oxidative metabolism. The FFA response depended on the triglyceride concentration and was associated with a prompt rise in oxygen consumption. Plasma catecholamines did not alter after heparin and the increase in oxygen uptake was proportional to the rise in FFA. The use of heparin, therefore, has metabolic disadvantages which may outweigh the potential benefits, for example in the management of myocardial infarction where heparin may increase the metabolic demand on the heart by increasing FFA levels. PMID:7443592

  11. Heparin, free fatty acids and an increased metabolic demand for oxygen.

    PubMed Central

    Jung, R. T.; Shetty, P. S.; James, W. P.

    1980-01-01

    Obese and lean subjects were given heparin with or without Intralipid in order to assess the effect of heparin on plasma concentration of free fatty acids (FFA) and oxidative metabolism. The FFA response depended on the triglyceride concentration and was associated with a prompt rise in oxygen consumption. Plasma catecholamines did not alter after heparin and the increase in oxygen uptake was proportional to the rise in FFA. The use of heparin, therefore, has metabolic disadvantages which may outweigh the potential benefits, for example in the management of myocardial infarction where heparin may increase the metabolic demand on the heart by increasing FFA levels. PMID:7443592

  12. Urinary dopamine in man and rat: effects of inorganic salts on dopamine excretion.

    PubMed

    Ball, S G; Oats, N S; Lee, M R

    1978-08-01

    1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject. 2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney. 3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl. 4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3. 5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion. PMID:28196

  13. Metabolic engineering of Aspergillus oryzae NRRL 3488 for increased production of L-malic acid.

    PubMed

    Brown, Stephen H; Bashkirova, Lena; Berka, Randy; Chandler, Tyler; Doty, Tammy; McCall, Keith; McCulloch, Michael; McFarland, Sarah; Thompson, Sheryl; Yaver, Debbie; Berry, Alan

    2013-10-01

    Malic acid, a petroleum-derived C4-dicarboxylic acid that is used in the food and beverage industries, is also produced by a number of microorganisms that follow a variety of metabolic routes. Several members of the genus Aspergillus utilize a two-step cytosolic pathway from pyruvate to malate known as the reductive tricarboxylic acid (rTCA) pathway. This simple and efficient pathway has a maximum theoretical yield of 2 mol malate/mol glucose when the starting pyruvate originates from glycolysis. Production of malic acid by Aspergillus oryzae NRRL 3488 was first improved by overexpression of a native C4-dicarboxylate transporter, leading to a greater than twofold increase in the rate of malate production. Overexpression of the native cytosolic alleles of pyruvate carboxylase and malate dehydrogenase, comprising the rTCA pathway, in conjunction with the transporter resulted in an additional 27 % increase in malate production rate. A strain overexpressing all three genes achieved a malate titer of 154 g/L in 164 h, corresponding to a production rate of 0.94 g/L/h, with an associated yield on glucose of 1.38 mol/mol (69 % of the theoretical maximum). This rate of malate production is the highest reported for any microbial system. PMID:23925533

  14. Chlorogenic acid ameliorates intestinal mitochondrial injury by increasing antioxidant effects and activity of respiratory complexes.

    PubMed

    Zhou, Yan; Zhou, Lili; Ruan, Zheng; Mi, Shumei; Jiang, Min; Li, Xiaolan; Wu, Xin; Deng, Zeyuan; Yin, Yulong

    2016-05-01

    Dietary polyphenols are thought to be beneficial for human health by acting as antioxidants. Chlorogenic acid (CGA) is abundant in plant-based foods as an ester of caffeic acid and quinic acid. In this study, we investigated the effects of CGA on mitochondrial protection. Our results demonstrated that pretreatment with CGA ameliorated the intestinal mitochondrial injury induced by H2O2; membrane potential was increased, mitochondrial swelling, levels of reactive oxygen species, contents of 8-hydroxy-2-deoxyguanosine, and cytochrome c released were decreased. The beneficial effects of CGA were accompanied by an increase in antioxidant and respiratory-chain complex I, IV, and V activities. In trinitrobenzene-sulfonic acid-induced colitic rats indicated that CGA supplementation improved mitochondria ultrastructure and decreased mitochondrial injury. Our results suggest a promising role for CGA as a mitochondria-targeted antioxidant in combating intestinal oxidative injury. Daily intake of diets containing CGA, such as coffee and honeysuckle, may be useful for prevention of intestinal diseases. PMID:26824685

  15. Acidic pH increases airway surface liquid viscosity in cystic fibrosis.

    PubMed

    Tang, Xiao Xiao; Ostedgaard, Lynda S; Hoegger, Mark J; Moninger, Thomas O; Karp, Philip H; McMenimen, James D; Choudhury, Biswa; Varki, Ajit; Stoltz, David A; Welsh, Michael J

    2016-03-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3- concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator-dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID:26808501

  16. Acidic pH increases airway surface liquid viscosity in cystic fibrosis

    PubMed Central

    Tang, Xiao Xiao; Ostedgaard, Lynda S.; Hoegger, Mark J.; Moninger, Thomas O.; Karp, Philip H.; McMenimen, James D.; Choudhury, Biswa; Varki, Ajit; Stoltz, David A.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3– concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator–dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID:26808501

  17. Effects of feeding outer bran fraction of rice on lipid accumulation and fecal excretion in rats.

    PubMed

    Ijiri, Daichi; Nojima, Tsutomu; Kawaguchi, Mana; Yamauchi, Yoko; Fujita, Yoshikazu; Ijiri, Satoru; Ohtsuka, Akira

    2015-01-01

    Outer bran fraction of rice (OBFR) contains higher concentrations of crude fiber, γ-oryzanol, and phytic acid compared to whole rice bran (WRB). In this study, we examined the effects of feeding OBFR on lipid accumulation and fecal excretion in rats. Twenty-one male rats at seven-week-old were divided into a control group and two treatment groups. The control group was fed a control diet, and the treatment groups were fed OBFR- or WRB-containing diet for 21 days. There was no significant difference in growth performance. Feeding OBFR diet increased fecal number and weight accompanied by increased fecal lipid content, while it did not affect mRNA expressions encoding lipid metabolism-related protein in liver. In addition, feeding OBFR-diet decreased the abdominal fat tissue weight and improved plasma lipid profiles, while WRB-containing diet did not affect them. These results suggested that feeding OBFR-diet might prevent lipid accumulation via enhancing fecal lipid excretion in rats. PMID:25867004

  18. The influence of dissolved organic matter (DOM) on sodium regulation and nitrogenous waste excretion in the zebrafish (Danio rerio).

    PubMed

    Al-Reasi, Hassan A; Smith, Scott D; Wood, Chris M

    2016-08-01

    Dissolved organic matter (DOM) is both ubiquitous and diverse in composition in natural waters, but its effects on the branchial physiology of aquatic organisms have received little attention relative to other variables (e.g. pH, hardness, salinity, alkalinity). Here, we investigated the effects of four chemically distinct DOM isolates (three natural, one commercial, ranging from autochthonous to highly allochthonous, all at ∼6 mg C l(-1)) on the physiology of gill ionoregulation and nitrogenous waste excretion in zebrafish acclimated to either circumneutral (7.0-8.0) or acidic pH (5.0). Overall, lower pH tended to increase net branchial ammonia excretion, net K(+) loss and [(3)H]PEG-4000 clearance rates (indicators of transcellular and paracellular permeability, respectively). However, unidirectional Na(+) efflux, urea excretion and drinking rates were unaffected. DOM sources tended to stimulate unidirectional Na(+) influx rate and exerted subtle effects on the concentration-dependent kinetics of Na(+) uptake, increasing maximum transport capacity. All DOM sources reduced passive Na(+) efflux rates regardless of pH, but exerted negligible effects on nitrogenous waste excretion, drinking rate, net K(+) loss or [(3)H]PEG-4000 clearance, so the mechanism of Na(+) loss reduction remains unclear. Overall, these actions appear beneficial to ionoregulatory homeostasis in zebrafish, and some may be related to physico-chemical properties of the DOM sources. They are very different from those seen in a recent parallel study on Daphnia magna using the same DOM isolates, indicating that DOM actions may be both species and DOM specific. PMID:27207642

  19. (Uncommon) Mechanisms of Branchial Ammonia Excretion in the Common Carp (Cyprinus carpio) in Response to Environmentally Induced Metabolic Acidosis.

    PubMed

    Wright, Patricia A; Wood, Chris M; Hiroi, Junya; Wilson, Jonathan M

    2016-01-01

    Freshwater fishes generally increase ammonia excretion in acidic waters. The new model of ammonia transport in freshwater fish involves an association between the Rhesus (Rh) protein Rhcg-b, the Na(+)/H(+) exchanger (NHE), and a suite of other membrane transporters. We tested the hypothesis that Rhcg-b and NHE3 together play a critical role in branchial ammonia excretion in common carp (Cyprinus carpio) chronically exposed to a low-pH environment. Carp were exposed to three sequential environmental treatments-control pH 7.6 water (24 h), pH 4.0 water (72 h), and recovery pH 7.6 water (24 h)-or in a separate series were simply exposed to either control (72 h) or pH 4.0 (72 h) water. Branchial ammonia excretion was increased by ∼2.5-fold in the acid compared with the control period, despite the absence of an increase in the plasma-to-water partial pressure NH3 gradient. Alanine aminotransferase activity was higher in the gills of fish exposed to pH 4 versus control water, suggesting that ammonia may be generated in gill tissue. Gill Rhcg-b and NHE3b messenger RNA levels were significantly elevated in acid-treated relative to control fish, but at the protein level Rhcg-b decreased (30%) and NHE3b increased (2-fold) in response to water of pH 4.0. Using immunofluorescence microscopy, NHE3b and Rhcg-b were found to be colocalized to ionocytes along the interlamellar space of the filament of control fish. After 72 h of acid exposure, Rhcg-b staining almost disappeared from this region, and NHE3b was more prominent along the lamellae. We propose that ammoniagenesis within the gill tissue itself is responsible for the higher rates of branchial ammonia excretion during chronic metabolic acidosis. Unexpectedly, gill Rhcg-b does not appear to be important in gill ammonia transport in low-pH water, but the strong induction of NHE3b suggests that some NH4(+) may be eliminated directly in exchange for Na(+). These findings contrast with previous studies in larval zebrafish

  20. Humic substances increase survival of freshwater shrimp Caridina sp. D to acid mine drainage.

    PubMed

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

    2013-02-01

    Humic substances (HS) are known to decrease the toxicity of heavy metals to aquatic organisms, and it has been suggested that they can provide buffering protection in low pH conditions. Despite this, little is known about the ability for HS to increase survival to acid mine drainage (AMD). In this study, the ability of HS to increase survival of the freshwater shrimp (Caridina sp. D sensu Page et al. in Biol Lett 1:139-142, 2005) to acid mine drainage was investigated using test waters collected from the Mount Morgan open pit in Central Queensland with the addition of Aldrich humic acid (AHA). The AMD water from the Mount Morgan open pit is highly acidic (pH 2.67) as well as contaminated with heavy metals (1780 mg/L aluminum, 101 mg/L copper [Cu], 173 mg/L manganese, 51.8 mg/L zinc [Zn], and 51.8 mg/L iron). Freshwater shrimp were exposed to dilutions in the range of 0.5 % to 5 % AMD water with and without the addition of 10 or 20 mg/L AHA. In the absence of HS, all shrimp died in the 2.5 % AMD treatment. In contrast, addition of HS increased survival in the 2.5 % AMD treatment by ≤66 % as well as significantly decreased the concentration of dissolved Cu, cobalt, cadmium, and Zn. The decreased toxicity of AMD in the presence of HS is likely to be due to complexation and precipitation of heavy metals with the HS; it is also possible that HS caused changes to the physiological condition of the shrimp, thus increasing their survival. These results are valuable in contributing to an improved understanding of potential role of HS in ameliorating the toxicity of AMD environments. PMID:23135152

  1. Proton-facilitated ammonia excretion by ionocytes of medaka (Oryzias latipes) acclimated to seawater.

    PubMed

    Liu, Sian-Tai; Tsung, Lin; Horng, Jiun-Lin; Lin, Li-Yih

    2013-08-01

    The proton-facilitated ammonia excretion is critical for a fish's ability to excrete ammonia in freshwater. However, it remains unclear whether that mechanism is also critical for ammonia excretion in seawater (SW). Using a scanning ion-selective electrode technique (SIET) to measure H(+) gradients, an acidic boundary layer was detected at the yolk-sac surface of SW-acclimated medaka (Oryzias latipes) larvae. The H(+) gradient detected at the surface of ionocytes was higher than that of keratinocytes in the yolk sac. Treatment with Tricine buffer or EIPA (a NHE inhibitor) reduced the H(+) gradient and ammonia excretion of larvae. In situ hybridization and immunochemistry showed that slc9a2 (NHE2) and slc9a3 (NHE3) were expressed in the same SW-type ionocytes. A real-time PCR analysis showed that transfer to SW downregulated branchial mRNA expressions of slc9a3 and Rhesus glycoproteins (rhcg1, rhcg2, and rhbg) but upregulated that of slc9a2. However, slc9a3, rhcg1, rhcg2, and rhbg expressions were induced by high ammonia in SW. This study suggests that SW-type ionocytes play a role in acid and ammonia excretion and that the Na(+)/H(+) exchanger and Rh glycoproteins are involved in the proton-facilitated ammonia excretion mechanism. PMID:23678031

  2. Increase in fatty acid oxidation in calvaria cells cultured with diphosphonates.

    PubMed Central

    Felix, R; Fleisch, H

    1981-01-01

    1. Cultured calvaria cells oxidized palmitate and octanoate to CO2 and water-soluble products. 2. When these cells were treated for 6 days with 0.025 and 0.25 mM-dichloromethanediphosphonate, oxidation of palmitate was increased, whereas that of octanoate was influenced less. 3. When the rate of oxidation was raised by increasing the palmitate concentration in the medium, the effect of the diphosphonate was decreased and finally disappeared. 4. 1-Hydroxyethane-1,1-diphosphonate had only minor effects. 5. The increase in palmitate oxidation appeared 2 days after the addition of dichloromethanediphosphonate, simultaneously with a fall in lactate production. (Inhibition of glycolysis by diphosphonates has already been shown.) 6. Cycloheximide, an inhibitor of protein synthesis, did not influence the effect of dichloromethanediphosphonate on the oxidation of palmitate and the production of lactate. 7. Cells cultured with dichloromethanediphosphonate showed a faster uptake of palmitic acid than did control cells. However, this observation did not explain the increased palmitate oxidation, since uptake was much faster than oxidation, and was therefore not the rate-limiting step. 8. 2-Bromopalmitate, an inhibitor of fatty acid oxidation, did not influence the inhibition of glycolysis by the diphosphonates. This inhibition, therefore, did not result from the increased oxidation of palmitate. It is also unlikely that the increased oxidation of palmitate is connected with the inhibition of glycolysis. PMID:6458286

  3. Impairment of renal sodium excretion in tropical residents - phenomenological analysis

    NASA Astrophysics Data System (ADS)

    Arthur, S. K.; Aryee, P. A.; Amuasi, J.; Hesse, I. F. A.; Affram, R. K.

    There is evidence of impaired renal sodium excretion in salt-sensitive African Blacks. A decreased rate of renal sodium chloride (NaCl) excretion, low plasma renin activity and a tendency to elevated blood pressure are the hallmarks of salt sensitivity. Recent evidence indicates that increased proximal and distal tubular fluid reabsorption in some tropical residents may explain the impaired sodium excretion in these people. In this study of a cohort population, we speculated that subjects selected from that population might be salt-sensitive. We therefore measured the sodium balance in 10 normotensive male subjects over 10 consecutive days, after they had ingested a normal or a high amount of sodium, as NaCl (salt) in their diet. We quantified their renal sodium excretion rate by phenomenological analysis of their sodium balance data. We also measured plasma renin activity for 7 consecutive days in a separate group of 6 male and 4 female subjects in order to assess the state of their renin/angiotensin system. We selected all our subjects from a cohort population of 269 subjects randomly selected from a community known to have a high prevalence of primary hypertension. Our data on two separate groups of subjects from the same cohort population revealed delayed renal sodium excretion with t1/2 of about 5 days, compared to published data for normal individuals with t1/2 of less than 24 h. Also, plasma renin activity levels were low. Hence, our subjects are salt-sensitive. Quantification of their renal impairment is important for various reasons: it heightens one's appreciation of the problem of salt retention in African Blacks who are salt-sensitive and it also underlines the importance of the need for further research into the benefits of dietary salt restriction for reducing cardiovascular mortality in African populations, as has been done in some Western countries.

  4. Increasing Fatty Acid Oxidation Remodels the Hypothalamic Neurometabolome to Mitigate Stress and Inflammation

    PubMed Central

    McFadden, Joseph W.; Aja, Susan; Li, Qun; Bandaru, Veera V. R.; Kim, Eun-Kyoung; Haughey, Norman J.; Kuhajda, Francis P.; Ronnett, Gabriele V.

    2014-01-01

    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. PMID:25541737

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

    PubMed

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

    1992-03-01

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

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

    PubMed

    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. PMID:27038174

  7. Determination of arsenic metabolic complex excreted in human urine after administration of sodium 2,3-dimercapto-1-propane sulfonate.

    PubMed

    Gong, Zhilong; Jiang, Guifeng; Cullen, William R; Aposhian, H Vasken; Le, X Chris

    2002-10-01

    Sodium 2,3-dimercapto-1-propane sulfonate (DMPS) has been used to treat acute arsenic poisoning. Presumably DMPS functions by chelating some arsenic species to increase the excretion of arsenic from the body. However, the excreted complex of DMPS with arsenic has not been detected. Here we describe a DMPS complex with monomethylarsonous acid (MMA(III)), a key trivalent arsenic in the arsenic methylation process, and show the presence of the DMPS-MMA(III) complex in human urine after the administration of DMPS. The DMPS-MMA(III) complex was characterized using electrospray tandem mass spectrometry and determined by using HPLC separation with hydride generation atomic fluorescence detection (HGAFD). The DMPS-MMA(III) complex did not form a volatile hydride with borohydride treatment. On-line digestion with 0.1 M sodium hydroxide following HPLC separation decomposed the DMPS-MMA(III) complex and allowed for the subsequent quantification by hydride generation atomic fluorescence. Arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), MMA(III), and DMPS-MMA(III) complex were analyzed in urine samples from human subjects collected after the ingestion of 300 mg of DMPS. The administration of DMPS resulted in a decrease of the DMA(V) concentration and an increase of the MMA(V) concentration excreted in the urine, confirming the previous results. The finding of the DMPS-MMA(III) complex in human urine after DMPS treatment provides an explanation for the inhibition of arsenic methylation by DMPS. Because MMA(III) is the substrate for the biomethylation of arsenic from MMA(V) to DMA(V), the formation of DMPS-MMA(III) complex would reduce the availability of MMA(III) for the subsequent biomethylation. PMID:12387631

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

    PubMed

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

    2013-08-01

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

  9. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).

    PubMed

    Ziegler, Kerstin; Kerimi, Asimina; Poquet, Laure; Williamson, Gary

    2016-06-01

    Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid. PMID:26854723

  10. Effects of increasing docosahexaenoic acid intake in human healthy volunteers on lymphocyte activation and monocyte apoptosis

    PubMed Central

    Mebarek, Saïda; Ermak, Natalia; Benzaria, Amal; Vicca, Stéphanie; Dubois, Madeleine; Némoz, Georges; Laville, Martine; Lacour, Bernard; Véricel, Evelyne; Lagarde, Michel; Prigent, Annie-France

    2009-01-01

    Dietary intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However most human studies examined the combined effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate (TPA) plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL (oxLDL). Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800 and 1600mg) in a triacylglycerol form containing DHA as the only PUFA, for two weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400mg DHA/day. The TPA plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400mg DHA/day, with a maximum after 800mg intake, and was positively correlated (P<0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxLDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. OxLDL apoptotic effect was significantly attenuated after 400mg DHA/day and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxLDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis. PMID:18710607

  11. Salicylic acid biosynthesis is enhanced and contributes to increased biotrophic pathogen resistance in Arabidopsis hybrids.

    PubMed

    Yang, Li; Li, Bosheng; Zheng, Xiao-yu; Li, Jigang; Yang, Mei; Dong, Xinnian; He, Guangming; An, Chengcai; Deng, Xing Wang

    2015-01-01

    Heterosis, the phenotypic superiority of a hybrid over its parents, has been demonstrated for many traits in Arabidopsis thaliana, but its effect on defence remains largely unexplored. Here, we show that hybrids between some A. thaliana accessions show increased resistance to the biotrophic bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000. Comparisons of transcriptomes between these hybrids and their parents after inoculation reveal that several key salicylic acid (SA) biosynthesis genes are significantly upregulated in hybrids. Moreover, SA levels are higher in hybrids than in either parent. Increased resistance to Pst DC3000 is significantly compromised in hybrids of pad4 mutants in which the SA biosynthesis pathway is blocked. Finally, increased histone H3 acetylation of key SA biosynthesis genes correlates with their upregulation in infected hybrids. Our data demonstrate that enhanced activation of SA biosynthesis in A. thaliana hybrids may contribute to their increased resistance to a biotrophic bacterial pathogen. PMID:26065719

  12. Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans.

    PubMed

    Schlittler, Maja; Goiny, Michel; Agudelo, Leandro Z; Venckunas, Tomas; Brazaitis, Marius; Skurvydas, Albertas; Kamandulis, Sigitas; Ruas, Jorge L; Erhardt, Sophie; Westerblad, Håkan; Andersson, Daniel C

    2016-05-15

    Physical exercise has emerged as an alternative treatment for patients with depressive disorder. Recent animal studies show that exercise protects from depression by increased skeletal muscle kynurenine aminotransferase (KAT) expression which shifts the kynurenine metabolism away from the neurotoxic kynurenine (KYN) to the production of kynurenic acid (KYNA). In the present study, we investigated the effect of exercise on kynurenine metabolism in humans. KAT gene and protein expression was increased in the muscles of endurance-trained subjects compared with untrained subjects. Endurance exercise caused an increase in plasma KYNA within the first hour after exercise. In contrast, a bout of high-intensity eccentric exercise did not lead to increased plasma KYNA concentration. Our results show that regular endurance exercise causes adaptations in kynurenine metabolism which can have implications for exercise recommendations for patients with depressive disorder. PMID:27030575

  13. Salicylic acid biosynthesis is enhanced and contributes to increased biotrophic pathogen resistance in Arabidopsis hybrids

    PubMed Central

    Yang, Li; Li, Bosheng; Zheng, Xiao-yu; Li, Jigang; Yang, Mei; Dong, Xinnian; He, Guangming; An, Chengcai; Deng, Xing Wang

    2015-01-01

    Heterosis, the phenotypic superiority of a hybrid over its parents, has been demonstrated for many traits in Arabidopsis thaliana, but its effect on defence remains largely unexplored. Here, we show that hybrids between some A. thaliana accessions show increased resistance to the biotrophic bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000. Comparisons of transcriptomes between these hybrids and their parents after inoculation reveal that several key salicylic acid (SA) biosynthesis genes are significantly upregulated in hybrids. Moreover, SA levels are higher in hybrids than in either parent. Increased resistance to Pst DC3000 is significantly compromised in hybrids of pad4 mutants in which the SA biosynthesis pathway is blocked. Finally, increased histone H3 acetylation of key SA biosynthesis genes correlates with their upregulation in infected hybrids. Our data demonstrate that enhanced activation of SA biosynthesis in A. thaliana hybrids may contribute to their increased resistance to a biotrophic bacterial pathogen. PMID:26065719

  14. Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance

    PubMed Central

    Yew Tan, Chong; Virtue, Samuel; Murfitt, Steven; Robert, Lee D.; Phua, Yi Hui; Dale, Martin; Griffin, Julian L.; Tinahones, Francisco; Scherer, Philipp E.; Vidal-Puig, Antonio

    2015-01-01

    The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced Δ9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT Δ9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue. PMID:26679101

  15. Human Insulin Resistance Is Associated With Increased Plasma Levels of 12α-Hydroxylated Bile Acids

    PubMed Central

    Haeusler, Rebecca A.; Astiarraga, Brenno; Camastra, Stefania; Accili, Domenico; Ferrannini, Ele

    2013-01-01

    Bile acids (BAs) exert pleiotropic metabolic effects, and physicochemical properties of different BAs affect their function. In rodents, insulin regulates BA composition, in part by regulating the BA 12α-hydroxylase CYP8B1. However, it is unclear whether a similar effect occurs in humans. To address this question, we examined the relationship between clamp-measured insulin sensitivity and plasma BA composition in a cohort of 200 healthy subjects and 35 type 2 diabetic (T2D) patients. In healthy subjects, insulin resistance (IR) was associated with increased 12α-hydroxylated BAs (cholic acid, deoxycholic acid, and their conjugated forms). Furthermore, ratios of 12α-hydroxylated/non–12α-hydroxylated BAs were associated with key features of IR, including higher insulin, proinsulin, glucose, glucagon, and triglyceride (TG) levels and lower HDL cholesterol. In T2D patients, BAs were nearly twofold elevated, and more hydrophobic, compared with healthy subjects, although we did not observe disproportionate increases in 12α-hydroxylated BAs. In multivariate analysis of the whole dataset, controlling for sex, age, BMI, and glucose tolerance status, higher 12α-hydroxy/non–12α-hydroxy BA ratios were associated with lower insulin sensitivity and higher plasma TGs. These findings suggest a role for 12α-hydroxylated BAs in metabolic abnormalities in the natural history of T2D and raise the possibility of developing insulin-sensitizing therapeutics based on manipulations of BA composition. PMID:23884887

  16. Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice

    PubMed Central

    Matsuoka, T; Adair, J E; Lih, F B; Hsi, L C; Rubino, M; Eling, T E; Tomer, K B; Yashiro, M; Hirakawa, K; Olden, K; Roberts, J D

    2010-01-01

    Background: Dietary (n-6)-polyunsaturated fatty acids influence cancer development, but the mechanisms have not been well characterised in gastric carcinoma. Methods: We used two in vivo models to investigate the effects of these common dietary components on tumour metastasis. In a model of experimental metastasis, immunocompromised mice were fed diets containing linoleic acid (LA) at 2% (LLA), 8% (HLA) or 12% (VHLA) by weight and inoculated intraperitoneally (i.p.) with human gastric carcinoma cells (OCUM-2MD3). To model spontaneous metastasis, OCUM-2MD3 tumours were grafted onto the stomach walls of mice fed with the different diets. In in vitro assays, we investigated invasion and ERK phosphorylation of OCUM-2MD3 cells in the presence or absence of LA. Finally, we tested whether a cyclooxygenase (COX) inhibitor, indomethacin, could block peritoneal metastasis in vivo. Results: Both the HLA and VHLA groups showed increased incidence of tumour nodules (LA: 53% HLA: 89% VHLA: 100% P<0.03); the VHLA group also displayed increased numbers of tumour nodules and higher total volume relative to LLA group in experimental metastasis model. Both liver invasion (78%) and metastasis to the peritoneal cavity (67%) were more frequent in VHLA group compared with the LLA group (22% and 11%, respectively; P<0.03) in spontaneous metastasis model. We also found that the invasive ability of these cells is greatly enhanced when exposed to LA in vitro. Linoleic acid also increased invasion of other scirrhous gastric carcinoma cells, OCUM-12, NUGC3 and MKN-45. Linoleic acid effect on OCUM-2MD3 cells seems to be dependent on phosphorylation of ERK. The data suggest that invasion and phosphorylation of ERK were dependent on COX. Indomethacin decreased the number of tumours and total tumour volume in both LLA and VHLA groups. Finally, COX-1, which is known to be an important enzyme in the generation of bioactive metabolites from dietary fatty acids, appears to be responsible for the

  17. Phytate utilization and phosphorus excretion by broiler chickens fed diets containing cereal grains varying in phytate and phytase content

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poor digestibility of phytate P by poultry leads to supplementation of poultry diets with inorganic P thereby increasing feed costs and also increasing the excretion of P by the birds. In order to quantify phytate utilization and P excretion by poultry, eighty, 12 day-old, male broiler chicks, weig...

  18. Twice-weekly consumption of farmed Atlantic salmon increases plasma content of phospholipid n-3 fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated intake of the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is related to risk reduction of cardiovascular and other diseases. Increased consumption of seafood such as farmed Atlantic salmon is an effective way to consume n-3 but there is a paucity of data as ...

  19. Reducing Isozyme Competition Increases Target Fatty Acid Accumulation in Seed Triacylglycerols of Transgenic Arabidopsis1[OPEN

    PubMed Central

    van Erp, Harrie; Shockey, Jay; Zhang, Meng; Adhikari, Neil D.; Browse, John

    2015-01-01

    One goal of green chemistry is the production of industrially useful fatty acids (FAs) in crop plants. We focus on hydroxy fatty acids (HFAs) and conjugated polyenoic FAs (α-eleostearic acids [ESAs]) using Arabidopsis (Arabidopsis thaliana) as a model. These FAs are found naturally in seed oils of castor (Ricinus communis) and tung tree (Vernicia fordii), respectively, and used for the production of lubricants, nylon, and paints. Transgenic oils typically contain less target FA than that produced in the source species. We hypothesized that competition between endogenous and transgenic isozymes for substrates limits accumulation of unique FAs in Arabidopsis seeds. This hypothesis was tested by introducing a mutation in Arabidopsis diacylglycerol acyltransferase1 (AtDGAT1) in a line expressing castor FA hydroxylase and acyl-Coenzyme A:RcDGAT2 in its seeds. This led to a 17% increase in the proportion of HFA in seed oil. Expression of castor phospholipid:diacylglycerol acyltransferase 1A in this line increased the proportion of HFA by an additional 12%. To determine if our observations are more widely applicable, we investigated if isozyme competition influenced production of ESA. Expression of tung tree FA conjugase/desaturase in Arabidopsis produced approximately 7.5% ESA in seed lipids. Coexpression of VfDGAT2 increased ESA levels to approximately 11%. Overexpression of VfDGAT2 combined with suppression of AtDGAT1 increased ESA accumulation to 14% to 15%. Our results indicate that isozyme competition is a limiting factor in the engineering of unusual FAs in heterologous plant systems and that reduction of competition through mutation and RNA suppression may be a useful component of seed metabolic engineering strategies. PMID:25739701

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

    PubMed Central

    Bunn, Janice Y; Ugrasbul, Figen

    2005-01-01

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

  1. Effect of increased protein intake on renal acid load and renal hemodynamic responses.

    PubMed

    Teunissen-Beekman, Karianna F M; Dopheide, Janneke; Geleijnse, Johanna M; Bakker, Stephan J L; Brink, Elizabeth J; de Leeuw, Peter W; van Baak, Marleen A

    2016-03-01

    Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high-protein diets reduce renal function. Effects of acute and 4-week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy-nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty-four-hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein- or maltodextrin-load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P ≤ 0.001). Postprandial filtration fraction decreased further after the protein-supplemented breakfast than after the maltodextrin-supplemented breakfast after 4 weeks of supplementation (P ≤ 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin-converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function. PMID:26997623

  2. Blood pressure, sodium intake, insulin resistance, and urinary nitrate excretion.

    PubMed

    Facchini, F S; DoNascimento, C; Reaven, G M; Yip, J W; Ni, X P; Humphreys, M H

    1999-04-01

    The objective of this study was to investigate the relationships among various humoral factors thought to be involved in the regulation of blood pressure during high NaCl intake. Nineteen healthy subjects underwent sequential 5-day periods ingesting a low-sodium (25 mmol/d) or high-sodium (200 mmol/d) diet. Insulin resistance was assessed by the steady-state plasma glucose concentration at the end of a 3-hour insulin suppression test. Insulin resistance correlated inversely with natriuresis (P=0.04) and directly with increase in weight (P=0.03). The increase in mean arterial pressure associated with the high-sodium diet correlated directly with the gain in weight (P<0.05) and inversely with the increase in urinary nitrate excretion (P<0.0001). In a multiple regression model, more than 2/3 of the variance in mean arterial pressure was accounted for by the gain in weight and change in urinary nitrate excretion. The steady-state plasma glucose concentrations obtained with the 2 diets were similar, indicating that insulin resistance was unaffected by sodium intake. During high sodium intake, plasma renin activity and aldosterone decreased and plasma atrial natriuretic peptide increased; these changes did not correlate with the change in mean arterial pressure, insulin resistance, or change in urinary nitrate excretion. To the extent that urinary nitrate excretion reflects activity of the endogenous nitric oxide system, these results suggest that the salt sensitivity of mean arterial pressure may be related to blunted generation of endogenous nitric oxide. The results also demonstrate that insulin-resistant individuals have an impaired natriuretic response to high sodium intake. PMID:10205239

  3. Organic amendments increase soil solution phosphate concentrations in an acid soil: A controlled environment study

    SciTech Connect

    Schefe, C.R.; Patti, A.F.; Clune, T.S.; Jackson, R.

    2008-04-15

    Soil acidification affects at least 4 million hectares of agricultural land in Victoria, Australia. Low soil pH can inhibit plant growth through increased soluble aluminum (Al) concentrations and decreased available phosphorus (P). The addition of organic amendments may increase P availability through competition for P binding sites, solubilization of poorly soluble P pools, and increased solution pH. The effect of two organic amendments (lignite and compost) on P solubility in an acid soil was determined through controlled environment (incubation) studies. Three days after the addition of lignite and compost, both treatments increased orthophosphate and total P measured in soil solution, with the compost treatments having the greatest positive effect. Increased incubation time (26 days) increased soil solution P concentrations in both untreated and amended soils, with the greatest effect seen in total P concentrations. The measured differences in solution P concentrations between the lignite- and compost-amended treatments were likely caused by differences in solution chemistry, predominantly solution pH and cation dynamics. Soil amendment with lignite or compost also increased microbial activity in the incubation systems, as measured by carbon dioxide respiration. Based on the results presented, it is proposed that the measured increase in soil solution P with amendment addition was likely caused by both chemical and biological processes, including biotic and abiotic P solubilization reactions, and the formation of soluble organic-metal complexes.

  4. Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner.

    PubMed

    Kottyan, Leah C; Collier, Ann R; Cao, Khanh H; Niese, Kathryn A; Hedgebeth, Megan; Radu, Caius G; Witte, Owen N; Khurana Hershey, Gurjit K; Rothenberg, Marc E; Zimmermann, Nives

    2009-09-24

    The microenvironment of the lung in asthma is acidic, yet the effect of acidity on inflammatory cells has not been well established. We now demonstrate that acidity inhibits eosinophil apoptosis and increases cellular viability in a dose-dependent manner between pH 7.5 and 6.0. Notably, acidity induced eosinophil cyclic adenosine 5'-monophosphate (cAMP) production and enhanced cellular viability in an adenylate cyclase-dependent manner. Furthermore, we identify G protein-coupled receptor 65 (GPR65) as the chief acid-sensing receptor expressed by eosinophils, as GPR65-deficient eosinophils were resistant to acid-induced eosinophil cAMP production and enhanced viability. Notably, GPR65(-/-) mice had attenuated airway eosinophilia and increased apoptosis in 2 distinct models of allergic airway disease. We conclude that eosinophil viability is increased in acidic microenvironments in a cAMP- and GPR65-dependent manner. PMID:19641187

  5. Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner

    PubMed Central

    Kottyan, Leah C.; Collier, Ann R.; Cao, Khanh H.; Niese, Kathryn A.; Hedgebeth, Megan; Radu, Caius G.; Witte, Owen N.; Khurana Hershey, Gurjit K.; Rothenberg, Marc E.

    2009-01-01

    The microenvironment of the lung in asthma is acidic, yet the effect of acidity on inflammatory cells has not been well established. We now demonstrate that acidity inhibits eosinophil apoptosis and increases cellular viability in a dose-dependent manner between pH 7.5 and 6.0. Notably, acidity induced eosinophil cyclic adenosine 5′-monophosphate (cAMP) production and enhanced cellular viability in an adenylate cyclase–dependent manner. Furthermore, we identify G protein-coupled receptor 65 (GPR65) as the chief acid-sensing receptor expressed by eosinophils, as GPR65-deficient eosinophils were resistant to acid-induced eosinophil cAMP production and enhanced viability. Notably, GPR65−/− mice had attenuated airway eosinophilia and increased apoptosis in 2 distinct models of allergic airway disease. We conclude that eosinophil viability is increased in acidic microenvironments in a cAMP- and GPR65-dependent manner. PMID:19641187

  6. Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux

    PubMed Central

    Patterson, Robert N; Johnston, Brian T; Ardill, Joy E S; Heaney, Liam G; McGarvey, Lorcan P A

    2007-01-01

    Background Acid reflux may aggravate airway disease including asthma and chronic cough. One postulated mechanism concerns a vagally‐mediated oesophageal‐tracheobronchial reflex with airway sensory nerve activation and tachykinin release. Aim To test the hypothesis that patients with airways disease and reflux have higher airway tachykinin levels than those without reflux. Methods Thirty‐two patients with airways disease (16 with mild asthma and 16 non‐asthmatic subjects with chronic cough) underwent 24 h oesophageal pH monitoring. Acid reflux was defined as increased total oesophageal acid exposure (% total time pH <4 of >4.9% at the distal probe). All subjects underwent sputum induction. Differential cell counts and concentrations of substance P (SP), neurokinin A (NKA), albumin and α2‐macroglobulin were determined. Results SP and NKA levels were significantly higher in patients with reflux than in those without (SP: 1434 (680) pg/ml vs 906 (593) pg/ml, p = 0.026; NKA: 81 (33) pg/ml vs 52 (36) pg/ml, p = 0.03). Significantly higher tachykinin levels were also found in asthmatic patients with reflux than in asthmatic patients without reflux (SP: 1508 (781) pg/ml vs 737 (512) pg/ml, p = 0.035; NKA: median (interquartile range 108 (85–120) pg/ml vs 75 (2–98) pg/ml, p = 0.02). In patients with asthma there was a significant positive correlation between distal oesophageal acid exposure and SP levels (r = 0.59, p = 0.01) and NKA levels (r = 0.56, p = 0.02). Non‐significant increases in SP and NKA were measured in patients with cough with reflux (SP: 1534.71 (711) pg/ml vs 1089 (606) pg/ml, p = 0.20; NKA: 56 (43) pg/ml vs 49 (17) pg/ml, p = 0.71). No significant difference in differential cell counts or any other biochemical parameter was noted between study groups. Conclusion This study demonstrates increased airway tachykinin levels in patients with asthma and cough patients with

  7. Urinary CYP Eicosanoid Excretion Correlates with Glomerular Filtration in African-Americans with Chronic Kidney Disease

    PubMed Central

    Dreisbach, Albert W; Smith, Stanley V; Kyle, Patrick B; Ramaiah, Manjunath; Amenuke, Margaret; Garrett, Michael R; Lirette, Seth T; Griswold, Michael E; Roman, Richard J

    2015-01-01

    Previous studies have indicated that cytochrome P450 (CYP) metabolites of arachidonic acid (AA), i.e., 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs), play an important role in the regulation of renal tubular and vascular function. The present study for the first time profiled HETEs and epoxygenase derived dihydroxyeicosatetraenoic acid diHETEs levels in spot urines and plasma in 262 African American patients from the University of Mississippi Chronic Kidney Disease Clinic and 31 African American controls. Significant correlations in eGFR and urinary 20-HETE/creatinine and 19-HETE/ creatinine levels were observed. The eGFR increased by 17.47 [p=0.001] and 60.68 [(p=0.005] ml/min/ for each ng/mg increase in 20-HETE and 19-HETE levels, respectively. Similar significant positive associations were found between the other urinary eicosanoids and eGFR and also with 19-HETE/urine creatinine concentration and proteinuria. We found that approximately 80% of plasma HETEs and 30% diHETEs were glucuronidated and the fractional excretion of 20-HETE was less than 1%. These results suggest that there is a significant hepatic source of urinary 20-HETE glucuronide and EETs with extensive renal biotransformation to metabolites which may play a role in the pathogenesis of CKD. PMID:25151892

  8. Comparison of celecoxib metabolism and excretion in mouse, rabbit, dog, cynomolgus monkey and rhesus monkey.

    PubMed

    Paulson, S K; Zhang, J Y; Jessen, S M; Lawal, Y; Liu, N W; Dudkowski, C M; Wang, Y F; Chang, M; Yang, D; Findlay, J W; Berge, M A; Markos, C S; Breau, A P; Hribar, J D; Yuan, J

    2000-07-01

    1. The metabolism and excretion of celecoxib, a specific cyclooxygenase 2 (COX-2) inhibitor, was investigated in mouse, rabbit, the EM (extensive) and PM (poor metabolizer) dog, and rhesus and cynomolgus monkey. 2. Some sex and species differences were evident in the disposition of celecoxib. After intravenous (i.v.) administration of [14C]celecoxib, the major route of excretion of radioactivity in all species studied was via the faeces: EM dog (80.0%), PM dog (83.4%), cynomolgus monkey (63.5%), rhesus monkey (83.1%). After oral administration, faeces were the primary route of excretion in rabbit (72.2%) and the male mouse (71.1%), with the remainder of the dose excreted in the urine. After oral administration of [14C]celecoxib to the female mouse, radioactivity was eliminated equally in urine (45.7%) and faeces (46.7%). 3. Biotransformation of celecoxib occurs primarily by oxidation of the aromatic methyl group to form a hydroxymethyl metabolite, which is further oxidized to the carboxylic acid analogue. 4. An additional phase I metabolite (phenyl ring hydroxylation) and a glucuronide conjugate of the carboxylic acid metabolite was produced by rabbit. 5. The major excretion product in urine and faeces of mouse, rabbit, dog and monkey was the carboxylic acid metabolite of celecoxib. PMID:10963063

  9. Effect of Colesevelam on Fecal Bile Acids and Bowel Functions in Diarrhea-Predominant Irritable Bowel Syndrome

    PubMed Central

    Camilleri, Michael; Acosta, Andres; Busciglio, Irene; Boldingh, Amy; Dyer, Roy B.; Zinsmeister, Alan R.; Lueke, Alan; Gray, Amber; Donato, Leslie J.

    2015-01-01

    Background About one-third of patients with IBS-diarrhea (IBS-D) have evidence of increased bile acid (BA) synthesis or excretion. Aims To assess effects of the BA sequestrant, colesevelam, on fecal excretion of BAs, hepatic BA synthesis and diarrhea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-hour total fecal BA excretion and proportions of the main BAs excreted; to study the fecal fat excretion in response to colesevelam. Methods Study design: A single-center, unblinded, single-dose trial of effects of colesevelam, 1875mg [3 tablets (625mg tablets)] orally, twice daily, for 10 days on total 48-hour fecal BA excretion and fasting serum C4 (surrogate of hepatic BA synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48-hour samples and fasting serum were collected for fecal fat, fecal BA and serum C4. Results Colesevelam was associated with significantly increased fecal total BA excretion and deoxycholic acid excretion, increased serum C4, and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total BA sequestered into stool during the last 48 hours of treatment. Random stool samples did not accurately reflect 48-hour total or individual fecal BA excretion. Sequestration of BAs by colesevelam did not increase fecal fat. Conclusions Colesevelam increases delivery of BAs to stool while improving stool consistency, and increases hepatic BA synthesis, avoiding steatorrhea in patients with IBS-D. Overall effects are consistent with luminal BA sequestration by colesevelam. PMID:25594801

  10. Acidic Residues in the Hfq Chaperone Increase the Selectivity of sRNA Binding and Annealing.

    PubMed

    Panja, Subrata; Santiago-Frangos, Andrew; Schu, Daniel J; Gottesman, Susan; Woodson, Sarah A

    2015-11-01

    Hfq facilitates gene regulation by small non-coding RNAs (sRNAs), thereby affecting bacterial attributes such as biofilm formation and virulence. Escherichia coli Hfq recognizes specific U-rich and AAN motifs in sRNAs and target mRNAs, after which an arginine patch on the rim promotes base pairing between their complementary sequences. In the cell, Hfq must discriminate between many similar RNAs. Here, we report that acidic amino acids lining the sRNA binding channel between the inner pore and rim of the Hfq hexamer contribute to the selectivity of Hfq's chaperone activity. RNase footprinting, in vitro binding and stopped-flow fluorescence annealing assays showed that alanine substitution of D9, E18 or E37 strengthened RNA interactions with the rim of Hfq and increased annealing of non-specific or U-tailed RNA oligomers. Although the mutants were less able than wild-type Hfq to anneal sRNAs with wild-type rpoS mRNA, the D9A mutation bypassed recruitment of Hfq to an (AAN)4 motif in rpoS, both in vitro and in vivo. These results suggest that acidic residues normally modulate access of RNAs to the arginine patch. We propose that this selectivity limits indiscriminate target selection by E. coli Hfq and enforces binding modes that favor genuine sRNA and mRNA pairs. PMID:26196441

  11. High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degeneration.

    PubMed

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

    2009-05-01

    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

  12. Urinary excretion of hydroxylysine and its glycosides as an index of collagen degradation.

    PubMed Central

    Krane, S M; Kantrowitz, F G; Byrne, M; Pinnell, S R; Singer, F R

    1977-01-01

    Urimary excretion of hydroxyprolin (Hyp) is one index of total collagen degradation, from all sources. Since some of the Hyp released from collagen may be further metabolized before it is excreted, other markers are necessary to measure collagen breakdown. Excretion of the glycosides of hydroxylysine (Hyl), glucosyl galactosyl hydroxylysine (Hy1[Gl)cGa1]), and galactosyl hydroxylysine (Hyl[Ga)]), more accurately reflects collagen metabolism since these products occur in specificratios in different tissue collagens and are themselves metabolized only to a minor degree. The ratios of total Hy1/Hyp and Hyl(GlcGal)/Hyl(Ga1) were measured in the urine of norma. subjects and of patients with Paget's disease of bone, hyperphosphatasia, and extensive thermal burns. In patients with extensive thermal burns the pattern of urinary Hy1 and its glycosides was consistent with degradation of collagen in dermis and fascia. When bone collagen degradation was dominant, the pattern of urinary metabolites reflected that source. Pagetic bone collagen has an amino acid composition similar to normal bone and Hy1(G1cGa1/Hyl(G1) of 0.396-0.743,vs. normal of 0.474+/-0.088. In untreated patients with severe Paget's disease of bone or hyperphosphatasia (urinary Hyp greater than 2.0 micronmol/mg creatinine) urinary Hyl/Hyp averaged 0.052+/-0.042 (0.042+/-0.009 in normal bone) and Hy1(G1cGa1)/Hy1(Ga1) 0.601+/-0.017 (0.47+/-0.009 in normal bone). When bone resorption was decreased sufficiently with calcitonin or disodium etidronate in these patients, both the urinary ratios of Hy1/Hyp and Hy1(G1cGa1)/Hyl(Gal) rose. In normal subjects treated with calcitonin and excreting relatively little Hyp, the ratio of Hy1/H)P approached 0.7 and Hy1(G1ycGa1)/Hy1(Ga1) approached 3.5. There increased ratios reveal the existence of a source of collagen breakdown other than skin or bone. The first subcompoent of complement, Clq, which has collagen-like sequences, relatively high amounts of Hy1, and most of the

  13. Experimentally caused proliferation of lysosomes in cultured BHK cells involving an increase of biphosphatidic acids and triglycerides.

    PubMed

    Brotherus, J; Niinioja, T; Sandelin, K; Renkonen, O

    1977-05-01

    When cultured hamster fibroblasts (BHK 21 cells) were incubated in a synthetic serum-free medium up to 4 days, they developed signs of a progressive proliferation of lysosomes. The cells became filled with vacuoles that contained polymorphic debris and showed acid phosphatase activity. The specific activities of acid protease and acid phosphatase in the cell cultures increased three- to fourfold. The process was accompanied by a marked decrease in the contents of protein, deoxyribonucleic acid, and total phospholipids of the cultures. The concentration of lysobisphosphatidic acid increased during the incubation from about 1.5% to 3-6% of the cellular phospholipids. The concentrations of two related lipids, bisphosphatidic acid and semilysobisphosphatidic acid also increased substantially. The triglyceride content of the cells increased several fold, whereas the concentration of phosphatidylcholine decreased markedly. Lysobisphosphatidic acid did not increase upon induction of vacuolization by exogenous sucrose, nor when there was an accumulation of triglyceride due to addition of oleic acid to the growth medium. These findings suggest that the formation of the bisphosphatidic acids may be specifically linked to the autolysis of the phospholipids of the cellular membranes and the formation of triglycerides associated with this process. PMID:864326

  14. Adverse effects of free fatty acid associated with increased oxidative stress in postischemic isolated rat hearts.

    PubMed

    Gambert, Ségolène; Vergely, Catherine; Filomenko, Rodolphe; Moreau, Daniel; Bettaieb, Ali; Opie, Lionel H; Rochette, Luc

    2006-02-01

    The mechanisms of the adverse effects of free fatty acids on the ischemic-reperfused myocardium are not fully understood. Long-chain fatty acids, including palmitate, uncouple oxidative phosphorylation and should therefore promote the formation of oxygen-derived free radicals, with consequent adverse effects. Conversely, the antianginal agent trimetazidine (TMZ), known to inhibit cardiac fatty acid oxidation, could hypothetically lessen the formation of reactive oxygen species (ROS) and thus improve reperfusion mechanical function. Isolated perfused rat hearts underwent 30 min of total global ischemia followed by 30 min of reperfusion. Hearts were perfused with glucose 5.5 mmol/l or palmitate 1.5 mmol/l with or without TMZ (100 micromol/l). Ascorbyl free radical (AFR) release during perfusion periods was measured by electron spin resonance as a marker of oxidative stress. Post-ischemic recovery in the palmitate group of heart was lower than in the glucose group with a marked rise in diastolic tension and reduction in left ventricular developed pressure (Glucose: 85 +/- 11 mmHg; Palmitate: 10 +/- 6 mmHg; p < 0.001). TMZ decreased diastolic tension in both glucose- and in palmitate-perfused hearts. Release of AFR within the first minute of reperfusion was greater in palmitate-perfused hearts and in hearts perfused with either substrate, this marker of oxidative stress was decreased by TMZ (expressed in arbitrary units/ml; respectively: 8.49 +/- 1.24 vs. 1.06 +/- 0.70 p < 0.05; 12.47 +/- 2.49 vs. 3.37 +/- 1.29 p < 0.05). Palmitate increased the formation of ROS and reperfusion contracture. TMZ, a potential inhibitor of palmitate-induced mitochondrial uncoupling, decreased the formation of free radicals and improved postischemic mechanical dysfunction. The novel conclusion is that adverse effects of fatty acids on ischemic-reperfusion injury may be mediated, at least in part, by oxygen-derived free radicals. PMID:16444597

  15. Urinary excretion values in 2-day food-deprived, unrestrained chimpanzees.

    NASA Technical Reports Server (NTRS)

    Mcnew, J. J.; Sabbot, I. M.; Hoshizaki, T.; Mandell, A. J.; Spooner, C. E.; Marcus, I.; Adey, W. R.

    1972-01-01

    A study was conducted to determine the baseline 24-hr urinary excretion values in the young, unrestrained chimpanzee, and also changes in urinary values, if any, induced by the two-day food deprivation stress. Urine was analyzed for volume, osmolarity, creatinine, creatine, urea nitrogen, 17-hydroxycorticosteroids (17-OHCS), 3-methoxy-4-hydroxymandelic acid (VMA), calcium, and inorganic phosphorus. Significant increases due to food deprivation stress were observed for volume, creatine, urea nitrogen, 17-OHCS, VMA, and phosphorus values, with significant decreases in osmolarity and calcium. All values approached normal levels by the second poststress day. No significant changes were observed in creatinine. A comparison is drawn between human and chimpanzee adaptation to stress.

  16. Continuous synthesis and excretion of the compatible solute ectoine by a transgenic, nonhalophilic bacterium.

    PubMed

    Schubert, Torsten; Maskow, Thomas; Benndorf, Dirk; Harms, Hauke; Breuer, Uta

    2007-05-01

    The compatible solute 1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid (ectoine) acts in microorganisms as an osmotic counterweight against halostress and has attracted commercial attention as a protecting agent. Its production and application are restricted by the drawbacks of the discontinuous harvesting procedure involving salt shocks, which reduces volumetric yield, increases reactor corrosion, and complicates downstream processing. In order to synthesize ectoine continuously in less-aggressive media, we introduced the ectoine genes ectABC of the halophilic bacterium Chromohalobacter salexigens into an Escherichia coli strain using the expression vector pASK-IBA7. Under the control of a tet promoter, the transgenic E. coli synthesized 6 g liter-1 ectoine with a space-time yield of 40 mg liter-1 h-1, with the vast majority of the ectoine being excreted. PMID:17369334

  17. Biliary and renal excretions of cefpiramide in Eisai hyperbilirubinemic rats.

    PubMed Central

    Muraoka, I; Hasegawa, T; Nadai, M; Wang, L; Haghgoo, S; Tagaya, O; Nabeshima, T

    1995-01-01

    Eisai hyperbilirubinemic mutant rats (EHBRs) with conjugated hyperbilirubinemia were recently derived from Sprague-Dawley rats (SDRs). The pharmacokinetic characteristics of the beta-lactam antibiotic cefpiramide (CPM), which is mainly excreted into bile, were investigated in 10- and 20-week-old EHBRs and were compared with those in 20-week-old healthy SDRs. The pharmacokinetic parameters of CPM after an intravenous administration of 20 mg/kg of body weight were estimated for each rat by noncompartmental methods. When compared with age-matched healthy SDRs, significant decreases (by approximately 30%) in the systemic clearance of CPM were observed in 20-week-old EHBRs. The biliary clearance of CPM in 20-week-old EHBRs markedly decreased to less than 10% of that in age-matched healthy SDRs, while total urinary recovery of unchanged CPM increased to threefold and renal clearance doubled. However, no significant differences in any of the pharmacokinetic parameters of CPM were observed between the two groups of EHBRs. There were no significant differences among the three groups in the steady-state volume of distribution of CPM. The present study indicates that hyperbilirubinemia induces an increase in the urinary excretion ability of CPM in return for a reduction in the biliary excretion. PMID:7695332

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

    SciTech Connect

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

    1990-06-01

    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.

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

    PubMed Central

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    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 postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors. PMID:24971025

  20. Increased Missense Mutation Burden of Fatty Acid Metabolism Related Genes in Nunavik Inuit Population

    PubMed Central

    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

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:26010953

  1. AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation

    PubMed Central

    Herms, Albert; Bosch, Marta; Reddy, Babu J.N.; Schieber, Nicole L.; Fajardo, Alba; Rupérez, Celia; Fernández-Vidal, Andrea; Ferguson, Charles; Rentero, Carles; Tebar, Francesc; Enrich, Carlos; Parton, Robert G.; Gross, Steven P.; Pol, Albert

    2015-01-01

    Lipid droplets (LDs) are intracellular organelles that provide fatty acids (FAs) to cellular processes including synthesis of membranes and production of metabolic energy. While known to move bidirectionally along microtubules (MTs), the role of LD motion and whether it facilitates interaction with other organelles are unclear. Here we show that during nutrient starvation, LDs and mitochondria relocate on detyrosinated MT from the cell centre to adopt a dispersed distribution. In the cell periphery, LD–mitochondria interactions increase and LDs efficiently supply FAs for mitochondrial beta-oxidation. This cellular adaptation requires the activation of the energy sensor AMPK, which in response to starvation simultaneously increases LD motion, reorganizes the network of detyrosinated MTs and activates mitochondria. In conclusion, we describe the existence of a specialized cellular network connecting the cellular energetic status and MT dynamics to coordinate the functioning of LDs and mitochondria during nutrient scarcity. PMID:26013497

  2. IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism

    PubMed Central

    Grassian, Alexandra R.; Parker, Seth J.; Davidson, Shawn M.; Divakarun, Ajit S.; Green, Courtney R.; Zhang, Xiamei; Slocum, Kelly L.; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D.; Straub, Christopher; Growney, Joseph D.; Vander Heiden, Matthew G.; Murphy, Anne N.; Pagliarini, Raymond; Metallo, Christian M.

    2016-01-01

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed 13C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation. PMID:24755473

  3. Nicotinic acid increases the lipid content of rat brain synaptosomes. [Ethanol effects

    SciTech Connect

    Basilio, C.; Flores, M.

    1989-02-09

    Chronic administration of nicotinic acid (NA) increase hepatic lipids and potentiates a similar effect induced by ethanol. The amethystic properties of NA promoted us to study its effects on the lipid content of brain synaptosomes of native and ethanol treated rats. Groups of 10 Sprague-Dawley female rats received i.p. either saline, ethanol (4g/kg), NA (50mg/kg), or a mixture of both compounds once a week during 3 weeks. The sleeping time (ST) of the animals receiving ethanol was recorded, brain synaptosomes of all groups were prepared and total lipids (TL) and cholesterol (Chol) content were determined. NA, ethanol and ethanol + NA markedly increased both TL and Chol of synaptosomes. Animals treated with ethanol or ethanol + NA developed tolerance. The group treated with ethanol-NA showed the highest Chol content and slept significantly less than the one treated with ethanol alone indicating that the changes induced by NA favored the appearance of tolerance.

  4. Phosphatidic acid osmotically destabilizes lysosomes through increased permeability to K+ and H+.

    PubMed

    Yi, Y-P; Wang, X; Zhang, G; Fu, T-S; Zhang, G-J

    2006-06-01

    Lysosomal destabilization is a critical event not only for the organelle but also for living cells. However, what factors can affect lysosomal stability is not fully studied. In this work, the effects of phosphatidic acid (PA) on the lysosomal integrity were investigated. Through the measurements of lysosomal beta-hexosaminidase free activity, intralysosomal pH, leakage of lysosomal protons and lysosomal latency loss in hypotonic sucrose medium, we established that PA could increase the lysosomal permeability to K+ and H+, and enhance the lysosomal osmotic sensitivity. Treatment of lysosomes with PA promoted entry of K+ into the organelle via K+/H+ exchange, which could produce osmotic stresses and osmotically destabilize the lysosomes. In addition, PA-induced increase in the lysosomal osmotic sensitivity caused the lysosomes to become more liable to destabilization in osmotic shocks. The results suggest that PA may play a role in the lysosomal destabilization. PMID:16917129

  5. Zoledronic acid in vivo increases in vitro proliferation of rat mesenchymal stromal cells.

    PubMed

    Heino, Terhi J; Alm, Jessica J; Halkosaari, Heikki J; Välimäki, Ville-Valtteri

    2016-08-01

    Background and purpose - Bisphosphonates are widely used in the treatment of bone loss, but they might also have positive effects on osteoblastic cells and bone formation. We evaluated the effect of in vivo zoledronic acid (ZA) treatment and possible concomitant effects of ZA and fracture on the ex vivo osteogenic capacity of rat mesenchymal stromal cells (MSCs). Methods - A closed femoral fracture model was used in adult female rats and ZA was administered as a single bolus or as weekly doses up to 8 weeks. Bone marrow MSCs were isolated and cultured for in vitro analyses. Fracture healing was evaluated by radiography, micro-computed tomography (μCT), and histology. Results - Both bolus and weekly ZA increased fracture-site bone mineral content and volume. MSCs from weekly ZA-treated animals showed increased ex vivo proliferative capacity, while no substantial effect on osteoblastic differentiation was observed. Fracture itself did not have any substantial effect on cell proliferation or differentiation at 8 weeks. Serum biochemical markers showed higher levels of bone formation in animals with fracture than in intact animals, while no difference in bone resorption was observed. Interestingly, ex vivo osteoblastic differentiation of MSCs was found to correlate with in vivo serum bone markers. Interpretation - Our data show that in vivo zoledronic acid treatment can influence ex vivo proliferation of MSCs, indicating that bisphosphonates can have sustainable effects on cells of the osteoblastic lineage. Further research is needed to investigate the mechanisms. PMID:27196705

  6. Effects of increasing acidity on metal(loid) bioprecipitation in groundwater: column studies.

    PubMed

    Davis, Alexander C; Patterson, Bradley M; Grassi, Michelle E; Robertson, Blair S; Prommer, Henning; McKinley, Allan J

    2007-10-15

    Large-scale column experiments were carried out over a period of 545 days to assess the effect of increasing acidity on bacterial denitrification, sulfate reduction, and metal(loid) bioprecipitation in groundwater affected by acid mine drainage. At a groundwater pH of 5.5, denitrification and Cu2+ removal, probably via malachite (Cu2(OH)2CO3) precipitation, were observed in the ethanol-amended column. Sulfate reduction, sulfide production, and Zn2+ removal were also observed, with Zn2+ removal observed in the zone of sulfate reduction, indicating likely precipitation as sphalerite (ZnS). Se6+ removal was also observed in the sulfate reducing zone, probably as direct bioreduction to elemental selenium via ethanol/acetate oxidation or sulfide oxidation precipitating elemental sulfur. A step decrease in groundwater pH from 5.5 to 4.25 resulted in increased denitrification and sulfate reduction half-lives, migration of both these redox zones along the ethanol-amended column, and the formation of an elevated Cu2+ plume. Additionally, an elevated Zn2+ plume formed in the previous sulfate reducing zone of the ethanol-amended column, suggesting dissolution of precipitated sphalerite as a result of the reduction in groundwater pH. As Cu2+ passed through the zone of sphalerite dissolution, SEM imaging and EDS detection suggested that Cu2+ removal had occurred via chalcocite (Cu2S) or covellite (CuS) precipitation. PMID:17993159

  7. Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice.

    PubMed

    Hoyer, Friedrich Felix; Khoury, Mona; Slomka, Heike; Kebschull, Moritz; Lerner, Raissa; Lutz, Beat; Schott, Hans; Lütjohann, Dieter; Wojtalla, Alexandra; Becker, Astrid; Zimmer, Andreas; Nickenig, Georg

    2014-01-01

    The role of endocannabinoids such as anandamide during atherogenesis remains largely unknown. Fatty acid amide hydrolase (FAAH) represents the key enzyme in anandamide degradation, and its inhibition is associated with subsequent higher levels of anandamide. Here, we tested whether selective inhibition of FAAH influences the progression of atherosclerosis in mice. Selective inhibition of FAAH using URB597 resulted in significantly increased plasma levels of anandamide compared to control, as assessed by mass spectrometry experiments in mice. Apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-fat, cholesterol-rich diet to induce atherosclerotic conditions. Simultaneously, mice received either the pharmacological FAAH inhibitor URB597 1mg/kg body weight (n=28) or vehicle (n=25) via intraperitoneal injection three times a week. After eight weeks, mice were sacrificed, and experiments were performed. Vascular superoxide generation did not differ between both groups, as measured by L012 assay. To determine whether selective inhibition of FAAH affects atherosclerotic plaque inflammation, immunohistochemical staining of the aortic root was performed. Atherosclerotic plaque formation, vascular macrophage accumulation, as well as vascular T cell infiltration did not differ between both groups. Interestingly, neutrophil cell accumulation was significantly increased in mice receiving URB597 compared to control. Vascular collagen structures in atherosclerotic plaques were significantly diminished in mice treated with URB597 compared to control, as assessed by picro-sirius-red staining. This was accompanied by an increased aortic expression of matrix metalloproteinase-9, as determined by quantitative RT-PCR and western blot analysis. Inhibition of fatty acid amide hydrolase does not influence plaque size but increases plaque vulnerability in mice. PMID:24286707

  8. Reducing isozyme competition increases target fatty acid accumulation in seed triacylglycerols of transgenic Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One goal of green chemistry is the production of industrially useful fatty acids (FAs) in crop plants. We focus on the engineering of industrial FAs, specifically hydroxy fatty acids (HFA) and conjugated polyenoic fatty acids (a-eleostearic acid, ESA), using Arabidopsis (Arabidopsis thaliana) as a m...

  9. Increased fracture penetration and productivity using xanthan gelled acid in massive carbonate formations

    SciTech Connect

    Molon, J.P.; Fox, K.B.

    1983-03-01

    A measurable improvement in productivity can be achieved using xanthan gelled acid to stimulate carbonate formations. Well productivity results were compared to conventional acid fracture treatments. The significant improvements over classical acid fracturing techniques are due to the improved control of acid leakoff rates, retarded reaction rate and improved fracture width maintenance. The difficulties involved in acid fracturing massive Middle East carbonate formations are discussed and solutions are proposed using gelled acid technology. Some limitations in computer predictions of acid fracturing results are also discussed.

  10. Abnormal catecholamine urinary excretion after emotional stimulus in patients with cerebral hemorrhage.

    PubMed

    Stoica, E; Enulescu, O

    1981-01-01

    The epinephrine (E) and norepinephrine (NE) urinary excretion before and after a mild "emotional stimulus" (ES) was determined in 22 patients with cerebral infarction and 30 patients with cerebral hemorrhage, as well as in 18 normotensive and 18 hypertensive controls. In patients with cerebral infarction, the majority normotensive, the "emotional stimulus" induced a significant increase in NE excretion, but non-significant alterations in E excretion. Similar changes were noted in normotensive controls. In patients with cerebral hemorrhage, almost all hypertensive, and in hypertensive controls, ES brought about a consistent rise in E excretion without influencing significantly the NE excretion. The presence of a constant increase in E excretion after a mild emotion not only in patients with cerebral hemorrhage but also in subjects with uncomplicated essential hypertension, suggests that the E release found in patients with cerebral hemorrhage is related to the hypertensive state pre-existing the stroke rather than to hemorrhagic stroke itself. The pattern of catecholamine discharge in hypertensive patients might play a part in the occurrence of cerebral hemorrhagic accidents. The epinephrine discharges induce sudden increases in systolic blood pressure which could lead to the rupture of cerebral vessels with hyalinotic or atherosclerotic alterations. PMID:7245303

  11. Adaptation of in vivo amino acid kinetics facilitates increased amino acid availability for fetal growth in adolescent and adult pregnancies alike

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During pregnancy, adult women with a normal BMI synthesize extra amino acids after an overnight fast by increasing body protein breakdown and decreasing amino acid oxidation. It is not known whether adolescent girls can make these adaptations during pregnancy. The present study aimed to measure and ...

  12. Optical clearing of skin enhanced with hyaluronic acid for increased contrast of optoacoustic imaging.

    PubMed

    Liopo, Anton; Su, Richard; Tsyboulski, Dmitri A; Oraevsky, Alexander A

    2016-08-01

    Enhanced delivery of optical clearing agents (OCA) through skin may improve sensitivity of optical and optoacoustic (OA) methods of imaging, sensing, and monitoring. This report describes a two-step method for enhancement of light penetration through skin. Here, we demonstrate that topical application of hyaluronic acid (HA) improves skin penetration of hydrophilic and lipophilic OCA and thus enhances their performance. We examined the OC effect of 100% polyethylene and polypropylene glycols (PPGs) and their mixture after pretreatment by HA, and demonstrated significant increase in efficiency of light penetration through skin. Increased light transmission resulted in a significant increase of OA image contrast in vitro. Topical pretreatment of skin for about 30 min with 0.5% HA in aqueous solution offers effective delivery of low molecular weight OCA such as a mixture of PPG-425 and polyethylene glycol (PEG)-400. The developed approach of pretreatment by HA prior to application of clearing agents (PEG and PPG) resulted in a ∼ 47-fold increase in transmission of red and near-infrared light and significantly enhanced contrast of OA images. PMID:27232721

  13. Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids.

    PubMed

    Lachmandas, Ekta; van den Heuvel, Corina N A M; Damen, Michelle S M A; Cleophas, Maartje C P; Netea, Mihai G; van Crevel, Reinout

    2016-01-01

    Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis. PMID:27057552

  14. Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids

    PubMed Central

    Lachmandas, Ekta; van den Heuvel, Corina N. A. M.; Damen, Michelle S. M. A.; Cleophas, Maartje C. P.; Netea, Mihai G.; van Crevel, Reinout

    2016-01-01

    Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis. PMID:27057552

  15. Proteins implicated in the increase of adhesivity induced by suberoylanilide hydroxamic acid in leukemic cells.

    PubMed

    Grebeňová, D; Röselová, P; Pluskalová, M; Halada, P; Rösel, D; Suttnar, J; Brodská, B; Otevřelová, P; Kuželová, K

    2012-12-21

    We have previously shown that suberoylanilide hydroxamic acid (SAHA) treatment increases the adhesivity of leukemic cells to fibronectin at clinically relevant concentrations. Now, we present the results of the proteomic analysis of SAHA effects on leukemic cell lines using 2-DE and ProteomLab PF2D system. Histone acetylation at all studied acetylation sites reached the maximal level after 5 to 10 h of SAHA treatment. No difference in histone acetylation between subtoxic and toxic SAHA doses was observed. SAHA treatment induced cofilin phosphorylation at Ser3, an increase in vimentin and paxillin expression and a decrease in stathmin expression as confirmed by western-blotting and immunofluorescence microscopy. The interaction of cofilin with 14-3-3 epsilon was documented using both Duolink system and coimmunoprecipitation. However, this interaction was independent of cofilin Ser3 phosphorylation and the amount of 14-3-3-ε-bound cofilin did not rise following SAHA treatment. SAHA-induced increase in the cell adhesivity was associated with an increase in PAK phosphorylation in CML-T1 cells and was abrogated by simultaneous treatment with IPA-3, a PAK inhibitor. The effects of SAHA on JURL-MK1 cells were similar to those of other histone deacetylase inhibitors, tubastatin A and sodium butyrate. The proteome analysis also revealed several potential non-histone targets of histone deacetylases. PMID:23022583

  16. Excretion of copper complexed with thiomolybdate into the bile and blood in LEC rats.

    PubMed

    Komatsu, Y; Sadakata, I; Ogra, Y; Suzuki, K T

    2000-02-01

    Copper (Cu) accumulating in a form bound to metallothionein (MT) in the liver of Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disease, was removed with ammonium tetrathiomolybdate (TTM), and the fate of the Cu complexed with TTM and mobilized from the liver was determined. TTM was injected intravenously as a single dose of 2, 10 or 50 mg TTM/kg body weight into LEC and Wistar (normal Cu metabolism) rats, and then the concentrations of Cu and molybdenum (Mo) in the bile and plasma were monitored with time after the injection. In Wistar rats, most of the Mo was excreted into the urine, only a small quantity being excreted into the bile, while Cu excreted into the urine decreased. However, in LEC rats, Cu and Mo were excreted into the bile and blood, and the bile is recognized for the first time as the major route of excretion. The Cu excreted into both the bile and plasma was accompanied by an equimolar amount of Mo. The relative ratio of the amounts of Cu excreted into the bile and plasma was 40/60 for the low and high dose groups, and 70/30 for the medium dose group. The systemic dispositions of the Cu mobilized from the liver and the Mo complexed with the Cu were also determined for the kidneys, spleen and brain together with their urinal excretion. Although Mo in the three organs and Cu in the kidneys and spleen were increased or showed a tendency to increase, Cu in the brain was not increased at all doses of TTM. PMID:10728780

  17. Increased saturated fatty acids in obesity alter resolution of inflammation in part by stimulating prostaglandin production.

    PubMed

    Hellmann, Jason; Zhang, Michael J; Tang, Yunan; Rane, Madhavi; Bhatnagar, Aruni; Spite, Matthew

    2013-08-01

    Extensive evidence indicates that nutrient excess associated with obesity and type 2 diabetes activates innate immune responses that lead to chronic, sterile low-grade inflammation, and obese and diabetic humans also have deficits in wound healing and increased susceptibility to infections. Nevertheless, the mechanisms that sustain unresolved inflammation during obesity remain unclear. In this study, we report that saturated free fatty acids that are elevated in obesity alter resolution of acute sterile inflammation by promoting neutrophil survival and decreasing macrophage phagocytosis. Using a targeted mass spectrometry-based lipidomics approach, we found that in db/db mice, PGE2/D2 levels were elevated in inflammatory exudates during the development of acute peritonitis. Moreover, in isolated macrophages, palmitic acid stimulated cyclooxygenase-2 induction and prostanoid production. Defects in macrophage phagocytosis induced by palmitic acid were mimicked by PGE2 and PGD2 and were reversed by cyclooxygenase inhibition or prostanoid receptor antagonism. Macrophages isolated from obese-diabetic mice expressed prostanoid receptors, EP2 and DP1, and contained significantly higher levels of downstream effector, cAMP, compared with wild-type mice. Therapeutic administration of EP2/DP1 dual receptor antagonist, AH6809, decreased neutrophil accumulation in the peritoneum of db/db mice, as well as the accumulation of apoptotic cells in the thymus. Taken together, these studies provide new insights into the mechanisms underlying altered innate immune responses in obesity and suggest that targeting specific prostanoid receptors may represent a novel strategy for resolving inflammation and restoring phagocyte defects in obese and diabetic individuals. PMID:23785121

  18. Biochar enhances Aspergillus niger rock phosphate solubilization by increasing organic acid production and alleviating fluoride toxicity.

    PubMed

    Mendes, Gilberto de Oliveira; Zafra, David Lopez; Vassilev, Nikolay Bojkov; Silva, Ivo Ribeiro; Ribeiro, José Ivo; Costa, Maurício Dutra

    2014-05-01

    During fungal rock phosphate (RP) solubilization, a significant quantity of fluoride (F(-)) is released together with phosphorus (P), strongly inhibiting the process. In the present study, the effect of two F(-) adsorbents [activated alumina (Al2O3) and biochar] on RP solubilization by Aspergillus niger was examined. Al2O3 adsorbed part of the F(-) released but also adsorbed soluble P, which makes it inappropriate for microbial RP solubilization systems. In contrast, biochar adsorbed only F(-) while enhancing phosphate solubilization 3-fold, leading to the accumulation of up to 160 mg of P per liter. By comparing the values of F(-) measured in solution at the end of incubation and those from a predictive model, it was estimated that up to 19 mg of F(-) per liter can be removed from solution by biochar when added at 3 g liter(-1) to the culture medium. Thus, biochar acted as an F(-) sink during RP solubilization and led to an F(-) concentration in solution that was less inhibitory to the process. In the presence of biochar, A. niger produced larger amounts of citric, gluconic, and oxalic acids, whether RP was present or not. Our results show that biochar enhances RP solubilization through two interrelated processes: partial removal of the released F(-) and increased organic acid production. Given the importance of organic acids for P solubilization and that most of the RPs contain high concentrations of F(-), the proposed solubilization system offers an important technological improvement for the microbial production of soluble P fertilizers from RP. PMID:24610849

  19. Biochar Enhances Aspergillus niger Rock Phosphate Solubilization by Increasing Organic Acid Production and Alleviating Fluoride Toxicity

    PubMed Central

    Mendes, Gilberto de Oliveira; Zafra, David Lopez; Vassilev, Nikolay Bojkov; Silva, Ivo Ribeiro; Ribeiro, José Ivo

    2014-01-01

    During fungal rock phosphate (RP) solubilization, a significant quantity of fluoride (F−) is released together with phosphorus (P), strongly inhibiting the process. In the present study, the effect of two F− adsorbents [activated alumina (Al2O3) and biochar] on RP solubilization by Aspergillus niger was examined. Al2O3 adsorbed part of the F− released but also adsorbed soluble P, which makes it inappropriate for microbial RP solubilization systems. In contrast, biochar adsorbed only F− while enhancing phosphate solubilization 3-fold, leading to the accumulation of up to 160 mg of P per liter. By comparing the values of F− measured in solution at the end of incubation and those from a predictive model, it was estimated that up to 19 mg of F− per liter can be removed from solution by biochar when added at 3 g liter−1 to the culture medium. Thus, biochar acted as an F− sink during RP solubilization and led to an F− concentration in solution that was less inhibitory to the process. In the presence of biochar, A. niger produced larger amounts of citric, gluconic, and oxalic acids, whether RP was present or not. Our results show that biochar enhances RP solubilization through two interrelated processes: partial removal of the released F− and increased organic acid production. Given the importance of organic acids for P solubilization and that most of the RPs contain high concentrations of F−, the proposed solubilization system offers an important technological improvement for the microbial production of soluble P fertilizers from RP. PMID:24610849

  20. Factors affecting urinary excretion of testosterone metabolites conjugated with cysteine.

    PubMed

    Fabregat, Andreu; Marcos, Josep; Segura, Jordi; Ventura, Rosa; Pozo, Oscar J

    2016-01-01

    The implementation of the athlete steroidal passport in doping control analysis aims to detect intra-individual changes in the steroid profile related to the abuse of anabolic steroids. In this context, the study of intrinsic variations associated with each marker is of utmost importance. In the present work, the influence of several factors in the excretion of the recently reported testosterone metabolites conjugated with cysteine (Δ(1) -AED; 1,4-androstadien-3,17-dione, Δ(6) -AED; 4,6-androstadien-3,17-dione, Δ(6) -T; 4,6-androstadien-17β-ol-3-one, and Δ(15) -AD; 15-androsten-3,17-dione) is evaluated for the first time. Degradation experiments at 37 °C proved that, although the cysteinyl moiety is released, the variation for urinary Δ(1) -AED/Δ(6) -AED, Δ(1) -AED/Δ(6) -T ratios is less than 30%. Moreover, freeze/thaw cycle testing resulted in RSDs values below 15% for all the analytes. Regarding infradian variability, moderate variations (below 40%) were observed. Additionally, notable alterations in the excretion of these compounds have been observed in the earliest stages of pregnancy. UGT2B17 polymorphism, responsible for the low T/E ratio found in some population, does not influence the excretion of cysteinyl compounds whereas the intake of exogenous substances (alcohol or 5α-reductase inhibitors) dramatically affects their excretion. The urinary concentrations of Δ(1) -AED, Δ(6) -AED, and Δ(15) -AD decreased (<50 %) after the ethanol intake, whereas after the administration of dutasteride, an important increase was observed for the concentrations of Δ(6) -AED, Δ(6) -T and Δ(15) -AD. Overall, the presented data describes the stability of the urinary cysteinyl steroids under the influence of many factors, proving their potential as suitable parameters to be included in the steroidal module of the athlete's biological passport. PMID:25917157

  1. Increase of eicosapentaenoic acid in thraustochytrids through thraustochytrid ubiquitin promoter-driven expression of a fatty acid {delta}5 desaturase gene.

    PubMed

    Kobayashi, Takumi; Sakaguchi, Keishi; Matsuda, Takanori; Abe, Eriko; Hama, Yoichiro; Hayashi, Masahiro; Honda, Daiske; Okita, Yuji; Sugimoto, Shinichi; Okino, Nozomu; Ito, Makoto

    2011-06-01

    Thraustochytrids, marine protists known to accumulate polyunsaturated fatty acids (PUFAs) in lipid droplets, are considered an alternative to fish oils as a source of PUFAs. The major fatty acids produced in thraustochytrids are palmitic acid (C(16:0)), n - 6 docosapentaenoic acid (DPA) (C(22:5)(n) (- 6)), and docosahexaenoic acid (DHA) (C(22:6)(n) (- 3)), with eicosapentaenoic acid (EPA) (C(20:5)(n) (- 3)) and arachidonic acid (AA) (C(20:4)(n) (- 6)) as minor constituents. We attempted here to alter the fatty acid composition of thraustochytrids through the expression of a fatty acid Δ5 desaturase gene driven by the thraustochytrid ubiquitin promoter. The gene was functionally expressed in Aurantiochytrium limacinum mh0186, increasing the amount of EPA converted from eicosatetraenoic acid (ETA) (C(20:4)(n) (- 3)) by the Δ5 desaturase. The levels of EPA and AA were also increased by 4.6- and 13.2-fold in the transgenic thraustochytrids compared to levels in the mock transfectants when ETA and dihomo-γ-linolenic acid (DGLA) (C(20:3)(n) (- 6)) were added to the culture at 0.1 mM. Interestingly, the amount of EPA in the transgenic thraustochytrids increased in proportion to the amount of ETA added to the culture up to 0.4 mM. The rates of conversion and accumulation of EPA were much higher in the thraustochytrids than in baker's yeasts when the desaturase gene was expressed with the respective promoters. This report describes for the first time the finding that an increase of EPA could be accomplished by introducing the Δ5 desaturase gene into thraustochytrids and indicates that molecular breeding of thraustochytrids is a promising strategy for generating beneficial PUFAs. PMID:21478316

  2. Increase of Eicosapentaenoic Acid in Thraustochytrids through Thraustochytrid Ubiquitin Promoter-Driven Expression of a Fatty Acid Δ5 Desaturase Gene▿†

    PubMed Central

    Kobayashi, Takumi; Sakaguchi, Keishi; Matsuda, Takanori; Abe, Eriko; Hama, Yoichiro; Hayashi, Masahiro; Honda, Daiske; Okita, Yuji; Sugimoto, Shinichi; Okino, Nozomu; Ito, Makoto

    2011-01-01

    Thraustochytrids, marine protists known to accumulate polyunsaturated fatty acids (PUFAs) in lipid droplets, are considered an alternative to fish oils as a source of PUFAs. The major fatty acids produced in thraustochytrids are palmitic acid (C16:0), n − 6 docosapentaenoic acid (DPA) (C22:5n − 6), and docosahexaenoic acid (DHA) (C22:6n − 3), with eicosapentaenoic acid (EPA) (C20:5n − 3) and arachidonic acid (AA) (C20:4n − 6) as minor constituents. We attempted here to alter the fatty acid composition of thraustochytrids through the expression of a fatty acid Δ5 desaturase gene driven by the thraustochytrid ubiquitin promoter. The gene was functionally expressed in Aurantiochytrium limacinum mh0186, increasing the amount of EPA converted from eicosatetraenoic acid (ETA) (C20:4n − 3) by the Δ5 desaturase. The levels of EPA and AA were also increased by 4.6- and 13.2-fold in the transgenic thraustochytrids compared to levels in the mock transfectants when ETA and dihomo-γ-linolenic acid (DGLA) (C20:3n − 6) were added to the culture at 0.1 mM. Interestingly, the amount of EPA in the transgenic thraustochytrids increased in proportion to the amount of ETA added to the culture up to 0.4 mM. The rates of conversion and accumulation of EPA were much higher in the thraustochytrids than in baker's yeasts when the desaturase gene was expressed with the respective promoters. This report describes for the first time the finding that an increase of EPA could be accomplished by introducing the Δ5 desaturase gene into thraustochytrids and indicates that molecular breeding of thraustochytrids is a promising strategy for generating beneficial PUFAs. PMID:21478316

  3. Elaidate, an 18-Carbon Trans-monoenoic Fatty Acid, but not Physiological Fatty Acids Increases Intracellular Zn2+ in Human Macrophages

    PubMed Central

    Zacherl, Janelle R.; Tourkova, Irina; St Croix, Claudette M.; Robinson, Lisa J.; Peck Palmer, Octavia M.; Mihalik, Stephanie J.; Blair, Harry C.

    2015-01-01

    Artificial trans fatty acids promote atherosclerosis by blocking macrophage clearance of cell debris. Classical fatty-acid response mechanisms include TLR4-NF-κB activation, and Erk1/2 phosphorylation, but these may not indicate long-term mechanisms. Indeed, nuclear NF-κB was increased by 60 minute treatment by 30 μM of the 18 carbon trans unsaturated fatty acid elaidic acid (elaidate), the physiological cis-unsaturated fatty acid oleic acid (oleate), and the 18 or 16 carbon saturated fatty acids stearic and palmitic acid (stearate or palmitate). However, except for stearate, effects on related pathways were minimal at 44 hours. To determine longer term effects of trans fatty acids, we compared whole exome mRNA expression of (trans) elaidate to (cis) oleate, 30 μM, at 44 hours in human macrophages. We found that elaidate changed Zn2+-homeostasis gene mRNAs markedly. This might be important because Zn2+ is a major regulator of macrophage activity. Messenger RNAs of seven Zn2+-binding metallothioneins decreased 2–4 fold; the zinc importer SLC39A10 increased 2-fold, in elaidate relative to oleate-treated cells. Results were followed by quantitative PCR comparing cis, trans, and saturated fatty acid effects on Zn2+-homeostasis gene mRNAs. This confirmed that elaidate uniquely decreased metallothionein expression and increased SLC39A10 at 44 hours. Further, intracellular Zn2+ was measured using N-(carboxymethyl)-N-[2-[2-[2(carboxymethyl)amino]-5-(2,7,-difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-phenoxy]-ethoxy]-4-methoxyphenyl]glycine, acetoxymethyl ester (FluoZin-3-AM). This showed that, at 44 hours, only cells treated with elaidate had increased Zn2+. The durable effect of elaidate on Zn2+ activation is a novel and specific effect of trans fatty acids on peripheral macrophage metabolism. PMID:25358453

  4. Clinical study of urinary excretion of Ga-67

    SciTech Connect

    Nakano, S.; Hasegawa, Y.; Ibuka, K.; Hashizume, T.; Noguchi, A.; Kojima, J.; Sasakuma, F.; Ishigami, S. )

    1990-04-01

    Ga-67 urinary excretion was examined in 59 patients. The 72-hour urinary excretion rate ranged from 4.3 to 67.8% of the injected dose. Within the first 24 hours, 60.9% of the 72-hour urinary excretion was excreted. There was no significant difference in the Ga-67 urinary excretion rate between males and females, nor between the Ga-67 positive and negative cases. A significant negative correlation was found between the 72-hour Ga-67 urinary excretion rate and the unsaturated iron binding capacity. Notably, four patients with hyperferremia, which was considered secondary to leukemia and/or chemotherapy or liver cirrhosis, excreted more than 46.8% of Ga-67 within 72 hours. A significant negative correlation was also found between the 72-hour Ga-67 urinary excretion rate and age. Urinary excretion of Ga-67 may be related to the glomerular filtration rate, which decreases with age.

  5. Action of steroids on H+ and NH+4 excretion in the toad urinary bladder.

    PubMed

    Frazier, L W; Zachariah, N Y

    1979-09-14

    This study was done to determine if steroid compounds will stimulate the urinary bladder of the toad to increase its capacity to acidify the urine and excrete NH+4. Aldosterone, 17 beta-estradiol, dexamethasone, pregnenolone, and cholesterol were tested on the bladder. All compounds tested were found to stimulate the rate of acidification by the bladder, above that of a paired control hemibladder. In contrast, only the steroids aldosterone and 17 beta-estradiol were found to stimulate NH+4 excretion in the bladder. Cycloheximide was found to block the action of aldosterone on the NH+4 excretion, but did not have a significant effect on the stimulation of acidification by aldosterone. We conclude that steroids stimulate H+ and NH+4 excretion in the toad urinary bladder. In addition, the NH+4 excretory system seems to be more specific to this effect than is the H+ excretory system. PMID:113550

  6. Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes.

    PubMed

    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. PMID:26280739

  7. Placement in an acidic environment increase the solubility of white mineral trioxide aggregate

    PubMed Central

    Yavari, Hamid Reza; Borna, Zahra; Rahimi, Saeed; Shahi, Shahriar; Valizadeh, Hadi; Ghojazadeh, Morteza

    2013-01-01

    Aims: The aim of the present study was to evaluate solubility of white mineral trioxide aggregate (WMTA) in an acidic environment. Materials and Methods: Twenty-four metal rings were prepared, filled with WMTA and randomly divided into two groups. The samples in groups 1 and 2 were set in synthetic tissue fluid with pH values of 7.4 and 4.4, respectively and then were transferred to beakers containing synthetic tissue fluid with pH values of 7.7 and 4.4. Solubility of WMTA samples were calculated at the 9 experimental intervals. Data was analyzed with two-factor ANOVA and Bonferroni test (P < 0.03). Results: The total solubility of WMTA in groups 1 and 2 were −9.1796 ± 1.9158% and −1.1192 ± 2.6236%, (P = 0.028) with weight changes of 9.1574 ± 2.1432% and 7.3276 ± 1.5823%, respectively (P = 0.002). Statistical analysis revealed significant differences between the two groups. Conclusions: It was concluded that solubility of WMTA increases in acidic environments and additional therapeutic precautions should be taken to decrease inflammation in endodontic treatment. PMID:23833462

  8. Select microtubule inhibitors increase lysosome acidity and promote lysosomal disruption in acute myeloid leukemia (AML) cells.

    PubMed

    Bernard, Dannie; Gebbia, Marinella; Prabha, Swayam; Gronda, Marcela; MacLean, Neil; Wang, Xiaoming; Hurren, Rose; Sukhai, Mahadeo A; Cho, Eunice E; Manolson, Morris F; Datti, Alessandro; Wrana, Jeffrey; Minden, Mark D; Al-Awar, Rima; Aman, Ahmed; Nislow, Corey; Giaever, Guri; Schimmer, Aaron D

    2015-07-01

    To identify new biological vulnerabilities in acute myeloid leukemia, we screened a library of natural products for compounds cytotoxic to TEX leukemia cells. This screen identified the novel small molecule Deoxysappanone B 7,4' dimethyl ether (Deox B 7,4), which possessed nanomolar anti-leukemic activity. To determine the anti-leukemic mechanism of action of Deox B 7,4, we conducted a genome-wide screen in Saccharomyces cerevisiae and identified enrichment of genes related to mitotic cell cycle as well as vacuolar acidification, therefore pointing to microtubules and vacuolar (V)-ATPase as potential drug targets. Further investigations into the mechanisms of action of Deox B 7,4 and a related analogue revealed that these compounds were reversible microtubule inhibitors that bound near the colchicine site. In addition, Deox B 7,4 and its analogue increased lysosomal V-ATPase activity and lysosome acidity. The effects on microtubules and lysosomes were functionally important for the anti-leukemic effects of these drugs. The lysosomal effects were characteristic of select microtubule inhibitors as only the Deox compounds and nocodazole, but not colchicine, vinca alkaloids or paclitaxel, altered lysosome acidity and induced lysosomal disruption. Thus, our data highlight a new mechanism of action of select microtubule inhibitors on lysosomal function. PMID:25832785

  9. The Excretion of Renal Cells Following Necrosis of the Distal Segment of the Nephron by Hexadi-Methrine Bromide

    PubMed Central

    Davies, D. J.; Kennedy, A.; Roberts, C.

    1969-01-01

    The rate of excretion of renal cells was determined in rats with necrosis of the distal convoluted tubules and broad ascending limbs of the loops of Henle caused by injection of hexadimethrine bromide. The magnitude and the duration of abnormal cell excretion were correlated both with the dose of hexadimethrine and with the degree of damage that was evident on histological examination of the kidney. In general cell excretion studies provided a satisfactory indication of the degree of renal damage but the smallest lesions did not cause a significant increase in cell excretion and occasionally a rat with a very large lesion failed to show an increase in cell excretion rate. The changes in excretion rates observed in the present experiments were less than those found previously in animals with necrosis of proximal convoluted tubules caused by mercuric chloride. This is probably due firstly to the smaller number of cells in the distal nephron and secondly to the toxin causing disintegration of many of the cells. These findings have implications for the investigation of analgesic nephrotoxicity by measurement of urinary cell excretion rates. In order to appreciate the significance of increases in renal cell excretion following administration of various substances their site of action and the type of cell damage that they cause must first be established. ImagesFigs. 1-4 PMID:5792904

  10. Azetidine-2-carboxylic acid resistant mutants of Arabidopsis thaliana with increased salt tolerance

    SciTech Connect

    Lehle, F.R.; Murphy, M.A.; Khan, R.A. )

    1989-04-01

    Nineteen mutant Arabidopsis families resistant to the proline analog azetidine-2-carboxylic acid (ACA) were characterized in terms of NaCl tolerance and proline content. Mutants were selected from about 64,000 progeny of about 16,000 self-pollinated Columbia parents which had been mutated with ethyl methane sulfonate during seed imbibition. Selections were performed during seed germination on aseptic agar medium containing 0.2 to 0.25 mM ACA. Nineteen mutant families, 12 clearly independent, retained resistance to ACA in the M{sub 4} generation. Based on germination on 150 mM NaCl, 13 of the mutant families were more tolerant than the wild type. Two mutants of intermediate resistance to ACA were markedly more salt tolerant than the others. Four mutant families appeared to overproduce proline. Of these, only 3 showed slight increases in salt tolerance.

  11. Evidence that nitric acid increases relative humidity in low-temperature cirrus clouds.

    PubMed

    Gao, R S; Popp, P J; Fahey, D W; Marcy, T P; Herman, R L; Weinstock, E M; Baumgardner, D G; Garrett, T J; Rosenlof, K H; Thompson, T L; Bui, P T; Ridley, B A; Wofsy, S C; Toon, O B; Tolbert, M A; Kärcher, B; Peter, Th; Hudson, P K; Weinheimer, A J; Heymsfield, A J

    2004-01-23

    In situ measurements of the relative humidity with respect to ice (RHi) and of nitric acid (HNO3) were made in both natural and contrail cirrus clouds in the upper troposphere. At temperatures lower than 202 kelvin, RHi values show a sharp increase to average values of over 130% in both cloud types. These enhanced RHi values are attributed to the presence of a new class of HNO3-containing ice particles (Delta-ice). We propose that surface HNO3 molecules prevent the ice/vapor system from reaching equilibrium by a mechanism similar to that of freezing point depression by antifreeze proteins. Delta-ice represents a new link between global climate and natural and anthropogenic nitrogen oxide emissions. Including Delta-ice in climate models will alter simulated cirrus properties and the distribution of upper tropospheric water vapor. PMID:14739457

  12. Evidence That Nitric Acid Increases Relative Humidity in Low-Temperature Cirrus Clouds

    NASA Technical Reports Server (NTRS)

    Gao, R. S.; Popp, P. J.; Fahey, D. W.; Marcy, T. P.; Herman, R. L.; Weinstock, E. M.; Baumgardner, D. G.; Garrett, T. J.; Rosenlof, K. H.; Thompson, T. L.

    2004-01-01

    In situ measurements of the relative humidity with respect to ice (RH(sub(i)) and of nitric acid (HNO3) were made in both natural and contrail cirrus clouds in the upper troposphere. At temperatures lower than 202 kelvin, RH(sub i) values show a sharp increase to average values of over 130% in both cloud types. These enhanced RH(sub i) values are attributed to the presence of a new class of NHO3- containing ice particles (Delta-ice). We propose that surface HNO3 molecules prevent the ice/vapor system from reaching equilibrium by a mechanism similar to that of freezing point depression by antifreeze proteins. Delta-ice represents a new link between global climate and natural and anthropogenic nitrogen oxide emissions. Including Delta-ice in climate models will alter simulated cirrus properties and the distribution of upper tropospheric water vapor.

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

    SciTech Connect

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

    2009-01-15

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

  14. Coffee polyphenol caffeic acid but not chlorogenic acid increases 5'AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle.

    PubMed

    Tsuda, Satoshi; Egawa, Tatsuro; Ma, Xiao; Oshima, Rieko; Kurogi, Eriko; Hayashi, Tatsuya

    2012-11-01

    Chlorogenic acid is an ester of caffeic and quinic acids, and is one of the most widely consumed polyphenols because it is abundant in foods, especially coffee. We explored whether chlorogenic acid and its metabolite, caffeic acid, act directly on skeletal muscle to stimulate 5'-adenosine monophosphate-activated protein kinase (AMPK). Incubation of rat epitrochlearis muscles with Krebs buffer containing caffeic acid (≥0.1 mM, ≥30 min) but not chlorogenic acid increased the phosphorylation of AMPKα Thr(172), an essential step for kinase activation, and acetyl CoA carboxylase Ser(79), a downstream target of AMPK, in a dose- and time-dependent manner. Analysis of isoform-specific AMPK activity revealed that AMPKα2 activity increased significantly, whereas AMPKα1 activity did not change. This enzyme activation was associated with a reduction in phosphocreatine content and an increased rate of 3-O-methyl-d-glucose transport activity in the absence of insulin. These results suggest that caffeic acid but not chlorogenic acid acutely stimulates skeletal muscle AMPK activity and insulin-independent glucose transport with a reduction of the intracellular energy status. PMID:22227267

  15. Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats.

    PubMed

    Huang, Hui; Morisseau, Christophe; Wang, JingFeng; Yang, Tianxin; Falck, John R; Hammock, Bruce D; Wang, Mong-Heng

    2007-07-01

    Since epoxyeicosatrienoic acids (EETs) affect sodium reabsorption in renal tubules and dilate the renal vasculature, we have examined their effects on renal hemodynamics and sodium balance in male rats fed a high-fat (HF) diet by fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist and an inducer of cytochrome P-450 (CYP) epoxygenases; by N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH), a selective EET biosynthesis inhibitor; and by 12-(3-adamantane-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of soluble epoxide hydrolase. In rats treated with fenofibrate (30 mg.kg(-1).day(-1) ig) or AUDA (50 mg/l in drinking water) for 2 wk, mean arterial pressure, renal vascular resistance, and glomerular filtration rate were lower but renal blood flow was higher than in vehicle-treated control rats. In addition, fenofibrate and AUDA decreased cumulative sodium balance in the HF rats. Treatment with MSPPOH (20 mg.kg(-1).day(-1) iv) + fenofibrate for 2 wk reversed renal hemodynamics and sodium balance to the levels in control HF rats. Moreover, fenofibrate caused a threefold increase in renal cortical CYP epoxygenase activity, whereas the fenofibrate-induced elevation of this activity was attenuated by MSPPOH. Western blot analysis showed that fenofibrate induced the expression of CYP epoxygenases in renal cortex and microvessels and that the induction effect of fenofibrate was blocked by MSPPOH. These results demonstrate that the fenofibrate-induced increase of CYP epoxygenase expression and the AUDA-induced stabilization of EET production in the kidneys cause renal vascular dilation and reduce sodium retention, contributing to the improvement of abnormal renal hemodynamics and hypertension in HF rats. PMID:17442729

  16. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice.

    PubMed

    Strong, Randy; Miller, Richard A; Astle, Clinton M; Floyd, Robert A; Flurkey, Kevin; Hensley, Kenneth L; Javors, Martin A; Leeuwenburgh, Christiaan; Nelson, James F; Ongini, Ennio; Nadon, Nancy L; Warner, Huber R; Harrison, David E

    2008-10-01

    The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex,with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on life span in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses,might prove to postpone death and various age-related outcomes reproducibly in mice. PMID:18631321

  17. Effects of increasing acidity on metal(loid) bioprecipitation in groundwater: column studies

    SciTech Connect

    Alexander C. Davis; Bradley M. Patterson; Michelle E. Grassi; Blair S. Robertson; Henning Prommer; Allan J. McKinley

    2007-10-15

    Large-scale column experiments were carried out over a period of 545 days to assess the effect of increasing acidity on bacterial denitrification, sulfate reduction, and metal(loid) bioprecipitation in groundwater affected by acid mine drainage. At a groundwater pH of 5.5, denitrification and Cu{sup 2+} removal, probably via malachite (Cu{sub 2}(OH){sub 2}CO{sub 3}) precipitation, were observed in the ethanol-amended column. Sulfate reduction, sulfide production, and Zn{sup 2+} removal were also observed, with Zn{sup 2+} removal observed in the zone of sulfate reduction, indicating likely precipitation as sphalerite (ZnS). Se{sup 6+} removal was also observed in the sulfate reducing zone, probably as direct bioreduction to elemental selenium via ethanol/acetate oxidation or sulfide oxidation precipitating elemental sulfur. A step decrease in groundwater pH from 5.5 to 4.25 resulted in increased denitrification and sulfate reduction half-lives, migration of both these redox zones along the ethanol-amended column, and the formation of an elevated Cu{sup 2+} plume. Additionally, an elevated Zn{sup 2+} plume formed in the previous sulfate reducing zone of the ethanol-amended column, suggesting dissolution of precipitated sphalerite as a result of the reduction in groundwater pH. As Cu{sup 2+} passed through the zone of sphalerite dissolution, SEM imaging and EDS detection suggested that Cu{sup 2+} removal had occurred via chalcocite (Cu{sub 2}S) or covellite (CuS) precipitation. 23 refs., 8 figs.

  18. Mice Deficient in Transmembrane Prostatic Acid Phosphatase Display Increased GABAergic Transmission and Neurological Alterations

    PubMed Central

    Myöhänen, Timo T.; Voikar, Vootele; Mijatovic, Jelena; Segerstråle, Mikael; Herrala, Annakaisa M.; Kulesskaya, Natalia; Pulkka, Anitta E.; Kivinummi, Tanja; Abo-Ramadan, Usama; Taira, Tomi; Piepponen, T. Petteri; Rauvala, Heikki; Vihko, Pirkko

    2014-01-01

    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. PMID:24846136

  19. Suberoylanilide hydroxamic acid (SAHA) at subtoxic concentrations increases the adhesivity of human leukemic cells to fibronectin.

    PubMed

    Kuzelová, Katerina; Pluskalová, Michaela; Brodská, Barbora; Otevrelová, Petra; Elknerová, Klára; Grebenová, Dana; Hrkal, Zbynek

    2010-01-01

    Suberoylanilide hydroxamic acid (SAHA) is an inhibitor of histone deacetylases (HDACs) which is being introduced into clinic for the treatment of hematological diseases. We studied the effect of this compound on six human hematopoietic cell lines (JURL-MK1, K562, CML-T1, Karpas-299, HL-60, and ML-2) as well as on normal human lymphocytes and on leukemic primary cells. SAHA induced dose-dependent and cell type-dependent cell death which displayed apoptotic features (caspase-3 activation and apoptotic DNA fragmentation) in most cell types including the normal lymphocytes. At subtoxic concentrations (0.5-1 microM), SAHA increased the cell adhesivity to fibronectin (FN) in all leukemia/lymphoma-derived cell lines but not in normal lymphocytes. This increase was accompanied by an enhanced expression of integrin beta1 and paxillin, an essential constituent of focal adhesion complexes, both at the protein and mRNA level. On the other hand, the inhibition of ROCK protein, an important regulator of cytoskeleton structure, had no consistent effect on SAHA-induced increase in the cell adhesivity. The promotion of cell adhesivity to FN seems to be specific for SAHA as we observed no such effects with other HDAC inhibitors (trichostatin A and sodium butyrate). PMID:19911379

  20. Behavioral and Perceived Stressor Effects on Urinary Catecholamine Excretion in Adult Samoans

    PubMed Central

    Bergey, Meredith R.; Steele, Matthew S.; Bereiter, David A.; Viali, Satupaitea; McGarvey, Stephen T.

    2011-01-01

    Objectives The effects of perceptions and behaviors related to culturally-patterned socioeconomic obligations on catecholamine excretion rates were studied in a cross-sectional sample of Samoan adults. Methods 378 participants, ages 29-62 years, from 9 villages throughout Samoa, provided timed overnight urine specimens, and self-reported perceptions and behaviors associated with contributions to one's family, aiga, and chief, matai, and communal gift exchanges, fa'alavelave. Urinary norepinephrine and epinephrine excretion rates were measured by high performance liquid chromatography with electrochemical detection. Age (≤40 vs. >40 years) and gender-specific regression models were estimated to detect associations with catecholamine excretion. Results Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who view their contribution to their matai to be ‘just right’, had significantly higher residence-adjusted norepinephrine excretion. Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who consider their contribution to their aiga not to be a burden, had higher epinephrine excretion. Older men who contribute more to their aiga and who perceive their contribution to their aiga to be ‘just right’ had increased residence-adjusted epinephrine excretion. Conclusions Individual-level perceptions and behaviors related to traditional socioeconomic obligations are a significant correlate of increased overnight catecholamine excretion rates. Higher excretion rates may be attributed to psychosocial stress arousal associated with a discordance between personal desires for upward social mobility, and family and community-based socioeconomic obligations. Changes in patterns of individual-level psychosocial stress arousal may contribute to cardiovascular disease risk in modernizing Samoans. PMID:21793091

  1. Treatment with Potassium Bicarbonate Lowers Calcium Excretion and Bone Resorption in Older Men and Women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bicarbonate has been implicated in bone health in older subjects on acid-producing diets in short-term studies. The objective of this study was to determine the effects of potassium bicarbonate and its components on changes in bone resorption and calcium excretion over 3 months in older men and wom...

  2. Plasma Circulating Nucleic Acids Levels Increase According to the Morbidity of Plasmodium vivax Malaria

    PubMed Central

    Franklin, Bernardo S.; Vitorino, Barbara L. F.; Coelho, Helena C.; Menezes-Neto, Armando; Santos, Marina L. S.; Campos, Fernanda M. F.; Brito, Cristiana F.; Fontes, Cor J.; Lacerda, Marcus V.; Carvalho, Luzia H.

    2011-01-01

    Background Given the increasing evidence of Plasmodium vivax infections associated with severe and fatal disease, the identification of sensitive and reliable markers for vivax severity is crucial to improve patient care. Circulating nucleic acids (CNAs) have been increasingly recognized as powerful diagnostic and prognostic tools for various inflammatory diseases and tumors as their plasma concentrations increase according to malignancy. Given the marked inflammatory status of P. vivax infection, we investigated here the usefulness of CNAs as biomarkers for malaria morbidity. Methods and Findings CNAs levels in plasma from twenty-one acute P. vivax malaria patients from the Brazilian Amazon and 14 malaria non-exposed healthy donors were quantified by two different methodologies: amplification of the human telomerase reverse transcriptase (hTERT) genomic sequence by quantitative real time PCR (qPCR), and the fluorometric dsDNA quantification by Pico Green. CNAs levels were significantly increased in plasma from P. vivax patients as compared to healthy donors (p<0.0001). Importantly, plasma CNAs levels were strongly associated with vivax morbidity (p<0.0001), including a drop in platelet counts (p = 0.0021). These findings were further sustained when we assessed CNAS levels in plasma samples from 14 additional P. vivax patients of a different endemic area in Brazil, in which CNAS levels strongly correlated with thrombocytopenia (p = 0.0072). We further show that plasma CNAs levels decrease and reach physiological levels after antimalarial treatment. Although we found both host and parasite specific genomic sequences circulating in plasma, only host CNAs clearly reflected the clinical spectrum of P. vivax malaria. Conclusions Here, we provide the first evidence of increased plasma CNAs levels in malaria patients and reveal their potential as sensitive biomarkers for vivax malaria morbidity. PMID:21611202

  3. Retinoic Acid-Treated Pluripotent Stem Cells Undergoing Neurogenesis Present Increased Aneuploidy and Micronuclei Formation

    PubMed Central

    Sartore, Rafaela C.; Campos, Priscila B.; Trujillo, Cleber A.; Ramalho, Bia L.; Negraes, Priscilla D.; Paulsen, Bruna S.; Meletti, Tamara; Costa, Elaine S.; Chicaybam, Leonardo; Bonamino, Martin H.; Ulrich, Henning; Rehen, Stevens K.

    2011-01-01

    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 variation accompanies

  4. [Acceleration of the excretion of monomeric 239Pu-citrate from the body as effected by pentacyne encapsulated in liposomes].

    PubMed

    Il'in, L A; Smirnov, A A; Ivannikov, A T; Parfenova, I M

    1983-01-01

    Liposomes, obtained by a modified procedure involving reverse phases, contained 2-3-times more 14C-pentacyne than the multilayer Banchem;s liposomes. Efficiency of pentacyne encapsulated in liposomes was higher, as compared with a non-encapsulated preparation in studies of urinary excretion of monomeric 239Pu-citrate in rats. Liposomal pentacyne increased most effectively the rate of the radionuclide excretion from liver tissue and skeleton as compared with the action of non-encapsulated complex-forming agent; as a result of which the radionuclide was excreted from liver tissue at a 1.6-2-times and from skeleton--with the 1.4-times higher rates. The both preparations increased the 239Pu excretion with urine and feces. The liposomal pentacyne accelerated an additional excretion of the nuclide with urine. PMID:6353751

  5. Increased fatty acid unsaturation and production of arachidonic acid by homologous over-expression of the mitochondrial malic enzyme in Mortierella alpina

    PubMed Central

    Hao, Guangfei; Du, Kai; Huang, Xiaoyun; Song, Yuanda; Gu, Zhennan; Wang, Lei; Zhang, Hao; Chen, Wei; Chen, Yong Q.

    2015-01-01

    Malic enzyme (ME) catalyses the oxidative decarboxylation of L-malate to pyruvate and provides NADPH for intracellular metabolism, such as fatty acid synthesis. Here, the mitochondrial ME (mME) gene from Mortierella alpina was homologously over-expressed. Compared with controls, fungal arachidonic acid (ARA; 20:4 n-6) content increased by 60 % without affecting the total fatty acid content. Our results suggest that enhancing mME activity may be an effective mean to increase industrial production of ARA in M. alpina. PMID:24863290

  6. Feed ingredients differing in fermentable fibre and indigestible protein content affect fermentation metabolites and faecal nitrogen excretion in growing pigs.

    PubMed

    Jha, R; Leterme, P

    2012-04-01

    To study the fermentation characteristics of different non-conventional dietary fibre (DF) sources with varying levels of indigestible CP content and their effects on the production of fermentation metabolites and on faecal nitrogen (N) excretion, an experiment was conducted with 40 growing pigs (initial BW 23 kg) using wheat bran (WB), pea hulls (PH), pea inner fibres (PIF), sugar beet pulp (SBP) or corn distillers dried grains with solubles (DDGS). The diets also contained soya protein isolate, pea starch and sucrose, and were supplemented with vitamin-mineral premix. Faecal samples were collected for 3 consecutive days from day 10, fed with added indigestible marker (chromic oxide) for 3 days from day 13 and pigs were slaughtered on day 16 from the beginning of the experiment. Digesta from the ileum and colon were collected and analysed for short-chain fatty acids (SCFA) and ammonia (NH3) content. The apparent total tract N digestibility was the lowest (P < 0.001) in diets based on DDGS (74%), medium in diets with WB and SBP (76% each) and highest in those with PIF and PH (79% and 81%, respectively). Expressed per kg fermented non-starch polysaccharides (NSP), faecal N excretion was higher with DDGS and WB diets (130 and 113 g/kg NSP fermented, respectively) and lower with PIF, PH and SBP diets (42, 52 and 55 g/kg NSP fermented, respectively). The PH-based diets had the highest (P < 0.05) SCFA concentrations, both in the ileum and the colon (27 and 122 mMol/kg digesta, respectively). The highest NH3 concentration was also found in the colon of pigs fed with PH (132 mMol/kg digesta). Loading plot of principle component analysis revealed that the CP : NSP ratio was positively related with faecal N excretion and NH3 concentration in colon contents, whereas negatively related with SCFA concentration in colon contents. In conclusion, pea fibres and SBP increased SCFA and reduced NH3 concentration in the pig's intestine and reduced faecal N excretion, which makes pea

  7. A thraustochytrid diacylglycerol acyltransferase 2 with broad substrate specificity strongly increases oleic acid content in engineered Arabidopsis thaliana seeds

    PubMed Central

    Zhang, Chunyu; Iskandarov, Umidjon; Cahoon, Edgar B.

    2013-01-01

    Diacylglycerol acyltransferase (DGAT) catalyses the last step in acyl-CoA-dependent triacylglycerol (TAG) biosynthesis and is an important determinant of cellular oil content and quality. In this study, a gene, designated TaDGAT2, encoding a type 2 DGAT (DGAT2)-related enzyme was identified from the oleaginous marine protist Thraustochytrium aureum. The deduced TaDGAT2 sequence contains a ~460 amino acid domain most closely related to DGAT2s from Dictyostelium sp. (45–50% identity). Recombinant TaDGAT2 restored TAG biosynthesis to the Saccharomyces cerevisiae H1246 TAG-deficient mutant, and microsomes from the complemented mutant displayed DGAT activity with C16 and C18 saturated and unsaturated fatty acyl-CoA and diacylglycerol substrates. To examine its biotechnological potential, TaDGAT2 was expressed under control of a strong seed-specific promoter in wild-type Arabidopsis thaliana and the high linoleic acid fad3fae1 mutant. In both backgrounds, little change was detected in seed oil content, but a striking increase in oleic acid content of seeds was observed. This increase was greatest in fad3fae1 seeds, where relative amounts of oleic acid increased nearly 2-fold to >50% of total fatty acids. In addition, >2-fold increase in oleic acid levels was detected in the triacylglycerol sn-2 position and in the major seed phospholipid phosphatidylcholine. These results suggest that increased seed oleic acid content mediated by TaDGAT2 is influenced in part by the fatty acid composition of host cells and occurs not by enhancing oleic acid content at the TAG sn-3 position directly but by increasing total oleic acid levels in seeds, presumably by limiting flux through phosphatidylcholine-based desaturation reactions. PMID:23814277

  8. Awareness of folic acid use increases its consumption, and reduces the risk of spina bifida.

    PubMed

    Kondo, Atsuo; Morota, Nobuhito; Date, Hiroaki; Yoshifuji, Kazuhisa; Morishima, Toshibumi; Miyazato, Minoru; Shirane, Reizo; Sakai, Hideki; Pooh, Kyong Hon; Watanabe, Tomoyuki

    2015-07-14

    The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 μg/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case-control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0.48 in the first period, and 0.53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan. PMID:25999131

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

    PubMed

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

    2007-01-01

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

  10. Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans.

    PubMed

    Steck, Susan E; Chalecki, Allison M; Miller, Paul; Conway, Jason; Austin, Gregory L; Hardin, James W; Albright, Craig D; Thuillier, Philippe

    2007-05-01

    Conjugated linoleic acid (CLA) alters body composition in animal models, but few studies have examined the effects of CLA supplementation on body composition and clinical safety measures in obese humans. In the present study, we performed a randomized, double-blind, placebo-controlled trial to examine the changes in body composition and clinical laboratory values following CLA (50:50 ratio of cis-9, trans-11 and trans-10, cis-12 isomers) supplementation for 12 wk in otherwise healthy obese humans. Forty-eight participants (13 males and 35 females) were randomized to receive placebo (8 g safflower oil/d), 3.2 g/d CLA, or 6.4 g/d CLA for 12 wk. Changes in body fat mass and lean body mass were determined by dual-energy X-ray absorptiometry. Resting energy expenditure was assessed by indirect calorimetry. Clinical laboratory values and adverse-event reporting were used to monitor safety. Lean body mass increased by 0.64 kg in the 6.4 g/d CLA group (P < 0.05) after 12 wk of intervention. Significant decreases in serum HDL-cholesterol and sodium, hemoglobin, and hematocrit, and significant increases in serum alkaline phosphatase, C-reactive protein, and IL-6, and white blood cells occurred in the 6.4 g/d CLA group, although all values remained within normal limits. The intervention was well tolerated and no severe adverse events were reported, although mild gastrointestinal adverse events were reported in all treatment groups. In conclusion, whereas CLA may increase lean body mass in obese humans, it may also increase markers of inflammation in the short term. PMID:17449580

  11. Method for construction of bacterial strains with increased succinic acid production

    DOEpatents

    Donnelly, Mark I.; Sanville-Millard, Cynthia; Chatterjee, Ranjini

    2000-01-01

    A fermentation process for producing succinic acid is provided comprising selecting a bacterial strain that does not produce succinic acid in high yield, disrupting the normal regulation of sugar metabolism of said bacterial strain, and combining the mutant bacterial strain and selected sugar in anaerobic conditions to facilitate production of succinic acid. Also provided is a method for changing low yield succinic acid producing bacteria to high yield succinic acid producing bacteria comprising selecting a bacterial strain having a phosphotransferase system and altering the phosphotransferase system so as to allow the bacterial strain to simultaneously metabolize different sugars.

  12. Dietary Conjugated Linoleic Acid (CLA) increases milk yield without losing body weight in lactating sows.

    PubMed

    Lee, Sung-Hoon; Joo, Young-Kuk; Lee, Jin-Woo; Ha, Young-Joo; Yeo, Joon-Mo; Kim, Wan-Young

    2014-01-01

    This study was conducted to evaluate the effects of dietary conjugated linoleic acid (CLA) on the performance of lactating sows and piglets as well as the immunity of piglets suckling from sows fed CLA. Eighteen multiparous Duroc sows with an average body weight (BW) of 232.0 ± 6.38 kg were randomly selected and assigned to two dietary treatments (n = 9 for each treatment), control (no CLA addition) and 1% CLA supplementation. For the control diet, CLA was replaced with soybean oil. Experimental diets were fed to sows during a 28-day lactation period. Litter size for each sow was standardized to nine piglets by cross-fostering within 24 hours after birth. Sow milk and blood samples were taken from sows and piglets after 21 and 27 days of lactation, respectively. Loss of BW was significantly (p < 0.05) higher in sows fed control diet compared to sows fed CLA diet. Piglet weights at weaning and weight gain during suckling were significantly (p < 0.05) higher in sows fed CLA compared to sows fed control diet. Serum non-esterified fatty acid (NEFA) and urea nitrogen concentrations were significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil. IgG concentrations of the groups supplemented with CLA increased by 49% in sow serum (p < 0.0001), 23% in milk (p < 0.05), and 35% in piglet serum (p < 0.05) compared with the control group. Sows fed CLA showed an increase of 10% in milk yield compared with sows fed soybean oil (p < 0.05), even though there was no difference in daily feed intake between the treatments. Milk fat content was significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil. Solid-not-fat yield was significantly (p < 0.05) higher in sows supplemented with CLA than in sows fed control diet and also protein-to-fat ratio in milk was significantly (p < 0.05) higher in sows fed CLA compared with the control group. The results show that CLA supplementation to sows increased milk yield without losing BW during

  13. Activation of glucosidase via stress-induced polymerization rapidly increases active pools of abscisic acid.

    PubMed

    Lee, Kwang Hee; Piao, Hai Lan; Kim, Ho-Youn; Choi, Sang Mi; Jiang, Fan; Hartung, Wolfram; Hwang, Ildoo; Kwak, June M; Lee, In-Jung; Hwang, Inhwan

    2006-09-22

    Abscisic acid (ABA) is a phytohormone critical for plant growth, development, and adaptation to various stress conditions. Plants have to adjust ABA levels constantly to respond to changing physiological and environmental conditions. To date, the mechanisms for fine-tuning ABA levels remain elusive. Here we report that AtBG1, a beta-glucosidase, hydrolyzes glucose-conjugated, biologically inactive ABA to produce active ABA. Loss of AtBG1 causes defective stomatal movement, early germination, abiotic stress-sensitive phenotypes, and lower ABA levels, whereas plants with ectopic AtBG1 accumulate higher ABA levels and display enhanced tolerance to abiotic stress. Dehydration rapidly induces polymerization of AtBG1, resulting in a 4-fold increase in enzymatic activity. Furthermore, diurnal increases in ABA levels are attributable to polymerization-mediated AtBG1 activation. We propose that the activation of inactive ABA pools by polymerized AtBG1 is a mechanism by which plants rapidly adjust ABA levels and respond to changing environmental cues. PMID:16990135

  14. Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid

    PubMed Central

    Iyengar, Sloka S.; LaFrancois, John J.; Friedman, Daniel; Drew, Liam J.; Denny, Christine A.; Burghardt, Nesha S.; Wu, Melody V.; Hsieh, Jenny; Hen, René; Scharfman, Helen E.

    2016-01-01

    Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice with reduced adult neurogenesis, produced either by focal X-irradiation of the DG, or by pharmacogenetic deletion of dividing radial glial precursors. In the first 4 hrs after KA administration, when mice have the most robust seizures, mice with reduced adult neurogenesis had more severe convulsive seizures, exhibited either as a decreased latency to the first convulsive seizure, greater number of convulsive seizures, or longer convulsive seizures. Nonconvulsive seizures did not appear to change or they decreased. Four-21 hrs after KA injection, mice with reduced adult neurogenesis showed more interictal spikes (IIS) and delayed seizures than controls. Effects were greater when the anticonvulsant ethosuximide was injected 30 min prior to KA administration; ethosuximide allows forebrain seizure activity to be more easily examined in mice by suppressing seizures dominated by the brainstem. These data support the hypothesis that reduction of adult-born neurons increases the susceptibility of the brain to effects of KA. PMID:25476494

  15. A geographic cline in leaf salicylic acid with increasing elevation in Arabidopsis thaliana.

    PubMed

    Zhang, Nana; Tonsor, Stephen J; Traw, M Brian

    2015-01-01

    Salicylic acid (SA) occupies a key role as a hormone central to both plant resistance to bacterial pathogens and tolerance of abiotic stresses. Plants at high elevation experience colder temperatures and elevated UV levels. While it has been predicted that SA concentrations will be higher in plants from high elevation populations, few studies have addressed this question. Here, we asked how concentrations of SA vary in natural populations of Arabidopsis thaliana collected across an elevational gradient on the Iberian Peninsula. In a series of common garden experiments, we found that constitutive SA concentrations were highest in genotypes from the low elevation populations. This result was in the opposite direction from our prediction and is an exception to the general finding that phenolic compounds increase with increasing elevation. These data suggest that high constitutive SA is not associated with resistance to cold temperatures in these plants. Furthermore, we also found that leaf constitutive camalexin concentrations, an important defense against some bacterial and fungal enemies, were highest in the low elevation populations, suggesting that pathogen pressures may be important. Further examination of this elevational cline will likely provide additional insights into the interplay between phenolic compounds and biotic and abiotic stress. PMID:25875692

  16. A geographic cline in leaf salicylic acid with increasing elevation in Arabidopsis thaliana

    PubMed Central

    Zhang, Nana; Tonsor, Stephen J; Traw, M Brian

    2015-01-01

    Salicylic acid (SA) occupies a key role as a hormone central to both plant resistance to bacterial pathogens and tolerance of abiotic stresses. Plants at high elevation experience colder temperatures and elevated UV levels. While it has been predicted that SA concentrations will be higher in plants from high elevation populations, few studies have addressed this question. Here, we asked how concentrations of SA vary in natural populations of Arabidopsis thaliana collected across an elevational gradient on the Iberian Peninsula. In a series of common garden experiments, we found that constitutive SA concentrations were highest in genotypes from the low elevation populations. This result was in the opposite direction from our prediction and is an exception to the general finding that phenolic compounds increase with increasing elevation. These data suggest that high constitutive SA is not associated with resistance to cold temperatures in these plants. Furthermore, we also found that leaf constitutive camalexin concentrations, an important defense against some bacterial and fungal enemies, were highest in the low elevation populations, suggesting that pathogen pressures may be important. Further examination of this elevational cline will likely provide additional insights into the interplay between phenolic compounds and biotic and abiotic stress. PMID:25875692

  17. The diurnal variation in urine acidification differs between normal individuals and uric acid stone formers

    PubMed Central

    Cameron, Mary Ann; Maalouf, Naim M.; Poindexter, John; Adams-Huet, Beverley; Sakhaee, Khashayar; Moe, Orson W.

    2012-01-01

    Many biologic functions follow circadian rhythms driven by internal and external cues that synchronize and coordinate organ physiology to diurnal changes in the environment and behavior. Urinary acid-base parameters follow diurnal patterns and it is thought these changes are due to periodic surges in gastric acid secretion. Abnormal urine pH is a risk factor for specific types of nephrolithiasis and uric acid stones are typical of excessively low urine pH. Here we placed 9 healthy volunteers and 10 uric acid stone formers on fixed metabolic diets to study the diurnal pattern of urinary acidification. All showed clear diurnal trends in urinary acidification but none of the patterns were affected by inhibitors of the gastric proton pump. Uric acid stone formers had similar patterns of change through the day but their urine pH was always lower compared to healthy volunteers. Uric acid stone formers excreted more acid (normalized to acid ingestion) with the excess excreted primarily as titratable acid rather than ammonium. Urine base excretion was also lower in uric acid stone formers (normalized to base ingestion) along with lower plasma bicarbonate concentrations during part of the day. Thus, increased net acid presentation to the kidney and the preferential use of buffers, other than ammonium, result in much higher concentrations of un-dissociated uric acid throughout the day and consequently an increased risk of uric acid stones. PMID:22297671

  18. Ligand-directed stearic acid grafted chitosan micelles to increase therapeutic efficacy in hepatic cancer.

    PubMed

    Yang, Yuan; Yuan, Sheng-Xian; Zhao, Ling-Hao; Wang, Chao; Ni, Jun-Sheng; Wang, Zhen-Guang; Lin, Chuan; Wu, Meng-Chao; Zhou, Wei-Ping

    2015-02-01

    Targeted delivery system would be an interesting platform to enhance the therapeutic effect and to reduce the side effects of anticancer drugs. In this study, we have developed lactobionic acid (LA)-modified chitosan-stearic acid (CS-SA) (CSS-LA) to deliver doxorubicin (DOX) to hepatic cancer cells. The average particle size of CSS-LA/DOX was ∼100 nm with a high entrapment efficiency of >95%. Drug release studies showed that DOX release from pH-sensitive micelles is significantly faster at pH 5.0 than at pH 7.4. The LA conjugated micelles showed enhanced cellular uptake in HepG2 and BEL-7402 liver cancer cells than free drug and unconjugated micelles. Consistently, CSS-LA/DOX showed enhanced cell cytotoxicity in these two cell lines. Annexin-V/FITC and PI based apoptosis assay showed that the number of living cells greatly reduced in this group with marked presence of necrotic and apoptotic cells. LA-conjugated carrier induced typical chromatic condensation of cells; membrane blebbing and apoptotic bodies began to appear. In vivo, CSS-LA/DOX showed an excellent tumor regression profile with no toxic side effects. The active targeting moiety, long circulation profile, and EPR effect contributed to its superior anticancer effect in HepG2 based tumor. Our results showed that polymeric micelles conjugated with LA increased the therapeutic availability of DOX in the liver cancer cell based solid tumor without any toxic side effects. The active targeting ligand conjugated nanoparticulate system could be a promising therapeutic strategy in the treatment of hepatic cancers. PMID:25495890

  19. Urine bile acids relate to glucose control in patients with type 2 diabetes mellitus and a body mass index below 30 kg/m2.

    PubMed

    Taylor, David R; Alaghband-Zadeh, Jamshid; Cross, Gemma F; Omar, Sohail; le Roux, Carel W; Vincent, Royce P

    2014-01-01

    Bile acids are important endocrine signalling molecules, modulating glucose homeostasis through activation of cell surface and nuclear receptors. Bile acid metabolism is altered in type 2 diabetes mellitus; however, whether this is of pathogenic consequence is not fully established. In this study urinary bile acid excretion in individuals with type 2 diabetes and matched healthy volunteers was assessed. Urinary bile acid excretion in type 2 diabetes patients was considered in the context of prevailing glycaemia and the patient body mass index. Urine bile acids were measured by liquid chromatography-tandem mass spectrometry, allowing individual quantification of 15 bile acid species. Urinary bile acid excretion in patients with type 2 diabetes who were normal weight (BMI 18.5-24.9 kg/m2) and overweight (BMI 25-29.9 kg/m2) were elevated compared to healthy normal weight volunteers, both p<0.0001. In obese (BMI ≥ 30 kg/m2) type 2 diabetes patients, urinary bile acid excretion was significantly lower than in the normal and overweight type 2 diabetes groups (both p<0.01). Total bile acid excretion positively correlated with HbA1c in normal (rs=0.85, p=<0.001) and overweight (rs=0.61, p=0.02) but not obese type 2 diabetes patients (rs=-0.08, p=0.73). The glycaemia-associated increases in urine bile acid excretion in normal weight and overweight type 2 diabetes seen in this study may represent compensatory increases in bile acid signalling to maintain glucose homeostasis. As such alterations appear blunted by obesity; further investigation of weight-dependent effects of bile acid signalling on type 2 diabetes pathogenesis is warranted. PMID:24736330

  20. Urine Bile Acids Relate to Glucose Control in Patients with Type 2 Diabetes Mellitus and a Body Mass Index Below 30 kg/m2

    PubMed Central

    Taylor, David R.; Alaghband-Zadeh, Jamshid; Cross, Gemma F.; Omar, Sohail; le Roux, Carel W.; Vincent, Royce P.

    2014-01-01

    Bile acids are important endocrine signalling molecules, modulating glucose homeostasis through activation of cell surface and nuclear receptors. Bile acid metabolism is altered in type 2 diabetes mellitus; however, whether this is of pathogenic consequence is not fully established. In this study urinary bile acid excretion in individuals with type 2 diabetes and matched healthy volunteers was assessed. Urinary bile acid excretion in type 2 diabetes patients was considered in the context of prevailing glycaemia and the patient body mass index. Urine bile acids were measured by liquid chromatography-tandem mass spectrometry, allowing individual quantification of 15 bile acid species. Urinary bile acid excretion in patients with type 2 diabetes who were normal weight (BMI 18.5–24.9 kg/m2) and overweight (BMI 25–29.9 kg/m2) were elevated compared to healthy normal weight volunteers, both p<0.0001. In obese (BMI≥30 kg/m2) type 2 diabetes patients, urinary bile acid excretion was significantly lower than in the normal and overweight type 2 diabetes groups (both p<0.01). Total bile acid excretion positively correlated with HbA1c in normal (rs = 0.85, p = <0.001) and overweight (rs = 0.61, p = 0.02) but not obese type 2 diabetes patients (rs = −0.08, p = 0.73). The glycaemia-associated increases in urine bile acid excretion in normal weight and overweight type 2 diabetes seen in this study may represent compensatory increases in bile acid signalling to maintain glucose homeostasis. As such alterations appear blunted by obesity; further investigation of weight-dependent effects of bile acid signalling on type 2 diabetes pathogenesis is warranted. PMID:24736330

  1. Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

    SciTech Connect

    Johansson, E.; Gillespie, H.K.; Halldin, M.M. )

    1990-05-01

    The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.

  2. Leaching with Penicillium simplicissimum: Influence of Metals and Buffers on Proton Extrusion and Citric Acid Production

    PubMed Central

    Franz, Andreas; Burgstaller, Wolfgang; Schinner, Franz

    1991-01-01

    In the presence of insoluble metal oxides (industrial filter dust, zinc oxide, synthetic mixture of metal oxides), Penicillium simplicissimum developed the ability to excrete considerable amounts of citric acid (>100 mM). Parallel with the increase of citric acid concentration in the culture broth, zinc was solubilized from zinc oxide. The adsorption of filter dust onto the mycelium (the pellets formed were less than 1 mm in diameter) was required for not only the citric acid excretion but also the leaching of zinc. When the filter dust was replaced with a synthetic mixture of metal oxides or with zinc oxide in combination with trace elements, levels of adsorption and citric acid production were observed to be similar to those in experiments where industrial filter dust was used. The two most important properties of the filter dust were its heavy-metal content and its buffering capacity. These properties were simulated by adding heavy metals in soluble form (as chlorides, sulfates, or nitrates) or soluble buffers to the medium. Both heavy metals and buffers were not able to induce a citric acid efflux. As with citric acid production by Aspergillus niger, the addition of manganese lowered citric acid excretion (by 40% with metal oxide-induced citric acid efflux and by 100% with urea-induced citric acid efflux). Copper antagonized the effect of manganese. The mechanism for the bulk of citric acid excretion by P. simplicissimum, however, seemed to be different from that described for citric acid accumulation by A. niger. Because of the inefficiency of metals in solubilized form and of soluble buffers to induce a strong citric acid efflux, adsorption of an insoluble metal compound (zinc oxide) turned out to be essential. Surface phenomena possibly involving the plasma membrane H+-ATPase are thought to participate in the induction of citric acid excretion by P. simplicissimum in the presence of industrial filter dust. PMID:16348442

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

    EPA Science Inventory

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

  4. Methotrexate catabolism to 7-hydroxy methotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplements

    PubMed Central

    Baggott, Joseph E.; Morgan, Sarah L.

    2013-01-01

    Objective Urinary excretion of methotrexate (MTX) and its catabolite 7-hydroxy-MTX (7-OH-MTX) were measured in two 24-hour collections after MTX therapy in patients with rheumatoid arthritis. The effect of folic and folinic acid supplements on this catabolism was determined in patients and in vitro. The effect of this catabolism on MTX efficacy and in vivo retention was determined. Methods Urines were collected after 6 and 7 weeks of therapy. MTX and 7-OH-MTX concentrations were determined by a high performance liquid chromatography mass spectroscopy. Swelling (SW) and pain/tenderness (P/T) indices were measured before and at 6 and 7 weeks of therapy. Patients received either folic or folinic acid supplements (1mg/day) from week 6 to 7. Results Folic acid not folinic acid inhibited aldehyde oxidase (AO), the 7-OH-MTX producing enzyme. Excretion of 7-OH-MTX as % of dose or mg 7-OH-MTX / g creatinine was not normally distributed (n = 39). Patients with marked improvement in SW and P/T indices had lower mean 7-OH-MTX excretion (p <0.05). Folic acid supplementation lowered 7-OH-MTX excretion (p = 0.03). Relatively high 7-OH-MTX excretion was correlated (p<0.05) with relatively high MTX excretion and with relatively low in vivo MTX retention (n = 35). Conclusion Non-normal distribution of 7-OH-MTX excretion suggests at least two phenotypes for this catabolism. Lower 7-OH-MTX formation suggests folic acid inhibition of AO and a better clinical response. Higher 7-OH-MTX formation may interfere with MTX polyglutamylation and binding to enzymes and therefore increase MTX excretion, decrease in vivo MTX retention and efficacy. PMID:19644884

  5. Lead-acid battery with improved cycle life and increased efficiency for lead leveling application and electric road vehicles

    NASA Astrophysics Data System (ADS)

    Winsel, A.; Schulz, J.; Guetlich, K. F.

    1983-11-01

    Lifetime and efficiency of lead acid batteries are discussed. A gas lift pump was used to prevent acid stratification and to reduce the charging factor (down to 1.03 to 1.05). A re-expansion method was applied and an expander depot and a compound separation were built in. Cycle life is increased from 700 cycles to 1690 cycles. Efficiency is increased by energy and time saving due to the reduced charging factor and by the use of a recombination stopper and a charge indicator with remote control. It is suggested that the lead acid system is still one of the best possibilities for electric road vehicle applications.

  6. Life at acidic pH imposes an increased energetic cost for a eukaryotic acidophile.

    PubMed

    Messerli, Mark A; Amaral-Zettler, Linda A; Zettler, Erik; Jung, Sung-Kwon; Smith, Peter J S; Sogin, Mitchell L

    2005-07-01

    Organisms growing in acidic environments, pH<3, would be expected to possess fundamentally different molecular structures and physiological controls in comparison with similar species restricted to neutral pH. We begin to investigate this premise by determining the magnitude of the transmembrane electrochemical H+ gradient in an acidophilic Chlamydomonas sp. (ATCC PRA-125) isolated from the Rio Tinto, a heavy metal laden, acidic river (pH 1.7-2.5). This acidophile grows most rapidly at pH 2 but is capable of growth over a wide pH range (1.5-7.0), while Chlamydomonas reinhardtii is restricted to growth at pH>or=3 with optimal growth between pH 5.5 and 8.5. With the fluorescent H+ indicator, 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), we show that the acidophilic Chlamydomonas maintains an average cytosolic pH of 6.6 in culture medium at both pH 2 and pH 7 while Chlamydomonas reinhardtii maintains an average cytosolic pH of 7.1 in pH 7 culture medium. The transmembrane electric potential difference of Chlamydomonas sp., measured using intracellular electrodes at both pH 2 and 7, is close to 0 mV, a rare value for plants, animals and protists. The 40,000-fold difference in [H+] could be the result of either active or passive mechanisms. Evidence for active maintenance was detected by monitoring the rate of ATP consumption. At the peak, cells consume about 7% more ATP per second in medium at pH 2 than at pH 7. This increased rate of consumption is sufficient to account for removal of H+ entering the cytosol across a membrane with relatively high permeability to H+ (7x10(-8) cm s-1). Our results indicate that the small increase in the rate of ATP consumption can account for maintenance of the transmembrane H+ gradient without the imposition of cell surface H+ barriers. PMID:15961743

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

    PubMed

    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

    2015-10-15

    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 30mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague-Dawley (SD) rats for 28days. 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. PMID:26222700

  8. Investment in boney defensive traits alters organismal stoichiometry and excretion in fish.

    PubMed

    El-Sabaawi, Rana W; Warbanski, Misha L; Rudman, Seth M; Hovel, Rachel; Matthews, Blake

    2016-08-01

    Understanding how trait diversification alters ecosystem processes is an important goal for ecological and evolutionary studies. Ecological stoichiometry provides a framework for predicting how traits affect ecosystem function. The growth rate hypothesis of ecological stoichiometry links growth and phosphorus (P) body composition in taxa where nucleic acids are a significant pool of body P. In vertebrates, however, most of the P is bound within bone, and organisms with boney structures can vary in terms of the relative contributions of bones to body composition. Threespine stickleback populations have substantial variation in boney armour plating. Shaped by natural selection, this variation provides a model system to study the links between evolution of bone content, elemental body composition, and P excretion. We measure carbon:nitrogen:P body composition from stickleback populations that vary in armour phenotype. We develop a mechanistic mass-balance model to explore factors affecting P excretion, and measure P excretion from two populations with contrasting armour phenotypes. Completely armoured morphs have higher body %P but excrete more P per unit body mass than other morphs. The model suggests that such differences are driven by phenotypic differences in P intake as well as body %P composition. Our results show that while investment in boney traits alters the elemental composition of vertebrate bodies, excretion rates depend on how acquisition and assimilation traits covary with boney trait investment. These results also provide a stoichiometric hypothesis to explain the repeated loss of boney armour in threespine sticklebacks upon colonizing freshwater ecosystems. PMID:27075487

  9. Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders.

    PubMed

    Mika, Adriana; Stepnowski, Piotr; Chmielewski, Michal; Malgorzewicz, Sylwia; Kaska, Lukasz; Proczko, Monika; Ratnicki-Sklucki, Krzysztof; Sledzinski, Maciej; Sledzinski, Tomasz

    2016-07-01

    We recently reported the presence of various cyclopropane fatty acids-among them, cyclopropaneoctanoic acid 2-hexyl-in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2-hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2-hexyl was determined by gas chromatography-mass spectrometry (GC-MS) in non-obese controls, obese patients, obese patients after a 3-month low-calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2-hexyl than controls. Switching obese individuals to a low-calorie (low-lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2-hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2-hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia-related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2-hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI. PMID:27003900

  10. The comparative effects of feeding ammonium carbonate, ammonium sulfate, and ammonium chloride on urinary calcium excretion in the rat.

    PubMed

    Whiting, S J; Cole, D E

    1987-11-01

    When either sulfate or chloride is added to the diet, the resulting acid load causes a rise in urinary calcium excretion. There is, however, the possibility that sulfate, which has been shown to complex renal tubular calcium, will further decrease renal calcium reabsorption and thus produce a greater calciuria than chloride. Because addition of a fixed cation (e.g., sodium) to the diet may also stimulate calciuresis, experiments were conducted using metabolizable ammonium to minimize cation effects. Ammonium salts of sulfate, chloride, and carbonate (control) were added to the diets of male rats at 0.3 mequiv./g weight of diet. Twenty-four hour excretion rates of calcium, sulfate, chloride, and net acid were measured at various intervals up to 1 month. As expected, the chloride and sulfate diets were both associated with significantly elevated urine calcium and net acid excretion as compared with controls. However, those fed sulfate exhibited significantly less calcium and acid excretion and absorbed a smaller proportion of the anion load than those given chloride. In a second experiment, the amounts of supplemental sulfate and chloride were adjusted so that total absorptions were similar. At 2 weeks, both calcium and acid excretions in the fixed anion groups were no longer significantly different. Thus, in chronic feeding trials, there appears to be no measurable difference in the calciuretic properties of sulfate and chloride anions. PMID:3449184

  11. [Hepatoduodenal circulation and excretion of the new GABA derivative citrocard].

    PubMed

    Tiurenkov, I N; Perfilova, V N; Smirnova, L A; Riabukha, A F; Suchkov, E A; Lebedeva, S A

    2013-01-01

    Pharmacokinetic investigation of a new gamma-aminobutyric acid (GABA) derivative cirtocard showed that, upon the intravenous introduction, the drug is determined in high concentrations in organs of elimination--the liver and kidneys. The tissue accessibility amounts to 1.341 for the liver and 4.053 for the kidneys and the separation factor is 1.041 for the liver and 4.486 for the kidneys. The study of drug excretion showed that cirtocard is determined in the urine for 48 h, its nephritic clearance being 0.047 L/h and extra-nephritic clearance, 0.33 L/h. For the unchanged substance, a large significance ofhepatoduodenal circulation is low probable, since no more than 1 - 2% of the introduced dose was isolated with bile over entire experiment. It is established that the removal of the unchanged substance does not exceed 10% of the introduced dose. There is high probability of hepatoduodenal circulation and excretion of the preparation in the form of metabolites. PMID:23767103

  12. Excretion and metabolism of flunarizine in rats and dogs.

    PubMed

    Meuldermans, W; Hendrickx, J; Hurkmans, R; Swysen, E; Woestenborghs, R; Lauwers, W; Heykants, J

    1983-01-01

    The excretion and metabolism of (E)-1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine dihydrochloride (flunarizine hydrochloride, R 14 950, Sibelium) were studied after single oral doses in rats and dogs, using tritium-labelled as well as 14C-labelled drug. Flunarizine was well absorbed in both species. The mass balance for the unchanged drug and its major metabolites in urine, bile and faeces, as estimated with radio-HPLC, ALLOWED an explanation of the differences observed for the excretion pattern of the radioactivity in flunarizine-14C and flunarizine-3H dosed rats, and in male and female rats. Main metabolic pathway in male rats was the oxidative N-dealkylation resulting in bis(4-fluorophenyl)methanol and a number of complementary metabolites of the cinnamylpiperazine moiety, of which hippuric acid was the main one. In female rats and male dogs, however, hydroxy-flunarizine was the main metabolite, resulting from the aromatic hydroxylation of the phenyl ring of the cinnamyl moiety. Enterohepatic circulation of bis(4-fluorophenyl)methanol and hydroxy-flunarizine was proved by "donor-acceptor" coupling in rats; in bile and urine, these two metabolites were present mainly as glucuronides. The glucuronide of hydroxy-flunarizine was also the main plasma metabolite in dogs. PMID:6685491

  13. [The effect of aldosterone A on renal potassium excretion].

    PubMed

    Winther, Signe Abitz; Egfjord, Martin

    2011-01-10

    Recent studies have shown expression of the following regulatory WNK kinases in the kidney: the full-length WNK1 (L-WNK1), the shorter kidney specific WNK1 transcript (KS-WNK1), formed by alternative splicing, and WNK4. Aldosterone activates expression of KS-WNK1 and inhibits WNK4 via SGK1 - both leading to stimulation of ENaC and activation of ROMK, and increased potassium excretion. Thus, further characterization of the WNK system may lead to elucidation of the dual anti-natriuretic and kaliuretic effects of aldosterone, in situations where only activation of one of these effects is needed. PMID:21219845

  14. Pharmacokinetics: metabolism and renal excretion of quinolones in man.

    PubMed

    Vree, T B; Wijnands, W J; Guelen, P J; Baars, A M; Hekster, Y A

    1986-02-21

    The quinolones are relatively poorly absorbed from the gastrointestinal tract. The elimination proceeds mainly by renal excretion. The half-life of elimination depends on the molecular structure and varies between 2 and 10 h. Impaired kidney function is expected to increase the half-life of elimination, though this effect is not always observed. Since the 4-oxo-metabolites show a higher renal clearance than the parent drug, renal impairment will result in a cumulation of the metabolites in the body. PMID:3960691

  15. Acid diet (high meat protein) effects on calcium metabolism and bone health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose of review: Update recent advancements regarding the effect of high animal protein on calcium utilization and bone health. Recent findings: Increased potential renal acid load resulting from a high protein (meat) intake has been closely associated with increased urinary calcium excretion. How...

  16. Tracking and Increasing Viability of Topically Injected Fibroblasts Suspended in Hyaluronic Acid Filler.

    PubMed

    You, Hi-Jin; Namgoong, Sik; Rhee, Sung-Mi; Han, Seung-Kyu

    2016-03-01

    A new injectable tissue-engineered soft tissue consisting of a mixture of hyaluronic acid (HA) filler and cultured human fibroblasts have been developed by the authors. To establish this method as a standard treatment, a further study was required to determine whether the injected fibroblasts could stay at the injected place or move to other sites. In addition, effective strategies were needed to increase viability of the injected fibroblasts. The purpose of this study was to track the injected fibroblasts and to determine the effect of adding prostaglandin E1 (PGE1) or vitamin C on the viability of fibroblasts.Human fibroblasts labeled with fluorescence dye were suspended in HA filler and injected into 4 sites on the back of nude mice. The injected bioimplants consisted of one of the 4 followings: HA filler without cells (HA group), fibroblasts suspended in HA filler (HA + FB group), PGE1-supplemented fibroblasts in HA filler (HA + FB + PGE1 group), and vitamin C-supplemented fibroblasts in HA filler (HA + FB + VC group). At 4 weeks after injection, locations and intensities of the fluorescence signals were evaluated using a live imaging system.The fluorescence signals of the fibroblast-containing groups were visible only at the injected sites without dispersing to other sites. The HA +FB + PGE1 group showed a significantly higher fluorescence signal than the HA + FB and the HA + FB +VC groups (P < 0.05, each). There was no statistical difference between the HA + FB and HA + FB +VC groups (P = 0.69).The results of the current study collectively suggest that injected fibroblasts suspended in HA filler stay at the injected place without moving to other sites. In addition, PGE1 treatment may increase the remaining rhodamine B isothiocynanate dye at the injected site of the human dermal fibroblasts. PMID:26854786

  17. Increasing abscisic acid levels by immunomodulation in barley grains induces precocious maturation without changing grain composition.

    PubMed

    Staroske, Nicole; Conrad, Udo; Kumlehn, Jochen; Hensel, Götz; Radchuk, Ruslana; Erban, Alexander; Kopka, Joachim; Weschke, Winfriede; Weber, Hans

    2016-04-01

    Abscisic acid (ABA) accumulates in seeds during the transition to the seed filling phase. ABA triggers seed maturation, storage activity, and stress signalling and tolerance. Immunomodulation was used to alter the ABA status in barley grains, with the resulting transgenic caryopses responding to the anti-ABA antibody gene expression with increased accumulation of ABA. Calculation of free versus antibody-bound ABA reveals large excess of free ABA, increasing signficantly in caryopses from 10 days after fertilization. Metabolite and transcript profiling in anti-ABA grains expose triggered and enhanced ABA-functions such as transcriptional up-regulation of sucrose-to-starch metabolism, storage protein synthesis and ABA-related signal transduction. Thus, enhanced ABA during transition phases induces precocious maturation but negatively interferes with growth and development. Anti-ABA grains display broad constitutive gene induction related to biotic and abiotic stresses. Most of these genes are ABA- and/or stress-inducible, including alcohol and aldehyde dehydrogenases, peroxidases, chaperones, glutathione-S-transferase, drought- and salt-inducible proteins. Conclusively, ABA immunomodulation results in precocious ABA accumulation that generates an integrated response of stress and maturation. Repression of ABA signalling, occurring in anti-ABA grains, potentially antagonizes effects caused by overshooting production. Finally, mature grain weight and composition are unchanged in anti-ABA plants, although germination is somewhat delayed. This indicates that anti-ABA caryopses induce specific mechanisms to desensitize ABA signalling efficiently, which finally yields mature grains with nearly unchanged dry weight and composition. Such compensation implicates the enormous physiological and metabolic flexibilities of barley grains to adjust effects of unnaturally high ABA amounts in order to ensure and maintain proper grain development. PMID:26951372

  18. Increasing abscisic acid levels by immunomodulation in barley grains induces precocious maturation without changing grain composition

    PubMed Central

    Staroske, Nicole; Conrad, Udo; Kumlehn, Jochen; Hensel, Götz; Radchuk, Ruslana; Erban, Alexander; Kopka, Joachim; Weschke, Winfriede; Weber, Hans

    2016-01-01

    Abscisic acid (ABA) accumulates in seeds during the transition to the seed filling phase. ABA triggers seed maturation, storage activity, and stress signalling and tolerance. Immunomodulation was used to alter the ABA status in barley grains, with the resulting transgenic caryopses responding to the anti-ABA antibody gene expression with increased accumulation of ABA. Calculation of free versus antibody-bound ABA reveals large excess of free ABA, increasing signficantly in caryopses from 10 days after fertilization. Metabolite and transcript profiling in anti-ABA grains expose triggered and enhanced ABA-functions such as transcriptional up-regulation of sucrose-to-starch metabolism, storage protein synthesis and ABA-related signal transduction. Thus, enhanced ABA during transition phases induces precocious maturation but negatively interferes with growth and development. Anti-ABA grains display broad constitutive gene induction related to biotic and abiotic stresses. Most of these genes are ABA- and/or stress-inducible, including alcohol and aldehyde dehydrogenases, peroxidases, chaperones, glutathione-S-transferase, drought- and salt-inducible proteins. Conclusively, ABA immunomodulation results in precocious ABA accumulation that generates an integrated response of stress and maturation. Repression of ABA signalling, occurring in anti-ABA grains, potentially antagonizes effects caused by overshooting production. Finally, mature grain weight and composition are unchanged in anti-ABA plants, although germination is somewhat delayed. This indicates that anti-ABA caryopses induce specific mechanisms to desensitize ABA signalling efficiently, which finally yields mature grains with nearly unchanged dry weight and composition. Such compensation implicates the enormous physiological and metabolic flexibilities of barley grains to adjust effects of unnaturally high ABA amounts in order to ensure and maintain proper grain development. PMID:26951372

  19. Autolysis of Lactococcus lactis Is Increased upon d-Alanine Depletion of Peptidoglycan and Lipoteichoic Acids

    PubMed Central

    Steen, Anton; Palumbo, Emmanuelle; Deghorain, Marie; Cocconcelli, Pier Sandro; Delcour, Jean; Kuipers, Oscar P.; Kok, Jan; Buist, Girbe; Hols, Pascal

    2005-01-01

    Mutations in the genes encoding enzymes responsible for the incorporation of d-Ala into the cell wall of Lactococcus lactis affect autolysis. An L. lactis alanine racemase (alr) mutant is strictly dependent on an external supply of d-Ala to be able to synthesize peptidoglycan and to incorporate d-Ala in the lipoteichoic acids (LTA). The mutant lyses rapidly when d-Ala is removed at mid-exponential growth. AcmA, the major lactococcal autolysin, is partially involved in the increased lysis since an alr acmA double mutant still lyses, albeit to a lesser extent. To investigate the role of d-Ala on LTA in the increased cell lysis, a dltD mutant of L. lactis was investigated, since this mutant is only affected in the d-alanylation of LTA and not the synthesis of peptidoglycan. Mutation of dltD results in increased lysis, showing that d-alanylation of LTA also influences autolysis. Since a dltD acmA double mutant does not lyse, the lysis of the dltD mutant is totally AcmA dependent. Zymographic analysis shows that no degradation of AcmA takes place in the dltD mutant, whereas AcmA is degraded by the extracellular protease HtrA in the wild-type strain. In L. lactis, LTA has been shown to be involved in controlled (directed) binding of AcmA. LTA lacking d-Ala has been reported in other bacterial species to have an improved capacity for autolysin binding. Mutation of dltD in L. lactis, however, does not affect peptidoglycan binding of AcmA; neither the amount of AcmA binding to the cells nor the binding to specific loci is altered. In conclusion, d-Ala depletion of the cell wall causes lysis by two distinct mechanisms. First, it results in an altered peptidoglycan that is more susceptible to lysis by AcmA and also by other factors, e.g., one or more of the other (putative) cell wall hydrolases expressed by L. lactis. Second, reduced amounts of d-Ala on LTA result in decreased degradation of AcmA by HtrA, which results in increased lytic activity. PMID:15601695

  20. Climate change and increased zinc concentrations in a Rocky Mountain acid rock drainage stream

    NASA Astrophysics Data System (ADS)

    Crouch, C. M.; Todd, A. S.; McKnight, D. M.

    2009-12-01

    The Snake River Watershed in Colorado is impacted by acid rock drainage (ARD) originating from both natural sources and sources associated with the historic mining in the watershed. Downstream of mines, the high metal ion concentrations, low pH, and metal oxide deposition cause contamination which disrupts ecosystem functions, impairs biological diversity, and contaminates surface and groundwater drinking supplies. One obvious measure of the severity of this contamination is that the self-sustaining trout populations in the watershed are quite sparse. While elevated concentrations of numerous trace metals are present, dissolved zinc is used as an indicator of trout habitat water quality because the fish are so impacted by its presence. Water quality was monitored along the Snake River from 1980 to 1990 and since then less frequent sampling was conducted as part of research studies and efforts to designate portions of the watershed for mitigation. Metals concentrations during the seasonal low flows of September and October have been observed to increase significantly over that time. In particular, at a site in the headwaters well above the historic mining impacts, zinc concentrations, which were measured between 0.3 and 0.4 mg/L through the 1980s, have now exceeded 1.2 mg/L in the past several years. This four-fold increase in zinc concentrations is associated with an increase in sulfate concentrations, which indicates that these water quality changes are driven primarily by accelerated natural weathering of pyrite in the watershed. The observed increase in natural ARD - possibly the result of climate change - may have implications for mitigation. Currently, these trends are being evaluated by reanalyzing the archived samples to delineate the spatial and temporal changes in contamination. Processes which may be driving the accelerated natural weathering include the earlier occurrence of peak snowmelt due to climate change which causes lower stream flows and drier

  1. Increased production of apolipoprotein B and its lipoproteins by oleic acid in Caco-2 cells.

    PubMed

    Dashti, N; Smith, E A; Alaupovic, P

    1990-01-01

    The production of lipids, apolipoproteins (apo), and lipoproteins induced by oleic acid has been examined in Caco-2 cells. The rates of accumulation in the control medium of 15-day-old Caco-2 cells of triglycerides, unesterified cholesterol, and cholesteryl esters were 102 +/- 8, 73 +/- 5, and 11 +/- 1 ng/mg cell protein/h, respectively; the accumulation rates for apolipoproteins A-I, B, C-III, and E were 111 +/- 9, 53 +/- 4, 13 +/- 1, and 63 +/- 4 ng/mg cell protein/h, respectively. Whereas apolipoproteins A-IV and C-II were detected by immunoblotting, apoA-II was absent in most culture media. In contrast to an early production of apolipoproteins A-I and E occurring 2 days after plating, the apoB expression appeared to be differentiation-dependent and was not measurable in the medium until the sixth day post-confluency. In the control medium, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), and lipid-poor very high density lipoproteins (VHDL) accounted for 12%, 46%, 18%, and 24% of the total lipid and apolipoprotein contents, respectively. The triglyceride-rich VLDL contained mainly apoE (75%) and apoB (23%), while the protein moiety of LDL was composed of apoB (59%), apoE (20%), apoA-I (15%), and apoC-III (6%). The cholesterol-rich HDL contained mainly apoA-I (69%) and apoE (27%). In the control medium, major portions of apolipoproteins B and C-III (93-97%) were present in LDL, whereas the main parts of apoA-I (92%) and apoE (76%) were associated with HDL and VHDL. Oleate increased the production of triglycerides 10-fold, cholesteryl esters 7-fold, and apoB 2- to 4-fold. There was also a moderate increase (39%) in the production of apoC-III but no significant changes in those of apolipoproteins A-I and E. These increases were reflected mainly in a 55-fold elevation in the concentration of VLDL, and a 2-fold increase in the level of LDL; there were no significant changes in HDL and VHDL. VLDL contained the

  2. Minodronic acid ameliorates vertebral bone strength by increasing bone mineral density in 9-month treatment of ovariectomized cynomolgus monkeys.

    PubMed

    Tanaka, Makoto; Mori, Hiroshi; Kawabata, Kazuhito; Mashiba, Tasuku

    2016-07-01

    The effect of treatment for 9months with minodronic acid, a nitrogen-containing bisphosphonate, on vertebral mechanical strength was examined in ovariectomized (OVX) cynomolgus monkeys. Forty skeletally mature female monkeys were randomized into four OVX groups and one sham group (n=8) based on lumbar bone mineral density (BMD). OVX animals were treated orally with 15 and 150μg/kg QD of minodronic acid or 500μg/kg QD alendronate as a reference drug. Measurements of bone turnover markers and lumbar BMD were conducted at 0, 4 and 8months. Measurements of bone mechanical strength and minodronic acid concentration in vertebral bodies were also performed. OVX resulted in a decrease in lumbar BMD and an increase in bone turnover markers at 4 and 8months, compared to the sham group, and the ultimate load on the lumbar vertebra was decreased in OVX animals. Minodronic acid and alendronate prevented the OVX-induced increase in bone turnover markers and decrease in lumbar BMD. Minodronic acid at 150μg/kg increased the ultimate load on lumbar vertebra compared to untreated OVX animals. Regression analysis revealed that the ultimate load was correlated with lumbar BMD and bone mineral content (BMC), and most strongly with the increase in lumbar BMD and BMC over 8months. In a separate analysis within the sham-OVX controls and minodronic acid and alendronate treatment groups, the ultimate loads were also correlated with BMD and BMC. The load-BMD (BMC) correlation in the minodronic acid group showed a trend for a shift to a higher load from the basal relationship in the sham-OVX controls. These results indicate that treatment with minodronic acid for 9months increases vertebral mechanical strength in OVX monkeys, mainly by increasing BMD and BMC. PMID:27155564

  3. Novel biomarkers of the metabolism of caffeic acid derivatives in vivo.

    PubMed

    Rechner, A R; Spencer, J P; Kuhnle, G; Hahn, U; Rice-Evans, C A

    2001-06-01

    The purpose of this study was to investigate biomarkers of the bioavailability and metabolism of hydroxycinnamate derivatives through the determination of the pharmacokinetics of their urinary elimination and identification of the metabolites excreted. Coffee was used as a rich source of caffeic acid derivatives and human supplementation was undertaken. The results show a highly significant increase in the excretion of ferulic, isoferulic, dihydroferulic acid (3-(4-hydroxy-3-methoxyphenyl)-propionic acid), and vanillic acid postsupplementation relative to the levels presupplementation. Thus, ferulic, isoferulic, and dihydroferulic acids are specific biomarkers for the bioavailability and metabolism of dietary caffeic acid esters. Isoferulic acid is a unique biomarker as it is not a dietary component, however, dihydroferulic acid may well derive from other flavonoids with a structurally related B-ring. 3-Hydroxyhippuric acid has also been identified as an indicator for bioavailability and metabolism of phenolic compounds, and shows a highly significant excretion increase postsupplementation. The results reveal isoferulic acid (and possibly dihydroferulic acid) as novel markers of caffeoyl quinic acid metabolism. PMID:11368919

  4. Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo *

    PubMed Central

    Wang, Jun-ming; Sheng, Yu-chen; Ji, Li-li; Wang, Zheng-tao

    2014-01-01

    The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity. PMID:24903991

  5. Urinary Excretion of Neutrophil Gelatinase-Associated Lipocalin in Diabetic Rats

    PubMed Central

    Arellano-Buendía, Abraham Said; García-Arroyo, Fernando Enrique; Cristóbal-García, Magdalena; Loredo-Mendoza, María Lilia; Tapia-Rodríguez, Edilia; Sánchez-Lozada, Laura Gabriela; Osorio-Alonso, Horacio

    2014-01-01

    Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction. Methods. Diabetes was induced in rats by streptozotocin administration (50 mg/kg). Oxidative stress was assessed by measuring the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD); additionally, expression levels of 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), and oxidized protein (OP) were quantified. Whole glomerular filtration rate (GFR) was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin (uOPN), and N-acetyl-β-D-glucosaminidase (uNAG) was also determined. Results. Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction. Conclusion. The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes. PMID:25243053

  6. High Salt Diet Affects Renal Sodium Excretion and ERRα Expression

    PubMed Central

    Wang, Dan; Wang, Yang; Liu, Fu-Qiang; Yuan, Zu-Yi; Mu, Jian-Jun

    2016-01-01

    Kidneys regulate the balance of water and sodium and therefore are related to blood pressure. It is unclear whether estrogen-related receptor α (ERRα), an orphan nuclear receptor and transcription factor highly expressed in kidneys, affects the reabsorption of water and sodium. The aim of this study was to determine whether changes in the expressions of ERRα, Na+/K+-ATPase and epithelial sodium channel (ENaC) proteins affected the reabsorption of water and sodium in kidneys of Dahl salt-sensitive (DS) rats. SS.13BN rats, 98% homologous to the DS rats, were used as a normotensive control group. The 24 h urinary sodium excretion of the DS and SS.13BN rats increased after the 6-week high salt diet intervention, while sodium excretion was increased in DS rats with daidzein (agonist of ERRα) treatment. ERRα expression was decreased, while β- and γ-ENaC mRNA expressions were increased upon high sodium diet treatment in the DS rats. In the chromatin immunoprecipitation (CHIP) assay, positive PCR signals were obtained in samples treated with anti-ERRα antibody. The transcriptional activity of ERRα was decreased upon high salt diet intervention. ERRα reduced the expressions of β- and γ-ENaC by binding to the ENaC promoter, thereby increased Na+ reabsorption. Therefore, ERRα might be one of the factors causing salt-sensitive hypertension. PMID:27043552

  7. Absorption, metabolism, and excretion of fermented orange juice (poly)phenols in rats.

    PubMed

    Escudero-López, Blanca; Calani, Luca; Fernández-Pachón, María-Soledad; Ortega, Angeles; Brighenti, Furio; Crozier, Alan; Del Rio, Daniele

    2014-01-01

    Two milliliters of a fermented, pasteurized orange juice containing ~1% alcohol and 2.3 μmol of (poly)phenolic compounds was fed to rats by gavage after which plasma and urine collected over a 36 h period were analyzed by UHPLC-mass spectrometry. The main constituents in the juice were hesperetin and naringenin-O-glycosides, apigenin-6,8-C-diglucoside, and ferulic acid-4'-O-glucoside. Plasma contained seven flavanone glucuronides, with the principal metabolites, naringenin-7-O-glucuronide, naringenin-4'-O-glucuronide, and an isosakuranetin-O-glucuronide, peaking 6 h after intake at concentrations of ~10 nmol/L. Urinary excretion of four hesperetin glucuronides was equivalent to 0.28% of intake while that of the two naringenin glucuronides was 2.8% of intake. The plasma and urine data suggest that while some absorption occurred in the small intestine, the main site of uptake was the colon. Urine also contained dihydroferulic acid-4'-O-glucuronide and dihydroferulic acid-4'-O-sulfate which were excreted in quantities corresponding to 48.2% of the ingested ferulic acid-4'-glucoside. This indicates that the hydroxycinnamate is much more bioavailable than the flavanones in the rat model. Conversion of the ferulic acid glucoside to the dihydroferulic acid metabolites involves the action of colonic microbial glycosidases and reductases/hydrogenases followed by postabsorption phase II metabolism before renal excretion. PMID:24255025

  8. Geographical and temporal differences in the urinary excretion of inorganic arsenic: a Belgian population study.

    PubMed Central

    Buchet, J P; Staessen, J; Roels, H; Lauwerys, R; Fagard, R

    1996-01-01

    OBJECTIVE: This Belgian study assessed the geographical and temporal differences in the exposure of the population to inorganic arsenic, a known carcinogen. METHODS: In the CadmiBel study (1985-9) the 24 h urinary arsenic excretion was measured, as an index of recent exposure, in industrialised cities (Liège: n = 664, Charleroi: n = 291), in a rural control area (Hechtel-Eksel: n = 397), and in rural districts in which the population had possibly been exposed through the drinking water or the emissions of nonferrous smelters (Wezel: n = 93, Lommel: n = 111, and Pelt: n = 133). In the PheeCad study, in 1991-5, the rural areas (n = 609) were re-examined together with an urban control area (Leuven: n = 152). RESULTS: The CadmiBel results showed that after adjustment for sex, age, and body mass index, the 24 h arsenic excretion was on average low in Liège (91 nmol), Charleroi (155 nmol), Hechtel-Eksel (144 nmol), and Wezel (158 nmol), whereas the highest excretions were found in Lommel (570 nmol) and Pelt (373 nmol). During the PheeCad study, the mean 24 h arsenic excretion in the rural areas ranged from 81 to 111 nmol. This was lower than six years earlier and similar to the excretion in the control town (108 nmol). Longitudinal studies in 529 people living in the rural areas confirmed that their 24 h arsenic excretion had decreased (P < 0.001) from 222 to 100 nmol. As well as the drinking water, industry was likely to be a source of the increased exposure in Lommel and Pelt in 1985-9, because at that time the urinary arsenic excretion did not follow the regional differences in the arsenic content of the drinking water, because the fall in the arsenic excretion over time coincided with the implementation by industry of stricter environmental regulations, because in individual subjects the urinary arsenic excretion was inversely correlated with the distance to the nearest smelter, and because an increased arsenic excretion was only found downwind from the main

  9. The rolC gene increases caffeoylquinic acid production in transformed artichoke cells.

    PubMed

    Vereshchagina, Y V; Bulgakov, V P; Grigorchuk, V P; Rybin, V G; Veremeichik, G N; Tchernoded, G K; Gorpenchenko, T Y; Koren, O G; Phan, N H T; Minh, N T; Chau, L T; Zhuravlev, Y N

    2014-09-01

    Caffeoylquinic acids are found in artichokes, and they are currently considered important therapeutic or preventive agents for treating Alzheimer's disease and diabetes. We transformed artichoke [the cultivated cardoon or Cynara cardunculus var. altilis DC (Asteraceae)] with the rolC gene, which is a known inducer of secondary metabolism. High-performance liquid chromatography with UV and high-resolution mass spectrometry (HPLC-UV-HRMS) revealed that the predominant metabolites synthesized in the transgenic calli were 1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and chlorogenic acid. The rolC-transformed calli contained 1.5% caffeoylquinic acids by dry weight. The overall production of these metabolites was three times higher than that of the corresponding control calli. The enhancing effect of rolC remained stable over long-term cultivation. PMID:24938208

  10. A solid acid esterification catalyst which reduces waste and increases yields

    SciTech Connect

    Lundquist, E.G.

    1993-12-31

    Recent research on polymeric catalysts has led to the development of a new solid acid esterification catalyst which is highly active for the esterification of fatty acids and maleic anhydride at elevated temperatures. The use of this catalyst eliminates the need for a final neutralization step which is required when using traditional homogenous acid (H{sub 2}SO{sub 4} and HCl) catalysts. This neutralization step generates large amounts of waste salts and hurts efficiency since unconsumed organic acid reactants are also neutralized. In the high temperature esterification reactions studied here, the production of dialkyl ether by-products from the acid catalyzed self-condensation of alcohol is also greatly reduced allowing for both high activity and selectivity.

  11. Intake of n-3 Polyunsaturated Fatty Acids Increases Omega-3 Index in Aged Male and Female Spontaneously Hypertensive Rats

    PubMed Central

    Bačová, Barbara; Seč, Peter; Čertik, Milan

    2013-01-01

    The purpose of this study was to examine whether n-3 PUFA intake affects n-3 and n-6 FA levels in plasma and red blood cells as well as omega-3 index in old male and female spontaneously hypertensive (SHR) and healthy rats. Plasma linoleic acid and eicosapentaenoic acid increased due to n-3 PUFA intake in SHR and healthy rats. Comparing to healthy rats the levels of PUFA in red blood cells of SHR were lower in males and higher in females with exception of arachidonic acid, which was high in males and low in females. Feeding of rats with n-3 PUFA resulted in increase of red blood cells levels of eicosapentaenoic acid and/or docosahexaenoic acid in a sex- and strain-dependent manner. Moreover, n-3 PUFA intake decreased arachidonic acid in healthy female rats but increased it in SHR and did not affect it in males. Omega-3 index was lower in SHR comparing to healthy rats and it increased due to the consumption of n-3 PUFA. Results point out sex- and strain-related differences in red blood cells levels of n-3 and n-6 PUFA in basal conditions as well as in response to n-3 PUFA intake. PMID:24967252

  12. [Resorption of hydrocyanic acid from linseed].

    PubMed

    Schulz, V; Löffler, A; Gheorghiu, T

    1983-01-01

    Resorption of hydrocyanic acid after ingestion of linseed was investigated in 20 healthy volunteers and 5 patients. The persons investigated took a single dose of 30 g or of 100 g of linseed or they received throughout several weeks 15 g. t.i.d. One volunteer also took for purposes of comparison bitter almonds or potassium cyanide. Before, during and after the periods of ingestion plasma levels of hydrocyanic acid and of thiocyanate were normal. During long-term trials urinary excretion of thiocyanate was monitored regularly. Intake of linseed even in extremely high dosages never caused significant rises of plasma thiocyanate levels; this, however, was the case after intake of bitter almonds or potassium cyanide. Thus, it can be excluded, that intoxication by hydrocyanic acid can be caused by linseed. Long-term intake of linseed however, raised plasma levels of thiocyanate significantly; at the same time urinary excretion of thiocyanate increased. PMID:6302421

  13. Increased Flow of Fatty Acids toward β-Oxidation in Developing Seeds of Arabidopsis Deficient in Diacylglycerol Acyltransferase Activity or Synthesizing Medium-Chain-Length Fatty Acids1

    PubMed Central

    Poirier, Yves; Ventre, Giovanni; Caldelari, Daniela

    1999-01-01

    Synthesis of polyhydroxyalkanoates (PHAs) from intermediates of fatty acid β-oxidation was used as a tool to study fatty acid degradation in developing seeds of Arabidopsis. Transgenic plants expressing a peroxisomal PHA synthase under the control of a napin promoter accumulated PHA in developing seeds to a final level of 0.06 mg g−1 dry weight. In plants co-expressing a plastidial acyl-acyl carrier protein thioesterase from Cuphea lanceolata and a peroxisomal PHA synthase, approximately 18-fold more PHA accumulated in developing seeds. The proportion of 3-hydroxydecanoic acid monomer in the PHA was strongly increased, indicating a large flow of capric acid toward β-oxidation. Furthermore, expression of the peroxisomal PHA synthase in an Arabidopsis mutant deficient in the enzyme diacylglycerol acyltransferase resulted in a 10-fold increase in PHA accumulation in developing seeds. These data indicate that plants can respond to the inadequate incorporation of fatty acids into triacylglycerides by recycling the fatty acids via β-oxidation and that a considerable flow toward β-oxidation can occur even in a plant tissue primarily devoted to the accumulation of storage lipids. PMID:10594123

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

    PubMed Central

    FRAJESE, GIOVANNI VANNI; BENVENUTO, MONICA; FANTINI, MASSIMO; AMBROSIN, ELENA; SACCHETTI, PAMELA; MASUELLI, LAURA; GIGANTI, MARIA GABRIELLA; MODESTI, ANDREA; BEI, ROBERTO

    2016-01-01

    Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro. PMID:27313770

  16. Calyculin and okadaic acid promote perilipin phosphorylation and increase lipolysis in primary rat adipocytes.

    PubMed

    He, Jinhan; Jiang, Hongfeng; Tansey, John T; Tang, Chaoshu; Pu, Shenshen; Xu, Guoheng

    2006-02-01

    Lipolysis is primarily regulated by protein kinase A (PKA), which phosphorylates perilipin and hormone-sensitive lipase (HSL), and causes translocation of HSL from cytosol to lipid droplets in adipocytes. Perilipin coats lipid droplet surface and assumes to prevent lipase access to triacylglycerols, thus inhibiting basal lipolysis; phosphorylated perilipin facilitates lipolysis on PKA activation. Here, we induced lipolysis in primary rat adipocytes by inhibiting protein serine/threonine phosphatase with specific inhibitors, okadaic acid and calyculin. The incubation with calyculin promotes incorporation of 32Pi into perilipins, thus, confirming that perilipin is hyperphosphorylated. The lipolysis response to calyculin is gradually accompanied by increased accumulation of phosphorylated perilipin A in a concentration- and time-responsive manner. When perilipin phosphorylation is abrogated by the addition of N-ethylmaleimide, lipolysis ceases. Different from a considerable translocation of HSL upon PKA activation with isoproterenol, calyculin does not alter HSL redistribution in primary or differentiated adipocytes, as confirmed by both immunostaining and immunoblotting. Thus, we suggest that inhibition of the phosphatase by calyculin activates lipolysis via promoting perilipin phosphorylation rather than eliciting HSL translocation in adipocytes. Further, we show that when the endogenous phosphatase is inhibited by calyculin, simultaneous PKA activation with isoproterenol converts most of the perilipin to the hyperphosphorylated species, and induces enhanced lipolysis. Apparently, as PKA phosphorylates perilipin and stimulates lipolysis, the phosphatase acts to dephosphorylate perilipin and attenuate lipolysis. This suggests a two-step strategy governed by a kinase and a phosphatase to modulate the steady state of perilipin phosphorylation and hence the lipolysis response to hormonal stimulation. PMID:16545598