Marshall, Stephanie M; Gromovsky, Anthony D; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E
2014-01-01
The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.
Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Dávila-Román, Victor G; Ostlund, Richard E
2017-12-01
Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d 5 and the nonabsorbable stool marker sitostanol-d 4 . Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol ( r =-0.426; P <0.0001), total cholesterol ( r =-0.472; P ≤0.0001), and daily percent excretion of cholesterol from the rapidly mixing cholesterol pool ( r =-0.343; P =0.0012) and was positively correlated with percent cholesterol absorption ( r =+0.279; P =0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, low-density lipoprotein, high-density lipoprotein cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant ( P =0.0008). Excretion of endogenous cholesterol is strongly, independently, and negatively associated with carotid intima-media thickness. The reverse cholesterol transport pathway comprising the intestine and the rapidly mixing plasma, and tissue cholesterol pool could be an unrecognized determinant of cardiovascular disease risk not reflected in circulating lipoproteins. Further work is needed to relate measures of reverse cholesterol transport to atherosclerotic disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.
Beynen, A C; Meijer, G W; Lemmens, A G; Glatz, J F; Versluis, A; Katan, M B; Van Zutphen, L F
1989-06-01
In 2 inbred strains of rabbits with high or low response of plasma cholesterol to dietary cholesterol, excretion of steroids in the feces and efficiency of cholesterol absorption were determined. Rates of whole-body cholesterol synthesis, measured as fecal excretion of bile acids and neutral steroids minus cholesterol intake, were similar in hypo- and hyperresponders fed a low-cholesterol (8 mumol/100 g) diet. Transfer of the rabbits to a high-cholesterol (182 mumol/100 g) diet caused an increase in fecal bile acid excretion in hypo- but not in hyperresponders. Dietary cholesterol did not affect neutral steroid excretion in either rabbit strain. Hyperresponders tended to accumulate more cholesterol in their body than did hyporesponders. After the rabbits were switched back from the high- to the low-cholesterol diet, rates of whole-body cholesterol synthesis were significantly higher in the hypo- than in the hyperresponders. With the use of the simultaneous oral administration of [3H]cholesterol and beta-[14C]sitosterol, hyperresponders were found to absorb significantly higher percentages of cholesterol than hyporesponders. It is concluded that the differences in stimulation of bile acid excretion after cholesterol feeding and the efficiency of cholesterol absorption are important determinants of the phenomenon of hypo- and hyperresponsiveness in the 2 inbred rabbit strains.
Butteiger, Dustie N; Krul, Elaine S
2015-08-01
Custom diets are a convenient vector for oral administration of test articles, but the processing and physical form of a diet can affect its nutritional properties and how it is consumed. Here, the authors evaluated the feeding behavior and physiology of golden Syrian hamsters fed diets of either soy or caseinate protein in pelleted or powdered forms for 28 d to determine whether dietary processing and form mediates the physiological effects of dietary proteins. The authors compared body weight, food consumption, serum cholesterol concentration, serum triglyceride concentration, fecal weight and fecal excretion of bile acids between treatment groups. Hamsters fed powdered diets showed higher food consumption than hamsters fed pelleted diets, regardless of protein source. Hamsters fed soy pelleted diets showed lower serum cholesterol concentration and higher fecal excretion of bile acid than hamsters fed caseinate pelleted diets, and serum cholesterol concentration correlated strongly with fecal excretion of bile acid. This correlation suggests that the physiological effects of soy protein on cholesterol and excretion of bile acid might be related or similarly mediated through diet. The differences observed between hamsters on different diets indicate that dietary form can influence both feeding behavior and the physiological effects of a diet in hamsters.
Wang, Yuhuan; Liu, Xiaoxi; Pijut, Sonja S.; Li, Jianing; Horn, Jamie; Bradford, Emily M.; Leggas, Markos; Barrett, Terrence A.; Graf, Gregory A.
2015-01-01
Previous studies suggest an interdependent relationship between liver and intestine for cholesterol elimination from the body. We hypothesized that a combination of ursodiol (Urso) and ezetimibe (EZ) could increase biliary secretion and reduce cholesterol reabsorption, respectively, to promote cholesterol excretion. Treatment with Urso increased hepatic ABCG5 ABCG8 (G5G8) protein and both biliary and fecal sterols in a dose-dependent manner. To determine whether the drug combination (Urso-EZ) further increased cholesterol excretion, mice were treated with Urso alone or in combination with two doses of EZ. EZ produced an additive and dose-dependent increase in fecal neutral sterol (FNS) elimination in the presence of Urso. Finally, we sequentially treated wide-type and G5G8-deficient mice with Urso and Urso-EZ to determine the extent to which these effects were G5G8 dependent. Although biliary and FNS were invariably lower in G5G8 KO mice, the relative increase in FNS following treatment with Urso alone or the Urso-EZ combination was not affected by genotype. In conclusion, Urso increases G5G8, biliary cholesterol secretion, and FNS and acts additively with EZ to promote fecal sterol excretion. However, the stimulatory effect of these agents was not G5G8 dependent. PMID:25635125
Liang, Yintong; Chen, Jingnan; Zuo, Yuanyuan; Ma, Ka Ying; Jiang, Yue; Huang, Yu; Chen, Zhen-Yu
2013-04-01
The present study investigated the underlying mechanism associated with the hypocholesterolemic activity of blueberry anthocyanins by examining its effect on fecal sterol excretion and gene expression of major receptors, enzymes, and transporters involved in cholesterol metabolism. Hamsters were divided into three groups and fed a 0.1 % cholesterol diet containing 0 % (CTL), 0.5 % (BL), and 1.0 % (BH) blueberry anthocyanins, respectively, for six weeks. Plasma total cholesterol (TC), triacylglycerols (TAG), and non-high-density lipoproteins cholesterol (non-HDL-C) were measured using the enzymatic kits, and the gene expression of transporters, enzymes, and receptors involved in cholesterol absorption and metabolism was quantified using the quantitative PCR. GC analysis was used to quantify hepatic cholesterol and fecal acidic and neutral sterols. Dietary supplementation of 0.5 and 1.0 % blueberry anthocyanins for 6 weeks decreased plasma TC concentration by 6-12 % in a dose-dependent manner. This was accompanied by increasing the excretion of fecal neutral and acidic sterols by 22-29 % and 41-74 %, respectively. Real-time PCR analyses demonstrated that incorporation of blueberry anthocyanins into diet down-regulated the genes of NPC1L1, ACAT-2, MTP, and ABCG 8. In addition, blueberry anthocyanins were also able to down-regulate the gene expression of hepatic HMG-CoA reductase. The cholesterol-lowering activity of blueberry anthocyanins was most likely mediated by enhancing the excretion of sterols accompanied with down-regulation on gene expression of intestinal NPC1L1, ACAT-2, MTP, and ABCG 8.
Martínez, Inés; Perdicaro, Diahann J; Brown, Andrew W; Hammons, Susan; Carden, Trevor J; Carr, Timothy P; Eskridge, Kent M; Walter, Jens
2013-01-01
The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota.
Hosomi, Ryota; Fukunaga, Kenji; Arai, Hirofumi; Kanda, Seiji; Nishiyama, Toshimasa; Yoshida, Munehiro
2012-03-01
Fish consumption is well known to provide health benefits in both experimental animals and human subjects. Numerous studies have demonstrated the beneficial effects of various protein hydrolysates on lipid metabolism. In this context, this study examined the effect of fish protein hydrolysates (FPH) on cholesterol metabolism compared with the effect of casein. FPHs were prepared from Alaska pollock meat using papain as a protease. Male Wistar rats were divided into the following four dietary groups of seven rats each: either casein (20%) or FPH (10%) + casein (10%), with or without 0.5% cholesterol and 0.1% sodium cholate. Serum and liver lipid levels, fecal cholesterol and bile acid excretions, and the hepatic expression of genes encoding proteins involved in cholesterol homeostasis were examined. In rats fed the FPH diets compared with casein diets with or without cholesterol and sodium cholate, the indexes of cholesterol metabolism-namely, serum cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels-were significantly lower, whereas fecal cholesterol and bile acid excretions were higher. Rats fed the FPH diets compared with casein with cholesterol exhibited a lower liver cholesterol level via an increased liver cholesterol 7α-hydroxylase (CYP7A1) expression level. This study demonstrates that the intake of FPH has hypocholesterolemic effects through the enhancement of fecal cholesterol and bile acid excretions and CYP7A1 expression levels. Therefore, fish peptides prepared by papain digestion might provide health benefits by decreasing the cholesterol content in the blood, which would contribute to the prevention of circulatory system diseases such as arteriosclerosis.
Hong, Ki Bae; Hong, Sung-Yong; Joung, Eun Young; Kim, Byung Hee; Bae, Song-Hwan; Park, Yooheon; Suh, Hyung Joo
2015-01-01
The cauliflower culinary-medicinal mushroom, Sparassis crispa, possesses various biological activities that have been widely reported to have therapeutic applications. We examined the effects of S. crispa on serum cholesterol, hepatic enzymes related to cholesterol metabolism, and fecal sterol excretion in rats fed a cholesterol-rich diet for 4 weeks. Male Sprague-Dawley rats (8 weeks old) were randomly divided into 5 groups (n = 6 mice per group): normal diet (normal control [NC]), cholesterol-rich diet (cholesterol control [CC]), cholesterol-rich diet plus S. crispa fruiting body (SC), cholesterol-rich diet plus S. crispa extract (SCE), and cholesterol-rich diet plus S. crispa residue (SCR). SCE supplementation significantly enhanced hepatic cholesterol catabolism through the upregulation of cholesterol 7α-hydroxylase (CYP7A1) messenger RNA (mRNA) expression (2.55-fold compared with that in the NC group; P < 0.05) and the downregulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA expression (0.57-fold compared with that in the NC group; P < 0.05). Additionally, the SCE diet resulted in the highest fecal excretion of cholesterol and bile acid in hypercholesterolemic rats. In conclusion, mRNA expression of CYP7A1 and HMG-CoA reductase were significantly modulated by the absorption of SCE samples. Also, SCE samples had a significant effect on fecal bile acid and cholesterol excretion. These results suggest that SCE samples can induce hypocholesterolic effects through cholesterol metabolism and the reduction of circulating cholesterol levels.
Takiguchi, Shunichi; Ayaori, Makoto; Yakushiji, Emi; Nishida, Takafumi; Nakaya, Kazuhiro; Sasaki, Makoto; Iizuka, Maki; Uto-Kondo, Harumi; Terao, Yoshio; Yogo, Makiko; Komatsu, Tomohiro; Ogura, Masatsune; Ikewaki, Katsunori
2018-05-10
Reverse cholesterol transport (RCT) is a major mechanism by which HDL (high-density lipoprotein) protects against atherosclerosis. Endothelial lipase (EL) reportedly reduces HDL levels, which, in theory, would increase atherosclerosis. However, it remains unclear whether EL affects RCT in vivo. Adenoviral vectors expressing EL or luciferase were intravenously injected into mice, and a macrophage RCT assay was performed. As expected, hepatic EL overexpression markedly reduced HDL levels. In parallel, plasma 3 H-cholesterol counts from the EL-expressing mice decreased by 85% compared with control. Surprisingly, there was no difference in fecal 3 H-cholesterol excretion between the groups. Kinetic studies revealed increased catabolism/hepatic uptake of 3 HDL-cholesteryl ether, resulting in no change in fecal HDL-cholesteryl ester excretion in the mice. To explore underlying mechanisms for the preservation of RCT despite low HDL levels in the EL-expressing mice, we investigated the effects of hepatic SR-BI (scavenger receptor class B type I) knockdown. RCT assay revealed that knockdown of SR-BI alone reduced fecal excretion of macrophage-derived 3 H-cholesterol. Interestingly, hepatic EL overexpression under SR-BI inhibition further attenuated fecal tracer counts as compared with control. Finally, we observed that EL overexpression enhanced in vivo RCT under pharmacological inhibition of hepatic ABCA1 (ATP-binding cassette transporter A1) by probucol. Hepatic EL expression compensates for reduced macrophage-derived cholesterol efflux to plasma because of low HDL levels by promoting cholesterol excretion to bile/feces via an SR-BI pathway, maintaining overall RCT in vivo. In contrast, EL-modified HDL might negatively regulate RCT via hepatic ABCA1. Despite extreme hypoalphalipoproteinemia, RCT is maintained in EL-expressing mice via SR-BI/ABCA1-dependent pathways. © 2018 American Heart Association, Inc.
Vrins, Carlos L. J.; van der Velde, Astrid E.; van den Oever, Karin; Levels, Johannes H. M.; Huet, Stephane; Oude Elferink, Ronald P. J.; Kuipers, Folkert; Groen, Albert K.
2009-01-01
Peroxisome proliferator-activated receptor delta (PPARδ) is involved in regulation of energy homeostasis. Activation of PPARδ markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobiliary cholesterol secretion, nor by reduced cholesterol absorption. To test the hypothesis that PPARδ activation leads to stimulation of transintestinal cholesterol efflux (TICE), we quantified it by intestine perfusions in FVB mice treated with PPARδ agonist GW610742. To exclude the effects on cholesterol absorption, mice were also treated with cholesterol absorption inhibitor ezetimibe or ezetimibe/GW610742. GW601742 treatment had little effect on plasma lipid levels but stimulated both fecal neutral sterol excretion (∼200%) and TICE (∼100%). GW610742 decreased intestinal Npc1l1 expression but had no effect on Abcg5/Abcg8. Interestingly, expression of Rab9 and LIMPII, encoding proteins involved in intracellular cholesterol trafficking, was increased upon PPARδ activation. Although treatment with ezetimibe alone had no effect on TICE, it reduced the effect of GW610742 on TICE. These data show that activation of PPARδ stimulates fecal cholesterol excretion in mice, primarily by the two-fold increase in TICE, indicating that this pathway provides an interesting target for the development of drugs aiming at the prevention of atherosclerosis. PMID:19439761
Thandapilly, Sijo J; Ndou, Saymore P; Wang, Yanan; Nyachoti, Charles M; Ames, Nancy P
2018-06-20
The cholesterol-lowering effect of barley β-glucan has been proposed to be the result of a pleiotropic effect, which involves several biological mechanisms such as gut fermentation, inhibition of intestinal cholesterol absorption and increased bile acid excretion and its synthesis. However, one of the recent studies from our laboratory indicated that increased bile acid excretion and subsequent increase in its synthesis, but not the inhibition of cholesterol absorption or synthesis might be responsible for the cholesterol-lowering effect of barley β-glucan. Accordingly, the primary objective of the present study was to investigate the concentration of bile acids (BA), neutral sterols (NS) and short chain fatty acids (SCFA) excreted through the feces by mildly hypercholesterolemic subjects who consumed diets containing barley β-glucan with varying molecular weights (MW) and concentrations. In a controlled, four phase, crossover trial, 30 mildly hypercholesterolemic but otherwise healthy subjects were randomly assigned to receive breakfast containing 3 g high MW (HMW), 5 g low MW (LMW), 3 g LMW barley β-glucan or a control diet for 5 weeks. The concentrations of BA, NS and SCFA in the feces were measured at the end of each treatment phase. Compared to the other treatment groups, 3 g day-1 HMW barley β-glucan consumption resulted in increased lithocholic acid (LCA) excretion (P < 0.001) but not LMW β-glucan, even at the high dose of 5 g day-1. Increased fermentability of fibre was also evident from a significant increase in fecal total SCFA concentrations in response to the 3 g HMW β-glucan diet compared to the 3 g LMW barley β-glucan and control diet (P = 0.0015). In summary, the current results validate our previous report on the role of fecal bile acid excretion in cholesterol lowering through the consumption of barley β-glucan. In addition, increased SCFA concentrations indicate that an increase in β-glucan molecular weight promotes hindgut fermentation, which might also be playing a role in attenuating cholesterol levels.
Greater bile acid excretion with soy bean than with cow milk in infants.
Potter, J M; Nestel, P J
1976-05-01
The excretion of fecal sterols and bile acids was measured in five infants from the 1st week of life to 2 or 3 months of age as the composition of their diet was changed from cow milk to soy bean milk. Bile acid excretion, adjusted for body weight, was initially lower during the 1st than during the 3rd week, when it reached adult values. The average excretion of bile acids was 6.8 mg/kg per day with soy bean milk and 3.6 mg/kg per day with cow milk. Net sterol excretion (total sterol output minus cholesterol intake) was also twice as high with soy bean milk and probably reflected enhancement of cholesterol re-excretion as well as of synthesis since the cholesterol content of soy beans is nil. However, net sterol excretion remained higher with soy bean than with cow milk even when egg yolk cholesterol was added to the soy bean milk. It is concluded that the substitution of soy bean milk for cow milk, which lowered the plasma cholesterol in all infants (even in the presence of dietary cholesterol) leads to an increase in bile acids and probably also in cholesterol excretion in young infants.
Hjerpsted, Julie; Leedo, Eva; Tholstrup, Tine
2011-12-01
Despite its high content of saturated fatty acids, cheese does not seem to increase plasma total and LDL-cholesterol concentrations when compared with an equivalent intake of fat from butter. This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat. The objective was to compare the effects of diets of equal fat content rich in either hard cheese or butter or a habitual diet on blood pressure and fasting serum blood lipids, C-reactive protein, glucose, and insulin. We also examined whether fecal fat excretion differs with the consumption of cheese or butter. The study was a randomized dietary intervention consisting of two 6-wk crossover periods and a 14-d run-in period during which the subjects consumed their habitual diet. The study included 49 men and women who replaced part of their habitual dietary fat intake with 13% of energy from cheese or butter. After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-cholesterol concentrations and higher glucose concentrations than did the butter intervention. Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with the run-in period, during which total fat and saturated fat intakes were lower. Fecal fat excretion did not differ between the cheese and butter periods. Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.
Ezetimibe Increases Endogenous Cholesterol Excretion in Humans
Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E
2017-01-01
Objective Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers LDL cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly-mixing endogenous cholesterol pool into the stool. Approach and Results In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with LDL cholesterol 100–200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/day or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d7 in a lipid emulsion and dietary cholesterol with cholesterol-d5 and sitostanol-d4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30 ± 4.3% (SE, P < 0.0001) and LDL cholesterol 19.8 ± 1.9% (P = 0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6 ± 12.2% (P < 0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7 ± 14.3% (P < 0.0001) while plasma cholesterol turnover rose 26.2 ± 3.6% (P = 0.0096). Fecal bile acids were unchanged. Conclusions Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly-mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. PMID:28279967
Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.
Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E
2017-05-01
Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.
Omega 3 Fatty Acids Promote Macrophage Reverse Cholesterol Transport in Hamster Fed High Fat Diet
Kasbi Chadli, Fatima; Nazih, Hassane; Krempf, Michel; Nguyen, Patrick; Ouguerram, Khadija
2013-01-01
The aim of this study was to investigate macrophage reverse cholesterol transport (RCT) in hamster, a CETP-expressing species, fed omega 3 fatty acids (ω3PUFA) supplemented high fat diet (HFD). Three groups of hamsters (n = 6/group) were studied for 20 weeks: 1) control diet: Control, 2) HFD group: HF and 3) HFD group supplemented with ω3PUFA (EPA and DHA): HFω3. In vivo macrophage-to-feces RCT was assessed after an intraperitoneal injection of 3H-cholesterol-labelled hamster primary macrophages. Compared to Control, HF presented significant (p<0.05) increase in body weight, plasma TG (p<0.01) and cholesterol (p<0.001) with an increase in VLDL TG and in VLDL and LDL cholesterol (p<0.001). Compared to HF, HFω3 presented significant decrease in body weight. HFω3 showed less plasma TG (p<0.001) and cholesterol (p<0.001) related to a decrease in VLDL TG and HDL cholesterol respectively and higher LCAT activity (p<0.05) compared to HF. HFω3 showed a higher fecal bile acid excretion (p<0.05) compared to Control and HF groups and higher fecal cholesterol excretion (p<0.05) compared to HF. This increase was related to higher gene expression of ABCG5, ABCA1 and SR-B1 in HFω3 compared to Control and HF groups (<0.05) and in ABCG1 and CYP7A1 compared to HF group (p<0.05). A higher plasma efflux capacity was also measured in HFω3 using 3H- cholesterol labeled Fu5AH cells. In conclusion, EPA and DHA supplementation improved macrophage to feces reverse cholesterol transport in hamster fed HFD. This change was related to the higher cholesterol and fecal bile acids excretion and to the activation of major genes involved in RCT. PMID:23613796
Temel, Ryan E.; Brown, J. Mark
2015-01-01
Cardiovascular disease (CVD) remains the largest cause of mortality in most developed countries. Although recent failed clinical trials and Mendelian randomization studies have called into question the high density lipoprotein (HDL) hypothesis, it remains well accepted that stimulating the process of reverse cholesterol transport (RCT) can prevent or even regress atherosclerosis. The prevailing model for RCT is that cholesterol from the artery wall must be delivered to the liver where it is secreted into bile before leaving the body through fecal excretion. However, many studies have demonstrated that RCT can proceed through a non-biliary pathway known as transintestinal cholesterol excretion (TICE). The goal of this review is to discuss the current state of knowledge of the TICE pathway, with emphasis on points of therapeutic intervention. PMID:25930707
Marshall, Stephanie M; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; McDaniel, Allison L; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E
2014-01-01
An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg) mice, which predominantly excrete cholesterol via TICE, and wild type (WT) littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG) and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.
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 excretion is most likely the primary mechanism responsible for the lipid-lowering action of beta-cyclodextrin. In contrast, other mechanisms involving the alterations in the biliary bile acid profile or repressed hepatic lipogenesis, e.g., VLDL production, appear to be involved in the hypolipidemic effect of resistant starch.
Thorning, Tanja K; Raziani, Farinaz; Bendsen, Nathalie T; Astrup, Arne; Tholstrup, Tine; Raben, Anne
2015-09-01
Heart associations recommend limited intake of saturated fat. However, effects of saturated fat on low-density lipoprotein (LDL)-cholesterol concentrations and cardiovascular disease risk might depend on nutrients and specific saturated fatty acids (SFAs) in food. We explored the effects of cheese and meat as sources of SFAs or isocaloric replacement with carbohydrates on blood lipids, lipoproteins, and fecal excretion of fat and bile acids. The study was a randomized, crossover, open-label intervention in 14 overweight postmenopausal women. Three full-diet periods of 2-wk duration were provided separated by 2-wk washout periods. The isocaloric diets were as follows: 1) a high-cheese (96-120-g) intervention [i.e., intervention containing cheese (CHEESE)], 2) a macronutrient-matched nondairy, high-meat control [i.e., nondairy control with a high content of high-fat processed and unprocessed meat in amounts matching the saturated fat content from cheese in the intervention containing cheese (MEAT)], and 3) a nondairy, low-fat, high-carbohydrate control (i.e., nondairy low-fat control in which the energy from cheese fat and protein was isocalorically replaced by carbohydrates and lean meat (CARB). The CHEESE diet caused a 5% higher high-density lipoprotein (HDL)-cholesterol concentration (P = 0.012), an 8% higher apo A-I concentration (P < 0.001), and a 5% lower apoB:apo A-I ratio (P = 0.008) than did the CARB diet. Also, the MEAT diet caused an 8% higher HDL-cholesterol concentration (P < 0.001) and a 4% higher apo A-I concentration (P = 0.033) than did the CARB diet. Total cholesterol, LDL cholesterol, apoB, and triacylglycerol were similar with the 3 diets. Fecal fat excretion was 1.8 and 0.9 g higher with the CHEESE diet than with CARB and MEAT diets (P < 0.001 and P = 0.004, respectively) and 0.9 g higher with the MEAT diet than with the CARB diet (P = 0.005). CHEESE and MEAT diets caused higher fecal bile acid excretion than did the CARB diet (P < 0.05 and P = 0.006, respectively). The dominant type of bile acids excreted differed between CHEESE and MEAT diets. Diets with cheese and meat as primary sources of SFAs cause higher HDL cholesterol and apo A-I and, therefore, appear to be less atherogenic than is a low-fat, high-carbohydrate diet. Also, our findings confirm that cheese increases fecal fat excretion. This trial was registered at clinicaltrials.gov as NCT01739153. © 2015 American Society for Nutrition.
Tamura, Tomoko; Inoue, Naoko; Shimizu-Ibuka, Akiko; Tadaishi, Miki; Takita, Toshichika; Arai, Soichi; Mura, Kiyoshi
2012-01-01
Feeding a high-cholesterol diet with a water-soluble peanut skin polyphenol fraction to rats reduced their plasma cholesterol level, with an increase in fecal cholesterol excretion. The hypocholesterolemic effect was greater with the lower-molecular-weight rather than higher-molecular-weight polyphenol fraction. This effect was possibly due to some oligomeric polyphenols which reduced the solubility of dietary cholesterol in intestinal bile acid-emulsified micelles.
Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice.
Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W; Wolters, Justina C; Kuivenhoven, Jan A; Tietge, Uwe J F; Brufau, Gemma; Groen, Albert K
2016-08-01
Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we investigated the effects on cholesterol metabolism in mice in detail. Surprisingly, direct measurement of whole body cholesterol synthesis revealed that cholesterol synthesis was robustly increased in statin-treated mice. Measurement of organ-specific cholesterol synthesis demonstrated that the liver is predominantly responsible for the increase in cholesterol synthesis. Excess synthesized cholesterol did not accumulate in the plasma, as plasma cholesterol decreased. However, statin treatment led to an increase in cholesterol removal via the feces. Interestingly, enhanced cholesterol excretion in response to rosuvastatin and lovastatin treatment was mainly mediated via biliary cholesterol secretion, whereas atorvastatin mainly stimulated cholesterol removal via the transintestinal cholesterol excretion pathway. Moreover, we show that plasma cholesterol precursor levels do not reflect cholesterol synthesis rates during statin treatment in mice. In conclusion, cholesterol synthesis is paradoxically increased upon statin treatment in mice. However, statins potently stimulate the excretion of cholesterol from the body, which sheds new light on possible mechanisms underlying the cholesterol-lowering effects of statins. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.
Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice
Schonewille, Marleen; Freark de Boer, Jan; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.
2016-01-01
Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we investigated the effects on cholesterol metabolism in mice in detail. Surprisingly, direct measurement of whole body cholesterol synthesis revealed that cholesterol synthesis was robustly increased in statin-treated mice. Measurement of organ-specific cholesterol synthesis demonstrated that the liver is predominantly responsible for the increase in cholesterol synthesis. Excess synthesized cholesterol did not accumulate in the plasma, as plasma cholesterol decreased. However, statin treatment led to an increase in cholesterol removal via the feces. Interestingly, enhanced cholesterol excretion in response to rosuvastatin and lovastatin treatment was mainly mediated via biliary cholesterol secretion, whereas atorvastatin mainly stimulated cholesterol removal via the transintestinal cholesterol excretion pathway. Moreover, we show that plasma cholesterol precursor levels do not reflect cholesterol synthesis rates during statin treatment in mice. In conclusion, cholesterol synthesis is paradoxically increased upon statin treatment in mice. However, statins potently stimulate the excretion of cholesterol from the body, which sheds new light on possible mechanisms underlying the cholesterol-lowering effects of statins. PMID:27313057
Red blood cells play a role in reverse cholesterol transport.
Hung, Kimberly T; Berisha, Stela Z; Ritchey, Brian M; Santore, Jennifer; Smith, Jonathan D
2012-06-01
Reverse cholesterol transport (RCT) involves the removal of cholesterol from peripheral tissue for excretion in the feces. Here, we determined whether red blood cells (RBCs) can contribute to RCT. We performed a series of studies in apolipoprotein AI-deficient mice where the high-density lipoprotein-mediated pathway of RCT is greatly diminished. RBCs carried a higher fraction of whole blood cholesterol than plasma in apolipoprotein AI-deficient mice, and as least as much of the labeled cholesterol derived from injected foam cells appeared in RBCs compared with plasma. To determine whether RBCs mediate RCT to the fecal compartment, we measured RCT in anemic and control apolipoprotein AI-deficient mice and found that anemia decreased RCT to the feces by over 35% after correcting for fecal mass. Transfusion of [(3)H]cholesterol-labeled RBCs led to robust delivery of the labeled cholesterol to the feces in apolipoprotein AI-deficient hosts. In wild-type mice, the majority of the blood cholesterol mass, as well as [(3)H]cholesterol derived from the injected foam cells, was found in plasma, and anemia did not significantly alter RCT to the feces after correction for fecal mass. The RBC cholesterol pool is dynamic and facilitates RCT of peripheral cholesterol to the feces, particularly in the low high-density lipoprotein state.
Zhao, Yimin; Liu, Jianhui; Hao, Wangjun; Zhu, Hanyue; Liang, Ning; He, Zouyan; Ma, Ka Ying; Chen, Zhen-Yu
2017-12-20
Previous studies have shown that short-chain fatty acids (SCFAs) are capable of decreasing plasma cholesterol. However, the relative plasma-cholesterol-lowering activity of individual SCFAs and the underlying mechanisms by which SCFAs decrease plasma cholesterol remain largely unknown. The present study was done to compare the plasma-cholesterol-lowering potencies of four common SCFAs with 2-5 carbons and to investigate their interactions with gene expressions of key regulatory factors involved in cholesterol metabolism. For 6 weeks, five groups of male Golden hamsters were fed either a control high-cholesterol diet (HCD) or one of the four experimental HCDs containing 0.5 mol of acetate (Ac), propionate (Pr), butyrate (Bu), or valerate (Va) per kilogram of the diet. The results showed that Ac, Pr, and Bu significantly reduced plasma total cholesterol (TC) by 24, 18, and 17% (P < 0.05), respectively. All four SCFAs could decrease non-HDL cholesterol (non-HDL-C) and the non-HDL-C/HDL-C ratio. The addition of Ac, Pr, or Bu into the diet significantly promoted fecal excretion of bile acids by 121, 113, or 120% (P < 0.05), respectively, and upregulated the gene expressions of sterol-regulatory-element-binding protein 2 (SREBP2), low-density-lipoprotein receptor (LDLR), and cholesterol 7α-hydroxylase (CYP7A1) in the liver. It was concluded that SCFAs with 2-4 carbons (Ac, Pr, and Bu) are more hypocholesterolemic than Va, which has 5 carbons, via enhancing fecal excretion of bile acids and promoting the hepatic uptake of cholesterol from the blood.
Zanotti, Ilaria; Greco, Daniela; Lusardi, Giulia; Zimetti, Francesca; Potì, Francesco; Arnaboldi, Lorenzo; Corsini, Alberto; Bernini, Franco
2013-01-01
Despite the efficacy in reducing acute rejection events in organ transplanted subjects, long term therapy with cyclosporine A is associated with increased atherosclerotic cardiovascular morbidity. We studied whether this drug affects the antiatherogenic process of the reverse cholesterol transport from macrophages in vivo. Cyclosporine A 50 mg/kg/d was administered to C57BL/6 mice by subcutaneous injection for 14 days. Macrophage reverse cholesterol transport was assessed by following [(3)H]-cholesterol mobilization from pre-labeled intraperitoneally injected macrophages, expressing or not apolipoprotein E, to plasma, liver and feces. The pharmacological treatment significantly reduced the amount of radioactive sterols in the feces, independently on the expression of apolipoprotein E in the macrophages injected into recipient mice and in absence of changes of plasma levels of high density lipoprotein-cholesterol. Gene expression analysis revealed that cyclosporine A inhibited the hepatic levels of cholesterol 7-alpha-hydroxylase, concomitantly with the increase in hepatic and intestinal expression of ATP Binding Cassette G5. However, the in vivo relevance of the last observation was challenged by the demonstration that mice treated or not with cyclosporine A showed the same levels of circulating beta-sitosterol. These results indicate that treatment of mice with cyclosporine A impaired the macrophage reverse cholesterol transport by reducing fecal sterol excretion, possibly through the inhibition of cholesterol 7-alpha-hydroxylase expression. The current observation may provide a potential mechanism for the high incidence of atherosclerotic coronary artery disease following the immunosuppressant therapy in organ transplanted recipients.
Carden, Trevor J; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P
2015-01-01
Background: Elevated concentrations of LDL cholesterol are associated with the development of atherosclerosis and therefore are considered an important target for intervention to prevent cardiovascular diseases. The inhibition of cholesterol absorption in the small intestine is an attractive approach to lowering plasma cholesterol, one that is addressed by drug therapy as well as dietary supplementation with plant sterols and plant sterol esters (PSEs). Objective: This study was conducted to test the hypothesis that the cholesterol-lowering effects of PSE require hydrolysis to free sterols (FSs). Methods: Male Syrian hamsters were fed atherogenic diets (AIN-93M purified diet containing 0.12% cholesterol and 8% coconut oil) to which one of the following was added: no PSEs or ethers (control), 5% sterol stearate esters, 5% sterol palmitate esters (PEs), 5% sterol oleate esters (OEs), 5% sterol stearate ethers (STs; to mimic nonhydrolyzable PSE), or 3% FSs plus 2% sunflower oil. The treatments effectively created a spectrum of PSE hydrolysis across which cholesterol metabolism could be compared. Metabolic measurements included cholesterol absorption, plasma and liver lipid concentration, and fecal neutral sterol and bile acid excretion. Results: The STs and the PEs and SEs were poorly hydrolyzed (1.69–4.12%). In contrast, OEs were 88.3% hydrolyzed. The percent hydrolysis was negatively correlated with cholesterol absorption (r = −0.85; P < 0.0001) and positively correlated with fecal cholesterol excretion (r = 0.92; P < 0.0001), suggesting that PSE hydrolysis plays a central role in the cholesterol-lowering properties of PSE. Conclusions: Our data on hamsters suggest that PSE hydrolysis and the presence of FSs is necessary to induce an optimum cholesterol-lowering effect and that poorly hydrolyzed PSEs may lower cholesterol through an alternative mechanism than that of competition with cholesterol for micelle incorporation. PMID:25972524
Carden, Trevor J; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P
2015-07-01
Elevated concentrations of LDL cholesterol are associated with the development of atherosclerosis and therefore are considered an important target for intervention to prevent cardiovascular diseases. The inhibition of cholesterol absorption in the small intestine is an attractive approach to lowering plasma cholesterol, one that is addressed by drug therapy as well as dietary supplementation with plant sterols and plant sterol esters (PSEs). This study was conducted to test the hypothesis that the cholesterol-lowering effects of PSE require hydrolysis to free sterols (FSs). Male Syrian hamsters were fed atherogenic diets (AIN-93M purified diet containing 0.12% cholesterol and 8% coconut oil) to which one of the following was added: no PSEs or ethers (control), 5% sterol stearate esters, 5% sterol palmitate esters (PEs), 5% sterol oleate esters (OEs), 5% sterol stearate ethers (STs; to mimic nonhydrolyzable PSE), or 3% FSs plus 2% sunflower oil. The treatments effectively created a spectrum of PSE hydrolysis across which cholesterol metabolism could be compared. Metabolic measurements included cholesterol absorption, plasma and liver lipid concentration, and fecal neutral sterol and bile acid excretion. The STs and the PEs and SEs were poorly hydrolyzed (1.69-4.12%). In contrast, OEs were 88.3% hydrolyzed. The percent hydrolysis was negatively correlated with cholesterol absorption (r = -0.85; P < 0.0001) and positively correlated with fecal cholesterol excretion (r = 0.92; P < 0.0001), suggesting that PSE hydrolysis plays a central role in the cholesterol-lowering properties of PSE. Our data on hamsters suggest that PSE hydrolysis and the presence of FSs is necessary to induce an optimum cholesterol-lowering effect and that poorly hydrolyzed PSEs may lower cholesterol through an alternative mechanism than that of competition with cholesterol for micelle incorporation. © 2015 American Society for Nutrition.
Lin, Xiaobo; Racette, Susan B.; Lefevre, Michael; Ma, Lina; Spearie, Catherine Anderson; Steger-May, Karen; Ostlund, Richard E.
2011-01-01
Background Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that ezetimibe combined with phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo + phytosterol placebo, (2) 10 mg ezetimibe/day + phytosterol placebo, and (3) 10 mg ezetimibe/day + 2.5 g phytosterols/day, for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and LDL cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/day, 95% CI 368 to 828) relative to control (2161 mg/day, 1112 to 3209) and ezetimibe alone (1054 mg/day, 546 to 1561, both P < 0.0001). Fecal cholesterol excretion was significantly greater (P < 0.0001) with combined treatment (962 mg/day, 757 to 1168) relative to control (505 mg/day, 386 to 625) and ezetimibe alone (794 mg/day, 615 to 973). Plasma LDL cholesterol values during control, ezetimibe alone, and ezetimibe + phytosterols averaged 129 (95% CI: 116 to 142), 108 (97 to 119), and 101 (90 to 112) mg/dL (P < 0.0001 relative to control). Conclusion The addition of phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma LDL cholesterol. The large cumulative action of combined dietary and pharmacologic treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. PMID:21768544
Tea Dietary Fiber Improves Serum and Hepatic Lipid Profiles in Mice Fed a High Cholesterol Diet.
Guo, Wenxin; Shu, Yang; Yang, Xiaoping
2016-06-01
Tea dietary fiber (TDF) was prepared from tea residues and modified to get cellulose-modified TDF (CTDF) by cellulase or micronized TDF (MTDF) by ultrafine grinding. The in vitro lipid-binding capacities of the three fibers and their effects on serum and hepatic lipid profiles in mice fed a high cholesterol diet were evaluated. The results showed that the three fibers had excellent lipid-binding capacities, and the cholesterol- and sodium cholate-binding capacities of CTDF and MTDF were significantly higher than those of TDF. Animal studies showed that, compared to model control, the three fibers significantly decreased mice average daily gain, gain: feed, and liver index, reduced total cholesterol (TC), triglyceride, and low density lipoprotein-cholesterol of serum and liver, increased serum and hepatic high density lipoprotein-cholesterol to TC ratio, and promoted the excretion of fecal lipids, and they also significantly increased the activities of superoxide dismutase and glutathione peroxidase of serum and liver, and decreased lipid peroxidation; moreover, the effects of CTDF and MTDF were better than that of TDF. It was concluded that the three fibers could improve serum and hepatic lipid profiles in mice fed a high cholesterol diet and the mechanism of action might be due to the promotion of fecal excretion of lipids through their lipid-binding ability and the inhibition of lipid peroxidation. These findings suggest that tea dietary fiber has the potential to be used as a functional ingredient to control cardiovascular disease.
Tomotake, Hiroyuki; Yamamoto, Naoe; Yanaka, Noriyuki; Ohinata, Hiroshi; Yamazaki, Rikio; Kayashita, Jun; Kato, Norihisa
2006-02-01
This study evaluated the physiologic properties of high protein buckwheat flour (PBF) by examining its effects on serum cholesterol and body fat in rats and on cholesterol gallstone formation in mice. Animals were fed experimental diets that contained casein, buckwheat protein extract (BWP), or PBF as a protein source (net protein content 200 g/kg). In experiment 1, consumption of PBF and BWP for 10 d caused 33% and 31% decreases, respectively, in serum cholesterol of rats fed cholesterol-enriched diets when compared with consumption of casein (P < 0.05). Dietary PBF caused a significant decrease in liver cholesterol, whereas dietary BWP caused only a slight decrease (P > 0.05). Fecal excretion of neutral and acidic steroids in the PBF group was significantly higher than those in the BWP and casein groups. In experiment 2, consumption of PBF for 10 d significantly suppressed adipose tissue weight and hepatic activity of fatty acid synthase in rats fed cholesterol-free diets compared with consumption of casein (P < 0.05), whereas that of BWP for this period caused only a slight decrease in adipose tissue weight (P > 0.05). In experiment 3, dietary PBF and BWP significantly decreased the incidence of cholesterol gallstones and lithogenic index in mice fed cholesterol-enriched diets for 27 d, which was associated with increased fecal excretion of acidic steroids. This study demonstrated that PBF has strong activities against hypercholesterolemia, obesity, and gallstone formation, suggesting a potential usefulness of PBF as functional ingredient.
Chou, Tsui-Wei; Ma, Chien-Ya; Cheng, Hsing-Hsien; Chen, Ya-Yen; Lai, Ming-Hoang
2009-01-01
The aim of this study was to determine the effects of rice bran oil (RBO) on lipid metabolism and insulin resistance in rats with streptozotocin/nicotinamide-induced type 2 diabetes mellitus (T2DM). Rats were divided into two groups: the control group (15% soybean oil, contains 0 g γ-oryzanol and 0 g γ-tocotrienol/150 g oil for 5 weeks) and the RBO group (15% RBO, contains 5.25 g γ-oryzanol and 0.9 g γ-tocotrienol/150 g oil for 5 weeks). Compared with the control group, the RBO group had a lower plasma nonesterified fatty acid concentration, ratio of total to high-density-lipoprotein cholesterol, hepatic cholesterol concentration, and area under the curve for insulin. The RBO group had a higher high-density-lipoprotein cholesterol concentration and greater excretion of fecal neutral sterols and bile acid than did the control group. RBO may improve lipid abnormalities, reduce the atherogenic index, and suppress the hyperinsulinemic response in rats with streptozotocin/nicotinamide-induced T2DM. In addition, RBO can lead to increased fecal neutral sterol and bile acid excretion. PMID:19590704
Freark de Boer, Jan; Annema, Wijtske; Schreurs, Marijke; van der Veen, Jelske N.; van der Giet, Markus; Nijstad, Niels; Kuipers, Folkert; Tietge, Uwe J. F.
2012-01-01
Type I diabetes mellitus (T1DM) increases atherosclerotic cardiovascular disease; however, the underlying pathophysiology is still incompletely understood. We investigated whether experimental T1DM impacts HDL-mediated reverse cholesterol transport (RCT). C57BL/6J mice with alloxan-induced T1DM had higher plasma cholesterol levels (P < 0.05), particularly within HDL, and increased hepatic cholesterol content (P < 0.001). T1DM resulted in increased bile flow (2.1-fold; P < 0.05) and biliary secretion of bile acids (BA, 10.5-fold; P < 0.001), phospholipids (4.5-fold; P < 0.001), and cholesterol (5.5-fold; P < 0.05). Hepatic cholesterol synthesis was unaltered, whereas BA synthesis was increased in T1DM (P < 0.001). Mass fecal BA output was significantly higher in T1DM mice (1.5-fold; P < 0.05), fecal neutral sterol excretion did not change due to increased intestinal cholesterol absorption (2.1-fold; P < 0.05). Overall in vivo macrophage-to-feces RCT, using [3H]cholesterol-loaded primary mouse macrophage foam cells, was 20% lower in T1DM (P < 0.05), mainly due to reduced tracer excretion within BA (P < 0.05). In vitro experiments revealed unchanged cholesterol efflux toward T1DM HDL, whereas scavenger receptor class BI-mediated selective uptake from T1DM HDL was lower in vitro and in vivo (HDL kinetic experiments) (P < 0.05), conceivably due to increased glycation of HDL-associated proteins (+65%, P < 0.01). In summary, despite higher mass biliary sterol secretion T1DM impairs macrophage-to-feces RCT, mainly by decreasing hepatic selective uptake, a mechanism conceivably contributing to increased cardiovascular disease in T1DM. PMID:22180634
Liu, Yanjun; Shi, Di; Tian, Yingying; Liu, Yuntao; Zhan, Qiping; Xu, Jie; Wang, Jingfeng; Xue, Changhu
2017-02-01
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Disturbed cholesterol metabolism plays a crucial role in the development of NAFLD. The present study was conducted to evaluate the effects of EPA-PC extracted from sea cucumber on liver steatosis and cholesterol metabolism in NAFLD. Male Wistar rats were randomly divided into seven groups (normal control group, model group, lovastatin group, low- and high-dose EPA groups, and low- and high-dose EPA-PC groups). Model rats were established by administering a diet containing 1% orotic acid. To determine the possible cholesterol metabolism promoting mechanism of EPA-PC, we analyzed the transcription of key genes and transcriptional factors involved in hepatic cholesterol metabolism. EPA-PC dramatically alleviated hepatic lipid accumulation, reduced the serum TC concentration, and elevated HDLC levels in NAFLD rats. Fecal neutral cholesterol excretion was also promoted by EPA-PC administration. Additionally, EPA-PC decreased the mRNA expression of hydroxymethyl glutaric acid acyl (HMGR) and cholesterol 7α-hydroxylase (CYP7A), and increased the transcription of sterol carrying protein 2 (SCP2). Moreover, EPA-PC stimulated the transcription of peroxisome proliferators-activated receptor α (PPARα) and adenosine monophosphate activated protein kinase (AMPK) as well as its modulators, liver kinase B1 (LKB1) and Ca 2+ /calmodulin-dependent kinase kinase (CAMKK). Based on the results, the promoting effects of EPA-PC on NAFLD may be partly associated with the suppression of cholesterol synthesis via HMGR inhibition and the enhancement of fecal cholesterol excretion through increased SCP2 transcription. The underlying mechanism may involve stimulation of PPARα and AMPK.
Quifer-Rada, Paola; Choy, Ying Yng; Calvert, Christopher C; Waterhouse, Andrew L; Lamuela-Raventos, Rosa M
2016-10-01
This work aims to evaluate changes in the fecal metabolomic profile due to grape seed extract (GSE) intake by untargeted and targeted analysis using high resolution mass spectrometry in conjunction with multivariate statistics. An intervention study with six crossbred female pigs was performed. The pigs followed a standard diet for 3 days, then they were fed with a supplemented diet containing 1% (w/w) of MegaNatural® Gold grape seed extract for 6 days. Fresh pig fecal samples were collected daily. A combination of untargeted high resolution mass spectrometry, multivariate analysis (PLS-DA), data-dependent MS/MS scan, and accurate mass database matching was used to measure the effect of the treatment on fecal composition. The resultant PLS-DA models showed a good discrimination among classes with great robustness and predictability. A total of 14 metabolites related to the GSE consumption were identified including biliary acid, dicarboxylic fatty acid, cholesterol metabolites, purine metabolites, and eicosanoid metabolites among others. Moreover, targeted metabolomics using GC-MS showed that cholesterol and its metabolites fecal excretion was increased due to the proanthocyanidins from grape seed extract. The results show that oligomeric procyanidins from GSE modifies bile acid and steroid excretion, which could exert a hypocholesterolemic effect. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Asai, Saori; Kusada, Mio; Watanabe, Suzuyo; Kawashima, Takuji; Nakamura, Tadashi; Shimada, Masaya; Goto, Tsuyoshi; Nagaoka, Satoshi
2014-01-01
Royal jelly (RJ) intake lowers serum cholesterol levels in animals and humans, but the active component in RJ that lowers serum cholesterol level and its molecular mechanism are unclear. In this study, we set out to identify the bile acid-binding protein contained in RJ, because dietary bile acid-binding proteins including soybean protein and its peptide are effective in ameliorating hypercholesterolemia. Using a cholic acid-conjugated column, we separated some bile acid-binding proteins from RJ and identified the major RJ protein 1 (MRJP1), MRJP2, and MRJP3 as novel bile acid-binding proteins from RJ, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Purified MRJP1, which is the most abundant protein of the bile acid-binding proteins in RJ, exhibited taurocholate-binding activity in vitro. The micellar solubility of cholesterol was significantly decreased in the presence of MRJP1 compared with casein in vitro. Liver bile acids levels were significantly increased, and cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein tended to increase by MRJP1 feeding compared with the control. CYP7A1 mRNA and protein levels were significantly increased by MRJP1 tryptic hydrolysate treatment compared with that of casein tryptic hydrolysate in hepatocytes. MRJP1 hypocholesterolemic effect has been investigated in rats. The cholesterol-lowering action induced by MRJP1 occurs because MRJP1 interacts with bile acids induces a significant increase in fecal bile acids excretion and a tendency to increase in fecal cholesterol excretion and also enhances the hepatic cholesterol catabolism. We have identified, for the first time, a novel hypocholesterolemic protein, MRJP1, in RJ. Interestingly, MRJP1 exhibits greater hypocholesterolemic activity than the medicine β-sitosterol in rats. PMID:25144734
Suanarunsawat, Thamolwan; Devakul Na Ayutthaya, Watcharaporn; Songsak, Thanapat; Thirawarapan, Suwan; Poungshompoo, Somlak
2011-01-01
The present study was conducted to investigate the lipid-lowering and antioxidative activities of Ocimum sanctum L. (OS) leaf extracts in liver and heart of rats fed with high-cholesterol (HC) diet for seven weeks. The results shows that OS suppressed the high levels of serum lipid profile and hepatic lipid content without significant effects on fecal lipid excretion. Fecal bile acids excretion was increased in HC rats treated with OS. The high serum levels of TBARS as well as AST, ALT, AP, LDH, CK-MB significantly decreased in HC rats treated with OS. OS suppressed the high level of TABARS and raised the low activities of GPx and CAT without any impact on SOD in the liver. As for the cardiac tissues, OS lowered the high level of TABARS, and raised the activities of GPx, CAT, and SOD. Histopathological results show that OS preserved the liver and myocardial tissues. It can be concluded that OS leaf extracts decreased hepatic and serum lipid profile, and provided the liver and cardiac tissues with protection from hypercholesterolemia. The lipid-lowering effect is probably due to the rise of bile acids synthesis using cholesterol as precursor, and antioxidative activity to protect liver from hypercholesterolemia. PMID:21949899
Corradini, Stefano Ginanni; Eramo, Annarita; Lubrano, Carla; Spera, Giovanni; Cornoldi, Alessandra; Grossi, Antonio; Liguori, Francesca; Siciliano, Maria; Pisanelli, Massimo Codacci; Salen, Gerald; Batta, Ashok Kumir; Attili, Adolfo Francesco; Badiali, Marco
2005-03-01
The presence of hypercholesterolemia is currently not considered a selection criteria for performing gastric restrictive or diversionary bariatric surgery. We prospectively investigated the effects of the bilio-intestinal bypass (BI-bypass) with a wide cholecysto-jejunal anastomosis and of adjustable gastric banding (AGB) on blood lipid concentrations in obese patients. To clarify the mechanism of the hypocholesterolemic effect of the BI-bypass, daily fecal sterol excretion was measured by gas-liquid chromatography (GLC). At 1 year after BI-bypass compared to baseline, the hypercholesterolemic (n=18) and the normocholesterolemic (n=19) patients significantly reduced total (-38% and -27%, respectively), LDL (-47% and -24%, respectively) and HDL (-11% and -13%, respectively) cholesterol and total / HDL cholesterol ratio (-25% and -13%, respectively). At 1 year after AGB, the total / HDL cholesterol ratio was significantly decreased (-11%) compared to baseline in hypercholesterolemic (n=12) but not in normocholesterolemic (n=6) patients, while total and LDL cholesterol were not affected in both groups. At 3 years after BI-bypass compared to baseline, the hypercholesterolemic (n=9) and the normocholesterolemic (n=11) patients significantly reduced total (-43% and -28%, respectively) and LDL (-53% and -29%, respectively) cholesterol and total / HDL cholesterol ratio (-38% and -21%, respectively). The BI-bypass induced a significant (P <0.005; n=7) 6-fold increase in mean fecal cholesterol output. The BI-bypass but not the AGB leads to a persistent and marked beneficial effect on blood LDL cholesterol associated with an increased cholesterol fecal output. BI-bypass but not AGB is indicated in morbidly obese patients with hypercholesterolemia.
Wilson, T A; DeSimone, A P; Romano, C A; Nicolosi, R J
2000-09-01
The aims of this study were to compare the cholesterol-lowering properties of corn fiber oil (CFO) to corn oil (CO), whether the addition of soy stanols or soy sterols to CO at similar levels in CFO would increase CO's cholesterol-lowering properties, and the mechanism(s) of action of these dietary ingredients. Fifty male Golden Syrian hamsters were divided into 5 groups of 10 hamsters each, based on similar plasma total cholesterol (TC) levels. The first group of hamsters was fed a chow-based hypercholesterolemic diet containing either 5% coconut oil + 0.24% cholesterol (coconut oil), 5% CO, 5% CFO, 5% CO + 0.6% soy sterols (sterol), or 5% CO + 0.6% soy stanols (stanol) in place of the coconut oil for 4 weeks. The stanol diet significantly inhibited the elevation of plasma TC compared to all other dietary treatments. Also, the CFO and sterol diets significantly inhibited the elevation of plasma TC compared to the CO and coconut oil diets. The CFO, sterol, and stanol diets significantly inhibited the elevation of plasma non-high density lipoprotein cholesterol compared to the CO and coconut oil diets. The stanol diet significantly inhibited the elevation of plasma high density lipoprotein cholesterol (HDL-C) compared to all other dietary treatments. The sterol diet significantly inhibited the elevation of plasma HDL-C compared to the CO and coconut oil diets, whereas the CFO diet significantly inhibited the elevation of plasma HDL-C compared to the coconut oil diet only. No differences were observed between the CFO and CO for plasma HDL-C. There were no differences observed between groups for plasma triglycerides. The CO and CFO diets had significantly less hepatic TC compared to the coconut oil, sterol, and stanol diets. The CO and CFO diets had significantly less hepatic free cholesterol compared to the sterol and stanol diets but not compared to the coconut oil diet; whereas the coconut oil and sterol diets had significantly less hepatic free cholesterol compared to the stanol diet. The CFO, sterol, and stanol diets excreted significantly more fecal cholesterol compared to the coconut oil and CO diets. In summary, CFO reduces plasma and hepatic cholesterol concentrations and increases fecal cholesterol excretion greater than CO through some other mechanism(s) in addition to increase dietary sterols and stanols-possibly oryzanols.
Mechanism for the cholesterol-lowering action of egg white protein in rats.
Matsuoka, Ryosuke; Kimura, Mamoru; Muto, Ayano; Masuda, Yasunobu; Sato, Masao; Imaizumi, Katsumi
2008-06-01
Eggs are a popular source of dietary cholesterol, but their consumption does not necessarily result in an increased serum cholesterol concentration. We investigated the cholesterol-lowering activity of egg white protein (EWP) and its potential mechanism in rats. The consumption of EWP resulted in a decreased concentration of cholesterol in the serum, liver and intestinal mucosa. The excretion of fecal neutral sterols and bile acids was greater by rats fed with EWP than by those fed with casein. The ratio of cholesterol and bile acids in the micellar phase to those in the solid phase was lower in the intestinal contents from rats fed with EWP than from those fed with casein. These results suggest that the cholesterol-lowering activity of EWP can be attributed to lowering the cholesterol absorption by intervening in the micellar formation in the intestines.
Yamato, Mayumi; Shiba, Takeshi; Ide, Tomomi; Seri, Naoko; Kudo, Wataru; Ando, Makoto; Yamada, Ken-ichi; Kinugawa, Shintaro; Tsutsui, Hiroyuki
2012-01-01
Tumor necrosis factor-α (TNF-α) is one of the main mediators of inflammatory response activated by fatty acids in obesity, and this signaling through TNF-α receptor (TNFR) is responsible for obesity-associated insulin resistance. Recently, TNF-α has shown to affect lipid metabolism including the regulation of lipase activity and bile acid synthesis. However, there is scanty in vivo evidence for the involvement of TNF-α in this process, and the mechanistic role of TNFR remains unclear. In this study, TNFR2 knockout mice (R2KO) and wild-type (WT) mice were fed commercial normal diet (ND) or high-fat diet (HFD) for 8 weeks. In R2KO/HFD mice, the increase in body weight and the accumulation of fat were significantly ameliorated compared with WT/HFD mice in association with the decrease in plasma total cholesterol (137.7±3.1 vs. 98.6±3.1 mg/dL, P<0.005), glucose (221.9±14.7 vs. 167.3±8.1 mg/dL, P<0.01), and insulin (5.1±0.3 vs. 3.4±0.3 ng/mL, P<0.05). Fecal excretion of lipid contents was significantly increased in R2KO mice. In R2KO/HFD mice, the decrease in hepatic cholesterol-7a-hydroxylase activity, the rate-limiting enzyme in bile acid synthesis, was inhibited (1.7±0.2 vs. 8.1±1.0 pmol/min/mg protein, P<0.01). These results suggested that HFD-induced obesity with metabolic derangements could be ameliorated in mice lacking TNF-α receptor 2 via increasing fecal bile acid and lipid content excretion. Therefore, TNF-α signaling through TNFR2 is essentially involved in the bile acid synthesis and excretion of lipids, resulting in its beneficial effects.
Dumas, Laurent S; Briand, François; Clerc, Romain; Brousseau, Emmanuel; Montemagno, Christopher; Ahmadi, Mitra; Bacot, Sandrine; Soubies, Audrey; Perret, Pascale; Riou, Laurent M; Devoogdt, Nick; Lahoutte, Tony; Barone-Rochette, Gilles; Fagret, Daniel; Ghezzi, Catherine; Sulpice, Thierry; Broisat, Alexis
2017-07-01
The addition of ezetimibe, an intestinal cholesterol absorption inhibitor, to statin therapy has recently shown clinical benefits in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial by reducing low-density-lipoprotein (LDL) cholesterol levels more than statin therapy alone. Here, we investigated the mechanisms by which inhibition of intestinal cholesterol absorption might contribute to the clinically observed reduction in cardiovascular events by evaluating its effect on inflammatory plaque development in apolipoprotein E -/- mice. Methods: Apolipoprotein E -/- mice were fed the Paigen diet (1.25% cholesterol, 0.5% cholic acid, and 15% fat) without or with ezetimibe (7 mg/kg/d) for 6 wk. In a first set of mice ( n = 15), we intravenously injected 3 H-cholesteryl oleate-labeled human LDL to test whether ezetimibe promotes LDL-derived cholesterol fecal excretion. In a second set ( n = 20), we used the imaging agent 99m Tc-cAbVCAM1-5 to evaluate expression of an inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1), in atherosclerotic plaques. In a third set ( n = 21), we compared VCAM-1 expression with 99m Tc-cAbVCAM1-5 uptake in various tissues. Results: Mice treated with ezetimibe showed a 173% higher LDL-cholesteryl ester plasma disappearance rate ( P < 0.001 vs. control) after 3 H-cholesteryl oleate-labeled LDL injection. At 96 h after injection, the hepatic fraction of 3 H-tracer was 61% lower in mice treated with ezetimibe ( P < 0.001). Meanwhile, LDL-derived 3 H-cholesterol excretion in the feces was 107% higher ( P < 0.001). The antiatherogenic effect of ezetimibe monitored by 99m Tc-cAbVCAM1-5 SPECT showed a 49% reduction in aortic tracer uptake (percentage injected dose per cubic centimeter, 0.95 ± 0.04 vs. 1.87 ± 0.11; P < 0.01). In addition to hypercholesterolemia, the proinflammatory Paigen diet significantly increased VCAM-1 expression with respect to the control group in various tissues, including the aorta, and this expression correlated strongly with 99m Tc-cAbVCAM1-5 uptake ( r = 0.75; P < 0.05). Conclusion: Inhibition of intestinal cholesterol absorption with ezetimibe promotes antiatherosclerotic effects through increased LDL cholesterol catabolism and LDL-derived cholesterol fecal excretion and reduces inflamed atherosclerotic plaques. These mechanisms may contribute to the benefits of adding ezetimibe to a statin therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.
Matsuo, M
2000-02-01
To popularize defatted soy ontjom (DSB-ontjom, soy product fermented with Neurospora intermedia) as a new food, I examined the plasma cholesterol-reducing effects of DSB-ontjom and DSB in rats fed cholesterol-free diets and compared the efficiencies of these effects. DSB-ontjom greatly reduced the plasma cholesterol level and increased fecal steroid excretion as compared to DSB. DSB-ontjom was rich in pepsin-resistant protein having a high bile acid binding capacity and was abundant in isoflavone-aglycones, especially daizein. The dietary fiber (DF) of DSB-ontjom stimulated the production of short-chain fatty acids (SCFAs) by intestinal microflora. The effect of DSB-ontjom on plasma cholesterol reduction was attributed to the collaborative effects of pepsin-resistant-protein, isoflavone-aglycones and SCFA-producing DF in DSB-ontjom.
Characteristics of human hypo- and hyperresponders to dietary cholesterol.
Katan, M B; Beynen, A C
1987-03-01
The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.
Wilson, Thomas A; Nicolosi, Robert J; Delaney, Bryan; Chadwell, Kim; Moolchandani, Vikas; Kotyla, Timothy; Ponduru, Sridevi; Zheng, Guo-Hua; Hess, Richard; Knutson, Nathan; Curry, Leslie; Kolberg, Lore; Goulson, Melanie; Ostergren, Karen
2004-10-01
Consumption of concentrated barley beta-glucan lowers plasma cholesterol because of its soluble dietary fiber nature. The role of molecular weight (MW) in lowering serum cholesterol is not well established. Prior studies showed that enzymatic degradation of beta-glucan eliminates the cholesterol-lowering activity; however, these studies did not evaluate the MW of the beta-glucan. The current study was conducted to evaluate whether barley beta-glucan concentrates, partially hydrolyzed to reduce MW, possess cholesterol-lowering and antiatherogenic activities. The reduced MW fraction was compared with a high MW beta-glucan concentrate from the same barley flour. Concentrated beta-glucan preparations were evaluated in Syrian Golden F(1)B hamsters fed a hypercholesterolemic diet (HCD) with cholesterol, hydrogenated coconut oil, and cellulose. After 2 wk, hamsters were fed HCD or diets that contained high or reduced MW beta-glucan at a concentration of 8 g/100 g at the expense of cellulose. Decreases in plasma total cholesterol (TC) and non-HDL-cholesterol (non-HDL-C) concentrations occurred in the hamsters fed reduced MW and high MW beta-glucan diets. Plasma HDL-C concentrations did not differ. HCD-fed hamsters had higher plasma triglyceride concentrations. Liver TC, free cholesterol, and cholesterol ester concentrations did not differ. Aortic cholesterol ester concentrations were lower in the reduced MW beta-glucan-fed hamsters. Consumption of either high or reduced MW beta-glucan increased concentrations of fecal total neutral sterols and coprostanol, a cholesterol derivative. Fecal excretion of cholesterol was greater than in HCD-fed hamsters only in those fed the reduced MW beta-glucan. Study results demonstrate that the cholesterol-lowering activity of barley beta-glucan may occur at both lower and higher MW.
Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.
Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans
2018-03-01
Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Cholesterol kinetic effects of dietary fat in CBA/J and C57BR/cdJ mice
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stewart, J.; Kuan, Soniu; Seagrave, R.
1990-02-26
Small differences in dietary fats cause marked differences in cholesterol metabolism in different strains of mice. CBA/J mice adjust HMGCOA reductase activity and C57BR/cdJ mice change fecal excretion of cholesterol. Phenomenological compartmental modeling of movement of 4{sup 14}C-cholesterol in the two strains of mice fed 40 en % fat, P/S = 0.24 (SFA) or 30 en % fat, P/S = 1 (PUFA) was used to analyze rates of movement between serum, liver, heart, and carcass. The C57 mice had slower movement between all compartments than CBA. Residence times in tissues were longer in mice fed SFA than those fed PUFAmore » diet. The kinetic results are in agreement with the organ concentrations and enzyme activities measured.« less
Meissner, Maxi; Lombardo, Elisa; Havinga, Rick; Tietge, Uwe J F; Kuipers, Folkert; Groen, Albert K
2011-10-01
Regular physical activity decreases the risk for atherosclerosis but underlying mechanisms are not fully understood. We questioned whether voluntary wheel running provokes specific modulations in cholesterol turnover that translate into a decreased atherosclerotic burden in hypercholesterolemic mice. Male LDLR-deficient mice (8 weeks old) had either access to a voluntary running wheel for 12 weeks (RUN) or remained sedentary (CONTROL). Both groups were fed a western-type/high cholesterol diet. Running activity and food intake were recorded. At 12 weeks of intervention, feces, bile and plasma were collected to determine fecal, biliary and plasma parameters of cholesterol metabolism and plasma cytokines. Atherosclerotic lesion size was determined in the aortic root. RUN weighed less (∼13%) while food consumption was increased by 17% (p=0.004). Plasma cholesterol levels were decreased by 12% (p=0.035) and plasma levels of pro-atherogenic lipoproteins decreased in RUN compared to control. Running modulated cholesterol catabolism by enhancing cholesterol turnover: RUN displayed an increased biliary bile acid secretion (68%, p=0.007) and increased fecal bile acid (93%, p=0.009) and neutral sterol (33%, p=0.002) outputs compared to control indicating that reverse cholesterol transport was increased in RUN. Importantly, aortic lesion size was decreased by ∼33% in RUN (p=0.033). Voluntary wheel running reduces atherosclerotic burden in hypercholesterolemic mice. An increased cholesterol turnover, specifically its conversion into bile acids, may underlie the beneficial effect of voluntary exercise in mice. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Aqul, Amal; Lopez, Adam M.; Posey, Kenneth S.; Taylor, Anna M.; Repa, Joyce J.; Burns, Dennis K.
2014-01-01
Cholesteryl ester storage disease (CESD) results from loss-of-function mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL). Hepatomegaly and deposition of esterified cholesterol (EC) in multiple organs ensue. The present studies quantitated rates of synthesis, absorption, and disposition of cholesterol, and whole body cholesterol pool size in a mouse model of CESD. In 50-day-old lal−/− and matching lal+/+ mice fed a low-cholesterol diet, whole animal cholesterol content equalled 210 and 50 mg, respectively, indicating that since birth the lal−/− mice sequestered cholesterol at an average rate of 3.2 mg·day−1·animal−1. The proportion of the body sterol pool contained in the liver of the lal−/− mice was 64 vs. 6.3% in their lal+/+ controls. EC concentrations in the liver, spleen, small intestine, and lungs of the lal−/− mice were elevated 100-, 35-, 15-, and 6-fold, respectively. In the lal−/− mice, whole liver cholesterol synthesis increased 10.2-fold, resulting in a 3.2-fold greater rate of whole animal sterol synthesis compared with their lal+/+ controls. The rate of cholesterol synthesis in the lal−/− mice exceeded that in the lal+/+ controls by 3.7 mg·day−1·animal−1. Fractional cholesterol absorption and fecal bile acid excretion were unchanged in the lal−/− mice, but their rate of neutral sterol excretion was 59% higher than in their lal+/+ controls. Thus, in this model, the continual expansion of the body sterol pool is driven by the synthesis of excess cholesterol, primarily in the liver. Despite the severity of their disease, the median life span of the lal−/− mice was 355 days. PMID:25147230
Nicolle, Catherine; Cardinault, Nicolas; Gueux, Elyett; Jaffrelo, Lydia; Rock, Edmond; Mazur, Andrzej; Amouroux, Pierre; Rémésy, Christian
2004-08-01
It is often assumed that fruits and vegetables contribute to protect against degenerative pathologies such as cardiovascular diseases. Besides epidemiological observations, scientific evidences for their mechanism of action are scarce. In the present study, we investigated the mean term and post-prandial effects of lettuce ingestion on lipid metabolism and antioxidant protection in the rat. Feeding rats a 20% lettuce diet for 3 weeks resulted in a decrease cholesterol LDL/HDL ratio and a marked decrease of liver cholesterol levels (-41%). Concurrently, fecal total steroid excretion increased (+44%) and apparent absorption of dietary cholesterol was significantly depressed (-37%) by the lettuce diet. Lettuce diet also displayed an improvement of vitamin E/TG ratio in plasma and limited lipid peroxidation in heart as evidenced by TBARS. In post-prandial experiment, lettuce intake significantly increased both ascorbic acid and alpha-tocopherol plasma levels which contribute to improve plasma antioxidant capacity within 2 h of consumption. Other lipid-soluble antioxidants (lutein and vitamin E) may also improve the plasma antioxidant capacity. Lettuce consumption increases the total cholesterol end-products excretion and improves antioxidant status due to the richness in antioxidants (vitamins C, E and carotenoids). In our model, lettuce clearly shows a beneficial effect on lipid metabolism and on tissue oxidation. Therefore regular consumption of lettuce should contribute to improve protection against cardiovascular diseases. Copyright 2003 Elsevier Ltd.
Xanthohumol, a hop-derived prenylated flavonoid, promotes macrophage reverse cholesterol transport.
Hirata, Hiroshi; Uto-Kondo, Harumi; Ogura, Masatsune; Ayaori, Makoto; Shiotani, Kazusa; Ota, Ami; Tsuchiya, Youichi; Ikewaki, Katsunori
2017-09-01
Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increases high-density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol promotes reverse cholesterol transport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated the effects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [ 3 H]-cholesterol-labeled macrophages. Ex vivo experiments were then employed to investigate the detailed mechanism by which xanthohumol enhanced RCT. Cholesterol efflux capacity from macrophages was 1.5-fold higher in xanthohumol-fed hamsters compared with the control group. In addition, protein expression and lecithin-cholesterol acyltransferase activity in the HDL fraction were significantly higher in xanthohumol-fed hamsters compared with the control, suggesting that xanthohumol promoted HDL maturation. Hepatic transcript analysis revealed that xanthohumol increased mRNA expression of abcg8 and cyp7a1. In addition, protein expressions of liver X receptor α and bile pump export protein were increased in the liver by xanthohumol administration when compared with the control, implying that it stimulated bile acid synthesis and cholesterol excretion to feces. In conclusion, our data demonstrate that xanthohumol improves RCT in vivo through cholesterol efflux from macrophages and excretion to feces, leading to antiatherosclerosis effects. It remains to be elucidated whether enhancement of RCT by xanthohumol could prove valuable in humans. Copyright © 2017 Elsevier Inc. All rights reserved.
Stellaard, Frans
2017-01-01
The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded. PMID:28321334
Lee, Yujin; Ba, Zhaoyong; Roberts, Robert F; Rogers, Connie J; Fleming, Jennifer A; Meng, Huicui; Furumoto, Emily J; Kris-Etherton, Penny M
2017-06-29
Some probiotics have hypocholesterolemic effects in animal studies, which are mediated, in part, by increases in fecal short chain fatty acids (SCFAs). Clinical trials of probiotics on lipids/lipoproteins are inconsistent. We examined the effects of Bifidobacterium animalis subsp. lactis BB-12 ® (BB-12 ® ) (3.16 × 10 9 CFUs/day) on lipids and lipoproteins and fecal excretion of SCFAs in healthy adults. In a randomized, partially blinded, 4-period, crossover study, 30 adults (11 men, 19 women) aged 18-40 years were randomly assigned to: 1) yogurt smoothie with no BB-12 ® (YS), 2) yogurt smoothie with BB-12 ® added pre-fermentation (PRE), 3) yogurt smoothie with BB-12 ® added post-fermentation (POST), 4) BB-12 ® containing capsule (CAP). We measured serum lipids/lipoproteins, glucose, insulin, C-reactive protein (CRP), and fecal SCFAs at baseline and after each treatment period. Total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides (TGs) did not differ after the PRE, POST, and CAP periods versus the YS or between treatments. Compared to baseline, fecal acetate was significantly increased after the YS (Δ = 211.89 ± 75.87 μg/g, P = 0.007) and PRE (Δ = 204.98 ± 75.70 μg/g, P = 0.009) periods. The percent increase in fecal acetate was significantly greater after the YS versus the POST period (52.2 ± 13.2% vs. 24.5 ± 13.2%, P = 0.023). Fecal total SCFAs, propionate and butyrate did not differ between treatment periods. Fecal total SCFAs were negatively associated with TC (r = -0.22, P = 0.01), LDL-C (r = -0.24, P = 0.004), age (r = -0.33, P < 0.001), and waist circumference (r = -0.25, P = 0.003). BB-12 ® supplementation did not improve lipids, lipoproteins and total and individual fecal SCFAs. Fecal SCFAs were negatively associated with TC, LDL-C, age, and waist circumference. This trial was registered at clinicaltrials.gov as NCT01399996 .
Isoflavone-free soy protein prepared by column chromatography reduces plasma cholesterol in rats.
Fukui, Kensuke; Tachibana, Nobuhiko; Wanezaki, Satoshi; Tsuzaki, Shinichi; Takamatsu, Kiyoharu; Yamamoto, Takashi; Hashimoto, Yukio; Shimoda, Tadahisa
2002-09-25
To know whether isoflavones are responsible for the hypocholesterolemic effect of soy protein, the effect on plasma cholesterol of isoflavone-free soy protein prepared by column chromatography was examined in rats. Five-week-old male Sprague-Dawley rats were fed cholesterol-enriched AIN-93G diets containing either 20% casein (CAS), 20% soy protein isolate (SPI), 20% isoflavone-free SPI (IF-SPI), 19.7% IF-SPI + 0.3% isoflavone-rich fraction (isoflavone concentrate, IC), or 20% CAS + 0.3% IC for 2 weeks. Plasma total cholesterol concentrations of rats fed SPI and IF-SPI were comparable and were significantly lower than that of rats fed CAS. The addition of IC to the CAS and IF-SPI did not influence plasma cholesterol level. Fecal steroid excretion of the three SPI groups was higher than that of the two CAS groups, whereas the addition of IC showed no effect. Thus, a significant fraction of the cholesterol-lowering effect of SPI in rats can be attributed to the protein content, but the isoflavones and other minor constituents may also play a role.
Xie, Ping; Jia, Lin; Ma, Yinyan; Ou, Juanjuan; Miao, Hongming; Wang, Nanping; Guo, Feng; Yazdanyar, Amirfarbod; Jiang, Xian-Cheng; Yu, Liqing
2013-05-01
Controversies have arisen from recent mouse studies about the essential role of biliary sterol secretion in reverse cholesterol transport (RCT). The objective of this study was to examine the role of biliary cholesterol secretion in modulating macrophage RCT in Niemann-Pick C1-Like 1 (NPC1L1) liver only (L1(LivOnly)) mice, an animal model that is defective in both biliary sterol secretion and intestinal sterol absorption, and determine whether NPC1L1 inhibitor ezetimibe facilitates macrophage RCT by inhibiting hepatic NPC1L1. L1(LivOnly) mice were generated by crossing NPC1L1 knockout (L1-KO) mice with transgenic mice overexpressing human NPC1L1 specifically in liver. Macrophage-to-feces RCT was assayed in L1-KO and L1(LivOnly) mice injected intraperitoneally with [(3)H]-cholesterol-labeled peritoneal macrophages isolated from C57BL/6 mice. Inhibition of biliary sterol secretion by hepatic overexpression of NPC1L1 substantially reduced transport of [(3)H]-cholesterol from primary peritoneal macrophages to the neutral sterol fraction in bile and feces in L1(LivOnly) mice without affecting tracer excretion in the bile acid fraction. Ezetimibe treatment for 2 weeks completely restored both biliary and fecal excretion of [(3)H]-tracer in the neutral sterol fraction in L1(LivOnly) mice. High-density lipoprotein kinetic studies showed that L1(LivOnly) mice compared with L1-KO mice had a significantly reduced fractional catabolic rate without altered hepatic and intestinal uptake of high-density lipoprotein-cholesterol ether. In mice lacking intestinal cholesterol absorption, macrophage-to-feces RCT depends on efficient biliary sterol secretion, and ezetimibe promotes macrophage RCT by inhibiting hepatic NPC1L1 function.
Reduction in fecal excretion of Giardia cysts: effect of cholestasis and diet.
Erlandsen, Stanley
2005-12-01
Bile is a major growth factor for the proliferation of Giardia spp. trophozoites in the small intestine and, at high concentrations, stimulates encystment of trophozoites. This report demonstrates that surgical cholestasis to interrupt the flow of bile from liver to intestine or the use of bile-binding resins in the diet can both dramatically decrease the fecal excretion of Giardia muris cysts. Cholestasis produced a 3 log reduction in excretion of G. muris cysts within 24 hr of surgery and a 4 log reduction after 3 days. Sham controls showed no difference in cyst excretion from presurgical control values. Two isocaloric diets were studied: a control diet (N) of Purina mouse chow containing 5% celufil and an experimental diet (CR) containing 5% cholestyramine, a resin that binds bile. Compared with the N diet, the CR diet was associated with reductions in cyst excretion of 3 logs within 1 day. Despite lowered excretion of G. muris cysts in mice fed the cholestyramine diet, the trophozoite recovery from the duodenum was similar with both diets. Cyclic feeding of the CR diet and the N diet at 3-day intervals produced significant oscillations (changes of 3-4 logs) in fecal cyst shedding. The significant reductions in fecal excretion of cysts observed with agents that bind bile suggests that diets capable of binding bile might be a therapeutic means to minimize the fecal excretion of cysts and thereby may help to reduce the risk of spreading giardiasis through fecal-oral contamination.
Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.
Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J
2013-04-01
Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.
Yang, Jieping; Zhang, Song; Henning, Susanne M; Lee, Rupo; Hsu, Mark; Grojean, Emma; Pisegna, Rita; Ly, Austin; Heber, David; Li, Zhaoping
2018-02-01
It has been demonstrated in animal studies that both polyphenol-rich pomegranate extract (PomX) and the polysaccharide inulin, ameliorate metabolic changes induced by a high-fat diet, but little is known about the specific mechanisms. This study evaluated the effect of PomX (0.25%) and inulin (9%) alone or in combination on cholesterol and lipid metabolism in mice. Male C57BL/6 J mice were fed high-fat/high-sucrose [HF/HS (32% energy from fat, 25% energy from sucrose)] diets supplemented with PomX (0.25%) and inulin (9%) alone or in combination for 4 weeks. At the end of intervention, serum and hepatic cholesterol, triglyceride levels, hepatic gene expression of key regulators of cholesterol and lipid metabolism as well as fecal cholesterol and bile acid excretion were determined. Dietary supplementation of the HF/HS diet with PomX and inulin decreased hepatic and serum total cholesterol. Supplementation with PomX and inulin together resulted in lower hepatic and serum total cholesterol compared to individual treatments. Compared to HF/HS control, PomX increased gene expression of Cyp7a1 and Cyp7b1, key regulators of bile acid synthesis pathways. Inulin decreased gene expression of key regulators of cholesterol de novo synthesis Srebf2 and Hmgcr and significantly increased fecal elimination of total bile acids and neutral sterols. Only PomX in combination with inulin reduced liver and lipid weight significantly compared to the HF/HS control group. PomX showed a trend to decrease liver triglyceride (TG) levels, while inulin or PomX-inulin combination had no effect on either serum or liver TG levels. Dietary PomX and inulin supplementation decreased hepatic and serum total cholesterol by different mechanisms and the combination leading to a significant enhancement of the cholesterol-lowering effect. Copyright © 2017 Elsevier Inc. All rights reserved.
de Miranda, Aline Mayrink; Rossoni Júnior, Joamyr Victor; Souza E Silva, Lorena; Dos Santos, Rinaldo Cardoso; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia
2017-06-01
The sun mushroom (Agaricus brasiliensis) is considered a major source of bioactive compounds with potential health benefits. Mushrooms typically act as lipid-lowering agents; however, little is known about the mechanisms of action of A. brasiliensis in biological systems. This study aimed to determine the underlying mechanism involved in the cholesterol-lowering effect of A. brasiliensis through the assessment of fecal and serum lipid profiles in addition to gene expression analysis of specific transcription factors, enzymes, and transporters involved in cholesterol homeostasis. Twenty-four albino Fischer rats approximately 90 days old, with an average weight of 205 g, were divided into four groups of 6 each and fed a standard AIN-93 M diet (C), hypercholesterolemic diet (H), hypercholesterolemic diet +1 % A. brasiliensis (HAb), or hypercholesterolemic diet +0.008 % simvastatin (HS) for 6 weeks. Simvastatin was used as a positive control, as it is a typical drug prescribed for lipid disorders. Subsequently, blood, liver, and feces samples were collected for lipid profile and quantitative real-time polymerase chain reaction gene expression analyses. Diet supplementation with A. brasiliensis significantly improved serum lipid profiles, comparable to the effect observed for simvastatin. In addition, A. brasiliensis dietary supplementation markedly promoted fecal cholesterol excretion. Increased expression of 7α-hydroxylase (CYP7A1), ATP-binding cassette subfamily G-transporters (ABCG5/G8), and low-density lipoprotein receptor (LDLR) was observed following A. brasiliensis administration. Our results suggest that consumption of A. brasiliensis improves the serum lipid profile in hypercholesterolemic rats by modulating the expression of key genes involved in hepatic cholesterol metabolism.
Effects of diet on titratable acid-base excretion in grasshoppers.
Frazier, M R; Harrison, J F; Behmer, S T
2000-01-01
Despite the potential for diet to affect organismal acid-base status, especially in herbivores, little is known about the effects of diet on acid-base loading and excretion. We tested the effects of diet on acid-base loading and excretion in grasshoppers by (a) comparing the fecal acid-base content of 15 grasshopper species collected from the field and (b) comparing fecal acid-base excretion rates of Schistocerca americana grasshoppers fed vegetable diets that differed in their ashed and raw acid-base contents. The field experiments indicated that grass-feeding species excrete fairly neutral fecal pellets, while forb/mixed-feeding species vary widely in their fecal acid-base contents. In the laboratory experiment, acid-base excretion rates were positively correlated with dietary ashed base intake rates but were not correlated with the acid-base content of raw, unashed diet or feeding rate. These experiments suggest that some diets could strongly challenge the acid-base homeostasis of herbivores; in some grasshoppers, dietary acid-base loads could produce certainly lethal 1-unit changes in average body pH within 6 h if they were not excreted.
Dougherty, R M; Allman, M A; Iacono, J M
1995-05-01
Ten middle-aged males participated in a crossover study to determine the cholesterolemic effect of high amounts of stearic acid in a natural diet. They consumed a 20-d stabilization diet followed by two 40-d intervention diets containing either 1.5% of energy as stearic (18:0) acid and 7.3% of energy as palmitic (16:0) acid (low stearate: LS) or 2.4% of energy as 16:0 and 7.3% of energy as 18:0 (high stearate: HS). The experimental diets also contained approximately 10% of energy each as saturated and monounsaturated fatty acids and 7.2-8% of energy as polyunsaturated fatty acids. The primary source of 18:0 in the HS diet was sheanut oil (commercially referred to as shea butter) and palm oil and butter in the LS diet. Plasma total, low-density-lipoprotein, and high-density-lipoprotein cholesterol were significantly lower with the HS than with the LS diet. Total fecal fatty acid excretion was higher throughout the HS period. Apparent digestibility of the major dietary fatty acids showed that all of the selected fatty acids, except 18:0, were > or = 95% absorbed. These data demonstrate that feeding diets containing about two times the usual amount of stearic acid consumed in the United States, contributed to an increase in plasma lipoprotein concentrations at 40 d from an earlier decrease at 20 d. The time required to achieve stable cholesterol concentrations appears to vary depending on the kind of saturated fatty acids present in the diet.
Kojima, Makiko; Arishima, Toshiharu; Shimizu, Ryoma; Kohno, Mitsutaka; Kida, Haruyasu; Hirotsuka, Motohiko; Ikeda, Ikuo
2013-01-01
We examined the fecal fat excretion of mildly hypertriacylglycerolemic subjects who ingested soft cookies containing 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) for 7 days. The subjects included 14 healthy men (average age; 44.9 ± 1.7) whose fasting plasma triacylglycerol level ranged from 150 to 250 mg/dL. Every day for 7 days, the subjects ate 5 soft cookies containing margarine with the BOO-rich experimental oil (BOO intake, 2.46 g/day). The placebo group ate soft cookies containing margarine without BOO. This study was a randomized double-blind, placebo-controlled, crossover study. Feces were collected for 3 days prior to the end of the treatment period, and fecal fat and fatty acid composition were determined. The fecal wet weight was significantly increased in BOO group compared with that in the placebo group. Moreover, fecal fat and fatty acid level were significantly higher in the BOO group than in the placebo group. There were no significant differences in the fecal fatty acid composition of the BOO and placebo groups. These results suggest that dietary BOO increases fecal excretion of dietary fat in humans. However, BOO does not increase the excretion of specific fatty acids; it increases the excretion of all fatty acids of dietary origin, which may lead to lower and delay intestinal absorption of dietary fat.
Inhibition of cholesterol absorption and synthesis in rats by sesamin.
Hirose, N; Inoue, T; Nishihara, K; Sugano, M; Akimoto, K; Shimizu, S; Yamada, H
1991-04-01
The effects of sesamin, a lignan from sesame oil, on various aspects of cholesterol metabolism were examined in rats maintained on various dietary regimens. When given at a dietary level of 0.5% for 4 weeks, sesamin reduced the concentration of serum and liver cholesterol significantly irrespective of the presence or absence of cholesterol in the diet, except for one experiment in which the purified diet free of cholesterol was given. On feeding sesamin, there was a decrease in lymphatic absorption of cholesterol accompanying an increase in fecal excretion of neutral, but not acidic, steroids, particularly when the cholesterol-enriched diet was given. Sesamin inhibited micellar solubility of cholesterol, but not bile acids, whereas it neither bound taurocholate nor affected the absorption of fatty acids. Only a marginal proportion (ca. 0.15%) of sesamin administered intragastrically was recovered in the lymph. There was a significant reduction in the activity of liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase after feeding sesamin, although the activity of hepatic cholesterol 7 alpha-hydroxylase, drug metabolizing enzymes, and alcohol dehydrogenase remained uninfluenced. Although the weight and phospholipid concentration of the liver increased unequivocally on feeding sesamin, the histological examination by microscopy showed no abnormality, and the activity of serum GOT and GPT remained unchanged. Since sesamin lowered both serum and liver cholesterol levels by inhibiting absorption and synthesis of cholesterol simultaneously, it deserves further study as a possible hypocholesterolemic agent of natural origin.
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
de Souza, Melina Oliveira; Souza E Silva, Lorena; de Brito Magalhães, Cíntia Lopes; de Figueiredo, Bianca Barros; Costa, Daniela Caldeira; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia
2012-12-01
Previous studies have demonstrated that the ingestion of açaí pulp can improve serum lipid profile in various animal models; therefore, we hypothesized that açaí pulp (Euterpe oleracea Mart.) may modulate the expression of the genes involved in cholesterol homeostasis in the liver and increase fecal excretion, thus reducing serum cholesterol. To test this hypothesis, we analyzed the expression of 7α-hydroxylase and ATP-binding cassette, subfamily G transporters (ABCG5 and ABCG8), which are genes involved with the secretion of cholesterol in the rat. We also evaluated the expression of sterol regulatory element-binding protein 2, 3-hydroxy-3-methylglutaryl CoA reductase, low-density lipoprotein receptor (LDL-R), and apolipoprotein B100, which are involved in cholesterol biosynthesis. Female Fischer rats were divided into 4 groups: the C group, which was fed a standard AIN-93 M diet; the CA group, which was fed a standard diet supplemented with 2% açaí pulp; the H group, which was fed a hypercholesterolemic diet (25% soy oil and 1% cholesterol); and the HA group, which was fed a hypercholesterolemic diet supplemented with 2% açaí pulp. At the end of the experimental period, the rats were euthanized, and their blood and livers were collected. The HA group exhibited a significant decrease in serum total cholesterol, low-density lipoprotein cholesterol, and atherogenic index and also had increased high-density lipoprotein cholesterol and cholesterol excretion in feces compared with the H group. In addition, the expression of the LDL-R, ABCG5, and ABCG8 genes was significantly increased by the presence of açaí pulp. These results suggest that açaí pulp promotes a hypocholesterolemic effect in a rat model of dietary-induced hypercholesterolemia through an increase in the expression of ATP-binding cassette, subfamily G transporters, and LDL-R genes. Copyright © 2012 Elsevier Inc. All rights reserved.
Wilson, T A; Romano, C; Liang, J; Nicolosi, R J
1998-08-01
Cholazol H (Alpha-Beta Technology, Worcester, MA), a chemically functionalized, insoluble dietary fiber with bile acid sequestrant properties, was studied in 30 male F1 B Golden Syrian hamsters for its effect on plasma lipid concentrations and early atherogenesis in experiment 1. In experiment 2, 30 male Golden Syrian hamsters were studied for the effects on plasma lipids and fecal excretion of bile acids. In experiment 1, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 5% coconut oil and 0.1% cholesterol for 6 weeks. After 6 weeks, hamsters were continued on the diet with either 0% drug (hypercholesterolemic diet [HCD]), 0.5% cholestyramine (CSTY), or 0.5% Cholazol H for 8 weeks. Fasting plasma lipids were measured at weeks 6, 10, and 14, and early atherosclerosis (fatty streak formation) was measured at week 14. Relative to HCD, CSTY and Cholazol H significantly lowered plasma total cholesterol (TC) (-37%, P < .03, and -30%, P < .04, respectively) and plasma very-low and low-density lipoprotein-cholesterol (nonHDL-C) (-45%, P < .02, and -36%, P < .03, respectively) with no significant effects on plasma HDL-C or triglycerides (TG). Despite similar reductions in nonHDL-C, only Cholazol H significantly prevented early atherosclerosis (-38%, P < .02) relative to HCD. In experiment 2, three groups of 10 hamsters each were fed a chow-based hypercholesterolemic diet supplemented with 10% coconut oil and 0.05% cholesterol and either 0% drug HCD, 0.5% CSTY, or 0.5% Cholazol H for 4 weeks. Fasting plasma lipids were measured at weeks 2 and 4, and fecal bile acids were measured at week 4. Both Cholazol H and CSTY were equally effective in significantly lowering plasma TC (-16%, P < .003, and -13%, P < .01, respectively) and nonHDL-C (-22%, P < .004, and -18%, P < .02, respectively), with no significant effect on HDL-C and TG relative to HCD. Cholazol H and CSTY produced a significantly greater concentration of fecal total bile acids (39%, P < .001, and 28%, P < .002, respectively) relative to HCD. Also, there was a 48% (P < .002) and 65% (P < .001) greater fecal concentration of cholic acid (CA) for Cholazol H-treated hamsters compared with HCD- and CSTY-treated hamsters, respectively. Cholazol H also significantly increased fecal concentration of deoxycholic acid (DCA; 56%, P < .02) compared with HCD. In summary, Cholazol H is as effective as CSTY for prevention of diet-induced hypercholesterolemia and early atherosclerosis in hamsters.
Lin, Yuguang; Vermeer, Mario A.; Trautwein, Elke A.
2011-01-01
Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols. PMID:19228775
Lin, Yuguang; Vermeer, Mario A; Trautwein, Elke A
2011-01-01
Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols.
Lee, Do Kyung; Jang, Seok; Baek, Eun Hye; Kim, Mi Jin; Lee, Kyung Soon; Shin, Hea Soon; Chung, Myung Jun; Kim, Jin Eung; Lee, Kang Oh; Ha, Nam Joo
2009-06-11
Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as lower cholesterol. Although present in many foods, most trials have been in spreads or dairy products. Here we tested whether Bifidobacteria isolates could lower cholesterol, inhibit harmful enzyme activities, and control fecal water content. In vitro culture experiments were performed to evaluate the ability of Bifidobacterium spp. isolated from healthy Koreans (20 approximately 30 years old) to reduce cholesterol-levels in MRS broth containing polyoxyethanylcholesterol sebacate. Animal experiments were performed to investigate the effects on lowering cholesterol, inhibiting harmful enzyme activities, and controlling fecal water content. For animal studies, 0.2 ml of the selected strain cultures (108 approximately 109 CFU/ml) were orally administered to SD rats (fed a high-cholesterol diet) every day for 2 weeks. B. longum SPM1207 reduced serum total cholesterol and LDL levels significantly (p < 0.05), and slightly increased serum HDL. B. longum SPM1207 also increased fecal LAB levels and fecal water content, and reduced body weight and harmful intestinal enzyme activities. Daily consumption of B. longum SPM1207 can help in managing mild to moderate hypercholesterolemia, with potential to improve human health by helping to prevent colon cancer and constipation.
Arango-Sabogal, J C; Paré, J; Labrecque, O; Côté, G; Roy, J P; Buczinski, S; Wellemans, V; Fecteau, G
2017-12-01
Paratuberculosis is a chronic and contagious enteric disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). This disease of worldwide distribution is responsible for significant economic losses and the bacteria itself has been linked to human Crohn's disease. Paratuberculosis control programs focus on reducing MAP transmission by implementing better management practices that target infection routes. In Québec, a Voluntary Paratuberculosis Prevention and Control Program (QVPPCP) was launched in 2007. The objectives of this prospective cohort study were threefold. The first was to describe the changes in the incidence of fecal excretion of MAP in cows born before and after farm enrolment in the QVPPCP. The second was to estimate the impact of the risk of within-herd transmission of MAP (measured by the risk assessment score (RAS)) on the incidence of fecal excretion of MAP. And the third was to evaluate the impact of calf rearing practices on the incidence of fecal excretion of MAP. Eighteen MAP-positive herds were visited annually from 2011 to 2015. At each visit, individual fecal samples from all adult cows were collected. MAP was cultured using liquid media and an automated system. A risk assessment questionnaire was completed upon enrolment in the QVPPCP and at each visit. The RAS of the farm was attributed to each cow according to its birthdate. Cox proportional hazards models were used to estimate the hazard ratios (HR) for the exposure variables. Herd clustering was taken into account using robust standard errors. A total of 2158 cows were included (cohort born before n=919; cohort born after n=1239). The incidence and hazard of fecal excretion were significantly lower for the cohort-after than the cohort-before (incidence rate ratio=0.38; 95% CI: 0.18-0.78 and HR=0.48; 95% CI: 0.23-0.98). The HR of fecal excretion for cows exposed to a high RAS was 2.20 times (95% CI: 1.21-3.99) that of cows exposed to a low RAS. Poor calving cow hygiene (HR=3.41; 95% CI: 1.40-8.31) and contact between pre-weaned heifers and adult cows or their feces were significantly associated with an increased hazard of fecal excretion of MAP (HR=2.66; 95% CI: 1.08-6.56). Our results suggest that enrolment in the QVPPCP reduces the risk of MAP fecal excretion. They support the hypothesis that contact between calves and adult cows or their feces increases MAP transmission. The incidence results also suggest that MAP prevalence could be reduced to low levels regardless of initial MAP prevalence. Copyright © 2017. Published by Elsevier B.V.
Charbonneau, Duane; Gibb, Roger D.; Quigley, Eamonn M.M.
2013-01-01
Certain randomized, placebo-controlled trials of oral supplementation with B. infantis 35624 have demonstrated the amelioration of symptoms of irritable bowel syndrome. Potential GI colonization by B. infantis 35624 or effects of supplementation on resident GI microbiota may pertain to these clinical observations. In this study, fecal excretion of B. infantis 35624 before, during and after 8 weeks of daily treatment was compared in subjects with IBS who received either the encapsulated oral supplement (n = 39) or placebo (n = 37) and in healthy subjects who received the supplement (n = 41). Secondarily, changes in assessed fecal microbiota and IBS symptoms were determined. Supplementation significantly increased fecal B. infantis 35624 excretion vs. placebo in IBS subjects; excretion in healthy subjects receiving supplement was quantitatively similar. Fecal levels of the probiotic declined and approached baseline once dosing ceased, documenting that colonization is transient. Although supplementation increased numbers of B infantis 35624 within the GI tract, limited changes in 10 other fecal taxa were observed either in healthy subjects or those with IBS. No impact on IBS symptoms was observed. Detection of bacterial DNA in fecal samples suggests that the probiotic is able to survive transit through the GI tract, although strain selective culture techniques were not performed to confirm viability of B. infantis 35624 in the feces. Continuous probiotic administration was necessary to maintain steady-state transit. Given the complex spectrum of GI microbiota, however, monitoring perturbations in selected taxa may not be not a useful indicator of probiotic function. PMID:23549409
de Beer, Maria C.; Wroblewski, Joanne M.; Noffsinger, Victoria P.; Meyer, Jason M.; van der Westhuyzen, Deneys R.
2013-01-01
Studies suggest that inflammation impairs reverse cholesterol transport (RCT). We investigated whether serum amyloid A (SAA) contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT) mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO) were injected intraperitoneally with 3H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. 3H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of 3H-cholesterol was unaltered in either WT or SAAKO mice by LPS treatment. Radioactivity present in bile and feces of LPS-injected WT mice 24 hr after macrophage injection was reduced by 36% (P < 0.05) and 80% (P < 0.001), respectively. In contrast, in SAAKO mice, LPS did not significantly reduce macrophage-derived 3H-cholesterol in bile, and fecal excretion was reduced by only 45% (P < 0.05). Injection of cholesterol-loaded allogeneic J774 cells, but not syngeneic bone-marrow-derived macrophages, transiently induced SAA in C57BL/6 mice. Our study confirms reports that acute inflammation impairs steps in the RCT pathway and establishes that SAA plays only a minor role in this impairment. PMID:23431457
de Beer, Maria C; Wroblewski, Joanne M; Noffsinger, Victoria P; Ji, Ailing; Meyer, Jason M; van der Westhuyzen, Deneys R; de Beer, Frederick C; Webb, Nancy R
2013-01-01
Studies suggest that inflammation impairs reverse cholesterol transport (RCT). We investigated whether serum amyloid A (SAA) contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT) mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO) were injected intraperitoneally with (3)H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. (3)H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of (3)H-cholesterol was unaltered in either WT or SAAKO mice by LPS treatment. Radioactivity present in bile and feces of LPS-injected WT mice 24 hr after macrophage injection was reduced by 36% (P < 0.05) and 80% (P < 0.001), respectively. In contrast, in SAAKO mice, LPS did not significantly reduce macrophage-derived (3)H-cholesterol in bile, and fecal excretion was reduced by only 45% (P < 0.05). Injection of cholesterol-loaded allogeneic J774 cells, but not syngeneic bone-marrow-derived macrophages, transiently induced SAA in C57BL/6 mice. Our study confirms reports that acute inflammation impairs steps in the RCT pathway and establishes that SAA plays only a minor role in this impairment.
Gordon, M E; Edwards, M S; Sweeney, C R; Jerina, M L
2013-08-01
The objective of this study was to test the hypothesis that an equine diet formulated with chelated trace minerals, organic selenium, yeast culture, direct-fed microbials (DFM) and Yucca schidigera extract would decrease excretion of nutrients that have potential for environmental impact. Horses were acclimated to 100% pelleted diets formulated with (ADD) and without (CTRL) the aforementioned additives. Chelated sources of Cu, Zn, Mn, and Co were included in the ADD diet at a 100% replacement rate of sulfate forms used in the CTRL diet. Additionally, the ADD diet included organic selenium yeast, DFM, and Yucca schidigera extract. Ten horses were fed the 2 experimental diets during two 42-d periods in a crossover design. Total fecal and urine collection occurred during the last 14 d of each period. Results indicate no significant differences between Cu, Zn, Mn, and Co concentrations excreted via urine (P > 0.05) due to dietary treatment. There was no difference between fecal Cu and Mn concentrations (P > 0.05) based on diet consumed. Mean fecal Zn and Co concentrations excreted by horses consuming ADD were greater than CTRL (P < 0.003). Differences due to diet were found for selenium fecal (P < 0.0001) and urine (P < 0.0001) excretions, with decreased concentrations found for horses consuming organic selenium yeast (ADD). In contrast, fecal K (%) was greater (P = 0.0421) for horses consuming ADD, whereas concentrations of fecal solids, total N, ammonia N, P, total ammonia, and fecal output did not differ between dietary treatments (P > 0.05). In feces stockpiled to simulate a crude composting method, no differences (P > 0.05) due to diet were detected for particle size, temperature, moisture, OM, total N, P, phosphate, K, moisture, potash, or ammonia N (P > 0.05). Although no difference (P = 0.2737) in feces stockpile temperature due to diet was found, temperature differences over time were documented (P < 0.0001). In conclusion, the addition of certain chelated mineral sources, organic Se yeast, DFM, and Yucca schidigera extract did not decrease most nutrient concentrations excreted. Horses consuming organic selenium as part of the additive diet had lower fecal and urine Se concentrations, as well as greater fecal K concentrations.
Effects of feeding outer bran fraction of rice on lipid accumulation and fecal excretion in rats.
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.
Biliary excretion of intravenous (/sup 14/C) omeprazole in humans
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lind, T.; Andersson, T.; Skanberg, I.O.
1987-11-01
We have studied the biliary excretion of (/sup 14/C) omeprazole in humans. The study was performed in eight healthy subjects and the technique used was based on multiple marker dilution principles with double-lumen tubes placed in both the stomach and intestine. The results obtained show a 16% biliary excretion of (/sup 14/C) omeprazole. These data suggest a minimal spillover of omeprazole from the gastric mucosa into the gastric lumen in humans. The results also agree with previous data of the fecal recovery of radiolabeled omeprazole that suggest that the fecal excretion of intravenous omeprazole in humans is entirely accounted formore » by biliary excretion.« less
Yokoyama, Wallace; Anderson, William H K; Albers, David R; Hong, Yun-Jeong; Langhorst, Marsha L; Hung, Shao-Ching; Lin, Jiann-Tsyh; Young, Scott A
2011-10-26
In animal studies, hydroxypropyl methylcellulose (HPMC) intake results in increased fecal fat excretion; however, the effects on dietary saturated fatty acids (SATs) and trans-fatty acids (TRANS) remain unknown. This study investigated the effect of HPMC on digestion and absorption of lipids in male Golden Syrian hamsters fed either freeze-dried ground pizza (PZ), pound cake (PC), or hamburger and fries (BF) supplemented with dietary fiber from either HPMC or microcrystalline cellulose (MCC) for 3 weeks. We observed greater excretion of SATs and TRANS by both diets supplemented with HPMC or MCC as compared to the feed. SAT, TRANS, and unsaturated fatty acids (UNSAT) contents of feces of the PZ diet supplemented with HPMC were 5-8 times higher than diets supplemented with MCC and tended to be higher in the PC- and BF-HPMC supplemented diets as well. We also observed significant increases in fecal excretion of bile acids (2.6-3-fold; P < 0.05), sterols (1.1-1.5-fold; P < 0.05), and unsaturated fatty acids (UNSAT, 1.7-4.5-fold; P < 0.05). The animal body weight gain was inversely correlated with the excretion of fecal lipid concentrations of bile acids (r = -0.56; P < 0.005), sterols (r = -0.48; P < 0.005), SAT (r = -0.69; P < 0.005), UNSAT (r = -0.67; P < 0.005), and TRANS (r = -0.62; P < 0.005). Therefore, HPMC may be facilitating fat excretion in a biased manner with preferential fecal excretion of both TRANS and SAT in hamsters fed fast food diets.
[Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].
Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric
2014-10-01
The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases. © 2014 médecine/sciences – Inserm.
USDA-ARS?s Scientific Manuscript database
Objective—To evaluate the association between fecal excretion of Mycobacterium avium subsp paratuberculosis (MAP) by dairy cows in the periparturient period and detection of MAP DNA in colostrum specimens and on teat skin surfaces. Design—Cross-sectional study. Animals—112 Holstein cows. Procedures—...
Longitudinal fecal steroid excretion in maned wolves (Chrysocyon brachyurus).
Velloso, A L; Wasser, S K; Monfort, S L; Dietz, J M
1998-10-01
This study used a fecal steroid monitoring technique to evaluate reproductive cycles in male (4) and female (15) maned wolves, endangered South American canids. A radiolabeled testosterone infusion on a male revealed a fast and predominantly fecal route of excretion for this steroid. Testosterone was also excreted as eight unidentified metabolites, which was not the primary form of this steroid quantified in our assays. Fecal steroid concentrations (estradiol, E2; progestins, P; testosterone, T) in males and acyclic, nonpregnant (pseudo-pregnant), and pregnant females were monitored over four breeding seasons (October-January). Significant differences were detected between longitudinal P profiles of cyclic and acyclic females during estrus, luteal phase, and after birth/end of pseudo-pregnancy. Concentrations of P were also significantly higher in pregnant, compared to nonpregnant females, from proestrus to the end of the pregnant luteal phase. Although levels of T were higher in males than in females throughout the breeding season, no cyclicity in male fecal T concentrations was detected. Values of fecal P, T, and the ratio P/T were useful for differentiating gender and detecting pregnancy in females. Similarities to available data on other canids and the management and conservation implications of these findings were discussed. Copyright 1998 Academic Press.
Zhang, Huijuan; Bartley, Glenn E; Mitchell, Cheryl R; Zhang, Hui; Yokoyama, Wallace
2011-10-26
The physiological effects of the hydrolysates of white rice protein (WRP), brown rice protein (BRP), and soy protein (SP) hydrolyzed by the food grade enzyme, alcalase2.4 L, were compared to the original protein source. Male Syrian Golden hamsters were fed high-fat diets containing either 20% casein (control) or 20% extracted proteins or their hydrolysates as the protein source for 3 weeks. The brown rice protein hydrolysate (BRPH) diet group reduced weight gain 76% compared with the control. Animals fed the BRPH supplemented diet also had lower final body weight, liver weight, very low density lipoprotein cholesterol (VLDL-C), and liver cholesterol, and higher fecal fat and bile acid excretion than the control. Expression levels of hepatic genes for lipid oxidation, PPARα, ACOX1, and CPT1, were highest for hamsters fed the BRPH supplemented diet. Expression of CYP7A1, the gene regulating bile acid synthesis, was higher in all test groups. Expression of CYP51, a gene coding for an enzyme involved in cholesterol synthesis, was highest in the BRPH diet group. The results suggest that BRPH includes unique peptides that reduce weight gain and hepatic cholesterol synthesis.
Dietary Wheat Bran Oil Is Equally as Effective as Rice Bran Oil in Reducing Plasma Cholesterol.
Lei, Lin; Chen, Jingnan; Liu, Yuwei; Wang, Lijun; Zhao, Guohua; Chen, Zhen-Yu
2018-03-21
Rice bran oil (RBO) possesses a plasma cholesterol-lowering activity, while effect of wheat bran oil (WBO) on plasma cholesterol remains unknown. The present study compared the cholesterol-lowering activity of WBO with that of RBO in hamsters. Fifty-four male hamsters were divided into seven groups fed either a noncholesterol diet (NCD) or one of six high-cholesterol diets, namely HCD diet (0.2% cholesterol +9.5% lard), HCD+C diet (0.2% cholesterol +9.5% lard +0.5% cholestyramine), WL diet (0.2% cholesterol +4.8% Lard +4.8% WBO), WH diet (0.2% cholesterol +9.5% WBO), RL diet (0.2% cholesterol +4.8% Lard +4.8% RBO), and RH diet (0.2% cholesterol +9.5% RBO). Plasma total cholesterol (TC) in HCD group was 327.4 ± 31.8 mg/dL, while plasma TC in two WBO and two RBO groups was 242.2 ± 20.8, 243.1 ± 31.7, 257.1 ± 16.3, and 243.4 ± 46.0 mg/dL, respectively, leading to a decrease in plasma TC by 22-26% ( P < 0.01). No significant difference in cholesterol-lowering potency was seen between WBO and RBO. Plasma cholesterol-lowering activity of WBO and RBO was accompanied by down-regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase and fatty acid synthase, while up-regulation of cholesterol-7α-hydroxylase. WL, WH, RL, and RH diets increased the fecal excretion of total neutral sterols by 72.8%, 106.9%, 5.4%, and 36.8% ( P < 0.01) respectively. Results indicated WBO and RBO could inhibit cholesterol absorption via down-regulation of intestinal Niemann-Pick C1 like 1 protein, acyl CoA:cholesterol acyltransferase 2, and ATP binding cassette transporter 5. In summary, WBO was equally effective as RBO in decreasing plasma cholesterol in hypercholesterolemia hamsters.
St-Onge, Marie-Pierre; Farnworth, Edward R; Savard, Tony; Chabot, Denise; Mafu, Akier; Jones, Peter JH
2002-01-01
Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as the total amount of fecal short chain fatty acids. Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent. PMID:11825344
Tsuchida, Takuma; Shiraishi, Muneshige; Ohta, Tetsuya; Sakai, Kaoru; Ishii, Shinichi
2012-07-01
Type 2 diabetes mellitus is frequently accompanied by fatty liver/nonalcoholic fatty liver disease. Hence, accumulation of lipids in the liver is considered to be one of the risk factors for insulin resistance and metabolic syndrome. Ursodeoxycholic acid (UDCA) is widely used for the treatment of liver dysfunction. We investigated the therapeutic effects of UDCA on type 2 diabetes mellitus exacerbating hepatic steatosis and the underlying mechanisms of its action using KK-A(y) mice fed a high-fat diet. KK-A(y) mice were prefed a high-fat diet; and 50, 150, and 450 mg/kg of UDCA was orally administered for 2 or 3 weeks. Administration of UDCA decreased fasting hyperglycemia and hyperinsulinemia. Hyperinsulinemic-euglycemic clamp analyses showed that UDCA improved hepatic (but not peripheral) insulin resistance. Hepatic triglyceride and cholesterol contents were significantly reduced by treatment with UDCA, although the genes involved in the synthesis of fatty acids and cholesterol, including fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, were upregulated. Fecal levels of bile acids, neutral sterols, fatty acids, and phospholipids were significantly increased by UDCA treatment. The gene expression levels and protein phosphorylation levels of endoplasmic reticulum stress markers were not changed by UDCA treatment. These results indicate that UDCA ameliorates hyperglycemia and hyperinsulinemia by improving hepatic insulin resistance and steatosis in high-fat diet-fed KK-A(y) mice. Reduction of hepatic lipids might be due to their excretion in feces, followed by enhanced utilization of glucose for the synthesis of fatty acids and cholesterol. Ursodeoxycholic acid should be effective for the treatment of type 2 diabetes mellitus accompanying hepatic steatosis. Copyright © 2012 Elsevier Inc. All rights reserved.
Boot, Hein J.; Kasteel, Daniella T. J.; Buisman, Anne-Marie; Kimman, Tjeerd G.
2003-01-01
The emergence of circulating vaccine-derived poliovirus (cVDPV) strains in suboptimally vaccinated populations is a serious threat to the global poliovirus eradication. The genetic determinants for the transmissibility phenotype of polioviruses, and in particularly of cVDPV strains, are currently unknown. Here we describe the fecal excretion of wild-type poliovirus, oral polio vaccine, and cVDPV (Hispaniola) strains after intraperitoneal injection in poliovirus receptor-transgenic mice. Both the pattern and the level of fecal excretion of the cVDPV strains resemble those of wild-type poliovirus type 1. In contrast, very little poliovirus was present in the feces after oral polio vaccine administration. This mouse model will be helpful in elucidating the genetic determinants for the high fecal-oral transmission phenotype of cVDPV strains. PMID:12743311
USDA-ARS?s Scientific Manuscript database
Bile acids (BAs) have an important role in the control of fat, glucose and cholesterol metabolism. Synthesis of bile acids is the major pathway for the metabolism of cholesterol and for the excretion of excess cholesterol in mammals. Bile acid intermediates and/or their metabolites are excreted in...
Goto, Moritaka; Furuta, Shinji; Yamashita, Satoko; Hashimoto, Hiroyuki; Yano, Wataru; Inoue, Noriyuki; Kato, Noriaki; Kaku, Kohei
2018-05-13
Recent data showed that DPP-4 inhibitors exert a lipid-lowering effect in diabetic patients. However, the mechanism of action is not yet clearly understood. We investigated the effect of anagliptin on cholesterol metabolism and transport in the small intestine using non-diabetic hyperlipidemic animals, to clarify the mechanisms underlying the cholesterol-lowering action. Male ApoE-deficient mice were orally administered anagliptin in the normal chow. Serum cholesterol levels and lipoprotein profiles were measured, and cholesterol transport was assessed by measuring the radioactivity in the tissues after oral loading of 14 C-labeled cholesterol ( 14 C-Chol). In additional experiments, effects of exendin-4 in mice and of anagliptin in DPP-4-deficient rats were assessed. Effect on target gene expressions in the intestine were analyzed by qPCR in normal mice. The serum total and non-HDL cholesterol concentrations decreased after anagliptin treatment in the ApoE-deficient mice. The cholesterol-lowering effect was predominantly observed in the chylomicron fraction. The plasma 14 C-Chol radioactivity was significantly decreased by 26% at 2 hours after cholesterol loading, and the fecal 14 C-Chol excretion was significantly increased by 38% at 72 hours. The aforementioned effects on cholesterol transport were abrogated in rats lacking DPP-4 activity, and exendin-4 had no effect on the 14 C-Chol transport in ApoE-deficient mice. Furthermore, significant decreases of the intestinal cholesterol transport related MTTP, ACAT2, ApoA2 and ApoC2 mRNA expressions were observed in the mice treated with repeated doses of anagliptin. These findings suggest that anagliptin may exert a cholesterol-lowering action via DPP-4-dependent and GLP-1-independent suppression of intestinal cholesterol transport. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Arellano-Martínez, Gloria Leticia; Granados, Omar; Palacios-González, Berenice; Torres, Nimbe; Medina-Vera, Isabel; Tovar, Armando R
2014-06-28
Several studies using different animal models have demonstrated that the consumption of soya protein (SP) reduces serum cholesterol concentrations by increasing the excretion of bile acids (BA). However, the mechanism by which SP enhances BA excretion is not fully understood. Therefore, the aim of the present study was to determine whether the consumption of SP regulates the expression of key enzymes involved in hepatic BA synthesis and the transporters involved in reverse cholesterol transport (RCT) via fibroblast growth factor 15 (FGF15) and/or small heterodimer protein (SHP) in rats. To achieve this aim, four groups of rats were fed experimental diets containing 20 % casein (C) or SP with or without the addition of 0·2 % cholesterol and the expression of hepatic genes involved in BA synthesis and the ileal and hepatic RCT was measured. Rats fed the SP diet had higher concentrations of ileal FGF15 and hepatic FGF15 receptor (FGFR4) and increased expression of SHP and liver receptor homolog 1 (LRH1) than those fed the C diet; as a result, the excretion of faecal BA was greater. The addition of cholesterol to the diet repressed the protein abundance of FGF15 and FGFR4; however, SP increased the expression of SHP and LRH1 to a lesser extent. Nonetheless, the expression of ABCG5/8 was increased in the intestine of rats fed the SP diet, and the effect was enhanced by the addition of cholesterol to the diet. In conclusion, SP in the presence of cholesterol increases BA synthesis via the repressions of FGF15 and SHP and accelerates BA excretion to prevent cholesterol overload in the enterocytes by increasing RCT.
Wilson, Thomas A; Kritchevsky, David; Kotyla, Timothy; Nicolosi, Robert J
2006-03-01
The effects of structured triglycerides containing one long chain fatty acid (oleic acid, C18:1) and one short chain saturated fatty acid (caprylic acid, 8:0) on lipidemia, liver and aortic cholesterol, and fecal neutral sterol excretion were investigated in male Golden Syrian hamsters fed a hypercholesterolemic regimen consisting of 89.9% commercial ration to which was added 10% coconut oil and 0.1% cholesterol (w/w). After 2 weeks on the HCD diet, the hamsters were bled, following an overnight fast (16 h) and placed into one of three dietary treatments of eight animals each based on similar plasma cholesterol levels. The hamsters either continued on the HCD diet or were placed on diets in which the coconut oil was replaced by one of two structured triglycerides, namely, 1(3),2-dicaproyl-3(1)-oleoylglycerol (OCC) or 1,3-dicaproyl-2-oleoylglycerol (COC) at 10% by weight. Plasma total cholesterol (TC) in hamsters fed the OCC and COC compared to the HCD were reduced 40% and 49%, respectively (P<0.05). Similarly, hamsters fed the OCC and COC diets reduced their plasma nonHDL cholesterol levels by 47% and 57%, respectively (P<0.05), compared to hamsters fed the HCD after 2 weeks of dietary treatment. Although hamsters fed the OCC (-26%) and COC (-32%) had significantly lower plasma HDL levels compared to HCD, (P<0.05), the plasma nonHDL/HDL cholesterol ratio was significantly lower (P<0.05) compared to the HCD for the OCC-fed (-27%) and the COC-fed (-38%) hamsters, respectively. Compared to the HCD group, aortic esterified cholesterol was 20% and 53% lower for the OCC and COC groups, respectively, with the latter reaching statistical significance, P<0.05. In conclusion, the hamsters fed the structured triglyceride oils had lower blood cholesterol levels and lower aortic accumulation of cholesterol compared to the control fed hamsters.
Venkatesan, Nandini; Devaraj, S Niranjali; Devaraj, H
2003-10-01
Research has focussed on the hypocholesterolemic effects of certain types of dietary fiber such as enhancing conversion of hepatic cholesterol to bile acids or increase in catabolism of low density lipoprotein (LDL) via the apo B,E receptor. The effect of oral administration of a unique fibre cocktail of fenugreek seed powder, guar gum and wheat bran (Fibernat) and its varied effects on some aspects of lipid metabolism and cholesterol homeostasis in rats were examined. Rats were administered Fibernat along with the atherogenic diet containing 1.5 % cholesterol and 0.1 % cholic acid. Amounts of hepatic lipids, hepatic and fecal bile acids and activity of hepatic triglyceride lipase (HTGL) were determined. Transmission electron microscopic examination of the liver tissue and extent of uptake of (125)I-LDL and (125)I-VLDL by the hepatic apo B,E receptor was carried out. Food intake and body weight gain were similar between the 3 different dietary groups. Fibernat intake significantly increased apo B,E receptor expression in rat liver as reflected by an increase in the maximum binding capacity (B(max)) of the apo B,E receptor to (125)I-LDL and (125)I-VLDL. The activity of HTGL was increased by approximately 1.5-fold in Fibernat-fed rats as compared to those fed the atherogenic diet alone. A marked hypocholesterolemic effect was observed. Cholesterol homeostasis was achieved in Fibernat-fed rats. Two possible mechanisms are postulated to be responsible for the observed hypocholesterolemic effect a) an increase in conversion of cholesterol to bile acids and b) possibly by intra-luminal binding which resulted in increased fecal excretion of bile acids and neutral sterols. The resulting reduction in cholesterol content of liver cells coupled with upregulation of hepatic apo B,E receptors and increased clearance of circulating atherogenic lipoproteins-LDL and very low density lipoprotein (LDL and VLDL)-is the main mechanism involved in the hypocholesterolemic effect of Fibernat. The results suggest that Fibernat's effect on plasma LDL concentration is also possibly mediated by increased receptor-mediated catabolism of VLDL. Thus, Fibernat therapy is an effective adjunct to diet therapy and might find potential use in the therapy of hyperlipidemic subjects.
Wang, Yanping; Xu, Nv; Xi, Aodeng; Ahmed, Zaheer; Zhang, Bin; Bai, Xiaojia
2009-08-01
The objective of this study was to evaluate the effects of Lactobacillus plantarum MA2, an isolate from Chinese traditional Tibet kefir, on cholesterol-lowering and microflora of rat in vivo. Rats were fed on cholesterol-enriched experimental diet, supplemented with lyophilized L. plantarum MA2 powder, with a dose of 10(11) cells/day per mice. The results showed that L. plantarum MA2 feeding significantly lowered serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides level, while there was no change in high-density lipoprotein cholesterol. In addition, liver total cholesterol and triglycerides was also decreased. However, fecal cholesterol and triglycerides was increased significantly (P < 0.05) in comparison with the control. Also, L. plantarum MA2 increased the population of lactic acid bacteria and bifidobacteria in the fecal, but it did not change the number of Escherichia coli as compared to control. Moreover, pH, moisture, and organic acids in the fecal were also measured. The present results indicate the probiotic potential of the L. plantarum MA2 strain in hypocholesterolemic effect and also increasing the probiotic count in the intestine.
Antharam, Vijay C; McEwen, Daniel C; Garrett, Timothy J; Dossey, Aaron T; Li, Eric C; Kozlov, Andrew N; Mesbah, Zhubene; Wang, Gary P
2016-01-01
Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.
Comparison of plutonium systemic distribution in rats and dogs with published data in humans.
Melo, Dunstana R; Weber, Waylon; Doyle-Eisele, Melanie; Guilmette, Raymond A
2014-11-01
This manuscript compares the behavior of monomeric (239)Pu(4+)-citrate injected intravenously in rats and dogs with a comparison of available humans' data. The experimental design for these two studies consisted of eight groups sacrificed at predetermined time-points post exposure. All organs and tissues as well as daily urinary and fecal excretion were analyzed. Liver and skeleton were the organs with the highest (239)Pu uptake in both species; 76% in dogs and 70% in rats at 24 hours (h) post IV administration. By the end of the study (28 days, d), the activity in skeleton and liver was 85% in dogs and 65% in rats. The urinary excretion function seems to be similar for rats, dogs and humans but the daily fecal to urinary excretion ratio differs between species. A rapid clearance from the liver of rats was observed compared to dogs. Skeleton-to-liver ratios are variable between species. Urinary and fecal excretion patterns for dogs are consistent with human data, indicating that dogs seem to represent better the (239)Pu behavior in humans. The data confirm that the better animal model to evaluate the efficacy of (239)Pu chelating compounds is the canine model.
Sudan stain of fecal fat: new insight into an old test.
Khouri, M R; Huang, G; Shiau, Y F
1989-02-01
The 72-h fecal fat determination is used as the gold standard to document the presence of steatorrhea. Although the Sudan stain for fecal fat is advocated as a sensitive screening test, a quantitative correlation between the 72-h fecal fat quantitation and the fecal Sudan stain is lacking. This study was designed to examine the staining properties of different classes of purified lipids in an experimentally defined artificial matrix, and to elucidate the reasons for the lack of quantitative correlation between these two tests. Our results indicate that the "neutral fat" stain without acidification or heating identifies triglyceride; and at an appropriate pH, the "neutral stain" also identifies fatty acid. The "split fat" stain with acidification and heating identifies both triglyceride and fatty acid. After acidification, fatty acid soaps are converted to the nonionized fatty acid. Thus, fatty acid soaps can be identified indirectly as fat droplets that are stained by the split fat stain. Although cholesterol is stained with Sudan stain after heating, upon cooling, cholesterol forms crystals of anhydrous cholesterol, making its staining pattern distinct. Neither the neutral fat nor the split fat stain can detect phospholipid or cholesteryl ester. The 72-h fecal fat determination is a measure of the total fatty acid content after a specimen is saponified. The resulting fatty acids are derived from a variety of endogenous and exogenous sources, including free fatty acids, soaps of fatty acids, triglycerides, cholesterol esters, and phospholipids. Therefore, the 72-h fecal fat quantitation does not differentiate between the primary sources of the measured fatty acid. It is concluded that the 72-h fecal fat determination is not specific for documenting triglyceride (fat) malabsorption. Until new methods are developed that specifically measure fecal triglyceride and fatty acid, the Sudan stain of fecal fat appears to be a more specific method for detecting the presence of triglyceride and fatty acid in a matrix.
Curry, E; Roth, T L; MacKinnon, K M; Stoops, M A
2012-12-01
The objectives of this study were to assess the effects of season, breeding activity, age and latitude on fecal testosterone metabolite concentrations in captive, adult male polar bears (Ursus maritimus). Fourteen polar bears from 13 North American zoos were monitored for 12-36 months, producing 25-year-long testosterone profiles. Results indicated that testosterone was significantly higher during the breeding season (early January through the end of May) compared with the non-breeding season with the highest concentrations excreted from early January through late March. Variations in excretion patterns were observed among individuals and also between years within an individual, with testosterone peaks closely associated with breeding activity. Results indicate that fecal testosterone concentrations are influenced by season, breeding activity and age, but not by latitude. This is the first report describing longitudinal fecal testosterone metabolite concentrations in individual adult male polar bears. © 2012 Blackwell Verlag GmbH.
Del Bas, Josep Maria; Crescenti, Anna; Arola-Arnal, Anna; Oms-Oliu, Gemma; Arola, Lluís; Caimari, Antoni
2015-12-01
Cardiovascular disease (CVD) is one of the most prevalent noncommunicable diseases in humans. Different studies have identified dietary procyanidins as bioactive compounds with beneficial properties against CVD by improving lipid homeostasis, among other mechanisms. The aim of this work was to assess whether grape seed procyanidin consumption at a physiological dose during the perinatal period could influence the CVD risk of the offspring. Wistar rat dams were treated with a grape seed procyanidin extract (GSPE; 25mg/kg of body weight per day) or vehicle during gestation and lactation. The adult male offspring of GSPE-treated dams presented decreased high-density lipoprotein cholesterol (HDL-C) levels, increased total cholesterol-to-HDL-C ratios and an exacerbated fasting triglyceride-to-HDL-C ratios (atherogenic index of plasma) compared to the control group. Impaired reverse cholesterol transport (RCT) was evidenced by the accumulation of cholesterol in skeletal muscle and by decreased fecal excretion of cholesterol and bile acids, which was consistent with the observed mRNA down-regulation of the rate-limiting enzyme in the hepatic bile acid synthesis pathway Cyp7A1. Conversely, GSPE programming also resulted in up-regulated gene expression of different key components of the RCT process, such as hepatic Npc1, Abcg1, Abca1, Lxra, Srebp2, Lcat, Scarb1 and Pltp, and the repression of microRNA miR-33a expression, a key negative controller of hepatic RCT at the gene expression level. Our results show that maternal intake of grape procyanidins during the perinatal period impacts different components of the RCT process, resulting in increased CVD risk in the adult offspring. Copyright © 2015 Elsevier Inc. All rights reserved.
Kootte, Ruud S.; Smits, Loek P.; van der Valk, Fleur M.; Dasseux, Jean-Louis; Keyserling, Constance H.; Barbaras, Ronald; Paolini, John F.; Santos, Raul D.; van Dijk, Theo H.; Dallinga-van Thie, Geesje M.; Nederveen, Aart J.; Mulder, Willem J. M.; Hovingh, G. Kees; Kastelein, John J. P.; Groen, Albert K.; Stroes, Erik S.
2015-01-01
Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8–29.1] mg/dl; apoA-I, 28.7 [7.9–59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm2 (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients. PMID:25561459
Kootte, Ruud S; Smits, Loek P; van der Valk, Fleur M; Dasseux, Jean-Louis; Keyserling, Constance H; Barbaras, Ronald; Paolini, John F; Santos, Raul D; van Dijk, Theo H; Dallinga-van Thie, Geesje M; Nederveen, Aart J; Mulder, Willem J M; Hovingh, G Kees; Kastelein, John J P; Groen, Albert K; Stroes, Erik S
2015-03-01
Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8-29.1] mg/dl; apoA-I, 28.7 [7.9-59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm(2) (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.
Dietary corn fractions reduce atherogenesis in low-density lipoprotein receptor knockout mice.
Masisi, Kabo; Le, Khuong; Ghazzawi, Nora; Moghadasian, Mohammed H; Beta, Trust
2017-01-01
Accumulating evidence has suggested that intake of whole grains is a protective factor against pathogenesis of coronary artery disease. The exact mechanisms, however, are still not clearly understood. In this study, we hypothesized that adequate intake of corn fractions (aleurone, endosperm and germ) can modify lipid profiles in relation to atherosclerotic lesion development in low-density lipoprotein receptor knockout (LDLr-KO) mice. The purpose of the present study was to investigate the potential cardiovascular benefits of corn fractions in LDLr-KO mice through a number of biomarkers including lipid profile, and morphologic and morphometrical analysis of atherosclerotic lesions in aortic root. Four groups of male LDLr-KO mice were fed with the experimental diets supplemented with (3 treated) or without (control) 5% (wt/wt) of each of corn fractions for 10 weeks. All diets were supplemented with 0.06% (wt/wt) cholesterol. Compared with mice in the control group, atherosclerotic lesions in the aortic roots were significantly reduced (P=.003) in the mice that were fed diet supplemented with aleurone and germ fractions. This effect was associated with significant reductions in plasma total (P=.02) and LDL (P=.03) cholesterol levels, and an increase in fecal cholesterol excretion (P=.04). Furthermore, abdominal fat mass was significantly reduced by consumption of aleurone (P=.03). In summary, the consumption of aleurone and germ may help attenuate atherosclerosis by reducing plasma total and LDL cholesterol levels. Copyright © 2016 Elsevier Inc. All rights reserved.
Yang, Tsung-Han; Yao, Hsien-Tsung; Chiang, Meng-Tsan
2017-10-01
The purpose of this study was to investigate the effects of Gelidium amansii (GA) hot-water extracts (GHE) on lipid metabolism in hamsters. Six-week-old male Syrian hamsters were used as the experimental animals. Hamsters were divided into four groups: (1) control diet group (CON); (2) high-fat diet group (HF); (3) HF with GHE diet group (HF + GHE); (4) HF with probucol diet group (HF + PO). All groups were fed the experimental diets and drinking water ad libitum for 6 weeks. The results showed that GHE significantly decreased body weight, liver weight, and adipose tissue (perirenal and paraepididymal) weight. The HF diet induced an increase in plasma triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol levels. However, GHE supplementation reversed the increase of plasma lipids caused by the HF diet. In addition, GHE increased fecal cholesterol, TG and bile acid excretion. Lower hepatic TC and TG levels were found with GHE treatment. GHE reduced hepatic sterol regulatory element-binding proteins (SREBP) including SREBP 1 and SREBP 2 protein expressions. The phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) protein expression in hamsters was decreased by the HF diet; however, GHE supplementation increased the phosphorylation of AMPK protein expression. Our results suggest that GHE may ameliorate lipid metabolism in hamsters fed a HF diet. Copyright © 2017. Published by Elsevier B.V.
Lever, Michael; George, Peter M.; Atkinson, Wendy; Elmslie, Jane L.; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.
2012-01-01
Background Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease. Methods The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic. Principal findings In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = −0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = −0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion. Conclusions Betaine excretion correlates with homocysteine in subjects with elevated blood lipids. PMID:22396767
London, Lis E E; Kumar, Arun H S; Wall, Rebecca; Casey, Pat G; O'Sullivan, Orla; Shanahan, Fergus; Hill, Colin; Cotter, Paul D; Fitzgerald, Gerald F; Ross, R Paul; Caplice, Noel M; Stanton, Catherine
2014-12-01
Probiotic bacteria have been associated with a reduction in cardiovascular disease risk, a leading cause of death and disability. The aim of this study was to assess the impact of dietary administration of exopolysaccharide-producing probiotic Lactobacillus cultures on lipid metabolism and gut microbiota in apolipoprotein E (apoE)-deficient mice. First, we examined lipid metabolism in response to dietary supplementation with recombinant β-glucan-producing Lactobacillus paracasei National Food Biotechnology Centre (NFBC) 338 expressing the glycosyltransferase (Gtf) gene from Pediococcus parvulus 2.6 (GTF), and naturally exopolysaccharide-producing Lactobacillus mucosae Dairy Product Culture Collection (DPC) 6426 (DPC 6426) compared with the non-β-glucan-producing isogenic control strain Lactobacillus paracasei NFBC 338 (PNZ) and placebo (15% wt:vol trehalose). Second, we examined the effects on the gut microbiota of dietary administration of DPC 6426 compared with placebo. Probiotic Lactobacillus strains at 1 × 10(9) colony-forming units/d per animal were administered to apoE(-/-) mice fed a high-fat (60% fat)/high-cholesterol (2% wt:wt) diet for 12 wk. At the end of the study, aortic plaque development and serum, liver, and fecal variables involved in lipid metabolism were analyzed, and culture-independent microbial analyses of cecal content were performed. Total cholesterol was reduced in serum (P < 0.001; ∼33-50%) and liver (P < 0.05; ∼30%) and serum triglyceride concentrations were reduced (P < 0.05; ∼15-25%) in mice supplemented with GTF or DPC 6426 compared with the PNZ or placebo group, respectively. In addition, dietary intervention with GTF led to increased amounts of fecal cholesterol excretion (P < 0.05) compared with all other groups. Compositional sequencing of the gut microbiota revealed a greater prevalence of Porphyromonadaceae (P = 0.001) and Prevotellaceae (P = 0.001) in the DPC 6426 group and lower proportions of Clostridiaceae (P < 0.05), Peptococcaceae (P < 0.001), and Staphylococcaceae (P < 0.01) compared with the placebo group. Ingestion of exopolysaccharide-producing lactobacilli resulted in seemingly favorable improvements in lipid metabolism, which were associated with changes in the gut microbiota of mice. © 2014 American Society for Nutrition.
Ordovas, Jose M; Tai, E Shyong
2002-01-01
Hypercholesterolaemia is a major risk factor for coronary heart disease (CHD). Therefore, the reduction of low-density lipoprotein (LDL) cholesterol is one of the primary targets of the current recommendations to decrease CHD risk in the population. Whereas, the mechanisms involved in de novo cholesterol synthesis and its uptake by cells via the LDL receptor are well known, we still need better understanding about the mechanisms involved in intestinal cholesterol absorption and excretion. The recent discovery of ABCG5 and ABCG8 transporters will significantly improve our understanding of cholesterol trafficking and it will lead to better and new therapeutic strategies to maintain cholesterol homeostasis.
Starch blockers--their effect on calorie absorption from a high-starch meal.
Bo-Linn, G W; Santa Ana, C A; Morawski, S G; Fordtran, J S
1982-12-02
It has been known for more than 25 years that certain plant foods, such as kidney beans and wheat, contain a substance that inhibits the activity of salivary and pancreatic amylase. More recently, this antiamylase has been purified and marketed for use in weight control under the generic name "starch blockers." Although this approach to weight control is highly popular, it has never been shown whether starch-blocker tablets actually reduce the absorption of calories from starch. Using a one-day calorie-balance technique and a high-starch (100 g) meal (spaghetti, tomato sauce, and bread), we measured the excretion of fecal calories after normal subjects had taken either placebo or starch-blocker tablets. If the starch-blocker tablets had prevented the digestion of starch, fecal calorie excretion should have increased by 400 kcal. However, fecal calorie excretion was the same on the two test days (mean +/- S.E.M., 80 +/- 4 as compared with 78 +/- 2). We conclude that starch-blocker tablets do not inhibit the digestion and absorption of starch calories in human beings.
Harris, Breanna N.; Saltzman, Wendy; de Jong, Trynke R.; Milnes, Matthew R.
2012-01-01
The California mouse, Peromyscus californicus, is an increasingly popular animal model in behavioral, neural, and endocrine studies, but little is known about its baseline hypothalamicpituitary-adrenal (HPA) axis activity or HPA responses to stressors. We characterized plasma corticosterone (CORT) concentrations in P. californicus under baseline conditions across the diurnal cycle, in response to pharmacological manipulation of the HPA axis, and in response to a variety of stressors at different times of day. In addition, we explored the use of fecal samples to monitor adrenocortical activity non-invasively. California mice have very high baseline levels of circulating CORT that change markedly over 24 hours, but that do not differ between the sexes. This species may be somewhat glucocorticoid-resistant in comparison to other rodents as a relatively high dose of dexamethasone (5 mg/kg, s.c.) was required to suppress plasma CORT for 8 h post-injection. CORT responses to stressors and ACTH injection differed with time of day, as CORT concentrations were elevated more readily during the morning (inactive period) than in the evening (active period) when compared to time-matched control. Data from 3H-CORT injection studies show that the time course for excretion of fecal CORT, or glucocorticoid metabolites, differs with time of injection. Mice injected in the evening excreted the majority of fecal radioactivity 2–4 h post-injection whereas mice injected during the morning did so at 14–16 h post-injection. Unfortunately, the antibody we used does not adequately bind the most prevalent fecal glucocorticoid metabolites and therefore we could not validate its use for fecal assays. PMID:23026495
Intestinal blood loss during cow milk feeding in older infants: quantitative measurements.
Jiang, T; Jeter, J M; Nelson, S E; Ziegler, E E
2000-07-01
To determine the response, in terms of fecal hemoglobin excretion and clinical symptoms, of normal 9 1/2-month-old infants to being fed cow milk. Longitudinal (before-after) trial in which each infant was fed formula for 1 month (baseline) followed by 3 months during which cow milk was fed. Healthy infants living in Iowa City, Iowa, a town with a population of about 60,000. Hemoglobin concentration in spot stools, 96-hour quantitative fecal hemoglobin excretion, stool characteristics, feeding-related behaviors, and iron nutritional status. Fecal hemoglobin concentration during formula feeding (baseline) was higher than previously observed in younger infants. Nine of 31 infants responded to cow milk feeding with increased fecal hemoglobin concentration. Fecal hemoglobin concentration (mean +/- SD) of the 9 responders rose from 1,395 +/- 856 microg/g of dry stool (baseline) to 2,711 +/- 1,732 microg/g of dry stool (P=.01). The response rate (29%) was similar to that in younger infants, but the intensity of the response was much less. Quantitative hemoglobin excretion was in general agreement with estimates based on spot stool hemoglobin concentrations. Cow milk feeding was not associated with recognizable changes in stool characteristics, nor were there clinical signs related to fecal blood loss. Iron status was similar, except that after 3 months of cow milk feeding responders showed lower (P= .047) ferritin concentrations than nonresponders. Cow milk-induced blood loss is present in 9 1/2-month-old infants but is of such low intensity that its clinical significance seems questionable. Nevertheless, infants without cow milk-induced blood loss were in better iron nutritional status than infants who showed blood loss.
Repa, J J; Lund, E G; Horton, J D; Leitersdorf, E; Russell, D W; Dietschy, J M; Turley, S D
2000-12-15
Sterol 27-hydroxylase (CYP27) participates in the conversion of cholesterol to bile acids. We examined lipid metabolism in mice lacking the Cyp27 gene. On normal rodent chow, Cyp27(-/-) mice have 40% larger livers, 45% larger adrenals, 2-fold higher hepatic and plasma triacylglycerol concentrations, a 70% higher rate of hepatic fatty acid synthesis, and a 70% increase in the ratio of oleic to stearic acid in the liver versus Cyp27(+/+) controls. In Cyp27(-/-) mice, cholesterol 7alpha-hydroxylase activity is increased 5-fold, but bile acid synthesis and pool size are 47 and 27%, respectively, of those in Cyp27(+/+) mice. Intestinal cholesterol absorption decreases from 54 to 4% in knockout mice, while fecal neutral sterol excretion increases 2.5-fold. A compensatory 2.5-fold increase in whole body cholesterol synthesis occurs in Cyp27(-/-) mice, principally in liver, adrenal, small intestine, lung, and spleen. The mRNA for the cholesterogenic transcription factor sterol regulatory element-binding protein-2 (SREBP-2) and mRNAs for SREBP-2-regulated cholesterol biosynthetic genes are elevated in livers of mutant mice. In addition, the mRNAs encoding the lipogenic transcription factor SREBP-1 and SREBP-1-regulated monounsaturated fatty acid biosynthetic enzymes are also increased. Hepatic synthesis of fatty acids and accumulation of triacylglycerols increases in Cyp27(-/-) mice and is associated with hypertriglyceridemia. Cholic acid feeding reverses hepatomegaly and hypertriglyceridemia but not adrenomegaly in Cyp27(-/-) mice. These studies confirm the importance of CYP27 in bile acid synthesis and they reveal an unexpected function of the enzyme in triacylglycerol metabolism.
Wasser, Samuel K; Hunt, Kathleen E
2005-06-01
There is an urgent need for noninvasive methods to study reproduction and environmental stress in at-risk species such as the northern spotted owl (Strix occidentalis caurina). Two related owl species (barred owl and great horned owl) were used as surrogates to validate hormone assays for fecal metabolites of progesterone, 17beta-estradiol, testosterone, and corticosterone. Infusions of radiolabeled hormones showed that the owls excreted most hormone within 6 h. Feces and urine contained roughly equal amounts of hormone, and most fecal hormone metabolites were quite polar. The testosterone and corticosterone assays in this study bound to the major excreted metabolites of these hormones, but two progesterone assays did not appreciably bind to the major progesterone metabolites. All assays showed excellent parallelism with hydrolyzed and unhydrolyzed samples and with previously dried or undried fecal samples. Thus, samples do not require hydrolysis or prior drying. Samples from a female barred owl had significantly higher fecal estrogen, lower fecal testosterone, and higher fecal estrogen/testosterone ratio than samples from two male barred owls. The fecal estrogen/testosterone ratio was the most accurate predictor of owl gender, particularly if two or more samples are available from the same individual. Fecal corticosterone metabolites also demonstrated considerable utility for wild northern spotted owls. Fecal glucocorticoid levels varied by gender and breeding stage, being highest in male northern spotted owls early in the breeding season and highest in females when nestlings were fledging. Collectively, these studies show that noninvasive fecal hormone measurements show great promise for noninvasive assessment of reproduction and stress in wild owls.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.
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 inmore » 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.« less
Hypocholesterolemic Properties and Prebiotic Effects of Mexican Ganoderma lucidum in C57BL/6 Mice.
Meneses, María E; Martínez-Carrera, Daniel; Torres, Nimbe; Sánchez-Tapia, Mónica; Aguilar-López, Miriam; Morales, Porfirio; Sobal, Mercedes; Bernabé, Teodoro; Escudero, Helios; Granados-Portillo, Omar; Tovar, Armando R
2016-01-01
Edible and medicinal mushrooms contain bioactive compounds with promising effects on several cardiovascular risk biomarkers. However, strains of Ganoderma lucidum of Mexican origin have not yet been studied. Standardized extracts of G. lucidum (Gl) were given to C57BL/6 mice fed a high-cholesterol diet compared with the drug simvastatin. The effects of the extracts on serum biochemical parameters, liver lipid content, cholesterol metabolism, and the composition of gut microbiota were assessed. Acetylsalicylic acid (10 mM) added to the cultivation substrate modulated properties of Gl extracts obtained from mature basidiomata. Compared to the high-cholesterol diet group, the consumption of Gl extracts significantly reduced total serum cholesterol (by 19.2% to 27.1%), LDL-C (by 4.5% to 35.1%), triglyceride concentration (by 16.3% to 46.6%), hepatic cholesterol (by 28.7% to 52%) and hepatic triglycerides (by 43.8% to 56.6%). These effects were associated with a significant reduction in the expression of lipogenic genes (Hmgcr, Srebp1c, Fasn, and Acaca) and genes involved in reverse cholesterol transport (Abcg5 and Abcg8), as well as an increase in Ldlr gene expression in the liver. No significant changes were observed in the gene expression of Srebp2, Abca1 or Cyp7a1. In several cases, Gl-1 or Gl-2 extracts showed better effects on lipid metabolism than the drug simvastatin. A proposed mechanism of action for the reduction in cholesterol levels is mediated by α-glucans and β-glucans from Gl, which promoted decreased absorption of cholesterol in the gut, as well as greater excretion of fecal bile acids and cholesterol. The prebiotic effects of Gl-1 and Gl-2 extracts modulated the composition of gut microbiota and produced an increase in the Lactobacillaceae family and Lactobacillus genus level compared to the control group, high-cholesterol diet group and group supplemented with simvastatin. Mexican genetic resources of Gl represent a new source of bioactive compounds showing hypocholesterolemic properties and prebiotic effects.
Hypocholesterolemic Properties and Prebiotic Effects of Mexican Ganoderma lucidum in C57BL/6 Mice
Meneses, María E.; Martínez-Carrera, Daniel; Torres, Nimbe; Sánchez-Tapia, Mónica; Aguilar-López, Miriam; Morales, Porfirio; Sobal, Mercedes; Bernabé, Teodoro; Escudero, Helios; Granados-Portillo, Omar; Tovar, Armando R.
2016-01-01
Edible and medicinal mushrooms contain bioactive compounds with promising effects on several cardiovascular risk biomarkers. However, strains of Ganoderma lucidum of Mexican origin have not yet been studied. Standardized extracts of G. lucidum (Gl) were given to C57BL/6 mice fed a high-cholesterol diet compared with the drug simvastatin. The effects of the extracts on serum biochemical parameters, liver lipid content, cholesterol metabolism, and the composition of gut microbiota were assessed. Acetylsalicylic acid (10 mM) added to the cultivation substrate modulated properties of Gl extracts obtained from mature basidiomata. Compared to the high-cholesterol diet group, the consumption of Gl extracts significantly reduced total serum cholesterol (by 19.2% to 27.1%), LDL-C (by 4.5% to 35.1%), triglyceride concentration (by 16.3% to 46.6%), hepatic cholesterol (by 28.7% to 52%) and hepatic triglycerides (by 43.8% to 56.6%). These effects were associated with a significant reduction in the expression of lipogenic genes (Hmgcr, Srebp1c, Fasn, and Acaca) and genes involved in reverse cholesterol transport (Abcg5 and Abcg8), as well as an increase in Ldlr gene expression in the liver. No significant changes were observed in the gene expression of Srebp2, Abca1 or Cyp7a1. In several cases, Gl-1 or Gl-2 extracts showed better effects on lipid metabolism than the drug simvastatin. A proposed mechanism of action for the reduction in cholesterol levels is mediated by α-glucans and β-glucans from Gl, which promoted decreased absorption of cholesterol in the gut, as well as greater excretion of fecal bile acids and cholesterol. The prebiotic effects of Gl-1 and Gl-2 extracts modulated the composition of gut microbiota and produced an increase in the Lactobacillaceae family and Lactobacillus genus level compared to the control group, high-cholesterol diet group and group supplemented with simvastatin. Mexican genetic resources of Gl represent a new source of bioactive compounds showing hypocholesterolemic properties and prebiotic effects. PMID:27438015
OBSERVATIONS CONCERNING THE PRODUCTION AND EXCRETION OF CHOLESTEROL IN MAMMALS
Byers, Sanford O.; Friedman, Meyer; Biggs, Max W.; Gunning, Barbara
1953-01-01
Accumulation of cholate in plasma is the immediate cause of hypercholesteremia in the rat with bile duct ligation and in the normal rat given intravenous sodium cholate. The hypercholesteremia induced by cholate administration does not appear to be dependent upon any preceding change in the rates of absorption, excretion, synthesis, or redistribution of cholesterol in the tissues of the animal. Cholate administration seems to induce hypercholesteremia by impeding the normal rate of passage of cholesterol from the plasma into the liver; this impedance is probably due to an alteration of the cholesterol-binding power of plasma proteins induced by cholate. The chemical and physiological implications of this finding are discussed. PMID:13052817
Effect of ethanol on the retention of americium-241 in the baboon liver.
Cohen, N; Antonelli, R; Lo Sasso, T; Wrenn, M E
1978-01-01
The oral administration of ethyl alcohol enhanced the excretion of 241Am from the liver of a baboon by 2.5 times that of a control animal. After ethanol administration, increases in the total content of 241Am excreted in feces were accompanied by corresponding increases in fecal volumes, although administration of nonalcoholic cathartics would not be expected to produce a similar effect. The effectiveness of ethanol as a decorporating agent may result from its ability to mobilize intracellularly bound 241Am from the liver, thereby making the nuclide more available for metabolic secretory mechanisms occurring via liver-bile-fecal route.
USDA-ARS?s Scientific Manuscript database
During the postnatal feeding period, formula-fed infants have higher cholesterol synthesis rates, and lower circulating cholesterol concentrations as compared to their breastfed counterparts. Although this disparity has been attributed to the uniformly low dietary cholesterol content of typical inf...
[Fecal sIgS and lysozyme excretion in breast feeding and formula feeding].
Eschenburg, G; Heine, W; Peters, E
1990-05-01
The bioavailability of sIgA and lysozyme from human milk was investigated in a total of 41 infants by radial immunodiffusion and by the Micrococcus lysodeicticus method, respectively. In four different pools of human milk used for balance studies the sIgA concentrations ranged between 2,200 and 17,850 mg/l. The lysozyme concentration varied from 64.5 to 283.5 mg/l. On human milk feeding the excretion of sIgA in 19 infants was 3,200 (0-8,200) mg per litre and 9.7 (0-131) mg lysozyme per litre, respectively. Corresponding values on formula feeding in 22 infants were 1030 (0-6400) and 2.6 (0-9) mg/l. Fecal sIgA excretion was significantly higher on human milk than on formula feeding. Balances of sIgA and lysozyme intake and excretion as performed in 9 infants revealed a less than 1% fecal excretion of both the protective substances. In vitro digestion of raw human milk with pepsin at pH 2 and 3 resulted in a rapid disappearance of immunologically reactive sIgA within 30 minutes after starting the incubation, while no changes in sIgA content were detectable at pH 4. Lysozyme proved to be resistant against peptic digestion. Tryptic digestion at pH 8 did not result in a decrease of human milk sIgA within 120 minutes of incubation at 37 degrees C while under analogous conditions lysozyme concentration approached to 0. These results point at the full bioavailability of both sIgA and lysozyme from human milk. The differing resistance of these protective substances against pepsin and trypsin is apparently adapted to physiological particularities of the digestive tract in early infancy.
Cohen, David E
2016-12-13
Cholesterol homeostasis is achieved by balancing rates of endogenous synthesis, absorption, and elimination. Although biliary secretion into the intestinal lumen is classically considered as the only significant route for cholesterol elimination, Jakulj et al. (2016) reveal in this issue how transintestinal cholesterol excretion (TICE) accounts for substantial cholesterol losses. Copyright © 2016. Published by Elsevier Inc.
Pharmacokinetics of TAK-475, a Squalene Synthase Inhibitor, in Rats and Dogs.
Ebihara, T; Teshima, K; Kondo, T; Tagawa, Y; Moriwaki, T; Asahi, S
2016-06-01
The pharmacokinetics of TAK-475 (lapaquistat acetate), a squalene synthase inhibitor, was investigated in rats and dogs. After oral administration of (14)C-labeled TAK-475 ([(14)C]TAK-475) to rats and dogs at a dose of 10 mg/kg, the bioavailability (BA) was relatively low at 3.5 and 8.2%, respectively. The main component of the radioactivity in the plasma was M-I, which has a comparable pharmacological activity to TAK-475 in vitro. The radioactivity in the portal plasma after intraduodenal administration of [(14)C]TAK-475 to portal vein-cannulated rat was also mainly M-I, suggesting that most of the TAK-475 was hydrolyzed to M-I during the permeable process in the intestine. The concentrations of M-I in the liver, the main organ of cholesterol biosynthesis, were much higher than those in the plasma after oral administration of [(14)C]TAK-475 to rats. The main elimination route of the radioactivity was fecal excretion after oral administration of [(14)C]TAK-475 to rats and dogs, and the absorbed radioactivity was mainly excreted via the bile as M-I in rats. M-I excreted into the bile was partially subjected to enterohepatic circulation. These results suggest that although the BA values of TAK-475 are low, M-I can exert compensatory pharmacological effects in the animals. These pharmacokinetic characteristics in animals were also confirmed in the clinical studies. The evaluation of M-I disposition is important for the pharmacokinetics, pharmacodynamics and toxicity of TAK-475 in animals and humans. © Georg Thieme Verlag KG Stuttgart · New York.
Gidenne, T; Fortun-Lamothe, L; Bannelier, C; Molette, C; Gilbert, H; Chemit, M L; Segura, M; Benitez, F; Richard, F; Garreau, H; Drouilhet, L
2017-03-01
Two rabbit lines have been created to result in better feed efficiency: the ConsoResidual line was selected for a lower residual feed intake under ad libitum feeding, and the ADGrestrict line was selected for higher ADG under restricted feeding (-20% of ad libitum). The present study aimed to analyze the digestion and excretion of N and minerals from 29 to 63 d of age of these 2 lines compared with an unselected control line (G0) under 2 feeding levels (ad libitum or restricted). The ADGrestrict line had greater digestibility compared with G0 (+1.3% for OM and N; < 0.05), and the ConsoResidual line had intermediate values. There was no genetic line effect on the digestibility of N and P and on minerals concentrations (P, Zn, and Cu) in the feces and in the urine. The N balance was improved for the 2 selected lines (+5%; < 0.05), leading to a reduced N output through the feces (0.06 g/d compared with G0; < 0.001) and the urine (-0.07 g/d; < 0.05) and to an improved N retention ratio (+3% compared with G0). Over the whole fattening period (d 29-63), significant differences were observed among lines only when fed ad libitum, with 13% greater DM fecal output and 5% greater N fecal output for G0. The N excretion in urine was 2 g less in the 2 selected lines, leading to a reduction of total N release of 4.4 g (compared with G0). The P excretion in feces (12 g) or urine (0.1 g) did not differ among the 3 lines. Over the whole fattening period and for ad libitum-fed rabbits, the 5% improvement in feed efficiency ( < 0.01) for the 2 selected lines corresponded to 400 g less feed intake (-8%) and to 20 g less N intake. The fecal excretion of the ADGrestrict and ConsoResidual lines were reduced by 200 g DM ( < 0.01), corresponding to 417 g fresh matter and 5 g of N. The excretion in minerals (P, Zn, and Cu) was not affected by the line. The feeding level strongly reduced the fecal and urine outputs (-50 and -60%, respectively; < 0.001). Higher digestibility coefficients ( < 0.001) were found in restricted-fed rabbits for OM (+6%), N (+8%), and P (+11%). The N balance was substantially improved by the restriction, with 40% less total (feces + urine) N excretion ( < 0.001). The P balance was improved by the restriction (0.469 vs. 0.360). Over the fattening period, the P fecal output was 37% less (-6 g) with 24% less feed intake and the Zn and Cu outputs were reduced by 27 (-130 mg) and 29% (-30 mg), respectively.
Effect of cocoa bran on low-density lipoprotein oxidation and fecal bulking.
Jenkins, D J; Kendall, C W; Vuksan, V; Vidgen, E; Wong, E; Augustin, L S; Fulgoni, V
Legumes have reported benefits in terms of reduced risk for coronary heart disease and of colonic health. A novel legume fiber, cocoa bran, also may have favorable health effects on serum lipid levels, low-density lipoprotein (LDL) cholesterol oxidation, and fecal bulk. Twenty-five healthy normolipidemic subjects (13 men and 12 women) (mean +/- SEM age, 37 +/- 2 years; mean +/- SEM body mass index [calculated as weight in kilograms divided by the square of height in meters], 24.6 +/- 0.7) ate cocoa-bran and chocolate-flavored low-fiber breakfast cereals for 2-week periods, with 2-week washout, in a double-blind crossover study. The cocoa-bran cereal provided 25.0 g/d of total dietary fiber (TDF). The low-fiber cereal (5.6 g/d TDF) was of similar appearance and energy value. Fasting blood samples were obtained at the start and end of each period, and 4-day fecal collections were made from days 11 through 14. High-density lipoprotein (HDL) cholesterol level was higher (7.6% +/- 2.9%; P =.02) and the LDL/HDL cholesterol ratio was lower (6.7% +/- 2.3%; P =.007) for cocoa-bran compared with low-fiber cereal at 2 weeks. No effect was seen on LDL cholesterol oxidation. Mean fecal output was significantly higher for cocoa-bran than for low-fiber cereal (56 +/- 14 g/d; P<.001) and equal to the increase seen in the same subjects with wheat fiber in a previous study. A chocolate-flavored cocoa-bran cereal increased fecal bulk similarly to wheat bran and was associated with a reduction in the LDL/HDL cholesterol ratio. In view of the low-fat, high-fiber nature of the material, these results suggest a possible role for this novel fiber source in the diets of normal, hyperlipidemic, and constipated subjects.
Rahman, Hafeedza Abdul; Sahib, Najla Gooda; Saari, Nazamid; Abas, Faridah; Ismail, Amin; Mumtaz, Muhammad Waseem; Hamid, Azizah Abdul
2017-02-22
Obesity is a major health concern both in developed and developing countries. The use of herbal medicines became the subject of interest for the management of obesity due to its natural origin, cost effectiveness and minimal side effects. The present study aimed at investigating anti-obesity potential of ethanolic extract from Cosmos caudatus Kunth leaf (EECCL). In this study, the rats were randomly divided into six groups i.e., (1) Normal Diet (ND); (2) Normal Diet and 175 mg/kgBW of EECCL (ND + 175 mg/kgBW); (3) Normal Diet and 350 mg/kgBW of EECCL (ND + 350 mg/kgBW); (4) High Fat Diet (HFD); (5) High Fat Diet and 175 mg/kgBW of EECCL (HFD + 175 mg/kgBW); (6) High Fat Diet and 350 mg/kgBW of EECCL (HFD + 350 mg/kgBW). The anti-obesity potential was evaluated through analyses of changes in body weight, visceral fat weight, and blood biochemicals including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), leptin, insulin, adiponectin, ghrelin and fecal fat content. In addition, metabolite profiling of EECCL was carried out using NMR spectroscopy. Rats receiving EECCL together with HFD showed significant (p < 0.05) reduction in body weight gain compared to rats receiving HFD only. At the end of study, the body weight gain of EECCL treated rats was not significantly (p > 0.05) different with those of ND rats. Other related obesity biomarkers including plasma lipid profiles, insulin, leptin, ghrelin and adiponectin levels also showed significant improvement (p < 0.05). Administration of EECCL caused significant (p < 0.05) increase in fecal fat excretion, which validates the hypothesis of lipase inhibition, an anti-obesity mechanism similar to standard drug of Orlistat. The 1 H-NMR spectra of EECCL ascertained the presence of catechin, quercetin, rutin, kaempherol and chlorogenic acid in the extract. Conclusively, EECCL showed anti-obesity properties by inhibition of intestinal lipid absorption and modulation of adipocytes markers.
Heijnen, M L; van den Berg, G J; Beynen, A C
1996-09-01
Dietary raw (RS2) vs. retrograded resistant starch (RS3) raises apparent magnesium absorption in rats. The mechanism proposed is that RS2 enhances magnesium avaibility for absorption; it does this by increasing ileal solubility of magnesium due to a reduction in pH as a consequence of RS2 fermentation in the gut. The mechanism implies that dietary RS2 vs. RS3 would raise true magnesium absorption and stimulate reabsorption of endogenous magnesium, leading to a lower fecal excretion of endogenous magnesium. Dietary lactulose vs. glucose raises apparent magnesium absorption, and the mechanism proposed is similar to that for the stimulatory effect of RS2 vs. RS3. Thus, we measured in rats fed RS3, RS2, glucose or lactulose true magnesium absorption on the basis of the retention of the orally and intraperitoneally administered radiotracer 28Mg. Feeding rats RS2 instead of RS3 significantly enhanced apparent but not true magnesium absorption, because RS2 lowered fecal excretion of endogenous magnesium. When compared with dietary glucose, lactulose significantly raised both apparent and true magnesium absorption, but did not affect fecal excretion of endogenous magnesium. It is suggested that the proposed mechanism by which RS2 and lactulose would enhance magnesium absorption is disproved by the present data.
Karaya root saponin exerts a hypocholesterolemic response in rats fed a high-cholesterol diet.
Afrose, Sadia; Hossain, Md S; Maki, Takaaki; Tsujii, Hirotada
2009-05-01
Different sources of saponins are known to have hypocholesterolemic activity with varying degrees of efficacy. We hypothesize that karaya root saponin would efficiently reduce cholesterol. The aim of this study is to examine the comparative hypocholesterolemic effect of karaya root saponin in rats fed a high-cholesterol diet. Sixty male Wister-Imamichi rats were divided into 5 groups of 12 rats each constituting of the following: control group, soybean saponin-supplemented group, karaya root saponin-supplemented group, quillaja saponin-supplemented group, and tea saponin-supplemented group. Compared with the control diet, both the karaya root- and quillaja saponin-supplemented diets significantly reduced (P < .05) serum cholesterol and atherogenic index. Karaya root saponin significantly increased the serum high-density lipoprotein cholesterol, high-density lipoprotein cholesterol/cholesterol ratio, and fecal cholesterol concentrations (P < .05). The triacylglycerol concentration was significantly reduced only in the quillaja saponin-supplemented rats (P < .05). All the tea, soybean, karaya root, and quillaja saponins significantly reduced low-density lipoprotein cholesterol, and the greatest reduction was observed with karaya root saponin. Highest fecal bile acid concentration was found with quillaja saponin, whereas highest liver bile acid concentration was observed with karaya root saponin-supplemented rats (P < .05). These results collectively suggest that karaya root saponin can efficiently reduce serum cholesterol concentration in rats.
Parolini, Cinzia; Caligari, Silvia; Gilio, Donatella; Manzini, Stefano; Busnelli, Marco; Montagnani, Marco; Locatelli, Marcello; Diani, Erika; Giavarini, Flavio; Caruso, Donatella; Roda, Enrico; Roda, Aldo; Sirtori, Cesare R; Chiesa, Giulia
2012-10-01
Apolipoprotein (apo)A-I(M) (ilano), is a molecular variant of apoA-I(wild-type), associated with dramatically low HDL-cholesterol levels, but no increased risk for cardiovascular disease. In view of the present uncertainties on the role of apoA-I in liver cholesterol removal by way of bile acids and neutral sterols, and of the greater capacity of apoA-I(M) (ilano) to remove arterial cholesterol, biliary sterol metabolism was evaluated in transgenic mice expressing apoA-I(M) (ilano). ApoA-I(M) (ilano) mice were fed a high-cholesterol/high-fat diet, and compared with human apoA-I(wild-type) mice. Plasma lipid levels, hepatic bile flow and composition, hepatic and intestinal cholesterol and bile acid content, and faecal sterol content were measured. Moreover, the expression of hepatic ABCA1, SR-B1 and that of hepatic and intestinal genes involved in bile acid metabolism were evaluated. The dietary treatment led to a strong elevation in HDL-cholesterol levels in A-I(M) (ilano) mice, associated with an increased expression of hepatic ABCA1. ApoA-I(M) (ilano) mice showed lower cholesterol output from the liver compared with apoA-I(wild-type) mice, in the absence of liver sterol accumulation. Faecal excretion of neutral sterols and bile acids was similar in the two mouse lines. In spite of a different response to the dietary challenge, with an increased ABCA1 expression and a lower hepatic cholesterol output in apoA-I(M) (ilano) mice, the net sterol excretion is comparable in the two transgenic lines. © 2012 John Wiley & Sons A/S.
Fecal Calprotectin Excretion in Preterm Infants during the Neonatal Period
Rougé, Carole; Butel, Marie-José; Piloquet, Hugues; Ferraris, Laurent; Legrand, Arnaud; Vodovar, Michel; Voyer, Marcel; de la Cochetière, Marie-France; Darmaun, Dominique; Rozé, Jean-Christophe
2010-01-01
Background Fecal calprotectin has been proposed as a non-invasive marker of intestinal inflammation in inflammatory bowel disease in adults and children. Fecal calprotectin levels have been reported to be much higher in both healthy full-term and preterm infants than in children and adults. Objective To determine the time course of fecal calprotectin (f-calprotectin) excretion in preterm infants from birth until hospital discharge and to identify factors influencing f-calprotectin levels in the first weeks of life, including bacterial establishment in the gut. Methodology F-calprotectin was determined using an ELISA assay in 147 samples obtained prospectively from 47 preterm infants (gestational age, and birth-weight interquartiles 27–29 weeks, and 880–1320 g, respectively) at birth, and at 2-week intervals until hospital discharge. Principal Findings Although median f-calprotectin excretion was 138 µg/g, a wide range of inter- and intra-individual variation in f-calprotectin values (from day 3 to day 78) was observed (86% and 67%, respectively). In multivariate regression analysis, f-calprotectin correlated negatively with ante and per natal antibiotic treatment (p = 0.001), and correlated positively with the volume of enteral feeding (mL/kg/d) (p = 0.009), the need to interrupt enteral feeding (p = 0.001), and prominent gastrointestinal colonization by Clostridium sp (p = 0.019) and Staphylococcus sp (p = 0.047). Conclusion During the first weeks of life, the high f-calprotectin values observed in preterm infants could be linked to the gut bacterial establishment. PMID:20552029
Hiraki, Eri; Furuta, Shoko; Kuwahara, Rika; Takemoto, Naomichi; Nagata, Toshiro; Akasaka, Taiki; Shirouchi, Bungo; Sato, Masao; Ohnuki, Koichiro; Shimizu, Kuniyoshi
2017-07-01
Hericium erinaceus (H. erinaceus) improves the symptoms of menopause. In this study, using ovariectomized mice as a model of menopause, we investigated the anti-obesity effect of this mushroom in menopause. Mice fed diets containing H. erinaceus powder showed significant decreases in the amounts of fat tissue, plasma levels of total cholesterol, and leptin. To determine the mechanism, groups of mice were respectively fed a diet containing H. erinaceus powder, a diet containing ethanol extract of H. erinaceus, and a diet containing a residue of the extract. As a result, H. erinaceus powder was found to increase fecal lipid levels in excreted matter. Further in vitro investigation showed that ethanol extract inhibited the activity of lipase, and four lipase-inhibitory compounds were isolated from the extract: hericenone C, hericenone D, hericenone F, and hericenone G. In short, we suggest that H. erinaceus has an anti-obesity effect during menopause because it decreases the ability to absorb lipids.
Wilson, Thomas A; Nicolosi, Robert J; Woolfrey, Benjamin; Kritchevsky, David
2007-02-01
Our laboratory has reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Because RBO has a greater content of the unsaponifiables, which also lower cholesterol compared to most vegetable oils, we wanted to know whether oryzanol or ferulic acid, two major unsaponifiables in RBO, has a greater cholesterol-lowering activity. Forty-eight F(1)B Golden Syrian hamsters (Mesocricetus auratus) (BioBreeders, Watertown, MA) were group housed (three per cage) in cages with bedding in an air-conditioned facility maintained on a 12-h light/dark cycle. The hamsters were fed a chow-based hypercholesterolemic diet (HCD) containing 10% coconut oil and 0.1% cholesterol for 2 weeks, at which time they were bled after an overnight fast (16 h) and segregated into 4 groups of 12 with similar plasma cholesterol concentrations. Group 1 (control) continued on the HCD, group 2 was fed the HCD containing 10% RBO in place of coconut oil, group 3 was fed the HCD plus 0.5% ferulic acid and group 4 was fed the HCD plus 0.5% oryzanol for an additional 10 weeks. After 10 weeks on the diets, plasma total cholesterol (TC) and non-high-density lipoprotein cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the RBO (-64% and -70%, respectively), the ferulic acid (-22% and -24%, respectively) and the oryzanol (-70% and -77%, respectively) diets compared to control. Plasma TC and non-HDL-C concentrations were also significantly lower in the RBO (-53% and -61%, respectively) and oryzanol (-61% and -70%, respectively) diets compared to the ferulic acid. Compared to control and ferulic acid, plasma HDL-C concentrations were significantly higher in the RBO (10% and 20%, respectively) and oryzanol (13% and 24%, respectively) diets. The ferulic acid diet had significantly lower plasma HDL-C concentrations compared to the control (-9%). The RBO and oryzanol diets were significantly lower for plasma triglyceride concentrations compared to the control (-53% and -65%, respectively) and ferulic acid (-47% and -60%, respectively) diets. Hamsters fed the control and ferulic acid diets had significantly higher plasma vitamin E concentrations compared to the RBO (201% and 161%, respectively) and oryzanol (548% and 462%, respectively) diets; the ferulic acid and oryzanol diets had significantly lower plasma lipid hydroperoxide levels than the control (-57% and -46%, respectively) diet. The oryzanol-fed hamsters excreted significantly more coprostenol and cholesterol in their feces than the ferulic acid (127% and 120%, respectively) diet. The control diet had significantly greater aortic TC and FC accumulation compared to the RBO (115% and 89%, respectively), ferulic acid (48% and 58%, respectively) and the oryzanol (74% and 70%, respectively) diets. However, only the RBO and oryzanol diets had significantly lower aortic cholesterol ester accumulation compared to the control (-73% and -46%, respectively) diet. The present study suggests that at equal dietary levels, oryzanol has a greater effect on lowering plasma non-HDL-C levels and raising plasma HDL-C than ferulic acid, possibly through a greater extent to increase fecal excretion of cholesterol and its metabolites. However, ferulic acid may have a greater antioxidant capacity via its ability to maintain serum vitamin E levels compared to RBO and oryzanol. Thus, both oryzanol and ferulic acid may exert similar antiatherogenic properties, but through different mechanisms.
Chijimatsu, Takeshi; Umeki, Miki; Okuda, Yuji; Yamada, Koji; Oda, Hiroaki; Mochizuki, Satoshi
2011-02-01
We investigated whether the fat and protein fractions of freshwater clam (Corbicula fluminea) extract (FCE) could ameliorate hypercholesterolaemia in rats fed a high-cholesterol diet. We also explored the mechanism and the components that exert the hypocholesterolaemic effect of FCE. The doses of the fat and protein fractions were equivalent to those in 30 % FCE. The fat and protein fractions of FCE, two major components of FCE, significantly reduced the serum and hepatic cholesterol levels. The fat fraction more strongly reduced serum cholesterol levels than the same level of total FCE. The excretion of faecal neutral sterols increased in rats fed the total the FCE and the fat fraction of FCE. On the other hand, faecal bile acid levels were greater in rats fed the total FCE and the fat and protein fractions of FCE than in control animals. The hepatic gene expression of ATP-binding cassette transporter G5 and cholesterol 7α-hydroxylase was up-regulated by the administration of the total FCE and both the fat and protein fractions of FCE. These results showed that the fat and protein fractions of FCE had hypocholesterolaemic properties, and that these effects were greater with the fat fraction than with the protein fraction. The present study indicates that FCE exerts its hypocholesterolaemic effects through at least two different mechanisms, including enhanced excretion of neutral sterols and up-regulated biosynthesis of bile acids.
Bainbridge, Melissa; Kraft, Jana
2016-01-01
Transfer efficiencies of rumen-protected n-3 fatty acids (FA) to milk are low, thus we hypothesized that rumen-protection technologies allow for biohydrogenation and excretion of n-3 FA. The objectives of this study were to i) investigate the ruminal protection and post-ruminal release of the FA derived from the lipid-encapsulated echium oil (EEO), and ii) assess the bioavailability and metabolism of the EEO-derived FA through measuring the FA content in plasma lipid fractions, feces, and milk. The EEO was tested for rumen stability using the in situ nylon bag technique, then the apparent total-tract digestibility was assessed in vivo using six Holstein dairy cattle. Diets consisted of a control (no EEO); 1.5% of dry matter (DM) as EEO and 1.5% DM as encapsulation matrix; and 3% DM as EEO. The EEO was rumen-stable and had no effect on animal production. EEO-derived FA were incorporated into all plasma lipid fractions, with the highest proportion of n-3 FA observed in cholesterol esters. Fecal excretion of EEO-derived FA ranged from 7–14%. Biohydrogenation products increased in milk, plasma, and feces with EEO supplementation. In conclusion, lipid-encapsulation provides inadequate digestibility to achieve an optimal transfer efficiency of n-3 FA to milk. PMID:27741299
Zhang, Qi; Wang, Guang-ji; A, Ji-ye; Wu, Di; Zhu, Ling-ling; Ma, Bo; Du, Yu
2009-01-01
Aim: To evaluate the lipid-regulating effects of extract from Ginkgo biloba leaves (EGB) using pharmacological methods and metabonomic profiling in a rat model of diet-induced hyperlipidemia. Methods: EGB was orally administered at a dose level of 40 mg/kg in both the EGB-prevention and -treatment groups. All rat samples obtained were examined for known and potential biomarkers and enzyme activity using commercial assay kits and GC/MS-based metabonomic profiling coupled with principal component analysis (PCA). Results: The data obtained from the assay kits indicated that EGB reduced total cholesterol and low density lipoprotein cholesterol levels and increased high density lipoprotein cholesterol levels in rat plasma obtained from both the EGB-prevention and –treatment groups compared with those of the diet-induced hyperlipidemia group. EGB also increased the activities of lipoprotein lipase and hepatic lipase and excretion of fecal bile acid in rats from the EGB-prevention and–treatment groups. Using GC/MS-based metabonomic analysis, more than 40 endogenous metabolites were identified in rat plasma. PCA of rat plasma samples obtained using GC/MS produced a distinctive separation of the four treatment groups and sampling points within each group. Metabolic changes during hyperlipidemia formation and improvement resulting from EGB treatment were definitively monitored with PCA score plots. Furthermore, elevated levels of sorbitol, tyrosine, glutamine and glucose, and decreased levels of citric acid, galactose, palmitic acid, arachidonic acid, acetic acid, cholesterol, butyrate, creatinine, linoleate, ornithine and proline, were observed in the plasma of rats treated with EGB. Conclusion: EGB exerts multi-directional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMGCoA and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA). Further experiments are warranted to explore the mechanisms of action underlying the lipid-regulating effects of EGB against hyperlipidemia. PMID:19960012
Zhang, Qi; Wang, Guang-ji; A, Ji-ye; Wu, Di; Zhu, Ling-ling; Ma, Bo; Du, Yu
2009-12-01
To evaluate the lipid-regulating effects of extract from Ginkgo biloba leaves (EGB) using pharmacological methods and metabonomic profiling in a rat model of diet-induced hyperlipidemia. EGB was orally administered at a dose level of 40 mg/kg in both the EGB-prevention and -treatment groups. All rat samples obtained were examined for known and potential biomarkers and enzyme activity using commercial assay kits and GC/MS-based metabonomic profiling coupled with principal component analysis (PCA). The data obtained from the assay kits indicated that EGB reduced total cholesterol and low density lipoprotein cholesterol levels and increased high density lipoprotein cholesterol levels in rat plasma obtained from both the EGB-prevention and -treatment groups compared with those of the diet-induced hyperlipidemia group. EGB also increased the activities of lipoprotein lipase and hepatic lipase and excretion of fecal bile acid in rats from the EGB-prevention and-treatment groups. Using GC/MS-based metabonomic analysis, more than 40 endogenous metabolites were identified in rat plasma. PCA of rat plasma samples obtained using GC/MS produced a distinctive separation of the four treatment groups and sampling points within each group. Metabolic changes during hyperlipidemia formation and improvement resulting from EGB treatment were definitively monitored with PCA score plots. Furthermore, elevated levels of sorbitol, tyrosine, glutamine and glucose, and decreased levels of citric acid, galactose, palmitic acid, arachidonic acid, acetic acid, cholesterol, butyrate, creatinine, linoleate, ornithine and proline, were observed in the plasma of rats treated with EGB. EGB exerts multi-directional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMGCoA and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA). Further experiments are warranted to explore the mechanisms of action underlying the lipid-regulating effects of EGB against hyperlipidemia.
Zhu, Ru-Gang; Sun, Yan-Di; Li, Tuo-Ping; Chen, Gang; Peng, Xue; Duan, Wen-Bin; Zheng, Zheng-Zheng; Shi, Shu-Lei; Xu, Jing-Guo; Liu, Yan-Hua; Jin, Xiao-Yi
2015-08-05
This study aims to compare the effects of feeding haw pectin (HP), haw pectin hydrolyzates (HPH), and haw pectin pentasaccharide (HPPS) on the cholesterol metabolism of hypercholesterolemic hamsters induced by high-cholesterol diets. The animals were fed a standard diet (SD), high-cholesterol diet (HCD), or HCD plus HP, HPH, or HPPS at a dose of 300mg/kg body weight for 4weeks. Results showed that HPPS was more effective than HP and HPH in decreasing the body weight gain (by 38.2%), liver weight (by 16.4%), and plasma and hepatic total cholesterol (TC; by 23.6% and 27.3%, respectively) of hamsters. In addition, the bile acid levels in the feces were significantly higher by 39.8% and 132.8% in the HPH and HPPS groups than in the HCD group. Such changes were not noted in the HP group. However, the HP group had higher cholesterol excretion capacities than the HPH and HPPS groups by inhibiting cholesterol absorption in the diet, with a 21.7% increase in TC excretion and a 31.1% decrease in TC absorption. Thus, HPPS could be a promising anti-atherogenic dietary ingredient for the development of functional food to improve cholesterol metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Liu, Hshuan-Chen; Chang, Chun-Ju; Yang, Tsung-Han; Chiang, Meng-Tsan
2017-07-01
This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC) and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model. Copyright © 2016. Published by Elsevier B.V.
Wang, Yu-Xin; Li, Yang; Sun, An-Min; Wang, Feng-Jiao; Yu, Guo-Ping
2014-09-16
The aqueous enzymatic extract from rice bran (AEERB) was rich in protein, γ-oryzanol and tocols. The aim of this study was to investigate the effects of AEERB on the regulation of lipid metabolism and the inhibition of oxidative damage. The antioxidant activity of AEERB in vitro was measured in terms of radical scavenging capacity, ferric reducing ability power (FRAP) and linoleic acid emulsion system-ferric thiocyanate method (FTC). Male Wistar rats were fed with a normal diet and a high-fat and high-cholesterol diet with or without AEERB. After treatment, biochemical assays of serum, liver and feces lipid levels, the antioxidant enzyme activity, malondialdehyde (MDA) and protein carbonyl were determined. AEERB is completely soluble in water and rich in hydrophilic and lipophilic functional ingredients. AEERB scavenged DPPH• and ABTS•+ and exhibited antioxidant activity slightly lower than that of ascorbic acid in the linoleic acid system. The administration of AEERB reduced serum lipid levels and the atherogenic index compared with those of the hyperlipidemic diet group (HD). The administration of AEERB significantly lowered liver lipid levels, inhibited hepatic 3-hydroxyl-3-methylglutaryl CoA reductase activity, and efficiently promoted the fecal excretion of total lipids and total cholesterol (TC) (p < 0.05). Dietary AEERB enhanced antioxidant status in the serum, liver and brain by increasing the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and decreasing the content of MDA and protein carbonyl. The results indicated that AEERB might act as a potent hypolipidemic and antioxidant functional food.
Cho, Yun-Young; Kwon, Eun-Young; Kim, Hye-Jin; Jeon, Seon-Min; Lee, Ki-Teak; Choi, Myung-Sook
2011-01-20
Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schiller, L.R.; Hogan, R.B.; Morawski, S.G.
1987-01-01
We studied radiolabeled fecal bile acid excretion in 11 normal subjects and 17 patients with idiopathic chronic diarrhea for three major purposes: to establish normal values for this test in the presence of increased stool volumes (induced in normal subjects by ingestion of poorly absorbable solutions); to test for bile acid malabsorption in the patients and to correlate this with an independent test of ileal function, the Schilling test; and to compare the results of the bile acid excretion test with the subsequent effect of a bile acid binding agent (cholestyramine) on stool weight. In normal subjects fecal excretion ofmore » the radiolabel was increased with increasing stool volumes. As a group, patients with idiopathic chronic diarrhea excreted radiolabeled bile acid more rapidly than normal subjects with induced diarrhea (t1/2 56 +/- 8 vs. 236 +/- 60 h, respectively, p less than 0.005). There was a statistically significant positive correlation between t1/2 of radiolabeled bile acid and Schilling test results in these patients. Although 14 of 17 patients absorbed labeled taurocholic acid less well than any of the normal subjects with comparable volumes of induced diarrhea, cholestyramine had no statistically significant effect on stool weight in the patient group, and in none of the patients was stool weight reduced to within the normal range. In summary, most patients with idiopathic chronic diarrhea have bile acid malabsorption (as measured by fecal excretion of labeled bile acid), but they do not respond to cholestyramine therapy with a significant reduction in stool weight. Although the significance of these findings was not clearly established, the most likely interpretation is that bile acid malabsorption is a manifestation of an underlying intestinal motility or absorptive defect rather than the primary cause of diarrhea.« less
Fuhrmeister, Erica R; Schwab, Kellogg J; Julian, Timothy R
2015-10-06
Understanding the excretion and treatment of human waste (feces and urine) in low and middle income countries (LMICs) is necessary to design appropriate waste management strategies. However, excretion and treatment are often difficult to quantify due to decentralization of excreta management. We address this gap by developing a mechanistic, stochastic model to characterize phosphorus, nitrogen, biochemical oxygen demand (BOD), and fecal coliform pollution from human excreta for 108 LMICs. The model estimates excretion and treatment given three scenarios: (1) use of existing sanitation systems, (2) use of World Health Organization-defined "improved sanitation", and (3) use of best available technologies. Our model estimates that more than 10(9) kg/yr each of phosphorus, nitrogen and BOD are produced. Of this, 22(19-27)%, 11(7-15)%, 17(10-23)%, and 35 (23-47)% (mean and 95% range) BOD, nitrogen, phosphorus, and fecal coliforms, respectively, are removed by existing sanitation systems. Our model estimates that upgrading to "improved sanitation" increases mean removal slightly to between 17 and 53%. Under the best available technology scenario, only approximately 60-80% of pollutants are treated. To reduce impact of nutrient and microbial pollution on human and environmental health, improvements in both access to adequate sanitation and sanitation treatment efficiency are needed.
Sipari, Saana; Ylönen, Hannu; Palme, Rupert
2017-03-01
The bank vole is a commonly used model species in behavioral and ecophysiological studies. Thus, presenting a validated method for noninvasive monitoring of corticosterone and testosterone secretion is of high relevance. Here, we evaluated the effect of time of day and an ACTH challenge test on measured fecal corticosterone (FCM) and testosterone (FTM) metabolites in both sexes. Furthermore, we performed radiometabolism experiments for both steroids and sexes to study metabolism and excretion of 3 H-corticosterone and 3 H-testosterone. FCM and FTM were analysed with a 5α-pregnane-3β,11β,21-triol-20-one enzyme immunoassay (EIA) and a testosterone (measuring 17β-hydroxyandrostanes) EIA, respectively. Males had significantly higher FCM levels than females and their main excretion route was via the feces (∼72%), whereas females excreted nearly equal portions in both feces and urine. For testosterone the main excretion route was via the feces in both sexes (∼80%). The time course of excretion was similar in both sexes, but for the first time a significant difference between injected steroids was found: Corticosterone was excreted faster than testosterone, both in urine (median of peak levels: 4h vs 6h) and feces (6h vs 8h). Several metabolites were present in the feces and the tested EIAs reacted with some of them. Time of day had a significant effect on measured fecal steroid metabolites. As expected, males had significantly higher FTM levels than females. ACTH administration significantly increased FCM values; peaks were observed 4-8h after injection. In conclusion, both tested EIAs proved suited for a noninvasive measurement of glucocorticoids and androgens in bank voles. Copyright © 2016 Elsevier Inc. All rights reserved.
Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery.
Clerici, C; Gentili, G; Boschetti, E; Santucci, C; Aburbeh, A G; Natalini, B; Pellicciari, R; Morelli, A
1994-12-01
In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (< 35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.
Moran-Gilad, Jacob; Mendelson, Ella; Burns, Cara C; Bassal, Ravit; Gdalevich, Michael; Sofer, Danit; Oberste, M Steven; Shulman, Lester M; Kaliner, Ehud; Hindiyeh, Musa; Hindiye, Musa; Mor, Orna; Shahar, Liora; Iber, Jane; Yishay, Ruth; Manor, Joseph; Lev, Boaz; Gamzu, Ronni; Grotto, Itamar
2015-05-01
Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1) into Israel in early 2013 was detected in Southern Israel via routine environmental surveillance without clinical cases. To estimate the rate of WPV1 excretion by age and residence and inform decision-making regarding supplemental immunization with OPV. A convenience sample of Bedouin and Jewish residential areas in the epicenter of the incident, focusing on under 8 year-olds who not previously given OPV. Fecal samples were directly tested for WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold standard cell culture and subject to genotyping. Overall, 2196 non-duplicate fecal samples were collected and analyzed. WPV1 was detected in 61 samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were 5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2% and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than culture) and 100% specificity. The rapid performance of a field study to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection rates among children under 8 years in Southern Israel, thus informing the decision to vaccinate this age group with bOPV and risk communication to both healthcare personnel and the public. Rapid development and implementation of molecular screening can thus underpin risk assessment and management in complex epidemiological situations. Copyright © 2015 Elsevier B.V. All rights reserved.
Bundgaard, Cathrine Juel; Kalliokoski, Otto; Abelson, Klas S P; Hau, Jann
2012-01-01
Stress associated with transport and change of environment may have widespread effects on physiological parameters in laboratory animals. To investigate the time needed for mice to acclimatize to a new environment, based on fecal IgA and corticosterone excretion, eightweek-old BALB/c mice of both genders were housed either in groups of eight in different cage types in open conventional cages, in Individual Ventilated Cages (IVC), in open conventional cages inside a plastic isolator, or in different group sizes (8, 4, 8, 10 or 12 mice in each group) in open conventional cages. Feces were collected from each cage on routine cage changing. There was no significant difference in corticosterone excretion in feces between animals housed in the different cage types or between animals housed in different group sizes. IgA excretion for both males and females was found to be affected by transfer of mice into a novel cage, and it was found that it takes at least four weeks for the mice to acclimatize to a new environment with respect to this parameter.
Ray, Partha; Knowlton, Katharine F.; Shang, Chao; Xia, Kang
2014-01-01
Cephapirin, a cephalosporin antibiotic, is used by the majority of dairy farms in the US. Fecal and urinary excretion of cephapirin could introduce this compound into the environment when manure is land applied as fertilizer, and may cause development of bacterial resistance to antibiotics critical for human health. The environmental loading of cephapirin by the livestock industry remains un-assessed, largely due to a lack of appropriate analytical methods. Therefore, this study aimed to develop and validate a cephapirin quantification method to capture the temporal pattern of cephapirin excretion in dairy cows following intramammary infusion. The method includes an extraction with phosphate buffer and methanol, solid-phase extraction (SPE) clean-up, and quantification using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The LOQ values of the developed method were 4.02 µg kg−1 and 0.96 µg L−1 for feces and urine, respectively. This robust method recovered >60% and >80% cephapirin from spiked blank fecal and urine samples, respectively, with acceptable intra- and inter-day variation (<10%). Using this method, we detected trace amounts (µg kg−1) of cephapirin in dairy cow feces, and cephapirin in urine was detected at very high concentrations (133 to 480 µg L−1). Cephapirin was primarily excreted via urine and its urinary excretion was influenced by day (P = 0.03). Peak excretion (2.69 mg) was on day 1 following intramammary infusion and decreased sharply thereafter (0.19, 0.19, 0.08, and 0.17 mg on day 2, 3, 4, and 5, respectively) reflecting a quadratic pattern of excretion (Quadratic: P = 0.03). The described method for quantification of cephapirin in bovine feces and urine is sensitive, accurate, and robust and allowed to monitor the pattern of cephapirin excretion in dairy cows. This data will help develop manure segregation and treatment methods to minimize the risk of antibiotic loading to the environment from dairy farms. PMID:25375097
Diagnosis-based treatment of helminths in captive and wild cheetahs (Acinonyx jubatus).
Mény, Marie; Schmidt-Küntzel, Anne; Marker, Laurie L
2012-12-01
This study was designed to identify endoparasites in captive cheetahs (Acinonyx jubatus) living in a seminatural captive environment in north-central Namibia. Results were used to assess the need for anthelmintic treatment and for the selection of an appropriate drug. The study assessed fecal parasite excretion qualitatively and quantitatively using a fecal flotation method during the winter of 2009. Four different species of parasites (two nematodes and two coccidias) were identified. Parasite excretion rates were found to be significantly lower than that of wild cheetahs living in the same area. Samples of the wild cheetahs were obtained at the time of anesthesia or were attributed to the wild individuals using genetic profiling. Captive cheetahs were dewormed with fenbendazole, whereas wild cheetahs were treated using ivermectin. Efficacy of these treatments was demonstrated at the end of the study.
EXCRETION OF P$sup 32$ AFTER THERAPY FOR POLYCYTHEMIA RUBRA VERA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weijer, D.L.; Duggan, H.E.; Scott, D.B.
1962-09-01
Fifteen subjects undergoing treatment for polycythemia rubra vera were given P/sup 32/. Carrier-free P/sup 32/ was administered intravenously in 11 and orally in 6. Total excretion studies were carried out in each case for periods of 5 to 22 days. Average urinary excretion of P/sup 32/, as a percentage of the initial dose to the end of 3 days for the entire series, was 14.3%, with limits of 6.4 and 18.7%. The corresponding 5-day average amounted to 17.8%, with limits of 7.5 and 22.5%. In the six patients treated orally, the average 3-day urinary excretion was 11.2% and for 5more » days was 14.2%. For the 11 patients treated intravenously, the average 3-day excretion was 16.1%, the average 5-day excretion 19.8%. The average fecal excretion as a percentage of the initial dose to the end of 3 days was 1.7%, with limits of 0.1 and 5.5%, and the average 5-day excretion was 2.5%, with limits 0.5 and 5.9%. In the orally treated fasting group the total stool excretion to the end of 3 days was 2.0 and 2.5% at the end of 5 days. Of the 10 polycythemia patients treated intravenously, the stool excretion to the end of 3 days was 1.5% and at 5 days 2.5%. Under fasting conditions (both before and after the administration of P/sup 32/) with little or no carrier added, the fecal excretion of P/sup 32/is small. Thus, the total excretion of P/sup 32/ does not differ significantly for oral and intravenous administration. Hence, despite contrary reports, it appears that under fasting conditions of administration it is not necessary to increase the oral dose of P/ sup 32/ to 4/3 of the intravenous dose in order to obtain equivalent absorption of the administered dose. It is concluded that the P/sup 32/ content of urine in the first 24 hr after therapy, by either route of administration, indicates whether or not a particular patient will retain the dose within normal limits. (BBB)« less
Ross, Colleen M.; Pleydell, Eve J.; Muirhead, Richard W.
2012-01-01
Dairy cows have been identified as common carriers of Campylobacter jejuni, which causes many of the human gastroenteritis cases reported worldwide. To design on-farm management practices that control the human infection sourced from dairy cows, the first step is to acquire an understanding of the excretion patterns of the cow reservoir. We monitored the same 35 cows from two dairy farms for C. jejuni excretion fortnightly for up to 12 months. The objective was to examine the concentration of C. jejuni and assess the genetic relationship of the C. jejuni populations excreted by individual cows. Significant differences (P < 0.01) in C. jejuni fecal concentration were observed among the 35 cows, with median concentrations that varied by up to 3.6 log10 · g−1 feces. A total of 36 different genotypes were identified from the 514 positive samples by using enterobacterial repetitive intergenic consensus (ERIC)-PCR. Although 22 of these genotypes were excreted by more than one cow, the analysis of frequencies and distribution of the genotypes by model-based statistics revealed a high degree of individuality in the C. jejuni population in each cow. The observed variation in the frequency of excretion of a genotype among cows and the analysis by multilocus sequence typing (MLST) of these genotypes suggest that excretion of C. jejuni in high numbers is due to a successful adaptation of a particular genotype to a particular cow's gut environment, but that animal-related factors render some individual cows resistant to colonization by particular genotypes. The reasons for differences in C. jejuni colonization of animals warrant further investigation. PMID:22904055
Wang, Yu-Xin; Li, Yang; Sun, An-Min; Wang, Feng-Jiao; Yu, Guo-Ping
2014-01-01
Purpose: The aqueous enzymatic extract from rice bran (AEERB) was rich in protein, γ-oryzanol and tocols. The aim of this study was to investigate the effects of AEERB on the regulation of lipid metabolism and the inhibition of oxidative damage. Methods: The antioxidant activity of AEERB in vitro was measured in terms of radical scavenging capacity, ferric reducing ability power (FRAP) and linoleic acid emulsion system-ferric thiocyanate method (FTC). Male Wistar rats were fed with a normal diet and a high-fat and high-cholesterol diet with or without AEERB. After treatment, biochemical assays of serum, liver and feces lipid levels, the antioxidant enzyme activity, malondialdehyde (MDA) and protein carbonyl were determined. Result: AEERB is completely soluble in water and rich in hydrophilic and lipophilic functional ingredients. AEERB scavenged DPPH• and ABTS•+ and exhibited antioxidant activity slightly lower than that of ascorbic acid in the linoleic acid system. The administration of AEERB reduced serum lipid levels and the atherogenic index compared with those of the hyperlipidemic diet group (HD). The administration of AEERB significantly lowered liver lipid levels, inhibited hepatic 3-hydroxyl-3-methylglutaryl CoA reductase activity, and efficiently promoted the fecal excretion of total lipids and total cholesterol (TC) (p < 0.05). Dietary AEERB enhanced antioxidant status in the serum, liver and brain by increasing the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and decreasing the content of MDA and protein carbonyl. Conclusions: The results indicated that AEERB might act as a potent hypolipidemic and antioxidant functional food. PMID:25230211
2011-01-01
Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC. PMID:21247503
Urinary Excretion of N-Nitroso Compounds in Rats Fed Sodium Nitrite and/or Hot Dogs
2015-01-01
Nitrite-treated meat is a reported risk factor for colon cancer. Mice that ingested sodium nitrite (NaNO2) or hot dogs (a nitrite-treated product) showed increased fecal excretion of apparent N-nitroso compounds (ANC). Here, we investigated for the first time whether rats excrete increased amounts of ANC in their urine after they are fed NaNO2 and/or hot dogs. Rats were treated for 7 days with NaNO2 in drinking water or were fed hot dogs. Their 24 h urine samples were analyzed for ANC by thermal energy analysis on days 1–4 after nitrite or hot dog treatment was stopped. For two rats fed 480 mg NaNO2/L drinking water, mean urinary ANC excretion on days 1–4 was 30, 5.2, 2.5, and 0.8 nmol/day, respectively. For two to eight rats/dose given varied NaNO2 doses, mean urinary ANC output on day 1 increased from 0.9 (for no nitrite) to 37 (for 1000 mg NaNO2/L drinking water) nmol ANC/day. Urine samples of four rats fed 40–60% hot dogs contained 12–13 nmol ANC on day 1. Linear regression analysis showed highly significant correlations between urinary ANC excretion on day 1 after stopping treatment and varied (a) NaNO2 level in drinking water for rats fed semipurified or commercials diet and (b) hot dog levels in the diet. Some correlations remained significant up to 4 days after nitrite treatment was stopped. Urinary output of ANC precursors (compounds that yield ANC after mild nitrosation) for rats fed semipurified or commercial diet was 11–17 or 23–48 μmol/day, respectively. Nitrosothiols and iron nitrosyls were not detected in urinary ANC and ANCP. Excretion of urinary ANC was about 60% of fecal ANC excretion for 1 to 2 days after NaNO2 was fed. Administered NaNO2 was not excreted unchanged in rat urine. We conclude that urinary ANC excretion in humans could usefully be surveyed to indicate exposure to N-nitroso compounds. PMID:25183213
Sohn, Chan Wok; Kim, Hyunae; You, Bo Ram; Kim, Min Jee; Kim, Hyo Jin; Lee, Ji Yeon; Sok, Dai-Eun; Kim, Jin Hee; Lee, Kun Jong; Kim, Mee Ree
2012-05-01
Garlic protects against degenerative diseases such as hyperlipidemia and cardiovascular diseases. However, raw garlic has a strong pungency, which is unpleasant. In this study, we examined the effect of high temperature/high pressure-processed garlic on plasma lipid profiles in rats. Sprague-Dawley rats were fed a normal control diet, a high cholesterol (0.5% cholesterol) diet (HCD) only, or a high cholesterol diet supplemented with 0.5% high temperature/high pressure-processed garlic (HCP) or raw garlic (HCR) for 10 weeks. The body weights of the rats fed the garlic-supplemented diets decreased, mostly because of reduced fat pad weights. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride (TG) in the HCP and HCR groups decreased significantly compared with those in the HCD group. Additionally, fecal TC and TG increased significantly in the HCP and HCR groups. It is notable that no significant differences in plasma or fecal lipid profiles were observed between the HCP and HCR groups. High temperature/high pressure-processed garlic contained a higher amount of S-allyl cysteine than raw garlic (P<.05). The results suggest that high temperature/high pressure-processed garlic may be useful as a functional food to improve lipid profiles.
Sohn, Chan Wok; Kim, Hyunae; You, Bo Ram; Kim, Min Jee; Kim, Hyo Jin; Lee, Ji Yeon; Sok, Dai-Eun; Kim, Jin Hee; Lee, Kun Jong
2012-01-01
Abstract Garlic protects against degenerative diseases such as hyperlipidemia and cardiovascular diseases. However, raw garlic has a strong pungency, which is unpleasant. In this study, we examined the effect of high temperature/high pressure-processed garlic on plasma lipid profiles in rats. Sprague–Dawley rats were fed a normal control diet, a high cholesterol (0.5% cholesterol) diet (HCD) only, or a high cholesterol diet supplemented with 0.5% high temperature/high pressure-processed garlic (HCP) or raw garlic (HCR) for 10 weeks. The body weights of the rats fed the garlic-supplemented diets decreased, mostly because of reduced fat pad weights. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride (TG) in the HCP and HCR groups decreased significantly compared with those in the HCD group. Additionally, fecal TC and TG increased significantly in the HCP and HCR groups. It is notable that no significant differences in plasma or fecal lipid profiles were observed between the HCP and HCR groups. High temperature/high pressure-processed garlic contained a higher amount of S-allyl cysteine than raw garlic (P<.05). The results suggest that high temperature/high pressure-processed garlic may be useful as a functional food to improve lipid profiles. PMID:22404600
The effect of supplemental oral phosphate on the bone mineral changes during prolonged bed rest
Hulley, Stephen B.; Vogel, John M.; Donaldson, Charles L.; Bayers, Jon H.; Friedman, Ronald J.; Rosen, Sheldon N.
1971-01-01
Five healthy young men were studied during 24-30 wk of continuous bed rest. During the first 12 wk of bed rest, untreated subjects increased calcium excretion in the urine by 109 mg/day and in the feces by 147 mg/day. The rate of total body calcium loss was 0.5-0.7% per month. Losses of central calcaneus mineral, assessed by gamma ray transmission scanning, occurred at a tenfold higher rate, whereas the mineral content of the radius did not change. Changes in phosphorus balance resembled the calcium pattern, and increased excretion of nitrogen and hydroxyproline also occurred during bed rest. Upon reambulation, the subjects' calcium balance became positive in 1 month and recovery of their calcaneus mineral was complete within 10-20 wk. Treatment with potassium phosphate supplements (1327 mg P/day) entirely prevented the hypercalciuria of bed rest, but fecal calcium tended to increase. During the first 12 wk, calcium balance was slightly less negative (mean - 193 mg/day) than during bed rest without added phosphate (mean - 267 mg/day). This effect was not seen during the second 12 wk of bed rest. The patterns of magnesium excretion were similar to those of calcium. Fecal and urinary phosphorus excretions were doubled, and phosphorus balance became positive (+ 113 mg/day). Mineral loss from the central calcaneus was similar to that of untreated subjects. It is concluded that this form of phosphate supplementation reduces urinary calcium excretion but does not prevent bone loss during bed rest. PMID:5129304
Vijayakumar, S; Presannakumar, G; Vijayalakshmi, N R
2009-01-01
Oral administration of flavonoids extracted from unripe fruits of Musa paradisiaca showed significant hypolipidemic activities in male rats (Sprague Dawley strain) at a dose of 1 mg/100 g body weight (BW)/day. Concentrations of cholesterol, phospholipids, free fatty acids, and triglycerides showed significant decrease in the serum, liver, kidney, and brain of experimental animals. HMG CoA reductase activity was found to be enhanced, while activities of glucose-6-phosphate dehydrogenase and malate dehydrogenase were significantly reduced. Activities of lipoprotein lipase and plasma LCAT showed significant enhancement. A significant increase in the concentrations of hepatic and fecal bile acids and fecal neutral sterols was also observed indicating a higher rate of degradation of cholesterol. The present study indicates that although there is an increase in the rate of synthesis of cholesterol in the liver, the process of degradation exceeds the rate of synthesis.
Effect of a rice bran fiber diet on serum glucose levels of diabetic patients in Brazil.
Rodrigues Silva, Cecilia; Dutra de Oliveira, José Eduardo; de Souza, Rui Augusto Hudari Gonçalves; Silva, Hugo Candido
2005-03-01
Eleven diabetic patients: 5, type 1 and 6, type 2 received a low-fiber diet (I) during 1 week and during the next 7 days the same diet, enriched with 40 g of fiber (30.6% insoluble and 11.7% soluble components) from rice bran (II) per day. Results showed that mean fasting and postprandial serum glucose levels were reduced, but values of high fiber diet were significantly lower (p < 0.001) than that of the lower fiber diet. For all patients, the high-fiber diet increased fecal weight. This increase was due to the fiber excreted, rather than water retained. There was no relationship between the increase in fiber intake and its fecal excretion. Sucrose and raffinose were found in the bran, but not in the feces. Lactose was present in the stools of the patients receiving enriched diet.
Quantitation of calcium metabolism in postmenopausal osteoporosis and in scoliosis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bronner, F.; Richelle, L. J.; Saville, P. D.
1963-06-01
By a combination of balance and isotope techniques, the following parameters of Ca metabolism were measured: pool size, rate of loss from pool, urinary excretion, fecal excretion, intake, endogenous fecal Ca, absorption, balance, bone formation, and bone resorption. The subjects were two normal women and five women with postmenopausal osteoporosis, aged 41 to 74 years, and four patients with scoliosis, aged 12 to 22 years. The latter were studied before, shortly after, and many months after immobilization in plaster casts. On the basis of observed relationships, it appeared that the negative Ca balance observed in the older women was duemore » to the low intensity of the various vectors of Ca metabolism, without clearcut distinction between the subjects with and without osteoporosis. Conversely, in the young patients with scoliosis, the negative balance incident to treatment by immobilization was associated with vectors of relatively high intensity whose relationships were altered temporarily.« less
Effect of phosphorus and calcium on zinc metabolism in man
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spencer, H.; Kramer, L.; Lesniak, M.
The effect of phosphorus on zinc metabolism was studied in adult men receiving different calcium intakes ranging from 200 to 2000 mg/day. The diet and urinary and fecal excretions were analyzed for Zn, P and Ca. Metabolic balances of these elements were determined for several weeks in each study phase. In control studies the dietary intake was 800 mg/day and in the experimental studies it was increased to 2000 mg/day by adding sodium glycerophosphate to the constant diet. The dietary Zn intake averaged 14.5 mg/day in the different studies. These studies have shown that increasing the P intake by amore » factor of 2.5, from 800 to 2000 mg/day, did not affect urinary or fecal Zn excretions nor the Zn balance. Similar results were obtained on increasing the Ca intake from 200 to 2000 mg/day.« less
Dietary fat and gut microbiota interactions determine diet-induced obesity in mice.
Kübeck, Raphaela; Bonet-Ripoll, Catalina; Hoffmann, Christina; Walker, Alesia; Müller, Veronika Maria; Schüppel, Valentina Luise; Lagkouvardos, Ilias; Scholz, Birgit; Engel, Karl-Heinz; Daniel, Hannelore; Schmitt-Kopplin, Philippe; Haller, Dirk; Clavel, Thomas; Klingenspor, Martin
2016-12-01
Gut microbiota may promote positive energy balance; however, germfree mice can be either resistant or susceptible to diet-induced obesity (DIO) depending on the type of dietary intervention. We here sought to identify the dietary constituents that determine the susceptibility to body fat accretion in germfree (GF) mice. GF and specific pathogen free (SPF) male C57BL/6N mice were fed high-fat diets either based on lard or palm oil for 4 wks. Mice were metabolically characterized at the end of the feeding trial. FT-ICR-MS and UPLC-TOF-MS were used for cecal as well as hepatic metabolite profiling and cecal bile acids quantification, respectively. Hepatic gene expression was examined by qRT-PCR and cecal gut microbiota of SPF mice was analyzed by high-throughput 16S rRNA gene sequencing. GF mice, but not SPF mice, were completely DIO resistant when fed a cholesterol-rich lard-based high-fat diet, whereas on a cholesterol-free palm oil-based high-fat diet, DIO was independent of gut microbiota. In GF lard-fed mice, DIO resistance was conveyed by increased energy expenditure, preferential carbohydrate oxidation, and increased fecal fat and energy excretion. Cecal metabolite profiling revealed a shift in bile acid and steroid metabolites in these lean mice, with a significant rise in 17β-estradiol, which is known to stimulate energy expenditure and interfere with bile acid metabolism. Decreased cecal bile acid levels were associated with decreased hepatic expression of genes involved in bile acid synthesis. These metabolic adaptations were largely attenuated in GF mice fed the palm-oil based high-fat diet. We propose that an interaction of gut microbiota and cholesterol metabolism is essential for fat accretion in normal SPF mice fed cholesterol-rich lard as the main dietary fat source. This is supported by a positive correlation between bile acid levels and specific bacteria of the order Clostridiales (phylum Firmicutes ) as a characteristic feature of normal SPF mice fed lard. In conclusion, our study identified dietary cholesterol as a candidate ingredient affecting the crosstalk between gut microbiota and host metabolism.
Del Vecchyo-Tenorio, Georgina; Rodríguez-Cruz, Maricela; Andrade-Cetto, Adolfo; Cárdenas-Vázquez, René
2016-01-01
Creosote bush, Larrea tridentata (Sesse y Moc. Ex DC, Zygophyllaceae) is a shrub found in the deserts of Northern Mexico and Southwestern United States. In traditional medicine, it is used to treat a variety of illnesses including type 2 diabetes. The present study aims to investigate the effects of creosote bush ethanolic extract on plasma and liver parameters associated with the metabolic syndrome in hamsters fed a high fat and cholesterol diet (HFD), comparing them with those induced by ezetimibe (EZ). Seven groups of six hamsters each were formed. Six groups were fed HFD for 2 weeks. The following 2 weeks, the HFD groups received: (1) only HFD, (2) HFD + 3 mg% EZ, (3) HFD + 0.2% creosote bush ethanolic extract, (4) only standard diet (Std Diet), (5) Std Diet + 3 mg% EZ, (6) Std Diet + 0.2% creosote bush ethanolic extract. The beneficial effects of creosote bush ethanolic extract in the HFD hamster model were a reduction of insulin resistance, associated with lower serum insulin and leptin, lower hepatic lipid peroxidation and higher liver antioxidant capacity. Plasma and liver lipids tended or were reduced to values closer to those of animals fed standard diet. A similar effect on lipids was induced by EZ, although with even lower hepatic cholesterol and total lipids concentrations. In general, the change from HFD to standard diet plus ethanolic extract induced the same but deeper changes, including a reduction in plasma glucose and an increase in the percentage of HDL cholesterol. Unlike creosote bush extract, EZ increased food consumption and neutral fecal steroids, with no significant effect on body weight, epididymal fat pads, liver peroxidation or antioxidant capacity. Also EZ did not modify serum insulin and leptin. However, insulin sensitivity improved to values similar to those induced by the extract. This suggests that the mechanism of action of creosote bush ethanolic extract is different to inhibition of cholesterol absorption or increase excretion. The ethanolic extract of L. tridentata could be useful in the treatment of the metabolic syndrome. PMID:27445827
Risk factors of weaning diarrhea in puppies housed in breeding kennels.
Grellet, Aurélien; Chastant-Maillard, Sylvie; Robin, Coralie; Feugier, Alexandre; Boogaerts, Cassandre; Boucraut-Baralon, Corine; Grandjean, Dominique; Polack, Bruno
2014-11-01
Diarrhea represents one of the most frequent disorders in dogs. In puppies, degradation of feces quality is associated with a reduced daily weight gain and an increased risk of death. Prevention of diarrhea in puppies requires a global approach encompassing enteropathogens, environment and management practices especially when housed in groups. The purpose of this study was to determine prevalence of enteropathogens in puppies in breeding kennels and to identify risk factors of diarrhea. Two hundred and sixty six puppies (between 5 and 14 weeks of age) from 29 French breeding kennels were included. For each kennel, data about environment, management of the kennel and puppies' characteristics (age, sex and breed) were collected. For each puppy, fecal consistency and fecal excretion of enteropathogens (viruses and parasites) was evaluated. At least one enteropathogen was identified in 77.1% of puppies and 24.8% of puppies presented abnormal feces. The main risk factor of weaning diarrhea was fecal excretion of canine parvovirus type 2 (odds ratio=5; confidence interval 95%: 1.7-14.7). A targeted sanitary and medical prophylaxis against canine parvovirus type 2 should be implemented to decrease risk of weaning diarrhea. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Zinc and copper balances in healthy adult males during and after 17 wk of bed rest
NASA Technical Reports Server (NTRS)
Krebs, J. M.; Schneider, V. S.; LeBlanc, A. D.; Kuo, M. C.; Spector, E.; Lane, H. W.
1993-01-01
The effects of long-term bed rest on zinc and copper balances were measured in seven healthy men. Volunteers aged 22-54 y (mean +/- SD, 34 +/- 12 y), 168-185 cm in height (173 +/- 5 cm), and 64-86 kg in weight (74 +/- 9 kg) remained on a metabolic ward for 29 wk. Subjects were ambulatory during weeks 1-5, remained in continuous bed rest for weeks 6-22, and were reambulated during weeks 23-29. Copper and zinc were measured in weekly urine and fecal composites. Dietary intakes provided (mean +/- SD) 19.2 +/- 1.2 mumol Cu (1.22 +/- 0.08 mg), 211 +/- 11 mumol Zn (13.81 +/- 0.72 mg), 25.2 +/- 1.2 mmol Ca (1011 +/- 46 mg), 1086 +/- 46 mmol N (15.21 +/- 0.65 g), and 48.1 +/- 1.4 mmol K (1489 +/- 44 mg)/d. Bed rest increased fecal zinc excretion and decreased zinc balance, whereas copper balance was unchanged. Reambulation decreased fecal zinc excretion and increased both zinc and copper balances. These results suggest that during long-term bed rest or space flight, individuals will lose total body zinc and will retain more zinc and copper when they reambulate.
Supplement of a chitosan and ascorbic acid mixture for Crohn's disease: a pilot study.
Tsujikawa, Tomoyuki; Kanauchi, Osamu; Andoh, Akira; Saotome, Takao; Sasaki, Masaya; Fujiyama, Yoshihide; Bamba, Tadao
2003-02-01
Although the pathogenesis of Crohn's disease remains unclear, dietary fat is thought to exacerbate intestinal inflammation. Chitosan is a water-insoluble dietary fiber, and a chitosan and ascorbic acid mixture has been shown in rats to increase fecal fat excretion without affecting protein digestibility. However, it remains unclear whether a chitosan and ascorbic acid mixture is safe and effective for patients with Crohn's disease. We designed a pilot trial to investigate the tolerability and amount of fat excretion after the oral administration of a chitosan and ascorbic mixture for inactive Crohn's disease. Eleven outpatients were given seven tablets daily of a chitosan and ascorbic mixture (chitosan was given at 1.05 g/d) for 8 wk. Patients did not interrupt their respective therapies for Crohn's disease. The bowel movements of most patients increased slightly during the study. Nutritional and inflammatory markers in patients did not differ before and after treatment. The chitosan and ascorbic acid mixture significantly increased the fat concentration in the feces during treatment. These results indicated that oral administration of a chitosan and ascorbic acid mixture in patients with Crohn's disease is tolerable and increases fecal fat excretion without affecting disease activity.
Chiba, T; Ohi, R
1998-01-01
Short-gut syndrome is likely to impair enteric fat utilization. This study was undertaken to develop a clinical test of lipid absorption without fecal collection. The absorption of enterally fed radioactive long-chain fatty acid, beta-methyl-p-(123I)-iodophenylpentadecanoic acid was investigated with continuous chyle collection in rats. The changes in excretion and time-dependent biodistribution of radioactivity of the enterally fed agent were assessed in normal control animals. Similarly, sequential urinary excretion and biodistribution were studied along with scintigraphy using sham-operated and short-gut animals. Approximately 64% of the enterally fed radioactivity was recovered in the collected chyle (24 hours). A comparison of normal control, sham-operated, and short-gut animals showed significantly less urinary and greater fecal excretions of radioactivity in short-gut animals. With the use of sequential scintigraphy, the small intestine, whole-body soft tissues, and urinary bladder were well visualized in sham-operated animals, whereas the large intestine and feces were demonstrated earlier in short-gut animals. Our results suggest that enteral feeding of the agent might be feasible for determining lipid absorption from the the dynamic changes of radioactivity in visualized abdominal organs and in urine.
Blackshear, J L; Baker, V S; Holland, A; Litin, S C; Ahlquist, D A; Hart, R G; Ellefson, R; Koehler, J
1996-03-25
Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy. To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalization ratio,<1.5] plus 325 mg/d of enteric-coated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin. Among the 63 at high risk of stroke, abnormal values (>2mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean ( +/- SD) values were more for those randomly assigned to receive combined therapy (1.7 +/- 3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0 +/- 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (+/- SD) HemoQuant value of 0.8 +/- 0.7mg of hemoglobin per gram of stool 1 month after entry in the study. Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.
Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India.
Mohanty, Madhu Chhanda; Madkaikar, Manisha Rajan; Desai, Mukesh; Taur, Prasad; Nalavade, Uma Prajwal; Sharma, Deepa Kailash; Gupta, Maya; Dalvi, Aparna; Shabrish, Snehal; Kulkarni, Manasi; Aluri, Jahnavi; Deshpande, Jagadish Mohanrao
2017-10-01
Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014-April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). We isolated 8 enteroviruses (3 polioviruses and 5 nonpolio enteroviruses) in cell culture of 105 fecal samples collected from 42 patients. Only 1 patient with severe combined immunodeficiency was identified as a long-term VDPV3 excreter (for 2 years after identification of infection). Our results show that the risk of enterovirus excretion among children in India with PID is low; however, systematic screening is necessary to identify long-term poliovirus excreters until the use of oral polio vaccine is stopped.
Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India
Madkaikar, Manisha Rajan; Desai, Mukesh; Taur, Prasad; Nalavade, Uma Prajwal; Sharma, Deepa Kailash; Gupta, Maya; Dalvi, Aparna; Shabrish, Snehal; Kulkarni, Manasi; Aluri, Jahnavi; Deshpande, Jagadish Mohanrao
2017-01-01
Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014–April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). We isolated 8 enteroviruses (3 polioviruses and 5 nonpolio enteroviruses) in cell culture of 105 fecal samples collected from 42 patients. Only 1 patient with severe combined immunodeficiency was identified as a long-term VDPV3 excreter (for 2 years after identification of infection). Our results show that the risk of enterovirus excretion among children in India with PID is low; however, systematic screening is necessary to identify long-term poliovirus excreters until the use of oral polio vaccine is stopped. PMID:28930011
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
Effect of dietary fiber and crude protein content in feed on nitrogen retention in pigs.
Patrás, P; Nitrayová, S; Brestenský, M; Heger, J
2012-12-01
Eight gilts (29.9 ± 1.7 kg initial BW) were used to evaluate effects of dietary (crude) fiber on N excretion via feces and urine at 2 levels of dietary CP. Pigs were fed 4 dietary treatments according to a double 4 × 4 Latin square. Treatments were low (14%) CP and low (3.25%) (crude) fiber (LPAA), low CP and high (4.46%) fiber (LPAABP), high (18.8%) CP and low fiber (HP), and high CP and high fiber (HPBP). Diets were based on soybean (Glycine max) meal, wheat (Triticum aestivum), and maize (Zea mays) and were supplemented with crystalline AA. High fiber diets contained 15% dried beet (Beta vulgaris) pulp. Pigs were housed in metabolic cages and fed 2 equal meals at 0700 and 1700 h at a daily rate of 90 g/kg BW(0.75). Water was offered ad libitum. Each experimental period consisted of a 6-d adaptation followed by a 4-d collection of feces and urine (bladder catheters). Data were analyzed using ANOVA. Differences between means (P < 0.05) were assessed using Fisher's LSD procedure. The N intake, fecal N excretion and absorption, and N retention increased (P < 0.05) in pigs fed high-CP diets with added fiber (HP vs. HPBR). With added fiber, urinary N excretion (g/d) was reduced (P < 0.02) only for the low-CP diet. Urinary N as a percentage of N intake was reduced (P < 0.01) in both groups fed high-fiber diets irrespective of dietary CP content. Dietary fiber level did not affect DMI. Fecal DM excretion (g/d) was higher (P < 0.02) in pigs fed diets with high CP and high fiber content than in pigs fed diets with high CP and low fiber content. In conclusion, beet pulp fiber added to diets increased fecal N and reduced urinary N and in diets with higher CP content increased overall N retention.
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. Copyright © 2015 the American Physiological Society.
Effect of chronic ingestion of lead on gastrointestinal transit in rats
DOE Office of Scientific and Technical Information (OSTI.GOV)
Walsh, C.T.; Ryden, E.B.
1984-09-30
GI symptoms such as constipation and abdominal colic are signs of lead poisoning in man, but mechanisms of these effects have not been elucidated. To evaluate GI transit, male Wistar rats were dosed with 1% lead or 0.7% sodium acetate in their diet (AIN-76A). After 7 weeks, lead-treated animals exhibited decreased hematocrit, increased 24-hr urinary excretion of delta-ALA, increased kidney/body weight ratio, and decreased body weight. Blood-lead concentrations were elevated to 196 +/- 57 micrograms/dl. Lead treatment, however, did not result in change in GI transit of a nonabsorbable marker, 51Cr, 15 min or 6 hr after po administration. Theremore » was also no change in fecal percentage water content. Since in control animals the semipurified diet AIN-76A markedly decreased fecal excretion rate of 51Cr compared to a cereal-based diet, NIH-07, the latter was used in subsequent experiments. Rats fed 2 or 4% lead acetate in NIH-07 for 8 weeks exhibited renal and hematologic toxicity as in the initial experiment. Weight gain was impaired in the 4% group compared to pair-fed controls. No significant differences were observed in the 1-hr gastric emptying or the fecal excretion of 51Cr in the 2 or 4% lead-treated animals, although there was a trend for slower transit in rats receiving the higher dose. These observations indicate that concentrations of lead sufficient to induce renal and hematologic toxicity in rats do not substantially affect GI transit.« less
Hattori, Y; Tazuma, S; Yamashita, G; Ochi, H; Sunami, Y; Nishioka, T; Hyogo, H; Yasumiba, S; Kajihara, T; Nakai, K; Tsuboi, K; Asamoto, Y; Sakomoto, M; Kajiyama, G
2000-07-01
Phospholipase A2 plays a role in cholesterol gallstone development by hydrolyzing bile phospholipids into lysolecithin and free fatty acids. Lysolecithin and polyunsaturated free fatty acids are known to stimulate the synthesis and/or secretion of gallbladder mucin via a prostanoid pathway, leading to enhancing cholesterol crystal nucleation and growth, and therefore, the action of phospholipase A2 is associated, in part, with bile phospholipid fatty acid. To clarify this hypothesis, we evaluated the effect on bile lipid metastability in vitro of replacing phospholipids with lysolecithin and various free fatty acids. Supersaturated model biles were created with an identical composition (cholesterol saturation index, 1.8; egg yolk lecithin, 34 mM; taurocholate, 120 mM; cholesterol, 25 mM) except for 5%, 10%, or 20% replacement of egg yolk lecithin with a combination of palmitoyl-lysolecithin and a free fatty acid (palmitate, stearate, oleate, linoleate, or arachidonate), followed by time-sequentially monitoring of vesicles and cholesterol crystals using spectrophotometer and video-enhanced differential contrast microscopy. Replacement with hydrophilic fatty acids (linoleate and arachidonate) reduced vesicle formation and promoted cholesterol crystallization, whereas an enhanced cholesterol-holding capacity was evident after replacement with hydrophobic fatty acids (palmitate and stearate). These results indicate that the effect of phospholipase A2 on bile lithogenecity is modulated by the fatty acid species in bile phospholipids, and therefore, that the role of phospholipase A2 in cholesterol gallstone formation is dependent, in part, on biliary phospholipid species selection at the site of hepatic excretion.
de Oliveira, Paola Raquel B; da Costa, Cristiane A; de Bem, Graziele F; Cordeiro, Viviane S C; Santos, Izabelle B; de Carvalho, Lenize C R M; da Conceição, Ellen Paula S; Lisboa, Patrícia Cristina; Ognibene, Dayane T; Sousa, Pergentino José C; Martins, Gabriel R; da Silva, Antônio Jorge R; de Moura, Roberto S; Resende, Angela C
2015-01-01
The aim of this study was to investigate the effect of a polyphenol-rich Açaí seed extract (ASE, 300 mg/kg-1d-1) on adiposity and hepatic steatosis in mice that were fed a high-fat (HF) diet and its underlying mechanisms based on hepatic lipid metabolism and oxidative stress. Four groups were studied: C57BL/6 mice that were fed with standard diet (10% fat, Control), 10% fat + ASE (ASE), 60% fat (HF), and 60% fat + ASE (HF + ASE) for 12 weeks. We evaluated the food intake, body weight gain, serum glucose and lipid profile, hepatic cholesterol and triacyglycerol (TG), hepatic expression of pAMPK, lipogenic proteins (SREBP-1c, pACC, ACC, HMG-CoA reductase) and cholesterol excretion transporters, ABCG5 and ABCG8. We also evaluated the steatosis in liver sections and oxidative stress. ASE reduced body weight gain, food intake, glucose levels, accumulation of cholesterol and TG in the liver, which was associated with a reduction of hepatic steatosis. The increased expressions of SREBP-1c and HMG-CoA reductase and reduced expressions of pAMPK and pACC/ACC in HF group were antagonized by ASE. The ABCG5 and ABCG8 transporters expressions were increased by the extract. The antioxidant effect of ASE was demonstrated in liver of HF mice by restoration of SOD, CAT and GPx activities and reduction of the increased levels of malondialdehyde and protein carbonylation. In conclusion, ASE substantially reduced the obesity and hepatic steatosis induced by HF diet by reducing lipogenesis, increasing cholesterol excretion and improving oxidative stress in the liver, providing a nutritional resource for prevention of obesity-related adiposity and hepatic steatosis.
de Bem, Graziele F.; Cordeiro, Viviane S. C.; Santos, Izabelle B.; de Carvalho, Lenize C. R. M.; da Conceição, Ellen Paula S.; Lisboa, Patrícia Cristina; Ognibene, Dayane T.; Sousa, Pergentino José C.; Martins, Gabriel R.; da Silva, Antônio Jorge R.; de Moura, Roberto S.; Resende, Angela C.
2015-01-01
The aim of this study was to investigate the effect of a polyphenol-rich Açaí seed extract (ASE, 300 mg/kg-1d-1) on adiposity and hepatic steatosis in mice that were fed a high-fat (HF) diet and its underlying mechanisms based on hepatic lipid metabolism and oxidative stress. Four groups were studied: C57BL/6 mice that were fed with standard diet (10% fat, Control), 10% fat + ASE (ASE), 60% fat (HF), and 60% fat + ASE (HF + ASE) for 12 weeks. We evaluated the food intake, body weight gain, serum glucose and lipid profile, hepatic cholesterol and triacyglycerol (TG), hepatic expression of pAMPK, lipogenic proteins (SREBP-1c, pACC, ACC, HMG-CoA reductase) and cholesterol excretion transporters, ABCG5 and ABCG8. We also evaluated the steatosis in liver sections and oxidative stress. ASE reduced body weight gain, food intake, glucose levels, accumulation of cholesterol and TG in the liver, which was associated with a reduction of hepatic steatosis. The increased expressions of SREBP-1c and HMG-CoA reductase and reduced expressions of pAMPK and pACC/ACC in HF group were antagonized by ASE. The ABCG5 and ABCG8 transporters expressions were increased by the extract. The antioxidant effect of ASE was demonstrated in liver of HF mice by restoration of SOD, CAT and GPx activities and reduction of the increased levels of malondialdehyde and protein carbonylation. In conclusion, ASE substantially reduced the obesity and hepatic steatosis induced by HF diet by reducing lipogenesis, increasing cholesterol excretion and improving oxidative stress in the liver, providing a nutritional resource for prevention of obesity-related adiposity and hepatic steatosis. PMID:26630290
Maize and resistant starch enriched breads reduce postprandial glycemic responses in rats.
Brites, Carla M; Trigo, Maria J; Carrapiço, Belmira; Alviña, Marcela; Bessa, Rui J
2011-04-01
White wheat bread is a poor source of dietary fiber, typically containing less than 2%. A demand exists for the development of breads with starch that is slowly digestible or partially resistant to the digestive process. The utilization of maize flour and resistant starch is expected to reduce the release and absorption of glucose and, hence, lower the glycemic index of bread. This study was undertaken to investigate the hypothesis that a diet of maize bread, as produced and consumed in Portugal, would have beneficial metabolic effects on rats compared to white wheat bread. We also hypothesized that the effect of resistant starch on glycemic response could be altered by the use of different formulations and breadmaking processes for wheat and maize breads. Resistant starch (RS) was incorporated into formulations of breads at 20% of the inclusion rate of wheat and maize flours. Assays were conducted with male Wistar rats (n = 36), divided into four groups and fed either wheat bread, RS-wheat bread, maize bread, and RS-maize bread to evaluate feed intake, body weight gain, fecal pH, and postprandial blood glucose response (glycemic response). Blood triglycerides, total cholesterol concentrations, and liver weights were also determined. The maize bread group presented higher body weight gain and cholesterol level, lower fecal pH, and postprandial blood glucose response than the wheat bread group. The RS-wheat bread group showed significant reductions in feed intake, fecal pH, postprandial blood glucose response, and total cholesterol. The RS-maize group displayed significant reductions of body weight gain, fecal pH, and total cholesterol levels; however, for the glycemic response, only a reduction in fasting level was observed. These results suggest that maize bread has a lower glycemic index than wheat bread, and the magnitude of the effect of RS on glycemic response depends of type of bread. Copyright © 2011 Elsevier Inc. All rights reserved.
Metabolism of 1,2,3,4-, 1,2,3,5-, and 1,2,4,5-tetrachlorobenzene in the squirrel monkey
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schwartz, H.; Chu, I.; Villeneuve, D.C.
1987-01-01
The metabolism of three tetrachlorobenzene isomers (TeCB) was investigated in the squirrel monkey. The animals were administered orally 6 single doses of /sup 14/C-labeled 1,2,3,4-, 1,2,4,5-, or 1,2,3,5-tetrachlorobenzene over a 3-wk period at levels ranging from 50 to 100 mg/kg body weight (b.w) and kept in individual metabolism cages to collect urine and feces for radioassay. Approximately 38% (1,2,3,4-TeCB), 36% (1,2,3,5-TeCB), and 18% (1,2,4,5-TeCB) of the doses were excreted respectively in the feces 48 h post administration. In monkeys dosed with 1,2,3,4-TeCB, unchanged compound accounted for 50% of the fecal radioactivity. Unchanged compound accounted for more than 50% of themore » fecal radioactivity found in the monkeys dosed with 1,2,3,5-TeCB. The fecal metabolites were identified in both groups. No metabolites were detected in the feces of monkeys dosed with 1,2,4,5-TeCB. While the fecal route represented the major route of excretion for 1,2,3,4-TeCB, the other two isomers were eliminated exclusively in the feces. The above data in the squirrel monkey are different from those obtained with the rat and the rabbit, and demonstrate the different metabolic pathways for the isomers.« less
Márquez-Aguirre, Ana Laura; Camacho-Ruiz, Rosa Maria; Arriaga-Alba, Myriam; Padilla-Camberos, Eduardo; Kirchmayr, Manuel Reinhart; Blasco, José Luis; González-Avila, Marisela
2013-08-01
Fructans are dietary fibers with beneficial effects on the gastrointestinal physiology and offer a promising approach for the treatment of some metabolic disorders associated with obesity. In vitro and in vivo studies were developed to test the safety of fructans obtained from Agave tequilana Weber var. azul. Additionally, an in vivo experiment using a diet-induced obesity model was performed to compare the effect of agave fructans with different degree of polymerization (DP) profiles: agave fructans with DP > 10 (LcF), agave FOS with DP < 10 (ScF), and agave fructans with and without demineralization (dTF, TF) versus commercial chicory fructans (OraftiSynergy1™) on the body weight change, fat, total cholesterol, triglycerides and count of fecal Lactobacillus spp. and Bifidobacterium spp. Results showed that A. tequilana fructans were not mutagenic and were safe even at a dose of 5 g per kg b.w. Obese mice that received ScF showed a significant decrease in body weight gain, fat tissue and total cholesterol without increasing the count of fecal Bifidobacteria. Whereas, obese mice that received LcF and TF showed decreased triglycerides and an increased count of fecal Bifidobacteria. Interestingly, although obese mice that received dTF did not show changes in body weight gain, fat tissue, total cholesterol or triglycerides, they showed an increase in the count of Bifidobacteria. These results demonstrate that both the degree of polymerization and the demineralization process can influence the biological activity of agave fructans.
Distribution of creatinine following intravenous and oral administration to rats.
Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S
1981-05-01
To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boyd, G.S.; Merrick, M.V.; Monks, R.
Four selenium-labeled free bile acids and four selenium-labeled conjugated bile acids, labeled with Se-75 at the C-19, C-22, C-23, or C-24 position, have been synthesized and their absorption and excretion compared with that of (24-/sup 14/C)cholic acid, following both oral and intravenous administration. All but one of the compounds is absorbed and excreted in bile to a significant extent. One compound, SeHCAT, has been selected for particular study. It is quantitatively absorbed from the gut at the same rate as cholic acid, and both are excreted into the bile at the same rate. It remains almost entirely confined to themore » enterohepatic circulation (the gut, liver, and biliary tree) and excretion is exclusively fecal. Such a compound offers the possibility of a simple, novel, and aesthetically acceptalbe method investigating small-bowel disease.« less
Ohtsu, Yoshiaki; Gibbons, Jacqueline A; Suzuki, Katsuhiro; Fitzsimmons, Michael E; Nozawa, Kohei; Arai, Hiroshi
2017-08-01
Enzalutamide is an androgen receptor inhibitor that has been approved in several countries. Absorption, distribution, metabolism, and excretion (ADME) data in animals would facilitate understanding of the efficacy and safety profiles of enzalutamide, but little information has been reported in public. The purpose of this study was to clarify the missing ADME profile in animals. ADME of 14 C-enzalutamide after oral administration as Labrasol solution were investigated in non-fasted male Sprague-Dawley rats and beagle dogs. Plasma concentrations of 14 C-enzalutamide peaked in rats and dogs at 6-8 h after a single oral administration. In most tissues, radioactivity concentration peaked at 4 h after administration. Excluding the gastrointestinal tract, tissues with the highest concentration of radioactivity were liver, fat, and adrenal glands. The tissue concentrations of radioactivity declined below the limit of quantitation or <0.89 % of maximum concentration by 168 h post-dose. Two known metabolites (M1 and M2) and at least 15 novel possible metabolites were detected in this study. M1 was the most abundant metabolite in both rats and dogs. Unchanged drug was a minor component in excreta. In intact rats, the mean urinary and fecal excretion of radioactivity accounted for 44.20 and 49.80 % of administered radioactivity, respectively. In intact dogs, mean urinary and fecal excretion was 62.00 and 22.30 % of the administered radioactivity, respectively. Rapid oral absorption was observed in rats and dogs when 14 C-enzalutamide was administered as Labrasol solution. Tissue distribution in rats was clarified. The elimination of enzalutamide is mediated primarily by metabolism. Species differences were observed in excretion route.
Rideout, Todd C.; Carrier, Bradley; Wen, Shin; Raslawsky, Amy; Browne, Richard W.; Harding, Scott V.
2015-01-01
To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (−55%) than either the PS (−24%) or the αLA (−25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (−47%) or in combination with PS (−54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21–22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone. PMID:25664679
Probiotic Properties of Lactobacillus Strains Isolated from Tibetan Kefir Grains
Zheng, Yongchen; Lu, Yingli; Wang, Jinfeng; Yang, Longfei; Pan, Chenyu; Huang, Ying
2013-01-01
The objective of this study was to evaluate the functional properties of lactic acid bacteria (LAB) isolated from Tibetan kefir grains. Three Lactobacillus isolates identified as Lactobacillus acidophilus LA15, Lactobacillus plantarum B23 and Lactobacillus kefiri D17 that showed resistance to acid and bile salts were selected for further evaluation of their probiotic properties. The 3 selected strains expressed high in vitro adherence to Caco-2 cells. They were sensitive to gentamicin, erythromycin and chloramphenicol and resistant to vancomycin with MIC values of 26 µg/ml. All 3 strains showed potential bile salt hydrolase (BSH) activity, cholesterol assimilation and cholesterol co-precipitation ability. Additionally, the potential effect of these strains on plasma cholesterol levels was evaluated in Sprague-Dawley (SD) rats. Rats in 4 treatment groups were fed the following experimental diets for 4 weeks: a high-cholesterol diet, a high-cholesterol diet plus LA15, a high-cholesterol diet plus B23 or a high-cholesterol diet plus D17. The total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in the serum were significantly (P<0.05) decreased in the LAB-treated rats compared with rats fed a high-cholesterol diet without LAB supplementation. The high-density lipoprotein cholesterol levels in groups B23 and D17 were significantly (P<0.05) higher than those in the control and LA15 groups. Additionally, both fecal cholesterol and bile acid levels were significantly (P<0.05) increased after LAB administration. Fecal lactobacilli counts were significantly (P<0.05) higher in the LAB treatment groups than in the control groups. Furthermore, the 3 strains were detected in the rat small intestine, colon and feces during the feeding trial. The bacteria levels remained high even after the LAB administration had been stopped for 2 weeks. These results suggest that these strains may be used in the future as probiotic starter cultures for manufacturing novel fermented foods. PMID:23894554
Gallium-67 complexes as radioactive markers to assess gastric and colonic transit
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bellen, J.C.; Chatterton, B.E.; Penglis, S.
1995-03-01
Constipation and gastroparesis are gastrointestinal tract disorders that can be assessed by using radioactive markers in conjunction with scintigraphic techniques. Indium-111-DTPA is the radiopharmaceutical of choice for treating colonic transit in constipated patients, but it is an expensive product and its availability has been unreliable. Indium-113m-DTPA was the tracer used in our study to determine the liquid gastric emptying rate in dual-isotope solid-liquid emptying studies, however, cessation of the {sup 113}Sn/{sup 113m}In generator production makes it unavailable. Thus, development of alternative tracers to {sup 111}In-DTPA and {sup 113m}In-DTPA was essential. Gallium-67-citrate and {sup 67}Ga-EDTA were compared to {sup 111}In-DTPA tomore » assess their efficacy for exclusive retention in the GI tract. These markers were orally administered into rats and their three-day cumulative fecal excretion, urine excretion and carcass retention were measured. An in vitro gastric emptying model was used to determine liquid phase partitioning of {sup 113m}In-DTPA, {sup 67}Ga-citrate and {sup 67}Ga-EDTA at 37{degrees}. Gallium-67-citrate was predominantly excreted in the feces (97.2% {+-} 0.2%) after three days, with negligible urine excretion (0.1% {+-} 0.0%) and carcass retention (0.6% {+-} 0.2%). These results are analogous to those obtained for {sup 111}In-DTPA for fecal excretion (96.7% {+-} 2.6%), urine excretion (0.6% {+-} 0.0%) and retention in the carcass (0.2% {+-} 0.0%). Gallium-67-EDTA showed similar partitioning in the liquid phase of the gastric emptying model compared with {sup 113m}In-DTPA. Gallium-67-citrate is an economical and readily available alternative to {sup 111}In-DTPA as a colonic transit radiopharmaceutical. Gallium-67-EDTA is also an alternative to {sup 113m}In-DTPA for assessing liquid-phase emptying in a dual-isotope solid/liquid gastric emptying study. 17 refs., 3 figs., 2 tabs.« less
Effects of a fire alarm strobe light on fecal corticosterone metabolite concentrations in mice.
Godfrey, Denice; Silverman, Jerald
2009-02-01
The type and location of fire alarms are important considerations in animal facility design. The Guide for the Care and Use of Laboratory Animals recommends minimizing animal exposure to such alarms. Nevertheless, it is often necessary to maintain fire alarms within animal housing or procedural areas. The authors exposed male mice to the flashing strobe light component of a standard fire alarm and evaluated mouse fecal corticosterone concentration, which is known to be an indicator of stress. Mice were exposed to the strobe light for 5 min during either the light or the dark phase of the light:dark cycle. The authors collected fecal samples every 6 h for 24 h before exposing mice to the alarm and every 6 h for 24 h after exposure. Fecal samples taken before exposure (baseline samples) showed a normal circadian pattern of corticosterone metabolite excretion. In fecal samples taken after mice were exposed to the fire alarm, metabolite concentrations did not significantly differ from baseline concentrations over time.
Färber Lorda, Jaime; Tateda, Yutaka; Fowler, Scott W
2017-08-01
To clarify the relationship between zooplankton biomass and the environmental kinetics of the natural radionuclide 210 Po during a one-year period (October 1995 to November 1996) in northwestern Mediterranean coastal waters, a modelling analysis was applied. Using 210 Po concentrations in seawater and zooplankton, the 210 Po uptake rate constant from food for zooplankton was evaluated using a biokinetics calculation involving the uptake and the excretion rate constants between seawater and zooplankton. Using the transfer constants obtained, the 210 Po concentrations in zooplankton were reconstructed and validated by observed concentrations. The simulation results were in good agreement with the measured 210 Po concentrations in zooplankton. Assuming that 210 Po fecal excretion represents the majority of the excretion of 210 Po from zooplankton, the fecal matter associated 210 Po vertical flux was calculated, and compared with the observed vertical fluxes of 210 Po measured in sediment traps. The modelling evaluation showed that fecal pellet vertical transport could not fully explain the observed sinking fluxes of particulate organic matter at 150 m depth, suggesting that other sinking biodetrital aggregates are also important components of the plankton-derived vertical flux of 210 Po. The relationship between 210 Po concentration in seawater and that in rain and dry fallout and their potential effect on 210 Po concentrations in zooplankton at this location were also examined. A similar, but diphased trend between 210 Po in zooplankton and 210 Po in rain and dry fallout deposition rate was demonstrated. 210 Po concentrations in the dissolved phase of seawater tended to diminish as mean daily rainfall increased suggesting that rain inputs serve as a 210 Po dilution mechanism in seawater at this location. Copyright © 2016 Elsevier Ltd. All rights reserved.
Zhang, Y C; Perzanowski, M S; Chew, G L
2005-07-01
Several epidemiology studies have found an increase in the major cockroach allergen Bla g 2 with reported pesticide use. Our aim was to investigate the effect on the excretion of Bla g 1 and Bla g 2 allergens by cockroaches exposed to sub-lethal doses of the pesticides, boric acid and hydramethylnon gel. German cockroaches in separate colonies were fed either boric acid or hydramethylnon gel at concentrations of 0.2, 0.1 and 0.01% in their water supply over a 2 week period. Ten colonies were exposed to each treatment concentration. Bla g 1 and Bla g 2 in fecal pellets were measured by ELISA. Cockroaches exposed to boric acid excreted fecal pellets with significantly higher concentrations of Bla g 2 (35,400 U/g) than did controls (12,700 U/g) (P = 0.001). Bla g 1 concentrations were not significantly different. There was no difference in either Bla g 1 or Bla g 2 concentrations between cockroaches that ingested hydramethylnon gel and those in the controls colonies. The application of boric acid, a common pesticide, appears to paradoxically increase the production of Bla g 2, a major allergen, by the surviving cockroaches. This may have important implications in avoidance strategies.
Dissolved and fecal pellet carbon and nitrogen release by zooplankton in tropical waters
NASA Astrophysics Data System (ADS)
Small, Lawrence F.; Fowler, Scott W.; Moore, Stanley A.; LaRosa, Jacques
1983-12-01
Carbon (C) and nitrogen (N) release by tropical zooplankton (mostly copepods) and micronekton (euphausiids, pelagic red crabs, and salps) was investigated near VERTEX particle traps at 18°N, 108°W (in 1981) and 15°40'N, 107°30'W (in 1982). The objective was to assess the significance of fecal pellet release relative to respiratory and dissolved excretory release of C and N and relative to primary production in the same waters. For small (< 300 μm) and large (300 to 500 μm) zooplankton, 38 to 49% more ammonium-nitrogen was excreted than C was respired, relative to body concentrations of N and C, respectively. However, for the same zooplankton, 40 to 54% less fecal N was egested than fecal C, again relative to body C and N contents. This apparent compensation yielded a relatively constant body C:N ratio, and, because of the relatively low ratio of respiratory C to excretory N, implied a protein-based metabolism. The same compensatory relationships were found for euphausiids and red crabs, except the percentages of C and N losses were lower than for the zooplankton. No such compensatory relationship was found for the salps, using respiratory—excretory data from the literature and our own observations of fecal pellet production. Either the literature data were not applicable to our salps, or the salps had a more lipid-based metabolism. Reasonably balanced C and N loss budgets were computed for the small and large zooplankton. Daily fecal pellet C egestion represented only 2 to 3% of both large and small zooplankton body C content, and daily fecal pellet N egestion was <2% of zooplankton body N. Likewise, daily fecal pellet production by small and large zooplankton together accounted for <2% of the daily primary C and N production in the top 100 m of water; that is, 'new' primary production would have had to replace losses of <2% per day to balance fecal pellet losses from large and small zooplankton, presuming all fecal pellets sank below 100 m without being eaten or remineralized. However, the estimate of total C flux through 120 m (from particle trap data) was only 4.4% of primary production, so the fecal pellet flux from small and large zooplankton could have accounted for up to 41% of the total flux. From corollary data, it was estimated that the total vertical C flux could result almost entirely from combined fecal pellet production by the existing zooplankton and micronekton concentrations. The vast majority of the primary C production (95.6%) was supported by respired and dissolved excreted compounds plus any atmospheric inputs.
NASA Astrophysics Data System (ADS)
Wong, K.; Shaw, T. I.; Oladeinde, A.; Molina, M.
2013-12-01
Fecal pollution of environmental waters is a major concern for the general public because exposure to fecal-associated pathogens can have severe impacts on human health. Stream and river impairment due to fecal pollution is largely the result of agricultural activities in the United States. In the last few years, numerous metagenomic studies utilized next generation sequencing to develop microbial community profiles by massively sequencing the 16sRNA hypervariable region. This technology supports the application of water quality assessment such as pathogen detection and fecal source tracking. The bacteria communities of samples in these studies were determined when they were freshly collected; therefore, little is known about how feces age or how environmental stress influences the microbial ecology of fecal materials. In this study we monitored bacteria community changes in cattle feces for 57 days after excretion (day 0, 2, 4 8, 15, 22, 29, 43, 57) by sequencing the 16s variable region 4, using Illumnia MiSeq. Twelve cattle feces were studied; half of the samples were directly exposed to sunlight (unshaded) and half were shaded. Results indicate that the relative abundance (RA) profile in both shaded and unshaded samples rapidly changed from day 0 to 15, but stabilized from day 22 to 57. Firmcutes were the most abundant phylum (~40%) at day 0, but were reduced to <10% by day 57. The RA of Proteobacteria was only 1% at day 0, but increased to ~50% by day 57in both shaded and unshaded samples. By the end of the study, shaded and unshaded samples had a similar RA of Firmcutes and Proteobacteria but the RA of Bacteroidetes and Actinobacteria was, respectively, about 7% lower and 10% higher for unshaded samples. UV intensity, moisture, and temperature were significantly different between shaded and unshaded plots, indicating that these environmental stresses could influence the structure of fecal bacteria community in the natural environment. According to the rarefaction curve analysis, richness of bacteria diversity in feces decreased as time progressed. Some pathogens such as Campylobacter were detected only at the beginning, meaning they substantially decayed during the course of our study. Overall, this study indicated: (1) sunlight can influence the community structure and (2) after excretion the fecal bacteria diversity can be significantly changed over time. Future studies should therefore use not only the microbial signature of fresh but also moderately aged fecal samples to develop more accurate community profiles for fecal source tracking.
Vitaglione, Paola; Mennella, Ilario; Ferracane, Rosalia; Rivellese, Angela A; Giacco, Rosalba; Ercolini, Danilo; Gibbons, Sean M; La Storia, Antonietta; Gilbert, Jack A; Jonnalagadda, Satya; Thielecke, Frank; Gallo, Maria A; Scalfi, Luca; Fogliano, Vincenzo
2015-02-01
Epidemiology associates whole-grain (WG) consumption with several health benefits. Mounting evidence suggests that WG wheat polyphenols play a role in mechanisms underlying health benefits. The objective was to assess circulating concentration, excretion, and the physiologic role of WG wheat polyphenols in subjects with suboptimal dietary and lifestyle behaviors. A placebo-controlled, parallel-group randomized trial with 80 healthy overweight/obese subjects with low intake of fruit and vegetables and sedentary lifestyle was performed. Participants replaced precise portions of refined wheat (RW) with a fixed amount of selected WG wheat or RW products for 8 wk. At baseline and every 4 wk, blood, urine, feces, and anthropometric and body composition measures were collected. Profiles of phenolic acids in biological samples, plasma markers of metabolic disease and inflammation, and fecal microbiota composition were assessed. WG consumption for 4-8 wk determined a 4-fold increase in serum dihydroferulic acid (DHFA) and a 2-fold increase in fecal ferulic acid (FA) compared with RW consumption (no changes). Similarly, urinary FA at 8 wk doubled the baseline concentration only in WG subjects. Concomitant reduction in plasma tumor necrosis factor-α (TNF-α) after 8 wk and increased interleukin (IL)-10 only after 4 wk with WG compared with RW (P = 0.04) were observed. No significant change in plasma metabolic disease markers over the study period was observed, but a trend toward lower plasma plasminogen activator inhibitor 1 with higher excretion of FA and DHFA in the WG group was found. Fecal FA was associated with baseline low Bifidobacteriales and Bacteroidetes abundances, whereas after WG consumption, it correlated with increased Bacteroidetes and Firmicutes but reduced Clostridium. TNF-α reduction correlated with increased Bacteroides and Lactobacillus. No effect of dietary interventions on anthropometric measurements and body composition was found. WG wheat consumption significantly increased excreted FA and circulating DHFA. Bacterial communities influenced fecal FA and were modified by WG wheat consumption. This trial was registered at clinicaltrials.gov as NCT01293175. © 2015 American Society for Nutrition.
Sabin and wild polioviruses from apparently healthy primary school children in northeastern Nigeria.
Baba, M M; Oderinde, B S; Patrick, P Z; Jarmai, M M
2012-02-01
Despite significant success of the Global Polio Eradication Initiative (GPEI) in Nigeria, Afghanistan, India, Pakistan, wild poliovirus still occurs due to persistently high proportions of under and unimmunized children. The study aimed at determining the type of poliovirus often excreted into the environment. Four hundred nine fecal samples collected from apparently healthy school children aged 5-16 years in Borno and Adamawa States, northeastern Nigeria, were tested for poliovirus by tissue culture technique. The isolates were characterized further by intratypic differentiation testing and genetic sequencing. Three wild poliovirus type, 11 Sabin type, combination of Sabin-types 1 + 2 and 2 + 3 poliovirus, and 22 non-polio enteroviruses were obtained. The continued excretion of wild-type poliovirus among children above 5 years old vaccinated with oral polio vaccine contributes to the persistent circulation of these viruses in the environment and may limit the population immunity. However, the excreted Sabin poliovirus is capable of immunizing the unvaccinated children and promotes herd immunity. Similarly, the excretion of combination of two polio serotypes indicates the child susceptibility to the missing serotype (s) and therefore indicates an immunity gap. The common unhygienic practices in the environment could aid the spread of these viruses through oral-fecal route. Asymptomatic transmission of wild poliovirus among older oral polio vaccine-vaccinated children poses a serious threat to polio eradication program in Nigeria and therefore, environmental and serological surveillance with larger sample size are important for monitoring poliovirus circulation in Nigeria. Copyright © 2011 Wiley Periodicals, Inc.
Heacox, Hayley N; Gillman, Patricia L; Zwart, Sara R; Smith, Scott M
2017-01-01
Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions. Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis. Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m2): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA. Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR (P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group (P < 0.05). Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients. PMID:28490676
Heacox, Hayley N; Gillman, Patricia L; Zwart, Sara R; Smith, Scott M
2017-06-01
Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions. Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis. Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m 2 ): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA. Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR ( P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group ( P < 0.05). Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients. © 2017 American Society for Nutrition.
Lee, Do Kyung; Park, Shin Young; Jang, Seok; Baek, Eun Hye; Kim, Mi Jin; Huh, Sun Min; Choi, Kyung Soon; Chung, Myung Jun; Kim, Jin Eung; Lee, Kang Oh; Ha, Nam Joo
2011-01-01
Probiotics such as lactic acid bacteria (LAB) and prebiotics such as fiber are generally considered beneficial for health. These affect the microflora composition and fermentation metabolites and consequently contribute to local and systemic effects in humans. The beneficial effects of probiotics can be improved when combined with prebiotics. Here we investigated the effects of a mixed LAB supplement combined with dietary fiber on the population of LAB in the gut, as well as on serum cholesterol levels, fecal water content and microbial harmful enzyme activities. For animal studies, 0.2 mL of mixed LAB (Bifidobacterium longum SPM1205, Lactobacillus acidophilus, and SAFELAC isolated from Pediococcus pentosaceus) supplement (10(7) ∼ 10(8) colony forming units per day) was orally administered to male Sprague-Dawley rats every day for 2 weeks along with a diet containing 5% or 10% cellulose. The mixed LAB supplement combined with dietary cellulose significantly (p < 0.05) reduced serum total cholesterol and LDL levels. This combination also significantly (p < 0.05) increased the population of LAB and the fecal water content and significantly (p < 0.05) reduced microbial harmful enzyme (β-glucosidase, β-glucuronidase and tryptophanase) activities. These effects of LAB were particularly improved by its combination with 5% cellulose compared to the control (a diet without cellulose), and the 5% cellulose combination was more effective than the 10% cellulose combination. In conclusion, the incorporation of a fibrous diet such as cellulose with lactic acid bacteria improved the population of LAB, and daily consumption of this combination could reduce the serum cholesterol levels and activities of harmful enzymes such as β-glucosidase, β-glucuronidase, tryptophanase, urease in rats.
Sahin, N; Sahin, K; Onderci, M; Gursu, M F; Cikim, G; Vijaya, J; Kucuk, O
2005-08-01
1. The effects of chromium picolinate and biotin supplementation alone and in combination on performance, carcase characteristics, malondialdehyde (MDA), vitamin C, vitamin E, glucose and cholesterol levels were evaluated in Japanese quail exposed to high ambient temperature. 2. Two hundred and forty quails (10d old) were assigned randomly to 4 dietary treatments at room temperature (22 degrees C; thermoneutral, TN) or ambient (34 degrees C for 8 h/d; heat stress, HS). Both TN and HS were fed either on a basal (control) diet or the basal diet supplemented with 400 microg of Cr/kg (Cr group), 0.5 mg of biotin/kg of diet (biotin group) or both (Cr + Biotin group). 3. Supplementing the diet of heat-stressed quails with chromium picolinate improved live weight gain, feed intake, feed efficiency and carcase traits. Biotin supplementation during TN and HS conditions did not have any beneficial effects on body weight gain, feed intake, feed efficiency or carcase traits. 4. Either in combination or alone, chromium picolinate increased serum concentrations of vitamins C and E, but decreased MDA, glucose and cholesterol concentrations in birds kept at high ambient temperature. There was no difference in vitamins C and E and MDA concentrations between birds given chromium picolinate and birds receiving chromium picolinate plus biotin, while glucose and cholesterol levels were significantly lower in all groups. The lowest concentrations of cholesterol and glucose were found in the combination group under both TN and HS conditions. An interaction between diet and temperature was detected for glucose and cholesterol concentrations. 5. Excretion rates for zinc, iron and chromium were lower in TN groups than in the corresponding HS groups. Supplementing diet with chromium picolinate and chromium picolinate plus biotin decreased excretion of minerals while biotin alone did not effect excretion of minerals. 6. Chromium supplementation, but not biotin supplementation, attenuated the decline in performance and antioxidant status resulting from heat stress.
Martinez, C M; Chung, Y-H; Ishler, V A; Bailey, K W; Varga, G A
2009-07-01
Two experiments (Exp. 1 and 2) were conducted using a 4 x 4 Latin square design with 2 replications (n = 8) to evaluate effects of feeding Holstein dairy cows a total mixed ration containing 50 or 60% of ration dry matter (DM) from forages with or without supplementation of monensin. In Exp. 1, alfalfa silage (AS) was used as the major forage (55% forage DM), and corn silage (CS; 45% forage DM) was used to make up the rest of the forage portion of diets (55AS:45CS). In Exp. 2, CS was used as the major forage (70% forage DM) and alfalfa hay (AH; 30% forage DM) was used to make up the rest of the forage portion of diets (70CS:30AH). Experimental diets were arranged in a 2 x 2 factorial with 50 or 60% ration DM from forages and monensin supplemented at 0 or 300 mg/cow daily. In Exp. 1 (55AS:45CS), feeding 60% forage diets decreased DM intake (DMI; 27.3 vs. 29.6 kg/d) but maintained the same levels of milk (45.8 vs. 47.0 kg/d) compared with 50% forage diets. The efficiency of converting feed to milk or 3.5% fat-corrected milk was greater for cows fed 60% compared with 50% forage diets (1.7 vs. 1.6 kg milk or 3.5% fat-corrected milk/kg of DMI, respectively). Increasing dietary forage level from 50 to 60% of ration DM increased milk fat percentage (3.4 to 3.5%); however, adding monensin to the 60% forage diet inhibited the increase in milk fat percentage. Feeding 60% forage diets decreased feed cost, but this decrease ($0.5/head per day) in feed cost did not affect income over feed cost. Feeding 60% forage diets decreased fecal excretion of DM (10.6 to 9.6 kg/d) and nitrogen (N; 354 to 324 g/d) and improved apparent digestibility of neutral detergent fiber from 43 to 49% and apparent efficiency of feed N utilization from 32.3 to 35.9% compared with 50% forage diets. In Exp. 2 (70CS:30AH), feeding 60% forage diets decreased DMI from 29.6 to 28.2 kg but maintained the same level of milk (41.1 vs. 40.8 kg/d) and therefore increased the efficiency of converting feed to milk (1.46 vs. 1.38 kg milk/kg DMI) compared with 50% forage diets. Daily feed cost for feeding 60% forage diets was $0.3/head lower than for the 50% forage diets. Fecal excretion of DM (10.3 vs. 11.5 kg/d) was lower and fecal excretion of N (299 vs. 328 g/d) tended to be lower for 60% compared with 50% forage diets. Results from these 2 experiments suggest that a 60% forage diet consisting of either AS or CS as the major forage can be fed to high producing Holstein dairy cows without affecting milk production while improving or maintaining the efficiency of converting feed to milk and the apparent efficiency of utilization of feed N. Cows receiving a 60% forage diet had a similar or improved digestibility of nutrients with a similar or reduced fecal excretion of nutrients. Effects of monensin under the conditions of the current experiments were minimal.
Evaluating adrenal activity in African wild dogs (Lycaon pictus) by fecal corticosteroid analysis.
Monfort, S L; Mashburn, K L; Brewer, B A; Creel, S R
1998-06-01
A noninvasive corticosteroid hormone monitoring technique was validated for use in African wild dogs (Lycaon pictus). The double-antibody 125I radioimmunoassay for corticosterone was validated by demonstrating parallelism between serial dilutions of wild dog fecal extracts and the standard curve, recovery of corticosterone added to fecal extracts, and the time course of fecal corticoid excretion after an exogenous adrenocorticotropic hormone (ACTH) challenge. All feces were collected from three female and two male African wild dogs for 72 hr before and 144 hr after i.m. injection of long-acting ACTH (Acthar Gel, 400 IU). Fecal corticosterone immunoreactivity increased 10-30-fold within 24 hr of ACTH administration in all individuals, with peak concentrations from 1,200-8,000 ng/g. High-pressure liquid chromatography analysis revealed that >90% of all corticosterone immunoreactivity was associated with a single peak that exhibited intermediate polarity relative to cortisol and corticosterone reference tracers. Fecal corticosterone immunoreactivity appears to reflect adrenal activity in the African wild dog and, therefore, may be useful for evaluating stress. From a conservation perspective, these techniques can complement in situ and ex situ research studies designed to evaluate how environmental conditions and management strategies affect overall animal health.
Plath, C; Greese, R; Pfeiffer, H; Thonig, S; Tomczack, H; Uhlemann, M; Erben, R; Gilberg, E; Hüniken, M
1989-04-01
Faecal excretion of fat and carbohydrates was studied in 14 preterm infants fed on raw mother's milk (group I) or banked fortified human milk (group II) at days 7, 14, 21 and 28 of postnatal life: group I: n = 5; 31.0 +/- 2.0 weeks; 1954 +/- 441 g; group II: n = 9; 32.0 +/- 1.0 weeks; 1806 +/- 176 g. Mixtures of amino acids, peptides, minerals, dextrine and maltose were designed for fortifying banked human milk. There were no significant differences between faecal excretion of fat and carbohydrates in both feeding groups. The investigated human milk fortifier helps to realize the protein-energy ratio needed in preterm infants with well tolerable volumes of feeding and without stressing their limited digestive capacity.
Mung bean decreases plasma cholesterol by up-regulation of CYP7A1.
Yao, Yang; Hao, Liu; Shi, Zhenxing; Wang, Lixia; Cheng, Xuzhen; Wang, Suhua; Ren, Guixing
2014-06-01
Our results affirmed that supplementation of 1 or 2% mung bean could decrease plasma total cholesterol and triacylglycerol level. Mung bean increased mRNA 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. Most importantly, mung bean increased not only the protein level of cholesterol-7α-hydroxylase (CYP7A1) but also mRNA CYP7A1. It was concluded that the hypocholesterolemic activity of mung bean was most probable mediated by enhancement of bile acid excretion and up-regulation of CYP7A1.
Ebert, P J; Bailey, E A; Shreck, A L; Jennings, J S; Cole, N A
2017-03-01
Condensed tannins (CT) may decrease greenhouse gas emissions and alter the site of N excreted by ruminants. We evaluated the effect of top-dressing a steam-flaked corn-based finishing diet (14.4% CP and NEg 1.47 Mcal/kg) for beef cattle with a commercially available CT extract at 3 levels (0, 0.5, and 1.0% of diet, DM basis). Angus-crossbred steers ( = 27; 350 ± 32 kg initial BW) were individually fed via Calan gates for 126 d. Diet digestibility and N balance were estimated after 34 and 95 d on feed (Phase 1 and Phase 2, respectively) using titanium dioxide as a marker of fecal output and the creatinine:BW ratio as a marker for urine output. Ruminal CH and metabolic CO fluxes were measured using a GreenFeed system (C-Lock Inc., Rapid City, SD) for 2 sampling periods that coincided with fecal and urine sampling. Urine energy loss was estimated from urine N excretion, assuming all excreted N was urea. Oxygen consumption was estimated from CO production assuming a respiratory quotient of 1.05. Average daily gain (2.08, 2.14, and 2.08 kg/d for 0, 0.5, and 1.0% CT, respectively) and G:F did not differ ( = 0.88) among treatments. Starch intake and OM intake did not differ ( ≥ 0.42) among treatments during each phase. Apparent total tract starch digestibility during Phase 1 linearly decreased ( = 0.04) with inclusion of CT. Apparent total tract digestibility of OM and starch were not different among treatments ( ≥ 0.13) during Phase 2. Nitrogen intake did not differ ( ≥ 0.16) among treatments during each phase, but fecal N excretion linearly increased ( = 0.05) with inclusion of CT during Phase 1. Urinary N excretion was not different ( ≥ 0.39) among treatments during both phases, but urinary N as a proportion of total N excretion linearly decreased ( = 0.01) when CT was included in the diet during Phase 1. Retained N was not different ( ≥ 0.27) among treatments during each phase. Fluxes of CO were similar ( ≥ 0.37) among treatments during both phases. No differences ( ≥ 0.23) were observed for percentage of GE intake lost as CH (2.99, 3.12, and 3.09% in Phase 1 and 3.54, 3.55, and 4.35% in Phase 2) for 0, 0.5, and 1.0% CT, respectively. No difference ( ≥ 0.42) was observed for heat production lost as a percent of GE intake during both phases. Growth performance, gas emissions, and energetic losses were not affected by the inclusion CT in a steam-flaked corn-based finishing diet.
Bofill-Mas, Sílvia; Rusiñol, Marta; Fernandez-Cassi, Xavier; Carratalà, Anna; Hundesa, Ayalkibet
2013-01-01
Many different viruses are excreted by humans and animals and are frequently detected in fecal contaminated waters causing public health concerns. Classical bacterial indicator such as E. coli and enterococci could fail to predict the risk for waterborne pathogens such as viruses. Moreover, the presence and levels of bacterial indicators do not always correlate with the presence and concentration of viruses, especially when these indicators are present in low concentrations. Our research group has proposed new viral indicators and methodologies for determining the presence of fecal pollution in environmental samples as well as for tracing the origin of this fecal contamination (microbial source tracking). In this paper, we examine to what extent have these indicators been applied by the scientific community. Recently, quantitative assays for quantification of poultry and ovine viruses have also been described. Overall, quantification by qPCR of human adenoviruses and human polyomavirus JC, porcine adenoviruses, bovine polyomaviruses, chicken/turkey parvoviruses, and ovine polyomaviruses is suggested as a toolbox for the identification of human, porcine, bovine, poultry, and ovine fecal pollution in environmental samples. PMID:23762826
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lembcke, B.; Loesler, A.C.; Caspary, W.F.
1986-08-01
In order to delineate the clinical value of a dual-isotope fat absorption test system (FATS) using glycerol (/sup 75/Se)triether as lipid-phase marker and glycerol (/sup 125/I)trioleate as the test lipid, fecal isotope ratios from single stools (and a 72-hr stool homogenate) were compared to quantitative fecal fat excretion. The study included 11 patients without and 24 patients with steatorrhea. With a figure of 0.8% as the upper limit of normal, the test was a reliable indicator of steatorrhea with 87.5% sensitivity and 81.8% specificity; efficiency was 85.7%. Related to a prevalence of steatorrhea of 45.9% as the mean value ofmore » 1269 consecutive 72-hr specimens investigated for steatorrhea during 1978-1982, the positive (negative) predictive value of the FATS is 80.3% (87.2%). With 2% as the upper limit of normal, no false positive results ensued. It is concluded that a two-step interpretation of the FATS (0.8% limit and 2% limit) may be regarded a valid qualitative index for steatorrhea. The FATS isotope ratio using single stools correlated well with FATS ratios in the 72-hr stool homogenates (r = 0.97). FATS therefore allows a convenient estimate of steatorrhea from measuring single stools. As a quantitative measure of fecal fat excretion, the FATS is unreliable.« less
Lieske, John C; Tremaine, William J; De Simone, Claudio; O'Connor, Helen M; Li, Xujian; Bergstralh, Eric J; Goldfarb, David S
2010-12-01
We examined the effect of a controlled diet and two probiotic preparations on urinary oxalate excretion, a risk factor for calcium oxalate kidney stone formation, in patients with mild hyperoxaluria. Patients were randomized to a placebo, a probiotic, or a synbiotic preparation. This tested whether these probiotic preparations can increase oxalate metabolism in the intestine and/or decrease oxalate absorption from the gut. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake from food. Urinary oxalate excretion and calcium oxalate supersaturation on the controlled diet were significantly lower compared with baseline on a free-choice diet. Neither study preparation reduced urinary oxalate excretion nor calcium oxalate supersaturation. Fecal lactobacilli colony counts increased on both preparations, whereas enterococcal and yeast colony counts were increased on the synbiotic. Total urine volume and the excretion of oxalate and calcium were all strong independent determinants of urinary calcium oxalate supersaturation. Hence, dietary oxalate restriction reduced urinary oxalate excretion, but the tested probiotics did not influence urinary oxalate levels in patients on a restricted oxalate diet. However, this study suggests that dietary oxalate restriction is useful for kidney stone prevention.
Yeh, J K; Aloia, J F; Semla, H M; Chen, S Y
1986-02-01
Mineral metabolism was studied by the metabolic balance technique in rats with and without administration of caffeine. Caffeine was injected subcutaneously each day at either 2.5 mg or 10 mg/100 g body weight for 2 wk before the balance studies. Urinary volume excretion was higher in the group given caffeine than in the control group, but the creatinine clearance was not different. Urinary excretion of potassium, sodium, inorganic phosphate, magnesium and calcium, but not of zinc and copper, was also higher in the rats given caffeine. The rank order of the difference was the same as the percent of ingested mineral excreted in urine in the absence of caffeine. Caffeine caused a negative balance of potassium, sodium and inorganic phosphate. There was no significant difference from the control levels and in the apparent metabolic balance of calcium and magnesium. The urinary and fecal excretion of zinc and copper were found to be unaffected by caffeine. It is suggested that chronic administration of caffeine may lead to a tendency toward deficiency of those minerals that are excreted primarily in urine.
2014-01-01
Background Lupin proteins exert hypocholesterolemic effects in man and animals, although the underlying mechanism remains uncertain. Herein we investigated whether lupin proteins compared to casein modulate sterol excretion and mRNA expression of intestinal sterol transporters by use of pigs as an animal model with similar lipid metabolism as humans, and cellular cholesterol-uptake by Caco-2 cells. Methods Two groups of pigs were fed cholesterol-containing diets with either 230 g/kg of lupin protein isolate from L. angustifolius or 230 g/kg casein, for 4 weeks. Faeces were collected quantitatively over a 5 d period for analysis of neutral sterols and bile acids by gas chromatographically methods. The mRNA abundances of intestinal lipid transporters were analysed by real-time RT-PCR. Cholesterol-uptake studies were performed with Caco-2 cells that were incubated with lupin conglutin γ, phytate, ezetimibe or albumin in the presence of labelled [4-14C]-cholesterol. Results Pigs fed the lupin protein isolate revealed lower cholesterol concentrations in total plasma, LDL and HDL than pigs fed casein (P < 0.05). Analysis of faeces revealed a higher output of cholesterol in pigs that were fed lupin protein isolate compared to pigs that received casein (+57.1%; P < 0.05). Relative mRNA concentrations of intestinal sterol transporters involved in cholesterol absorption (Niemann-Pick C1-like 1, scavenger receptor class B, type 1) were lower in pigs fed lupin protein isolate than in those who received casein (P < 0.05). In vitro data showed that phytate was capable of reducing the uptake of labelled [4-14C]-cholesterol into the Caco-2 cells to the same extend as ezetimibe when compared to control (−20.5% vs. −21.1%; P < 0.05). Conclusions Data reveal that the cholesterol-lowering effect of lupin protein isolate is attributable to an increased faecal output of cholesterol and a reduced intestinal uptake of cholesterol. The findings indicate phytate as a possible biofunctional ingredient of lupin protein isolate. PMID:24490902
Rhouma, Mohamed; Fairbrother, John Morris; Thériault, William; Beaudry, Francis; Bergeron, Nadia; Laurent-Lewandowski, Sylvette; Letellier, Ann
2017-01-05
Enterotoxigenic Escherichia coli (ETEC) strains producing multiple enterotoxins are important causes of post-weaning diarrhea (PWD) in pigs. The aim of the present study was to investigate the fecal presence of ETEC enterotoxin as well as F4 and F18 genes as an indicator of colistin sulfate (CS) efficacy for treatment of PWD in pigs. Forty-eight piglets were weaned at the age of 21 days, and were divided into four groups: challenged treated, challenged untreated, unchallenged treated, and unchallenged untreated. Challenge was performed using 10 9 CFU of an ETEC: F4 strain, and treatment was conducted using oral CS at the dose of 50,000 IU/kg. The fecal presence of genes encoding for STa, STb, LT, F4 and F18 was detected using PCR. The PCR amplification of ETEC virulence genes showed that nearly 100% of pigs excreted genes encoding for STa and STb toxins in the feces before the challenge. These genes, in the absence of the gene encoding F4, were considered as a marker for F4-negative ETEC. One day after ETEC: F4 oral challenge pigs in the two challenged groups excreted the genes encoding LT and F4 in the feces. These genes were considered as a marker for F4-positive ETEC. However, the gene encoding F18 was not detected in any fecal samples of the 4 groups throughout the experiment. After only 3 days of successive oral treatment with CS, a significant reduction in both the F4-positive and negative ETEC populations was observed in the challenged treated group compared to the challenged untreated group (p < 0.0001). Our study is among the first to report that under controlled farming conditions, oral CS treatment had a significant effect on both fecal F4-positive and F4-negative ETEC in pigs. However, CS clinical efficiency was correlated with non-detection of F4-positive ETEC in the feces. Furthermore the fecal presence of F4-negative ETEC was not associated with clinical symptoms of post-weaning diarrhea in pigs.
Vitamin C modulates lead excretion in rats.
Lihm, Hoseob; Kim, Hyun; Chang, Heekyung; Yoon, Myunghee; Lee, Kayoung; Choi, Jongsoon
2013-12-01
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, H.Z.; Lee, S.P.; Schy, A.L.
1991-06-01
Ceftriaxone, a third-generation cephalosporin, is partially excreted into bile. With its clinical use, the formation of gallbladder sludge detected by ultrasonography has been reported. Four surgical specimens were examined and no gallstones were found. Instead, fine precipitates of 20-250 microns were present. Microscopically, there was a small number of cholesterol monohydrate crystals and bilirubin granules among an abundant amount of granular-crystalline material that was not morphologically cholesterol monohydrate crystals. The chemical composition of the precipitates (n = 4) was determined. There was a small amount of cholesterol (1.7% +/- 0.8%) and bilirubin (13.9% +/- 0.74%). The major component of themore » precipitate was a residue. On further analysis using thin-layer chromatography, high-performance liquid chromatography, and electron microprobe analysis, the residue was identified as a calcium salt of ceftriaxone. The residue also had identical crystal morphology and chromatographic elution profile as authentic calcium-ceftriaxone standards. It is concluded that ceftriaxone, after excretion and being concentrated in the gallbladder bile, can form a precipitate. The major constituent has been identified as a ceftriaxone-calcium salt.« less
Yabe, John; Nakayama, Shouta M M; Ikenaka, Yoshinori; Yohannes, Yared B; Bortey-Sam, Nesta; Kabalo, Abel Nketani; Ntapisha, John; Mizukawa, Hazuki; Umemura, Takashi; Ishizuka, Mayumi
2018-07-01
Lead (Pb) and cadmium (Cd) are toxic metals that exist ubiquitously in the environment. Children in polluted areas are particularly vulnerable to metal exposure, where clinical signs and symptoms could be nonspecific. Absorbed metals are excreted primarily in urine and reflect exposure from all sources. We analyzed Pb and Cd concentrations in blood, feces and urine of children from polluted townships near a lead-zinc mine in Kabwe, Zambia, to determine concurrent childhood exposure to the metals. Moreover, the study determined the Pb and Cd relationships among urine, feces and blood as well as accessed the potential of urine and fecal analysis for biomonitoring of Pb and Cd exposure in children. Fecal Pb (up to 2252 mg/kg, dry weight) and urine Pb (up to 2914 μg/L) were extremely high. Concentrations of Cd in blood (Cd-B) of up to 7.7 μg/L, fecal (up to 4.49 mg/kg, dry weight) and urine (up to 18.1 μg/L) samples were elevated. metal levels were higher in younger children (0-3 years old) than older children (4-7). Positive correlations were recorded for Pb and Cd among blood, urine and fecal samples whereas negative correlations were recorded with age. These findings indicate children are exposed to both metals at their current home environment. Moreover, urine and feces could be useful for biomonitoring of metals due to their strong relationships with blood levels. There is need to conduct a clinical evaluation of the affected children to fully appreciate the health impact of these metal exposure. Copyright © 2018. Published by Elsevier Ltd.
Schneider, Mark J; Fiering, Steven N; Thai, B; Wu, Sing-yung; St Germain, Emily; Parlow, Albert F; St Germain, Donald L; Galton, Valerie Anne
2006-01-01
The type 1 deiodinase (D1) is thought to be an important source of T3 in the euthyroid state. To explore the role of the D1 in thyroid hormone economy, a D1-deficient mouse (D1KO) was made by targeted disruption of the Dio1 gene. The general health and reproductive capacity of the D1KO mouse were seemingly unimpaired. In serum, levels of T4 and rT3 were elevated, whereas those of TSH and T3 were unchanged, as were several indices of peripheral thyroid status. It thus appears that the D1 is not essential for the maintenance of a normal serum T3 level in euthyroid mice. However, D1 deficiency resulted in marked changes in the metabolism and excretion of iodothyronines. Fecal excretion of endogenous iodothyronines was greatly increased. Furthermore, when compared with both wild-type and D2-deficient mice, fecal excretion of [125I]iodothyronines was greatly increased in D1KO mice during the 48 h after injection of [125I]T4 or [125I]T3, whereas urinary excretion of [125I]iodide was markedly diminished. From these data it was estimated that a majority of the iodide generated by the D1 was derived from substrates other than T4. Treatment with T3 resulted in a significantly higher serum T3 level and a greater degree of hyperthyroidism in D1KO mice than in wild-type mice. We conclude that, although the D1 is of questionable importance to the wellbeing of the euthyroid mouse, it may play a major role in limiting the detrimental effects of conditions that alter normal thyroid function, including hyperthyroidism and iodine deficiency.
Li, Lingyun; Harrison, Stephen D; Cope, M Jamie; Park, Craig; Lee, Lawrence; Salaymeh, Faleh; Madsen, Deidre; Benton, Wade W; Berman, Lance; Buysse, Jerry
2016-09-01
Hyperkalemia is a potentially life-threatening condition, and patients who have chronic kidney disease, who are diabetic, or who are taking renin-angiotensin-aldosterone system inhibitors are at increased risk. Therapeutic options for hyperkalemia tend to have limited effectiveness and can be associated with serious side effects. Colonic potassium secretion can increase to compensate when urinary potassium excretion decreases in patients with renal impairment, but this adaptation is insufficient and hyperkalemia still results. Patiromer is a novel, spherical, nonabsorbed polymer designed to bind and remove potassium, primarily in the colon, thereby decreasing serum potassium in patients with hyperkalemia. Patiromer has been found to decrease serum potassium in patients with hyperkalemia having chronic kidney disease who were on renin-angiotensin-aldosterone system inhibitors. Results of nonclinical studies and an early phase clinical study are reported here. Two studies with radiolabeled drug, one in rats and the other in dogs, confirmed that patiromer was not absorbed into the systemic circulation. Results of an in vitro study showed that patiromer was able to bind 8.5 to 8.8 mEq of potassium per gram of polymer at a pH similar to that found in the colon and had a much higher potassium-binding capacity compared with other resins, including polystyrene sulfonate. In a study in hyperkalemic rats, a decrease in serum potassium was observed via an increase in fecal potassium excretion. In a clinical study in healthy adult volunteers, a significant increase in fecal potassium excretion and a significant decrease in urinary potassium excretion were observed. Overall, patiromer is a high-capacity potassium binder, and the chemical and physical characteristics of patiromer may lead to good clinical efficacy, tolerability, and patient acceptance. © The Author(s) 2016.
Harrison, Stephen D.; Cope, M. Jamie; Park, Craig; Lee, Lawrence; Salaymeh, Faleh; Madsen, Deidre; Benton, Wade W.; Berman, Lance; Buysse, Jerry
2016-01-01
Hyperkalemia is a potentially life-threatening condition, and patients who have chronic kidney disease, who are diabetic, or who are taking renin–angiotensin–aldosterone system inhibitors are at increased risk. Therapeutic options for hyperkalemia tend to have limited effectiveness and can be associated with serious side effects. Colonic potassium secretion can increase to compensate when urinary potassium excretion decreases in patients with renal impairment, but this adaptation is insufficient and hyperkalemia still results. Patiromer is a novel, spherical, nonabsorbed polymer designed to bind and remove potassium, primarily in the colon, thereby decreasing serum potassium in patients with hyperkalemia. Patiromer has been found to decrease serum potassium in patients with hyperkalemia having chronic kidney disease who were on renin–angiotensin–aldosterone system inhibitors. Results of nonclinical studies and an early phase clinical study are reported here. Two studies with radiolabeled drug, one in rats and the other in dogs, confirmed that patiromer was not absorbed into the systemic circulation. Results of an in vitro study showed that patiromer was able to bind 8.5 to 8.8 mEq of potassium per gram of polymer at a pH similar to that found in the colon and had a much higher potassium-binding capacity compared with other resins, including polystyrene sulfonate. In a study in hyperkalemic rats, a decrease in serum potassium was observed via an increase in fecal potassium excretion. In a clinical study in healthy adult volunteers, a significant increase in fecal potassium excretion and a significant decrease in urinary potassium excretion were observed. Overall, patiromer is a high-capacity potassium binder, and the chemical and physical characteristics of patiromer may lead to good clinical efficacy, tolerability, and patient acceptance. PMID:26856345
Importance of colonic support for energy absorption as small-bowel failure proceeds.
Nordgaard, I; Hansen, B S; Mortensen, P B
1996-08-01
Digestive processes in the human colon are affected by the bacterial fermentation of malabsorbed carbohydrates and protein to short-chain fatty acids, which are absorbed and supply energy. Energy absorption was measured by assessing fecal bomb calorimetry in 148 patients with extremely different small-bowel lengths. Colectomy increased fecal loss of energy by 0.8 MJ/d and carbohydrate excretion fivefold in patients with a small-bowel length between normal and 150-200 cm. Patients with 100-150 cm small bowel, with and without a colon, excreted 1.3 +/- 0.3 and 4.7 +/- 0.5 MJ/d, respectively (P = 0.002), a difference of 3.4 MJ/d. Patients with < 100 cm small bowel excreted 3.1 +/- 0.4 and 8.0 +/- 1.3 MJ/d, respectively (P = 0.03), a difference of 4.9 MJ/d. Similar and highly significant differences were calculated by linear-regression analysis. Considerably less energy was excreted as carbohydrate than as fat in patients with preserved colonic function, probably because fermentation removed carbohydrate as absorbed short-chain fatty acids, whereas a comparable amount of energy was lost as carbohydrate and fat in patients without colonic function. The correlation between malabsorbed energy and small-bowel length was poor (r = -0.41) but increased when data for patients with and without a colon were separated (r = -0.56 and r = -0.58, respectively). Small-bowel length, however, was still an inaccurate measure of intestinal failure to absorb nutrient energy. In conclusion, colonic digestion may support energy supply with up to approximately 4.2 MJ/d as small-bowel failure proceeds, but it is of minor importance in patients with a small-bowel length > 200 cm or malabsorption < 2.1 MJ/d.
USDA-ARS?s Scientific Manuscript database
Intrinsic phytase in swine feeds may alter phytate utilization and solubility of excreted phosphorus. Therefore, the objective of this experiment was to quantify changes in fecal phosphorus composition from swine fed various cereal grains with a range of phytate concentrations and endogenous phytase...
Morita, K; Matsueda, T; Iida, T
1997-05-01
This paper presents the liver distribution and fecal excretion of polychlorinated biphenyls (PCB), polychlorinated dibenzofurans (PCDF) congeners and polychlorinated dibenzo-p-dioxins (PCDD) congeners, in male rats fed with powdered green tea (matcha). The rats were given a treatment diet containing 10% matcha for the first five days. Then, the animals were administered 4 g of 10% matcha diet containing 0.5 ml of the casual rice-bran oil of Yusho that had occurred in the Southwest part of Japan in 1968 and kept on the same diet for another five days. The fecal excretion of PCB, PCDF and PCDD in the group fed with 10% matcha were 4.4, 2.4-9.1 and 2.5-4.7 times higher (p < 0.01), respectively, than that in the control group. The liver distribution of PCB, PCDF and PCDD in the same groups were 79%, 20-75% and 26-67% of the control group, respectively. These findings suggest that administration of matcha is useful as a treatment of Yusho patients exposed to PCB, PCDF and PCDD.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boyd, G.S.; Merrick, M.V.; Monks, R.
Four selenium-labeled free bile acids and four selenium-labeled conjugated bile acids, labeled with Se-75 at the C-19, C-22, C-23, or C-24 position, have been synthesized and their absorption and excretion compared with that of (24-14C)cholic acid, following both oral and intravenous administration. All but one of the compounds is absorbed and excreted in bile to a significant extent. One compound, SeHCAT, has been selected for particular study. It is quantitatively absorbed from the gut at the same rate as cholic acid, and both are excreted into the bile at the same rate. It remains almost entirely confined to the enterohepaticmore » circulation (the gut, liver, and biliary tree) and excretion is exclusively fecal. Whole-body retention, measured for 41 days, and tissue distributions suggest that the absorbed radiation dose would be small compared with that in many established tests. Such a compound offers the possibility of a simple, novel, and aesthetically acceptable method of investigating small-bowel disease. It therefore merits further investigation.« less
Diurnal fluctuations in nematode egg excretion in naturally and in experimentally infected chickens.
Wongrak, Kalyakorn; Gauly, Matthias; Daş, Gürbüz
2015-03-15
We investigated whether nematode egg excretion through feces of naturally or experimentally infected chickens follow certain patterns within a day, which may allow determining the most appropriate sampling time for the highest parasite egg concentration. Feces samples (n=864) from chickens (n=36) with naturally occurring mixed nematode infections (trials N1, N2) or with an experimental Ascaridia galli infection (E) were collected quantitatively every 4h for four consecutive days. Number of eggs per gram of feces (EPG) was determined, and accumulative egg output (AEO) at each sampling time as well as total number of eggs excreted within 24h (eggs per day, EPD) were then estimated. At the end of the collection period, the hens were necropsied and their worm burdens determined. Naturally infected hens harbored Heterakis gallinarum (100%), Capillaria spp. (95.7%) and A. galli (91.3%). The experimental A. galli infection produced patent infections in all the birds. In general, both fecal egg concentration (EPG) and the amount of feces increased (P<0.05) sharply from the early morning to early-noon (10:00 a.m.) and remained at a high level until evenings which thereafter decreased to their initial levels during the night both in naturally and experimentally infected birds. This resulted in a more apparent increase or a decrease in AEO at the corresponding time points, respectively, and led to much higher egg excretions during the daytime than the nights. Despite the apparent within day fluctuations in egg excretion, neither EPG (P=0.704) nor AEO (P=0.499) nor EPD (P=0.149) was significantly different among the four collection days. Similarly, there was no significant interaction (P>0.05) between effects of sampling hours and days on EPG and AEO, suggesting the existence of repeatable diurnal fluctuations within each day. Although an association between climatic parameters (e.g., ambient temperature and relative humidity) and the nematode egg excretion was quantified, a causal relationship could not be demonstrated. We conclude that nematode egg excretion through chicken feces in both natural and experimental infections shows repeatable diurnal fluctuations, which may indicate adaptive strategies by nematodes and eventually favor parasite spread. Since analytic sensitivity of fecal egg counts suffers from low egg concentrations in feces, samples taken during the daytime have a higher diagnostic value. Copyright © 2015 Elsevier B.V. All rights reserved.
The effects of cholesterol on learning and memory.
Schreurs, Bernard G
2010-07-01
Cholesterol is vital to normal brain function including learning and memory but that involvement is as complex as the synthesis, metabolism and excretion of cholesterol itself. Dietary cholesterol influences learning tasks from water maze to fear conditioning even though cholesterol does not cross the blood brain barrier. Excess cholesterol has many consequences including peripheral pathology that can signal brain via cholesterol metabolites, pro-inflammatory mediators and antioxidant processes. Manipulations of cholesterol within the central nervous system through genetic, pharmacological, or metabolic means circumvent the blood brain barrier and affect learning and memory but often in animals already otherwise compromised. The human literature is no less complex. Cholesterol reduction using statins improves memory in some cases but not others. There is also controversy over statin use to alleviate memory problems in Alzheimer's disease. Correlations of cholesterol and cognitive function are mixed and association studies find some genetic polymorphisms are related to cognitive function but others are not. In sum, the field is in flux with a number of seemingly contradictory results and many complexities. Nevertheless, understanding cholesterol effects on learning and memory is too important to ignore.
Mangione, Antonio M; Dearing, M Denise; Karasov, William H
2004-07-01
Although many plant secondary compounds are known to have serious consequences for herbivores, the costs of processing them are generally unknown. Two potential costs of ingestion and detoxification of secondary compounds are elevation of the minimum drinking water requirement and excretion of energetically expensive metabolites (i.e., glucuronides) in the urine. To address these impacts, we studied the costs of ingestion of resin from creosote bush (Larrea tridentata) on desert woodrats (Neotoma lepida). The following hypotheses were tested: ingestion of creosote resin by woodrats (1) increases minimum water requirement and (2) reduces energy available by increasing fecal and urinary energy losses. We tested the first hypothesis, by measuring the minimum water requirement of woodrats fed a control diet with and without creosote resin. Drinking water was given in decreasing amounts until woodrats could no longer maintain constant body mass. In two separate experiments, the minimum drinking water requirement of woodrats fed resin was higher than that of controls by 18-30% (about 1-1.7 ml/d). We tested several potential mechanisms of increased water loss associated with the increase in water requirement. The rate of fecal water loss was higher in woodrats consuming resin. Neither urinary water nor evaporative water loss was affected by ingestion of resin. Hypothesis 2 was tested by measuring energy fluxes of woodrats consuming control vs. resin-treated diets. Woodrats on a resin diet had higher urinary energy losses and, thus, metabolized a lower proportion of the dietary energy than did woodrats on control diet. Fecal energy excretion was not affected by resin. The excretion of glucuronic acid represented almost half of the energy lost as a consequence of resin ingestion. The increased water requirement and energy losses of woodrats consuming a diet with resin could have notable ecological consequences.
Prados, L F; Sathler, D F T; Silva, B C; Zanetti, D; Valadares Filho, S C; Alhadas, H M; Detmann, E; Santos, S A; Mariz, L D S; Chizzotti, M L
2017-04-01
Weaned Nellore bulls ( = 36; 274 ± 34 kg) were used in a randomized block design with a 2 × 2 factorial arrangement of treatments to evaluate intake, fecal excretion, and performance with different concentrations of minerals. Experimental diets were formulated with 2 concentrations of Ca and P (macromineral factor; diet supplying 100% of Ca and P according to BR-CORTE () [CaP+] or diet without limestone and dicalcium phosphate [CaP-]) and 2 concentrations of microminerals (micromineral factor; diet with supplementation of microminerals [Zn, Mn, and Cu; CuMnZn+] or diet without supplementation of microminerals [Zn, Mn, and Cu; CuMnZn-]). The factor CaP- was formulated without the addition of limestone and dicalcium phosphate, and the factor CuMnZn- was formulated without inorganic supplementation of microminerals (premix). The diets were isonitrogenous (13.3% CP). Intake was individually monitored every day. Indigestible NDF was used as an internal marker for digestibility estimates. The bulls were slaughtered (84 or 147 d on feed), and then carcass characteristics were measured and liver and rib samples were collected. Feed, feces, rib bones, and liver samples were analyzed for DM, ash, CP, ether extract (EE), Ca, P, Zn, Mn, and Cu. There were no significant interactions ( ≥ 0.06) between macro- and micromineral supplementation for any variables in the study. Calcium, P, and micromineral concentrations did not affect ( ≥ 0.20) intake of DM, OM, NDF, EE, CP, TDN, and nonfiber carbohydrates (NFC). Calcium and P intake were affected ( < 0.01) by macromineral factor. Animals fed without Ca and P supplementation consumed less of these minerals. Dry matter and nutrient fecal excretion (OM, NDF, EE, CP, and NFC) were similar ( ≥ 0.23) among all factors. Performance and carcass characteristics were similar ( ≥ 0.09) among diets. The content of ash in rib bones was not affected by diets ( ≥ 0.06). Plasma P and phosphatase alkaline concentrations were similar ( ≥ 0.52) among diets. Supplementation of microminerals decreased ( < 0.01) plasma Ca concentration; nevertheless, all analyzed blood metabolites were within the reference values. Supplementation of Ca and P increased ( < 0.01) fecal excretion of these minerals. These results indicate that mineral supplementation (Ca, P, Zn, Mn, and Cu) of conventional feedlot diets for Nellore bulls may be not necessary. Dietary reductions in these minerals would represent a decrease in the cost of feedlot diets. Dietary reduction in Ca and P content cause a decrease in fecal excretion of these minerals, which, in turn, represents an opportunity to reduce the environmental impact of feedlot operations.
Calci, K R; Burkhardt, W; Watkins, W D; Rippey, S R
1998-12-01
Male-specific bacteriophage (MSB) densities were determined in animal and human fecal wastes to assess their potential impact on aquatic environments. Fecal samples (1,031) from cattle, chickens, dairy cows, dogs, ducks, geese, goats, hogs, horses, seagulls, sheep, and humans as well as 64 sewerage samples were examined for MSB. All animal species were found to harbor MSB, although the great majority excreted these viruses at very low levels. The results from this study demonstrate that in areas affected by both human and animal wastes, wastewater treatment plants are the principal contributors of MSB to fresh, estuarine, and marine waters.
Calci, Kevin R.; Burkhardt, William; Watkins, William D.; Rippey, Scott R.
1998-01-01
Male-specific bacteriophage (MSB) densities were determined in animal and human fecal wastes to assess their potential impact on aquatic environments. Fecal samples (1,031) from cattle, chickens, dairy cows, dogs, ducks, geese, goats, hogs, horses, seagulls, sheep, and humans as well as 64 sewerage samples were examined for MSB. All animal species were found to harbor MSB, although the great majority excreted these viruses at very low levels. The results from this study demonstrate that in areas affected by both human and animal wastes, wastewater treatment plants are the principal contributors of MSB to fresh, estuarine, and marine waters. PMID:9835602
Hypolipidemic effects of different angiocarp parts of Alpinia zerumbet.
Chuang, Chao-Ming; Wang, Hui-Er; Peng, Chiung-Chi; Chen, Kuan Chou; Peng, Robert Y
2011-12-01
In utilization of Alpinia zerumbet (Pers.) Burtt and Smith (Zingiberaceae) (AZ), usually the angiocarps are discarded without further use. We speculate whether the angiocarps could show hypolipidemic effect. Several diets were prepared: Alpinia seed powder (ASP); Alpinia seed powder/husk (ASH): 40/60; and Alpinia seed essential oil (ASO): 0.01-0.10%. Sprague-Dawley rats divided into 11 groups were fed these diets for 8 weeks and tested for the hypolipidemic bioactivity. The fecal neutral cholesterol excretion was increased, and the serum total triglyceride (TG) was significantly reduced from 153.7 mg/dL in the high-fat group (H) to 114.3-119.8 mg/dL by ASO; to 116.3-147.9 mg/dL by ASP; and to 116.2-145.3 mg/dL by ASH. Activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were almost unaffected. The high-density lipoprotein (HDL) levels were mostly raised by ASO to 180.3-200.8 mg/dL. The lowdensity lipoprotein (LDL) levels were mostly reduced to 66.8-82.6 mg/dL by ASH. The level of arachidonic acid was mostly raised to 0.50-0.60% by ASO, compared with 0.37% of group H. More importantly, the significant reduction in hepatic TG and total cholesterol (TC) implicated a crucial liver protective effect. ASP and ASH consisted of high crude-fiber content, while ASO consisted of seed essential oil. Both the seed essential oil and the whole powder of AZ previously had been reported to possess potent hypolipidemic bioactivity. Conclusively, the hypolipidemic effect can be attributed to the combined effect of the essential oil and the crude fiber.
Briand, François; Brousseau, Emmanuel; Quinsat, Marjolaine; Burcelin, Rémy; Sulpice, Thierry
2018-01-05
The use of rat and mouse models limits the translation to humans for developing novel drugs targeting nonalcoholic steatohepatitis (NASH). Obeticholic acid (OCA) illustrates this limitation since its dyslipidemic effect in humans cannot be observed in these rodents. Conversely, Golden Syrian hamsters have a lipoprotein metabolism mimicking human dyslipidemia since it does express the cholesteryl ester transfer protein (CETP). We therefore developed a Diet-Induced NASH (DIN) hamster model and evaluated the impact of OCA. Compared with chow fed controls, hamsters fed for 20 weeks with a free-choice (FC) diet, developed obesity, insulin resistance, dyslipidemia and NASH (microvesicular steatosis, inflammation, hepatocyte ballooning and perisinusoidal to bridging fibrosis). After 20 weeks of diet, FC fed hamsters were treated without or with obeticholic acid (15mg/kg/day) for 5 weeks. Although a non-significant trend towards higher dietary caloric intake was observed, OCA significantly lowered body weight after 5 weeks of treatment. OCA significantly increased CETP activity and LDL-C levels by 20% and 27%, and reduced HDL-C levels by 20%. OCA blunted hepatic gene expression of Cyp7a1 and Cyp8b1 and reduced fecal bile acids mass excretion by 64% (P < 0.05). Hamsters treated with OCA showed a trend towards higher scavenger receptor Class B type I (SR-BI) and lower LDL-receptor hepatic protein expression. OCA reduced NAS score for inflammation (P < 0.01) and total NAS score, although not significantly. Compared to mouse and rat models, the DIN hamster replicates benefits and side effects of OCA as observed in humans, and should be useful for evaluating novel drugs targeting NASH. Copyright © 2017 Elsevier B.V. All rights reserved.
Periago, María Jesús; Martín-Pozuelo, Gala; González-Barrio, Rocío; Santaella, Marina; Gómez, Victoria; Vázquez, Nuria; Navarro-González, Inmaculada; García-Alonso, Javier
2016-10-12
The aims of the present study were to ascertain, indirectly, the prebiotic role of tomato juice, by analyzing its effect on the content of short chain fatty acids (SCFA) in feces of rats, and to determine the plausible mechanisms related to the hypocholesterolemic effects of tomato juice and lycopene, evaluating the activity of hepatic HMGCR and the formation of propionic acid. Two commercially available tomato juices with differing contents of lycopene (low and high lycopene contents: Llyc and Hlyc tomato juices) were used. Sprague-Dawley male rats were randomly divided into three experimental groups (n = 8): control group, normal diet and water; group 1, normal diet and Llyc tomato juice; and group 2, normal diet and Hlyc tomato juice, which were fed ad libitum for three weeks. Feces were collected at the beginning and the end of the study to determine SCFA, and blood and liver were obtained (after sacrificing the animals) to analyze the lipid plasmatic parameters and the HMGCR activity and total cholesterol, respectively. No significant differences were observed in the plasmatic parameters, except that HDL-cholesterol increased significantly after consumption of both tomato juices. Lycopene was accumulated in the liver in proportion to the amount ingested, and was observed to have an inhibitory effect on the HMGCR enzyme, according to the amount of lycopene in the liver. In relation to the SCFA in feces, no differences were observed in acetate and propionate after the consumption of tomato juice, but a significant increase in butyrate was observed in group 2 after the intake of Hlyc tomato juice. The content of this carboxylic acid together with excreted lycopene in feces could have a beneficial effect on colonic cells.
Eriksson, Per; Mourkas, Evangelos; González-Acuna, Daniel; Olsen, Björn; Ellström, Patrik
2017-01-01
ABSTRACT Introduction: Advances in the development of nucleic acid-based methods have dramatically facilitated studies of host–microbial interactions. Fecal DNA analysis can provide information about the host’s microbiota and gastrointestinal pathogen burden. Numerous studies have been conducted in mammals, yet birds are less well studied. Avian fecal DNA extraction has proved challenging, partly due to the mixture of fecal and urinary excretions and the deficiency of optimized protocols. This study presents an evaluation of the performance in avian fecal DNA extraction of six commercial kits from different bird species, focusing on penguins. Material and methods: Six DNA extraction kits were first tested according to the manufacturers’ instructions using mallard feces. The kit giving the highest DNA yield was selected for further optimization and evaluation using Antarctic bird feces. Results: Penguin feces constitute a challenging sample type: most of the DNA extraction kits failed to yield acceptable amounts of DNA. The QIAamp cador Pathogen kit (Qiagen) performed the best in the initial investigation. Further optimization of the protocol resulted in good yields of high-quality DNA from seven bird species of different avian orders. Conclusion: This study presents an optimized approach to DNA extraction from challenging avian fecal samples. PMID:29152162
Zanetti, D; Godoi, L A; Estrada, M M; Engle, T E; Silva, B C; Alhadas, H M; Chizzotti, M L; Prados, L F; Rennó, L N; Valadares Filho, S C
2017-04-01
The objectives of this study were to quantify the mineral balance of Nellore cattle fed with and without Ca, P, and micromineral (MM) supplementation and to estimate the net and dietary mineral requirement for cattle. Nellore cattle ( = 51; 270.4 ± 36.6 kg initial BW and 8 mo age) were assigned to 1 of 3 groups: reference ( = 5), maintenance ( = 4), and performance ( = 42). The reference group was slaughtered prior to the experiment to estimate initial body composition. The maintenance group was used to collect values of animals at low gain and reduced mineral intake. The performance group was assigned to 1 of 6 treatments: sugarcane as the roughage source with a concentrate supplement composed of soybean meal and soybean hulls with and without Ca, P, and MM supplementation; sugarcane as the roughage source with a concentrate supplement composed of soybean meal and ground corn with and without Ca, P, and MM supplementation; and corn silage as the roughage source with a concentrate supplement composed of soybean meal and ground corn with and without Ca, P, and MM supplementation. Orthogonal contrasts were adopted to compare mineral intake, fecal and urinary excretion, and apparent retention among treatments. Maintenance requirements and true retention coefficients were generated with the aid of linear regression between mineral intake and mineral retention. Mineral composition of the body and gain requirements was assessed using nonlinear regression between body mineral content and mineral intake. Mineral intake and fecal and urinary excretion were measured. Intakes of Ca, P, S, Cu, Zn, Mn, Co, and Fe were reduced in the absence of Ca, P, and MM supplementation ( < 0.05). Fecal excretion of Ca, Cu, Zn, Mn, and Co was also reduced in treatments without supplementation ( < 0.01). Overall, excretion and apparent absorption and retention coefficients were reduced when minerals were not supplied ( < 0.05). The use of the true retention coefficient instead of the true absorption coefficient provided a better estimate of mineral requirements. Dietary mineral requirements were lower for P, Cu, and Zn and greater for Fe compared with previously published recommendations. This study provides useful information about mineral requirements and mineral supplementation to obtain adequate dietary mineral supply of Nellore cattle in tropical conditions.
USDA-ARS?s Scientific Manuscript database
A study was conducted to evaluate the role of bacteriophage (BP) against Salmonella enterica serovar Enteritidis (SE) internal organs colonization and ileum immune response in laying hens. Hens were challenged both orally and intracloacally with 108 cfu/mL cells of nalidixic acid resistant Salmonell...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Beyer, K.H. Jr.; Fehr, D.M.; Gelarden, R.T.
Salt intake is restricted under clinical conditions for which thiazide diuretics are customarily used. Dietary iodide intake offsets any effect of thiazide on iodide loss. However, our correlation coefficients relating Na+ to Cl- to I- excretion indicate that as thiazide administration or sodium chloride intake increases renal Na+ and Cl- excretion, I- reabsorption by the nephron coordinately decreases. Increased sodium chloride and water intake by the dog doubled I-excretion rates. Hydrochlorothiazide increased the sodium chloride and water enhanced I-excretion rate as much as eight-fold. Without added NaCl, hydrochlorothiazide increased the excretion rate of 131I by three- to eightfold, acutely. Withinmore » five to seven days after 131I oral administration, hydrochlorothiazide (1 or 2 mg/kg twice daily) doubled the rate of 131I disappearance from plasma, reduced the fecal output of 131I, and increased its rate of renal excretion. When hydrochlorothiazide was administered, as much 131I was excreted in the first 24 hours as occurred in 48 hours when sodium chloride and water were given without hydrochlorothiazide. Thiazide administration in customary clinical dosage twice a day with substantial sodium chloride and water for the first two days after exposure to 131I, should therefore facilitate the safe excretion of 131I. This accelerated removal of 131I might be enhanced even more if thyroid uptake of 131I is blocked by administration of potassium iodide, as judged by the greater 131I recovery from thyroidectomized dogs.« less
Effect of neomycin on azoxymethane-induced colon carcinogenesis in F344 rats.
Reddy, B S; Furuya, K; Lowenfels, A
1984-07-01
The effect of oral administration of neomycin (100 and 200 micrograms/ml in drinking water) on colon tumors induced by azoxymethane [(AOM); CAS: 25843-45-2] was studied in female F344 rats. Five-week-old rats were fed NIH-07 diet and given daily in drinking water 0, 100, and 200 micrograms neomycin/ml (0, 100, and 200 ppm). At 7 weeks of age, all animals except vehicle-treated groups received weekly sc injections of 8 mg AOM/kg body weight for 8 weeks. The AOM- or vehicle-treated groups were necropsied 30 weeks after the last injection of AOM. The combined incidence of adenomas and adenocarcinomas of the colon did not differ significantly among the 3 groups. The animals in the groups given 100 and 200 micrograms neomycin had a higher incidence of colon adenocarcinomas than did those in the control group. Colonic and cecal bacterial beta-glucuronidase activity was significantly lower in the group given 200 micrograms neomycin than it was in the control group. The excretion of fecal cholesterol, total bile acids, and deoxycholic acid was increased significantly in animals given 100 and 200 micrograms neomycin as compared to animals given no neomycin. These results suggest that long-term oral administration of neomycin increases the incidence of colon adenocarcinomas.
Red wine consumption is associated with fecal microbiota and malondialdehyde in a human population.
Cuervo, Adriana; Reyes-Gavilán, Clara G de Los; Ruas-Madiedo, Patricia; Lopez, Patricia; Suarez, Ana; Gueimonde, Miguel; González, Sonia
2015-01-01
Red wine intake has been associated with a lower risk of cardiovascular disease; its polyphenol content is the primary cause of antioxidant and anti-inflammatory properties attributed to this beverage. However, the way in which these activities are exerted is not yet clear, although some authors have proposed that intestinal microbiota could be implicated. The association between red wine intake, inflammation, and oxidative stress parameters and fecal microbial populations has been explored in 38 adult volunteers. Food intake was recorded by means of an annual food frequency questionnaire (FFQ). Energy, cholesterol, and ethanol intake were analyzed using the nutrient Food Composition Tables developed by Centro de Enseñanza Superior de Nutrición y Dietética (CESNID) and polyphenol intake was obtained from the Phenol-Explorer Database. Fecal levels of Akkermansia, Bacteroides, Bifidobacterium, Blautia coccoides group, Clostridium leptum group, Lactobacillus group, and Faecalibacterium prausnitzii were determined by quantitative polymerase chain reaction. Serum concentrations of C-reactive protein (CRP), malondialdehyde (MDA), total antioxidant capacity (TAC), cholesterol, triglycerides and glucose were analyzed by standard methods. Subjects with regular consumption of red wine (mean = 100 ml/day) had lower serum concentrations of MDA and lower fecal levels of B. coccoides, C. leptum, Bifidobacterium, and Lactobacillus. A positive association between MDA levels and B. coccoides and Lactobacillus was also found. Regular consumption of red wine appears to be associated with a reduced serum lipoperoxidation in which the intestinal microbiota may be involved.
Pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe (Part I).
Asami, Akitoshi; Shimada, Tsutomu; Mizuhara, Yasuharu; Asano, Takayuki; Takeda, Shuichi; Aburada, Takashi; Miyamoto, Ken-Ichi; Aburada, Masaki
2010-07-01
To investigate the pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe, the pharmacokinetic parameters were determined by using (14)C-[6]-shogaol (labeled compound) and [6]-shogaol (non-labeled compound). When the labeled compound was orally administered to rats, the maximum plasma concentration (C (max)) and the area under the curve (AUC) of plasma radioactivity concentration increased in a dose-dependent manner. When the labeled compound was orally administered at a dose of 10 mg/kg, 20.0 + or - 1.8% of the radioactivity administered was excreted into urine, 64.0 + or - 12.9% into feces, and 0.2 + or - 0.1% into breath. Thus, more of the radioactivity was excreted into feces than into urine, and almost no radioactivity was excreted into breath. Furthermore, when the labeled compound was orally administered at a dose of 10 mg/kg, cumulative biliary radioactivity excretion over 48 h was 78.5 + or - 4.5% of the radioactivity administered, and cumulative urinary radioactivity excretion over 48 h was 11.8 + or - 2.7%, showing that about 90% of the dose administered orally was absorbed from the digestive tract and most of the fecal excretion was via biliary excretion. On the other hand, when the non-labeled compound [6]-shogaol was orally administered, the plasma concentration and biliary excretion of the unchanged form were extremely low. When these results are combined with those obtained with the labeled compound, it would suggest that [6]-shogaol is mostly metabolized in the body and excreted as metabolites.
Diet and fecal steroid profile in a South Asian population with a low colon-cancer rate.
McKeigue, P M; Adelstein, A M; Marmot, M G; Henly, P J; Owen, R W; Hill, M J; Thompson, M H
1989-07-01
South Asian immigrants to England and Wales have low mortality from colon cancer and high mortality from coronary heart disease compared with the general population. In a survey of a predominantly Gujarati population in northwest London, both vegetarians and nonvegetarians had similar total dietary fat intake to the native British population but higher dietary fiber intake. Total fecal bile acid and neutral animal sterol concentrations were lower in South Asians than in a native British comparison group. Sixty-two percent of South Asians excreted detectable quantities of free primary bile acids, which were not present in stools from native British subjects. The ratio of fecal coprostanol to total neutral animal sterols was also lower in South Asians. Low risk of colon cancer in this population may be related to reduced microbial activity in the bowel and low levels of tumor-promoting secondary bile acids.
NASA Technical Reports Server (NTRS)
Sabbot, I. M.; Mcnew, J. J.; Hoshizaki, T.; Sedgwick, C. J.; Adey, W. R.
1972-01-01
An unrestrained chimpanzee was studied in an isolation chamber and in his home cage environment. The study consisted of 49 urine collection days (14 days pre-, 5 days post- and 30 days of isolation), and then of 10 days in the home cage. Dietary intake, urine and fecal data were obtained. The effect of isolation on various excretory parameters was studied. Urine samples were analyzed for volume, osmolarity, creatinine, creatine, urea-N, 17-hydroxy corticosteroids, VMA, calcium and inorganic phosphorus. One way analyses of variance performed on the urinary excretion parameters showed all except creatinine excretion to vary significantly during periods of the study. The changes observed in calcium and phosphorus were highly significant. The data suggests that the calcium to phosphorus excretion ratio might serve as a physiological stress indicator of Selye's adaptation syndrome (period of resistance).
Ammonia as a respiratory gas in water and air-breathing fishes.
Randall, David J; Ip, Yuen K
2006-11-01
Ammonia is produced in the liver and excreted as NH(3) by diffusion across the gills. Elevated ammonia results in an increase in gill ventilation, perhaps via stimulation of gill oxygen chemo-receptors. Acidification of the water around the fish by carbon dioxide and acid excretion enhances ammonia excretion and constitutes "environmental ammonia detoxification". Fish have difficulties in excreting ammonia in alkaline water or high concentrations of environmental ammonia, or when out of water. The mudskipper, Periphthalmodon schlosseri, is capable of active NH(4)(+) transport, maintaining low internal levels of ammonia. To prevent a back flux of NH(3), these air-breathing fish can increase gill acid excretion and reduce the membrane NH(3) permeability by modifying the phospholipid and cholesterol compositions of their skin. Several air-breathing fish species can excrete ammonia into air through NH(3) volatilization. Some fish detoxify ammonia to glutamine or urea. The brains of some fish can tolerate much higher levels of ammonia than other animals. Studies of these fish may offer insights into the nature of ammonia toxicity in general.
Effects of soya oligosaccharides and soya oligopeptides on lipid metabolism in hyperlipidaemic rats.
Xie, Shali; Zhu, Jundong; Zhang, Yanqi; Shi, Kai; Shi, Yuangang; Ma, Xiao
2012-08-01
In the present study, we aimed to examine the effects of soya oligosaccharides (SOS) and soya oligopeptides (SOP) on blood lipid levels, release of vasoactive substances, antioxidant activity and faecal bile acid (FBA) excretion in rats fed a high-fat diet (HFD). Male Sprague-Dawley rats were evenly divided into five groups according to diets as follows: regular diet (control), HFD, HFD enriched with 2 % of SOS (SOS), HFD enriched with 3 % of SOP (SOP) and HFD enriched with 2 % SOS and 3 % SOP (SOSP). The results showed that SOS and SOP significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, whereas HDL-cholesterol concentration was significantly increased. Furthermore, SOS and SOP reduced plasma apoB, apoE and the apoB:apoAI ratio, whereas apoAI was significantly increased. Moreover, SOS and SOP also reduced plasma thromboxane A₂ (TXA₂) and the TXA₂:prostacyclin (PGI₂) ratio, whereas plasma PGI₂ and nitric oxide were significantly increased. In addition, SOS and SOP significantly reduced serum and liver malondialdehyde concentrations and increased FBA excretion. However, we did not observe obvious influences of SOS and SOP on superoxide dismutase activities in the liver of HFD-fed rats. The combination of 2 % SOS and 3 % SOP showed a more marked effect than SOS or SOP alone in improving the lipid profile, release of vasoactive substances and increasing FBA excretion (P < 0.05). In summary, SOS and SOP might help prevent atherosclerosis through improving abnormal blood lipid levels, regulating vasoactive substances and protecting against oxidative stress.
Kim, Yunhye; Yoon, Sun; Lee, Sun Bok; Han, Hye Won; Oh, Hayoun; Lee, Wu Joo; Lee, Seung-Min
2014-01-01
We aimed to investigate whether in vitro fermentation of soy with L. plantarum could promote its beneficial effects on lipids at the molecular and physiological levels. Rats were fed an AIN76A diet containing 50% sucrose (w/w) (CTRL), a modified AIN76A diet supplemented with 1% (w/w) cholesterol (CHOL), or a CHOL diet where 20% casein was replaced with soy milk (SOY) or fermented soy milk (FSOY). Dietary isoflavone profiles, serum lipids, hepatic and fecal cholesterol, and tissue gene expression were examined. The FSOY diet had more aglycones than did the SOY diet. Both the SOY and FSOY groups had lower hepatic cholesterol and serum triglyceride (TG) than did the CHOL group. Only FSOY reduced hepatic TG and serum free fatty acids and increased serum HDL-CHOL and fecal cholesterol. Compared to CHOL, FSOY lowered levels of the nuclear forms of SREBP-1c and SREBP-2 and expression of their target genes, including FAS, SCD1, LDLR, and HMGCR. On the other hand, FSOY elevated adipose expression levels of genes involved in TG-rich lipoprotein uptake (ApoE, VLDLR, and Lrp1), fatty acid oxidation (PPARα, CPT1α, LCAD, CYP4A1, UCP2, and UCP3), HDL-biogenesis (ABCA1, ApoA1, and LXRα), and adiponectin signaling (AdipoQ, AdipoR1, and AdipoR2), as well as levels of phosphorylated AMPK and ACC. SOY conferred a similar expression profile in both liver and adipose tissues but failed to reach statistical significance in many of the genes tested, unlike FSOY. Our data indicate that fermentation may be a way to enhance the beneficial effects of soy on lipid metabolism, in part via promoting a reduction of SREBP-dependent cholesterol and TG synthesis in the liver, and enhancing adiponectin signaling and PPARα-induced expression of genes involved in TG-rich lipoprotein clearance, fatty acid oxidation, and reverse cholesterol transport in adipose tissues.
Han, Hye Won; Oh, Hayoun; Lee, Wu Joo; Lee, Seung-Min
2014-01-01
We aimed to investigate whether in vitro fermentation of soy with L. plantarum could promote its beneficial effects on lipids at the molecular and physiological levels. Rats were fed an AIN76A diet containing 50% sucrose (w/w) (CTRL), a modified AIN76A diet supplemented with 1% (w/w) cholesterol (CHOL), or a CHOL diet where 20% casein was replaced with soy milk (SOY) or fermented soy milk (FSOY). Dietary isoflavone profiles, serum lipids, hepatic and fecal cholesterol, and tissue gene expression were examined. The FSOY diet had more aglycones than did the SOY diet. Both the SOY and FSOY groups had lower hepatic cholesterol and serum triglyceride (TG) than did the CHOL group. Only FSOY reduced hepatic TG and serum free fatty acids and increased serum HDL-CHOL and fecal cholesterol. Compared to CHOL, FSOY lowered levels of the nuclear forms of SREBP-1c and SREBP-2 and expression of their target genes, including FAS, SCD1, LDLR, and HMGCR. On the other hand, FSOY elevated adipose expression levels of genes involved in TG-rich lipoprotein uptake (ApoE, VLDLR, and Lrp1), fatty acid oxidation (PPARα, CPT1α, LCAD, CYP4A1, UCP2, and UCP3), HDL-biogenesis (ABCA1, ApoA1, and LXRα), and adiponectin signaling (AdipoQ, AdipoR1, and AdipoR2), as well as levels of phosphorylated AMPK and ACC. SOY conferred a similar expression profile in both liver and adipose tissues but failed to reach statistical significance in many of the genes tested, unlike FSOY. Our data indicate that fermentation may be a way to enhance the beneficial effects of soy on lipid metabolism, in part via promoting a reduction of SREBP-dependent cholesterol and TG synthesis in the liver, and enhancing adiponectin signaling and PPARα-induced expression of genes involved in TG-rich lipoprotein clearance, fatty acid oxidation, and reverse cholesterol transport in adipose tissues. PMID:24520358
32 CFR 199.18 - Uniform HMO Benefit.
Code of Federal Regulations, 2012 CFR
2012-07-01
... schedule, including frequency or age specifications for: (i) Laboratory and x-ray tests, including blood lead, rubella, cholesterol, fecal occult blood testing, and mammography; (ii) Pap smears; (iii) Eye exams; (iv) Immunizations; (v) Periodic health promotion and disease prevention exams; (vi) Blood...
32 CFR 199.18 - Uniform HMO Benefit.
Code of Federal Regulations, 2011 CFR
2011-07-01
... schedule, including frequency or age specifications for: (i) Laboratory and x-ray tests, including blood lead, rubella, cholesterol, fecal occult blood testing, and mammography; (ii) Pap smears; (iii) Eye exams; (iv) Immunizations; (v) Periodic health promotion and disease prevention exams; (vi) Blood...
32 CFR 199.18 - Uniform HMO Benefit.
Code of Federal Regulations, 2013 CFR
2013-07-01
... schedule, including frequency or age specifications for: (i) Laboratory and x-ray tests, including blood lead, rubella, cholesterol, fecal occult blood testing, and mammography; (ii) Pap smears; (iii) Eye exams; (iv) Immunizations; (v) Periodic health promotion and disease prevention exams; (vi) Blood...
da Teixeira, Catarine S C; de Carvalho, Gleidson G P; Nicory, Isis C M; Santos, Aracele V; Dos Pina, Douglas S; de Júnior, José E F; de Araújo, Maria L G M L; de Rufino, Luana M A; Cirne, Luís G A; Pires, Aureliano J V
2018-04-01
Two experiments were conducted to evaluate the number of days required for total fecal collection and the viability of using the indigestible dry matter (iDM), indigestible neutral detergent fiber (iNDF), and indigestible acid detergent fiber (iADF) internal markers to determine the fecal excretion of dry matter (FEDM) and digestibility in nutritional trials with small ruminants. Eight sheep in the first experiment and eight goats in the second experiment were distributed into two 4 × 4 Latin square designs. There were no significant differences between days of total fecal collection for FEDM; digestibility of dry matter (DM), organic matter (OM), crude protein (CP), ether extract (EE), neutral detergent fiber corrected for ash and protein (NDFap), and non-fibrous carbohydrates corrected for ash and protein (NFCap); and total digestible nutrients (TDN) in both species. The results suggest that only 1 day of total collection is sufficient to obtain the FEDM and the digestibility of the nutritional components in sheep and goats. The markers are efficient in determining fecal production and digestibility in these animal species.
Lutale, Janet Joy Kachuchuru; Thordarson, Hrafnkell; Abbas, Zulfiqarali Gulam; Vetvik, Kåre
2007-01-01
Background The prevalences and risk factors of microalbuminuria are not full described among black African diabetic patients. This study aimed at determining the prevalence of microalbuminuria among African diabetes patients in Dar es Salaam, Tanzania, and relate to socio-demographic features as well as clinical parameters. Methods Cross sectional study on 91 Type 1 and 153 Type 2 diabetic patients. Two overnight urine samples per patient were analysed. Albumin concentration was measured by an automated immunoturbidity assay. Average albumin excretion rate (AER) was used and were categorised as normalbuminuria (AER < 20 ug/min), microalbuminuria (AER 20–200 ug/min), and macroalbuminuria (AER > 200 ug/min). Information obtained also included age, diabetes duration, sex, body mass index, blood pressure, serum total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides, serum creatinine, and glycated hemoglobin A1c. Results Overall prevalence of microalbuminuria was 10.7% and macroalbuminuria 4.9%. In Type 1 patients microalbuminuria was 12% and macroalbuminuria 1%. Among Type 2 patients, 9.8% had microalbuminuria, and 7.2% had macroalbuminuria. Type 2 patients with abnormal albumin excretion rate had significantly longer diabetes duration 7.5 (0.2–24 yrs) than those with normal albumin excretion rate 3 (0–25 yrs), p < 0.001. Systolic and diastolic blood pressure among Type 2 patients with abnormal albumin excretion rate were significantly higher than in those with normal albumin excretion rate, (p < 0.001). No significant differences in body mass index, glycaemic control, and cholesterol levels was found among patients with normal compared with those with elevated albumin excretion rate either in Type 1 or Type 2 patients. A stepwise multiple linear regression analysis among Type 2 patients, revealed AER (natural log AER) as the dependent variable to be predicted by [odds ratio (95% confidence interval)] diabetes duration 0.090 (0.049, 0.131), p < 0.0001, systolic blood pressure 0.012 (0.003–0.021), p < 0.010 and serum creatinine 0.021 (0.012, 0.030). Conclusion The prevalence of micro and macroalbuminuria is higher among African Type 1 patients with relatively short diabetes duration compared with prevalences among Caucasians. In Type 2 patients, the prevalence is in accordance with findings in Caucasians. The present study detects, however, a much lower prevalence than previously demonstrated in studies from sub-Saharan Africa. Abnormal AER was significantly related to diabetes duration and systolic blood pressure. PMID:17224056
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kramer, L.
The effect of drugs such as glucocorticoids and thyroid extract on calcium metabolism is unknown. However, several other medications affect the excretion and intestinal absorption of calcium. A controlled study was carried out to investigate these aspects. Urinary calcium was determined for 3 months during the long-term intake of the antituberculous drug isoniazid (INH) and of the antibiotic tetracycline. The effect of the diuretics furosemide and hydrochlorothiazide, of several aluminum-containing antacids, of thyroid extract and of corticosteroids was also studied. Metabolic balances of calcium, phosphorus, magnesium and zinc were determined, as well as the intestinal absorption of calcium using Camore » 47. Plasma levels, urinary and fecal excretions of Ca 47 were determined. All drugs tested increased urinary calcium except for the diuretic hydrochlorothiazide. Regarding the effect of corticosteroids: the intestinal absorption of calcium was unchanged after the short-term use and was very high after long-term use. The studies have shown that several commonly used drugs induce an increase in urinary calcium excretion which may contribute to calcium loss, if this increase persists for prolonged periods of time. Urinary excretions of phosphorus, magnesium and zinc increased in some of the studies.« less
NASA Technical Reports Server (NTRS)
Krebs, J. M.; Schneider, V. S.; LeBlanc, A. D.
1988-01-01
The effects of bed rest and fluoride supplementation on zinc, copper, and nitrogen balances and Zn and Cu serum levels were measured in 15 healthy males. Subjects aged 19-54 y remained on a metabolic research ward for 10 wk. During weeks 1-5, subjects were ambulatory. During wks 6-10 they remained in continuous bed rest. During weeks 3-10 nine subjects received 10 or 20 mg F/d as sodium fluoride. Daily urine and weekly fecal composites were made and biweekly fasting blood samples were taken. Dietary intakes were 1.40 +/- 0.17 mg Cu/d (22.0 +/- 2.7 mumol Cu/d), 10.82 +/- 0.49 mg Zn/d (165.6 +/- 7.6 mumol Zn/d), and 14.27 +/- 0.23 g N/d (1019 +/- 16 mmol N/d). Bed rest increased urinary Zn and N excretions and fecal Zn excretions and decreased Zn balance (p less than 0.05) whereas Cu balance was unchanged. During bed rest, F supplementation increased Zn and N balances compared with untreated control subjects (p less than 0.05). These results are compatible with bone and muscle atrophy during bed rest and increased bone formation with F supplementation.
Hiel, Sophie; Neyrinck, Audrey M; Rodriguez, Julie; Pachikian, Barbara D; Bouzin, Caroline; Thissen, Jean-Paul; Cani, Patrice D; Bindels, Laure B; Delzenne, Nathalie M
2018-04-25
Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 ( Apoc3 , inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk.
Hiel, Sophie; Rodriguez, Julie; Pachikian, Barbara D.; Thissen, Jean-Paul; Delzenne, Nathalie M.
2018-01-01
Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 (Apoc3, inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk. PMID:29693598
Ten Bruggencate, Sandra J; Frederiksen, Pernille D; Pedersen, Simon M; Floris-Vollenbroek, Esther G; Lucas-van de Bos, Elly; van Hoffen, Els; Wejse, Peter L
2016-02-01
The milk-fat-globule membrane (MFGM) contains phospholipids and membrane glycoproteins that have been shown to affect pathogen colonization and gut barrier integrity. In the present study, we determined whether commercial heat-treated MFGM can increase resistance to diarrheagenic Escherichia coli. A randomized, placebo-controlled, double-blind, 4-wk parallel-intervention study was conducted in healthy adults. Participants were randomly assigned to a milk protein concentrate rich in MFGM [10 g Lacprodan PL-20 (Arla Foods Ingredients Group P/S), twice daily; n = 30; MFGM group) or a control [10 g Miprodan 30 (sodium caseinate), twice daily; n = 28]. After 2 wk, participants were orally challenged with live, attenuated diarrheagenic E. coli (10(10) colony-forming units). Primary outcomes were infection-induced diarrhea and fecal diarrheagenic E. coli excretion. Secondary outcomes were gastrointestinal symptoms [Gastrointestinal Symptom Rating Scale (GSRS)], stool frequency, and stool consistency (Bristol Stool Scale). Diarrheagenic E. coli resulted in increased fecal output, lower relative fecal dry weight, increased fecal E. coli numbers, and an increase in stool frequency and gastrointestinal complaints at day 1 after challenge. MFGM significantly decreased the E. coli-induced changes in reported stool frequency (1.1 ± 0.1 stools/d in the MFGM group; 1.6 ± 0.2 stools/d in the control group; P = 0.04) and gastrointestinal complaints at day 2 (1.1 ± 0.5 and 2.5 ± 0.6 GSRS scores in the MFGM and control groups, respectively; P = 0.05). MFGM did not affect fecal wet weight and E. coli excretion at day 2 after challenge. The attenuated diarrheagenic E. coli strain transiently induced mild symptoms of a food-borne infection, with complete recovery of reported clinical symptoms within 2 d. The present diarrheagenic E. coli challenge trial conducted in healthy adults indicates that a milk concentrate rich in natural, bioactive phospho- and sphingolipids from the MFGM may improve in vivo resistance to diarrheagenic E. coli. This trial was registered at clinicaltrials.gov as NCT01800396. © 2016 American Society for Nutrition.
Stoops, M A; MacKinnon, K M; Roth, T L
2012-12-01
The objective was to identify suitable enzyme immunoassays to monitor gonadal and placental function in the female polar bear. Immunoreactive progesterone, progesterone metabolite (PdG), estrogen, and androgen metabolite (T) concentrations were measured in fecal samples collected over 24 mo from captive female bears (N = 20). Whereas fecal extracts produced displacement curves parallel to the standard curve for each respective steroid, T and PdG more accurately reflected reproductive events. Concentrations of fecal T increased (P < 0.05) during the breeding season, and brief spikes were associated with estrus and mating. A postovulatory increase in PdG was not always detected, but sustained baseline T after mating appeared consistent with ovulation. Parturient bears excreted higher PdG concentrations (P < 0.05) during expected time of embryo implantation in Fall, and a late gestational rise in fecal T occurred 30 days prepartum. Many nonparturient bears also had a PdG rise in the Fall, suggesting they experienced either pregnancy loss or a pseudopregnancy. Differentiating pregnant and pseudopregnant states was not achieved using fecal PdG alone, but when combined with fecal T, comprehensive diagnoses could be made. Nonparturient bears demonstrated elevated (P < 0.05) fecal T during summer months, whereas parturient bears did not. In summary, noninvasive hormone monitoring techniques were established for the female polar bear. Although this study was directed at facilitating management and breeding efforts of captive polar bears, the methods could be applied to studies of reproductive function in wild populations. Copyright © 2012 Elsevier Inc. All rights reserved.
Gelzo, Monica; Sica, Concetta; Elce, Ausilia; Dello Russo, Antonio; Iacotucci, Paola; Carnovale, Vincenzo; Raia, Valeria; Salvatore, Donatello; Corso, Gaetano; Castaldo, Giuseppe
2016-09-01
Low cholesterol is typically observed in the plasma of patients with cystic fibrosis (CF) contrasting with the subcellular accumulation of cholesterol demonstrated in CF cells and in mice models. However, the homeostasis of cholesterol has not been well investigated in patients with CF. We studied the plasma of 26 patients with CF and 33 unaffected controls campesterol and β-sitosterol as markers of intestinal absorption and lathosterol as a marker of de novo cholesterol biosynthesis by gas chromatography (GC-FID and GC-MS). Plasma campesterol and β-sitosterol results were significantly (p=0.01) lower while plasma lathosterol was significantly higher (p=0.001) in patients with CF as compared to control subjects. Plasma cholesterol results were significantly lower (p=0.01) in CF patients. Our data suggest that the impaired intestinal absorption of exogenous sterols in patients with CF stimulates the endogenous synthesis of cholesterol, but the levels of total cholesterol in plasma remain lower. This may be due to the CFTR dysfunction that reduces cholesterol blood excretion causing the accumulation of cholesterol in liver cells and in other tissues contributing to trigger CF chronic inflammation.
Regulation of plasma cholesterol by hepatic low-density lipoprotein receptors.
Kovanen, P T
1987-02-01
The endogenous lipoprotein system (very low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL] cascade) holds the key to understanding the mechanisms by which hormones, diet, and drugs interact to regulate the plasma cholesterol level. Crucial components of this system are hepatic LDL receptors that mediate the uptake and degradation of plasma LDL. With experimental animals, it has been possible to demonstrate that hepatic LDL receptors are sensitive to hormonal, dietary, and pharmacologic manipulation. The decrease in number of hepatic LDL receptors in hypothyroidism or after cholesterol feeding leads to elevation of plasma LDL cholesterol levels. Conversely, the increase in number of hepatic LDL receptors results in lowering of plasma LDL cholesterol levels. This can be observed in hyperthyroidism, during administration of pharmacologic doses of 17 alpha-ethinyl estradiol, or during treatment with cholesterol-lowering drugs such as the bile acid-binding resins and cholesterol-synthesis inhibitors. Since cholesterol excretion from the body occurs via the liver, the increased efficiency of disposal of plasma cholesterol by increasing hepatic LDL receptors will ultimately lead to depletion of excessive body cholesterol. Pharmacologic regulation of hepatic LDL receptors should be a valuable tool in the prevention and therapy of atherosclerosis.
Effect of Roux-en-Y Gastric Bypass Surgery on Bile Acid Metabolism in Normal and Obese Diabetic Rats
Bhutta, Hina Y; Rajpal, Neetu; White, Wendy; Freudenberg, Johannes M.; Liu, Yaping; Way, James; Rajpal, Deepak; Cooper, David C.; Young, Andrew; Tavakkoli, Ali; Chen, Lihong
2015-01-01
In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA metabolism to further understand the role of BAs in RYGB-induced metabolic effects in humans. PMID:25798945
Zhai, Qian-Qian; Pang, Jing; Li, Guo-Qing; Li, Cong-Ran; Wang, Yu-Cheng; Yu, Li-Yan; Li, Jian; YOUm, Xue-Fu
2017-01-01
(E)-Methyl-4-aryl-4-oxabut-2-enoate, designated YH-8, is a novel Serflhr protein kinase B (PknB) inhibitor, which is designed for the treatment of tuberculosis. The aim of this study was to investigate the pharmacokinetics, bioavailability, tissue distribution and excretion characteristics of YH-8 in rats and study its plasma protein binding in vitro. The pharmacokinetic properties were examined after intravenously injected YH-8 at 10 and 20 mg/kg and oral administrated YH-8 at 50, 100 and 200 mg/kg to rats. The concentrations of YH-8 in plasma were determined with LC-MS/MS, with a liquid-liquid extraction. The tissue distribution and urinary, fecal and -biliary excretion patterns of YH-8 were investigated following a single oral dosing of 100 mg/kg. The plasma protein binding rates of YH-8 were determined using ultra-filtration method. After intra- venous and oral administration, YH-8 showed dose-independent pharmacokinetic characteristics, with T(1/2) of approximately 5.5 h and 7.1 h, respectively. The oral absolute bioavailability of YH-8 was relatively low (about 12%). YH-8 was widely distributed in various tissues and showed substantial deposition in intestine, stomach, liver, lung and kidney. The drug was mainly eliminated via fecal excretion and its binding rate with plasma protein was concentration-dependent. In conclusion, this study as first provided the full pharmacokinetic characteristics of YH-8, which would be helpful for its further development and clinical application.
Cystine alters the renal and hepatic disposition of inorganic mercury and plasma thiol status
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zalups, Rudolfs K.; Lash, Lawrence H.
2006-07-01
In the present study, we determined whether cystine can inhibit, under certain conditions, the renal tubular uptake of inorganic mercury in vivo. We co-injected (i.v.) cystine with a non-toxic dose of mercuric chloride to rats and then studied the disposition of inorganic mercury during the next 24 h. We also determined if pretreatment with cystine influences the disposition of administered inorganic mercury. Moreover, plasma thiol status was examined after the intravenous administration of cystine with or without mercuric chloride. During the initial hour after co-injection, the renal tubular uptake of mercuric ions was diminished significantly relative to that in controlmore » rats. The inhibitory effects of cystine were evident in both the renal cortex and outer stripe of the outer medulla. In contrast, the renal accumulation of mercury increased significantly between the 1st and 12th hour after co-treatment. Urinary excretion and fecal excretion of mercury were greatly elevated in the rats co-treated with cystine and mercuric chloride. Thus, when cystine and mercury are administered simultaneously, cystine can serve as an inhibitor of the renal tubular uptake of mercury during the initial hour after co-treatment. In rats pretreated with cystine, the renal uptake of inorganic mercury was enhanced significantly relative to that in rats not pretreated with cystine. This enhanced accumulation of inorganic mercury correlated with the increased circulating concentrations of the reduced cysteine and glutathione. Additionally, the present findings indicate that thiol status is an important determinant of renal and hepatic disposition, and urinary and fecal excretion, of inorganic mercury.« less
On the enterohepatic cycle of triiodothyronine in rats; importance of the intestinal microflora
DOE Office of Scientific and Technical Information (OSTI.GOV)
de Herder, W.W.; Hazenberg, M.P.; Pennock-Schroeder, A.M.
1989-01-01
Until 70 h after a single iv injection of 10 uCi ({sup 125}I)triiodothyronine (T{sub 3}), normal rats excreted 15.8 {plus minus} 2.8% of the radioactivity with the feces and 17.5 {plus minus} 2.7% with the urine, while in intestine-decontaminated rats fecal and urinary excretion over this period amounted to 25.1 {plus minus} 7.2% and 23.6 {plus minus} 4.0% of administered radioactivity, respectively (mean {plus minus} SD, n=4). In fecal extracts of decontaminated rats 11.5 {plus minus} 6.8% of the excreted radioactivity consisted of T{sub 3} glucuronide (T{sub 3}G) and 10.9 {plus minus} 2.8% of T{sub 3} sulfate (T{sub 3}S), whereasmore » no conjugates were detected in feces from normal rats. Until 26 h after ig administration of 10 uCi ({sup 125}I)T{sub 3}, integrated radioactivity in blood of decontaminated rats was 1.5 times higher than that in normal rats. However, after ig administration of 10 uCi ({sup 125}I)T{sub 3}G or ({sup 125}I)T{sub 3}S, radioactivity in blood of decontaminated rats was 4.9- and 2.8-fold lower, respectively, than in normal rats. The radioactivity in the serum of control animals was composed of T{sub 3} and iodide in proportions independent of the tracer injected, while T{sub 3} conjugates represented <10 % of serum radioactivity. These results suggest an important role of the intestinal microflora in the enterohepatic circulation of T{sub 3} in rats.« less
Zhang, Liang; Han, Yuhui; Xu, Liwei; Liang, Yuhong; Chen, Xin; Li, Junsong; Wan, Xiaochun
2015-07-01
In Southwest China, tea polyphenols are usually utilized by way of butter tea. Tea polyphenols inhibit the absorption and biosynthesis of fatty acids in vivo, but the effects of butter on the pharmacokinetics of tea polyphenols have drawn less concern. A rapid UHPLC-MS/MS method was used to quantitatively determine the catechins in the plasma, feces and bile of rats after the oral administration of tea polyphenol or its combination with butter. In comparison with the single tea polyphenol treatment, the maximum plasma concentrations (Cmax) of the free EGCG, EGC, EC, GCG, GC and ECG significantly decreased after the co-administration of butter. The mean residence times (MRT) of the free EGCG, EGC, EC, GC and ECG were also significantly prolonged. When the plasma samples were treated with β-glucuronidase and arylsulfatase, the pharmacokinetic parameters of the total catechins (free and conjugated forms) were not affected by the co-administration of butter. These results indicated that the total absorption of catechins was not affected by butter, but the metabolism of catechins had been changed. Furthermore, the fecal catechins were significantly increased by butter. The total fecal amount and excretion ratio of all catechins were increased highly. The biliary excretion of EGCG, EGC, EC, GCG and GC was significantly increased by the co-administration of butter. To sum up, the butter changed the metabolism of catechins in vivo by decreasing the plasma concentration of the free catechins but increasing the conjugated catechins.
Disposition and excretion of 2,3,4,7,8-pentachlorodibenzofuran in the rat.
Brewster, D W; Birnbaum, L S
1987-09-15
The disposition of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), a highly toxic environmental contaminant which accumulates in human tissues, was examined in the male Fischer rat after iv and oral exposure. Greater than 70% of an oral dose of 0.1, 0.5, or 1.0 mumol PeCDF/kg body wt was absorbed by the gastrointestinal system. After either oral or iv administration of 0.1 mumol/kg, the dibenzofuran was rapidly removed from the blood and accumulated in the liver and adipose tissue and to a lesser extent in the skin and muscle. Three days after administration, 70% of the iv dose of PeCDF was found in the liver, 7% in the fat, 1% in the skin, and 0.5% in the muscle. Route of exposure had little effect on tissue distribution. TLC analyses indicated that greater than 99% of the [14C]-PeCDF-derived radioactivity which had accumulated in the liver and adipose tissue was unmetabolized PeCDF which was eliminated very slowly (t1/2 = 193 and 69 days, respectively). The whole body half-life calculated from the daily fecal excretion rate was approximately 64 days. Excretion occurred primarily via the feces. No radioactivity was detected in expired air and less than 0.02% was detected in the urine. TLC analysis of fecal extracts indicated greater than 90% of the [14C]PeCDF-derived radioactivity in the feces was polar metabolites of the parent compound. Pretreatment with 500 micrograms PeCDF/kg body wt caused biliary excretion to nearly double. Treatment of bile with beta-glucuronidase or arylsulfatase had little effect on the chromatographic profile. Therefore, PeCDF was readily absorbed from the gastrointestinal tract, concentrated primarily in the liver, and was slowly eliminated from the body as polar metabolites. The long half-life and high body burden of PeCDF suggest that the toxicity of this chemical may be enhanced due to bioaccumulation upon chronic low-level exposure.
Phytosterol glycosides reduce cholesterol absorption in humans
Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.
2009-01-01
Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received ∼300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4–5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6 ± 4.8% (P < 0.0001) and phytosterol esters 30.6 ± 3.9% (P = 0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content. PMID:19246636
Binding effect of polychlorinated compounds and environmental carcinogens on rice bran fiber.
Sera, Nobuyuki; Morita, Kunimasa; Nagasoe, Masami; Tokieda, Hisako; Kitaura, Taeko; Tokiwa, Hiroshi
2005-01-01
To accelerate the fecal excretion of polycyclic biphenyl (PCB), polychlorinated dibenzofurans (PCDFs), polychlorinated-p-dioxines (PCDDs) and various mutagens and carcinogens, their binding effect on rice bran fiber (RBF) was investigated for nine heterocyclic amines, six nitroarenes, 4-nitroquinoline-N-oxide, benzo[a]pyrene, furylfuramide, two kinds of flavonoid compounds and formaldehyde and ascorbic acid. PCBs, PCDFs and PCDDs suspended in nonane were incubated with RBF (10 mg/ml) at 37 degrees C and after centrifugation, unbound chemicals in the supernatant were analyzed by high-performance liquid chromatography (HPLC) and gas chromatography (GC). The binding effects on RBF were enhanced more than other dietary fibers (DFs), which were tested including corn, wheat bran, spinach, Hijiki (a kind of seaweed), sweet potatoes and burdock fibers. It was found that the binding effects were related to lignin contents. Binding of 3-amino-1(or 1,4)-dimethyl-5H-pyrido[4,3-b]indole (Trp-p-1 and Trp-p-2), food-derived carcinogens and 1-nitropyrene (1-NP), suspended in methanol, to RBF occurred within 10 min of incubation at 37 degrees C at pH 5-7, and decreased below pH 4; binding of food-derived carcinogens was pH dependent. The binding effects to RBF and pulp lignin were obtained at ratio of over 90%, while corn fiber and cellulose were at ratios of 4-30%. Polycyclic aromatic compounds were related to the number of rings, showing high binding effects to chemical structures with triple rings. Binding of 1-NP and PCB to RBF was not influenced in any aerobic and anaerobic bacterial cultures. It was also found that RBF was capable of binding even conjugates containing mutagens such as glucuronides and sulfates, as well as metabolites in urine. It was suggested, therefore, that mutagens and carcinogens were available for the fecal excretion of residual chemicals and their metabolites, and also for the fecal excretion of PCBs, PCDFs and related compound residues in patients of Yusho disease, who suffered food poisoning due to rice oil contaminated with PCB in Japan.
Champagne, Cory D; Kellar, Nicholas M; Trego, Marisa L; Delehanty, Brendan; Boonstra, Rudy; Wasser, Samuel K; Booth, Rebecca K; Crocker, Daniel E; Houser, Dorian S
2018-05-29
Several hormones are potential indicators of stress in free-ranging animals and provide information on animal health in managed-care settings. In response to stress, glucocorticoids (GC, e.g. cortisol) first appear in circulation but are later incorporated into other tissues (e.g. adipose) or excreted in feces or urine. These alternative matrices can be sampled remotely, or by less invasive means, than required for blood collection and are especially valuable in highly mobile species, like marine mammals. We characterized the timing and magnitude of several hormones in response to a stressor in bottlenose dolphins (Tursiops truncatus) and the subsequent incorporation of cortisol into blubber, and its metabolites excreted in feces. We evaluated the endocrine response to an acute stressor in bottlenose dolphins under managed care. We used a standardized stress protocol where dolphins voluntarily beached onto a padded platform and remained out of water for two hours; during the stress test blood samples were collected every 15 min and blubber biopsies were collected every hour (0, 60, and 120 min). Each subject was studied over five days: voluntary blood samples were collected on each of two days prior to the stress test; 1 and 2 h after the conclusion of the out-of-water stress test; and on the following two days after the stress test. Fecal samples were collected daily, each afternoon. The acute stressor resulted in increases in circulating ACTH, cortisol, and aldosterone during the stress test, and each returned to baseline levels within 2 h of the dolphin's return to water. Both cortisol and aldosterone concentrations were correlated with ACTH, suggesting both corticosteroids are at least partly regulated by ACTH. Thyroid hormone concentrations were generally unaffected by the acute stressor. Blubber cortisol increased during the stress test, and fecal GC excretion was elevated on the day of the stress test. We found that GCs in bottlenose dolphins can recover within hours of acute stress, and that cortisol release can be detected in alternate matrices within a few hours-within 2 h in blubber, and 3.5-5 h in fecal samples. Copyright © 2018 Elsevier Inc. All rights reserved.
Dietary safflower phospholipid reduces liver lipids in laying hens.
An, B K; Nishiyama, H; Tanaka, K; Ohtani, S; Iwata, T; Tsutsumi, K; Kasai, M
1997-05-01
This experiment was conducted to determine the effects of dietary safflower phospholipids (crude safflower phospholipid and purified safflower phospholipid) on performance and lipid metabolism of laying hens. Sixty-week-old Single Comb White Leghorn laying hens were divided into four groups of seven birds each, and were given one of four experimental diets containing 5% beef tallow (served as a control, tallow), a mixture of safflower oil and palm oil (SP-oil), crude safflower phospholipid (Saf-PLcrude), or purified safflower phospholipid (Saf-PL) for 7 wk. Egg production ratio and daily egg mass were significantly higher in hens fed Saf-PLcrude diets than in hens of the other diet groups. There were no significant differences in egg weight among groups. Liver cholesterol and triglyceride contents were significantly decreased in all treated groups as compared with the control. The activity of hepatic 3-hydroxy-3 methylglutaryl coenzyme A reductase was the highest in hens fed the Saf-PLcrude diet. Serum esterified cholesterol concentration was decreased by feeding of SP-oil, Saf-PLcrude, or Saf-PL diets. Serum lecithin-cholesterol acyltransferase activity was highest in hens fed the tallow diet. Excreta neutral steroid excretion was significantly increased in the Saf-PLcrude or Saf-PL diet groups, although acidic steroid excretion was not affected by dietary treatments. Total cholesterol, triglyceride, and phospholipid contents in egg yolks were not different for any dietary treatments. The fatty acid compositions of egg yolks from hens fed Saf-PLcrude diets were not different with those fed the SP-oil diet, although eggs of hens fed the Saf-PL diet showed lower total polyunsaturated fatty acids. These results suggest that dietary safflower phospholipids may be a valuable ingredient to layers for reducing liver triglycerides and serum cholesterol without any adverse effects.
Effect of dietary phytate on zinc homeostasis in young and elderly Korean women.
Kim, Jihye; Paik, Hee Young; Joung, Hyojee; Woodhouse, Leslie R; Li, Shanji; King, Janet C
2007-02-01
Previous studies suggest that consumption of predominantly plant-based diets with high phytate content contribute to zinc deficiency by inhibiting zinc absorption. Age of the individual may also affect the ability to maintain zinc homeostasis. This study was designed to determine the effect of dietary phytate on zinc homeostasis and to evaluate the effect of age on the capacity to maintain the zinc homeostasis with changes in dietary phytate in young and elderly Korean women. Seven healthy young women (22-24 yr) and 10 healthy elderly women (66-75 yr) were studied consecutively for 3 months in 2 metabolic periods (MP) in two different metabolic units. During MP1 the women consumed a high phytate (HP) diet (P:Zn molar ratio = 23) for 9 days. After a 10 d wash-out period at home eating their usual diets, a lower phytate diet (LP) (P:Zn molar ratio = 10) was fed in MP2 for 9 d. Phytase was added to selected foods in the high phytate diet to reduce the phytate content of the meals in the LP period. The zinc content of both diets was about 6.5 mg/d. Stable isotopes of Zn ((70)Zn) were administered intravenously on d 5 of MP 1 and 2 for measuring endogenous fecal zinc excretion. Plasma samples were also collected on d 5 for measuring plasma zinc concentrations by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). 24 hr urine samples were collected for 5 d and complete fecal samples were collected for 9 d after isotope administration. Fractional zinc absorption (FZA) was calculated from mass balance corrected for endogenous fecal zinc (EFZ) excretion and EFZ was determined by using an isotopic dilution technique. Isotopic ratios for FZA and EFZ were measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Statistical analyses were done using ANOVA. Both the young and elderly women were in negative zinc balance during the HP period. This was due to a significant decrease in FZA and total absorbed zinc (TAZ) with a HP diet (43 vs 22% in young women, 34 vs 20% in elderly women, p < 0.001). EFZ excretion did not differ in the young and elderly women during the LP and HP periods. Dietary phytate did not alter plasma zinc concentrations or and urinary zinc excretion in either group. Adjustments in zinc homeostasis with an increase in dietary phytate did not differ between young and elderly women in this study.
1291 cases of cholelithiasis treated with electric shock on otoacupoints.
Zhang, Y; Zhang, L; Yang, H; Zhang, H; Zhu, Y
1991-06-01
Since 1985, the authors began to use electric shock on otoacupoints of varying electric resistance for the treatment of cholelithiasis. The instrument used was the Channel Therapeutic Instrument made in China, and the otoacupoints of varying electric resistance were Sympathetic, Pancreas--Gall Bladder, Stomach, Liver, Sanjiao, Endocrine, and Ermigen. In the 1291 cases treated, the total effective rate was 99.69%, the rate of calculus excretion was 91.32%, and the rate of total excretion was 19.51%. The composition of the calculi was cholesterol crystals (31.25%), bilirubin crystals (28.17%), and mixed crystals (40.58%). The largest calculus excreted was an extrahepatic biliary duct calculus of 1.75 cm X 1.5 cm; the largest number of calculi excreted was 152 cholecystic stones 0.3 cm X 0.5 cm in size. In 100 random cases, the biliary system was shown to manifest vigorous dilations and constrictions under Ultrasonic B-scan when the relevant otoacupoints were stimulated with electric shock. Among the 78 control cases, no cholecystic stones were excreted, inspite of the Magnesium Sulfate, Folium Cassiae and fatty meals administered to many cases with constipation.
Diagnostic Methods for Bile Acid Malabsorption in Clinical Practice
Vijayvargiya, Priya; Camilleri, Michael; Shin, Andrea; Saenger, Amy
2013-01-01
Altered bile acid (BA) concentrations in the colon may cause diarrhea or constipation. BA malabsorption (BAM) accounts for >25% of patients with irritable bowel syndrome (IBS) with diarrhea and chronic diarrhea in Western countries. As BAM is increasingly recognized, proper diagnostic methods are desired in clinical practice to help direct the most effective treatment course for the chronic bowel dysfunction. This review appraises the methodology, advantages and disadvantages of 4 tools that directly measure BAM: 14C-glycocholate breath and stool test, 75Selenium HomotauroCholic Acid Test (SeHCAT), 7 α-hydroxy-4-cholesten-3-one (C4) and fecal BAs. 14C-glycocholate is a laborious test no longer widely utilized. 75SeHCAT is validated, but not available in the United States. Serum C4 is a simple, accurate method that is applicable to a majority of patients, but requires further clinical validation. Fecal measurements to quantify total and individual fecal BAs are technically cumbersome and not widely available. Regrettably, none of these tests are routinely available in the U.S., and a therapeutic trial with a BA binder is used as a surrogate for diagnosis of BAM. Recent data suggest there is an advantage to studying fecal excretion of the individual BAs and their role in BAM; this may constitute a significant advantage of the fecal BA method over the other tests. Fecal BA test could become a routine addition to fecal fat measurement in patients with unexplained diarrhea. In summary, availability determines the choice of test among C4, SeHCAT and fecal BA; more widespread availability of such tests would enhance clinical management of these patients. PMID:23644387
Van Rooyen, Derrick M; Larter, Claire Z; Haigh, W Geoffrey; Yeh, Matthew M; Ioannou, George; Kuver, Rahul; Lee, Sum P; Teoh, Narci C; Farrell, Geoffrey C
2011-10-01
Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH. Alms1 mutant (foz/foz) and wild-type NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. Hepatic cholesterol accumulation was attributed to up-regulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol levels exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
Van Rooyen, Derrick M; Larter, Claire Z; Haigh, W Geoffrey; Yeh, Matthew M; Ioannou, George; Kuver, Rahul; Lee, Sum P; Teoh, Narci C; Farrell, Geoffrey C
2011-01-01
Background & Aims Type-2 diabetes and non-alcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to pathogenesis of NASH. Methods Alms1 mutant (foz/foz) and wild-type (WT) NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. Results Hepatic cholesterol accumulation was attributed to up-regulation of low density lipoprotein receptor (LDLR) via activation of sterol regulatory element binding protein-2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and LDLR and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. Conclusions In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. PMID:21703998
Juhel, Christine; Tosini, Fredéric; Steib, Marlène; Wils, Daniel; Guerin-Deremaux, Laetitia; Lairon, Denis; Cara, Louis
2011-03-01
NUTRIOSE6 is a new wheat starch-based low-digestible carbohydrate. This study investigated the effect of this soluble non-viscous fiber on cholesterol metabolism. Hamsters fed with 0.25% cholesterol-enriched diet (CHO) were given graded amounts of NUTRIOSE6, i.e., 0% (cellulose, CHO), 3% (N3), 6% (N6) or 9% (N9) (w:w). As compared to CHO diet, 9% NUTRIOSE6 significantly lowered plasma and LDL cholesterol by 14.5 and 23.8%, respectively. The LDL-cholesterol lowering effect was also significant with the 6% dose (-21.4%). NUTRIOSE6 diets prevented hepatic cholesterol accumulation (-10 to -20%) and significantly decreased bile cholesterol (-47 to -68%) and phospholipids (-30 to -45%) concentrations. The 9% NUTRIOSE6 diet significantly decreased the rate of dietary cholesterol absorption (-25%) and markedly stimulated faecal neutral sterol (+81%) and bile salts (+220%) excretion. No significant change in cholesterol 7-alpha-hydroxylase or LDL-receptor activities was observed whereas 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was reduced by 29%. Reduced cholesterol and bile salt absorptions and lowered cholesterol synthesis are likely mechanisms underlying the cholesterol lowering effect of NUTRIOSE6. Results suggest the use of NUTRIOSE6 as a new dietary cholesterol-lowering agent that should be tested in humans as treatment and evenly prevention of mild hypercholesterolemia.
Schär, Manuel Y.; Corona, Giulia; Soycan, Gulten; Dine, Clemence; Kristek, Angelika; Alsharif, Sarah N. S.; Behrends, Volker; Lovegrove, Alison; Shewry, Peter R.
2017-01-01
Scope Wholegrain has been associated with reduced chronic disease mortality, with oat intake particularly notable for lowering blood cholesterol and glycemia. To better understand the complex nutrient profile of oats, we studied urinary excretion of phenolic acids and avenanthramides after ingestion of oat bran in humans. Methods and results After a 2‐d (poly)phenol‐low diet, seven healthy men provided urine 12 h before and 48 h after consuming 60 g oat bran (7.8 μmol avenanthramides, 139.2 μmol phenolic acids) or a phenolic‐low (traces of phenolics) control in a crossover design. Analysis by ultra‐high performance liquid chromatography (UPLC)–MS/MS showed that oat bran intake resulted in an elevation in urinary excretion of 30 phenolics relative to the control, suggesting that they are oat bran‐derived. Mean excretion levels were elevated between 0–2 and 4–8 h, following oat bran intake, and amounted to a total of 33.7 ± 7.3 μmol total excretion (mean recovery: 22.9 ± 5.0%), relative to control. The predominant metabolites included: vanillic acid, 4‐ and 3‐hydroxyhippuric acids, and sulfate‐conjugates of benzoic and ferulic acids, which accounted collectively for two thirds of total excretion. Conclusion Oat bran phenolics follow a relatively rapid urinary excretion, with 30 metabolites excreted within 8 h of intake. These levels of excretion suggest that bound phenolics are, in part, rapidly released by the microbiota. PMID:29024323
Hypolipidemic effect of hemicellulose component of coconut fiber.
Sindhurani, J A; Rajamohan, T
1998-08-01
The neutral detergent fiber (NDF) isolated from coconut kernel was digested with cellulase and hemicellulase and the residual fiber rich in hemicellulose (without cellulose) and cellulose (with out hemicellulose) were fed to rats and compared with a fiber free group. The results indicate that hemicellulose rich fiber showed decreased concentration of total cholesterol, LDL + VLDL cholesterol and increased HDL cholesterol, while cellulose rich fiber showed no significant alteration. There was increased HMG CoA reductase activity and increased incorporation of labeled acetate into free cholesterol. Rats fed hemicellulose rich coconut fiber produced lower concentration of triglycerides and phospholipids and lower release of lipoproteins into circulation. There was increased concentration of hepatic bile acids and increased excretion of faecal sterols and bile acids. These results indicate that the hemicellulose component of coconut fiber was responsible for the observed hypolipidemic effect.
THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS
Hirsch, Robert L.; Kellner, Aaron
1956-01-01
Mice rendered hyperlipemic by means of intravenous or subcutaneous injections of triton WR 1339 were found to have an increase in the total amount of cholesterol in their bodies. This observation indicates that the injected surface-active agent affects the metabolism of cholesterol and brings about hyperlipemia by augmenting the synthesis of lipides, or by interfering with their degradation or excretion, or by some combination of these factors. The implications of the findings for the pathogenesis of the hyperlipemia induced by triton are discussed further in the accompanying paper (16). PMID:13332176
Patterns of fecal gonadal hormone metabolites in the maned wolf (Chrysocyon brachyurus).
Songsasen, N; Rodden, M; Brown, J L; Wildt, D E
2006-10-01
Ex situ populations of maned wolves are not viable due to low reproductive efficiency. The objective of this study was to increase knowledge regarding the reproductive physiology of maned wolves to improve captive management. Fecal samples were collected 3-5 d/wk from 12 females of various reproductive age classes (young, prime breeding and aged) and reproductive histories (conceived and raised pups, conceived but lost pups, pseudo-pregnant and unpaired). Ovarian steroids were extracted from feces and assessed by enzyme immunoassay. Concentrations of estrogen metabolites gradually increased, beginning 2-5 d before breeding, and declined to baseline on the day of lordosis and copulation. Fecal progestin metabolite concentrations increased steadily during the periovulatory period, when sexual receptivity was observed, and remained elevated during pregnancy and pseudo-pregnancy. During the luteal phase, young and prime breeding-age females excreted larger amounts of progestins than those of older age classes. Furthermore, progestin concentrations were higher during the luteal phase of pregnant versus pseudo-pregnant bitches. Profiles of fecal progestin metabolites for three singleton females were unchanged throughout the breeding season, suggesting ovulation is induced in this species. However, this finding could be confounded by age, as these females were either young or aged.
Beyond Reasonable Doubt: Who Is the Culprit in Lipotoxicity in NAFLD/NASH?
Arteel, Gavin E.
2016-01-01
BACKGROUND & AIMS Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH. METHODS Alms1 mutant (foz/foz) and wild-type NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. RESULTS Hepatic cholesterol accumulation was attributed to up-regulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol levels exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. CONCLUSIONS In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. PMID:22422583
Hypocholesterolemic effect of sericin-derived oligopeptides in high-cholesterol fed rats.
Lapphanichayakool, Phakhamon; Sutheerawattananonda, Manote; Limpeanchob, Nanteetip
2017-01-01
The beneficial effect of cholesterol-lowering proteins and/or peptides derived from various dietary sources is continuously reported. A non-dietary protein from silk cocoon, sericin, has also demonstrated cholesterol-lowering activity. A sericin hydrolysate prepared by enzymatic hydrolysis was also expected to posses this effect. The present study was aimed at investigating the cholesterol-lowering effect of sericin peptides, so called "sericin-derived oligopeptides" (SDO) both in vivo and in vitro. The results showed that SDO at all three doses tested (10 mg kg -1 day -1 , 50 mg kg -1 day -1 , and 200 mg kg -1 day -1 ) suppressed serum total and non-HDL cholesterol levels in rats fed a high-cholesterol diet. Triglyceride and HDL-cholesterol levels were not significantly changed among all groups. The fecal contents of bile acids and cholesterol did not differ among high-cholesterol fed rats. SDO dose-dependently reduced cholesterol solubility in lipid micelles, and inhibited cholesterol uptake in monolayer Caco-2 cells. SDO also effectively bound to all three types of bile salts including taurocholate, deoxytaurocholate, and glycodeoxycholate. Direct interaction with bile acids of SDO may disrupt micellar cholesterol solubility, and subsequently reduce the absorption of dietary cholesterol in intestines. Taking all data together, SDO or sericin peptides exhibit a beneficial effect on blood cholesterol levels and could be potentially used as a health-promoting dietary supplement or nutraceutical product.
Disposition and pharmacokinetics in rats of McN-5707, a potential antidepressant drug
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ng, K.T.; Holland, M.L.; Hills, J.F.
1986-03-01
A single 80 mg/kg oral solution dose of McN-5707-/sup 14/C x HBr (trans-6-(2-chlorophenyl)-1,2,3,5,6,10b-hexahydropyrrolo(2,1-a)isoquinoline hydrobromide (1:1)) was administered orally to 40 Wistar rats. Total /sup 14/C concentrations in plasma were high (> 4.5 ..mu..g x equiv/mL) for at least 24 hours after dosing. Unchanged McN-5707 represented < 10% of the total /sup 14/C concs in plasma at 45 min and < 1% at 24 hours after dosing. In the 8 days following dose administration, 23% of the dose was excreted in urine and 70% of the dose was excreted in feces. Analysis (HPLC and TLC) of glusulase treated urine, plasma andmore » fecal samples revealed the presence of multiple metabolites of McN-5707. Unchanged McN-5707 was found only in fecal extracts (2-7% of dose). Single solution doses of McN-5707 x HBr were administered p.o. (20 mg/kg) and i.v. (4 mg/kg) to 39 Wistar rats. Plasma samples were analyzed for McN-5707 using a capillary GC assay. These studies indicated that McN-5707 was well absorbed and extensively metabolized in rats following oral doses.« less
Park, Hyo Jin; Kim, Hye-Jin; Kim, Sang Ryong; Choi, Myung-Sook; Jung, Un Ju
2017-03-01
This study investigated the biological and molecular mechanisms underlying the antiobesity effect of omija fruit ethanol extract (OFE) in mice fed a high-fat diet (HFD). C57BL/6J mice were fed an HFD (20% fat, w/w) with or without OFE (500 mg/kg body weight) for 16 weeks. Dietary OFE significantly increased brown adipose tissue weight and energy expenditure while concomitantly decreasing white adipose tissue (WAT) weight and adipocyte size by up-regulating the expression of brown fat-selective genes in WAT. OFE also improved hepatic steatosis and dyslipidemia by enhancing hepatic fatty acid oxidation-related enzymes activity and fecal lipid excretion. In addition to steatosis, OFE decreased the expression of pro-inflammatory genes in the liver. Moreover, OFE improved glucose tolerance and lowered plasma glucose, insulin and homeostasis model assessment of insulin resistance, which may be linked to decreases in the activity of hepatic gluconeogenic enzymes and the circulating level of gastric inhibitory polypeptide. These findings suggest that OFE may protect against diet-induced adiposity and related metabolic disturbances by controlling brown-like transformation of WAT, fatty acid oxidation, inflammation in the liver and fecal lipid excretion. Improved insulin resistance may be also associated with its antiobesity effects. Copyright © 2017 Elsevier Inc. All rights reserved.
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
2016-05-26
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. 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). 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). 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.
Effect of age and lactose on sup 67 Cu utilization in rats
DOE Office of Scientific and Technical Information (OSTI.GOV)
Link, J.; Dowdy, R.; Michelmann, E.
1991-03-15
Young and old male Fischer 344 rats were fed a control diet or a lactose diet. After four weeks rats were gavaged with approximately 6.24 uCl {sup 67}Cu, placed in metabolism cages, and fed their respective diets for an additional two weeks. Daily whole body, urine and fecal radioactivity measurements were made. Rats were killed on day 42 and livers removed for radioactivity determination. Diet had no effect on whole body retention of {sup 67}Cu in the old rats; approximately 20% of the initial dose was retained by the end of the study. In the young rats, however, lactose appearedmore » to enhance initial {sup 67}Cu retention; by day three young control rats retained only 30% of the initial dose, while the young lactose rats retained about 50%. Retention of {sup 67}Cu at the end of the study was approximately 15% and 20% for young control and young lactose rats, respectively. During the first four days post dosing, cumulative fecal {sup 67}Cu excretion was approximately 83% for young control rats and 69% for young lactose rats indicating enhancement of {sup 67}Cu absorption by lactose in the young rats. For old rats cumulative {sup 67}Cu excretion in feces was about 50% regardless of diet. Cumulative urinary {sup 67}Cu excretion was approximately 6% and 8% for young control and lactose rats, respectively vs about 11% for old rats. {sup 67}Cu retention in liver was greater in old rats regardless of diet. The early increase in {sup 67}Cu absorption after a bolus dose may have therapeutic implications. In light of current concern regarding Cu-carbohydrate interactions, the apparent enhancement Cu retention by lactose in young rats deserves further attention.« less
Matsuda, Ikki; Sha, John C M; Ortmann, Sylvia; Schwarm, Angela; Grandl, Florian; Caton, Judith; Jens, Warner; Kreuzer, Michael; Marlena, Diana; Hagen, Katharina B; Clauss, Marcus
2015-10-01
Behavioral observations and small fecal particles compared to other primates indicate that free-ranging proboscis monkeys (Nasalis larvatus) have a strategy of facultative merycism(rumination). In functional ruminants (ruminant and camelids), rumination is facilitated by a particle sorting mechanism in the forestomach that selectively retains larger particles and subjects them to repeated mastication. Using a set of a solute and three particle markers of different sizes (b2, 5 and 8mm),we displayed digesta passage kinetics and measured mean retention times (MRTs) in four captive proboscis monkeys (6–18 kg) and compared the marker excretion patterns to those in domestic cattle. In addition, we evaluated various methods of calculating and displaying passage characteristics. The mean ± SD dry matter intake was 98 ± 22 g kg−0.75 d−1, 68 ± 7% of which was browse. Accounting for sampling intervals in MRT calculation yielded results that were not affected by the sampling frequency. Displaying marker excretion patterns using fecal marker concentrations (rather than amounts) facilitated comparisons with reactor theory outputs and indicated that both proboscis and cattle digestive tracts represent a series of very few tank reactors. However, the separation of the solute and particle marker and the different-sized particle markers, evident in cattle, did not occur in proboscis monkeys, in which all markers moved together, at MRTs of approximately 40 h. The results indicate that the digestive physiology of proboscis monkeys does not show typical characteristics of ruminants, which may explain why merycism is only a facultative strategy in this species.
Ghassemi Nejad, Jalil; Sung, Kyung-Il
2017-01-01
This study was conducted to investigate the behavioral and physiological changes of heat stressed Corriedale ewes exposed to water deprivation. Nine Corriedale ewes (average BW = 45 ± 3.7 kg) were individually fed diets based on maintenance requirements in metabolic crates. Ewes were assigned into three groups (9 sheep per treatment) according to a 3 × 3 Latin square design for 3 periods with 21-d duration for each period. The control (CON) group was given free access to water, 2 h water deprivation (2hWD), and 3 h water deprivation (3hWD) following feeding. No differences were found in fecal excretion frequency, standing frequency (number/d), and sitting frequency among the groups ( p > 0.05). Measurements of standing duration (min/d) and urine excretion frequency (number/d) showed a significant decrease whereas sitting duration (min/d) showed a significant increase in the 2hWD and 3hWD groups when compared with the CON group ( p < 0.05). Fecal score and heart rate (number/min) were not different among the groups ( p > 0.05). However, respiratory rate (number/min) and panting score were found to be significantly higher in the 2hWD and 3hWD groups than in the CON group ( p < 0.05). It is concluded that water deprivation following feeding intensifies physiological heat stress related indicators such as respiratory rate and panting score and changes behavioral parameters such as water intake and urine excretion frequency in heat stressed ewes. Daily adaptation to the extreme environmental conditions may occur actively in ewes.
Kuwano, Takashi; Bi, Xin; Cipollari, Eleonora; Yasuda, Tomoyuki; Lagor, William R.; Szapary, Hannah J.; Tohyama, Junichiro; Millar, John S.; Billheimer, Jeffrey T.; Lyssenko, Nicholas N.; Rader, Daniel J.
2017-01-01
Phospholipid transfer protein (PLTP) may affect macrophage reverse cholesterol transport (mRCT) through its role in the metabolism of HDL. Ex vivo cholesterol efflux capacity and in vivo mRCT were assessed in PLTP deletion and PLTP overexpression mice. PLTP deletion mice had reduced HDL mass and cholesterol efflux capacity, but unchanged in vivo mRCT. To directly compare the effects of PLTP overexpression and deletion on mRCT, human PLTP was overexpressed in the liver of wild-type animals using an adeno-associated viral (AAV) vector, and control and PLTP deletion animals were injected with AAV-null. PLTP overexpression and deletion reduced plasma HDL mass and cholesterol efflux capacity. Both substantially decreased ABCA1-independent cholesterol efflux, whereas ABCA1-dependent cholesterol efflux remained the same or increased, even though preβ HDL levels were lower. Neither PLTP overexpression nor deletion affected excretion of macrophage-derived radiocholesterol in the in vivo mRCT assay. The ex vivo and in vivo assays were modified to gauge the rate of cholesterol efflux from macrophages to plasma. PLTP activity did not affect this metric. Thus, deviations in PLTP activity from the wild-type level reduce HDL mass and ex vivo cholesterol efflux capacity, but not the rate of macrophage cholesterol efflux to plasma or in vivo mRCT. PMID:28137768
Establishment of a C57BL/6N mouse model of giardiasis.
Lu, Siqi; Luo, Xiaobing; Chen, Xiaoning; Wang, Fengyun
2002-10-01
To establish a C57BL/6N mouse model infected with Giardia lamblia (G. lamblia) isolates from human origin. Two groups of C57BL/6N mouse were inoculated with purified cysts of two G. lamblia isolates (CD and XZ) by gavage separately. Patterns and curves of cyst excretion of the infected mice were observed and summarized. Histopathological changes of the small intestines of the infected mice were observed. Thirty-six mice receiving 1 x 10(4) cysts each were all infected. The C57BL/6N mouse showed high susceptibility to G. lamblia infection. There was no notable distinction between the two groups of the mice infected by the cysts of CD and XZ isolates. Cyst excretion occurred with intermittence. Of 36 infected mice, 32 (89%) passed cysts intermittently and 4 (11%) others persistently. The latent period of cyst excretion was 0 - 3 days p.i. (post-inoculation). The interruption of cyst excretion ranged from 12 to 20 days p.i. The fastigium of the cyst excretion was on day 6 p.i. The peak count of the cysts passed during a 2 h collection period was 2.3 x 10(7)/g fecal specimen. Edema, inflammation, cell infiltration, small blood vessels congestion, mitotic figures and mucosa necrosis appeared in sections of intestines. C57Bl/6N mouse is a suitable animal model of G. lamblia.
Beneficial effects of coconut water feeding on lipid metabolism in cholesterol-fed rats.
Sandhya, V G; Rajamohan, T
2006-01-01
The purpose of this study was to determine the effect of coconut water feeding in cholesterol-fed rats. Male albino rats were fed tender coconut water and mature coconut water at a dose level of 4 mL/100 g of body weight. Cholesterol feeding caused a marked increase in total cholesterol, very low-density lipoprotein (VLDL) + low-density lipoprotein (LDL) cholesterol, and triglycerides in serum. Administration of coconut water counteracts the increase in total cholesterol, VLDL + LDL cholesterol, and triglycerides, while high-density lipoprotein cholesterol was higher. Lipid levels in the tissues viz. liver, heart, kidney, and aorta were markedly decreased in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased activities of 3-hydroxy-3-methylglutaryl-CoA reductase in liver, lipoprotein lipase in heart and adipose tissue, and plasma lecithin:cholesterol acyl transferase, while lipogenic enzymes showed decreased activities. An increased rate of cholesterol conversion to bile acid and an increased excretion of bile acids and neutral sterols were observed in rats fed coconut water. Histopathological studies of liver and aorta revealed much less fatty accumulation in these tissues in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased plasma L-arginine content, urinary nitrite level, and nitric oxide synthase activity. These results indicate that both tender and mature coconut water has beneficial effects on serum and tissue lipid parameters in rats fed cholesterol-containing diet.
Methods for diagnosis of bile acid malabsorption in clinical practice.
Vijayvargiya, Priya; Camilleri, Michael; Shin, Andrea; Saenger, Amy
2013-10-01
Altered concentrations of bile acid (BA) in the colon can cause diarrhea or constipation. More than 25% of patients with irritable bowel syndrome with diarrhea or chronic diarrhea in Western countries have BA malabsorption (BAM). As BAM is increasingly recognized, proper diagnostic methods are needed to help direct the most effective course of treatment for the chronic bowel dysfunction. We review the methodologies, advantages, and disadvantages of tools that directly measure BAM: the (14)C-glycocholate breath and stool test, the (75)selenium homotaurocholic acid test (SeHCAT), and measurements of 7 α-hydroxy-4-cholesten-3-one (C4) and fecal BAs. The (14)C-glycocholate test is laborious and no longer widely used. The (75)SeHCAT has been validated but is not available in the United States. Measurement of serum C4 is a simple and accurate method that can be used for most patients but requires further clinical validation. Assays to quantify fecal BA (total and individual levels) are technically cumbersome and not widely available. Regrettably, none of these tests are routinely available in the United States; assessment of the therapeutic effects of a BA binder is used as a surrogate for diagnosis of BAM. Recent data indicate the advantages to studying fecal excretion of individual BAs and their role in BAM; these could support the use of the fecal BA assay, compared with other tests. Measurement of fecal BA levels could become a routine addition to the measurement of fecal fat in patients with unexplained diarrhea. Availability ultimately determines whether the C4, SeHCAT, or fecal BA test is used; more widespread availability of such tests would enhance clinical management of these patients. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
The measurement of radiation exposure of astronauts by radiochemical techniques
NASA Technical Reports Server (NTRS)
Brodzinski, R. L.
1971-01-01
The concentrations of 23 major, minor, and trace elements in the fecal samples from the Apollo 12 and 13 astronauts are reported. Most elemental excretion rates are comparable to rates reported for earlier missions. Exceptions are noted for calcium, iron, and tin. Body calcium and iron losses appear to be reduced during the Apollo 12 and 13 missions such that losses now seem to be insignificant. Refined measurements of tin excretion rates agree with normal dietary intakes. Earlier reported tin values are in error. A new passive dosimetry canister was designed which contains foils of tantalum, copper, titanium, iron, cobalt, aluminum, and scandium. By measuring the concentrations of the various products of nuclear reactions in these metals after space exposure, the characteristics of the incident cosmic particles can be determined.
Ha, Ae Wha; Ying, Tian
2015-01-01
BACKGROUD/OBEJECTIVES The mechanism of how black garlic effects lipid metabolism remains unsolved. Therefore, the objectives of this study were to determine the effects of black garlic on lipid profiles and the expression of related genes in rats fed a high fat diet. MATERIALS/METHODS Thirty-two male Sqrague-Dawley rats aged 4 weeks were randomly divided into four groups (n=8) and fed the following diets for 5 weeks: normal food diet, (NF); a high-fat diet (HF); and a high-fat diet + 0.5% or 1.5% black garlic extract (HFBG0.5 or HFBG1.5). Body weights and blood biochemical parameters, including lipid profiles, and expressions of genes related to lipid metabolism were determined. RESULTS Significant differences were observed in the final weights between the HFBG1.5 and HF groups. All blood biochemical parameters measured in the HFBG1.5 group showed significantly lower values than those in the HF group. Significant improvements of the plasama lipid profiles as well as fecal excretions of total lipids and triglyceride (TG) were also observed in the HFBG1.5 group, when compared to the HF diet group. There were significant differences in the levels of mRNA of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G6PDH) in the HFBG1.5 group compared to the HF group. In addition, the hepatic expression of (HMG-CoA) reductase and Acyl-CoA cholesterol acyltransferase (ACAT) mRNA was also significantly lower than the HF group. CONCLUSIONS Consumption of black garlic extract lowers SREBP-1C mRNA expression, which causes downregulation of lipid and cholestrol metahbolism. As a result, the blood levels of total lipids, TG, and cholesterol were decreased. PMID:25671065
Bo, Tao; Shao, Shanshan; Wu, Dongming; Niu, Shaona; Zhao, Jiajun; Gao, Ling
2017-08-01
Recent studies performed provide mechanistic insight into effects of the microbiota on cholesterol metabolism, but less focus was given to how cholesterol impacts the gut microbiota. In this study, ApoE -/- Sprague Dawley (SD) rats and their wild-type counterparts (n = 12) were, respectively, allocated for two dietary condition groups (normal chow and high-cholesterol diet). Total 16S rDNA of fecal samples were extracted and sequenced by high-throughput sequencing to determine differences in microbiome composition. Data were collected and performed diversity analysis and phylogenetic analysis. The influence of cholesterol on gut microbiota was discussed by using cholesterol dietary treatment as exogenous cholesterol disorder factor and genetic modification as endogenous metabolic disorder factor. Relative microbial variations were compared to illustrate the causality and correlation of cholesterol and gut microbiota. It turned out comparing to genetically modified rats, exogenous cholesterol intake may play more effective role in changing gut microbiota profile, although the serum cholesterol level of genetically modified rats was even higher. Relative abundance of some representative species showed that the discrepancies due to dietary variation were more obvious, whereas some low abundance species changed because of genetic disorders. Our results partially demonstrated that gut microbiota are relatively more sensitive to dietary variation. Nevertheless, considering the important effect of bacteria in cholesterol metabolism, the influence to gut flora by "genetically caused cholesterol disorder" cannot be overlooked. Manipulation of gut microbiota might be an effective target for preventing cholesterol-related metabolic disorders. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.
Kent, Dorothea Stark; Remer, Thomas; Blumenthal, Caron; Hunt, Sharon; Simonds, Sharon; Egert, Sarah; Gaskin, Kevin J
2018-05-01
The 'gold standard' test for the indirect determination of pancreatic function status in infants with cystic fibrosis (CF), the 72-hour fecal fat excretion test, is likely to become obsolete in the near future. Alternative indirect pancreatic function tests with sufficient sensitivity and specificity to determine pancreatic phenotype need further evaluation in CF infants. Evaluation of the clinical utility of both the noninvasive, nonradioactive C-mixed triglyceride (MTG) breath test and fecal elastase-1 (FE1) in comparison with the 72-hour fecal fat assessment in infants with CF. C-MTG breath test and the monoclonal and polyclonal FE1 assessment in stool was compared with the 72-hour fecal fat assessment in 24 infants with CF. Oral pancreatic enzyme substitution (PERT; if already commenced) was stopped before the tests. Sensitivity rates between 82% and 100% for CF patients with pancreatic insufficiency assessed by both the C-MTG breath test and the FE1 tests proved to be high and promising. The C-MTG breath test (31%-38%) as well as both FE1 tests assessed by the monoclonal (46%-54%) and the polyclonal (45%) ELISA kits, however, showed unacceptably low-sensitivity rates for the detection of pancreatic-sufficient CF patients in the present study. The C-MTG breath test with nondispersive infrared spectroscopy (NDIRS) technique, as well as both FE1 tests, are not alternatives to the fecal fat balance test for the evaluation of pancreatic function in CF infants during the first year of life.
van Faassen, A; Bol, J; van Dokkum, W; Pikaar, N A; Ockhuizen, T; Hermus, R J
1987-12-01
In a metabolic ward 12 healthy male subjects consumed mixed Western (M), lacto-ovovegetarian (L), and vegan (V) diets in a randomized order for 20 d each. The concentrations of deoxycholic acid, isolithocholic acid, and total bile acids in 4-d composites of feces on the L and V diets were significantly lower than on the M diet. The chenodeoxycholic-to-isolithocholic plus lithocholic acid ratio was significantly higher on the V diet. The concentrations of coprostanol and of coprostanol plus cholesterol were highest on M diet and lowest on V diet. The number of fecal lactobacilli and enterococci on the V diet was significantly lower than on the M or the L diets. This study showed a decrease in the concentration of fecal (secondary) bile acids by the L and the V diets and an alteration of the fecal flora composition by the V diet.
Lin, Wen; Flarakos, Jimmy; Du, Yancy; Hu, Wenyu; He, Handan; Mangold, James; Tanaka, S. Ken
2016-01-01
ABSTRACT The absorption, distribution, metabolism, and excretion (ADME) of omadacycline, a first-in-class aminomethylcycline antibiotic with a broad spectrum of activity against Gram-positive, Gram-negative, anaerobic, and atypical bacteria, were evaluated in rats. Tissue distribution was investigated by quantitative whole-body autoradiography in male Long-Evans Hooded (LEH) rats. Following an intravenous (i.v.) dose of 5 mg/kg of body weight, radioactivity widely and rapidly distributed into most tissues. The highest tissue-to-blood concentration ratios (t/b) were observed in bone mineral, thyroid gland, and Harderian gland at 24 h post-i.v. dose. There was no evidence of stable accumulation in uveal tract tissue, suggesting the absence of a stable binding interaction with melanin. Following a 90 mg/kg oral dose in LEH rats, the highest t/b were observed in bone mineral, Harderian gland, liver, spleen, and salivary gland. The plasma protein binding levels were 26% in the rat and 15% to 21% in other species. Omadacycline plasma clearance was 1.2 liters/h/kg, and its half-life was 4.6 h; the steady-state volume of distribution (Vss) was 6.89 liters/kg. Major circulating components in plasma were intact omadacycline and its epimer. Consistent with observations in human, approximately 80% of the dose was excreted into the feces as unchanged omadacycline after i.v. administration. Fecal excretion was primarily the result of biliary excretion (∼40%) and direct gastrointestinal secretion (∼30%). However, urinary excretion (∼30%) was equally prominent after i.v. dosing. PMID:27821446
Shimada, Takuya; Nishii, Eriko; Saitoh, Takashi
2011-12-01
Mammalian herbivores adopt various countermeasures against dietary tannins, which are among the most widespread plant secondary metabolites. The large Japanese wood mouse Apodemus speciosus produces proline-rich salivary tannin-binding proteins in response to tannins. Proline-rich proteins (PRPs) react with tannins to form stable complexes that are excreted in the feces. Here, we developed a new method for estimating the tannin intake of free-living small rodents, by measuring fecal proline content, and applied the method to a field investigation. A feeding experiment with artificial diets containing various levels of tannic acid revealed that fecal proline content was clearly related to dietary tannin content in three species (A. speciosus, Apodemus argenteus, and Myodes rufocanus). We then used fecal proline content to estimate the tannin intakes of these three forest-dwelling species in a forest in Hokkaido. In the autumn, estimated tannin intakes increased significantly in the Apodemus species, but not in M. rufocanus. We speculated that an increase in tannin intake during autumn may result from consumption of tannin-rich acorns. This hypothesis was consistent with population fluctuation patterns of the three species, which were well-synchronized with acorn abundance for the Apodemus species but not for M. rufocanus.
Jorgensen, Matthew J; Aycock, S Tyler; Clarkson, Thomas B; Kaplan, Jay R
2013-07-01
Our goal was to assess a nonhuman primate diet that mimicked the Western-type diet of humans with regard to palatability and the diet's effects on plasma lipid concentrations and other cardiometabolic risk factors. We evaluated male (n = 8) and female (n = 11) African green monkeys (vervets; Chlorocebus aethiops sabaeus) that initially were fed a standard diet. Each cohort then was divided into 2 groups, which received either standard chow or the Western diet. Food consumption and fecal quality were measured weekly. Body weight, waist circumference, and body-mass index were measured every 2 wk. CBC and clinical chemistry analyses were performed at baseline and 4 wk after the diet change. Plasma lipid concentrations, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose, insulin, and fructosamine were measured at baseline and at 4, 8, and 12 wk after the diet change. Isoflavones were measured in the male monkeys at 6 wk after diet change, and lipid particle size was measured in the female monkeys at the 12-wk point. Green monkeys readily ate the Western diet and maintained baseline body weight and morphometric measures, with no adverse effects on fecal quality or clinical measures. Total plasma cholesterol was higher in monkeys fed the Western diet compared with standard chow. Isoflavones were higher in male monkeys fed standard chow compared with the Western diet, but lipid particle size did not differ by diet in female monkeys. Our data indicate that the Western diet led to changes in various biomedical risk factors of green monkeys to become similar to those of humans in the United States.
Calcium Balance in Mature Rats Exposed to a Space Flight Model
NASA Technical Reports Server (NTRS)
Wolinsky, Ira
1996-01-01
Negative calcium balances are seen in humans during spaceflight and bed rest, an analog of space flight. Due to the infrequency and costliness of space flight and the difficulties, cost, and restraints in using invasive procedures in bed rest studies, several ground based animal models of space flight have been employed. The most useful and well developed of these models is hind limb unloading in the rat. In this model the hind limbs are non-weight bearing (unloaded) but still mobile; there is a cephalad fluid shift similar to that seen in astronauts in flight; the animals are able to feed, groom and locomote using their front limbs; the procedure is reversible; and, importantly, the model has been validated by comparison to space flight. Several laboratories have studied calcium balance using rats in hind limb unweighting. Roer and Dillaman used young male rats to study calcium balance in this model for 25 days. They found no differences in dietary calcium intake, percent calcium absorption, urinary and fecal excretion, hence indicating no differences in calcium balance between control and unloaded rats. In another study, employing 120 day old females, rats' hind limbs were unloaded for 28 days. While negative calcium balances were observed during a 25 day recovery period no balance measurements were possible during unweighting since the researchers did not employ appropriate metabolic cages. In a recent study from this laboratory, using 200 g rats in the space flight model for two weeks, we found depressed intestinal calcium absorption and increased fecal calcium excretion (indicating less positive calcium balances) and lower circulating 1,25-dihydroxyvitamin D. The above studies indicate that there remains a dearth of information on calcium balance during the hind limb unloading rat space flight model, especially in mature rats, whose use is a better model for planned manned space flight than juvenile or growing animals. With the aid of a newly designed metabolic cage developed in our laboratory it is now possible to accurately measure urinary and fecal calcium excretions in this space flight model. The purpose of this study, then, was to extend and enlarge our previous findings viz: to measure calcium balances in mature rats exposed to a space flight model.
Karl, J Philip; Meydani, Mohsen; Barnett, Junaidah B; Vanegas, Sally M; Barger, Kathryn; Fu, Xueyan; Goldin, Barry; Kane, Anne; Rasmussen, Helen; Vangay, Pajau; Knights, Dan; Jonnalagadda, Satya S; Saltzman, Edward; Roberts, Susan B; Meydani, Simin N; Booth, Sarah L
2017-10-01
Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined. Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation. Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8. Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation. Conclusion: Menaquinone concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear. This trial was registered at clinicaltrials.gov as NCT01902394. © 2017 American Society for Nutrition.
Färkkilä, M A; Kairemo, K J; Taavitsainen, M J; Strandberg, T A; Miettinen, T A
1996-04-01
1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids < 10 mg day-1 kg-1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day-1 kg-1, n = 13). 3. Faecal bile acid excretion was 5.9 +/- 1.0 mg day-1 kg-1 in control subjects and 45.7 +/- 6.1 mg day-1 kg-1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T1/2) was 95.6 +/- 16.3 h and 14.1 +/- 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 +/- 84 micrograms/ml compared with 400 +/- 59 micrograms/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P < 0.001), with 75SeHCAT T1/2 (r = -0.524, P < 0.05) and with Schilling test (r = -0.591, P < 0.05). Significant correlations were also obtained for delta 8-cholestenol with faecal bile acids (r = 0.784, P < 0.001) and 75SeHCAT (r = -0.505, P < 0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = -0.702, P < 0.001). Using mean+2 SD of lathosterol (In micrograms/ml cholesterol) as a cut-off value and 10 mg day-1 kg-1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.
Woolsey, Ian David; Webster, P; Thamsborg, S; Schnyder, Manuela; Monrad, Jesper; Kapel, C M O
2017-12-01
The French heartworm Angiostongylus vasorum is found in European red fox ( Vulpes vulpes ) and dog populations, where it appears to be spreading geographically. Once introduced into new areas, it establishes in local fox populations, typically to over 50% prevalence in a few years. High susceptibility and constant excretion of first stage larvae (L1) by the definitive hosts are prerequisites for sustaining high parasite biomass in a particular habitat. The present study explores the hypothesis that repeated ingestion of gastropods in nature will result in accumulation of adult worms and elevated excretion of L1 in feces. Experimentally infected foxes were subsequently inoculated via stomach tube once (9 weeks post initial inoculation) or twice (9 and 13 weeks post inoculation (wpi)) with 100 third stage A. vasorum larvae (L3) previously isolated from aquatic snails infected with L1 from a naturally infected dog. Despite large variation in fecal larval excretion for the individual animals within the groups, excretion of L1 was significantly higher in foxes twice inoculated as compared to foxes inoculated only once. With an outlier in the once inoculated group removed, excretion became significantly higher in the three times inoculated group. Establishment of adult worms varied and only a trend to higher worm burdens was found in the group of foxes inoculated three times. However, this became significant with the same single outlier removed. Overall, it appears that protective immunity to A. vasorum does not appear to occur in V. vulpes with animals exhibiting high infection intensities without obvious clinical signs. The increasing larval excretion in foxes being repeatedly exposed to A. vasorum L3 support the hypothesis that foxes under natural conditions may repeatedly ingest infected gastropods and remain a source of environmental contamination for several months, potentially contributing to the establishment of endemic foci through increasing L1 excretion.
Afrose, Sadia; Hossain, Md Sharoare; Salma, Ummay; Miah, Abdul Gaffar; Tsujii, Hirotada
2010-01-01
This study was conducted to elucidate the mechanism underlying the hypolipidemic action of karaya saponin or Rhodobacter (R.) capsulatus. A total of 40 laying hens (20-week-old) were assigned into four dietary treatment groups and fed a basal diet (as a control) or basal diets supplemented with either karaya saponin, R. capsulatus, or both for 60 days. The level of serum low-density-lipoprotein cholesterol and the levels of cholesterol and triglycerides in the serum, liver, and egg yolk were reduced by all the supplementations (P < .05). Liver bile acid concentration and fecal concentrations of cholesterol, triacylglycerol, and bile acid were simultaneously increased by the supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus (P < .05). The supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus suppressed the incorporation of (14)C from 1-(14)C-palmitic acid into the fractions of total lipids, phospholipids, triacylglycerol, and cholesterol in the liver in vitro (P < .05). These findings suggest that the hypocholesterolemic effects of karaya saponin and R. capsulatus are caused by the suppression of the cholesterol synthesis and the promotion of cholesterol catabolism in the liver.
Afrose, Sadia; Hossain, Md. Sharoare; Salma, Ummay; Miah, Abdul Gaffar; Tsujii, Hirotada
2010-01-01
This study was conducted to elucidate the mechanism underlying the hypolipidemic action of karaya saponin or Rhodobacter (R.) capsulatus. A total of 40 laying hens (20-week-old) were assigned into four dietary treatment groups and fed a basal diet (as a control) or basal diets supplemented with either karaya saponin, R. capsulatus, or both for 60 days. The level of serum low-density-lipoprotein cholesterol and the levels of cholesterol and triglycerides in the serum, liver, and egg yolk were reduced by all the supplementations (P < .05). Liver bile acid concentration and fecal concentrations of cholesterol, triacylglycerol, and bile acid were simultaneously increased by the supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus (P < .05). The supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus suppressed the incorporation of 14C from 1-14C-palmitic acid into the fractions of total lipids, phospholipids, triacylglycerol, and cholesterol in the liver in vitro (P < .05). These findings suggest that the hypocholesterolemic effects of karaya saponin and R. capsulatus are caused by the suppression of the cholesterol synthesis and the promotion of cholesterol catabolism in the liver. PMID:21490913
Metabolism of 4-chlorobenzotrichloride in rats
DOE Office of Scientific and Technical Information (OSTI.GOV)
Quistad, G.B.; Mulholland, K.M.; Skiles, G.
Special analytical methodology was developed for purification of 4-chloro(/sup 14/C)benzotrichloride, which is both volatile and hydrolytically unstable at milligram mass levels. When rats were given a single oral dose of 4-chloro(/sup 14/C)benzotrichloride at 1.5 mg/kg, within 4-6 days 87 and 9% of the applied /sup 14/C were excreted in urine and feces, respectively. The major urinary metabolite was identified as 4-chlorohippuric acid, representing 78% of the applied dose. While about two-thirds of the fecal /sup 14/C residues were unextractable with organic solvents, free 4-chlorobenzoic acid and ..cap alpha..,..cap alpha..,4,4'-tetrachlorostilbene contributed 10 and 8% of the fecal /sup 14/C. The metabolicmore » production of ..cap alpha..,..cap alpha..,4,4'-tetrachlorostilbene appears to occur by a novel metabolic pathway.« less
[Influence of intestinal microflora on the amino acid composition of lamb feces].
Combe, E
1976-01-01
6 conventional and 5 germfree male lambs were fed ad libitum a UHT sterilized cow milk. Body weight and food intake were recorded. Whole feces were collected for 5 consecutive days. Growth rate reached 259 g/d for the germfree. Daily fecal excretion of dry matter and nitrogenous compounds are not found different in the two groups of animals. The influence of intestinal microflora appears on the biochemical composition of the feces. As compared to the conventional fecal proteins from germfree lambs are very high in threonine and serine and low in lysine. Moreover the difference of amino acid composition between these two groups come not only from the histidine alanine and arginine composition of bacteries; it also involves the high levels of threonine serine cystine and tyrosine of the endogenous digestive proteins.
Jiang, Juquan; Knight, John; Easter, Linda H.; Neiberg, Rebecca; Holmes, Ross P.; Assimos, Dean G.
2011-01-01
Purpose Enteric colonization with Oxalobacter formigenes, a bacterium whose main energy source is oxalate, has been demonstrated to decrease the risk of recurrent calcium oxalate kidney stone formation. We assessed the impact of diets controlled in calcium and oxalate contents on urinary and fecal analytes in healthy subjects who were naturally colonized with O. formigenes or not colonized with O. formigenes. Materials and Methods A total of 11 O. formigenes colonized and 11 noncolonized subjects were administered diets controlled in calcium and oxalate contents. We assayed 24-hour urine collections and stool samples obtained on the last 4 days of each 1-week diet for stone risk parameters and O. formigenes levels. Mixed model analysis was used to determine the effects of colonization status on these variables. Results Urinary calcium and oxalate excretion were significantly altered by the dietary changes in O. formigenes colonized and noncolonized individuals. Mixed model analysis showed significant interaction between colonization status and oxalate excretion on a low calcium (400 mg daily)/moderate oxalate (250 mg daily) diet (p = 0.026). Urinary oxalate excretion was 19.5% lower in O. formigenes colonized subjects than in noncolonized subjects on the low calcium/moderate oxalate diet (mean ± SE 34.9 ± 2.6 vs 43.6 ± 2.6 mg, p = 0.031). Conclusions Results suggest that O. formigenes colonization decreases oxalate excretion during periods of low calcium and moderate oxalate intake. PMID:21575973
Corticosterone excretion patterns and affiliative behavior over development in ravens (Corvus corax)
Stöwe, Mareike; Bugnyar, Thomas; Schloegl, Christian; Heinrich, Bernd; Kotrschal, Kurt; Möstl, Erich
2015-01-01
Averse effects of social stress may be buffered by the presence of social allies, which mainly has been demonstrated in mammals and recently also in birds. However, effects of socio-positive behavior prior to fledging in relation to corticosterone excretion in altricial birds have not been investigated yet. We here monitored corticosterone excretion patterns in three groups of hand raised juvenile ravens (n=5, 6 and 11) in the nest, post-fledging (May–July) and when ravens would be independent from their parents (September–November). We related these corticosterone excretion patterns to socio-positive behavior. Behavioral data were collected via focal sampling in each developmental period considered. We analyzed amounts of excreted immunoreactive corticosterone metabolites (CM) using enzyme immuno assays. We collected fecal samples in each developmental period considered and evaluated the most appropriate assay via an isolation stress experiment. Basal CM was significantly higher during the nestling period than post-fledging or when birds were independent. The time nestlings spent allopreening correlated negatively with mean CM. Post-fledging, individuals with higher CM levels sat close to (distance <50 cm) conspecifics more frequently and tended to preen them longer. When birds were independent and a stable rank hierarchy was established, dominant individuals were preened significantly longer than subordinates. These patterns observed in ravens parallel those described for primates, which could indicate that animal species living in a complex social environment may deal with social problems in a similar way that is not restricted to mammals or primates. PMID:18022623
Rendón-Huerta, Juan A; Juárez-Flores, Bertha; Pinos-Rodríguez, Juan M; Aguirre-Rivera, J Rogelio; Delgado-Portales, Rosa E
2012-03-01
Fructans contribute significantly to dietary fiber with beneficial effects on gastrointestinal physiology in healthy individuals and offer a promising approach to treating some diseases. Two experiments (Experiment 1 = rats with normal weight; Experiment 2 = obese rats) were developed to compare the effects of three fructan sources (Cichorium intybus L. Asteraceae, Helianthus tuberosus L. Asteraceae and Agave angustifolia ssp. tequilana Haw, Agavaceae) on body weight change, blood metabolites and fecal bacteria in non-diabetic (ND) and diabetic (D) rats. In Experiment 1 total body weight gain and daily feed intake in D and ND rats decreased (P < 0.05) with supplements of fructan. Only in D rats, blood glucose concentrations, fecal Clostrodium spp. counts, and liver steatosis decreased, while blood HDL concentrations and fecal Lactobacillus spp. and Bifidobacterium spp. counts increased due to fructans. In Experiment 2, total body weight gain and feed intake in ND and D rats were also decreased by fructans. In ND rats, fructan decreased blood glucose concentrations. In D rats, fructans from A. angustifolia ssp. tequilana decreased blood cholesterol and LDL and liver steatosis. For both ND and D rats, fecal Lactobacillus spp. and Bifidobacterium spp. counts were higher (P < 0.05) with fructan supplements.
Harding, Scott V; Rideout, Todd C; Jones, Peter J H
2010-07-01
The effect of dietary plant sterols on cholesterol homeostasis has been well characterized in the intestine, but how plant sterols affect lipid metabolism in other lipid-rich tissues is not known. Changes in hepatic cholesterol homeostasis in response to high dietary intakes of plant sterols were determined in male golden Syrian hamsters fed hypercholesterolemia-inducing diets with and without 2% plant sterols (wt:wt; Reducol, Forbes Meditech) for 28 d. Plasma and hepatic cholesterol concentrations, cholesterol biosynthesis and absorption, and changes in the expression of sterol response element binding protein 2 (SREBP2) and liver X receptor-beta (LXRbeta) and their target genes were measured. Plant sterol feeding reduced plasma total cholesterol, non-HDL cholesterol, and HDL cholesterol concentrations 43% (P < 0.0001), 60% (P < 0.0001), and 21% (P = 0.001), respectively, compared with controls. Furthermore, there was a 93% reduction (P < 0.0001) in hepatic total cholesterol and >6-fold (P = 0.029) and >2-fold (P < 0.0001) increases in hepatic beta-sitosterol and campesterol concentrations, respectively, in plant sterol-fed hamsters compared with controls. Plant sterol feeding also increased fractional cholesterol synthesis >2-fold (P < 0.03) and decreased cholesterol absorption 83% (P < 0.0001) compared with controls. Plant sterol feeding increased hepatic protein expression of cytosolic (inactive) SREBP2, decreased nuclear (active) SREBP2, and tended to increase LXRbeta (P = 0.06) and ATP binding cassette transporter G5, indicating a differential modulation of the expression of proteins central to cholesterol metabolism. In conclusion, high-dose plant sterol feeding of hamsters changes hepatic protein abundance in favor of cholesterol excretion despite lower hepatic cholesterol concentrations and higher cholesterol fractional synthesis.
Fecal antibodies to Cryptosporidium parvum in healthy volunteers.
Dann, S M; Okhuysen, P C; Salameh, B M; DuPont, H L; Chappell, C L
2000-09-01
This study examined the intestinal antibody response in 26 healthy volunteers challenged with Cryptosporidium parvum oocysts. Fecal extracts were assayed for total secretory immunoglobulin A (IgA) and C. parvum-specific IgA reactivity. Specific IgA reactivity was standardized to IgA concentration and expressed as a reactivity index (RI). Anti-C. parvum fecal IgA (fIgA) increased significantly in 17 of 26 (65.4%) following oocyst ingestion. Of those with detectable responses, 59, 76.5, and 94.1% were positive by days 7, 14, and 30, respectively. Volunteers receiving high challenge doses (>1,000 and 300 to 500 oocysts) had higher RIs (RI = 5.57 [P = 0. 027] and RI = 1.68 [P = 0.039], respectively) than those ingesting low doses (30 to 100 oocysts; RI = 0.146). Subjects shedding oocysts and experiencing a diarrheal illness had the highest fIgA reactivity. When evaluated separately, oocyst excretion was associated with an increased fIgA response compared to nonshedders (RI = 1.679 versus 0. 024, respectively; P = 0.003). However, in subjects experiencing diarrhea with or without oocyst shedding, a trend toward a higher RI (P = 0.065) was seen. Extracts positive for fecal IgA were further examined for IgA subclass. The majority of stools contained both IgA1 and IgA2, and the relative proportions did not change following challenge. Also, no C. parvum-specific IgM or IgG was detected in fecal extracts. Thus, fecal IgA to C. parvum antigens was highly associated with infection in subjects who had no evidence of previous exposure and may provide a useful tool in detecting recent infections.
Control of hyperglycaemia and hyperlipidaemia by plant product.
Bhardwaj, P K; Dasgupta, D J; Prashar, B S; Kaushal, S S
1994-01-01
A herbal powder consisting of Guargum, Methi, Tundika and Meshasringi was administered to thirty control and thirty NIDDM patients twice daily before principal meals for four weeks. Oral GTT showed improvement in both control and patient groups. Serum total and LDL cholesterol also fell significantly in both the groups after the trial period. Test meal of the herbal powder with D-Xylose excretion was otherwise normal. Follow up for upto two years did not reveal any long term side effect of the powder. This powder, therefore, can be effectively used to reduce postprandial blood glucose and LDL cholesterol in NIDDM patients as a long term measure.
Choi, Myung-Sook; Park, Hyo Jin; Kim, Sang Ryong; Kim, Do Yeon; Jung, Un Ju
2017-12-01
This study evaluated whether long-term supplementation with dietary yerba mate has beneficial effects on adiposity and its related metabolic dysfunctions in diet-induced obese mice. C57BL/6J mice were randomly divided into two groups and fed their respective experimental diets for 16 weeks as follows: (1) control group fed with high-fat diet (HFD) and (2) mate group fed with HFD plus yerba mate. Dietary yerba mate increased energy expenditure and thermogenic gene mRNA expression in white adipose tissue (WAT) and decreased fatty acid synthase (FAS) mRNA expression in WAT, which may be linked to observed decreases in body weight, WAT weight, epididymal adipocyte size, and plasma leptin level. Yerba mate also decreased levels of plasma lipids (free fatty acids, triglycerides, and total cholesterol) and liver aminotransferase enzymes, as well as the accumulation of hepatic lipid droplets and lipid content by inhibiting the activities of hepatic lipogenic enzymes, such as FAS and phosphatidate phosphohydrolase, and increasing fecal lipid excretion. Moreover, yerba mate decreased the levels of plasma insulin as well as the homeostasis model assessment of insulin resistance, and improved glucose tolerance. Circulating levels of gastric inhibitory polypeptide and resistin were also decreased in the mate group. These findings suggest that long-term supplementation of dietary yerba mate may be beneficial for improving diet-induced adiposity, insulin resistance, dyslipidemia, and hepatic steatosis.
Waidyanatha, Suramya; Black, Sherry R; Snyder, Rodney W; Yueh, Yun Lan; Sutherland, Vicki; Patel, Purvi R; Watson, Scott L; Fennell, Timothy R
2018-07-15
With the removal of bisphenol A (BPA) from many consumer products, the potential use of alternatives such as bisphenol S (BPS) and its derivatives is causing some concerns. These studies investigated the comparative in vitro hepatic clearance and metabolism of BPS and derivatives and the disposition and metabolism of BPS in rats and mice following gavage and intravenous administration. The clearance of BPS and its derivatives was slower in human hepatocytes than in rodents. In male rats following gavage administration of 50, 150, and 500 mg/kg [ 14 C]BPS the main route of excretion was via urine; the urinary excretion decreased (72 to 48%) and the fecal excretion increased (16 to 30%) with increasing dose. The disposition was similar in female rats and male and female mice following gavage administration. Radioactivity remaining in tissues at 72 h in both species and sexes was ≤2.4%. In bile duct cannulated rats 53% of a gavage dose was secreted in bile suggesting extensive enterohepatic recirculation of [ 14 C]BPS. Following an intravenous dose in rats and mice, the pattern of excretion was similar to gavage. These data suggest that the dose excreted in feces folowing gavage administration is likely the absorbed dose. Urinary metabolites included the glucuronide and sulfate conjugates with a moderate amount of parent. The pattern of in vitro hepatic metabolsim was similar to in vivo with some difference among derivatives. These data suggest that similar to other bisphenol analogues, BPS was well absorbed following oral expsosure and extensively excreted with minimal tissue retention. Copyright © 2018 Elsevier Inc. All rights reserved.
Sandhya, V G; Rajamohan, T
2008-12-01
The coconut water presents a series of nutritional and therapeutic properties, being a natural, acid and sterile solution, which contains several biologically active components, l-arginine, ascorbic acid, minerals such as calcium, magnesium and potassium, which have beneficial effects on lipid levels. Recent studies in our laboratory showed that both tender and mature coconut water feeding significantly (P<0.05) reduced hyperlipidemia in cholesterol fed rats [Sandhya, V.G., Rajamohan, T., 2006. Beneficial effects of coconut water feeding on lipid metabolism in cholesterol fed rats. J. Med. Food 9, 400-407]. The current study evaluated the hypolipidemic effect of coconut water (4ml/100g body weight) with a lipid lowering drug, lovastatin (0.1/100g diet) in rats fed fat-cholesterol enriched diet ad libitum for 45 days. Coconut water or lovastatin supplementation lowered the levels of serum total cholesterol, VLDL+LDL cholesterol, triglycerides and increased HDL cholesterol in experimental rats (P<0.05). Coconut water feeding decreased activities of hepatic lipogenic enzymes and increased HMG CoA reductase and lipoprotein lipase activity (P<0.05). Incorporation of radioactive acetate into free and ester cholesterol in the liver were higher in coconut water treated rats. Coconut water supplementation increased hepatic bile acid and fecal bile acids and neutral sterols (P<0.05). Coconut water has lipid lowering effect similar to the drug lovastatin in rats fed fat-cholesterol enriched diet.
Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E
2017-01-01
Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blood, urine, feces and bile, as well as carcasses, were collected through 168 hours after dosing. Samples were analyzed for total radioactivity content by liquid scintillation counting, and carcasses were analyzed by quantitative whole-body autoradiography. Results [14C]APX001-derived radioactivity was rapidly and extensively absorbed and extensively distributed to most tissues for both routes of administration in both species. In rats, tissues with the highest radioactivity Cmax values included bile, abdominal fat, reproductive fat, subcutaneous fat, and liver, but radioactivity was also detected in tissues associated with IFI, including lung, brain and eye. In monkeys, the highest Cmax values were in bile, urine, uveal tract, bone marrow, abdominal fat, liver, and kidney cortex. Liver and kidney were the tissues with highest radioactivity, but as in the rat, radioactivity was also detected in lung, brain and eye tissues. In pigmented rats, radiocarbon was densely distributed into pigmented tissue and more slowly cleared than from other tissues. Mean recovery of radioactivity in rats was approximately 95–100%. In bile duct-intact rats, >90% of radioactivity was recovered in feces. In cannulated rats, biliary excretion of radioactivity was the major route of elimination and accounted for 88.8% of the dose, whereas urinary and fecal excretion of radioactivity was minor and accounted for 2.56% and 5.42% of the dose, respectively. In monkeys, the overall recovery of radioactivity was 87.6%, and was eliminated in feces (49.8% of dose) and to a lesser extent in urine (20.6% of dose). Conclusion Together, the results indicate that APX001-related radioactivity is extensively distributed to major tissues (including tissues relevant to IFI) in both rats and monkeys and cleared primarily by biliary/fecal excretion. Disclosures R. Mansbach, Amplyx Pharmaceuticals Inc.: Consultant, Consulting fee; K. J. Shaw, Amplyx Pharmaceuticals Inc.: Employee, Salary; M. R. Hodges, Amplyx Pharmaceuticals: Employee, Salary; S. Coleman, Covance Laboratories: Employee, Salary; M. E. Fitzsimmons, Covance Laboratories: Employee, Salary
Kurtsikidze, I
2006-08-01
Disturbances in lipid metabolism, intensification of lipid peroxidize oxidation and functions of sympatho-adrenal system play an important role in the development and progressing of ischaemic cardiac disease. As a result of investigations it has been established that microelement--selenium has an antiatherogenic action and suppresses peroxidize oxidation of lipids. The effect of treatment with selenium electrophoresis in patients suffering from ischaemic cardiac disease with a stable stenocardia of tension has been studied. Total of 76 patients with ICS:SST of I-II functional classes (FC) have been investigated. It has been established that treatment with selenium electrophoresis provokes a reduction of overall cholesterol, triglycerides and beta-lipoproteins content in blood serum, as well as a decrease of cholesterol amount in beta-lipoproteins, lipoproteins of low and very low density and diene conjugates in blood serum and adrenaline and norepinephrine excretion with urine; increase of lipoprotein amount of high density in blood serum, activity of catalase and selenium excretion with urine. Above-said positive changes in biochemical data were more pronounced for the ICS:SST of the first FC.
Mochizuki, H; Oda, H; Yokogoshi, H
2000-04-01
The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes was investigated in rats fed diets containing polychlorinated biphenyls (PCB) to determine whether taurine has an adaptive and protective function in xenobiotic-treated animals. Young male Wistar rats (60 g) were fed diets containing 0 or 0.2 g/kg diet PCB with or without 30 g/kg diet of taurine for 14 d. The rats fed the PCB-containing diets had greater liver weight, higher ascorbic acid concentrations in the liver and spleen and greater hepatic cytochrome P-450 contents than control rats that were not treated with PCB (P < 0.01). In PCB-fed rats, urinary ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in control rats. Dietary taurine significantly potentiated the increases in the urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were caused by PCB treatment. On the other hand, the supplementation of taurine to control diet did not alter these variables. Taurine may enhance the hepatic drug-metabolizing systems, leading to the stimulation of the ascorbic acid metabolism in rats fed diets containing PCB.
Pharmacokinetics, excretion of 8-cetylberberine and its main metabolites in rat urine.
Hu, Yuli; Fan, Shoujun; Liao, Xiaobing; Chen, Chao; Su, Liang; Li, Xuegang
2017-01-05
Berberine (BBR) is a bioactive plant ingredient derived from the roots and bark of Berberis aristata and Coptis chinensis and has a wide variety of pharmacological effects. 8-cetylberberine (8-BBR-C16) is the berberine (BBR) derivative reconstructed from adding octadecyl at C-8 of BBR to enhance its activity. This study presents a reliable method for the determination of BBR and 8-BBR-C16 in rat plasma, urine and feces. BBR and 8-BBR-C16 were determined by HPLC-UV after liquid-liquid extraction for plasma samples, and solid-phase extraction for urinary and fecal samples. The method was linear over the concentration range of 10-300 ng·ml -1 for the plasma samples, 25-2000 ng·ml -1 for the urinary samples, and 100-2000 ng·g -1 for the fecal samples. Furthermore, a metabolic investigation on urine was performed by LC/MS/MS analysis to identify the structures of 8-BBR-C16 metabolites by full scan and product ion scan. Adult Sprague-Dawley rats were divided into two groups. In the control group, rats received 80 mg·kg -1 BBR, and in the drug-treated group, rats received 80 mg·kg -1 8-BBR-C16. The results indicate that there were significant differences in the pharmacokinetic parameters and in the accumulated excretion levels between the control group and the drug-treated group. The C max and AUC 0-t of 8-BBR-C16 were 2.8 and 12.9 times higher than those of BBR, and the relative bioavailability of BBR to 8-BBR-C16 was 7.7%. The total excretion amount through the urine and feces of 8-BBR-C16 was 76.9%, but that of BBR was only 20.5%. Additionally, 8-BBR-C16 was metabolized in rat urine with phase I demethylation and phase II glucuronidation or sulfation. Copyright © 2016 Elsevier B.V. All rights reserved.
Curry, Erin; Browning, Lissa J; Reinhart, Paul; Roth, Terri L
2017-05-01
Red pandas (Ailurus fulgens styani) exhibit a variable gestation length and may experience a pseudopregnancy indistinguishable from true pregnancy; therefore, it is not possible to deduce an individual's true pregnancy status and parturition date based on breeding dates or fecal progesterone excretion patterns alone. The goal of this study was to evaluate the use of transabdominal ultrasonography for pregnancy diagnosis in red pandas. Two to three females were monitored over 4 consecutive years, generating a total of seven profiles (four pregnancies, two pseudopregnancies, and one lost pregnancy). Fecal samples were collected and assayed for progesterone (P4) and estrogen conjugate (EC) to characterize patterns associated with breeding activity and parturition events. Animals were trained for voluntary transabdominal ultrasound and examinations were performed weekly. Breeding behaviors and fecal EC data suggest that the estrus cycle of this species is 11-12 days in length. Fecal steroid metabolite analyses also revealed that neither P4 nor EC concentrations were suitable indicators of pregnancy in this species; however, a secondary increase in P4 occurred 69-71 days prior to parturition in all pregnant females, presumably coinciding with embryo implantation. Using ultrasonography, embryos were detected as early as 62 days post-breeding/50 days pre-partum and serial measurements of uterine lumen diameter were documented throughout four pregnancies. Advances in reproductive diagnostics, such as the implementation of ultrasonography, may facilitate improved husbandry of pregnant females and allow for the accurate prediction of parturition. © 2017 Wiley Periodicals, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rosoff, B.; Cohn, S.H.; Spencer, H.
The main pathway of Cs/sup 137/ excretion in man following either intravenous or oral administration is via the kidney. The urinary to fecal ratio is approximately 10 : 1. Orally administered Cs/137/ is rapidly and almost completely absorbed. The metabolism of the radioisotope was shown to be similar following either intravenous or oral administration. Cs/sup 137/ disappears very rapidly from plasma and is taken up by red blood cells. The biological half-life of cesium in man deterrained by analyses of excreta of two patients was found to be 50 and 60 days respectively. These values are similar to the biologicalmore » half- lives obtained by long term whole-body counting studies. The distribution of Cs/ sup 137/ in man is fairly uniform in the soft tissues and the concentration decreases with time at different rates. Attempts to enhance the excretion rate of Cs/sup 137/ with diuretics, corticosteroids, and ion exchange resins were unsuccessful. (auth)« less
Bone growth and calcium balance during simulated weightlessness in the rat
NASA Technical Reports Server (NTRS)
Roer, Robert D.; Dillaman, Richard M.
1990-01-01
Rats, age 28 days, experiencing tail suspension in modified metabolic cages for 1, 2, and 3 wk were compared with littermate controls. Food and water consumption, urinary and fecal Ca excretion, and serum Ca were measured; hearts, fore- and hindlimb bones, skulls, and mandibles were removed for determination of wet, dry, and ash weights and Ca concentration and for histological examination. Weight gain and Ca intake and excretion were the same for both groups; both displayed net Ca gain. Suspended rats had significantly lower wet, dry, and ash weights of femora and tibiae. Dry weights of the humeri and radii/ulnae were moderately higher, and the skull and mandible dry and ash weights were significantly higher in suspended than in control rats. Cortical thickness of the femur, but not humerus, was less in suspended rats. The data are consistent with the hypothesis that bone growth is influenced by the cardiovascular changes associated with tail suspension.
Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats
Lee, Jeong-A; Kim, Mi-Kyung; Paek, Hee-Jeong; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Jeong, Jayoung; Choi, Soo-Jin
2014-01-01
Purpose The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods Silica nanoparticles of two different sizes (20 nm and 100 nm) were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ distribution was not affected by particle size or animal sex. In vivo, silica nanoparticles were found to retain their particulate form, although more decomposition was observed in kidneys, especially for 20 nm particles. Urinary and fecal excretion pathways were determined to play roles in the elimination of silica nanoparticles, but 20 nm particles were secreted more rapidly, presumably because they are more easily decomposed. These findings will be of interest to those seeking to predict potential toxicological effects of silica nanoparticles on target organs. PMID:25565843
Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters[S
Dong, Bin; Young, Mark; Liu, Xueqing; Singh, Amar Bahadur; Liu, Jingwen
2017-01-01
The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-cholesterol (HDL-C) homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects have not yet been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR-modulated gene and the major receptor for HDL-C. We investigated the effects of OCA on hepatic SR-BI expression and correlated such effects with plasma HDL-C levels and hepatic cholesterol efflux in hyperlipidemic hamsters. We demonstrated that OCA induced a time-dependent reduction in serum HDL-C levels after 14 days of treatment, which was accompanied by a significant reduction of liver cholesterol content and increases in fecal cholesterol in OCA-treated hamsters. Importantly, hepatic SR-BI mRNA and protein levels in hamsters were increased to 1.9- and 1.8-fold of control by OCA treatment. Further investigations in normolipidemic hamsters did not reveal OCA-induced changes in serum HDL-C levels or hepatic SR-BI expression. We conclude that OCA reduces plasma HDL-C levels and promotes transhepatic cholesterol efflux in hyperlipidemic hamsters via a mechanism involving upregulation of hepatic SR-BI. PMID:27940481
Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters.
Dong, Bin; Young, Mark; Liu, Xueqing; Singh, Amar Bahadur; Liu, Jingwen
2017-02-01
The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-cholesterol (HDL-C) homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects have not yet been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR-modulated gene and the major receptor for HDL-C. We investigated the effects of OCA on hepatic SR-BI expression and correlated such effects with plasma HDL-C levels and hepatic cholesterol efflux in hyperlipidemic hamsters. We demonstrated that OCA induced a time-dependent reduction in serum HDL-C levels after 14 days of treatment, which was accompanied by a significant reduction of liver cholesterol content and increases in fecal cholesterol in OCA-treated hamsters. Importantly, hepatic SR-BI mRNA and protein levels in hamsters were increased to 1.9- and 1.8-fold of control by OCA treatment. Further investigations in normolipidemic hamsters did not reveal OCA-induced changes in serum HDL-C levels or hepatic SR-BI expression. We conclude that OCA reduces plasma HDL-C levels and promotes transhepatic cholesterol efflux in hyperlipidemic hamsters via a mechanism involving upregulation of hepatic SR-BI.
Connor, W E; Lin, D S
1974-04-01
The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia. To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat. Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast. In some instances [1alpha-(3)H]cholesterol was the radioactive marker. The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol. The amount of absorbed and reexcreted labeled cholesterol proved negligible. Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days. Plasma specific activity curves were usually maximal at 48 h. Normal subjects absorbed 44.5+/-9.3 (SD) of the administered cholesterol (range 25.9-60.3). Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 47.6+/-12.6% (range 29.3-67.3). Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (42.1+/-9.3 vs. 48.9+/-9.8%). Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk. At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered. Cholesterol absorption was 42.3+/-6.0% and 45.4+/-8.3% for the two dietary periods, respectively. The absolute cholesterol absorption was linearly related to the amount of cholesterol in the test meal, and absorption was not affected by background diets high or low in cholesterol content.
Tsuruya, Kazuhiko; Yoshida, Hisako; Nagata, Masaharu; Kitazono, Takanari; Iseki, Kunitoshi; Iseki, Chiho; Fujimoto, Shouichi; Konta, Tsuneo; Moriyama, Toshiki; Yamagata, Kunihiro; Narita, Ichiei; Kimura, Kenjiro; Kondo, Masahide; Asahi, Koichi; Kurahashi, Issei; Ohashi, Yasuo; Watanabe, Tsuyoshi
2015-12-01
The impact of the triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio on chronic kidney disease (CKD) is unclear. Longitudinal cohort study. 124,700 participants aged 39 to 74 years in the Japanese Specific Health Check and Guidance System, including 50,392 men, 74,308 women, 102,900 without CKD, and 21,800 with CKD. Quartiles of TG:HDL-C ratio. Changes in estimated glomerular filtration rate (eGFR) and urinary protein excretion during the 2-year study period. Incident CKD in participants without CKD, and progression of CKD in participants with CKD. In the entire study population, higher quartile of TG:HDL-C ratio at baseline was significantly associated with greater decline in eGFR and increase in urinary protein excretion during the 2-year study period, even after adjustment for confounding factors. A higher ratio was associated with higher risk of incident CKD in participants without CKD and higher risk of rapid decline in eGFR and increase in urinary protein excretion in participants with CKD. Higher TG:HDL-C ratio was more strongly associated with decline in eGFR (P for interaction = 0.002) and with incident CKD (P for interaction = 0.05) in participants with diabetes than without diabetes. Short observation period and single measurement of all variables. A higher TG:HDL-C ratio affects the decline in eGFR and incidence and progression of CKD in the Japanese population. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Ohtsu, Yoshiaki; Susaki, Yoko; Noguchi, Kiyoshi
2018-05-10
The helicase-primase inhibitor amenamevir (ASP2151) is a novel therapeutic agent which has been approved for the treatment of herpes zoster. The present study examined the pharmacokinetic profile of amenamevir in rodents and compared it with data from the literature of past and current established therapies (acyclovir and valaciclovir) to provide additional data to facilitate drug discovery and proper drug use. In situ absorption, blood and plasma radioactivity concentrations, tissue distribution, and excretion were determined using liquid scintillation counting. Plasma amenamevir concentrations were measured using a validated chromatographic method. Chemical structures of in vivo metabolites were investigated using liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. Amenamevir, after single intravenous administration to mice, had an elimination half-life of 2 h. Bioavailability was 40% after single oral administration. In situ absorption data indicated that amenamevir is mainly absorbed in the small intestine. The main component in mouse plasma was amenamevir, accounting for 87.9% of amenamevir-derived components. Our results suggest that the main elimination pathway in mice is oxidative metabolism at a methyl group and a 1,2,3-trisubstituted benzene ring followed by biliary and fecal excretion. Following oral administration of 14 C-amenamevir to mice, 100.63% of the dose (10.06% in urine and 90.46% in feces) was excreted by 96 h post-dose. The underlying mechanism of the improved pharmacokinetic profile of amenamevir was linked to an improved absorption ratio (not hepatic availability) compared to acyclovir, and qualitative differences in elimination (slow metabolism of amenamevir vs rapid urinary excretion of acyclovir/valaciclovir).
Secnidazole for control of giardiasis in dairy calves.
Volpato, Andreia; Fortuoso, Bruno F; Campigotto, Gabriela; Glombowsky, Patrícia; Bottari, Nathieli B; Lopes, Leandro S; Da Silva, Aleksandro Schafer
2018-06-01
The aim of this study was to verify whether secnidazole, given in a single oral dose (10 mg/kg), decreases or eliminates the excretion of Giardia duodenalis cysts. Holstein calves were raised from birth to 15 ± 2 days of age in individual stalls. Subsequently, 12 calves were grouped and housed in collective stalls. After seven days (day of life 21), we collected stool samples directly from the rectal ampulla in order to determine the degree of parasitic infection. Fecal examination was performed by a centrifugal-flotation technique, which allows for visualization and quantification of G. duodenalis cysts. After division into control and treatment groups, six animals were treated with one 400 mg secnidazole capsule. The first stool collection following treatment was performed on day 5 and the second on day 30. This experiment was repeated at 15 days, with a total of 24 calves studied. Animals on the farm where the experiment was conducted often suffer from giardiasis, despite hygiene care (disinfection) and adequate facilities. All 24 calves were excreting G. duodenalis cysts prior to starting treatment. Five days after receiving the treatment, animals in the experiment group were Giardia-negative, i.e., they did not excrete parasite cysts, whereas calves in the control group continued to excrete cysts. After 30 days of treatment, the stool of most treated animals (83.3%) remained free of G. duodenalis cysts. Therefore, we believe that secnidazole was 100% effective in eliminating the excretion of Giardia duodenalis cysts. Copyright © 2018 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cenedella, R.J.; Fleschner, C.R.
The origin of the cholesterol needed by the cornea for growth and cell turnover was addressed by comparing absolute rates of sterol synthesis with rates of sterol accumulation during early development of the rabbit. Linearity of incorporation of {sup 3}H{sub 2}O and ({sup 14}C)mevalonate into digitonin-precipitable sterols with time of incubation in vitro and a lack of accumulation of {sup 14}C in intermediates of sterol biosynthesis indicated that tritiated water can validly be used to measure rates of sterol synthesis by the cornea. The rate of sterol synthesis per unit weight of rabbit cornea was constant between 14 and 60more » days of age at an average 1.03 nmol of {sup 3}H of {sup 3}H{sub 2}O incorporated/mg dry cornea per 8 h. Essentially all of the synthesized cholesterol and most of the cholesterol mass was present in corneal epithelium. The cumulative sterol synthesized over the 46-day period studied exceeded the observed rate of cholesterol accumulation by sixfold. Cholesterol synthesized in excess of the growth requirement was likely used to support turnover of the epithelium which was estimated at 9 days. Removal of cholesterol from the cornea by excretion into tear fluid and clearance by high density lipoproteins are also considered.« less
The influence of serial fecal sampling on the diagnosis of giardiasis in humans, dogs, and cats.
Uchôa, Flávia Fernandes de Mendonça; Sudré, Adriana Pittella; Macieira, Daniel de Barros; Almosny, Nádia Regina Pereira
2017-08-24
Giardia infection is a common clinical problem in humans and pets. The diagnosis of giardiasis is challenging as hosts intermittently excrete protozoan cysts in their feces. In the present study, we comparatively evaluated two methods of serial fecal sampling in humans, dogs, and cats from Rio de Janeiro, Brazil. The Faust et al. technique was used to examine fecal specimens collected in triplicate from 133 patients (52 humans, 60 dogs, and 21 cats). Specimens from 74 patients were received from the group assigned to carry out sampling on consecutive days - 34 humans, 35 dogs, and 5 cats, and specimens from 59 patients were received from the group assigned to carry out sampling on non-consecutive, separate days - 18 human beings, 25 dogs, and 16 cats. G. duodenalis cysts were found in stools of 30 individuals. Multiple stool sampling resulted in an increase in the number of samples that were positive for Giardia in both groups. The authors therefore conclude that multiple stool sampling increases the sensitivity of the Faust et al . technique to detect G. duodenalis cysts in samples from humans, cats and dogs.
Wei, Xiao; Lu, Zongshi; Yang, Tao; Gao, Peng; Chen, Sijiao; Liu, Daoyan; Zhu, Zhiming
2018-03-16
High salt consumption is a major risk factor for hypertension, and sodium homeostasis is regulated by both intestinal sodium absorption and urinary sodium excretion. Chronic caffeine intake has been reported to attenuate salt-sensitive hypertension by promoting urinary sodium excretion; however, its exact role in intestinal sodium absorption remains unknown. Here, we investigated whether and how chronic caffeine consumption antagonizes salt-sensitive hypertension by inhibiting intestinal sodium absorption. Dahl salt-sensitive rats were fed 8% NaCl chow and 0.1% caffeine in their drinking water for 15 days. The blood pressure and fecal sodium content were measured. The effect of caffeine on the movement of Cl- in enterocyte cells was determined with the Ussing chamber assay. Rats that were treated with caffeine displayed significantly lower mean blood pressure and higher fecal sodium content than the controls. Consistent with these findings, caffeine intake decreased fluid absorption by the intestine in the fluid perfusion experiment. Further, the results from the Ussing chamber assay indicated that caffeine promoted Cl- secretion through enterocyte apical cystic fibrosis transmembrane conductance regulator (CFTR), and thus inhibited sodium absorption. Moreover, depletion of cAMP or inhibition of CFTR completely abolished the effect of caffeine on Cl- secretion. The results indicate that chronic caffeine consumption reduces sodium absorption by promoting CFTR-mediated Cl- secretion in the intestine, which contributes to the anti-hypertensive effect of caffeine in salt-sensitive rats. © 2018 The Author(s). Published by S. Karger AG, Basel.
Frommelt, Lena; Bielohuby, Maximilian; Stoehr, Barbara J M; Menhofer, Dominik; Bidlingmaier, Martin; Kienzle, Ellen
2014-01-01
Ketogenic low-carbohydrate, high-fat (LCHF) diets reduce growth and bone mineral density in children with epilepsy and in rats. Part of this effect might be due to a reduced availability of calcium in high-fat diets. The aim of this study was to determine mineral digestibility by total collection method in LCHF diets compared with a chow diet and a standard high-fat diet (HFD, high in fat and carbohydrates). Twelve-wk-old male Wistar rats were pair-fed isoenergetic amounts of either six different LCHF diets based on tallow and casein (crude fat 75%-50%, crude protein 10%-35%), with chow or with a HFD diet. Mineral-to-energy ratio was matched in all diets. Circulating parathyroid hormone was measured by immunoassay. The apparent digestibility of calcium was reduced in all HFDs (high-fat diets, LCHF diets and the HFD diet) by at least 30% compared with the chow diet (P < 0.001). Fecal calcium excretion correlated positively with fecal fat excretion, presumably because of formation of calcium soaps. Apparent digestibility of phosphorous was higher in all HFDs. This resulted in a decrease of the ratio of apparently digested calcium to apparently digested phosphorous in all HFDs below a ratio of 1:1. Plasma parathyroid hormone was not affected by any diet. The alteration of apparent calcium and phosphorus digestibility may affect the impact of HFDs on bone metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.
Voellmy, Irene K; Goncalves, Ines Braga; Barrette, Marie-France; Monfort, Steven L; Manser, Marta B
2014-11-01
Adrenal hormones likely affect anti-predator behavior in animals. With experimental field studies, we first investigated associations between mean fecal glucocorticoid metabolite (fGC) excretion and vigilance and with behavioral responses to alarm call playbacks in free-ranging meerkats (Suricata suricatta). We then tested how vigilance and behavioral responses to alarm call playbacks were affected in individuals administered exogenous cortisol. We found a positive association between mean fGC concentrations and vigilance behavior, but no relationship with the intensity of behavioral responses to alarm calls. However, in response to alarm call playbacks, individuals administered cortisol took slightly longer to resume foraging than control individuals treated with saline solution. Vigilance behavior, which occurs in the presence and absence of dangerous stimuli, serves to detect and avoid potential dangers, whereas responses to alarm calls serve to avoid immediate predation. Our data show that mean fGC excretion in meerkats was associated with vigilance, as a re-occurring anti-predator behavior over long time periods, and experimentally induced elevations of plasma cortisol affected the response to immediate threats. Together, our results indicate an association between the two types of anti-predator behavior and glucocorticoids, but that the underlying mechanisms may differ. Our study emphasizes the need to consider appropriate measures of adrenal activity specific to different contexts when assessing links between stress physiology and different anti-predator behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.
Effects of Astaxanthin on Reverse Cholesterol Transport and Atherosclerosis in Mice
Zou, Tang-Bin; Zhu, Shan-Shan; Luo, Fei; Li, Wei-Qiao
2017-01-01
High plasma level of HDL-cholesterol (HDL-C) has been consistently associated with a decreased risk of atherosclerosis (AS); thus, HDL-C is considered to be an antiatherogenic lipoprotein. The development of novel therapies to enhance the atheroprotective properties of HDL may have the possibility of further reducing the residual AS risk. Reverse cholesterol transport (RCT) is believed to be a primary atheroprotective activity of HDL, which has been shown to promote the efflux of excess cholesterol from macrophage-derived foam cells via ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) and then transport it back to the liver for excretion into bile and eventually into the feces. In the current study, we investigated the effects of astaxanthin on RCT and AS progression in mice. The results showed that short- and long-term supplementation of astaxanthin promote RCT in C57BL/6J and ApoE−/− mice, respectively. Moreover, astaxanthin can relieve the plaque area of the aortic sinus and aortic cholesterol in mice. These findings suggest that astaxanthin is beneficial for boosting RCT and preventing the development of AS. PMID:29226138
Kim, Kang Min; Kim, Myo Jeong; Kang, Jae Seon
2009-12-01
The pharmacokinetics of decursin and decursinol angelate (D/DA) was investigated in male SD rats following oral and intravenous administration. D/DA and metabolites obtained from in vitro samples were evaluated by LC/MS. The level of D/DA and metabolized decursinol in the blood following oral and intravenous administration declined according to first-order kinetics, with T1/2 values of 56.67, 58.01 and 57.22 h, respectively, being observed after administration of a dose of 2 mg/kg body weight. The large intestine was the major site of disposition following oral administration. These data indicate that D/DA is rapidly absorbed from the gastrointestinal tract. In in vitro experiment utilizing liver microsomal protein, the major metabolic reaction of D/DA occurred to change decursinol. The cumulative biliary, urinary, and fecal excretion of D/DA in bile duct-cannulated rats was 36.10+/-2.9, 25.35+/-3.8, and 34.20+/-3.2%, respectively, at 72 h after administration. These results indicate that the absorption of D/DA is almost complete, and that its metabolites are primarily excreted into feces through the bile. These results indicate that D/DA is subject to enterohepatic circulation.
Hindgut Innate Immunity and Regulation of Fecal Microbiota through Melanization in Insects*
Shao, Qimiao; Yang, Bing; Xu, Qiuyun; Li, Xuquan; Lu, Zhiqiang; Wang, Chengshu; Huang, Yongping; Söderhäll, Kenneth; Ling, Erjun
2012-01-01
Many insects eat the green leaves of plants but excrete black feces in an as yet unknown mechanism. Insects cannot avoid ingesting pathogens with food that will be specifically detected by the midgut immune system. However, just as in mammals, many pathogens can still escape the insect midgut immune system and arrive in the hindgut, where they are excreted out with the feces. Here we show that the melanization of hindgut content induced by prophenoloxidase, a key enzyme that induces the production of melanin around invaders and at wound sites, is the last line of immune defense to clear bacteria before feces excretion. We used the silkworm Bombyx mori as a model and found that prophenoloxidase produced by hindgut cells is secreted into the hindgut contents. Several experiments were done to clearly demonstrate that the blackening of the insect feces was due to activated phenoloxidase, which served to regulate the number of bacteria in the hindgut. Our analysis of the silkworm hindgut prophenoloxidase discloses the natural secret of why the phytophagous insect feces is black and provides insight into hindgut innate immunity, which is still rather unclear in mammals. PMID:22375003
Willis, Jessica E; McClure, J T; McClure, Carol; Spears, Jonathan; Davidson, Jeff; Greenwood, Spencer J
2014-03-03
A variety of human enteropathogens, including viruses, bacteria, and parasites, have been shown to bioaccumulate in suspension-feeding bivalve shellfish. Cryptosporidium parvum is a zoonotic protozoan parasite that has been detected in many shellfish species within both fecally contaminated and clean oyster growing areas across the globe. For this study, C. parvum oocysts (1000 and 10,000) were spiked into 10 L of water in static tank systems housing Crassostrea virginica. Oysters were either held in the contaminated aquaria for 7 days of exposure or were exposed for 24h and subsequently placed in a clean static tank system for the remainder of the trial. Individual oysters, fecal material, and tank water were analyzed for oocysts up to 7 days post-exposure via direct immunofluorescence. Oysters held under chronic exposure conditions gradually accumulated oocysts (1.5 or 34.4 oocysts/oyster/day for low or high dose exposure groups, respectively) between days 1 and 7, with an exponential uptake in oocysts observed within the first 24h post-exposure (mean uptake of 29.6 or 241.9 oocysts/oyster, respectively). Oysters that were transferred to clean water after 24h were capable of slowly depurating oocysts, following a linear trend. During chronic exposure trials 48-49% of the total spiked inoculum was recovered from oyster tissue, whereas 4.8-5.9% and 38-40% was recovered from tank water and from fecal material at day 7, respectively. In acute exposure trials, 30-31% of the total tank inoculum was found in oysters, suggesting that chronically exposed oysters were likely re-filtering some oocysts. Examinations of oyster fecal material from acute exposures revealed that 72-82% of oocysts recovered were already excreted at the time of oyster transfer (day 1), with only 18-28% being excreted during the static depuration phase. These data support that although most C. parvum oocysts are removed by C. virginica oysters within 24h, elimination after this point occurs slowly. Additionally, chronic exposures demonstrate that wild or cultured oysters in saline environments that are frequently exposed to sources of Cryptosporidium may be unable to eliminate the parasites at a rate that balances initial uptake. Copyright © 2013 Elsevier B.V. All rights reserved.
Queipo-Ortuño, María Isabel; Boto-Ordóñez, María; Murri, Mora; Gomez-Zumaquero, Juan Miguel; Clemente-Postigo, Mercedes; Estruch, Ramon; Cardona Diaz, Fernando; Andrés-Lacueva, Cristina; Tinahones, Francisco J
2012-06-01
Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota, and they focused mainly on single polyphenol molecules and select bacterial populations. The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits. Ten healthy male volunteers underwent a randomized, crossover, controlled intervention study. After a washout period, all of the subjects received red wine, the equivalent amount of de-alcoholized red wine, or gin for 20 d each. Total fecal DNA was submitted to polymerase chain reaction(PCR)-denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota. Several biochemical markers were measured. The dominant bacterial composition did not remain constant over the different intake periods. Compared with baseline, the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides-Eubacterium rectale groups (P < 0.05). In parallel, systolic and diastolic blood pressures and triglyceride, total cholesterol, HDL cholesterol, and C-reactive protein concentrations decreased significantly (P < 0.05). Moreover, changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number. This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans, which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet. This trial was registered at controlled-trials.com as ISRCTN88720134.
Studies of endocrine and affective functions in complex flight manoeuvres.
Pinter, E J; Peterfy, G; Cleghorn, J M
1975-01-01
Endocrine and metabolic changes, as well as affective functions, were studied in eight healthy volunteers anticipating and executing a prearranged sequence of aerobatic flight. Control measurements were made at complete physical and mental rest. The following were determined: anxiety and hostility levels, blood glucose, cholesterol, triglyceride, plasma free fatty acids (FFA), serum thyroxine (T4), corticosteroids, prolactin, growth hormone, immunoreactive insulin and urinary excretion of VMA. The pattern of response was uniform in all subjects. Significant changes were seen in plasma FFA, corticosteroids, growth hormone and immunoreactive insulin following aerobatic flight. Anticipation of flight induced anxiety arousal and significant directional changes in plasma FFA, corticosteroids, as well as in VMA excretion. Hostility scores were highest immediately upon termination of flight.
The metabolism of plant sterols is disturbed in postmenopausal women with coronary artery disease.
Gylling, Helena; Hallikainen, Maarit; Rajaratnam, Radhakrishnan A; Simonen, Piia; Pihlajamäki, Jussi; Laakso, Markku; Miettinen, Tatu A
2009-03-01
In postmenopausal coronary artery disease (CAD) women, serum plant sterols are elevated. Thus, we investigated further whether serum plant sterols reflect absolute cholesterol metabolism in CAD as in other populations and whether the ABCG5 and ABCG8 genes, associated with plant sterol metabolism, were related to the risk of CAD. In free-living postmenopausal women with (n = 47) and without (n = 62) CAD, serum noncholesterol sterols including plant sterols were analyzed with gas-liquid chromatography, cholesterol absorption with peroral isotopes, absolute cholesterol synthesis with sterol balance technique, and bile acid synthesis with quantitating fecal bile acids. In CAD women, serum plant sterol ratios to cholesterol were 21% to 26% (P < .05) higher than in controls despite similar cholesterol absorption efficiency. Absolute cholesterol and bile acid synthesis were reduced. Only in controls were serum plant sterols related to cholesterol absorption (eg, sitosterol; in controls: r = 0.533, P < .001; in CAD: r = 0.296, P = not significant). However, even in CAD women, serum lathosterol (relative synthesis marker) and lathosterol-cholestanol (relative synthesis-absorption marker) were related to absolute synthesis and absorption percentage (P range from .05 to <.001) similarly to controls. Frequencies of the common polymorphisms of ABCG5 and ABCG8 genes did not differ between coronary and control women. In conclusion, plant sterol metabolism is disturbed in CAD women; so serum plant sterols only tended to reflect absolute cholesterol absorption. Other relative markers of cholesterol metabolism were related to the absolute ones in both groups. ABCG5 and ABCG8 genes were not associated with the risk of CAD.
Ezetimibe prevents the formation of estrogen-induced cholesterol gallstones in mice
de Bari, Ornella; Wang, Helen H.; Portincasa, Piero; Paik, Chang-Nyol; Liu, Min; Wang, David Q.-H.
2014-01-01
Background Estrogen is an important risk factor for cholesterol cholelithiasis not only in women of childbearing age taking oral contraceptives and postmenopausal women undergoing hormone replacement therapy, but also in male patients receiving estrogen therapy for prostatic cancer. In women, hormonal changes occurring during pregnancy markedly increase the risk of developing gallstones. We investigated whether the potent cholesterol absorption inhibitor ezetimibe could prevent the formation of estrogen-induced cholesterol gallstones in mice. Design Following ovariectomy, female AKR mice were implanted subcutaneously with pellets releasing 17β-estradiol at 6 μg/day and fed a lithogenic diet supplemented with ezetimibe in doses of 0 or 8 mg/kg/day for 8 weeks. Cholesterol crystallization and gallstone prevalence, lipid concentrations and composition in bile, and biliary lipid output were analyzed by physical-chemical methods. Intestinal cholesterol absorption efficiency was determined by fecal dual-isotope ratio methods. Results Ezetimibe inhibited intestinal cholesterol absorption, while significantly reducing hepatic secretion of biliary cholesterol. Consequently, bile was desaturated through the formation of numerous unsaturated micelles and gallstones were prevented by ezetimibe in mice exposed to high doses of estrogen and fed the lithogenic diet. Ezetimibe did not influence mRNA levels of the classical estrogen receptors α (ERα) and ERβ, as well as a novel estrogen receptor the G protein-coupled receptor 30 (GPR30) in the liver. Conclusions Ezetimibe protects against the estrogen-mediated lithogenic actions on gallstone formation in mice. Our finding may provide an efficacious novel strategy for the prevention of cholesterol gallstones in high-risk subjects, especially those exposed to high levels of estrogen. PMID:25303682
Effects of Chronic 2.0% and 0.7% CO2 Exposures on the Well-Being, Growth and Renal Function of Rats
NASA Technical Reports Server (NTRS)
Lang, C. K.; Alexander, R. A.; Steele, M. K.; Wade, C. E.; Hargens, Alan R. (Technical Monitor)
1995-01-01
On the Space Shuttle and MIR, mean CO2 levels have been 0.3% which is ten times that of normal air. There have also been extended periods with levels of 0.7% CO2 with peak concentrations at 2.0%. The Space Station program had proposed that CO2 concentration levels be maintained, on average, at 0.7%, and not to exceed 1.0%. To ensure that these levels of CO2 would not compromise the integrity of the science performed on the Space Station, the effects of chronic exposure of rats to 2.0% and 0.7% CO2 were investigated. Ten male rats per group were placed in individual metabolic cages for monitoring of food and water consumption, as well as fecal and urine production. Cages were placed in a large (4W x 10L x 4H ft.) plexiglass chamber with a controlled atmospheric environment. Following 7 days of cage adaptation, animals were exposed to experimental (2.0% or 0.7% CO2) or control (ambient air) conditions for 30 days. Daily body weight, food and water intake, and fecal and urine excretions were measured for the last three days of adaptation and the first ten days of exposure and then every three to four days for the remaining three weeks. Urine was measured for pH and total CO2. During 2.0% and 0.7% CO2 exposures, animal growth, fecal production and food and water consumption were within normal ranges. Urine excretion was significantly (p less than 0.05) higher in both experimental groups compared to controls. Urine pH of animals exposed to 2.0% CO2 was decreased by 0.32 over the first 6 days of exposure, followed by a 0.63 increase by day 30. In animals exposed to 0.7% CO2, urine pH did not decrease early in the exposure period, but did increase by 0.37 by day 30. Urine CO2 excretion did not change the first 6 days of exposure, but significantly increased in both 2.0% and 0.7% CO2 by day 30 (897 and 402 mmol/day, respectively). These results of chronic exposure to 2.0% and 0.7% CO2 are consistent with renal compensation in response to an altered acid-base homeostasis. These findings may impact science conducted on the Space Shuttle or the Space Station if CO2 concentrations reach 0.7%.
Del Pozo, G; Davalos, P; Yamori, Y
1990-01-01
We examined the specific hypotheses linking the intake of sodium, potassium, calcium, magnesium, and protein to blood pressure (BP) and the relationship between dietary factors and mortality from the major cardiovascular diseases (CVD) in the Ecuadorian populations. Two Ecuadorian populations, the urban and the rural, were selected from Quito and Vilcabamba, respectively. From Quito: 87 men and 83 women; from Vilcabamba: 71 men and 91 women aged 50-54 were randomly selected for BP measurement, 24-h urine collection, and blood sampling according to the Cardiovascular Disease and Alimentary Comparison (CARDIAC) Study protocol. Samples were analyzed at CARDIAC center in Izumo, Japan. Mean systolic blood pressure (SBP) was not much different in the two populations, but mean diastolic blood pressure (DBP) and body mass index (BMI) were significantly lower in Vilcabamba (p less than 0.001). Mortality from stroke was higher in Vilcabamba, whereas coronary death rate was higher in Quito. Both sodium intake and sodium/potassium ratio were higher in Vilcabamba (p less than 0.001). Protein intake and serum cholesterol were higher in Quito (p less than 0.001). Urinary taurine excretion was higher in Quito. There was no difference in W3/W6 fatty acids ratio between the two populations. Multiple regression analyses of intracommunity correlation indicated that both SBP and DBP were highly significantly related with BMI in Quito and that urinary excretions were inversely related to SBP. Serum cholesterol was positively related to coronary death rate. Mortality from stroke was inversely related to both serum cholesterol and protein and was positively related to salt consumption.
Krawczyk, Marcin; Lütjohann, Dieter; Schirin-Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Miquel, Juan Francisco
2012-05-01
In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol GSD. Copyright © 2012 American Association for the Study of Liver Diseases.
Perez-Ternero, Cristina; Claro, Carmen; Parrado, Juan; Herrera, Maria Dolores; Alvarez de Sotomayor, Maria
2017-05-01
Rice bran is a by-product of rice milling and is rich in bioactive molecules such as γ-oryzanol, phytosterols, and tocotrienols. The rice bran enzymatic extract (RBEE) previously showed vessel remodeling prevention and lipid-lowering, antioxidant, anti-inflammatory, and antiapoptotic activities. The aim of this study was to identify RBEE hypolipidemic mechanisms and to study the effects of RBEE on the progression of atherosclerosis disease and linked vascular dysfunction and liver steatosis in apolipoprotein E-knockout (ApoE-/-) mice fed low- or high-fat (LFD, HFD, respectively) and cholesterol diets. ApoE-/- mice were fed LFD (13% kcal) or HFD (42% kcal) supplemented or not supplemented with 1 or 5% RBEE (w/w) for 23 wk. Then, serum, aorta, liver, and feces were collected and flash frozen for further analysis. RBEE supplementation of HFD improved serum values by augmenting high-density lipoprotein cholesterol and preventing total cholesterol and aspartate aminotransferase increase. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was attenuated (1 and 5% RBEE) and cholesterol excretion increased (5% RBEE). Diet supplementation with 5% RBEE reduced plaque development regardless of the diet. In HFD-fed mice, both doses of RBEE reduced lipid deposition and macrophage infiltration in the aortic sinus and downregulated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. None of these effects was observed in mice fed LFD. Liver steatosis was reduced by RBEE supplementation of LFD (1% RBEE) and HFD (1 and 5% RBEE) and nuclear peroxisome proliferator-activated receptor-α expression upregulated in the HDF 5% RBEE group. Regular consumption of RBEE-supplemented HFD reduced plaque development and liver steatosis by decreasing inflammation and hyperlipidemia through an HMG-CoA reductase activity and lipid excretion-related mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.
Haack, Sheridan K.; Duris, Joseph W.; Kolpin, Dana W.; Fogarty, Lisa R.; Johnson, Heather E.; Gibson, Kristen E.; Focazio, Michael J.; Schwab, Kellogg J.; Hubbard, Laura E.; Foreman, William T.
2015-01-01
Manure spills to streams are relatively frequent, but no studies have characterized stream contamination with zoonotic and veterinary pathogens, or fecal chemicals, following a spill. We tested stream water and sediment over 25 days and downstream for 7.6 km for: fecal indicator bacteria (FIB); the fecal indicator chemicals cholesterol and coprostanol; 20 genes for zoonotic and swine-specific bacterial pathogens by presence/absence polymerase chain reaction (PCR) for viable cells; one swine-specific Escherichia coli toxin gene (STII) by quantitative PCR (qPCR); and nine human and animal viruses by qPCR, or reverse-transcriptase qPCR. Twelve days post-spill, and 4.2 km downstream, water concentrations of FIB, cholesterol, and coprostanol were 1-2 orders of magnitude greater than those detected before, or above, the spill, and genes indicating viable zoonotic or swine-infectious Escherichia coli, were detected in water or sediment. STII increased from undetectable before, or above the spill, to 105 copies/100 mL water 12 days post-spill. Thirteen of 14 water (8/9 sediment) samples had viable STII-carrying cells post-spill. Eighteen days post-spill porcine adenovirus and teschovirus were detected 5.6 km downstream. Sediment FIB concentrations (per gram wet weight) were greater than in water, and sediment was a continuous reservoir of genes and chemicals post-spill. Constituent concentrations were much lower, and detections less frequent, in a runoff event (200 days post-spill) following manure application, although the swine-associated STII and stx2e genes were detected. Manure spills are an underappreciated pathway for livestock-derived contaminants to enter streams, with persistent environmental outcomes, and the potential for human and veterinary health consequences.
Sato, M; Yoshida, S; Nagao, K; Imaizumi, K
2000-06-01
The exogenously hypercholesterolemic (ExHC) rat is a strain segregated from SD rats with a high response to dietary cholesterol. To understand the underlying mechanism(s) for this hypercholesterolemia, the interactive effects of dietary fatty acid and the susceptibility of rats to dietary cholesterol on the serum cholesterol concentration and hepatic mRNA abundance of the low-density lipoprotein (LDL) receptor, cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) and 3-hydroxyl-3methylglutaryl (HMG) CoA reductase were examined. Both strains were fed on a diet supplemented with 10% each of olive, safflower or coconut oil with or without the addition of 1% cholesterol for one week. The ExHC rats fed on olive, safflower and coconut oil in combination with cholesterol respectively resulted in a 3.5-, 2.0- and 2.1-fold higher serum cholesterol concentration than that in the animals fed on the corresponding dietary fats without any supplementation of cholesterol (p < 0.01 by dietary cholesterol or type of fat). The dietary cholesterol dependent-elevation of serum cholesterol in the SD rats was less than 1.5-fold (p<0.01) and there was no dietary fat effect. The ExHC rats fed on the safflower oil-containing diet supplemented with cholesterol resulted in a higher mRNA abundance of the LDL receptor and 7alpha-hydroxylase than in the corresponding fat-fed rats without cholesterol (p<0.05). There was no dietary cholesterol-dependent change of mRNA abundance in either strain fed on olive or coconut oil, except for a decreased abundance of HMG CoA reductase mRNA in the olive oil-fed ExHC rats and coconut oil-fed Sprague-Dawley (SD) rats (p<0.05). These results indicate that the hepatic mRNA abundance of the LDL receptor and of 7alpha-hydroxylase depended on the dietary combination of cholesterol and a fatty acid and suggest that a linoleic acid-rich diet may alleviate exogenous hypercholesterolemia by activating the process involved in the hepatic uptake and biliary excretion of serum cholesterol.
Simons, Andrean L; Renouf, Mathieu; Murphy, Patricia A; Hendrich, Suzanne
2010-01-13
It was hypothesized that 5,7,4'-OH-flavonoids disappeared more rapidly from human fecal incubations and were less absorbable by humans than flavonoids without 5-OH moieties. Anaerobic fecal disappearance rates over 24 h were determined for 15 flavonoids in samples from 20 men and 13 women. In these anaerobic fecal mixtures, flavonoids with 5,7,4'-OH groups, genistein, apigenin, naringenin, luteolin, kaempferol, and quercetin (disappearance rate, k=0.46+/-0.10 h(-1)), and methoxylated flavonoids, hesperetin and glycitein (k=0.24+/-0.21 h(-1)), disappeared rapidly compared with flavonoids lacking 5-OH (e.g., daidzein, k=0.07+/-0.03 h(-1)). Apparent absorption of flavonoids that disappeared rapidly from in vitro fecal incubations, genistein, naringenin, quercetin, and hesperetin, was compared with that of daidzein, a slowly disappearing flavonoid, in 5 men and 5 women. Subjects ingested 104 micromol of genistein and 62 micromol of daidzein (soy milk), 1549 micromol of naringenin and 26 micromol of hesperetin (grapefruit juice), and 381 micromol of quercetin (onions) in three test meals, each separated by 1 week. Blood and urine samples were collected over 24 h after each test meal. Plasma flavonoid concentrations ranged from 0.01 to 1 microM. The apparent absorption, expressed as percentage of ingested dose excreted in urine, was significantly less for naringenin (3.2+/-1.7%), genistein (7.2+/-4.6%), hesperetin (7.3+/-3.2%), and quercetin (5.6+/-3.7%) compared with daidzein (43.4+/-15.5%, p=0.02). These data affirmed the hypothesis that the 5,7,4'-OH of flavonoids limited apparent absorption of these compounds in humans.
Sample treatment optimization for fish stool metabolomics.
Hano, Takeshi; Ito, Mana; Ito, Katsutoshi; Uchida, Motoharu
2018-06-07
Gut microbiota play an essential role in an organism's health. The fecal metabolite profiling content reflects these microbiota-mediated physiological changes in various organisms, including fish. Therefore, metabolomics analysis of fish feces should provide insight into the dynamics linking physiology and gut microbiota. However, metabolites are often unstable in aquatic environments, making fecal metabolites difficult to examine in fish. In this study, a novel method using gas chromatography-mass spectrometry (GC-MS) was developed and optimized for the preparation of metabolomics samples from the feces of the marine fish, red sea bream (Pagrus major). The preparation methodology was optimized, focusing on rinsing frequency and rinsing solvent. Feces (collected within 4 h of excretion) were rinsed three times with sterilized 2.5% NaCl solution or 3.0% artificial seawater (ASW). Among the 86 metabolites identified in the NaCl-rinsed samples, 57 showed superior recovery to that in ASW-rinsed samples, indicating that NaCl is a better rinsing solvent, particularly for amino acids, organic acids, and fatty acids. To evaluate rinsing frequency, fecal samples were rinsed with NaCl solution 0, 1, 3, or 5 times. The results indicate that three or more rinses enabled robust and stable detection of metabolites encapsulated within the solid fecal residue. Furthermore, these data suggest that rinsing is unnecessary when studying sugars, amino acids, and sterols, again highlighting the need for appropriate rinsing solvent and frequency. This study provides further insight into the use of fecal samples to evaluate and promote fish health during farming and supports the application of this and similar analyses to study the effects of environmental fluctuations and/or contamination. Copyright © 2018 Elsevier B.V. All rights reserved.
Khonmee, Jaruwan; Brown, Janine L; Rojanasthien, Suvichai; Thumasanukul, Dissakul; Kongphoemphun, Adisorn; Siriaroonrat, Boripat; Tipkantha, Wanlaya; Punyapornwithaya, Veerasak; Thitaram, Chatchote
2014-04-01
There is no information on the endocrinology of Chinese goral (Naemorhedus griseus), a high priority species for captive breeding and reintroduction in Thailand. This study characterized fecal androgen and glucocorticoid metabolites in male goral at Omkoi Wildlife Sanctuary to investigate seasonal relationships. Fecal samples were collected 3 days/week for 1 year from eight adult males. Mean androgen metabolite concentrations were greater (P<0.05) during the rainy season (289.82±9.18ng/g) and winter (224.09±11.97ng/g) compared to the summer (195.48±8.23ng/g), and were related to breeding activity. A similar pattern was observed for glucocorticoid concentrations (22.10±0.72ng/g compared to 21.98±0.98ng/g compared to 15.30±0.48ng/g), respectively, and this resulted in a positive correlation between the two hormones (P<0.05). There also were positive correlations between fecal androgen metabolite concentrations and temperature (P<0.05) and day length (P<0.05). In summary, this is the first study to assess endocrine function in male goral, and results showed seasonal variation in testicular and adrenal steroidogenic function, with greater activity in the rainy season and winter. Given that resources for captive male goral are consistent throughout the year, reproduction may be regulated primarily by photoperiod in this species. Copyright © 2014 Elsevier B.V. All rights reserved.
Errico, Teresa L; Méndez-Lara, Karen Alejandra; Santos, David; Cabrerizo, Núria; Baila-Rueda, Lucía; Metso, Jari; Cenarro, Ana; Pardina, Eva; Lecube, Albert; Jauhiainen, Matti; Peinado-Onsurbe, Julia; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco; Julve, Josep
2017-08-01
Diabesity and fatty liver have been associated with low levels of high-density lipoprotein cholesterol, and thus could impair macrophage-specific reverse cholesterol transport (m-RCT). Liver X receptor (LXR) plays a critical role in m-RCT. Abcg5/g8 sterol transporters, which are involved in cholesterol trafficking into bile, as well as other LXR targets, could be compromised in the livers of obese individuals. We aimed to determine m-RCT dynamics in a mouse model of diabesity, the db/db mice. These obese mice displayed a significant retention of macrophage-derived cholesterol in the liver and reduced fecal cholesterol elimination compared with nonobese mice. This was associated with a significant downregulation of the hepatic LXR targets, including Abcg5/g8. Pharmacologic induction of LXR promoted the delivery of total tracer output into feces in db/db mice, partly due to increased liver and small intestine Abcg5/Abcg8 gene expression. Notably, a favorable upregulation of the hepatic levels of ABCG5/G8 and NR1H3 was also observed postoperatively in morbidly obese patients, suggesting a similar LXR impairment in these patients. In conclusion, our data show that downregulation of the LXR axis impairs cholesterol transfer from macrophages to feces in db/db mice, whereas the induction of the LXR axis partly restores impaired m-RCT by elevating the liver and small intestine expressions of Abcg5/g8. Copyright © 2017 Elsevier Inc. All rights reserved.
Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili
2014-01-01
The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE−/−) mice. Eight-week-old ApoE−/− mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE−/− mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis. PMID:25261526
Mosele, Juana I; Gosalbes, María-José; Macià, Alba; Rubió, Laura; Vázquez-Castellanos, Jorge F; Jiménez Hernández, Nuria; Moya, Andrés; Latorre, Amparo; Motilva, María-José
2015-10-01
The purpose of the study was to evaluate the effect, regarding the metabolic and microbial profile of feces, of diet supplementation of healthy adults with pomegranate juice (PJ). Twelve healthy adults were recruited to the study, which consisted of the intake of 200 mL/day of PJ during 4 weeks. Feces were collected before and after the supplementation with PJ. Metabolites (phenolic catabolites, short-chain fatty acids, and fecal steroids) and microbial profile were analyzed at baseline and at 4 weeks. Fecal phenolic metabolites, 3-phenylpropionic acid, catechol, hydroxytyrosol, and urolithin A, showed a significant increase in their concentration after supplementation with PJ. Among fecal steroids, parallel to the significant increase of cholesterol concentration, a significant decrease of coprostanol was observed. Although no significant changes in the microbiota profile were observed, different relationships between initial microbiota and the metabolites produced were found. Catechol showed positive and negative correlation with Oscillospora and Paraprevotella genera, respectively, and 3-phenylpropionic acid was positively correlated with Odoribacter genus. Inclusion of PJ in the diet did not significantly alter the gut microbiota composition in healthy adults, but the individual bacterial composition could contribute to the generation of potential health-promoting phenolic metabolites. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Heijnen, M L; Beynen, A C
1997-09-01
To study the effect of resistant starch (RS) on the route of nitrogen excretion, we fed three groups of six cannulated piglets each a diet containing either uncooked resistant starch (RS2 ), retrograded resistant starch (RS3 ) or glucose. The use of piglets with a cannula at the end of the ileum allowed measurement of the amount of nitrogen that entered the colon. Ileal digesta, urine and feces were collected quantitatively and weighed, and dry matter, starch and nitrogen content were determined. We hypothesized that RS2 would lower colonic absorption of nitrogen when compared with RS3 , because RS2 may be more fermentable than RS3 , thus trapping more nitrogen in bacteria. The piglets fed RS3 had a significantly higher production of ileal digesta and feces than the piglets fed glucose or RS2 . In the piglets fed RS2 , 44% of the amount of RS fed was recovered in the ileal digesta; in the piglets fed RS3 , 71% was recovered. Thus, more fermentable material entered the colon in the RS3 -fed piglets than in the RS2 -fed piglets. Virtually no starch was recovered in the feces of any dietary group. Replacement of glucose by either RS2 or RS3 did not affect nitrogen retention but increased fecal nitrogen excretion. Compared with glucose, RS3 but not RS2 reduced urinary nitrogen excretion, mainly in the form of urea, and reduced the amount of nitrogen absorbed by the colon when expressed as a percentage of the amount of nitrogen entering the colon. This study provides evidence that RS3 , but not RS2 , shifts nitrogen excretion from urine to feces in cannulated piglets.
Wasser, Samuel K; Azkarate, Jurgi Cristòbal; Booth, Rebecca K; Hayward, Lisa; Hunt, Kathleen; Ayres, Katherine; Vynne, Carly; Gobush, Kathleen; Canales-Espinosa, Domingo; Rodríguez-Luna, Ernesto
2010-08-01
We developed and validated a non-invasive thyroid hormone measure in feces of a diverse array of birds and mammals. An I(131) radiolabel ingestion study in domestic dogs coupled with High Pressure Liquid Chromatography (HPLC) analysis, showed that peak excretion in feces occurred at 24-48h post-ingestion, with I(131)-labelled thyroid hormone metabolites excreted primarily as triiodothyronine (T3) and relatively little thyroxine (T4), at all excretion times examined. The immunoreactive T3 profile across these same HPLC fractions closely corresponded with the I(131) radioactive profile. By contrast, the T4 immunoreactive profile was disproportionately high, suggesting that T4 excretion included a high percentage of T4 stores. We optimized and validated T3 and T4 extraction and assay methods in feces of wild northern spotted owls, African elephants, howler monkeys, caribou, moose, wolf, maned wolf, killer whales and Steller sea lions. We explained 99% of the variance in high and low T3 concentrations derived from species-specific sample pools, after controlling for species and the various extraction methods tested. Fecal T3 reflected nutritional deficits in two male and three female howler monkeys held in captivity for translocation from a highly degraded habitat. Results suggest that thyroid hormone can be accurately and reliably measured in feces, providing important indices for environmental physiology across a diverse array of birds and mammals. Copyright 2010 Elsevier Inc. All rights reserved.
Christensen, Jennie R; Letcher, Robert J; Ross, Peter S
2009-10-01
Major pharmacokinetic processes influencing polychlorinated biphenyl (PCB) accumulation in mammals include uptake, biotransformation, respiration, and excretion. We characterized some of the factors underlying PCB accumulation/loss by evaluating PCB concentrations and patterns in pre- and posthibernation grizzly bears (Ursus arctos horribilis) and their prey. The PCB congeners with vicinal meta- and para-chlorine unsubstituted hydrogen positions consistently showed loss both before and during hibernation, supporting the idea of a dominant role for biotransformation. Retention of all other studied congeners relative to that of PCB 194 varied widely (from <1 to 100%) and was highly correlated with log octanol-water partition coefficient (p < 0.0001). A lack of loss for most of these other congeners during hibernation supports the notion that excretion (e.g., fecal or urinary) or lack of uptake during the feeding season underlies their lack of accumulation, because hibernating bears do not eat or excrete. We estimate that grizzly bears retain less than 10% of total PCBs taken up from their diet. Our results suggest that for grizzly bears, depuration of PCBs via biotransformation is important (explaining approximately 40% of loss), but that nonbiotransformation processes, such as excretion, may be more important (explaining approximately 60% of loss). These findings, together with the approximately 91% loss of the persistent PCB 153 congener relative to PCB 194 in grizzly bears, raise important questions about how one defines persistence of PCBs in wildlife and may have bearing on the interpretation of food-web biomagnification studies.
Kim, Hyunsook; Turowski, Maciej; Anderson, W H Kerr; Young, Scott A; Kim, Yookyung; Yokoyama, Wallace
2011-07-27
We investigated in Syrian Golden hamsters the biological impact and its underlying mechanism of single whole grain breads supplemented with 2-3% hydroxypropyl methylcellulose (HPMC), a semisynthetic viscous soluble dietary fiber (SDF) as a substitute for gluten. Hamsters were fed high-fat diets supplemented with 48-65% (w/w) differently ground, freeze-dried single grain breads including whole grain wheat, barley, barley supplemented with HPMC, debranned oat, and oat supplemented with HPMC which were compared to a diet containing microcrystalline cellulose (control). All single grain breads significantly lowered plasma LDL-cholesterol concentrations compared to the control. Enrichment with HPMC further lowered plasma and hepatic cholesterol concentrations. Despite the reduced molecular weight of naturally occurring soluble (1--->3),(1--->4)-β-d-glucan (β-glucan) caused by the bread-making process, whole grain barley breads downregulated hepatic expression of CYP7A1 and HMG-CoAR genes that are responsible for bile acid and cholesterol synthesis, suggesting a possible role of bioactive compounds such as short-chain fatty acids and phenolic compounds from barley bread. Barley bread enriched with HPMC downregulated expression of ABCG5 gene. Taken together, it appears that distinctive modulation of synthesis and excretion of hepatic cholesterol and bile acid contributes to the cholesterol-lowering properties of whole grain barley breads and breads enriched with HPMC. These data suggests that alternative whole grain breads supplemented with HPMC may provide consumers with a staple food that can assist in cholesterol management.
Huang, Fuqing; Zhang, Fen; Xu, Di; Zhang, Zhihong; Xu, Feng; Tao, Xueying; Qiu, Liang; Wei, Hua
2018-06-20
Enterococcus faecium WEFA23 is a potential probiotic strain from Chinese infants with the ability to decrease cholesterol levels. Aiming to explore the mechanism of E. faecium WEFA23 in lowering cholesterol in vivo, we examined the gene transcriptions related to cholesterol metabolism, the composition of bile acids in feces, the synthesis of trimethylamine N-oxide (TMAO) in liver, and the composition of the gut microbiota of rats. We found that E. faecium WEFA23 enhanced the synthesis of bile acids by promoting cholesterol excretion, upregulating the genes transcript level relevant to cholesterol decomposition and transportation, and downregulating the genes involved in cholesterol synthesis. In addition, E. faecium WEFA23 not only downregulated the transcript levels of farnesoid X receptor and fibroblast growth factor 15 as well as flavin-containing monooxygenase 3, but also decreased the TMAO production followed by increasing the CYP7A1 transcript level. Furthermore, when orally administered to rats for 35 d, E. faecium WEFA23 improved the gut microbiota diversity of rats fed a high-fat diet. Therein, the ratio of Bacteroidetes to Firmicutes and the abundance of Rikenellaceae increased, whereas the number of Veillonellaceae decreased. These results suggest that reduction of cholesterol level by E. faecium WEFA23 might be related to the changes in the gut microbiota. Our finding provides important information on lowering cholesterol by E. faecium and reveals that Enterococcus spp. might have the potential to decrease the TMAO level. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Marcovecchio, M. Loredana; Dalton, R. Neil; Prevost, A. Toby; Acerini, Carlo L.; Barrett, Timothy G.; Cooper, Jason D.; Edge, Julie; Neil, Andrew; Shield, Julian; Widmer, Barry; Todd, John A.; Dunger, David B.
2009-01-01
OBJECTIVE To explore the prevalence of lipid abnormalities and their relationship with albumin excretion and microalbuminuria in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS The study population comprised 895 young subjects with type 1 diabetes (490 males); median age at the baseline assessment was 14.5 years (range 10–21.1), and median diabetes duration was 4.8 years (0.2–17). A total of 2,194 nonfasting blood samples were collected longitudinally for determination of total cholesterol, LDL cholesterol, HDL cholesterol, TG, and non-HDL cholesterol. Additional annually collected data on anthropometric parameters, A1C, and albumin-to-creatinine ratio (ACR) were available. RESULTS Total cholesterol, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol were higher in females than in males (all P < 0.001). A significant proportion of subjects presented sustained lipid abnormalities during follow-up: total cholesterol >5.2 mmol/l (18.6%), non-HDL cholesterol >3.4 mmol/l (25.9%), TG >1.7 mmol/l (20.1%), and LDL cholesterol >3.4 mmol/l (9.6%). Age and duration were significantly related to all lipid parameters (P < 0.001); A1C was independently related to all parameters (P < 0.001) except HDL cholesterol, whereas BMI SD scores were related to all parameters (P < 0.05) except total cholesterol. Total cholesterol and non-HDL cholesterol were independently related to longitudinal changes in ACR (B coefficient ± SE): 0.03 ± 0.01/1 mmol/l, P = 0.009, and 0.32 ± 0.014/1 mmol/l, P = 0.02, respectively. Overall mean total cholesterol and non-HDL cholesterol were higher in microalbuminuria positive (n = 115) than in normoalbuminuric subjects (n = 780): total cholesterol 4.7 ± 1.2 vs. 4.5 ± 0.8 mmol/l (P = 0.04) and non-HDL cholesterol 3.2 ± 1.2 vs. 2.9 ± 0.8 mmol/l (P = 0.03). CONCLUSIONS In this longitudinal study of adolescents with type 1 diabetes, sustained lipid abnormalities were related to age, duration, BMI, and A1C. Furthermore, ACR was related to both total cholesterol and non-HDL cholesterol, indicating a potential role in the pathogenesis of diabetic nephropathy. PMID:19171721
Heistermann, Michael; Santema, Peter; Dantzer, Ben; Mausbach, Jelena; Ganswindt, Andre; Manser, Marta B.
2016-01-01
In mammals, glucocorticoid (i.e. GC) levels have been associated with specific life-history stages and transitions, reproductive strategies, and a plethora of behaviors. Assessment of adrenocortical activity via measurement of glucocorticoid metabolites in feces (FGCM) has greatly facilitated data collection from wild animals, due to its non-invasive nature, and thus has become an established tool in behavioral ecology and conservation biology. The aim of our study was to validate a fecal glucocorticoid assay for assessing adrenocortical activity in meerkats (Suricata suricatta), by comparing the suitability of three GC enzyme immunoassays (corticosterone, 11β-hydroxyetiocholanolone and 11oxo-etiocholanolone) in detecting FGCM increases in adult males and females following a pharmacological challenge with adrenocorticotropic hormone (ACTH) and biological stimuli. In addition, we investigated the time course characterizing FGCM excretion, the effect of age, sex and time of day on FGCM levels and assessed the potential effects of soil contamination (sand) on FGCM patterns. Our results show that the group specific 11β-hydroxyetiocholanolone assay was most sensitive to FGCM alterations, detecting significant and most distinctive elevations in FGCM levels around 25 h after ACTH administration. We found no age and sex differences in basal FGCM or on peak response levels to ACTH, but a marked diurnal pattern, with FGCM levels being substantially higher in the morning than later during the day. Soil contamination did not significantly affect FGCM patterns. Our results emphasize the importance of conducting assay validations to characterize species-specific endocrine excretion patterns, a crucial step to all animal endocrinology studies using a non-invasive approach. PMID:27077741
Muniz, Cinara Knychala; dos Santos, José Sebastião; Pfrimer, Karina; Ferrioli, Eduardo; Kemp, Rafael; Marchini, Júlio Sérgio; Cunha, Selma Freire
2014-04-01
This study aimed to compare the body composition, dietary intake and serum levels of vitamins and minerals, and exocrine pancreatic function in patients late after pancreaticoduodenectomy (PD) and healthy subjects. Fifteen patients (PD group) who had undergone PD over 1 year before the study and 15 health volunteers (control group) were included in the study. All volunteers underwent dietary intake evaluation, body composition, laboratory data, exocrine pancreatic function by elastase-1, and carbon (C )-labeled triglycerides in breath tests. The PD group subjects also underwent upper gastrointestinal endoscopy and small intestinal bacterial overgrowth analysis. Nutrient intake was adequate, and there were no differences in body mass index and mineral serum levels between the groups. The PD group showed lower serum levels of retinol, α-tocopherol, and ascorbic acid. Small intestinal bacterial overgrowth occurred in 39% of the patients. Fecal elastase-1 was lower in the PD group. The PD group had a higher C peak time; the cumulative label C recovery in 7 hours was similar in both groups. Fecal elastase-1 decreased, and the excretion of C in breath was similar to healthy controls. Although the data point toward an adaptation in the absorptive capacity of fats, A, C, and E hypovitaminosis indicate that some absorptive insufficiency persists late after PD.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cochran, R.C.
1985-01-01
Procedures used in estimating ruminal particle turnover and diet digestibility were evaluated in a series of independent experiments. Experiment 1 and 2 evaluated the influence of sampling site, mathematical model and intraruminal mixing on estimates of ruminal particle turnover in beef steers grazing crested wheatgrass or offered ad libitum levels of prairie hay once daily, respectively. Particle turnover rate constants were estimated by intraruminal administration (via rumen cannula) of ytterbium (Yb)-labeled forage, followed by serial collection of rumen digesta or fecal samples. Rumen Yb concentrations were transformed to natural logarithms and regressed on time. Influence of sampling site (rectum versusmore » rumen) on turnover estimates was modified by the model used to fit fecal marker excretion curves in the grazing study. In contrast, estimated turnover rate constants from rumen sampling were smaller (P < 0.05) than rectally derived rate constants, regardless of fecal model used, when steers were fed once daily. In Experiment 3, in vitro residues subjected to acid or neutral detergent fiber extraction (IVADF and IVNDF), acid detergent fiber incubated in cellulase (ADFIC) and acid detergent lignin (ADL) were evaluated as internal markers for predicting diet digestibility. Both IVADF and IVNDF displayed variable accuracy for prediction of in vivo digestibility whereas ADL and ADFIC inaccurately predicted digestibility of all diets.« less
Maukonen, Johanna; Aura, Anna-Marja; Niemi, Piritta; Raza, Gulam Shere; Niemelä, Klaus; Walkowiak, Jaroslaw; Mattila, Ismo; Poutanen, Kaisa; Buchert, Johanna; Herzig, Karl-Heinz
2017-05-10
Brewer's spent grain (BSG) is the major side-stream from brewing. As BSG is rich in dietary fiber and protein, it could be used in more valuable applications, such as nutritional additives for foods. Our aim was to elucidate whether an insoluble lignin-rich fraction (INS) from BSG is metabolized by mice gut microbiota and how it affects the microbiota. Our results indicated that lignin was partially degraded by the gut microbiota, degradation products were absorbed, and finally excreted in urine. Therefore, they contribute to the phenolic pool circulating in the mammalian body, and may have systemic effects on health. In addition, the effects of the test diets on the microbiota were significant. Most interestingly, diversities of predominant cecal and fecal bacteria were higher after the intervention diet containing INS than after the intervention diet containing cellulose. Since low fecal bacterial diversity has been linked with numerous diseases and disorders, the diversity increasing ability opens very interesting perspectives for the future.
Nakamura, Michiko; Miura, Sayaka; Takagaki, Akiko; Nanjo, Fumio
2017-05-01
Crude tea polysaccharide (crude TPS) was prepared from instant green tea by ethanol precipitation followed by ultrafiltration membrane treatment and its effects on blood lipid, liver lipid, and fecal lipid levels were examined with Sprague-Dawley rats fed a high-fat diet. Although crude TPS showed no effects on the serum lipid levels, it suppressed the liver lipid accumulation and increased the fecal excretion of dietary fat. Then, the structural features of crude TPS were investigated. After separation of crude TPS by DEAE-cellulose and gel-filtration column chromatography, two kinds of neutral tea polysaccharides (NTPS-LP and NTPS-HH) and an acidic polysaccharide (ATPS-MH) were obtained. According to monosaccharide composition, methylation, and NMR analyses, NTPS-LP, NPTS-HH, and ATPS-MH were presumed to be starch, arabinogalactan with β-1,3-linked galactosyl backbone blanched at position 6 and with 1,5-linked arabinofuranosyl residues, and α-1,4-linked galacturonic acid backbone with arabinogalactan region, respectively.
Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse
Pestka, James J.; Clark, Erica S.; Schwartz-Zimmermann, Heidi E.
2017-01-01
Based on prior observations that deoxynivalenol (DON) toxicity is sex-dependent, we compared metabolism and clearance of this toxin in male and female mice. Following intraperitoneal challenge with 1 mg/kg bw DON, the dose used in the aforementioned toxicity study, ELISA and LC–MS/MS analyses revealed that by 24 h, most DON and DON metabolites were excreted via urine (49–86%) as compared to feces (1.2–8.3%). Females excreted DON and its principal metabolites (DON-3-, DON-8,15 hemiketal-8-, and iso-DON-8-glucuronides) in urine more rapidly than males. Metabolite concentrations were typically 2 to 4 times higher in the livers and kidneys of males than females from 1 to 4 h after dosing. Trace levels of DON-3-sulfate and DON-15-sulfate were found in urine, liver and kidneys from females but not males. Fecal excretion of DON and DON sulfonates was approximately 2-fold greater in males than females. Finally, decreased DON clearance rates in males could not be explained by glucuronidation activities in liver and kidney microsomes. To summarize, increased sensitivity of male mice to DON’s toxic effects as compared to females corresponds to decreased ability to clear the toxin via urine but did not appear to result from differences in toxin metabolism. PMID:28777306
Lehtonen, Henna-Maria; Lehtinen, Outi; Suomela, Jukka-Pekka; Viitanen, Matti; Kallio, Heikki
2010-01-13
Glucuronidation and excretion of sea buckthorn and lingonberry flavonols were investigated in a postprandial trial by analyzing the intact forms of flavonol glycosides as well as glucuronides in plasma, urine, and feces. Four study subjects consumed sea buckthorn (study day 1) and lingonberry (study day 2) breakfasts, and blood, urine, and fecal samples were collected for 8, 24, and 48 h, respectively. Both glycosides and glucuronides of the flavonol quercetin as well as kaempferol glucuronides were detected in urine and plasma samples after the consumption of lingonberries; 14% of flavonols in urine were glycosides, and 86% were glucuronidated forms (wt %). After the consumption of sea buckthorn, 5% of flavonols excreted in urine were detected intact, and 95% as the glucuronides (wt %). Solely glucuronides of flavonols isorhamnetin and quercetin were found in plasma after the consumption of sea buckthorn berries. Only glycosides were detected in the feces after each berry trial. Flavonol glycosides and glucuronides remained in blood and urine quite long, and the peak concentrations appeared slightly later than previously described. The berries seemed to serve as a good flavonol supply, providing steady flavonol input for the body for a relatively long time.
Boini, Krishna M; Bhandaru, Madhuri; Mack, Andreas; Lang, Florian
2008-09-01
Insulin and insulin-like growth factor (IGF1) participate in the regulation of renal electrolyte excretion. Insulin- and IGF1-dependent signaling includes phosphatidylinositide-3 (PI3)-kinase, phosphoinositide-dependent kinase PDK1 as well as protein kinase B (PKB) and serum and glucocorticoid inducible kinase (SGK) isoforms, which in turn phosphorylate and thus inhibit glycogen synthase kinase GSK3alpha,beta. Replacement of the serines in the PKB/SGK consensus sequences by alanine (gsk3 ( KI )) confers resistance of GSK3 to PKB/SGK. To explore the role of PKB/SGK-dependent inhibition of GSK3 in the regulation of water/electrolyte metabolism, mice carrying the PKB/SGK resistant mutant (gsk3 ( KI )) were compared to their wild-type littermates (gsk3 ( WT ) ). Body weight was similar in gsk3 ( KI ) and gsk3 ( WT ) mice. Plasma aldosterone at 10 A.M: . and corticosterone concentrations at 5 P.M: . were significantly lower, but 24-h urinary aldosterone was significantly higher, and corticosterone excretion tended to be higher in gsk3 ( KI ) than in gsk3 ( WT ) mice. Food and water intake, fecal excretion, glomerular filtration rate, urinary flow rate, urine osmolarity, as well as urinary Na+, K+, urea excretion were significantly larger, and plasma Na+, urea, but not K+ concentration, were significantly lower in gsk3 ( KI ) than in gsk3 ( WT ) mice. Body temperature was significantly higher in gsk3 ( KI ) than in gsk3 ( WT ) mice. When allowed to choose between tap water and saline, gsk3 ( WT ) mice drank more saline, whereas gsk3 ( KI ) mice drank similar large volumes of tap water and saline. During high-salt diet, urinary vasopressin excretion increased to significantly higher levels in gsk3 ( KI ) than in gsk3 ( WT ) mice. After water deprivation, body weight decreased faster in gsk3 ( KI ) than in gsk3 ( WT ) mice. Blood pressure, however, was significantly higher in gsk3 ( KI ) than in gsk3 ( WT ) mice. The observations disclose a role of PKB/SGK-dependent GSK3 activity in the regulation of steroid hormone release, renal water and electrolyte excretion and blood pressure control.
Lee, Junga; Scheri, Richard C.; Curtis, Lawrence R.
2011-01-01
Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [14C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [14C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [14C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [14C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [14C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [14C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATPbinding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism. PMID:18387646
Lee, Junga; Scheri, Richard C; Curtis, Lawrence R
2008-06-15
Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [(14)C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [(14)C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [(14)C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [(14)C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [(14)C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [(14)C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism.
Lv, Yun-cheng; Yang, Jing; Yao, Feng; Xie, Wei; Tang, Yan-yan; Ouyang, Xin-ping; He, Ping-ping; Tan, Yu-lin; Li, Liang; Zhang, Min; Liu, Dan; Cayabyab, Francisco S; Zheng, Xi-Long; Tang, Chao-ke
2015-05-01
Diosgenin (Dgn), a structural analogue of cholesterol, has been reported to have the hypolipidemic and antiatherogenic properties, but the underlying mechanisms are not fully understood. Given the key roles of macrophages in cholesterol metabolism and atherogenesis, it is critical to investigate macrophage cholesterol efflux and development of atherosclerotic lesion after Dgn treatment. This study was designed to evaluate the potential effects of Dgn on macrophage cholesterol metabolism and the development of aortic atherosclerosis, and to explore its underlying mechanisms. Dgn significantly up-regulated the expression of ATP-binding cassette transporter A1 (ABCA1) protein, but didn't affect liver X receptor α levels in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by western blotting. The miR-19b levels were markedly down-regulated in Dgn-treated THP-1 macrophages/MPM-derived foam cells. Cholesterol transport assays revealed that treatment with Dgn alone or together with miR-19b inhibitor notably enhanced ABCA1-dependent cholesterol efflux, resulting in the reduced levels of total cholesterol, free cholesterol and cholesterol ester as determined by high-performance liquid chromatography. The fecal 3H-sterol originating from cholesterol-laden MPMs was increased in apolipoprotein E knockout mice treated with Dgn or both Dgn and antagomiR-19b. Treatment with Dgn alone or together with antagomiR-19b elevated plasma high-density lipoprotein levels, but reduced plasma low-density lipoprotein levels. Accordingly, aortic lipid deposition and plaque area were reduced, and collagen content and ABCA1 expression were increased in mice treated with Dgn alone or together with antagomiR-19b. However, miR-19b overexpression abrogated the lipid-lowering and atheroprotective effects induced by Dgn. The present study demonstrates that Dgn enhances ABCA1-dependent cholesterol efflux and inhibits aortic atherosclerosis progression by suppressing macrophage miR-19b expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Habumuremyi, Sosthene; Robbins, Martha M; Fawcett, Katie A; Deschner, Tobias
2014-02-01
Understanding the reproductive biology of endangered mountain gorillas (Gorilla beringei beringei) is essential for optimizing conservation strategies, determining any demographic impact of socioecological changes, and providing information for comparative studies of primates. Non-invasive techniques have been used to assess the reproductive function of many primates and the importance of validating the measurements of hormones metabolites is widely recognized because they may vary even within closely related species. To determine if it is possible to non-invasively monitor ovarian activity in wild mountain gorillas, we used enzyme immunoassays (EIA) to quantify both urinary and fecal excretion of immunoreactive pregnanediol-3-glucuronide (iPdG), defined as all metabolites detected by a pregnanediol-3-glucuronide immunoassay (PdG EIA). Simultaneously, we performed the liquid chromatography mass spectrometry (LC-MS) to quantify the excretion of pregnanediol in urine and feces. Samples were analyzed over nine cycles of five females from the habituated gorillas monitored by Karisoke Research Center, Rwanda. As an additional indicator for ovulation timing, estrone conjugates (E1C) were measured in a subset of urine samples. The concentrations of iPdG and pregnanediol measured in the same samples were significantly correlated. Urinary concentrations of iPdG and pregnanediol fluctuated over the menstrual cycle but did not reveal any cyclic pattern, whereas a typical preovulatory urinary E1C surge and postovulatory increases of fecal iPdG and pregnanediol were detected. The luteal peaks of iPdG and pregnanediol levels in feces were on average 2.8 and 7.6 times higher, respectively, than averaged levels in the corresponding follicular phase. The relative number of days with observed matings was higher within the presumed fertile window than in the preceding period. Overall, the results indicate that fecal analysis of iPdG and pregnanediol is suitable for detecting ovulation in female mountain gorillas. Urinary measurements using both EIA and LC-MS appeared to be uninformative for monitoring ovarian activity in this primate. © 2013 Wiley Periodicals, Inc.
Geusau, Alexandra; Schmaldienst, Sabine; Derfler, Kurt; Päpke, Olaf; Abraham, Klaus
2002-06-01
In spring 1998, two women were diagnosed with severe 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) intoxication. Over the following 3 years, TCDD levels were monitored under various attempts to enhance its elimination, and the half-lives were evaluated. Olestra, a non-digestible, non-absorbable dietary fat substitute, was continuously administered to the patients either as pure substance or in potato-chips. Additionally, in the more severely contaminated patient, we studied whether low-density lipoprotein (LDL)-apheresis, an extracorporeal means of blood lipid elimination, was effective in reducing the TCDD body burden. The blood concentrations initially measured in spring 1998 were 144,000 pg/g blood fat in patient 1 and 26,000 pg/g in patient 2, the highest levels ever measured in adults. In March 2001, concentrations in blood fat were 35,900 and 9,500 pg/g, corresponding to overall elimination half-lives of 560 days (1.5 years) in patient 1 and 1050 days (2.9 years) in patient 2, which are considerably shorter than median values of 7-9 years reported for background and moderate exposure levels. Calculations of the TCDD half-lives and measurements of TCDD elimination via different routes allowed the calculation of an unidentified route of elimination, representing 78 and 62% of the overall elimination in patient 1 and 2, respectively, probably due to an induced hepatic metabolism caused by the high TCDD exposure. As previously reported, administration of olestra was found to be effective in increasing the fecal excretion of TCDD. Due to the short half-lives in our patients, the effect of olestra on the overall elimination was relatively small, but is expected to be much greater for 'normal' half-lives. LDL-apheresis was shown to eliminate TCDD, corresponding to the eliminated blood fat. When employed twice a week, the amount of TCDD excreted by this method was comparable to fecal excretion. In view of costs and time involved, LDL-apheresis does not seem to be justified for enhancement of TCDD elimination.
Nery, J; Goudez, R; Biourge, V; Tournier, C; Leray, V; Martin, L; Thorin, C; Nguyen, P; Dumon, H
2012-08-01
Low-consistency, high-moisture feces have been observed in large dogs (Canis lupus familiaris), compared with small dogs, and particularly in sensitive breeds (e.g., German Shepherd dogs). The aim of this work was to determine if greater colonic protein fermentation is responsible for poorer fecal quality in large sensitive dogs. Twenty-seven bitches were allotted to 4 groups based on size and digestive sensitivity: small, medium, large tolerant, and large sensitive. Five experimental diets varying in protein source [highly digestible wheat gluten (WG) vs. medium digestible poultry meal (PM), and protein concentration from 21.4 to 21.6 (LP) to 38.2 to 39.2% CP (HP)] were tested. Diets were fed for 14 d and followed by a 12-d transition period. Digestive fermentation by-products were investigated in fresh stools [ammonia, phenol, indole, and short chain fatty acids including acetate, propionate, and butyrate (C2 to C4 SCFA), branched-chain fatty acids (BCFA), and valerate] and in urine (phenol and indole). Bacterial populations in feces were identified. The PM diets resulted in greater fecal concentrations of ammonia, BCFA, valerate, indole, and C2 to C4 SCFA than WG diets (P = 0.002, P < 0.001, P = 0.039, P = 0.003, and P = 0.012, respectively). Greater concentrations of ammonia, BCFA, and valerate were found in the feces of dogs fed HP compared with LP diets (P < 0.001, P < 0.001, and P = 0.012, respectively). The concentrations of ammonia, valerate, phenol, and indole in feces of large sensitive dogs were greater (P < 0.001, P < 0.001, P = 0.002, and P = 0.019, respectively) compared with the other groups. The Enterococcus populations were greater in feces of dogs fed with PMHP rather than WGLP diets (P = 0.006). Urinary phenol and indole excretion was greater when dogs were fed PM than WG diets (P < 0.001 and P = 0.038, respectively) and HP than LP diets (P = 0.001 and P = 0.087, respectively). Large sensitive dogs were prone to excrete a greater quantity of phenol in urine (P < 0.001). A diet formulated with highly digestible protein, such as WG, led to reduced concentrations of protein-based fermentation products in feces together with improved fecal quality in dogs, especially in large sensitive ones. Poor fecal quality in large sensitive dogs could be partly related to the pattern of protein fermentation in the hindgut.
Huang, Ying; Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili
2014-12-01
The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old ApoE(-/-) mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE(-/-) mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Rotifers ingest oocysts of Cryptosporidium parvum
Fayer, R.; Trout, J.M.; Walsh, E.; Cole, Rebecca A.
2000-01-01
Six genera of rotifers including Philodina, Monostyla, Epiphanes, Euchlanis, Brachionus, and Asplanchna were exposed to oocysts of Cryptosporidium parvum cleaned of fecal debris. Unstained oocysts and those stained with fluorescein-conjugated monoclonal antibody were added to suspensions of viable rotifers and were examined by phase-contrast, differential interference contrast, and fluorescence microscopy. Rotifers of all six genera were observed ingesting oocysts. A maximum of 25 oocysts was observed in the stomachs of Euchlanis and Brachionus. Euchlanis and Epiphanes were observed excreting boluses containing up to eight oocysts. It was not determined whether rotifers digested or otherwise rendered oocysts nonviable.
Benaicheta, Nora; Labbaci, Fatima Z; Bouchenak, Malika; Boukortt, Farida O
2016-01-14
Type 2 diabetes (T2D) is a major risk factor of CVD. The effects of purified sardine proteins (SP) were examined on glycaemia, insulin sensitivity and reverse cholesterol transport in T2D rats. Rats fed a high-fat diet (HFD) for 5 weeks, and injected with a low dose of streptozotocin, were used. The diabetic rats were divided into four groups, and they were fed casein (CAS) or SP combined with 30 or 5% lipids, for 4 weeks. HFD-induced hyperglycaemia, insulin resistance and hyperlipidaemia in rats fed HFD, regardless of the consumed protein. In contrast, these parameters lowered in rats fed SP combined with 5 or 30% lipids, and serum insulin values reduced in SP v. CAS. HFD significantly increased total cholesterol and TAG concentrations in the liver and serum, whereas these parameters decreased with SP, regardless of lipid intake. Faecal cholesterol excretion was higher with SP v. CAS, combined with 30 or 5% lipids. Lecithin:cholesterol acyltransferase (LCAT) activity and HDL3-phospholipids (PL) were higher in CAS-HF than in CAS, whereas HDL2-cholesteryl esters (CE) were lower. Otherwise, LCAT activity and HDL2-CE were higher in the SP group than in the CAS group, whereas HDL3-PL and HDL3-unesterified cholesterol were lower. Moreover, LCAT activity lowered in the SP-HF group than in the CAS-HF group, when HDL2-CE was higher. In conclusion, these results indicate the potential effects of SP to improve glycaemia, insulin sensitivity and reverse cholesterol transport, in T2D rats.
Oliveira, Fabiana S T; Vieira-Filho, Leucio D; Cabral, Edjair V; Sampaio, Luzia S; Silva, Paulo A; Carvalho, Vera C O; Vieyra, Adalberto; Einicker-Lamas, Marcelo; Lima, Vera L M; Paixão, Ana D O
2013-04-01
It has been demonstrated that reabsorption of Na⁺ in the thick ascending limb is reduced and the ability to concentrate urine can be compromised in undernourished individuals. Alterations in phospholipid and cholesterol content in renal membranes, leading to Na⁺ loss and the inability to concentrate urine, were investigated in undernourished rats. Sixty-day-old male Wistar rats were utilized to evaluate (1) phospholipid and cholesterol content in the membrane fraction of whole kidneys, (2) cholesterol content and the levels of active Na⁺ transporters, (Na⁺ + K⁺)ATPase and Na⁺-ATPase, in basolateral membranes of kidney proximal tubules, and (3) functional indicators of medullary urine concentration. Body weight in the undernourished group was 73 % lower than in control. Undernourishment did not affect the levels of cholesterol in serum or in renal homogenates. However, membranes of whole kidneys revealed 56 and 66 % reduction in the levels of total phospholipids and cholesterol, respectively. Furthermore, cholesterol and (Na⁺ + K⁺)ATPase activity in proximal tubule membranes were reduced by 55 and 68 %, respectively. Oxidative stress remained unaltered in the kidneys of undernourished rats. In contrast, Na⁺-ATPase activity, an enzyme with all regulatory components in membrane, was increased in the proximal tubules of undernourished rats. Free water clearance and fractional Na⁺ excretion were increased by 86 and 24 %, respectively, and urinary osmolal concentration was 21 % lower in undernourished rats than controls. Life-long undernutrition reduces the levels of total phospholipids and cholesterol in membranes of renal tubular cells. This alteration in membrane integrity could diminish (Na⁺ + K⁺)ATPase activity resulting in reduced Na⁺ reabsorption and urinary concentrating ability.
Liu, Peng; Peng, Liang; Zhang, Haojun; Tang, Patrick Ming-Kuen; Zhao, Tingting; Yan, Meihua; Zhao, Hailing; Huang, Xiaoru; Lan, Huiyao; Li, Ping
2018-01-01
The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro . In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux.
Guevara, M A; Bauer, L L; Garleb, K A; Fahey, G C; de Godoy, M R C
2016-05-01
The objectives were to examine in vitro fermentation characteristics, in vivo nutrient digestibility, fecal microbiota, and serum lipid profiles as affected by α-cyclodextrin (ACD) supplementation. Short-chain fatty acid (SCFA) production was measured after in vitro fermentation for 3, 6, 9, and 12 h of ACD, β-cyclodextrin, and γ-cyclodextrin. Five mixed-breed hounds were used in a Latin square design. Each experimental period comprised 14 d, including 10 d for diet adaptation and 4 d for fecal collection. Dogs were fed, twice a day, an extruded diet made with poultry byproduct meal and brewer's rice as the main ingredients. Dogs were supplemented with 0, 1, 2, 3, or 4 g of ACD diluted in 15 mL of water twice daily for a total of 0, 2, 4, 6, and 8 g ACD/d. Maximal in vitro production of total SCFA was lowest for ACD. However, the greatest maximal production of propionate was noted for ACD treatment. Total tract nutrient digestibility and fecal DM concentration linearly decreased ( < 0.05) for treatment groups receiving ACD; no changes were observed for ileal digestibility. Serum cholesterol and triglyceride concentrations were within normal ranges for dogs and were not different among treatments. Similarly, no changes in fecal microbiota were observed. Overall, ACD supplementation appears to have no effect on nutrient absorption in the small intestine but may alter fermentation in the large bowel, which could lead to a higher proportion of propionate production as observed in the in vitro experiment.
Mundlos, S; Rhodes, J B; Hofmann, A F
1987-09-01
A breath test for the detection of pancreatic insufficiency was developed and tested in rats. The test features the hydrophobic molecule cholesteryl-1-14C-octanoate, which liberates 14C-octanoic acid when hydrolyzed by carboxyl ester lipase (cholesterol esterase). The 14C-octanoate is absorbed passively and rapidly metabolized to 14CO2, which is excreted in expired air. The compound was administered as an emulsion of cholesteryl octanoate, triglyceride, and lecithin to rats with mild pancreatic insufficiency induced by injecting the pancreatic duct with zein. The animals had exocrine pancreatic hypofunction based on the enzyme content of pancreas at autopsy. Amylase was reduced by 97.1 +/- 1.4%, whereas chymotrypsin was reduced by 73 +/- 14%. The p-aminobenzoic acid test was abnormal at 1 wk (21.68 +/- 8.4%), but become normal at 3 months (72.08 +/- 5.8%) after zein injection. Despite this, the animals gained weight and absorbed fat normally. The 14CO2 excretion rate in the 110-min interval after feeding was significantly reduced to 60% of sham-operated animals. Peak 14CO2 collections 20 min after feeding were reduced by 75 +/- 11%. 14CO2 output was completely normalized by administration of pancreatin prior to the test meal. The results suggest that a sensitive, noninvasive method for detecting deficiency of pancreatic carboxyl ester lipase (cholesterol esterase) secretion in the rat has been developed.
Jiao, H P; Yan, T; McDowell, D A
2014-07-01
The objectives of the present study were to evaluate the effects of sex (steers vs. heifers) of young Holstein cattle on N and OM excretion in feces and urine and to use these data to develop prediction models for N and OM excretion. Data used were derived from a study with 20 autumn-born Holstein cattle (10 steers and 10 heifers) with N and OM intake and output measured at age of 6, 12, 18, and 22 mo, respectively. The cattle were offered a typical diet used on U.K. commercial farms containing a single grass silage mixed with concentrates. In each period, the cattle were housed as a single group in cubicle accommodation for the first 20 d, individually in metabolism units for the next 3 d, and then in calorimeter chambers for the final 5 d with feed intake, feces, and urine excretion measured during the final 4 d. Within each period, sex had no effect (P > 0.05) on N or OM intake or excretion or N utilization efficiency, with exceptions of steers having a greater intake of N (P = 0.036) and OM (P = 0.018) at age of 18 mo and a lower ratio of fecal N:N intake (P = 0.023) at age of 6 mo. A range of regression relationships (P < 0.05) were developed for prediction of N (g/d) and OM (kg/d) excretion in feces and urine. The present data were also used to calculate accumulated N and OM intake (kg) and excretion for the 2 sexes. Sex had no effects (P > 0.05) on accumulated N or OM intake or N or OM excretion in feces and urine or retained N and OM during the first or second year of life. On average for the 2 sexes at first and second year of age, the accumulated N excretions in feces were 11.4 and 21.1 kg and in urine 11.6 and 30.6 kg, respectively, and the corresponding values for accumulated OM excretions were respectively 241.5, 565.7, 30.3 and 81.5 kg. A number of equations were developed to predict accumulated N and OM excretion in feces and urine (kg) using BW (kg; P < 0.001, r(2) = 0.95 to 0.97). The accurate prediction of N and OM excretion in feces and urine is essential for reducing N pollution to ground and surface water and calculating methane and nitrous oxide emissions from manure management of dairy and beef production systems. These data can add novel information to the scientific literature and can be used to improve national inventories of manure N output and greenhouse gas emissions and to develop appropriate mitigation strategies for young Holstein cattle.
Particle size of roasted soybeans and the effect on milk production of dairy cows.
Dhiman, T R; Korevaar, A C; Satter, L D
1997-08-01
Fifteen cows were used in an experiment with a 5 x 5 replicated Latin square design to quantify the effect of particle size of roasted soybeans on milk production and fecal excretion of soybeans. The five experimental periods were each 2 wk long. Diets contained (percentage of dry matter) 33% alfalfa silage, 17% corn silage, 30.6% high moisture ear corn, 18% soybeans, and 1.4% mineral supplement. The five dietary treatments included raw whole soybeans or roasted soybeans in four particle sizes (whole and half, half and quarter, quarter and smaller, and coarsely ground). Mean particle sizes of the raw soybeans and of the roasted soybeans in whole and half sizes were > 4.75 mm. Mean particle sizes of the roasted soybeans in half and quarter, quarter and smaller, and coarsely ground roasted soybeans were 2.92, 2.01, and 1.59, respectively. During the normal handling of roasted soybeans, a large number of seeds was broken into halves in the treatment with whole and half sizes (36%, wt/wt basis). Production of 3.5% fat-corrected milk was 35.4, 37.7, 37.2, 35.1, and 35.4 kg/d for cows fed raw soybeans; roasted soybeans in whole and half, half and quarter, and quarter and smaller sizes; and ground roasted soybeans, respectively. Cows that were fed raw soybeans excreted the largest amount of visible soybean particles in feces, and cows that were fed ground roasted soybeans had the least amount of soybeans in the feces (61.3 vs. 10.6 g of soybeans/kg of fecal dry matter). Roasted soybeans in half and quarter sizes are optimal for milk production.
Moreira, V R; Satter, L D; Harding, B
2004-01-01
Performance of lactating dairy cows fed diets containing either mechanically delinted whole cottonseed (DWCS; 3.7% lint) or linted whole cottonseed (LWCS; 11.7% lint) was measured. Forty primiparous (86 +/- 39 d in milk) and 40 multiparous (88 +/- 30 d in milk) cows were fed a total mixed ration containing 13% (dry matter basis) DWCS or LWCS in two blocks of 112 d (n = 53 and 27, respectively). Other total mixed ration ingredients (dry matter basis) were corn silage (28.1%), alfalfa silage (23%), high moisture shelled corn (27.8%), soybean meal (1.8%), expeller soybean meal (1.8%), blood meal (2%), and mineral-vitamin supplements (2.5%). Dry matter intake and milk yield were measured daily and milk composition every other week. Fecal grab samples were taken during wk 3 and 13 of each block to estimate excretion of intact whole cottonseeds. Milk yield, 3.5% fat-corrected milk, energy-corrected milk, milk composition and dry matter intake were not affected by whole cottonseed source. Body condition score tended to increase more with DWCS (0.22 vs. 0.11) for primiparous cows, although this was not reflected in body weight change. Dry matter digestibilities, based on indigestible ADF, were 63.5 and 64.8% for the DWCS and LWCS diets. It was calculated that 2.5 and 1.5% of the consumed seeds were excreted as whole cottonseeds in feces with the DWCS and LWCS diets, respectively. Although statistically significant, treatment differences in the proportion of intact seeds in the fecal DM would have little nutritional consequence. Mechanically delinted WCS performed as well as LWCS for all of the cow performance and milk composition variables measured.
Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis.
Huang, Fen; Li, Yunlong; Yu, Wenhai; Jing, Shenrong; Wang, Jue; Long, Feiyan; He, Zhanlong; Yang, Chenchen; Bi, Yanhong; Cao, Wentao; Liu, Chengbo; Hua, Xiuguo; Pan, Qiuwei
2016-08-01
Hepatitis E virus (HEV) represents the main cause of acute hepatitis worldwide. HEV infection in immunocompromised patients involves a high risk for the development of chronic hepatitis. Because HEV is recognized as a zoonotic pathogen, it is currently believed that swine is the primary reservoir. However, this is not sufficient to justify the strikingly high seroprevalence of HEV in both developing and Western countries. Thus, this study aimed to identify new zoonotic sources that bear a high risk of transmission to humans. We collected fecal, blood, and milk samples of cows in a typical rural region of Yunnan Province in southwest China, where mixed farming of domestic animals is a common practice. HEV RNA was quantified by quantitative real-time polymerase chain reaction, and the whole genome was sequenced. HEV infectivity was assessed in rhesus macaques. We found a high prevalence of active HEV infection in cows as determined by viral RNA positivity in fecal samples. Surprisingly, we discovered that HEV is excreted into milk that is produced by infected cows. Phylogenetic analysis revealed that all HEV isolates from cow/milk belong to genotype 4 and subtype 4h. Gavage with HEV-contaminated raw and even pasteurized milk resulted in active infection in rhesus macaques. Importantly, a short period of boiling, but not pasteurization, could completely inactivate HEV. Infectious HEV-contaminated cow milk is recognized as a new zoonotic source that bears a high risk of transmission to humans; these results call attention to understanding and establishing proper measurement and control of HEV zoonotic transmission, particularly in the setting of mixed farming of domestic animals. (Hepatology 2016;64:350-359). © 2016 by the American Association for the Study of Liver Diseases.
Lv, Yun-Cheng; Tang, Yan-Yan; Peng, Juan; Zhao, Guo-Jun; Yang, Jing; Yao, Feng; Ouyang, Xin-Ping; He, Ping-Ping; Xie, Wei; Tan, Yu-Lin; Zhang, Min; Liu, Dan; Tang, Deng-Pei; Cayabyab, Francisco S; Zheng, Xi-Long; Zhang, Da-Wei; Tian, Guo-Ping; Tang, Chao-Ke
2014-09-01
Macrophage accumulation of cholesterol leads to foam cell formation which is a major pathological event of atherosclerosis. Recent studies have shown that microRNA (miR)-19b might play an important role in cholesterol metabolism and atherosclerotic diseases. Here, we have identified miR-19b binding to the 3'UTR of ATP-binding cassette transporter A1 (ABCA1) transporters, and further determined the potential roles of this novel interaction in atherogenesis. To investigate the molecular mechanisms involved in a miR-19b promotion of macrophage cholesterol accumulation and the development of aortic atherosclerosis. We performed bioinformatics analysis using online websites, and found that miR-19b was highly conserved during evolution and directly bound to ABCA1 mRNA with very low binding free energy. Luciferase reporter assay confirmed that miR-19b bound to 3110-3116 sites within ABCA1 3'UTR. MiR-19b directly regulated the expression levels of endogenous ABCA1 in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by qRT-PCR and western blot. Cholesterol transport assays revealed that miR-19b dramatically suppressed apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux, resulting in the increased levels of total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) as revealed by HPLC. The excretion of (3)H-cholesterol originating from cholesterol-laden MPMs into feces was decreased in mice overexpressing miR-19b. Finally, we evaluated the proatherosclerotic role of miR-19b in apolipoprotein E deficient (apoE(-/-)) mice. Treatment with miR-19b precursor reduced plasma high-density lipoprotein (HDL) levels, but increased plasma low-density lipoprotein (LDL) levels. Consistently, miR-19b precursor treatment increased aortic plaque size and lipid content, but reduced collagen content and ABCA1 expression. In contrast, treatment with the inhibitory miR-19b antisense oligonucleotides (ASO) prevented or reversed these effects. MiR-19b promotes macrophage cholesterol accumulation, foam cell formation and aortic atherosclerotic development by targeting ABCA1. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Song, Mingyue; Lopez-Pena, Cynthia Lyliam; McClements, David Julian; Decker, Eric Andrew; Xiao, Hang
2017-05-24
ε-Polylysine (ε-PL) is a potent cationic antimicrobial, but its application as a food additive is currently limited because it tends to precipitate with anionic species in food matrices. Previous research has shown that the formation of an electrostatic complex between cationic ε-PL and anionic pectin (P) improved the physical stability of ε-PL while maintaining its antimicrobial activity. However, the impact of complexation on the effects of ε-PL on health is currently unknown. A subchronic toxicity study was therefore carried out to determine the safety of ingested ε-PL-P complexes using high-fat diet-fed male and female mice. After a 13-week dietary treatment with P, ε-PL, or ε-PL-P complexes, no significant toxicological effects were observed on the survival, mean body weight, food consumption, and organ weights of the animals, suggesting that the complexes were safe for oral consumption. Interestingly, the ε-PL-P complexes were found to have several beneficial health effects: suppression of high-fat diet-induced elevation of serum aspartate aminotransferase and alanine aminotransferase activities, reduction in serum total triglyceride and cholesterol levels, and an increase in fecal excretion of triglycerides. These effects were much stronger in female mice than in male mice. Moreover, the lipid-lowering effects were observed only for the ε-PL-P complexes but not for ε-PL or P alone at the same doses. Overall, our results demonstrate the oral safety of ε-PL-P complexes and their gender-specific lipid-lowering effects in high-fat diet-fed mice, which provide an important basis for the utilization of ε-PL-P complexes in food systems as functional ingredients.
Detection of Bovine and Porcine Adenoviruses for Tracing the Source of Fecal Contamination
Maluquer de Motes, Carlos; Clemente-Casares, Pilar; Hundesa, Ayalkibet; Martín, Margarita; Girones, Rosina
2004-01-01
In this study, a molecular procedure for the detection of adenoviruses of animal origin was developed to evaluate the level of excretion of these viruses by swine and cattle and to design a test to facilitate the tracing of specific sources of environmental viral contamination. Two sets of oligonucleotides were designed, one to detect porcine adenoviruses and the other to detect bovine and ovine adenoviruses. The specificity of the assays was assessed in 31 fecal samples and 12 sewage samples that were collected monthly during a 1-year period. The data also provided information on the environmental prevalence of animal adenoviruses. Porcine adenoviruses were detected in 17 of 24 (70%) pools of swine samples studied, with most isolates being closely related to serotype 3. Bovine adenoviruses were present in 6 of 8 (75%) pools studied, with strains belonging to the genera Mastadenovirus and Atadenovirus and being similar to bovine adenoviruses of types 2, 4, and 7. These sets of primers produced negative results in nested PCR assays when human adenovirus controls and urban-sewage samples were tested. Likewise, the sets of primers previously designed for detection of human adenovirus also produced negative results with animal adenoviruses. These results indicate the importance of further studies to evaluate the usefulness of these tests to trace the source of fecal contamination in water and food and for environmental studies. PMID:15006765
Detection of bovine and porcine adenoviruses for tracing the source of fecal contamination.
Maluquer de Motes, Carlos; Clemente-Casares, Pilar; Hundesa, Ayalkibet; Martín, Margarita; Girones, Rosina
2004-03-01
In this study, a molecular procedure for the detection of adenoviruses of animal origin was developed to evaluate the level of excretion of these viruses by swine and cattle and to design a test to facilitate the tracing of specific sources of environmental viral contamination. Two sets of oligonucleotides were designed, one to detect porcine adenoviruses and the other to detect bovine and ovine adenoviruses. The specificity of the assays was assessed in 31 fecal samples and 12 sewage samples that were collected monthly during a 1-year period. The data also provided information on the environmental prevalence of animal adenoviruses. Porcine adenoviruses were detected in 17 of 24 (70%) pools of swine samples studied, with most isolates being closely related to serotype 3. Bovine adenoviruses were present in 6 of 8 (75%) pools studied, with strains belonging to the genera Mastadenovirus and Atadenovirus and being similar to bovine adenoviruses of types 2, 4, and 7. These sets of primers produced negative results in nested PCR assays when human adenovirus controls and urban-sewage samples were tested. Likewise, the sets of primers previously designed for detection of human adenovirus also produced negative results with animal adenoviruses. These results indicate the importance of further studies to evaluate the usefulness of these tests to trace the source of fecal contamination in water and food and for environmental studies.
Miller, D N; Berry, E D; Wells, J E; Ferrell, C L; Archibeque, S L; Freetly, H C
2006-09-01
Three beef cattle diets were assessed for their potential to produce odorous compounds from cattle feces excreted during the growing and finishing periods. Eight pens containing 51 steers of varying proportions of Brahman and MARC III genotypes were fed either a chopped bromegrass hay diet or a corn silage diet for a 119-d growing period. After the growing period, all steers were switched to the same high-corn finishing diet (high corn) and fed to a target weight of 560 kg (finishing period). Fecal slurries were prepared from a composite of fresh fecal pats collected in each pen during both periods and incubated anaerobically. In additional flasks, starch, protein, or cellulose was added to the composite fecal subsamples to determine the preferred substrates for fermentation and odorous compound production. The content and composition of the fermentation products varied both initially and during the incubation, depending on the diet fed to the steers. The corn silage and high corn feces had the greater initial content of VFA (381.0 and 524.4 micromol/g of DM, respectively) compared with the bromegrass feces (139.3 micromol/g of DM) and accumulated more VFA than the bromegrass feces during the incubation. l-Lactic acid and VFA accumulation in the high corn and corn silage feces was at the expense of starch, based on starch loss and the production of straight-chain VFA. In the bromegrass feces, accumulation of branched-chain VFA and aromatic compounds and the low starch availability indicated that the protein in the feces was the primary source for odorous compound production. Substrate additions confirmed these conclusions. We conclude that starch availability was the primary factor determining accumulation and composition of malodorous fermentation products, and when starch was unavailable, fecal microorganisms utilized protein.
Ghorbani, A; Sadri, H; Alizadeh, A R; Bruckmaier, R M
2012-10-01
Twenty-two newborn Holstein female calves (BW = 39.7 ± 0.40 kg) were used to investigate the effects of chromium-l-methionine (Cr-Met) supplementation of colostrum for 3d after birth and mature milk up to wk 8 on feed intake, growth performance, health status, and metabolic and endocrine traits. Calves were randomly assigned to 2 groups, each consisting of 11 animals: 1) control and 2) 0.03 mg of supplemental Cr/kg of BW(0.75). Body weight, height at withers, and hearth girth were measured weekly. Dry matter intake, rectal temperature, fecal score, and respiratory score were recorded daily. Blood samples were collected at 12, 24, and 72 h after birth, and then every week up to 8 wk. Chromium did not affect mean body weight, dry matter intake, and withers height, but it increased hearth girth and average daily gain, tended to increase final BW, and decreased feed conversion ratio. Respiration rate increased and fecal score decreased with Cr, and rectal temperature tended to decrease with Cr. No Cr × time interactions were observed for performance and health status results except for fecal score. Blood glucose, insulin, insulin-to-glucose ratio, insulin-like growth factor-I, total protein, and triiodothyronine were not affected, whereas blood β-hydroxybutyrate, nonesterified fatty acids, cholesterol, cortisol, and thyroxin were affected by Cr supplementation. Supplemental Cr-Met decreased blood β-hydroxybutyrate at 72 h and in wk 1, 3, 4, 5, and 6 and decreased blood nonesterified fatty acids at 12h and in wk 3, 4, and 5 after birth. Blood cholesterol decreased in all sampling times, except for 12h and wk 7. Chromium decreased blood cortisol at 24h and in wk 2, 4, and 8. In conclusion, the present results demonstrate the beneficial effects of colostrum and milk supplementation with Cr to improve the performance and metabolic status of newborn calves. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Plasma Retention and Systemic Kinetics of 90Sr Intramuscularly Injected in Female Nonhuman Primates
Poudel, Deepesh; Klumpp, John A.; Bertelli, Luiz; ...
2017-08-01
Thirteen female Rhesus macaques were intramuscularly injected with 90Sr(NO 3) 2 diluted in sodium citrate solution. The biokinetic data from these animals were compared against the predictions of the NCRP 156 wound models combined with the ICRP systemic models. We observed observed that the activities measured in plasma of these nonhuman primates (NHPs) were consistently lower than those predicted by the default human biokinetic models. The urinary excretion from the NHPs at times immediately after injection was much greater than that in humans. The fecal excretion rates were found to be in relatively better agreement with humans. Similarly, the activitiesmore » retained in the skeleton of the NHPs were lower than that in humans. These differences were attributed to the higher calcium diet of the NHPs (0.03 to 0.12 g/d/kg body weight) compared to that of humans. These observations were consistent with the early animal and human studies that showed the effect of calcium on strontium metabolism, specifically urinary excretion. Strontium is preferentially filtered at a much higher rate in kidneys than calcium because it is less completely bound to protein than is calcium. Furthermore, these differences, along with large inter-animal variability, should be considered when estimating the behavior of Sr in humans from the metabolic data in animals or vice-versa.« less
Effects of high ambient temperature on urea-nitrogen recycling in lactating dairy cows.
Obitsu, Taketo; Kamiya, Mitsuru; Kamiya, Yuko; Tanaka, Masahito; Sugino, Toshihisa; Taniguchi, Kohzo
2011-08-01
Effects of exposure to hot environment on urea metabolism were studied in lactating Holstein cows. Four cows were fed ad libitum a total mixed ration and housed in a temperature-controlled chamber at constant moderate (18°C) or high (28°C) ambient temperatures in a cross-over design. Urea nitrogen (N) kinetics was measured by determining urea isotopomer in urine after single injection of [(15) N(2) ]urea into the jugular vein. Both dry matter intake and milk yield were decreased under high ambient temperature. Intakes of total N and digestible N were decreased under high ambient temperature but urinary urea-N excretion was increased. The ratio of urea-N production to digestible N was increased, whereas the proportion of gut urea-N entry to urea-N production tended to be decreased under high ambient temperature. Neither return to the ornithine cycle, anabolic use nor fecal excretion of urea-N recycled to the gut was affected by ambient temperature. Under high ambient temperature, renal clearance of plasma urea was not affected but the gut clearance was decreased. Increase of urea-N production and reduction of gut urea-N entry, in relative terms, were associated with increased urinary urea-N excretion of lactating dairy cows in higher thermal environments. 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.
Plasma Retention and Systemic Kinetics of 90Sr Intramuscularly Injected in Female Nonhuman Primates
DOE Office of Scientific and Technical Information (OSTI.GOV)
Poudel, Deepesh; Klumpp, John A.; Bertelli, Luiz
Thirteen female Rhesus macaques were intramuscularly injected with 90Sr(NO 3) 2 diluted in sodium citrate solution. The biokinetic data from these animals were compared against the predictions of the NCRP 156 wound models combined with the ICRP systemic models. We observed observed that the activities measured in plasma of these nonhuman primates (NHPs) were consistently lower than those predicted by the default human biokinetic models. The urinary excretion from the NHPs at times immediately after injection was much greater than that in humans. The fecal excretion rates were found to be in relatively better agreement with humans. Similarly, the activitiesmore » retained in the skeleton of the NHPs were lower than that in humans. These differences were attributed to the higher calcium diet of the NHPs (0.03 to 0.12 g/d/kg body weight) compared to that of humans. These observations were consistent with the early animal and human studies that showed the effect of calcium on strontium metabolism, specifically urinary excretion. Strontium is preferentially filtered at a much higher rate in kidneys than calcium because it is less completely bound to protein than is calcium. Furthermore, these differences, along with large inter-animal variability, should be considered when estimating the behavior of Sr in humans from the metabolic data in animals or vice-versa.« less
He, Hongliang; Lancina, Michael G.; Wang, Jing; Korzun, William J.; Yang, Hu; Ghosh, Shobha
2017-01-01
Current atherosclerosis treatment strategies primarily focus on limiting further cholesteryl esters (CE) accumulation by reducing endogenous synthesis of cholesterol in the liver. No therapy is currently available to enhance the removal of CE, a crucial step to reduce the burden of the existing disease. Given a central role of hepatic cholesteryl ester hydrolase (CEH) in intrahepatic hydrolysis of CE and subsequent removal of the resulting free cholesterol, in this work, we applied galactose-functionalized polyamidoamine (PAMAM) dendrimer G5 (Gal-G5) for hepatocyte-specific delivery of CEH expression vector. The data presented herein show increased specific uptake of Gal-G5 by the hepatocytes in vitro and in vivo. Furthermore, the upregulated CEH expression in the hepatocytes significantly enhanced intracellular hydrolysis of HDL-CE and subsequent conversion/secretion of hydrolyzed free cholesterol (FC) as bile acids. Increased CEH expression in the liver significantly increased the flux of HDL-CE to biliary as well as fecal FC and bile acids. Meanwhile, Gal-G5 did not induce hepatic or renal toxicity. It was not immunotoxic. Because of these encouraging pre-clinical testing results, using this safe and highly efficient hepatocyte-specific gene delivery platform to enhance the hepatic processes involved in cholesterol elimination is a promising strategy for alleviation of atherosclerosis. PMID:28349866
Association between blood cholesterol and sodium intake in hypertensive women with excess weight.
Padilha, Bruna Merten; Ferreira, Raphaela Costa; Bueno, Nassib Bezerra; Tassitano, Rafael Miranda; Holanda, Lidiana de Souza; Vasconcelos, Sandra Mary Lima; Cabral, Poliana Coelho
2018-04-01
Restricted sodium intake has been recommended for more than 1 century for the treatment of hypertension. However, restriction seems to increase blood cholesterol. In women with excess weight, blood cholesterol may increase even more because of insulin resistance and the high lipolytic activity of adipose tissue.The aim of this study was to assess the association between blood cholesterol and sodium intake in hypertensive women with and without excess weight.This was a cross-sectional study with hypertensive and nondiabetic women aged 20 to 59 years, recruited at the primary healthcare units of Maceio, Alagoas, Brazilian Northeast. Excess weight was defined as body mass index (BMI) ≥25.0 kg/m. Sodium intake was estimated by the 24-hour urinary excretion of sodium. Blood cholesterol was the primary outcome investigated by this study, and its relationship with sodium intake and other variables was assessed by Pearson correlation and multivariate linear regression using a significance level of 5%.This study included 165 hypertensive women. Of these, 135 (81.8%) were with excess weight. The mean sodium intake was 3.7 g (±1.9) and 3.4 g (±2.4) in hypertensive women with and without excess weight, respectively. The multiple normal linear regression models fitted to the "blood cholesterol" in the 2 groups reveal that for the group of hypertensive women without excess weight only 1 independent variable "age" is statistically significant to explain the variability of the blood cholesterol levels. However, for the group of hypertensive women with excess weight, 2 independent variables, age and sodium intake, can statistically explain variations of the blood cholesterol levels.Blood cholesterol is statistically inversely related to sodium intake for hypertensive women with excess weight, but it is not statistically related to sodium intake for hypertensive women without excess weight.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yue, Jianmei; Department of Endocrinology, The First Hospital of Zibo, 4# E Mei Shan Dong Road, Zibo 255200; Li, Bo, E-mail: libosubmit@163.com
Objectives: Cholesterol efflux has been thought to be the main and basic mechanism by which free cholesterol is transferred from extra hepatic cells to the liver or intestine for excretion. Salvianolic acid B (Sal B) has been widely used for the prevention and treatment of atherosclerotic diseases. Here, we sought to investigate the effects of Sal B on the cholesterol efflux in THP-1 macrophages. Methods: After PMA-stimulated THP-1 cells were exposed to 50 mg/L of oxLDL and [{sup 3}H] cholesterol (1.0 μCi/mL) for another 24 h, the effect of Sal B on cholesterol efflux was evaluated in the presence of apoA-1, HDL{sub 2}more » or HDL{sub 3}. The expression of ATP binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and liver X receptor-alpha (LXRα) was detected both at protein and mRNA levels in THP-1 cells after the stimulation of Sal B. Meanwhile, specific inhibition of PPAR-γ and LXRα were performed to investigate the mechanism. Results: The results showed that Sal B significantly accelerated apoA-I- and HDL-mediated cholesterol efflux in both dose- and time-dependent manners. Meanwhile, Sal B treatment also enhanced the expression of ABCA1 at both mRNA and protein levels. Then the data demonstrated that Sal B increased the expression of PPAR-γ and LXRα. And the application of specific agonists and inhibitors of further confirmed that Sal exert the function through PPAR-γ and LXRα. Conclusion: These results demonstrate that Sal B promotes cholesterol efflux in THP-1 macrophages through ABCA1/PPAR-γ/LXRα pathway. - Highlights: • Sal B promotes the expression of ABCA1. • Sal B promotes cholesterol efflux in macrophages. • Sal B promotes the expression of ABCA1 and cholesterol efflux through PPAR-γ/LXRα signaling pathway.« less
Akaki, Junji; Tachi, Shiori; Nakamura, Naoki; Arai, Tetsuya; Yamasaki, Hiroo; Inoue, Makoto; Makino, Toshiaki
2018-06-28
Bofutsushosan (fangfengtongshengsan in Chinese, BTS) is a formula in traditional Japanese Kampo medicine and Chinese medicine comprising 18 crude drugs that is used for treating obesity and metabolic syndrome. We evaluated the promotive effects of BTS on lipid and cholesterol elimination in mice. Mice were reared with a high-fat diet containing boiled water extract of BTS for 30 days, and their biochemical parameters as well as the weight and lipid content of feces were measured. We also measured cholesterol uptake into Caco-2 cells cultured with or without BTS extract. The body weight and amounts of visceral fat and subcutaneous fat on day 28; the weights of epididymal, perirenal, and mesenteric fat; and the serum concentrations of triglyceride, glucose, and hemoglobin A1c on day 30 were significantly lower in the BTS extract-treated groups than in the control in a dose-dependent manner. The amounts of lipid and cholesterol in the feces collected from day 6-23 were significantly greater than in the control. When Caco-2 cells were incubated with BTS extract, the uptake of cholesterol into cells was significantly reduced in a concentration-dependent manner. Among the components of BTS, the methanol extracts of Platycodi Radix and Zingiberis Rhizoma contribute but the extracts of Ephedrae Herba and Rhei Rhizoma counteract the suppressive effect of BTS on cholesterol uptake into Caco-2 cells. BTS has beneficial effects on obesity and metabolic syndrome, and its mechanisms of action include the promotion of lipid elimination and the inhibition of cholesterol absorption in the intestine. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Danielsen, E Michael; Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte; Frenzel, Franz
2012-03-01
Transintestinal cholesterol efflux (TICE) has been proposed to represent a non-hepatobiliary route of cholesterol secretion directly "from blood to gut" and to play a physiologically significant role in excretion of neutral sterols, but so far little is known about the proteins involved in the process. We have previously observed that apolipoprotein A-1 (apoA-1) synthesized by enterocytes of the small intestine is mainly secreted apically into the gut lumen during fasting where its assembly into chylomicrons and basolateral discharge is at a minimal level. In the present work we showed, both by immunomicroscopy and subcellular fractionation, that a fraction of the apically secreted apoA-1 in porcine small intestine was not released from the cell surface but instead deposited in the brush border. Cholesterol was detected in immunoisolated microvillar apoA-1, and it was partially associated with detergent resistant membranes (DRMs), indicative of localization in lipid raft microdomains. The apolipoprotein was not readily released from microvillar vesicles by high salt or by incubation with phosphatidylcholine-specific phospholipase C or trypsin, indicating a relatively firm attachment to the membrane bilayer. However, whole bile or taurocholate efficiently released apoA-1 at low concentrations that did not solubilize the transmembrane microvillar protein aminopeptidase N. Based on these findings and the well known role played by apoA-1 in extrahepatic cellular cholesterol removal and reverse cholesterol transport (RCT), we propose that brush border-deposited apoA-1 in the small intestine acts in TICE by mediating cholesterol efflux into the gut lumen. Copyright © 2011 Elsevier B.V. All rights reserved.
Rethinking reverse cholesterol transport and dysfunctional high-density lipoproteins.
Gillard, Baiba K; Rosales, Corina; Xu, Bingqing; Gotto, Antonio M; Pownall, Henry J
2018-04-12
Human plasma high-density lipoprotein cholesterol concentrations are a negative risk factor for atherosclerosis-linked cardiovascular disease. Pharmacological attempts to reduce atherosclerotic cardiovascular disease by increasing plasma high-density lipoprotein cholesterol have been disappointing so that recent research has shifted from HDL quantity to HDL quality, that is, functional vs dysfunctional HDL. HDL has varying degrees of dysfunction reflected in impaired reverse cholesterol transport (RCT). In the context of atheroprotection, RCT occurs by 2 mechanisms: one is the well-known trans-hepatic pathway comprising macrophage free cholesterol (FC) efflux, which produces early forms of FC-rich nascent HDL (nHDL). Lecithin:cholesterol acyltransferase converts HDL-FC to HDL-cholesteryl ester while converting nHDL from a disc to a mature spherical HDL, which transfers its cholesteryl ester to the hepatic HDL receptor, scavenger receptor B1 for uptake, conversion to bile salts, or transfer to the intestine for excretion. Although widely cited, current evidence suggests that this is a minor pathway and that most HDL-FC and nHDL-FC rapidly transfer directly to the liver independent of lecithin:cholesterol acyltransferase activity. A small fraction of plasma HDL-FC enters the trans-intestinal efflux pathway comprising direct FC transfer to the intestine. SR-B1 -/- mice, which have impaired trans-hepatic FC transport, are characterized by high plasma levels of a dysfunctional FC-rich HDL that increases plasma FC bioavailability in a way that produces whole-body hypercholesterolemia and multiple pathologies. The design of future therapeutic strategies to improve RCT will have to be formulated in the context of these dual RCT mechanisms and the role of FC bioavailability. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.
Parnell, Jill A.; Reimer, Raylene A.
2013-01-01
Prebiotic fibres have been proposed to promote weight loss and lower serum cholesterol; however, the mechanisms are not fully understood. The aim of the present research was to identify possible mechanisms through which prebiotic fibres improve serum lipids. Lean and obese JCR:La-cp rats aged 8 weeks consumed one of three diets supplemented with 0, 10 or 20 % prebiotic fibre for 10 weeks. Rats were anaesthetised and a fasting blood sample was taken for lipid analysis. Real-time PCR was used to determine gene expression for cholesterol and fatty acid regulatory genes in liver tissue. Liver and caecal digesta cholesterol and TAG content were quantified. Both doses of prebiotic fibre lowered serum cholesterol levels by 24 % in the obese hyperlipidaemic rats (P<0·05). This change was associated with an increase in caecal digesta as well as an up-regulation of genes involved in cholesterol synthesis and bile production. Additionally, there was a 42 % reduction in TAG accumulation in the liver of the obese rats with 10 % prebiotic diet (P<0·05); however, no change in liver fatty acid synthase (FAS). Prebiotic fibres appear to lower cholesterol levels through increased cholesterol excretion in the form of bile and inhibit the accumulation of TAG in the liver through a mechanism unrelated to FAS. These effects appear to be limited to the obese model and particularly the 10 % dose. The present work is significant as it provides insight into the mechanisms of action for prebiotic fibres on lipid metabolism and furthers the development of dietary treatments for hypercholesterolaemia. PMID:20021705
Normani, M Z; Hussain, S S; Lim, J K; Albrink, M J; Gunnells, C K; Davis, G K
1981-10-01
Two experiments were conducted in the rat to determine the relationships of serum cholesterol (SC, mg/dl), apparent digestibility of dry matter (DDM, %), and digested energy intake (DE, kcal/day) at suboptimal level of energy. The energies in diet and feces were determined by calorimetry. DE as percentage of the National Research Council requirement (DE%) was suboptimal (70 to 85%). The experiments had four to five isofibrous diets, and no fiber diets, supplemented with 0.2% crystalline cholesterol (CChol). Animals in experiment 1 were fed varying amounts of feed with 18% coconut oil in the diets where as these in experiment 2 were given fixed amounts of feed with either 6 or 18% oil. The following regressions (p less than 0.001) for SC were found: experiment 1: -1157.7 -5.97 DDM +105.5 CCI -1.48 CCI2 (r2 0.35), where CCI = CChol, mg/day; -1888.4 -2.66 DE +120.97 CCI -1.62 CCI2 (r2 0.37). Experiment 2: 762.99 -6.15 DDM -0.8 fat cal % -0.87DE% (r2 0.31), where fat cal % = fat calories % of DE. Data indicate that at suboptimal energy intake, SC was inversely related to (1) DDM, (2) fat cal, and (3) total energy intake. Liver cholesterol lowering effect of the dietary fiber was also observed. The above findings help to elucidate various conflicting reports related to diet and blood cholesterol.
Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia
Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang
2015-01-01
Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia. PMID:26694461
Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia.
Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang
2015-12-17
Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.
SKELETAL DYNAMICS IN MAN MEASURED BY NONRADIOACTIVE STRONTIUM
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eisenberg, E.; Gordan, G.S.
Skeletal dynamics were calculated by usual dilution formulas, using stable strontium as a tracer, in 25 normal subjects, 14 athletes, 26 patients with postmenopausal osteoporosis, 28 with primary hyperparathyroidism, 3 with hyperadrenocorticism 8 with acromegaly, 7 with thyrotoxicosis, 11 with urclithiasis, 5 with Paget's disease of bone. and 1 with vitamin D poisoning. The technic requires that 10 mEq of strontium gluconate be injected intravenously and blood and urine concentrations be measured for 4 to 6 days. In normal subjects the rapidly miscible pool was equivalent to 42.7 + 1.1 L of serum, turning over at a rate of 13.5more » plus or minus 0.6 L daily, of which 3.9 + 0.2 L was excreted by the kidney and 9.6 + 0.4 L went to bone. Since only approximately 2.5% of the pool is excreted in the feces daily, fecal excretion was not measured routinely. Good reproducibility was found in 21 duplicate studies. Intense muscular exercise (athletes) was found to expand the pool greatly and to accelerate the rate of deposition in bone. Kinetically, two divergent types of osteoporosis were differentiated. A small pool and low rate of bone deposition were found in postmenopausal osteoporosis and Cushing's disease of long duration. The large pool and rapid rate of bone deposition in thyrotoxicosis was confirmed and also found in acromegaly. In these two, excessive bone resorption is postulated. Urinary excretion rate was excessive in Cushing's disease, thyrotoxicosis, and acromegaly. In hyperparathyroidism with clinically evident osteitis, expanded pools, greatly increased turnover, urinary excretion, and bone deposition rates were confirmed. In patients with normal roentgenographic appearance and phosphatase, bone involvement was shown by slight increase in bone deposition rate and microscopic foci of resorption on iliac crest biopsy. In seven patients without histological foci of resorption, the bone deposition rate was not increased. (auth)« less
Nanotechnology for Synthetic High Density Lipoproteins
Luthi, Andrea J.; Patel, Pinal C.; Ko, Caroline H.; Mutharasan, R. Kannan; Mirkin, Chad A.; Thaxton, C. Shad
2014-01-01
Atherosclerosis is the disease mechanism responsible for coronary heart disease (CHD), the leading cause of death worldwide. One strategy to combat atherosclerosis is to increase the amount of circulating high density lipoproteins (HDL), which transport cholesterol from peripheral tissues to the liver for excretion. The process, known as reverse cholesterol transport, is thought to be one of the main reasons for the significant inverse correlation observed between HDL blood levels and the development of CHD. This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD. PMID:21087901
Rousset, Elodie; Berri, Mustapha; Durand, Benoit; Dufour, Philippe; Prigent, Myriam; Delcroix, Thibault; Touratier, Anne; Rodolakis, Annie
2009-01-01
Q fever is a zoonosis caused by Coxiella burnetii, a bacterium largely carried by ruminants and shed into milk, vaginal mucus, and feces. The main potential hazard to humans and animals is due to shedding of bacteria that can then persist in the environment and be aerosolized. The purpose of this study was to evaluate shedding after an outbreak of Q fever abortion in goat herds and to assess the relationship with the occurrence of abortions and antibody responses. Aborting and nonaborting goats were monitored by PCR for C. burnetii shedding 15 and 30 days after the abortion episodes. PCR analysis of all samples showed that 70% (n = 50) of the aborting and 53% (n = 70) of the nonaborting goats were positive. C. burnetii was shed into vaginal mucus, feces, and milk of 44%, 21%, and 38%, respectively, of goats that aborted and 27%, 20%, and 31%, respectively, of goats that delivered normally. Statistical comparison of these shedding results did not reveal any difference between these two groups. PCR results obtained for the vaginal and fecal routes were concordant in 81% of cases, whereas those for milk correlated with only 49% of cases with either vaginal or fecal shedding status. Serological analysis, using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and complement fixation tests, showed that at least 24% of the seronegative goats shed bacteria. Positive vaginal and fecal shedding, unlike positive milk shedding, was observed more often in animals that were weakly positive or negative by ELISA or IFA. Two opposite shedding trends were thus apparent for the milk and vaginal-fecal routes. Moreover, this study showed that a nonnegligible proportion of seronegative animals that delivered normally could excrete C. burnetii.
Metabolism and Distribution of 131 I-labelled Albumin in the Pig *
Dich, John; Nielsen, Knud
1963-01-01
The biological behaviour of porcine 131I-albumin has been investigated in 11 normal pigs, weight appr. 20 kg. Mean values obtained from the experiments are: Albumin degradation: 15.1 ± 2.1 per cent/day (0.18 ± 0.01 g/kg/day), extravascular: intravascular albumin ratio: 1.71 ± 0.29. Fecal excretion of radio-activity ranged from 0.77—1.87 per cent of the dose (mean: 1.11 per cent) during the first 4 days of the experiment. The results are discussed with special reference to the rôle of the gastrointestinal tract in health and in various digestive disorders. PMID:17649473
Congenital Chloride Diarrhea - Novel Mutation in SLC26A3 Gene.
Bhardwaj, Swati; Pandit, Deepti; Sinha, Aditi; Hari, Pankaj; Cheong, Hae Il; Bagga, Arvind
2016-08-01
The authors report a case of congenital chloride diarrhea with molecular confirmation of diagnosis. A 10-mo-old boy presented with failure to thrive, voluminous diarrhea, dehydration, hyponatremia, hypokalemia, metabolic alkalosis and history of maternal polyhydramnios. The diagnosis of congenital chloride diarrhea was based on high fecal and low urinary chloride excretion, in addition to biochemical abnormalities. Genetic testing revealed a novel homozygous mutation in exon 4 of the SLC26A3 gene that encodes the protein regulating chloride bicarbonate absorption in distal ileum and colon. Therapy with oral fluids and electrolytes led to decrease in stool frequency and improvement in growth parameters.
Vega, Gloria Lena; Weiner, Myron F; Lipton, Anne M; Von Bergmann, Klaus; Lutjohann, Dieter; Moore, Carol; Svetlik, Doris
2003-04-01
The statin treatment of dyslipidemia is associated with a reduced risk of development of Alzheimer disease (AD). The effect may be mediated by a reduction in cholesterol biosynthesis in the brain, by lowering levels of apolipoprotein E (apo E)-containing lipoproteins, or by pleitropic effects such as reduction in beta-amyloid production. In the brain, cholesterol from damaged or dying neurons is converted to 24S-hydroxycholesterol by cholesterol 24-hydroxylase (CYP46). The oxysterol is subsequently transferred across the blood-brain barrier, transported to the liver by low-density lipoproteins (LDLs), and excreted as bile acids. Most of plasma 24S-hydroxycholesterol is derived from brain cholesterol; consequently, plasma levels of the oxysterol reflect brain cholesterol catabolism. To examine the effect of 3 statins and a nonstatin hypolipidemic agent on plasma levels of 24S-hydroxycholesterol and apo E in patients with AD. The study had a sequential parallel design. It was open-labeled and involved lipoprotein and 24S-hydroxycholesterol evaluations at baseline and at 6 weeks of treatment with 40 mg of lovastatin, simvastatin, or pravastatin sodium per day, or 1 g of extended-release niacin per day. Blood samples were drawn after a 12-hour fast for measurement of plasma sterols, oxysterols, lipoprotein cholesterol, and levels of apo E, plasma transaminases, and glucose. Measurements were made at baseline and during treatment. Statin treatment reduced levels of plasma lathosterol by 49.5%, 24S-hydroxycholesterol by 21.4%, LDL cholesterol by 34.9%, and total cholesterol by 25%. The ratios of lathosterol-campesterol and 24S-hydroxycholesterol-LDL cholesterol were reduced significantly, but the ratio of 24S-hydroxycholesterol-total cholesterol was unchanged. Extended-release niacin also significantly reduced levels of 24S-hydroxycholesterol by 10% and LDL cholesterol by 18.1%. None of the agents lowered plasma concentration of apo E. Statins lowered levels of plasma 24S-hydroxycholesterol without affecting levels of apo E. The LDL lowering was more pronounced than 24S-hydroxycholesterol reductions. The effect of statins on LDL partially explains the reduction of plasma oxysterol level.
Methods to improve routine bioassay monitoring for freshly separated, poorly transported plutonium
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bihl, D.E.; Lynch, T.P.; Carbaugh, E.H.
1988-09-01
Several human cases involving inhalation of plutonium oxide at Hanford have shown clearance half-times from the lung that are much longer than the 500-day half-time recommended for class Y plutonium in Publication 30 of the International Commission on Radiological Protection(ICRP). The more tenaciously retained material is referred to as super class Y plutonium. The ability to detect super class Y plutonium by current routine bioassay measurements is shown to be poor. Pacific Northwest Laboratory staff involved in the Hanford Internal Dosimetry Program investigated four methods to se if improvements in routine monitoring of workers for fresh super class Y plutoniummore » are feasible. The methods were lung counting, urine sampling, fecal sampling, and use of diethylenetriaminepentaacetate (DTPA) to enhance urinary excretion. Use of DTPA was determined to be not feasible. Routine fecal sampling was found to be feasible but not recommended. Recommendations were made to improve the detection level for routine annual urinalysis and routine annual lung counting. 12 refs., 9 figs., 7 tabs.« less
Gupta, Neeraj; Zhang, Steven; Pusalkar, Sandeepraj; Plesescu, Mihaela; Chowdhury, Swapan; Hanley, Michael J; Wang, Bingxia; Xia, Cindy; Zhang, Xiaoquan; Venkatakrishnan, Karthik; Shepard, Dale R
2018-06-01
This two-part, phase I study evaluated the mass balance, excretion, pharmacokinetics (PK), and safety of ixazomib in patients with advanced solid tumors. In Part A of the study, patients received a single 4.1 mg oral solution dose of [ 14 C]-ixazomib containing ~500 nCi total radioactivity (TRA), followed by non-radiolabeled ixazomib (4 mg capsule) on days 14 and 21 of the 35-day PK cycle. Patients were confined to the clinic for the first 168 h post dose and returned for 24 h overnight clinic visits on days 14, 21, 28, and 35. Blood, urine, and fecal samples were collected during Part A to assess the mass balance (by accelerator mass spectrometry), excretion, and PK of ixazomib. During Part B of the study, patients received non-radiolabeled ixazomib (4 mg capsules) on days 1, 8, and 15 of 28-day cycles. After oral administration, ixazomib was rapidly absorbed with a median plasma T max of 0.5 h and represented 70% of total drug-related material in plasma. The mean total recovery of administered TRA was 83.9%; 62.1% in urine and 21.8% in feces. Only 3.23% of the administered dose was recovered in urine as unchanged drug up to 168 h post dose, suggesting that most of the TRA in urine was attributable to metabolites. All patients experienced a treatment-emergent adverse event, which most commonly involved the gastrointestinal system. These findings suggest that ixazomib is extensively metabolized, with urine representing the predominant route of excretion of drug-related material.Trial ID: ClinicalTrials.gov # NCT01953783.
Calcium Kinetics During Space Flight
NASA Technical Reports Server (NTRS)
Smith, Scott M.; Wastney, Meryl E.; OBrien, Kimberly O.; Lane, Helen W.
1999-01-01
Bone loss is one of the most detrimental effects of space flight, threatening to limit the duration of human space missions. The ability to understand and counteract this loss will be critical for crew health and safety during and after extended-duration missions. The hypotheses to be tested in this project are that space flight alters calcium homeostasis and bone mineral metabolism, and that calcium homeostasis and bone mineral metabolism will return to baseline within days to weeks of return to Earth. These hypotheses will be evidenced by elevated rates of bone mineral resorption and decreased bone mineral deposition, decreased absorption of dietary calcium, altered calcitropic endocrine profiles, elevated excretion of calcium in urine and feces, and elevated excretion of markers of bone resorption. The second hypothesis will be evidenced by return of indices of calcium homeostasis and bone metabolism to preflight levels within days to weeks of return to Earth. Studies will be conducted on International Space Station astronauts before, during, and after extended-duration flights. Measurements of calcium kinetics, bone mass, and endocrine/biochemical markers of bone and calcium homeostasis will be conducted. Kinetic studies utilizing dual isotope tracer kinetic studies and mathematical modeling techniques will allow for determination of bone calcium deposition, bone calcium resorption, dietary calcium absorption and calcium excretion (both urinary and endogenous fecal excretion). These studies will build upon preliminary work conducted on the Russian Mir space station. The results from this project will be critical for clarifying how microgravity affects bone and calcium homeostasis, and will provide an important control point for assessment of countermeasure efficacy. These results are expected to aid in developing countermeasures for bone loss, both for space crews and for individuals on Earth who have metabolic bone diseases.
Siebers, Nicholas; Palmer, Melissa; Silberg, Debra G; Jennings, Lee; Bliss, Caleb; Martin, Patrick T
2018-02-01
Volixibat is a potent inhibitor of the apical sodium-dependent bile acid transporter in development for the treatment of nonalcoholic steatohepatitis. This phase 1, open-label study investigated the absorption, distribution, metabolism, and excretion of [ 14 C]-volixibat in heathy men. Eligible men (n = 8) aged 18-50 years (body mass index 18.0-30.0 kg/m 2 ; weight >50 kg) received a single oral dose of [ 14 C]-volixibat 50 mg containing ~5.95 µCi radioactivity. The primary objectives were to assess the pharmacokinetics of [ 14 C]-volixibat and to determine the total radioactivity in whole blood, plasma, urine, and feces at pre-selected time points over 6 days. The secondary objectives were to characterize metabolites and to assess the safety and tolerability. Low concentrations of volixibat (range 0-0.179 ng/mL) were detected in plasma up to 8 h following administration; the pharmacokinetic parameters could not be calculated. No radioactivity was observed in plasma or whole blood. The percentage (mean ± standard deviation) of total radioactivity in urine was 0.01 ± 0.007%. The vast majority (92.3 ± 5.25%) of volixibat was recovered in feces (69.2 ± 33.1% within 24 h). Unchanged volixibat was the only radioactive component detected in feces. Adverse events were mild in severity and mostly gastrointestinal. Changes in laboratory values were not clinically meaningful. Following oral administration, [ 14 C]-volixibat was excreted unchanged from the parent compound almost exclusively via fecal excretion, indicating that the drug is minimally absorbed. Consistent with other studies, adverse events were primarily gastrointestinal in nature. ClinicalTrials.gov identifier NCT02571192.
Racial differences in potassium homeostasis in response to differences in dietary sodium in girls123
Wigertz, Karin; Martin, Berdine R; Braun, Michelle; Pratt, J Howard; Peacock, Munro; Weaver, Connie M
2010-01-01
Background: Racial differences in the renal disposition of potassium may be related to mechanisms for the greater susceptibility to hypertension in blacks than in whites. Objective: Our objective was to study the racial differences in the renin-angiotensin-aldosterone system and in potassium balance in black and white girls consuming a controlled diet that was low in potassium with 2 amounts of sodium intake (low compared with high). Design: The studies reported here were performed in 40 black and 28 white girls, aged 11–15 y, under highly controlled metabolic conditions. The studies comprised 2 sessions of 20-d metabolic balance sessions, at 2 amounts of dietary sodium intake (58 and 170 mmol · L−1 · d−1), in a crossover design and with a constant dietary potassium intake of 50 mmol · L−1 · d−1. Repeated-measures analysis of variance was used to test for racial differences in potassium output and retention by sodium intakes. Results: Thirty black and 20 white girls completed the study. Urinary potassium excretion was lower in blacks than in whites, regardless of sodium intake (P < 0.05), with no differences in fecal or sweat potassium excretion. Cumulative potassium retention was significantly higher in blacks while consuming the low sodium diet. Plasma aldosterone concentrations after upright posture were significantly lower in blacks than in whites but were similar when supine, as were urinary aldosterone excretion rates. On week 3, blood pressure, body weight, urinary volume, creatinine, and serum sodium and potassium were similar. Conclusion: The well-known racial difference in urinary potassium excretion appears to be at least in part due to greater renal retention of potassium in black girls. PMID:20007307
The Garden of Eden: Implications for cardiovascular disease prevention.
Jenkins, D J; Jenkins, A L; Kendall, C W; Vuksan, V; Vidgen, E
2000-09-01
Creationists and evolutionists acknowledge that the human diet has passed through at least four phases. The original plant food-based diet; a second phase of increasing meat consumption; a third phase of agricultural dependence on starchy foods; and, finally, the supermarket high-saturated fat, low-fibre phase with minimal energy expenditure. Our aim is to define the value of the original or 'Garden of Eden' diet and to speculate on which components should be retained in the modern supermarket diet. The original plant-based diet would have been high in vegetable proteins, plant sterols, dietary fibre and antioxidants, and low in saturated fats with no trans fatty acids. This diet would increase fecal cholesterol losses from the body as bile acids and neutral sterols, while providing little stimulus to cholesterol synthesis. To replace the bile acid losses we would have adapted to a relatively high capacity for cholesterol synthesis. Now, in the high-saturated fat, low-fibre supermarket age, this may be a disadvantage and predisposes consumers to high serum cholesterol and increased risk of cardiovascular disease. We believe part of the solution is a return to the plant-based 'Garden of Eden' diet combined with physical activity. A lipid-lowering portfolio containing vegetable proteins, especially soy, plant sterols and high fibre intakes combined with low saturated and trans fatty acids and cholesterol, would go a long way to reducing serum lipids and coronary heart disease risk seen in the modern Western diet.
Buchman, Alan L; Fryer, Jon; Wallin, Anita; Ahn, Chul W; Polensky, Sharon; Zaremba, Karen
2006-01-01
Patients with short bowel syndrome have significant fluid losses. This represents a significant management problem, especially in patients with minimal residual intestine. We determined whether clonidine, an alpha2-adrenergic agonist, is effective in decreasing fecal water and sodium (Na) losses in patients with proximal jejunostomy. Eight parenteral nutrition (PN)-dependent subjects (3 men, 5 women), aged 49.9+/-10.2 years, with a residual small bowel length of 71.8+/-152.0 cm that ended in a jejunostomy, were studied. Subjects were admitted to the North-western General Clinical Research Center (GCRC) for a 2-day equilibrium period while receiving a self-selected 100 g fat diet with protein 1.5 g/kg/d and 30 kcal/kg/d and 1 L/d of oral rehydration solution. A D-xylose test was performed after an overnight fast. On days 3-5, all stool and urine were collected for volume, weight, fat, nitrogen, energy, sodium, magnesium, potassium, and calcium. Meals were provided in duplicate and the equivalent portions consumed by each patient were analyzed for fluid volume, fat, nitrogen, energy, sodium, magnesium, calcium, and potassium in order to calculate nutrient balances. At the conclusion of the stool and urine collections (day 6), a clonidine (0.3 mg) patch was applied to the shoulder. Subjects were restudied after 1 week. Daily fecal volume and weight were 4.514+/-1.769 L/d and 4394+/-1727 g/d, respectively, at baseline. Five subjects were net "secretors" in that excreted fecal volume exceeded oral intake. Fecal volume decreased by 427+/-562 mL/d (8.9%, p=.07). Fecal weight decreased by 438+/-527 g/d (9.4%, p=.05). Urine volume correspondingly increased by 747+/-1934 mL (18.9%, p=not significant [NS]). The increase in urine output was weakly and negatively correlated with the decrease in fecal volume and weight (r=-0.37 and -0.41, respectively, p=NS). Oral fluid intake decreased slightly from 3.328+/-1.246 L/d baseline to 3.203+/-1.119 L/d with clonidine therapy (-3.8%, p=NS). Fecal Na loss was significantly decreased from baseline (887+/-996 mg/d, 11.2+/-12.3%; p=.036). This was not related to decreased oral Na intake, which actually increased from baseline (3.799+/-2.271 g/d) to 3.933+/-1.314 g/d after clonidine therapy (p=NS). No patient developed hypotension. Our results show the transdermal administration of clonidine is associated with a modest but clinically significant decrease in fecal output in patients with short bowel syndrome and high-output proximal jejunostomy that require chronic parenteral fluid infusion. This is accompanied by decreased fecal Na loss.
Effects of abomasal oligofructose on blood and feces of Holstein steers.
Mainardi, S R; Hengst, B A; Nebzydoski, S J; Nemec, L M; Gressley, T F
2011-08-01
Subacute ruminal acidosis can result in increased flow of fermentable substrates to the hindgut, which can negatively affect animal health and productivity. However, animal responses to increased hindgut fermentation independent of subacute ruminal acidosis have rarely been evaluated. This study determined the impact of abomasal dosage of a fermentable carbohydrate on animal performance and blood and fecal variables. Six ruminally cannulated Holstein steers fed a lactating dairy cow ration were used in a crossover design study with 14-d periods. On d 13 of each period, steers were infused abomasally with a pulse dose of 0 (control) or 1 (Oligo) g of oligofructose/kg of BW. Blood samples collected at 0, 3, 6, 9, 12, and 24 h after abomasal oligofructose dose were evaluated for metabolites (blood urea N, β-hydroxybutyric acid, and NEFA) and systemic inflammatory markers (Cu, serum amyloid A, and haptoglobin). Fecal samples, rectal temperature, heart rate, and respiratory rate were taken at 0, 3, 6, 9, 12, 24, and 48 h after abomasal dosage. Fecal samples were assayed for pH, DM percentage, consistency score (1=liquid to 5=coarse), and organic acid concentrations. Data were evaluated using a model including the fixed effects of treatment, time after dosage, and their interaction. Effects of treatment or treatment × time were not significant for DMI, blood variables, rectal temperature, or respiratory rate. Fecal pH was slightly reduced for Oligo compared with control steers (6.76 vs. 7.02; P=0.04). A treatment × time interaction occurred for fecal DM (P < 0.001). Compared with control steers, DM content of feces was reduced in Oligo steers at 6 h (12.6 vs. 15.2%) but increased at 9 h (16.3 vs. 15.0%) and 12 h (16.5 vs. 15.0). Fecal consistency score was reduced by the Oligo treatment at 6 h (1.44 vs. 2.83; P < 0.001) and 9 h (1.83 vs. 2.67; P=0.005). A treatment × time interaction was detected for fecal concentrations of lactate and acetate (P < 0.05) and tended to occur for propionate and butyrate (P < 0.10). The greatest difference for all organic acids occurred at 12 h, when fecal concentrations of lactate, acetate, propionate, and butyrate were 0.5, 47, 11, and 4.0 mM in control steers and 5.3, 76, 15, and 6.8 mM in Oligo steers, respectively. In summary, abomasal dosage of 1 g of oligofructose/kg of BW increased fecal excretion of microbial fermentation products in steers without causing metabolic acidosis, metabolic disruption, or inflammation. © 2011 American Society of Animal Science. All rights reserved.
Tang, Minghua; Larson-Meyer, D Enette; Liebman, Michael
2008-05-01
High oxalate intake resulting from consuming supplemental doses of cinnamon and turmeric may increase risk of hyperoxaluria, a significant risk factor for urolithiasis. This study assessed urinary oxalate excretion from supplemental doses of cinnamon and turmeric as well as changes in fasting plasma glucose, cholesterol, and triacylglycerol concentrations. Eleven healthy subjects, aged 21-38 y, participated in an 8-wk, randomly assigned, crossover study that involved the ingestion of supplemental doses of cinnamon and turmeric for 4-wk periods that provided 55 mg oxalate/d. Oxalate load tests, which entailed the ingestion of a 63-mg dose of oxalate from the test spices, were performed after each 4-wk experimental period and at the study onset with water only (control treatment). Fasting plasma glucose and lipid concentrations were also assessed at these time points. Compared with the cinnamon and control treatments, turmeric ingestion led to a significantly higher urinary oxalate excretion during the oxalate load tests. There were no significant changes in fasting plasma glucose or lipids in conjunction with the 4-wk periods of either cinnamon or turmeric supplementation. The percentage of oxalate that was water soluble differed markedly between cinnamon (6%) and turmeric (91%), which appeared to be the primary cause of the greater urinary oxalate excretion/oxalate absorption from turmeric. The consumption of supplemental doses of turmeric, but not cinnamon, can significantly increase urinary oxalate levels, thereby increasing risk of kidney stone formation in susceptible individuals.
Hales, K E; Cole, N A; MacDonald, J C
2013-02-01
The use of wet distillers grains with solubles (WDGS) in feedlot diets has increased in the Southern Great Plains as a result of the growing ethanol industry. Nutrient balance and respiration calorimetry research evaluating the use of steam-flaked corn (SFC)-based diets in conjunction with WDGS is limited. Therefore, the effects of increasing concentrations of WDGS in a SFC-based diet on energy metabolism, C, and N balance, and enteric methane (CH4) production was evaluated in Jersey steers fed at 2 times maintenance, using respiration calorimetry chambers. Four treatments were used in two 4 × 4 Latin square designs, using 8 steers. Treatments consisted of: 1) SFC-based diet with 0% WDGS (SFC-0); 2) SFC-based diet with 15% WDGS (SFC-15); 3) SFC-based diet with 30% WDGS (SFC-30); and 4) SFC-based diet with 45% WDGS (SFC-45). Diets were balanced for degradable intake protein (DIP) by adding cottonseed meal to the SFC-0 diet. As a proportion of GE, fecal, urinary, and CH4 energy increased linearly (P < 0.03) as WDGS concentration increased in the diet. In contrast, DE, ME, and retained energy decreased linearly (P < 0.01) as a proportion of GE as WDGS concentration increased. Increasing concentration of WDGS in the diet did not affect (P > 0.78) heat production as a proportion of GE. As a result of greater N intake, total N excretion increased linearly (P < 0.01) with increasing WDGS inclusion in the diet. Fecal C loss and CH4-C respired increased linearly (P < 0.01) when WDGS concentration increased in the diet whereas CO2-C respired decreased (linear, P = 0.05) as WDGS concentration increased. We conclude that CH4 production as a proportion of GE increases linearly (P < 0.01) when WDGS concentration in the diet is increased; however, dietary inclusion of WDGS at up to 45% seems to have no effect (P > 0.78) on heat production as a proportion of GE. The reason for a linear decrease in retained energy as WDGS increased was likely because of increased fecal energy loss associated with feeding WDGS. Total N excretion, fecal C loss, and CH4-C respired increased linearly with increasing concentration of WDGS in the diet. We determined NEg values for WDGS to be 2.02, 1.61, and 1.38 Mcal/kg when included at 15%, 30%, and 45%, respectively, in a SFC-based diet. From these results we conclude that the energy value (NEg) of WDGS in a finishing cattle diet based on SFC must be decreased as the inclusion increases.
Maeda, Hiroaki; Zhu, Xia; Omura, Kazunobu; Suzuki, Shiho; Kitamura, Shinichi
2004-01-01
Lactobacillus kefiranofaciens was reported to produce an exopolysaccharide named kefiran. In the present study, we developed a new medium, rice hydrolyzate (RH) medium, for the culture of L. kefiranofaciens. Structural analyses revealed that the exopolysaccharide produced by L. kefiranofaciens from RH medium was composed of a hexasaccharide repeating unit, and essentially identical to the kefiran reported in previous studies. A study on the effects of kefiran in animals demonstrated that kefiran significantly suppressed increase of blood pressure and reduced the serum cholesterol levels in SHRSP/Hos rats when subjects consumed excessive dietary cholesterol. Kefiran supplementation demonstrated the ability to significantly lower blood glucose in KKAy mice. In addition, the administration of kefiran in constipated SD rats caused an obvious improvement in the levels of fecal moisture and wet weights of feces. These results suggest that kefiran could be used as a functional food to prevent some commonly occurring diseases.
Vinyard, J R; Hall, J B; Sprinkle, J E; Chibisa, G E
2018-05-18
Teff (Eragrostis tef cv. Moxie), a warm-season annual grass, could be an excellent forage for beef cattle. However, there is limited information on its nutritive value to cattle when harvested at different stages of maturity. Thus, the objective of this research was to determine the effect of feeding teff hay harvested at the boot (BT), early-heading (EH), or late-heading (LH) stages of maturity on nutrient intake, ruminal fermentation characteristics, omasal nutrient flow, and N utilization in beef cattle. Six ruminally cannulated beef heifers (mean initial BW ± SD, 476 ± 32.6) were used in a replicated 3 × 3 Latin square design with 28-d periods (18 d for adaptation and 10 d for measurements). Dry matter intake was measured daily. Indwelling pH loggers were used to measure ruminal pH from d 21 to 28. Ruminal fluid and omasal digesta were collected from d 26 to 28 to determine fermentation characteristics and omasal nutrient flow. Fecal and urine samples to quantify N excretion were also collected (d 26 to 28). Blood samples for plasma urea-N (PUN) determination were collected 3 h post-feeding on d 28. There were no changes (P > 0.28) in the ADF or NDF content of teff with advancing maturity, but iNDF increased (P < 0.01) with increasing maturity. Maturity had no effect (P ≥ 0.14) on DMI, and ruminal total short-chain fatty acid (SCFA) concentration, pH, digestibility and outflow of DM, OM, NDF, ADF, and CP. However, the CP content of BT hay was greater (P < 0.01) than for EH and LH hay (18.1, 14.1, and 11.5%, respectively, DM basis), and this resulted in the higher CP intake (P < 0.01) for heifers fed the BT than the EH and LH hay. Consequently, ruminal ammonia-N (NH3-N) concentration was greater (P < 0.01) for heifers fed BT than EH and LH hay, thereby possibly explaining the tendency for a decrease (P = 0.08) in PUN concentration, and a decrease (P < 0.01) in the excretion of total N, urine N and urea-N (UUN) with advancing maturity. However, fecal N excretion (g/d) did not differ (P = 0.76). In conclusion, despite a decrease in CP intake and ruminal NH3-N concentration, feeding beef heifers EH and LH compared to BT teff hay did not compromise ruminal digestion and outflow of DM, OM, NDF, ADF, and CP, and microbial protein synthesis. Advancing maturity in teff hay also resulted in a decrease in the excretion of total N and urine N and UUN when fed to cattle.
Hales, K E; Cole, N A; MacDonald, J C
2012-09-01
The growing ethanol industry in the Southern Great Plains has increased the use of wet distillers grains with solubles (WDGS) in beef cattle (Bos taurus) finishing diets. Few studies have used steam-flaked corn (Zea mays L.; SFC)-based diets to evaluate the effects of WDGS in finishing cattle diets, and a reliable estimate of the net energy value of WDGS has yet to be determined. Effects of corn processing method and WDGS on energy metabolism, C and N balance, and enteric methane (CH(4)) production were evaluated in a short-term study using 8 Jersey steers and respiration calorimetry chambers. A 2 by 2 factorial arrangement of treatments was used in a Latin square design. The 4 treatment combinations consisted of: i) SFC-based diet with 0% WDGS (SFC-0); ii) SFC-based diet with 30% WDGS (SFC-30); iii) dry-rolled corn (DRC)-based diet with 0% WDGS (DRC-0); and iv) DRC-based diet with 30% WDGS (DRC-30). Diets were balanced for degradable intake protein (DIP) and ether extract (EE) by the addition of cottonseed (Gossypium hirsutum L.) meal and yellow grease. As a proportion of GE, grain processing method did not affect (P ≥ 0.12) fecal, digestible, urinary, and ME, or heat production. Steers consuming SFC-based diets produced less (P < 0.04) CH(4) than steers consuming DRC-based diets. Retained energy tended to be greater (P = 0.09) for cattle consuming SFC- than DRC-based diets. Inclusion of WDGS did not affect (P ≥ 0.17) fecal, digestible, urinary, metabolizable, and retained energy, or heat production as a proportion of GE. Furthermore, neither inclusion of WDGS or grain processing method affected (P ≥ 0.17) daily CO(2) production. Due in part to greater N intake, cattle consuming diets containing 30% WDGS excreted more (P = 0.01) total N and excreted a greater (P < 0.01) quantity of N in the urine. From these results, we conclude that cattle consuming SFC-based diets produce less CH(4) and retain more energy than cattle fed DRC-based diets; however, dietary inclusion of WDGS at 30% seems to have little effect on CH(4) production and energy metabolism when diets are balanced for DIP and EE. Cattle excrete a greater amount of C when fed DRC compared with SFC-based diets, and dietary inclusion of 30% WDGS increases urinary N excretion. Finally, we determined the NE(g) values for WDGS were 1.66 and 1.65 Mcal/kg in a SFC or DRC-based diet, respectively, when WDGS replaced 30% of our control (SFC-0 and DRC-0) diets.
Shahbazi, Sajad; Kaur, Jagdeep; Kuanar, Ananya; Kar, Dattatreya; Singh, Shikha; Sobti, Ranbir Chander
Alzheimer's disease (AD), a worldwide renowned progressive neurodegenerative disorder, is the most common cause of dementia. There are several studies on the important role of cholesterol metabolism in AD pathogenesis, which indicated that the high concentrations of serum cholesterol increase the risk of AD. Biosynthesis of the plasma cholesterol and other isoprenoids is catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) through the conversion of HMG-CoA to mevalonic acid in mevalonate pathway. Normally, the high level of plasma cholesterol is downregulated by HGMCR inhibition as the result of degradation of LDL, but in abnormal conditions, for example, high blood glucose, the HMGCR over activated resulting in uncontrolled blood cholesterol. Selective HMGCR inhibitor drugs such as statins, which increase the catabolism of plasma LDL and reduce the plasma concentration of cholesterol, have been investigated as a possible treatment for AD. In the present study, we have identified the binding modes of 22 various derivatives of 3-sulfamoylpyrroles 16, prepared via a [3 + 2] cycloaddition of a münchnone with a sulfonamide-substituted alkyne, by using efficient biocomputational tools. Out of 22, 5 ligands, with code numbers 5b, 5c, 5d, 5i, and 5j, possessed most absorption, distribution, metabolism, and excretion (ADME) and toxicity profiles in acceptable ranges. Among ligands, 5j (sodium (3R,5R)-7-(3-(N,N-dimethylsulfamoyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate) could inhibit HMGCR enzyme in inhibitory binding site with affinity value -12.17 kcal/mol and binding energy -94.10 kcal/mol through 5 hydrogen bonds. It showed the best ADME and toxicity profiling and higher affinity values than other potent candidate and market drugs such as atorvastatin and rosuvastatin. Therefore, it is suggested for further in vivo investigation, the druggability of 5j and its cholesterol regulatory impact on AD.
Khelil-Arfa, H; Boudon, A; Maxin, G; Faverdin, P
2012-10-01
The increase in the worldwide demand for dairy products, associated with global warming, will emphasize the issue of water use efficiency in dairy systems. The evaluation of environmental issues related to the management of animal dejections will also require precise biotechnical models that can predict effluent management in farms. In this study, equations were developed and evaluated for predicting the main water flows at the dairy cow level, based on parameters related to cow productive performance and diet under thermoneutral conditions. Two datasets were gathered. The first one comprised 342 individual measurements of water balance in dairy cows obtained during 18 trials at the experimental farm of Méjussaume (INRA, France). Predictive equations of water intake, urine and fecal water excretion were developed by multiple regression using a stepwise selection of regressors from a list of seven candidate parameters, which were milk yield, dry matter intake (DMI), body weight, diet dry matter content (DM), proportion of concentrate (CONC) and content of crude protein (CP) ingested with forage and concentrate (CPf and CPc, g/kg DM). The second dataset was used for external validation of the developed equations and comprised 196 water flow measurements on experimental lots obtained from 43 published papers related to water balance or digestibility measurements in dairy cows. Although DMI was the first predictor of the total water intake (TWI), with a partial r(2) of 0.51, DM was the first predictive parameter of free water intake (FWI), with a partial r(2) of 0.57, likely due to the large variability of DM in the first dataset (from 11.5 to 91.4 g/100 g). This confirmed the compensation between water drunk and ingested with diet when DM changes. The variability of urine volume was explained mainly by the CPf associated with DMI (r.s.d. 5.4 kg/day for an average flow of 24.0 kg/day) and that of fecal water was explained by the proportion of CONC in the diet and DMI. External validation showed that predictive equations excluding DMI as predictive parameters could be used for FWI, urine and fecal water predictions if cows were fed a well-known total mixed ration. It also appeared that TWI and FWI were underestimated when ambient temperature increased above 25°C and possible means of including climatic parameters in future predictive equations were proposed.
Di Stefano, A. F. D.; Rusca, A.; Loprete, L.; Dröge, M. J.; Moro, L.; Assandri, A.
2011-01-01
The new oral 200-mg rifamycin SV MMX modified-release tablets, designed to deliver rifamycin SV directly into the colonic lumen, offer considerable advantages over the existing immediate-release antidiarrheic formulations. In two pharmacokinetics studies of healthy volunteers, the absorption, urinary excretion, and fecal elimination of rifamycin SV after single- and multiple-dose regimens of the new formulation were investigated. Concentrations in plasma of >2 ng/ml were infrequently and randomly quantifiable after single and multiple oral doses. The systemic exposure to rifamycin SV after single and multiple oral doses of MMX tablets under fasting and fed conditions or following a four-times-a-day (q.i.d.) or a twice-a-day (b.i.d.) regimen could be considered negligible. With both oral regimens, the drug was confirmed to be very poorly absorbable systemically. The amount of systemically absorbed antibiotic excreted by the renal route is far lower than 0.01% of the administered dose after both the single- and multiple-dose regimens. The absolute bioavailability, calculated as the mean percent ratio between total urinary excretion amounts (ΣXu) after a single intravenous injection and after a single oral dose under fasting conditions, was 0.0410 ± 0.0617. The total elimination of the unchanged rifamycin SV with feces was 87% of the administered oral dose. No significant effect of rifamycin SV on vital signs, electrocardiograms, or laboratory parameters was observed. PMID:21402860
Swann, Jonathan R; Tuohy, Kieran M; Lindfors, Peter; Brown, Duncan T; Gibson, Glenn R; Wilson, Ian D; Sidaway, James; Nicholson, Jeremy K; Holmes, Elaine
2011-08-05
The interaction between the gut microbiota and their mammalian host is known to have far-reaching consequences with respect to metabolism and health. We investigated the effects of eight days of oral antibiotic exposure (penicillin and streptomycin sulfate) on gut microbial composition and host metabolic phenotype in male Han-Wistar rats (n = 6) compared to matched controls. Early recolonization was assessed in a third group exposed to antibiotics for four days followed by four days recovery (n = 6). Fluorescence in situ hybridization analysis of the intestinal contents collected at eight days showed a significant reduction in all bacterial groups measured (control, 10(10.7) cells/g feces; antibiotic-treated, 10(8.4)). Bacterial suppression reduced the excretion of mammalian-microbial urinary cometabolites including hippurate, phenylpropionic acid, phenylacetylglycine and indoxyl-sulfate whereas taurine, glycine, citrate, 2-oxoglutarate, and fumarate excretion was elevated. While total bacterial counts remained notably lower in the recolonized animals (10(9.1) cells/g faeces) compared to the controls, two cage-dependent subgroups emerged with Lactobacillus/Enterococcus probe counts dominant in one subgroup. This dichotomous profile manifested in the metabolic phenotypes with subgroup differences in tricarboxylic acid cycle metabolites and indoxyl-sulfate excretion. Fecal short chain fatty acids were diminished in all treated animals. Antibiotic treatment induced a profound effect on the microbiome structure, which was reflected in the metabotype. Moreover, the recolonization process was sensitive to the microenvironment, which may impact on understanding downstream consequences of antibiotic consumption in human populations.
Greenwood, S L; Edwards, G R; Harrison, R
2012-02-01
The inclusion of the grape marc into livestock rations provides an opportunity not only to use a waste byproduct resourcefully, but also to induce beneficial metabolic changes in animals. Grape marc contains condensed tannins that could alter N metabolism, which would be beneficial from an environmental perspective. The objective was to determine if dietary grape marc could decrease urinary N excretion from nonlactating dairy cattle. Eighteen multiparous cows were randomly divided into 2 equal groups, receiving either (1) pasture+2 kg of dry matter (DM)/d energy pellet per cow (control group) or (2) pasture+2 kg of DM/d energy pellet per cow+3 kg of DM/d grape marc per cow. Urine, fecal, and blood samples were collected at baseline (d 0) and at d 9. Cows receiving grape marc excreted 22% more N in feces compared with the control group. Cows offered grape marc had lower plasma urea nitrogen concentrations (2.42 and 2.97±0.1 mmol/L from treatment and control cows, respectively), but had no significant difference in urine urea concentration compared with control animals (84.24 and 114.1±17.62 mmol/L from treatment and control cows, respectively). Overall, the potential exists to alter N metabolism in dairy cows using dietary grape marc. The exact mechanisms causing this shift in N metabolism require further investigation. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Steryl chlorin esters are formed by zooplankton herbivory
NASA Astrophysics Data System (ADS)
Harradine, Paul J.; Harris, Philip G.; Head, Robert N.; Harris, Roger P.; Maxwell, James R.
1996-06-01
Steryl chlorin esters (SCEs) were formed in laboratory feeding experiments when starved females of the copepod Calanus helgolandicus were allowed to graze on a culture of the diatom Thalassiosira weissflogii. They were found when the zooplankton had grazed for 48 hours and were also identified in fecal pellets subsequently left in seawater in the dark. The distribution contained the diatom sterols in approximately the same relative abundance as the free sterols in the substrate, as well as the most abundant copepod sterol, all esterified to the chlorophyll a degradation product, pyropheophorbide a. Hence, in studies aimed at using sedimentary SCE sterol distributions as indicators of phytoplankton community structure, cholesterol should not be considered since the cholesteryl ester of pyropheophorbide a was a significant component in the fecal pellet SCEs. The findings represent a step forward in unravelling the transformations undergone by chlorophyll a in aquatic environments, since the abundance and wide occurrence of sedimentary SCEs indicate that they are a significant preservational sink for the chlorophyll a biosynthesised in the photic zone.
Druart, Céline; Dewulf, Evelyne M; Cani, Patrice D; Neyrinck, Audrey M; Thissen, Jean-Paul; Delzenne, Nathalie M
2014-04-01
The aim of this human study was to assess the influence of prebiotic-induced gut microbiota modulation on PUFA-derived bacterial metabolites production. Therefore, we analyzed the circulating fatty acid profile including CLA/CLnA in obese women treated during 3 months with inulin-type fructan prebiotics. In these patients, we had already determined gut microbiota composition by phylogenetic microarray and qPCR analysis of 16S rDNA. Some PUFA-derived bacterial metabolites were detected in the serum of obese patients. Despite the prebiotic-induced modulation of gut microbiota, including changes in CLA/CLnA-producing bacteria, the treatment did not impact significantly on the circulating level of these metabolites. However, some PUFA-derived bacterial metabolites were positively correlated with specific fecal bacteria (Bifidobacterium spp., Eubacterium ventriosum and Lactobacillus spp.) and inversely correlated with serum cholesterol (total, LDL, HDL). These correlations suggest a potential beneficial effect of some of these metabolites but this remains to be confirmed by further investigation.
Hypocholesterolaemic effect of whole-grain highland hull-less barley in rats fed a high-fat diet.
Xia, Xuejuan; Li, Guannan; Song, Jiaxin; Zheng, Jiong; Kan, Jianquan
2018-05-01
Whole-grain highland hull-less barley (WHLB) contains high amounts of bioactive compounds that potentially exhibit cholesterol-lowering effects. This study investigated the hypocholesterolaemic effect of WHLB. A total of seventy-two male Sprague-Dawley rats were divided into four groups and were fed with the normal control diet, high-fat diet (HFD) and HFD containing low or high dose (10 or 48·95 %) of WHLB. High dose of WHLB significantly decreased the organ indexes of liver and abdominal fat and lipid levels of plasma and liver in HFD rats. The lipid regulation effect of WHLB, which was reconfirmed through hepatocyte morphologic observation, was accompanied by a large excretion of bile acids in the small intestinal contents and the faeces. Real-time PCR analyses, which were further reconfirmed through Western blot analyses, revealed that a high dose of WHLB significantly enhanced the hepatic expressions of AMP-activated protein kinase α, cholesterol 7α-hydroxylase, LDL receptor, liver X receptor, and PPARα and decreased the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. It also enhanced the ileal expression of farnesoid X receptor and resulted in the decrease of expression of apical sodium-dependent bile acid transporter. WHLB exhibited hypocholesterolaemic effects mainly by inhibiting cholesterol synthesis, cholesterol accumulation in peripheral tissue, and bile acid reabsorption and by stimulating bile acid synthesis.
Polychlorinated biphenyl exposure and effects in transformer repair workers.
Emmett, E A
1985-01-01
Fifty-five present and past transformer repair workers exposed to polychlorinated biphenyls (PCBs) and 56 unexposed comparison workers were evaluated in a clinical-epidemiologic study. The groups were similar in most demographic variables. Adipose tissue lipid and serum PCBs concentrations were higher in current exposed workers (geometric means adipose 2.1 ppm, serum 12.2 ppb). Concentrations in comparison (0.6 ppm and 4.6 ppb) and previously exposed (0.83 ppm and 5.9 ppb) workers were lower. Statistically significant differences in serum albumin and lactic dehydrogenase, but not in other liver function tests, were seen between the exposed and comparison groups; however, after adjustment for confounding variables, no correlations were observed between liver function tests and either adipose or serum PCBs concentrations. Statistically significant correlation both before and after adjustment for confounding variables were seen with adipose PCBs and 24-hr urinary 17-hydroxycorticosteroid excretion and with serum PCBs and serum gamma-glutamyl transpeptidase. Both associations could reflect microsomal enzyme induction among other possibilities. No differences were seen in fasting serum triglycerides, total cholesterol, LDL, HDL or VLDL cholesterol between the two exposure groups. A statistically significant correlation between serum PCBs and serum triglycerides, total cholesterol, and VLDL cholesterol was removed by adjusting for confounding variables. No correlation was seen between adipose PCBs concentrations and any serum lipid component. Partition phenomena could account for these findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2863134
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nakayama, K.; Ohtsuka, A.; Kuraishi, T.
1959-10-31
The digestion and absorption of proteins and fats were studied in patients following radical surgery for carcinoma of the digestive tract. Proteins labeled with phosphorus-32 were synthesized in vivo using goat milk, hen eggs, and intestinal membrane and liver of a dog. Protein labeled with sulfur-35 was obtained from yeast. Amino acid was labeled with carbon-14. Sesame oil labeled with iodine-131 was used as an indicator of fat absorption. The indicators were given orally in test meals. Blood level and fecal and urinary excretion were measured. Procedures are outlined for preparing the labeled indicators. Data are tabulated. (C.H.)
Kim, E; Jeon, S M; Choi, M S
2001-01-01
Currently, there is a growing need for food irradiation that is effective in food preservation and quality improvement. Accordingly, this study was designed to observe the effects of gamma-irradiated dietary fat on plasma lipid concentrations and hepatic cholesterol metabolism in rats. Male rats were fed 5-kGy-gamma-irradiated beef tallow (gammaBT), corn oil (gammaCO), perilla oil (gammaPO), and nonirradiated fats (BT, CO, and PO) for 6 weeks. The gamma-irradiated fat feeding did not affect the plasma lipid concentrations. However, the hepatic cholesterol content was significantly higher in the rats fed gamma-CO as compared with the rats fed nonirradiated CO (40.0 vs. 28.2 mg/g liver). The hepatic HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase activities were not significantly different between the controls and the gamma-irradiated fat fed groups. However, the hepatic ACAT (acyl-CoA:cholesterol acyltransferase) activity was significantly lower in the gammaPO group as compared with its control group (138.2 vs. 404.5 pmol min(-1) mg(-1)). Among the nonirradiated groups, the ACAT activities of the CO and PO groups were higher than that of the BT group. The amounts of coprostanone, cholesterol, and total fecal neutral sterol were significantly higher in the gammaPO group as compared with the other groups. These results indicate that although slight changes in the lipid metabolism were observed as a result of 5-kGy-gamma-irradiated fat feeding, they were relative to the fat type and had no harmful consequences. Copyright 2001 S. Karger AG, Basel
Rajkumar, Hemalatha; Kumar, Manoj; Das, Nilita; Kumar, S Nishanth; Challa, Hanumanth R; Nagpal, Ravinder
2015-05-01
This study investigated the effect of 6-week supplementation of a probiotic strain Lactobacillus salivarius UBL S22 with or without prebiotic fructo-oligosaccharide (FOS) on serum lipid profiles, immune responses, insulin sensitivity, and gut lactobacilli in 45 healthy young individuals. The patients were divided into 3 groups (15/group), that is, placebo, probiotic, and synbiotic. After 6 weeks, a significant reduction (P < .05) in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides and increase in high-density lipoprotein cholesterol was observed in the probiotic as well as in the synbiotic group when compared to placebo; however, the results of total cholesterol and LDL-cholesterol were more pronounced in the synbiotic group. Similarly, when compared to the placebo group, the serum concentrations of inflammatory markers such as high sensitivity C-reactive protein, interleukin (IL) 6, IL-1β, and tumor necrosis factor α were significantly (P < .05) reduced in both the experimental groups, but again the reduction in the synbiotic group was more pronounced. Also, an increase (P < .05) in the fecal counts of total lactobacilli and a decrease (P < .05) in coliforms and Escherichia coli was observed in both the experimental groups after 6 weeks of ingestion. Overall, the combination of L salivarius with FOS was observed to be more beneficial than L salivarius alone, thereby advocating that such synbiotic combinations could be therapeutically exploited for improved health and quality of life. © The Author(s) 2014.
ZHANG, XIAOQIAN
2013-01-01
The aim of this study was to investigate whether calcium dobesilate (calcium dihydroxy-2,5-benzenesulfonate) may be used to treat diabetic nephropathy. A total of 121 patients with type 2 diabetic nephropathy received calcium dobesilate (500 mg, 3 times a day) for 3 months. The levels of glycated hemoglobin, fasting serum C peptide, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, γ-glutamyl transferase, urea nitrogen, creatinine, hematocrit, plasma viscosity, whole blood reduced viscosity, high, medium and low shear rate whole blood viscosity, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and endothelin were determined. The urinary albumin excretion rate (UAER) was also determined once a month during the study. The UAER and medium and low shear rate whole blood viscosity were significantly lower in the treated patients. The rate of microalbuminuria normalization was 90%. During the treatment, the UAERs decreased. The results revealed that calcium dobesilate has therapeutic effects on type 2 diabetes patients with microalbuminuria. In addition, the benefit was positively correlated with the calcium dobesilate treatment time. The therapeutic effect may be due to decreases in the levels of PAI-1. PMID:23251286
Higgs, R J; Chase, L E; Van Amburgh, M E
2012-04-01
Nitrogen excretion is of particular concern on dairy farms, not only because of its effects on water quality, but also because of the subsequent release of gases such as ammonia to the atmosphere. To manage N excretion, accurate estimates of urinary N (UN) and fecal N (FN) are needed. On commercial farms, directly measuring UN and FN is impractical, meaning that quantification must be based on predictions rather than measured data. The purpose of this study was to use a statistical approach to develop equations and evaluate the Cornell Net Carbohydrate and Protein System's (CNCPS) ability to predict N excretion in lactating dairy cows, and to compare CNCPS predictions to other equations in the literature. Urinary N was over-predicted by the CNCPS due to inconsistencies in N accounting within the model that partitioned more N to feces than urine, although predicted total N excretion was reasonable. Data to refine model predictions were compiled from published studies (n=32) that reported total collection N balance results. Considerable care was taken to ensure the data included in the development data set (n=104) accounted for >90% of the N intake (NI). Unaccounted N for the compiled data set was 1.47±4.60% (mean ± SD). The results showed that FN predictions could be improved by using a modification of a previously published equation: FN (g/d) = [[NI (g/kg of organic matter) × (1 - 0.842)] + 4.3 × organic matter intake (kg/d)] × 1.20, which, when evaluated against the compiled N balance data, had a squared coefficient of determination based on a mean study effect R(MP)(2) of 0.73, concurrent correlation coefficient (CCC) of 0.83 and a root mean square error (RMSE) of 10.38 g/d. Urinary N is calculated in the CNCPS as the difference between NI and other N excretion and losses. Incorporating the more accurate FN prediction into the current CNCPS framework and correcting an internal calculation error considerably improved UN predictions (RMSE=12.73 g/d, R(MP)(2)=0.86, CCC=0.90). The changes to FN and UN translated into an improved prediction of total manure N excretion (RMSE=12.42 g/d, R(MP)(2)=0.96, CCC=0.97) and allows nutritionists and farm advisors to evaluate these factors during the ration formulation process. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Laos, Sirle; Caimari, Antoni; Crescenti, Anna; Lakkis, Jamileh; Puiggròs, Francesc; Arola, Lluís; del Bas, Josep Maria
2014-09-14
Various human trials and pre-clinical studies have suggested that dietary plant sterols possess hypotriacylglycerolaemic properties apart from their cholesterol-lowering properties. We hypothesised that phytosterols (PS) might attenuate triacylglycerolaemia by interfering with the deleterious effects of cholesterol overload in the liver. In the present study, twenty hamsters (Mesocricetus auratus) with diet-induced combined hyperlipidaemia were fed a high-fat diet (HFD, n 10) or a HFD supplemented with soyabean PS (n 10) for 40 d. In parallel, a healthy group was fed a standard diet (n 10). PS normalised fasting plasma cholesterol concentrations completely after 20 d and were also able to normalise serum TAG and NEFA concentrations after 40 d. HFD feeding caused microvesicular steatosis and impaired the expression of key genes related to fatty acid oxidation such as PPARA, carnitine palmitoyltransferase-Iα (CPT1A) and phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver. PS treatment completely protected against HFD-induced steatosis and resulted in a normalised hepatic gene expression profile. The protection of the hepatic function by PS was paralleled by increased faecal cholesterol excretion along with a 2-fold increase in the biliary bile acid (BA):cholesterol ratio. The present study supports the conclusion that long-term consumption of PS can reduce serum TAG and NEFA concentrations and can protect against the development of fatty liver via different mechanisms, including the enhancement of BA synthesis. The results of the present study place these compounds as promising hepatoprotective agents against fatty liver and its derived pathologies.
Liu, Suwen; You, Lu; Zhao, Yuhua; Chang, Xuedong
2018-05-01
The hypocholesterolemic effect of Lonicera caerulea berry extract rich in polyphenols (LCBP) on high cholesterol-induced hypercholesterolemia and lipoprotein metabolite changes was examined in Caco-2 cells and rats. Cyanidin-3-glucoside, catechin, and chlorogenic acid are the major phenolic components of LCBP. The cholesterol-reducing effect and antioxidant capacity of these components were compared in Caco-2 cells. LCBP (80 μg/mL) and cyanidin-3-glucoside, catechin, and chlorogenic acid (50 μM) were found to be effective (p < 0.05). Rats were fed a high cholesterol diet (HCD) with or without LCBP supplementation (75, 150, and 300 mg/kg body weight intragastrically once daily) for 12 weeks. Compared with the HCD control group, LCBP supplementation at 150 and 300 mg/kg decreased the levels of TC, TG, and LDL-C, but increased that of HDL-C. LCBP treatment promoted greater neutral and acidic sterol excretion (p < 0.05) and improved the antioxidant capacity of the colon tissue, colon contents, and blood. Moreover, trimethylamine N-oxide (TMAO) levels were decreased in serum (p < 0.05). NPC1L1, ACAT2, and MTP mRNA and protein expression were reduced and ABCG5/8 expression was increased (p < 0.05) after LCBP treatment. Our results suggest that LCBP could be used as a functional food for the prevention and treatment of diseases related to excessive cholesterol accumulation. Copyright © 2018 Elsevier Ltd. All rights reserved.
Marsch, Elke; Demandt, Jasper A F; Theelen, Thomas L; Tullemans, Bibian M E; Wouters, Kristiaan; Boon, Mariëtte R; van Dijk, Theo H; Gijbels, Marion J; Dubois, Ludwig J; Meex, Steven J R; Mazzone, Massimiliano; Hung, Gene; Fisher, Edward A; Biessen, Erik A L; Daemen, Mat J A P; Rensen, Patrick C N; Carmeliet, Peter; Groen, Albert K; Sluimer, Judith C
2016-10-14
Normalization of hypercholesterolaemia, inflammation, hyperglycaemia, and obesity are main desired targets to prevent cardiovascular clinical events. Here we present a novel regulator of cholesterol metabolism, which simultaneously impacts on glucose intolerance and inflammation. Mice deficient for oxygen sensor HIF-prolyl hydroxylase 1 (PHD1) were backcrossed onto an atherogenic low-density lipoprotein receptor (LDLR) knockout background and atherosclerosis was studied upon 8 weeks of western-type diet. PHD1 -/- LDLR -/- mice presented a sharp reduction in VLDL and LDL plasma cholesterol levels. In line, atherosclerotic plaque development, as measured by plaque area, necrotic core expansion and plaque stage was hampered in PHD1 -/- LDLR -/- mice. Mechanistically, cholesterol-lowering in PHD1 deficient mice was a result of enhanced cholesterol excretion from blood to intestines and ultimately faeces. Additionally, flow cytometry of whole blood of these mice revealed significantly reduced counts of leucocytes and particularly of Ly6C high pro-inflammatory monocytes. In addition, when studying PHD1 -/- in diet-induced obesity (14 weeks high-fat diet) mice were less glucose intolerant when compared with WT littermate controls. Overall, PHD1 knockout mice display a metabolic phenotype that generally is deemed protective for cardiovascular disease. Future studies should focus on the efficacy, safety, and gender-specific effects of PHD1 inhibition in humans, and unravel the molecular actors responsible for PHD1-driven, likely intestinal, and regulation of cholesterol metabolism. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
Biochemical responses of the Skylab crewman
NASA Technical Reports Server (NTRS)
Leach, C. S.; Rambaut, P. C.
1974-01-01
The biochemical investigations of the Skylab crewmen were designed to study the physiological changes that were observed on flight crews returning from previous space flight missions as well as to study those changes expected to result from prolonged weightless exposure. These studies can be divided into two broad categories. One category included routine blood studies similar to those used in clinical medical practice. The second included research-type endocrine analyses used to investigate more thoroughly the metabolic/endocrine responses to the space flight environment. The premission control values indicated that all Skylab crewmen were healthy and were free from biochemical abnormalities. The routine results during and after flight showed slight but significant changes in electrolytes, glucose, total protein, osmolality, uric acid, cholesterol, and creatinine. Plasma hormal changes included adrenocorticotrophic hormone, cortisol, angiotensin I, aldosterone, insulin, and thyroxine. The 24-hour urine analyses results revealed increased excretion of cortisol, catecholamines, antidiuretic hormone, and aldosterone as well as excretion of significant electrolyte and uric acid during the Skylab flights.
Ahn-Jarvis, Jennifer; Clinton, Steven K.; Riedl, Kenneth M.; Vodovotz, Yael; Schwartz, Steven J.
2012-01-01
The role of food matrix and gender on soy isoflavone metabolism and biomarkers of activity were examined in twenty free-living adults (34.7±11.5 yrs old) with hypercholesterolemia (221.9 ±18.7mg/dL). In a randomized crossover design study, participants consumed soy-bread (3 wk) or soy-beverage (3 wk) containing 20 g soy protein with 99 and 93 mg isoflavones aglycone equivalents per day, respectively. During soy bread intervention, women had significantly greater microbial metabolite excretion (P=0.05) of isoflavonoids than men. In men, isoflavone metabolite excretion was not discernibly different between the two matrices. Significant reductions (P ≤ 0.05) in triglycerides (24.8%), LDL cholesterol (6.0%), apolipoprotein A-I (12.3%), and lipid oxidative stress capacity (25.5%), were observed after soy food intervention. Our findings suggest that the food matrix significantly impacts soy isoflavone metabolism, particularly microbial metabolites in women. PMID:22739802
Cactus (Opuntia humifusa) water extract ameliorates loperamide-induced constipation in rats.
Han, Sung Hee; Park, Kyungmi; Kim, Eun Young; Ahn, So Hyun; Lee, Hyun-Sun; Suh, Hyung Joo
2017-01-17
Korean cactus Cheonnyuncho (Opuntia humifusa) is rich in pectin, phenols, flavonoids, and minerals such as calcium and phosphorus. Some Koreans drink Cheonnyuncho juice prepared by grinding Cheonnyuncho with water. Cheonnyuncho is well known for its functional properties and antioxidant effects, but its effect on constipation has not been sufficiently studied. Loperamide (2 mg/kg) was injected subcutaneously to induce constipation in rats. The animals were divided into four groups: a normal group (NOR), constipation control group (CON), and two constipation groups receiving the Cheonnyuncho extract (CE) at two different concentrations in drinking water, 3% (L-CE group) and 6% (H-CE group), for 25 days. The fecal pellet numbers of NOR and L-CE were significantly increased from 35.67 ± 2.09 (CON) to 50.60 ± 1.38 and 46.50 ± 2.91 after loperamide treatment, respectively (p < 0.05). The water content of fecal excretions was significantly enhanced in only the L-CE group (33.05 ± 0.49%) compared to control (23.38 ± 1.26%) (p < 0.05) after loperamide treatment. The oral intake of CE (L-CE and H-CE groups) significantly increased levels of the intestinal transit ratio (45.25 ± 1.86% and 41.05 ± 2.47%, respectively) compared to the CON group (32.15 ± 2.05%) (p < 0.05). Treatment with the low concentration of CE significantly increased fecal levels of acetic, propionic, butyric, and valeric acids, as well as the total short-chain fatty acid (SCFA) concentration. Histological analyses revealed that the thickness of the distal colon also increased in the CE-treated groups in a dose-dependent manner. Constipation decreased when CE was fed to the rats. In particular, the fecal pellet number and water content, as well as histological parameters such as distal colon thickness, improved. The CE treatment also increased the fecal SCFA content. These results show that the extract of Cheonnyuncho (O. humifusa) alleviated the symptoms of loperamide-induced constipation.
Khonmee, Jaruwan; Brown, Janine L; Taya, Kazuyoshi; Rojanasthien, Suvichai; Punyapornwithaya, Veerasak; Thumasanukul, Dissakul; Kongphoemphun, Adisorn; Siriaroonrat, Boripat; Tipkantha, Wanlaya; Pongpiachan, Petai; Thitaram, Chatchote
2014-10-15
To date, there is no information on gonadal steroidogenic activity of female goral (Naemorhedus griseus), a threatened species of Thailand. Captive goral populations have been established to produce animals for ex situ conservation and reintroduction, but as yet none are self-sustaining. The objectives of the present study were to (1) determine the influence of season on ovarian steriodogenic function; and (2) examine the relationship between gonadal hormone excretion and sexual behaviors throughout the year. Fecal samples were collected 5 to 7 days/wk for 15 months from 8 adult females housed at Omkoi Wildlife Breeding Center in Thailand and analyzed for ovarian steroid metabolites using validated enzyme immunoassays. Observations of sexual behaviors and mating were conducted each morning for 30 min/session. Based on fecal estrogen and progestagen metabolite concentrations, the overall estrous cycle length was about 21 days, with a 2- to 3-day follicular phase and an 18- to 20-day luteal phase. Sexual behaviors, most notably tail-up, increased for 2 to 3 days during the time estrogens were elevated during mating. Fecal progestagens were elevated during luteal phases and increased further during gestation, which lasted approximately 7 months. The lactation period was 5 months, and females were anestrus for 2 to 5 of those months, with the exception of one that cycled continuously throughout. Two females conceived around 2 months postpartum and so were pregnant during lactation. Birth records over the past 21 years indicated young are born throughout the year. This combined with the hormonal data suggests that female gorals are not strongly seasonal, at least in captivity, although there was considerable variation among females in estrogen and progestagen patterns. In conclusion, fecal steroid metabolite monitoring is an effective means of assessing ovarian function in this species and will be a useful tool for breeding management and planned development of assisted reproductive techniques such as artificial insemination and embryo transfer. Copyright © 2014 Elsevier Inc. All rights reserved.
Wong, Julia M W; Kendall, Cyril W C; Marchie, Augustine; Liu, Zhen; Vidgen, Ed; Holmes, Candice; Jackson, Chung-Ja; Josse, Robert G; Pencharz, Paul B; Rao, A Venketeshwer; Vuksan, Vladimir; Singer, William; Jenkins, David J A
2012-03-01
Recent analyses have challenged the effectiveness of soy foods as part of a cardiovascular risk reduction diet. The objective of the study was to show whether equol status determines the effectiveness of soy foods to lower LDL cholesterol and to raise HDL cholesterol. Eighty-five hypercholesterolemic men and postmenopausal women (42 men, 43 women) participated in 1 of 3 studies that represented a range of soy interventions and that followed the same general protocol at a Canadian university hospital research center. Soy foods were provided for 1 mo at doses of 30-52 g/d for the 3 studies as follows: 1) soy foods with either high-normal (73 mg/d) or low (10 mg/d) isoflavones, 2) soy foods with or without a prebiotic to enhance colonic fermentation (10 g polyfructans/d), or 3) soy foods with a low-carbohydrate diet (26% carbohydrate). Studies 1 and 2 were randomized controlled crossover trials, and study 3 was a parallel study. The separation of the group into equol producers (n = 30) and nonproducers (n = 55) showed similar reductions from baseline in LDL cholesterol (-9.3 ± 2.5% and -11.1 ± 1.6%, respectively; P = 0.834), with preservation of HDL cholesterol and apolipoprotein A-I only in equol producers compared with reductions in nonproducers (HDL cholesterol: +0.9 ± 2.7% compared with -4.3 ± 1.1%, P = 0.006; apolipoprotein A-I: -1.0 ± 1.1% compared with -4.7 ± 1.0%; P = 0.011). The amount of urinary equol excreted did not relate to the changes in blood lipids. Soy foods reduced serum LDL cholesterol equally in both equol producers and nonproducers. However, in equol producers, ~35% of our study population, soy consumption had the added cardiovascular benefit of maintaining higher HDL-cholesterol concentrations than those seen in equol nonproducers. This trial was registered at clinicaltrials.gov as NCT00877825 (study 1), NCT00516594 (study 2), and NCT00256516 (study 3).
Choi, Won Hee; Gwon, So Young; Ahn, Jiyun; Jung, Chang Hwa; Ha, Tae Youl
2013-07-01
Rice has many health-beneficial components for ameliorating obesity, diabetes, and dyslipidemia. However, the effect of cooked rice as a useful carbohydrate source has not been investigated yet; so we hypothesized that cooked rice may have hypolipidemic effects. In the present study, we investigated the effect of cooked rice on hyperlipidemia and on the expression of hepatic genes involved in lipid metabolism. Golden Syrian hamsters were divided into 2 groups and fed a high-fat (15%, wt/wt)/cholesterol (0.5%, wt/wt) diet supplemented with either corn starch (HFD, 54.5% wt/wt) or cooked rice (HFD-CR, 54.5% wt/wt) as the main carbohydrate source for 8 weeks. In the HFD-CR group, the triglyceride and total cholesterol levels in the serum and liver were decreased, and the total lipid, total cholesterol, and bile acid levels in the feces were increased, compared with the HFD group. In the cooked-rice group, the messenger RNA and protein levels of 3-hydroxy-3-methylglutaryl CoA reductase were significantly downregulated; and the messenger RNA and protein levels of the low-density lipoprotein receptor and cholesterol-7α-hydroxylase were upregulated. Furthermore, the expressions of lipogenic genes such as sterol response element binding protein-1, fatty acid synthase, acetyl CoA carboxylase, and stearoyl CoA desaturase-1 were downregulated, whereas the β-oxidation related genes (carnitine palmitoyl transferase-1, acyl CoA oxidase, and peroxisome proliferator-activated receptor α) were upregulated, in the cooked-rice group. Our results suggest that the hypolipidemic effect of cooked rice is partially mediated by the regulation of hepatic genes involved in lipid metabolism, which results in the suppression of cholesterol and fatty acid synthesis and the enhancement of cholesterol excretion and fatty acid β-oxidation. Copyright © 2013 Elsevier Inc. All rights reserved.
Holscher, Hannah D; Guetterman, Heather M; Swanson, Kelly S; An, Ruopeng; Matthan, Nirupa R; Lichtenstein, Alice H; Novotny, Janet A; Baer, David J
2018-06-01
Epidemiologic data suggest that diets rich in nuts have beneficial health effects, including reducing total and cause-specific mortality from cancer and heart disease. Although there is accumulating preclinical evidence that walnuts beneficially affect the gastrointestinal microbiota and gut and metabolic health, these relations have not been investigated in humans. We aimed to assess the impact of walnut consumption on the human gastrointestinal microbiota and metabolic markers of health. A controlled-feeding, randomized crossover study was undertaken in healthy men and women [n = 18; mean age = 53.1 y; body mass index (kg/m2): 28.8]. Study participants received isocaloric diets containing 0 or 42 g walnuts/d for two 3-wk periods, with a 1-wk washout between diet periods. Fecal and blood samples were collected at baseline and at the end of each period to assess secondary outcomes of the study, including effects of walnut consumption on fecal microbiota and bile acids and metabolic markers of health. Compared with after the control period, walnut consumption resulted in a 49-160% higher relative abundance of Faecalibacterium, Clostridium, Dialister, and Roseburia and 16-38% lower relative abundances of Ruminococcus, Dorea, Oscillospira, and Bifidobacterium (P < 0.05). Fecal secondary bile acids, deoxycholic acid and lithocholic acid, were 25% and 45% lower, respectively, after the walnut treatment compared with the control treatment (P < 0.05). Serum LDL cholesterol and the noncholesterol sterol campesterol concentrations were 7% and 6% lower, respectively, after walnut consumption compared with after the control treatment (P < 0.01). Walnut consumption affected the composition and function of the human gastrointestinal microbiota, increasing the relative abundances of Firmicutes species in butyrate-producing Clostridium clusters XIVa and IV, including Faecalibacterium and Roseburia, and reducing microbially derived, proinflammatory secondary bile acids and LDL cholesterol. These results suggest that the gastrointestinal microbiota may contribute to the underlying mechanisms of the beneficial health effects of walnut consumption. This trial was registered at www.clinicaltrials.gov as NCT01832909.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brodzinski, R. L.; Rancitelli, L. A.; Haller, W. A.
1970-01-15
The urine and feces specimens from the Apollo 11 mission were analyzed for their radionuclide content. Estimates of cosmic radiation dose received by the astronauts were difficult to determine due to decay of the short-lived radionuclides during quarantine. The concentrations of {sup 7}Be, {sup 22}Na, {sup 40}K, {sup 59}Fe, {sup 60}Co, and {sup 137}Cs were determined. No {sup 147}Pm was observed in any of the samples. The concentrations of 16 major, minor, and trace elements were determined in fecal samples from Apollos 8 and 10. Large discrepancies between the excretion rates and normal dietary intakes were noted for cobalt, iron,more » tin , and potassium. An interpretation of the hazards these deviations may produce requires the determination of the elemental concentrations of the foodstuffs used during these missions. The fecal samples from the Apollo 11 mission were analyzed for glass fiber content. One anomalous sample was observed having a glass fiber content twofold greater than any previously measured specimen. A piece of the outer thermal coating of the Apollo 12 spacecraft was analyzed for cosmic-ray-induced radioactivity. Beryllium-7 was observed .« less
Occurrence of Giardia in Swedish Red Foxes ( Vulpes vulpes ).
Debenham, John J; Landuyt, Hanne; Troell, Karin; Tysnes, Kristoffer; Robertson, Lucy J
2017-07-01
Giardia duodenalis is an intestinal protozoan capable of causing gastrointestinal disease in a range of vertebrate hosts. It is transmitted via the fecal-oral route. Understanding the epidemiology of G. duodenalis in animals is important, both for public health and for the health of the animals it infects. We investigated the occurrence of G. duodenalis in wild Swedish red foxes ( Vulpes vulpes ), with the aim of providing preliminary information on how this abundant predator might be involved in the transmission and epidemiology of G. duodenalis . Fecal samples (n=104) were analysed for G. duodenalis using a commercially available direct immunofluorescent antibody test. Giardia duodenalis cysts were found in 44% (46/104) of samples, with foxes excreting 100 to 140,500 cysts per gram of feces (mean, 4,930; median, 600). Molecular analysis, using PCR with sequencing of PCR amplicons, was performed on 14 samples, all containing over 2,000 cysts per gram feces. Amplification only occurred in four samples at the tpi gene, sequencing of which revealed assemblage B in all four samples. This study provides baseline information on the role of red foxes in the transmission dynamics of G. duodenalis in Sweden.
Fagervold, Sonja K.; Romano, Chiara; Kalenitchenko, Dimitri; Borowski, Christian; Nunes-Jorge, Amandine; Martin, Daniel; Galand, Pierre E.
2014-01-01
The cornerstones of sunken wood ecosystems are microorganisms involved in cellulose degradation. These can either be free-living microorganisms in the wood matrix or symbiotic bacteria associated with wood-boring bivalves such as emblematic species of Xylophaga, the most common deep-sea woodborer. Here we use experimentally submerged pine wood, placed in and outside the Mediterranean submarine Blanes Canyon, to compare the microbial communities on the wood, in fecal pellets of Xylophaga spp. and associated with the gills of these animals. Analyses based on tag pyrosequencing of the 16S rRNA bacterial gene showed that sunken wood contained three distinct microbial communities. Wood and pellet communities were different from each other suggesting that Xylophaga spp. create new microbial niches by excreting fecal pellets into their burrows. In turn, gills of Xylophaga spp. contain potential bacterial symbionts, as illustrated by the presence of sequences closely related to symbiotic bacteria found in other wood eating marine invertebrates. Finally, we found that sunken wood communities inside the canyon were different and more diverse than the ones outside the canyon. This finding extends to the microbial world the view that submarine canyons are sites of diverse marine life. PMID:24805961
Fagervold, Sonja K; Romano, Chiara; Kalenitchenko, Dimitri; Borowski, Christian; Nunes-Jorge, Amandine; Martin, Daniel; Galand, Pierre E
2014-01-01
The cornerstones of sunken wood ecosystems are microorganisms involved in cellulose degradation. These can either be free-living microorganisms in the wood matrix or symbiotic bacteria associated with wood-boring bivalves such as emblematic species of Xylophaga, the most common deep-sea woodborer. Here we use experimentally submerged pine wood, placed in and outside the Mediterranean submarine Blanes Canyon, to compare the microbial communities on the wood, in fecal pellets of Xylophaga spp. and associated with the gills of these animals. Analyses based on tag pyrosequencing of the 16S rRNA bacterial gene showed that sunken wood contained three distinct microbial communities. Wood and pellet communities were different from each other suggesting that Xylophaga spp. create new microbial niches by excreting fecal pellets into their burrows. In turn, gills of Xylophaga spp. contain potential bacterial symbionts, as illustrated by the presence of sequences closely related to symbiotic bacteria found in other wood eating marine invertebrates. Finally, we found that sunken wood communities inside the canyon were different and more diverse than the ones outside the canyon. This finding extends to the microbial world the view that submarine canyons are sites of diverse marine life.
Fischer, M M; Kessler, A M; de Sá, L R M; Vasconcellos, R S; Filho, F O Roberti; Nogueira, S P; Oliveira, M C C; Carciofi, A C
2012-07-01
Considering the different potential benefits of divergent fiber ingredients, the effect of 3 fiber sources on energy and macronutrient digestibility, fermentation product formation, postprandial metabolite responses, and colon histology of overweight cats (Felis catus) fed kibble diets was compared. Twenty-four healthy adult cats were assigned in a complete randomized block design to 2 groups of 12 animals, and 3 animals from each group were fed 1 of 4 of the following kibble diets: control (CO; 11.5% dietary fiber), beet pulp (BP; 26% dietary fiber), wheat bran (WB; 24% dietary fiber), and sugarcane fiber (SF; 28% dietary fiber). Digestibility was measured by the total collection of feces. After 16 d of diet adaptation and an overnight period without food, blood glucose, cholesterol, and triglyceride postprandial responses were evaluated for 16 h after continued exposure to food. On d 20, colon biopsies of the cats were collected under general anesthesia. Fiber addition reduced food energy and nutrient digestibility. Of all the fiber sources, SF had the least dietary fiber digestibility (P < 0.05), causing the largest reduction of dietary energy digestibility (P < 0.05). The greater fermentability of BP resulted in reduced fecal DM and pH, greater fecal production [g/(cat × d); as-is], and greater fecal concentration of acetate, propionate, and lactate (P < 0.05). For most fecal variables, WB was intermediate between BP and SF, and SF was similar to the control diet except for an increased fecal DM and firmer feces production for the SF diet (P < 0.05). Postprandial evaluations indicated reduced mean glucose concentration and area under the glucose curve in cats fed the SF diet (P < 0.05). Colon mucosa thickness, crypt area, lamina propria area, goblet cell area, crypt mean size, and crypt in bifurcation did not vary among the diets. According to the fiber solubility and fermentation rates, fiber sources can induce different physiological responses in cats, reduce energy digestibility, and favor glucose metabolism (SF), or improve gut health (BP).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Colburn, W.A.; Vane, F.M.; Bugge, C.J.
The pharmacokinetics of isotretinoin and 4-oxoisotretinoin in blood, as well as the blood concentrations and urinary, biliary, and fecal excretion of carbon-14 were studied using liquid scintillation counting techniques and reverse phase HPLC methods following a single 80-mg oral suspension dose of UC-isotretinoin to four healthy male subjects and two patients with biliary T-tube drainage. Approximately 80% of the dose was recovered as UC in excreta during the course of the study of which about equal fractions were in the urine and feces. Secondary peaks in blood concentrations of UC were observed in the healthy subjects whereas they were notmore » seen in the patients with T-tubes. The harmonic mean apparent half-life for isotretinoin in the blood of the healthy subjects was 13.6 hr, whereas the corresponding value for the UC was 90 hr. The data for isotretinoin and 4-oxoisotretinoin coupled with the total carbon-14 data suggest that the oral dose of UC-isotretinoin is absorbed to a similar extent by the healthy subjects and T-tube patients, whereas T-tube patients clear the drug more rapidly. The biliary excretion and possible enterohepatic circulation of isotretinoin and its metabolites may have significant impact on the pharmacokinetic profile of isotretinoin in man.« less
Hallewell, J; Niu, Y D; Munns, K; McAllister, T A; Johnson, R P; Ackermann, H-W; Thomas, J E; Stanford, K
2014-07-01
The objectives of this study were to identify endemic bacteriophages (phages) in the feedlot environment and determine relationships of these phages to Escherichia coli O157:H7 from cattle shedding high and low numbers of naturally occurring E. coli O157:H7. Angus crossbred steers were purchased from a southern Alberta (Canada) feedlot where cattle excreting ≥ 10(4) CFU · g(-1) of E. coli O157:H7 in feces at a single time point were identified as supershedders (SS; n = 6), and cattle excreting <10(4) CFU · g(-1) of feces were identified as low shedders (LS; n = 5). Fecal pats or fecal grabs were collected daily from individual cattle for 5 weeks. E. coli O157:H7 in feces was detected by immunomagnetic separation and enumerated by direct plating, and phages were isolated using short- and overnight-enrichment methods. The total prevalence of E. coli O157:H7 isolated from feces was 14.4% and did not differ between LS and SS (P = 0.972). The total prevalence of phages was higher in the LS group (20.9%) than in the SS group (8.3%; P = 0.01). Based on genome size estimated by pulsed-field gel electrophoresis and morphology determined by transmission electron microscopy, T4- and O1-like phages of Myoviridae and T1-like phage of Siphoviridae were isolated. Compared to T1- and O1-like phages, T4-like phages exhibited a broad host range and strong lytic capability when targeting E. coli O157:H7. Moreover, the T4-like phages were more frequently isolated from feces of LS than SS, suggesting that endemic phages may impact the shedding dynamics of E. coli O157:H7 in cattle. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Treating chronic arsenic toxicity with high selenium lentil diets
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sah, Shweta; Vandenberg, Albert; Smits, Judit, E-mail: judit.smits@ucalgary.ca
2013-10-01
Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we comparemore » diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell response.« less
White, P A S; Cercato, L M; Batista, V S; Camargo, E A; De Lucca, W; Oliveira, A S; Silva, F T; Goes, T C; Oliveira, E R A; Moraes, V R S; Nogueira, P C L; De Oliveira E Silva, A M; Quintans-Junior, L J; Lima, B S; Araújo, A A S; Santos, M R V
2016-02-17
Due to the rise in obesity, the necessity for resources and treatments that could reduce the morbidity and mortality associated to this pandemia has emerged. The development of new anti-obesity drugs through herbal sources has been increasing in the past decades which are being used not only as medicine but also as food supplements. Previous studies with the aqueous extract of Chrysobalanus icaco L (AECI) have demonstrated activity on lowering blood glucose levels and body weight. Investigate C. icaco effects in overall adiposity and glycemic homeostasis. C57BL/6J mice were randomly assigned to standard chow (SC) or high-fat diet (HFD) and treated with AECI in 0.35mg/mL or 0.7mg/mL concentrations ad libitum. Food intake, feed efficiency, metabolic efficiency, body, fat pads and gastrocnemius weight, adiposity index, serum lipids, fecal lipid excretion, locomotor activity in the open field test and insulin and glucose tolerance tests were analyzed and compared. The major components of the extract were demonstrated through HPLC and its antioxidant activity analyzed through DPPH and lipid peroxidation. The AECI in the 0.35mg/mL concentration did not affect food intake or body weight. However, it promoted lower adipose tissue gain, TG levels, and fecal lipid excretion, increased locomotor activity and lean mass weight, and normalized insulin sensitivity and glucose tolerance. Moreover, AECI showed the presence of myricetin 3-O-glucuronide, rutin, quercitrin and myricitrin and demonstrated high-antioxidant activity. AECI in lower concentrations can prevent fat storage or enhance fat utilization through the increase of locomotor activity. Also, this reinforces its ability to maintain glucose homeostasis through the normalization of insulin sensitivity and glucose tolerance despite the high-fat diet intake. These activities could be associated to the extract's polyphenol content. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Behavioral Responses of CD-1 Mice to Six Predator Odor Components.
Sievert, Thorbjörn; Laska, Matthias
2016-06-01
Mammalian prey species are able to detect predator odors and to display appropriate defensive behavior. However, there is only limited knowledge about whether single compounds of predator odors are sufficient to elicit such behavior. Therefore, we assessed if predator-naïve CD-1 mice (n = 60) avoid sulfur-containing compounds that are characteristic components of natural predator odors and/or display other indicators of anxiety. A 2-compartment test arena was used to assess approach/avoidance behavior, general motor activity, and the number of fecal pellets excreted when the animals were presented with 1 of 6 predator odor components in one compartment and a blank control in the other compartment. We found that 2 of the 6 predator odor components (2-propylthietane and 3-methyl-1-butanethiol) were significantly avoided by the mice. The remaining 4 predator odor components (2,2-dimethylthietane, 3-mercapto-3-methylbutan-1-ol, 3-mercapto-3-methylbutyl-1-formate, and methyl-2-phenylethyl sulphide) as well as a nonpredator-associated fruity odor (n-pentyl acetate) were not avoided. Neither the general motor activity nor the number of excreted fecal pellets, both widely used measures of stress- or anxiety-related behavior, were systematically affected by any of the odorants tested. Further, we found that small changes in the molecular structure of a predator odor component can have a marked effect on its behavioral significance as 2-propylthietane was significantly avoided by the mice whereas the structurally related 2,2-dimethylthietane was not. We conclude that sulfur-containing volatiles identified as characteristic components of the urine, feces, and anal gland secretions of mammalian predators can be, but are not necessarily sufficient to elicit defensive behaviors in a mammalian prey species. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Trevisi, P; Colombo, M; Priori, D; Fontanesi, L; Galimberti, G; Calò, G; Motta, V; Latorre, R; Fanelli, F; Mezzullo, M; Pagotto, U; Gherpelli, Y; D'Inca, R; Bosi, P
2015-05-01
The development of effective feeding strategies to reduce the detrimental effect of enterotoxigenic F4ac (ETEC) plays a crucial role in reducing the occurrence of therapeutic intervention with antibiotics in livestock. The ability of CNCM I-4407 (SCC), supplied in different patterns to counteract ETEC infection in weaned pigs, was evaluated. Fifty pigs weaned at 24 d were then divided into 5 groups: control (CO), CO + colistin (AB), CO + 5 × 10(10) cfu of SCC/ kg feed, from d 0 to 21 (PR), CO + 5 × 10(10) cfu of SCC/ kg feed from d 7 to 11 (CM), and CO + 1 shot of 2 × 10(11) cfu of SCC when the first diarrhea appeared (CU). On d 7 postweaning, all the pigs were orally challenged with 10(8) cfu of ETEC. Blood samples were taken from the pigs (d 7, 8, 12, and 21) while the fecal excretion of ETEC was assessed on d 7 and 10. Fecal consistency was scored from 12 h before infection to 144 h postinfection (p.i.). On d 21, the pigs were sacrificed. The in vitro adhesion test on the intestinal villi confirmed individual susceptibility to ETEC, excluding the presence of resistant pigs. Growth performance did not differ between the treatments. Mortality was reduced in the AB group (P< 0.01) and, marginally, in the PR group (P = 0.089) when compared to the CO group. The CO group had a higher fecal score than AB in the period of observation (from P = 0.01 to P< 0.001). Yeast administration reduced the fecal score when compared to the CO group 12 and 48 h p.i. (P = 0.04). Total IgA never differed among the treatments, but the ETEC-specific IgA concentration was lower in the AB group than in CO (P = 0.04) at d 12. Four days p.i., the pigs fed live yeast had reduced ETEC excretion compared with the CO pigs (P = 0.05). Blood concentrations of dodecenoyl-L-carnitine (P < 0.01), glutaryl-L-carnitine/hydroxyhex¬anoyl-L-carnitine, phosphatidylcholine diacyl and phosphatidylcholine diacyl (P = 0.01 and P< 0.01, respectively), and α-amino adipic acid (P < 0.01) were reduced in the AB group compared to the CO group; PR + CM reduced the concentration of sphingomyelin-ceramide (P = 0.02) and increased the concentration of decadienyl-L-carnitine (C10:2; P= 0.02) vs. CO. The CM group had an increased concentration of C10:2 (P < 0.01) compared to the PR group. In conclusion, the administration of live yeast, even in concomitance with ETEC infections, reduces pig illness and mortality. The strain of SCC tested did not show a therapeutic effect.
Khonmee, Jaruwan; Brown, Janine L.; Rojanasthien, Suvichai; Aunsusin, Anurut; Thumasanukul, Dissakul; Kongphoemphun, Adisorn; Siriaroonrat, Boripat; Tipkantha, Wanlaya; Punyapornwithaya, Veerasak; Thitaram, Chatchote
2014-01-01
Chinese goral (Naemorhedus griseus) are a threatened species in Thailand and the focus of captive breeding for possible reintroduction. However, little is known of their biology or what factors in the captive environment affect welfare. Our objective was to determine the impact of gender, season, and management on goral adrenal activity. We hypothesized that differences in fecal glucocorticoid concentrations would be related to animal density. Fecal samples were collected 3 days/week for 1 year from 63 individuals (n = 32 males, 31 females) at two facilities that house the majority of goral in Thailand: Omkoi Wildlife Sanctuary (Omkoi), an off-exhibit breeding center that houses goral in individual pens (16 pens; n = 8 males, 8 females) and in small family groups (8 pens; n = 8 males, 8 females); and the Chiang Mai Night Safari (NS), a zoo that maintains 31 goral (n = 17 males, 14 females) in one large pen. Glucocorticoid metabolite concentrations were higher in male than female goral at Omkoi throughout the year, and there was a seasonal effect on adrenal activity (p<0.05). Goral at Omkoi and NS were used to test the effect of animal density on fecal glucocorticoid excretion of goral housed in similar-sized enclosures. Overall, the highest levels were found at NS (n = 31 adults/pen; 27 m2 per animal) compared to Omkoi (n = 2 adults/pen; 400 m2 per animal) (p<0.05). Overall findings support our hypothesis that animal density and aspects of the captive environment impact adrenal steroid activity in captive goral. In addition, gender and season also had significant effects on glucocorticoid metabolite production. Potential stressors pertaining to the welfare of this species were identified, which will guide future efforts to improve management and create self-sustaining and healthy populations of this threatened species. PMID:24637886
Khonmee, Jaruwan; Brown, Janine L; Rojanasthien, Suvichai; Aunsusin, Anurut; Thumasanukul, Dissakul; Kongphoemphun, Adisorn; Siriaroonrat, Boripat; Tipkantha, Wanlaya; Punyapornwithaya, Veerasak; Thitaram, Chatchote
2014-01-01
Chinese goral (Naemorhedus griseus) are a threatened species in Thailand and the focus of captive breeding for possible reintroduction. However, little is known of their biology or what factors in the captive environment affect welfare. Our objective was to determine the impact of gender, season, and management on goral adrenal activity. We hypothesized that differences in fecal glucocorticoid concentrations would be related to animal density. Fecal samples were collected 3 days/week for 1 year from 63 individuals (n = 32 males, 31 females) at two facilities that house the majority of goral in Thailand: Omkoi Wildlife Sanctuary (Omkoi), an off-exhibit breeding center that houses goral in individual pens (16 pens; n = 8 males, 8 females) and in small family groups (8 pens; n = 8 males, 8 females); and the Chiang Mai Night Safari (NS), a zoo that maintains 31 goral (n = 17 males, 14 females) in one large pen. Glucocorticoid metabolite concentrations were higher in male than female goral at Omkoi throughout the year, and there was a seasonal effect on adrenal activity (p<0.05). Goral at Omkoi and NS were used to test the effect of animal density on fecal glucocorticoid excretion of goral housed in similar-sized enclosures. Overall, the highest levels were found at NS (n = 31 adults/pen; 27 m2 per animal) compared to Omkoi (n = 2 adults/pen; 400 m2 per animal) (p<0.05). Overall findings support our hypothesis that animal density and aspects of the captive environment impact adrenal steroid activity in captive goral. In addition, gender and season also had significant effects on glucocorticoid metabolite production. Potential stressors pertaining to the welfare of this species were identified, which will guide future efforts to improve management and create self-sustaining and healthy populations of this threatened species.
The Chemical Basis of Species, Sex, and Individual Recognition Using Feces in the Domestic Cat.
Miyazaki, Masao; Miyazaki, Tamako; Nishimura, Takashi; Hojo, Wataru; Yamashita, Tetsuro
2018-04-01
Scents emitted from excretions provide important information about the owner. Volatile compounds with higher levels in a species and/or sex, or that vary among individuals could be odor cues for species and/or sex, or individual recognition. However, such compounds have been identified in only a few vertebrate species. In domestic cats (Felis silvestris catus), it is known that unburied cat feces are territorial markers asserting the border of their home range, but little was known which fecal compounds are scent cues for species, sex, and individual recognition in cats. In the present study, we demonstrated the chemical basis for species, sex, and individual recognition using feces of cats. For males, major contents were fatty acids and 3-mercapto-3-methyl-1-butanol (MMB), a derivative of the unusual amino acid, felinine. MMB emission levels from feces had sex-based differences (male > female) and dynamic temporal changes during aging. Cats distinguished fecal odors with and without MMB, and different fatty acid compositions among individuals. No cat-specific compound, such as MMB, was detectable from their anal odor emitting fatty acids. We concluded that fecal MMB is a male sex recognition pheromone in cats and also provides a temporal trace of the owner. After sensing MMB, they may distinguish individual differences of conspecific feces with variable subsets of fatty acids. In contrast to scent marks, since cats can obtain species information from visual cues before sniffing conspecific anal odors, they may use their efforts to distinguish individual differences of anal odors during sniffing.
Spercoski, Katherinne M; Morais, Rosana N; Morato, Ronaldo G; de Paula, Rogério C; Azevedo, Fernanda C; May-Júnior, Joares A; Santos, Jean P; Reghelin, Angela L; Wildt, David E; Songsasen, Nucharin
2012-11-01
In this study we measured excreted fecal corticoid metabolites (FCM) in maned wolves (Chrysocyon brachyurus) living within a protected reserve, on farmlands or in a boundary zone between the two habitats, and determined the impacts of season and reproductive status on adrenal activity. Feces were collected within a national park (n=191 samples), a park boundary zone (n=39) and on nearby farmlands (n=27), processed and analyzed by enzyme immunoassay. FCM amounts from samples collected on farmlands were higher (P<0.05) than in those collected inside the reserve and from the boundary zone. In relation to seasonality, FCM were elevated (P<0.05) in spring (September-November) when wolf pairs were raising young. We then divided the samples collected during breeding season (March-August) into cycling females and male/non-cycling females based on fecal progesterone: fecal testosterone ratio. FCM concentrations of the former collected inside the park were higher than (P<0.05) than the latter group. However, there were no differences in FCM levels between the two groups for samples collected in the boundary zone and on farmlands. Furthermore, FCM concentrations of male/non-cycling females samples collected on farmlands were 2- to 5-fold higher (P<0.05) than in counterparts collected inside the park. The consistently high FCM concentrations in samples collected on farmlands indicate that, in addition to seasonality, gender and reproductive status, anthropogenic pressures also contribute to elevating adrenal steroid for individuals living in altered habitat. Copyright © 2012 Elsevier Inc. All rights reserved.
Chronically infected wild boar can transmit genotype 3 hepatitis E virus to domestic pigs.
Schlosser, Josephine; Vina-Rodriguez, Ariel; Fast, Christine; Groschup, Martin H; Eiden, Martin
2015-10-22
Hepatitis E virus (HEV) causes acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialized nations. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with the consumption of raw and undercooked products from domestic pig and wild boar. As shown recently, naturally acquired HEV gt3 replicates efficiently in experimentally infected wild boar and is transmissible from a wild boar to domestic pigs. Generally, following an acute infection swine suffer from a transient febrile illness and viremia in connection with fecal virus shedding. However, little is known about sub-acute or chronic HEV infections in swine, and how and where HEV survives the immune response. In this paper, we describe the incidental finding of a chronic HEVgt3 infection in two naturally infected European wild boar which were raised and housed at FLI over years. The wild boar displayed fecal HEV RNA excretion and viremia over nearly the whole observation period of more than five months. The animal had mounted a substantial antibody response, yet without initial clearance of the virus by the immune system. Further analysis indicated a subclinical course of HEV with no evidence of chronic hepatitis. Additionally, we could demonstrate that this chronic wild boar infection was still transmissible to domestic pigs, which were housed together with this animal. Sentinel pigs developed fecal virus shedding accompanied by seroconversion. Wild boar should therefore be considered as an important reservoir for transmission of HEV gt3 in Europe. Copyright © 2015 Elsevier B.V. All rights reserved.
Dietary Shifts May Trigger Dysbiosis and Mucous Stools in Giant Pandas (Ailuropoda melanoleuca)
Williams, Candace L.; Dill-McFarland, Kimberly A.; Vandewege, Michael W.; Sparks, Darrell L.; Willard, Scott T.; Kouba, Andrew J.; Suen, Garret; Brown, Ashli E.
2016-01-01
Dietary shifts can result in changes to the gastrointestinal tract (GIT) microbiota, leading to negative outcomes for the host, including inflammation. Giant pandas (Ailuropoda melanoleuca) are physiologically classified as carnivores; however, they consume an herbivorous diet with dramatic seasonal dietary shifts and episodes of chronic GIT distress with symptoms including abdominal pain, loss of appetite and the excretion of mucous stools (mucoids). These episodes adversely affect the overall nutritional and health status of giant pandas. Here, we examined the fecal microbiota of two giant pandas’ non-mucoid and mucoid stools and compared these to samples from a previous winter season that had historically few mucoid episodes. To identify the microbiota present, we isolated and sequenced the 16S rRNA using next-generation sequencing. Mucoids occurred following a seasonal feeding switch from predominately bamboo culm (stalk) to leaves. All fecal samples displayed low diversity and were dominated by bacteria in the phyla Firmicutes and to a lesser extent, Proteobacteria. Fecal samples immediately prior to mucoid episodes had lower microbial diversity as compared to mucoids. Mucoids were mostly comprised of common mucosal-associated taxa including Streptococcus and Leuconostoc species, and exhibited increased abundance for bacteria in the family Pasteurellaceae. Taken together, these findings indicate that mucoids may represent an expulsion of the mucosal lining that is driven by changes in diet. We suggest that these occurrences serve to reset their GIT microbiota following changes in bamboo part preference, as giant pandas have retained a carnivorous GIT anatomy while shifting to an herbivorous diet. PMID:27199976
Dietary Shifts May Trigger Dysbiosis and Mucous Stools in Giant Pandas (Ailuropoda melanoleuca).
Williams, Candace L; Dill-McFarland, Kimberly A; Vandewege, Michael W; Sparks, Darrell L; Willard, Scott T; Kouba, Andrew J; Suen, Garret; Brown, Ashli E
2016-01-01
Dietary shifts can result in changes to the gastrointestinal tract (GIT) microbiota, leading to negative outcomes for the host, including inflammation. Giant pandas (Ailuropoda melanoleuca) are physiologically classified as carnivores; however, they consume an herbivorous diet with dramatic seasonal dietary shifts and episodes of chronic GIT distress with symptoms including abdominal pain, loss of appetite and the excretion of mucous stools (mucoids). These episodes adversely affect the overall nutritional and health status of giant pandas. Here, we examined the fecal microbiota of two giant pandas' non-mucoid and mucoid stools and compared these to samples from a previous winter season that had historically few mucoid episodes. To identify the microbiota present, we isolated and sequenced the 16S rRNA using next-generation sequencing. Mucoids occurred following a seasonal feeding switch from predominately bamboo culm (stalk) to leaves. All fecal samples displayed low diversity and were dominated by bacteria in the phyla Firmicutes and to a lesser extent, Proteobacteria. Fecal samples immediately prior to mucoid episodes had lower microbial diversity as compared to mucoids. Mucoids were mostly comprised of common mucosal-associated taxa including Streptococcus and Leuconostoc species, and exhibited increased abundance for bacteria in the family Pasteurellaceae. Taken together, these findings indicate that mucoids may represent an expulsion of the mucosal lining that is driven by changes in diet. We suggest that these occurrences serve to reset their GIT microbiota following changes in bamboo part preference, as giant pandas have retained a carnivorous GIT anatomy while shifting to an herbivorous diet.
Helminth Fauna in Captive European Gray Wolves (Canis lupus lupus) in Germany.
Bindke, Johanna Daniela; Springer, Andrea; Böer, Michael; Strube, Christina
2017-01-01
Captive as well as free-ranging wolves, which are currently recolonizing Germany, may harbor a variety of gastrointestinal parasites. This study investigated endoparasites in captive European gray wolves ( Canis lupus lupus ) using coproscopical methods. Fecal samples were collected monthly between October 2012 and November 2013 from 18 wolf enclosures in 14 German zoological gardens, representing 72 individual wolves. In total, 1,041 fecal samples including 26 bulk samples were analyzed by the sedimentation and flotation method. The most frequently detected egg morphotypes included five nematodes [Ancylostomatidae ( Ancylostoma or Uncinaria spp.), Toxocara canis, Toxascaris leonina, Trichuris vulpis , and Capillaria / Eucoleus spp.], one cestode (Taeniidae) and one trematode ( Alaria alata ). 44.76% of all samples were positive for at least one of these egg morphotypes. Overall, Ancylostomatidae showed the highest frequency (30.84% of all samples), followed by Capillaria/Eucoleus spp. (19.88%), Toxocara canis (5.19%), taeniids (3.75%), Trichuris vulpis and Alaria alata (3.65% each), and Toxascaris leonina (1.25%). As fecal samples were collected from the environment and could not be assigned to individual wolves, sample results were combined per zoo and month. General linear mixed models were employed to analyze the effect of season and management factors on the occurrence of Ancylostomatidae, Capillaria/Eucoleus spp., Toxocara canis and taeniids. No statistically significant effect of season was found, whereas anthelmintic treatment negatively affected Ancylostomatidae egg excretion. Detected parasites and their prevalences are comparable to previous studies on wolf parasitism conducted elsewhere in Europe. As many of the most prevalent helminths are of zoonotic importance, routine anthelmintic treatment of captive wolves should be recommended.
Palacios, Cristina; Wigertz, Karin; Braun, Michelle; Martin, Berdine R; McCabe, George P; McCabe, Linda; Pratt, J Howard; Peacock, Munro; Weaver, Connie M
2013-01-01
Background: Previously, we showed that black girls retained more calcium than white girls did and that salt loading negatively affected calcium retention. Racial differences likely exist in other bone minerals also, such as magnesium, in response to salt loading during growth. Objective: We studied racial differences in magnesium metabolism in response to dietary sodium and calcium during rapid bone growth. Design: Twenty-seven white and 40 black girls (11–15 y old) were studied for 3 wk while they consumed low-sodium (1.3 g/d) and high-sodium (3.8 g/d) diets by using a randomized-order, crossover metabolic study with 3 dietary calcium intakes; the magnesium dietary intake was fixed at 230 mg/d. Urine and feces were collected during each 3-wk period in 24-h pools and analyzed for magnesium. A mixed-model ANOVA was used to determine the effect of race and dietary sodium with calcium intake as a covariate. Results: Salt loading or calcium intake had no significant effect on urinary magnesium excretion. Blacks excreted significantly less urinary magnesium (mean ± SD: 83.8 ± 25.6 mg/d) than did whites (94.9 ± 27.3 mg/d; P < 0.05). No effects were observed in fecal magnesium excretion. Magnesium retention was higher with the low-sodium diet (50.1 ± 44.0 mg/d) than with the high-sodium diet (39.3 ± 49.8 mg/d) (P < 0.05), with no effects of race or calcium intake. Salt loading had no effect on biomarkers. Whites had higher 25-hydroxyvitamin D and insulin-like growth factor binding protein 3 but lower 1,25-dihydroxyvitamin D and parathyroid hormone concentrations. Conclusions: Blacks excreted less urinary magnesium than did whites. Magnesium retention was similar between races but higher with the low-sodium diet. Kinetic studies are needed to fully explain magnesium homeostasis. This trial was registered at clinicaltrials.gov as NCT01564238. PMID:23553157
Ganswindt, A; Palme, R; Heistermann, M; Borragan, S; Hodges, J K
2003-11-01
Adult male elephants periodically show the phenomenon of musth, a condition associated with increased aggressiveness, restlessness, significant weight reduction and markedly elevated androgen levels. It has been suggested that musth-related behaviours are costly and that therefore musth may represent a form of physiological stress. In order to provide data on this largely unanswered question, the first aim of this study was to evaluate different assays for non-invasive assessment of adrenocortical function in the male African elephant by (i) characterizing the metabolism and excretion of [3H]cortisol (3H-C) and [14C]testosterone (14C-T) and (ii) using this information to evaluate the specificity of four antibodies for determination of excreted cortisol metabolites, particularly with respect to possible cross-reactions with androgen metabolites, and to assess their biological validity using an ACTH challenge test. Based on the methodology established, the second objective was to provide data on fecal cortisol metabolite concentrations in bulls during the musth and non-musth condition. 3H-C (1 mCi) and 14C-T (100 microCi) were injected simultaneously into a 16 year old male and all urine and feces collected for 30 and 86 h, respectively. The majority (82%) of cortisol metabolites was excreted into the urine, whereas testosterone metabolites were mainly (57%) excreted into the feces. Almost all radioactive metabolites recovered from urine were conjugated (86% 3H-C and 97% 14C-T). In contrast, 86% and >99% of the 3H-C and 14C-T metabolites recovered from feces consisted of unconjugated forms. HPLC separations indicated the presence of various metabolites of cortisol in both urine and feces, with cortisol being abundant in hydrolysed urine, but virtually absent in feces. Although all antibodies measured substantial amounts of immunoreactivity after HPLC separation of peak radioactive samples and detected an increase in glucocorticoid output following the ACTH challenge, only two (in feces against 3alpha,11-oxo-cortisol metabolites, measured by an 11-oxo-etiocholanolone-EIA and in urine against cortisol, measured by a cortisol-EIA) did not show substantial cross-reactivity with excreted 14C-T metabolites and could provide an acceptable degree of specificity for reliable assessment of glucocorticoid output from urine and feces. Based on these findings, concentrations of immunoreactive 3alpha,11-oxo-cortisol metabolites were determined in weekly fecal samples collected from four adult bulls over periods of 11-20 months to examine whether musth is associated with increased adrenal activity. Results showed that in each male levels of these cortisol metabolites were not elevated during periods of musth, suggesting that in the African elephant musth is generally not associated with marked elevations in glucocorticoid output. Given the complex nature of musth and the variety of factors that are likely to influence its manifestation, it is clear, however, that further studies, particularly on free-ranging animals, are needed before a possible relationship between musth and adrenal function can be resolved. This study also clearly illustrates the potential problems associated with cross-reacting metabolites of gonadal steroids in EIAs measuring glucocorticoid metabolites. This has to be taken into account when selecting assays and interpreting results of glucocorticoid metabolite analysis, not only for studies in the elephant but also in other species.
Ticehurst, J; Popkin, T J; Bryan, J P; Innis, B L; Duncan, J F; Ahmed, A; Iqbal, M; Malik, I; Kapikian, A Z; Legters, L J
1992-02-01
Hepatitis E virus (HEV), a positive-strand RNA agent, has been associated with enterically transmitted non-A, non-B hepatitis in Asia, Africa, and Mexico. To evaluate the role of HEV in an outbreak of hepatitis in Pakistan, we used immune electron microscopy to detect 1) antibody to HEV, for evidence of infection, and 2) virus, to determine the pattern of HEV excretion. Paired sera from 2 patients were assayed for antibody by using reference HEV: one seroconverted, an atypical finding for HEV infections; the other had high levels of anti-HEV in both sera. Virus particles with the size (29 x 31 nm) and morphology of HEV were detected in feces from 10 of 85 patients and serologically identified as HEV by using reference antibodies from an HEV-infected chimpanzee. One of these HEV-containing specimens was collected 9 days before the onset of jaundice; it was among feces from 38 outpatients with nonspecific symptoms and biochemical hepatitis, 12 of whom subsequently developed jaundice. The other 9 feces with HEV were among 36 collected within 7 days of the onset of acute icteric hepatitis; all 11 feces from days 8 to 15 were negative for HEV. Fecal concentrations of HEV appeared to be lower than those of many enteric viruses: only one specimen contained as many as 5 particles per EM grid square. It is concluded that HEV was etiologically associated with the epidemic and was predominantly excreted at very low levels during the first week of jaundice.
Application of a canine 238Pu dosimetry model to human bioassay data
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hickman, Jr., A. W.
1991-08-01
Associated with the use of 2 238Pu in thermoelectric power sources for space probes and power supplies for cardiac devices is the potential for human exposure to 238Pu, primarily by inhalation. In the event of human internal exposure, a means is needed for assessing the level of intake and calculating radiation doses. Several bioassay/dosimetry models have been developed for 239Pu. However, results from studies with laboratory animals have indicated that the biokinetics, and therefore the descriptive models, of 238Pu are significantly different from those for 239Pu. A canine model accounting for these differences has been applied in this work tomore » urinary excretion data from seven humans occupationally exposed to low levels of an insoluble 238Pu compound. The modified model provides a good description of the urinary excretion kinetics observed in the exposed humans. The modified model was also used to provide estimates of the initial intakes of 238Pu for the seven individuals; these estimates ranged from 4.5 nCi (170 Bq) to 87 nCi (3200 Bq). Autopsy data on the amount and distribution of 238Pu retained in the organs may be used in the future to validate or refute both these estimates and the assumptions used to formulate the human model. Modification of the human model to simulate an injection exposure to 239Pu gave patterns of retention in the organs and urinary excretion comparable to those seen previously in humans; further modification of the model using fecal data (unavailable for the subjects of this study) is indicated.« less
Cavalera, Michele; Axling, Ulrika; Rippe, Catarina; Swärd, Karl; Holm, Cecilia
2017-06-01
Atherosclerosis is a disease in which atheromatous plaques develop inside arteries, leading to reduced or obstructed blood flow that in turn may cause stroke and heart attack. Rose hip is the fruit of plants of the genus Rosa, belonging to the Rosaceae family, and it is rich in antioxidants with high amounts of ascorbic acid and phenolic compounds. Several studies have shown that fruits, seeds and roots of these plants exert antidiabetic, antiobesity and cholesterol-lowering effects in rodents as well as humans. The aim of this study was to elucidate the mechanisms by which rose hip lowers plasma cholesterol and to evaluate its effects on atherosclerotic plaque formation. ApoE-null mice were fed either an HFD (CTR) or HFD with rose hip supplementation (RH) for 24 weeks. At the end of the study, we found that blood pressure and atherosclerotic plaques, together with oxidized LDL, total cholesterol and fibrinogen levels were markedly reduced in the RH group. Fecal cholesterol content, liver expression of Ldlr and selected reverse cholesterol transport (RCT) genes such as Abca1, Abcg1 and Scarb1 were significantly increased upon RH feeding. In the aorta, the scavenger receptor Cd36 and the proinflammatory Il1β genes were markedly down-regulated compared to the CTR mice. Finally, we found that RH increased nitric oxide-mediated dilation of the caudal artery. Taken together, these results suggest that rose hip is a suitable dietary supplement for preventing atherosclerotic plaques formation by modulating systemic blood pressure and the expression of RCT and inflammatory genes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spencer, H.
1977-01-01
Trace element studies of cadmium, copper, zinc, lead, manganese, and nickel were carried out under strictly controlled dietary conditions in adult males during different calcium intakes. Complete metabolic balances of the trace elements listed above were determined in each 6-day metabolic period for several weeks by analyzing the constant diet and the urinary and fecal excretions of these naturally occurring elements, using atomic absorption spectroscopy. Strontium-90 metabolism studies in man were carried out in order to complete previously initiated investigations. Publications and presentations of papers derived from studies carried out during the current contract period are listed.
Ruby, E. G.; Morin, J. G.
1979-01-01
Three taxa of luminous bacteria (Photobacterium fischeri, P. phosphoreum, and Beneckea spp.) were found in the enteric microbial populations of 22 species of surface- and midwater-dwelling fishes. These bacteria often occurred in concentrations ranging between 105 and 107 colony-forming units per ml of enteric contents. By using a genetically marked strain, it was determined that luminous cells entering the fish during ingestion of seawater or contaminated particles traversed the alimentary tract and survived the digestive processes. After excretion, luminous bacteria proliferated extensively on the fecal material and became distributed into the surrounding seawater. Thus, this enteric habitat may serve as an enrichment of viable cells entering the planktonic luminous population. PMID:16345429
Palmer, Melissa; Jennings, Lee; Silberg, Debra G; Bliss, Caleb; Martin, Patrick
2018-03-16
Accumulation of toxic free cholesterol in hepatocytes may cause hepatic inflammation and fibrosis. Volixibat inhibits bile acid reuptake via the apical sodium bile acid transporter located on the luminal surface of the ileum. The resulting increase in bile acid synthesis from cholesterol could be beneficial in patients with non-alcoholic steatohepatitis. This adaptive dose-finding study investigated the safety, tolerability, pharmacodynamics, and pharmacokinetics of volixibat. Overweight and obese adults were randomised 3:1 to double-blind volixibat or placebo, respectively, for 12 days. Volixibat was initiated at a once-daily dose of 20 mg, 40 mg or 80 mg. Based on the assessment of predefined safety events, volixibat dosing was either escalated or reduced. Other dose regimens (titrations and twice-daily dosing) were also evaluated. Assessments included safety, tolerability, stool hardness, faecal bile acid (FBA) excretion, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and lipids. All 84 randomised participants (volixibat, 63; placebo, 21) completed the study, with no serious adverse events at doses of up to 80 mg per day (maximum assessed dose). The median number of daily bowel evacuations increased from 1 (range 0-4) to 2 (0-8) during volixibat treatment, and stool was looser with volixibat than placebo. Volixibat was minimally absorbed; serum levels were rarely quantifiable at any dose or sampling time point, thereby precluding pharmacokinetic analyses. Mean daily FBA excretion was 930.61 μmol (standard deviation [SD] 468.965) with volixibat and 224.75 μmol (195.403) with placebo; effects were maximal at volixibat doses ≥20 mg/day. Mean serum C4 concentrations at day 12 were 98.767 ng/mL (standard deviation, 61.5841) with volixibat and 16.497 ng/mL (12.9150) with placebo. Total and low-density lipoprotein cholesterol levels decreased in the volixibat group, with median changes of - 0.70 mmol/L (range - 2.8 to 0.4) and - 0.6990 mmol/L (- 3.341 to 0.570), respectively. This study indicates that maximal inhibition of bile acid reabsorption, as assessed by FBA excretion, occurs at volixibat doses of ≥20 mg/day in obese and overweight adults, without appreciable change in gastrointestinal tolerability. These findings guided dose selection for an ongoing phase 2 study in patients with non-alcoholic steatohepatitis. ClinicalTrials.gov identifier: NCT02287779 (registration first received 6 November 2014).
Coblentz, W K; Hoffman, P C; Esser, N M; Bertram, M G
2013-10-01
Our objectives were to describe and test refined procedures for quantifying excreta produced from whole pens of dairy heifers. Previous research efforts attempting to make whole-pen measurements of excreta output have been complicated by the use of organic bedding, which requires cumbersome analytical techniques to quantify excreta apart from the bedding. Research pens equipped with sand-bedded freestalls offer a unique opportunity for refinement of whole-pen fecal collection methods, primarily because sand-bedded freestall systems contain no organic bedding; therefore, concentrations of ash within the manure, sand, and feces can be used to correct for contamination of manure by sand bedding. This study was conducted on a subset of heifers from a larger production-scale feeding trial evaluating ensiled eastern gamagrass [Tripsacum dactyloides (L.) L.] haylage (EGG) that was incorporated into a corn silage/alfalfa haylage-based blended diet at rates of 0, 9.1, 18.3, or 27.4% of total DM. The diet without EGG also was offered on a limit-fed basis. Eighty Holstein dairy heifers were blocked (heavy weight, 424 ± 15.9 kg; light weight, 324 ± 22.4 kg) and then assigned to 10 individual pens containing 8 heifers/pen. One pen per block was assigned to each of the 5 research diets, and whole-pen fecal collections were conducted twice for each pen. Grab fecal samples also were gathered from individual heifers within each pen, and subsequent analysis of these whole-pen composites allowed reasonable estimates of OM and NDF excreta output. Under the conditions of our experimental design, pooled SEM for the excreta DM, OM, NDF, and NDF (ash corrected) output were 0.113, 0.085, 0.093, and 0.075 kg·heifer(-1)·d(-1), respectively. For DM excretion, this represented about one-third of the SEM reported for previous whole-pen collections from bedded-pack housing systems. Subsequent calculations of apparent DM and OM digestibilities indicated that the technique was sensitive, and linear trends (P ≤ 0.027) associated with the inclusion rates of EGG within the diet were detected. This technique allows estimation of apparent diet digestibilities on multiple animals simultaneously, thereby mitigating the need for isolating individual animals to obtain digestibility coefficients. The approach appears viable but requires hand labor for collections of multiple pens and thorough mixing of large volumes of manure as well as analytical corrections for sand ingested by lounging heifers.
Genome-wide screen for modulation of hepatic apolipoprotein A-I (ApoA-I) secretion.
Miles, Rebecca R; Perry, William; Haas, Joseph V; Mosior, Marian K; N'Cho, Mathias; Wang, Jian W J; Yu, Peng; Calley, John; Yue, Yong; Carter, Quincy; Han, Bomie; Foxworthy, Patricia; Kowala, Mark C; Ryan, Timothy P; Solenberg, Patricia J; Michael, Laura F
2013-03-01
Control of plasma cholesterol levels is a major therapeutic strategy for management of coronary artery disease (CAD). Although reducing LDL cholesterol (LDL-c) levels decreases morbidity and mortality, this therapeutic intervention only translates into a 25-40% reduction in cardiovascular events. Epidemiological studies have shown that a high LDL-c level is not the only risk factor for CAD; low HDL cholesterol (HDL-c) is an independent risk factor for CAD. Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-c that mediates reverse cholesterol transport from tissues to the liver for excretion. Therefore, increasing ApoA-I levels is an attractive strategy for HDL-c elevation. Using genome-wide siRNA screening, targets that regulate hepatocyte ApoA-I secretion were identified through transfection of 21,789 siRNAs into hepatocytes whereby cell supernatants were assayed for ApoA-I. Approximately 800 genes were identified and triaged using a convergence of information, including genetic associations with HDL-c levels, tissue-specific gene expression, druggability assessments, and pathway analysis. Fifty-nine genes were selected for reconfirmation; 40 genes were confirmed. Here we describe the siRNA screening strategy, assay implementation and validation, data triaging, and example genes of interest. The genes of interest include known and novel genes encoding secreted enzymes, proteases, G-protein-coupled receptors, metabolic enzymes, ion transporters, and proteins of unknown function. Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor manumycin A caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. In total, this work underscores the power of functional genetic assessment to identify new therapeutic targets.
Xie, Liyang; Vance, Terrence; Kim, Bohkyung; Lee, Sang Gil; Caceres, Christian; Wang, Ying; Hubert, Patrice A; Lee, Ji-Young; Chun, Ock K; Bolling, Bradley W
2017-01-01
Former smokers are at increased risk for cardiovascular disease. We hypothesized that dietary aronia polyphenols would reduce biomarkers of cardiovascular disease risk, inflammation, and oxidative stress in former smokers. We also determined the extent these effects were associated with polyphenol bioavailability. A 12-week, randomized, placebo-controlled trial was conducted in 49 healthy adult former smokers (n = 24/placebo, n = 25/aronia) to evaluate if daily consumption of 500 mg aronia extract modulated plasma lipids, blood pressure, biomarkers of inflammation and oxidative stress, and lipid transport genes of peripheral blood mononuclear cells. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C) from baseline, and multivariate correlation analysis was performed to determine if changes in lipids were associated with urinary polyphenol excretion. Aronia consumption reduced fasting plasma total cholesterol by 8% (P = .0140), LDL-C by 11% (P = .0285), and LDL receptor protein in peripheral blood mononuclear cells (P = .0036) at 12 weeks compared with the placebo group. Positive changes in the urinary polyphenol metabolites peonidin-3-O-galactoside, 3-(4-hydroxyphenyl) propionic acid, and unmetabolized anthocyanin cyanidin-3-O-galactoside were associated with lower plasma total cholesterol and LDL-C in the aronia group. Aronia consumption did not change blood pressure or biomarkers of inflammation and oxidative stress. Aronia polyphenols reduced total and LDL-C in former smokers but did not improve biomarkers of oxidative stress and chronic inflammation. The cholesterol-lowering activity of aronia extract was most closely associated with urinary levels of cyanidin-3-O-galactoside and peonidin-3-O-galactoside, its methylated metabolite. This trial was registered at ClinicalTrials.gov as NCT01541826. Copyright © 2016 Elsevier Inc. All rights reserved.
Recent advances in role of chromium and its antioxidant combinations in poultry nutrition: A review
Haq, Z.; Jain, R. K.; Khan, N.; Dar, M. Y.; Ali, S.; Gupta, M.; Varun, T. K.
2016-01-01
Poultry is reared in open side houses in most of the tropical countries, which results in huge temperature variation in shed causing stress resulting in increased demand of antioxidant supplementation. Since cooling of poultry houses or environment control is very expensive, thus methods focused on nutritional modifications appears to be the much logical approach. Stress increases mineral and vitamin mobilization from tissues and their excretion. Effect of some minerals and vitamin supplements such as chromium (Cr) and ascorbic acid to elevate the negative effects of environmental stress is well documented. Cr functions as an antioxidant and its deficiency are said to disrupt carbohydrate and protein metabolism. Cr has been utilized for weight gain, to improve feed conversion ratio, increase relative organ weight, muscle development, decrease cholesterol, increase high-density lipoprotein cholesterol, and improve nutrient digestion. Therefore, the present review discusses the beneficial aspects of Cr with its effect in different doses and antioxidant combinations to explore and promote its optimum utilization in poultry nutrition and production. PMID:28096611
Pina, D S; Valadares Filho, S C; Tedeschi, L O; Barbosa, A M; Valadares, R F D
2009-03-01
This experiment evaluated the effect of 2 levels of diet concentrate (20 and 40% of DM) and 2 levels of ruminally undegraded protein (RUP: 25 and 40% of CP) on nutrient intake, total and partial apparent nutrient digestibility, microbial protein synthesis, and ruminal and physiological variables. Eight Nellore heifers (233 +/- 14 kg of BW) fitted with ruminal, abomasal, and ileal cannulas were used. The animals were held in individual sheltered pens of approximately 15 m(2) and fed twice daily at 0800 and 1600 h for ad libitum intake. Heifers were allocated in two 4 x 4 Latin square designs, containing 8 heifers, 4 experimental periods, and 4 treatments in a 2 x 2 factorial arrangement. All statistical analyses were performed using PROC MIXED of SAS. Titanium dioxide (TiO(2)) and chromic oxide (Cr(2)O(3)) were used to estimate digesta fluxes and fecal excretion. Purine derivative (PD) excretion and abomasal purine bases were used to estimate the microbial N (MN) synthesis. No significant interaction (P > 0.10) between dietary levels of RUP and concentrate was observed. There was no effect of treatment (P = 0.24) on DMI. Both markers led to the same estimates of fecal, abomasal, and ileal DM fluxes, and digestibilities of DM and individual nutrients. Ruminal pH was affected by sampling time (P < 0.001), but no interaction between treatment and sampling time was observed (P = 0.71). There was an interaction between treatment and sampling time (P < 0.001) for ruminal NH(3)-N concentration. A linear decrease (P = 0.04) over sampling time was observed for the higher level of RUP, whereas a quadratic effect (P < 0.001) of sampling time was observed for the lower level of RUP. The higher level of dietary concentrate led to greater MN yield regardless of the level of RUP. The MN yield and the efficiency of microbial yield estimated from urinary PD excretion produced greater (P < 0.01) values than those estimated by either TiO(2) or Cr(2)O(3), which did not differ (P = 0.63) from each other. However, all methods yielded values that were within the range reported in the literature. In conclusion, no interactions between dietary levels of RUP and concentrate were observed for ruminal and digestive parameters. Neither RUP nor concentrate level affected DMI. Titanium dioxide showed to be similar to Cr(2)O(3) as an external marker to measure digestibility and nutrient fluxes in cattle.
Zhao, Y G; Annett, R; Yan, T
2017-08-01
Thirty-six nonpregnant hill ewes (18 pure Scottish Blackface and 18 Swaledale × Scottish Blackface) aged 18 mo and weighing 48 ± 4.8 kg were allocated to 3 forage treatments balanced for genotype and BW. Each genotype was offered 3 forages (pelleted ryegrass, fresh lowland grass, and fresh hill grass) ad libitum with 6 ewes for each of the 6 genotype × diet combination treatments. Pelleted ryegrass was sourced from a commercial supplier (Drygrass South Western Ltd, Burrington, UK). Fresh lowland grass was harvested daily in the morning from a third regrowth perennial ryegrass () sward. Fresh hill grass was harvested from a seminatural hill grassland every 2 d and stored in plastic bags at 4 to 5°C until offered. The animals were individually housed in pens and offered experimental diets for 14 d before being transferred to 6 individual respiration chambers for a further 4 d, during which feed intake, fecal and urine outputs, and CH emissions were measured. There was no interaction between genotype and forage types on any variable measured. In a comparison of effects of the 3 forages, pelleted ryegrass had the greatest ( < 0.001) values in DMI, GE intake, CH emissions, N intake (NI), and fecal N (FN), urine N (UN), and manure N (MN) outputs, whereas hill grass had the lowest ( < 0.001) values in DMI, energy (GE, DE, and ME) intake, CH emissions, NI, UN, and MN. However, pelleted ryegrass had the lowest ratio in CH emissions per unit DMI ( = 0.022) or GE intake ( = 0.026) or UN excretion as a proportion of NI or MN ( < 0.001). Lowland grass had a greater ( < 0.001) digestibility of DM, OM, CP, NDF, ADF, and GE and a greater ( < 0.001) ME:GE ratio or retained N:NI ratio than pelleted ryegrass and hill grass. Genotypes of sheep had no effect on any variable in feed intake, digestibility, CH emissions, or N utilization. The CH conversion factors (CH energy/GE) for pelleted ryegrass, lowland grass, and hill grass were 4.4, 5.7, and 5.6%, respectively. All data were then pooled to develop regression equations between CH and DMI or between N excretions (FN, UN, and MN) and NI. Methane emissions and N excretions were positively related to DMI and NI ( < 0.001), respectively. However, increasing DMI could reduce CH emissions per kilogram DMI. These equations add new information in predicting enteric CH emissions and N utilization efficiency and can be used to quantify the environmental footprint of hill sheep production systems.
Cheong, Ai Mun; Jessica Koh, Jue Xi; Patrick, Nwabueze Okechukwu; Tan, Chin Ping; Nyam, Kar Lin
2018-03-01
This study aimed to evaluate the effect of kenaf seed oil (KSO), kenaf seed oil-in-water macroemulsion (KSOM), kenaf seed oil-in-water nanoemulsions (KSON), and emulsifier mixtures (EM) on serum lipid profile, liver oxidative status, and histopathological changes in high-cholesterol fed rats. Stability and characteristic of KSOM and KSON were carried out prior to in vivo study. Forty-two Sprague-Dawley rats were divided into 7 groups (6 rats each) and induced hypercholesterolemia by feeding high cholesterol diet (HCD) for 14 days prior to treatments. Different treatments were introduced on day 15 to 29 while supplemented with HCD and removal of HCD during treatment on day 30 to 43, except for HCD group. Body weight and serum lipid profiles were measured at 3 different points: after hypercholesterolemia was induced, on day 29, and at the end of the experiment. Relative liver weight, atherogenic index, coronary risk index, and fecal total bile acids were also determined at the end of experiment. KSON showed significantly higher stability than KSOM and FTIR exhibited good encapsulation of KSO after 1.5 years of storage. Serum total cholesterol, low density lipoprotein cholesterol, lipid peroxidation levels in HCD group without treatment were significantly higher compared to normal control group and all treatment groups. All samples demonstrated hypocholesterolemic effect, but KSON exhibited higher efficiency in cholesterol-lowering properties, weight control and decreased liver fat as confirmed by histopathological evaluation. The overall results revealed that the efficacy of different treatments was in descending order of KSON, KSO, KSOM, and EM. Kenaf seed oil-in-water nanoemulsion (KSON) has the potential to be used as a natural alternative to the synthetic hypocholesterolemic drug in the future. However, larger sample size and clinical trial are needed to confirm on this potential application. In addition, treatment with KSON was suggested to prevent cardiovascular disease and fatty liver. © 2018 Institute of Food Technologists®.
Lin, Shih-Hung; Huang, Kao-Jean; Weng, Ching-Feng; Shiuan, David
2015-01-01
Cholesterol plays an important role in living cells. However, a very high level of cholesterol may lead to atherosclerosis. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase is the key enzyme in the cholesterol biosynthesis pathway, and the statin-like drugs are inhibitors of human HMG-CoA reductase (hHMGR). The present study aimed to virtually screen for potential hHMGR inhibitors from natural product to discover hypolipidemic drug candidates with fewer side effects and lesser toxicities. We used the 3D structure 1HWK from the PDB (Protein Data Bank) database of hHMGR as the target to screen for the strongly bound compounds from the traditional Chinese medicine database. Many interesting molecules including polyphenolic compounds, polisubstituted heterocyclics, and linear lipophilic alcohols were identified and their ADMET (absorption, disrtibution, metabolism, excretion, toxicity) properties were predicted. Finally, four compounds were obtained for the in vitro validation experiments. The results indicated that curcumin and salvianolic acid C can effectively inhibit hHMGR, with IC50 (half maximal inhibitory concentration) values of 4.3 µM and 8 µM, respectively. The present study also demonstrated the feasibility of discovering new drug candidates through structure-based virtual screening.
Yoon, Jae-Sung; Park, Byung-Sung
2016-07-01
The objective of the present study was to determine the effect of feeding fermented earthworm casts (EEC) to layers on egg-laying performance, blood lipid profiles, cecal microflora, and fecal odor removing performance. A total of 200 Hyline Brown layer chicks at 33-week-old were used in this study. They were randomly assigned to two numerically equal groups with 100 replications per treatment for 10 weeks. All the birds were caged individually. The control group was not treated with EEC. The EEC group was treated with top dressing containing 3.5% EEC. The present study revealed that egg production and egg weight were increased after feeding diet containing EEC at the top dressing level. Haugh unit, eggshell thickness, and eggshell breaking strength of EEC group were higher than those of control group. Egg yolk was determined for fatty acid profiling. It was found that EEC group had higher ratio of unsaturated- to saturated fatty acid as compared to control group. Lower ratios of n-6 to n-3 fatty acids were found in the egg yolk of EEC group. Plasma triglyceride and total cholesterol contents were lower in the EEC group. However, high density lipoprotein-cholesterol content was higher in the EEC group as compared to that in control group. The number of cecal Lactobacillus was increased while the population of Escherichia coli and coliform bacteria decreased in the EEC group. Fecal ammonia and hydrogen sulfide contents were lower in the EEC group as compared to those in control group. Taken together, these results suggested that EEC could improve egg production and egg quality. In addition, it could remove odour from laying-hen manure.
Hazarika, Ankita; Kalita, Himadri; Kalita, Mohan Chandra; Devi, Rajlakshmi
2017-06-01
The "lipid hypothesis" determined that saturated fatty acid (SFA) raises low-density lipoprotein cholesterol, thereby increasing the risk for metabolic syndrome (MetS). The aim of this study was to investigate the effect of subchronic withdrawal from a high-carbohydrate, high-saturated fat (HCHF) diet during MetS with reference to changes in deleterious SFA (C12:0, lauric acid; C14:0, myristic acid; C16:0, palmitic acid; C18:0, stearic acid) distribution in liver, white adipose tissue (WAT), and feces. MetS induced by prolonged feeding of an HCHF diet in Wistar albino rat is used as a model of human MetS. The MetS-induced rats were withdrawn from the HCHF diet and changed to a basal diet for final 4 wk of the total experimental duration of 16 wk. SFA distribution in target tissues and hepatic low-density lipoprotein receptor (LDLr) expression were analyzed. Analyses of changes in SFA concentration of target tissues indicate that C16:0 and C18:0 reduced in WAT and liver after withdrawal of the HCHF diet. There was a significant (P < 0.001) decrease in fecal C12:0 with HCHF feeding, which significantly (P < 0.01) increased after withdrawal of this diet. Also, an improvement in expression of hepatic LDLr was observed after withdrawal of HCHF diet. The prolonged consumption of an HCHF diet leads to increased SFA accumulation in liver and WAT, decreased SFA excretion, and reduced hepatic LDLr expression during MetS, which is prominently reversed after subchronic withdrawal of the HCHF diet. This can contribute to better understanding of the metabolic fate of dietary SFA during MetS and may apply to the potential reversal of complications by the simple approach of nutritional modification. Copyright © 2017 Elsevier Inc. All rights reserved.
Pinna, Carlo; Vecchiato, Carla Giuditta; Bolduan, Carmen; Grandi, Monica; Stefanelli, Claudio; Windisch, Wilhelm; Zaghini, Giuliano; Biagi, Giacomo
2018-03-20
Feeding dogs with diets rich in protein may favor putrefactive fermentations in the hindgut, negatively affecting the animal's intestinal environment. Conversely, prebiotics may improve the activity of health-promoting bacteria and prevent bacterial proteolysis in the colon. The aim of this study was to evaluate the effects of dietary supplementation with fructooligosaccharides (FOS) on fecal microbiota and apparent total tract digestibility (ATTD) in dogs fed kibbles differing in protein content. Twelve healthy adult dogs were used in a 4 × 4 replicated Latin Square design to determine the effects of four diets: 1) Low protein diet (LP, crude protein (CP) 229 g/kg dry matter (DM)); 2) High protein diet (HP, CP 304 g/kg DM); 3) Diet 1 + 1.5 g of FOS/kg; 4) Diet 2 + 1.5 g of FOS/kg. The diets contained silica at 5 g/kg as a digestion marker. Differences in protein content were obtained using different amounts of a highly digestible swine greaves meal. Each feeding period lasted 28 d, with a 12 d wash-out in between periods. Fecal samples were collected from dogs at 0, 21 and 28 d of each feeding period. Feces excreted during the last five days of each feeding period were collected and pooled in order to evaluate ATTD. Higher fecal ammonia concentrations were observed both when dogs received the HP diets (p < 0.001) and the supplementation with FOS (p < 0.05). The diets containing FOS resulted in greater ATTD of DM, Ca, Mg, Na, Zn, and Fe (p < 0.05) while HP diets were characterized by lower crude ash ATTD (p < 0.05). Significant interactions were observed between FOS and protein concentration in regards to fecal pH (p < 0.05), propionic acid (p < 0.05), acetic to propionic acid and acetic + n-butyric to propionic acid ratios (p < 0.01), bifidobacteria (p < 0.05) and ATTD of CP (p < 0.05) and Mn (p < 0.001). A relatively moderate increase of dietary protein resulted in higher concentrations of ammonia in canine feces. Fructooligosaccharides displayed beneficial counteracting effects (such as increased bifidobacteria) when supplemented in HP diets, compared to those observed in LP diets and, in general, improved the ATTD of several minerals.
Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review.
Molnár, Gergő A; Kun, Szilárd; Sélley, Eszter; Kertész, Melinda; Szélig, Lívia; Csontos, Csaba; Böddi, Katalin; Bogár, Lajos; Miseta, Attila; Wittmann, István
2016-01-01
Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2(nd) and 3(rd) days (p<0.05 vs. controls), and the kinetics follows the intensity of the systemic inflammation correlating with serum procalcitonin levels. In a similar study subset, urinary meta-tyrosine excretion correlated with both need of daily insulin dose and the insulin-glucose product in non-diabetic septic cases (p<0.01 for both). Using linear regression model, meta-tyrosine excretion, urinary meta-tyrosine/para-tyrosine, urinary ortho-tyrosine/para-tyrosine and urinary (meta- + orthotyrosine)/ para-tyrosine proved to be markers of carbohydrate homeostasis. In a chronic rodent model, we tried to compensate the abnormal tyrosine isomers using para-tyrosine, the physiological amino acid. Rats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine. Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases.
Liu, Peng; Liu, Ruidong; Chen, Xia; Chen, Yingying; Wang, Debao; Zhang, Fengmei; Wang, Yangang
2015-12-01
To investigate the effect of levothyroxine (LT4) therapy on urinary albumin excretion rate (UAER) in early type 2 diabetic nephropathy (DN) and subclinical hypothyroidism (SCH) patients with mildly increased thyroid stimulating hormone (TSH) levels and serum thyroid peroxidase antibody (TPO-Ab) positivity. Application of randomized double-blind and placebo-controlled methods. A total of 136 normotensive patients with early type 2 DN and SCH (TSH 4.0-7.0 mIU/L and TPO-Ab positive) were selected, and were randomly divided into two groups for LT4 or placebo treatments, respectively. Changes in UAER, serum creatinine, glomerular filtration rate (GFR), blood pressure, serum uric acid and lipids in patients before and after 48 weeks of treatment were examined and compared between groups. There were no statistically significant differences in the baseline characteristics of study participants between two treatment groups (p > 0.05 for all). After 48 weeks of treatment, compared to the placebo treatment, the LT4 treatment was more effective in reducing total cholesterol (p < 0.05). Further comparison of therapy-related differences between groups showed that the LT4 treatment was better in reducing UAER, low-density lipoprotein cholesterol and uric acid than the placebo group (p < 0.01 for all). The LT4 treatment may decrease UAER and exert kidney protection effects in early type 2 DN and SCH patients with mildly increased TSH levels and serum TPO-Ab positivity. However, due to the short duration of follow-up and small number of cases, the results of this study need future trials with larger numbers of patients and longer follow-up periods to verify whether such a strategy can provide durable benefits.
Aggrey, S E; Lee, J; Karnuah, A B; Rekaya, R
2014-04-01
The understanding of the dynamics of ammonia detoxification and excretion in uricotelic species is lagging behind ureotelic species. The relative expression of genes involved in nitrogen recycling and feed efficiency in chickens is unknown. The objective of this study was to investigate the transcriptomics differences in key genes in the nitrogen (N) metabolism and purine biosynthesis pathway in a chicken population divergently selected for low (LRFI) or high (HRFI) residual feed intake at days 35 and 42 using duodenum, liver, pectoralis major (P. major) and kidney. There was a significant positive correlation between RFI and fecal N. The purine salvage pathway was activated in the LRFI compared with HRFI at days 42. The birds in the LRFI population attained greater feed efficiency by having lower FI, increasing their protein retention and producing adequate glutamine to maintain growth compared with the HRFI line. To maintain growth, excess N is deaminated mostly to generate purine nucleotides. Generating purine nucleotides primarily from the purine biosynthesis pathway is energetically costly, and to preserve energy, they preferentially generate nucleotides from the purine salvage pathway. The LRFI birds need to generate sufficient nucleotides to maintain growth despite reduced FI that then results in reduced fecal N. © 2013 Stichting International Foundation for Animal Genetics.
Shi, Yinghua; Guo, Rui; Wang, Xianke; Yuan, Dedi; Zhang, Senhao; Wang, Jie; Yan, Xuebing; Wang, Chengzhang
2014-01-01
To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE) and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD) rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC) and total bile acids (TBA) levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1) The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group) (P<0.05). (2) Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05). TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05). (3) mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05), as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05). The activities of these enzymes also paralleled the observed changes in mRNA levels. (4) There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1) the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2) the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia. PMID:24505463
Proteomic analysis of urine in rats chronically exposed to fluoride.
Kobayashi, Claudia Ayumi Nakai; Leite, Aline de Lima; da Silva, Thelma Lopes; dos Santos, Lucilene Delazari; Nogueira, Fábio César Sousa; Santos, Keity Souza; de Oliveira, Rodrigo Cardoso; Palma, Mario Sérgio; Domont, Gilberto Barbosa; Buzalaf, Marília Afonso Rabelo
2011-01-01
Urine is an ideal source of materials to search for potential disease-related biomarkers as it is produced by the affected tissues and can be easily obtained by noninvasive methods. 2-DE-based proteomic approach was used to better understand the molecular mechanisms of injury induced by fluoride (F(-)) and define potential biomarkers of dental fluorosis. Three groups of weanling male Wistar rats were treated with drinking water containing 0 (control), 5, or 50 ppm F(-) for 60 days (n = 15/group). During the experimental period, the animals were kept individually in metabolic cages, to analyze the water and food consumption, as well as fecal and urinary F(-) excretion. Urinary proteome profiles were examined using 2-DE and Colloidal Coomassie Brilliant Blue staining. A dose-response regarding F(-) intake and excretion was detected. Quantitative intensity analysis revealed 8, 11, and 8 significantly altered proteins between control vs. 5 ppm F(-), control vs. 50 ppm F(-) and 5 ppm F(-) vs. 50 ppm F(-) groups, respectively. Two proteins regulated by androgens (androgen-regulated 20-KDa protein and α-2μ-globulin) and one related to detoxification (aflatoxin-B1-aldehyde-reductase) were identified by MALDI-TOF-TOF MS/MS. Thus, proteomic analysis can help to better understand the mechanisms underlying F(-) toxicity, even in low doses. Copyright © 2010 Wiley Periodicals, Inc.
Christensen, Jennie R; Yunker, Mark B; MacDuffee, Misty; Ross, Peter S
2013-04-01
The present study characterizes the uptake and loss of persistent organic pollutants (POPs) in grizzly bears (Ursus arctos horribilis) by sampling and analyzing their terrestrial and marine foods and fecal material from a remote coastal watershed in British Columbia, Canada. The authors estimate that grizzly bears consume 341 to 1,120 µg of polychlorinated biphenyls (PCBs) and 3.9 to 33 µg of polybrominated diphenyl ethers daily in the fall when they have access to an abundant supply of returning salmon. The authors also estimate that POP elimination by grizzly bears through defecation is very low following salmon consumption (typically <2% of intake) but surprisingly high following plant consumption (>100% for PCBs and organochlorine pesticides). Excretion of individual POPs is largely driven by a combination of fugacity (differences between bear and food concentrations) and the digestibility of the food. The results of the present study are substantiated by a principal components analysis, which also demonstrates a strong role for log KOW in governing the excretion of different POPs in grizzly bears. Collectively, the present study's results reveal that grizzly bears experience a vegetation-associated drawdown of POPs previously acquired through the consumption of salmon, to such an extent that net biomagnification is reduced. Copyright © 2013 SETAC.
Polish, Louis B.; Robertson, Betty H.; Khanna, Bhawna; Krawczynski, Krzysztof; Spelbring, John; Olson, Fred; Shapiro, Craig N.
1999-01-01
Fecal excretion of hepatitis A virus (HAV) in 18 patients with HAV infection was evaluated by enzyme immunoassay (EIA) to detect viral antigen and by reverse transcription-PCR amplification followed by ethidium bromide staining (PCR-ETBr) or nucleic acid hybridization (PCR-NA) to detect viral genetic material. A gradation of sensitivity was observed in the detection of virus by the three methods. In persons who had detectable virus, serial stool samples were found to be positive by EIA for up to 24 days after the peak elevation of liver enzymes. Viral genetic material could be detected by PCR-ETBr for up to 34 days and by PCR-NA for up to 54 days after the peak elevation of liver enzymes. After intravenous inoculation of tamarins with stool suspensions categorized as highly reactive for HAV (positive by EIA, PCR-ETBr, and PCR-NA), moderately reactive (positive by PCR-ETBr and PCR-NA), or weakly reactive (positive by PCR-NA), only tamarins infected with highly reactive stool suspensions (EIA positive) developed HAV infection. We conclude that positivity of stool specimens for HAV by PCR-ETBr or PCR-NA indicates a lower potential for infectivity, compared to that of EIA-positive stools. PMID:10523563
Li, Kun; Lan, Yanfang; Luo, Houqiang; Zhang, Hui; Liu, Dongyu; Zhang, Lihong; Gui, Rui; Wang, Lei; Shahzad, Muhammad; Sizhu, Suolang; Li, Jiakui; Chamba, Yangzom
2016-01-01
Toxocara vitulorum has been rarely reported in yaks at high altitudes and remote areas of Sichuan Province of Tibetan Plateau of China. The current study was designed to investigate the prevalence, associated risk factors, and phylogenetic characteristics of T. vitulorum in yak calves on the Qinghai Tibetan plateau. Fecal samples were collected from 891 yak calves and were examined for the presence of T. vitulorum eggs by the McMaster technique. A multivariable logistic regression model was employed to explore variables potentially associated with exposure to T. vitulorum infection. T. vitulorum specimens were collected from the feces of yaks in Hongyuan of Sichuan Province, China. DNA was extracted from ascaris. After PCR amplification, the sequencing of ND1 gene was carried out and phylogenetic analyses was performed by MEGA 6.0 software. The results showed that 64 (20.1%; 95% CI 15.8–24.9%), 75 (17.2; 13.8–21.1), 29 (40.9; 29.3–53.2), and 5 (7.6; 2.5–16.8) yak calves were detected out to excrete T. vitulorum eggs in yak calve feces in Qinghai, Tibet, Sichuan, and Gansu, respectively. The present study revealed that high infection and mortality by T. vitulorum is wildly spread on the Qinghai Tibetan plateau, China by fecal examination. Geographical origin, ages, and fecal consistencies are the risk factors associated with T. vitulorum prevalence by logistic regression analysis. Molecular detection and phylogenetic analysis of ND1 gene of T. vitulorum indicated that T. vitulorum in the yak calves on the Qinghai Tibetan plateau are homologous to preveiously studies reported. PMID:27853122
Seymour, C; Dickerman, R W
1978-03-01
A total of 80 Neotropical bats of five species was inoculated with one of four strains of Venezuelan encephalitis (VE) virus. Virus was detected in the oropharynges of 56% of bats, and most regularly in Artibeus jamaicensis (75%). Titers of virus in oropharyngeal secretions were occasionally very high (8.5 log10 SMicLD50/ml in one A. jamaicensis). Only 2 of 123 urine samples from 50 bats and 2 of 86 fecal samples from 46 bats yielded VE virus. No contact or aerosol virus transmission from bat to bat was detected. VE virus passed transplacentally from two infected mothers to their fetuses, which were aborted. Virus did not pass from one infected mother to her nursing young.
Oxalobacter formigenes Colonization and Oxalate Dynamics in a Mouse Model
Li, Xingsheng; Ellis, Melissa L.
2015-01-01
Animal and human studies have provided compelling evidence that colonization of the intestine with Oxalobacter formigenes reduces urinary oxalate excretion and lowers the risk of forming calcium oxalate kidney stones. The mechanism providing protection appears to be related to the unique ability of O. formigenes to rely on oxalate as a major source of carbon and energy for growth. However, much is not known about the factors that influence colonization and host-bacterium interactions. We have colonized mice with O. formigenes OxCC13 and systematically investigated the impacts of diets with different levels of calcium and oxalate on O. formigenes intestinal densities and urinary and intestinal oxalate levels. Measurement of intestinal oxalate levels in mice colonized or not colonized with O. formigenes demonstrated the highly efficient degradation of soluble oxalate by O. formigenes relative to other microbiota. The ratio of calcium to oxalate in diets was important in determining colonization densities and conditions where urinary oxalate and fecal oxalate excretion were modified, and the results were consistent with those from studies we have performed with colonized and noncolonized humans. The use of low-oxalate purified diets showed that 80% of animals retained O. formigenes colonization after a 1-week dietary oxalate deprivation. Animals not colonized with O. formigenes excreted two times more oxalate in feces than they had ingested. This nondietary source of oxalate may play an important role in the survival of O. formigenes during periods of dietary oxalate deprivation. These studies suggest that the mouse will be a useful model to further characterize interactions between O. formigenes and the host and factors that impact colonization. PMID:25979889
Miyamoto, G; Sasabe, H
1984-01-01
The pharmacokinetics of 3, 4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- quin olinone ( OPC -8212) were studied after the administration of 14C- OPC -8212 or OPC -8212 to animals of different species. After oral doses of 10 mg/kg of 14C- OPC -8212 to rats and beagle dogs, the Tmax, Cmax and T1/2 values of OPC -8212 were 4 h, 2995 ng eq/ml, and 3-4 h in rats and 1 h, 2244 ng eq/ml and 5-6 h in beagle dogs, respectively. After oral doses of 10 mg/kg of 14C- OPC -8212 to rats, the radioactivity was distributed comparatively widely in the tissues. However, there was no evidence of accumulation of radioactivity in the tissues due to repeated oral doses of 10 mg/kg of 14C- OPC -8212 once a day for 21 days. After oral doses of 10 mg/kg of 14C- OPC -8212, the amounts of radioactivity excreted in the urine and feces in the first 72 h accounted for 29.25% and 60.24% of the dose in rats and 35.53% and 63.18% of the dose in beagle dogs, respectively. There were no apparent changes in the urinary and fecal excretions of radioactivity due to repeated oral doses of 10 mg/kg of 14C- OPC -8212 once a day for 21 days in rats. Biliary excretion of radioactivity was 22.41% of the dose after oral doses of 10 mg/kg 14C- OPC -8212 in rats. Enterohepatic circulation was 22.04% of the dose after an intraduodenal dose in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Cryptosporidiosis and other intestinal parasitic infections in patients with chronic diarrhea.
Mahdi, Nadham K; Ali, Naeel H
2004-09-01
To consider the relationship of the parasitic infections including cryptosporidium with chronic diarrhea. Also the effect of chronic disease as pulmonary tuberculosis (TB) and nosocomial infection on the occurrence rate of parasites in cases of chronic diarrhea. Stool samples were collected from 205 patients in teaching, general, child and maternity hospitals in Basrah, Iraq, suffering from chronic diarrhea during 2000. Out of these patients, there were 40 patients with pulmonary TB and 50 inpatients with nosocomial infection. Also 175 apparently healthy individuals who have no episodes of diarrhea for at least 2-months were served as a control group. Direct smear method and then formalin ether sedimentation method were carried out for stool samples to detect intestinal parasites. Fecal smears were prepared from the sediment and stained by the modified Ziehl Neelsen stain for the recovery of red pink oocysts of cryptosporidium. Out of the 205 examined patients, cryptosporidium oocysts were found to be excreted in 20 (9.7%) patients in comparing to 1.1% of the control group. The difference is statistically significant. There were 109 (53.2%) patients found to be positive for intestinal parasitic infections compared to 26 (14.8%) of the control group. The difference is also statistically significant. Out of the 40 TB patients, 2 (5%) were found to excrete cryptosporidium oocysts and also 27 (67.3%) were positive for intestinal parasites. In addition, there were 4 (8%) excreting cryptosporidium oocysts and 23 (46%) infecting by intestinal parasites among the in patients with nosocomial infection. Both acid and non-acid fast parasites should be considered in the differential diagnosis of undiagnosed chronic diarrhea especially among patients with pulmonary TB or nosocomial infection.
Neutral oligosaccharides in feces of breastfed and formula-fed infants at different ages.
Dotz, Viktoria; Adam, Rüdiger; Lochnit, Günter; Schroten, Horst; Kunz, Clemens
2016-12-01
Beneficial effects have been proposed for human milk oligosaccharides (HMO), as deduced from in vitro and animal studies. To date, in vivo evidence of the link between certain oligosaccharide structures in milk and their consumption by infant gut microbiota is still missing, although likely. Whereas many studies have described HMO patterns in human milk from larger cohorts, data on the excretion of HMO and possible metabolites produced in the infant gut are still very limited. From smaller-scale studies, an age-dependency according to infant gut maturation and microbiota adaptation has previously been hypothesized. To further investigate this, we profiled neutral fecal oligosaccharides from term-born infants who were exclusively breastfed, formula-fed or mixed-fed at the age of 2 months, and from a follow-up of a subgroup at 7 months of age (INFABIO study). Data on maternal antibiotic exposure was also included. Automated matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analyses revealed the presence of HMO and metabolites in the feces of most, but not all breastfed infants at 2 months, with highly varying patterns that appeared not to differ with maternal antibiotics exposure. Formula-fed infants at 2 months and most of the breastfed infants at 7 months did not excrete HMO-like structures in their feces, the latter corresponding to the hypothesis of age-dependency. Together with our previous results that were partly contradictory to what has been proposed by others, here, we suggest alternative explanations for the described association of oligosaccharide excretion with age and feeding type in infants below 7 months of age. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Colburn, W A; Vane, F M; Bugge, C J; Carter, D E; Bressler, R; Ehmann, C W
1985-01-01
The pharmacokinetics of isotretinoin and 4-oxoisotretinoin in blood, as well as the blood concentrations and urinary, biliary, and fecal excretion of carbon-14 were studied using liquid scintillation counting techniques and reverse phase HPLC methods following a single 80-mg oral suspension dose of 14C-isotretinoin to four healthy male subjects and two patients with biliary T-tube drainage. Approximately 80% of the dose was recovered as 14C in excreta during the course of the study of which about equal fractions were in the urine and feces. Secondary peaks in blood concentrations of 14C were observed in the healthy subjects whereas they were not seen in the patients with T-tubes. The harmonic mean apparent half-life for isotretinoin in the blood of the healthy subjects was 13.6 hr, whereas the corresponding value for the 14C was 90 hr. Although a rigorous comparison of pharmacokinetic parameters between healthy subjects and T-tube patients was not feasible due to the limited number of subjects studied, comparisons of certain trends in the pharmacokinetic profiles gave some possible insights into the role of biliary excretion and enterohepatic cycling on the disposition of isotretinoin. The data for isotretinoin and 4-oxoisotretinoin coupled with the total carbon-14 data suggest that the oral dose of 14C-isotretinoin is absorbed to a similar extent by the healthy subjects and T-tube patients, whereas T-tube patients clear the drug more rapidly. The biliary excretion and possible enterohepatic circulation of isotretinoin and its metabolites may have significant impact on the pharmacokinetic profile of isotretinoin in man.
Pharmacokinetics, Metabolism, and Excretion of the Antiviral Drug Arbidol in Humans
Deng, Pan; Zhong, Dafang; Yu, Kate; Zhang, Yifan; Wang, Ting
2013-01-01
Arbidol is a broad-spectrum antiviral drug that is used clinically to treat influenza. In this study, the pharmacokinetics, metabolism, and excretion of arbidol were investigated in healthy male Chinese volunteers after a single oral administration of 200 mg of arbidol hydrochloride. A total of 33 arbidol metabolites were identified in human plasma, urine, and feces. The principal biotransformation pathways included sulfoxidation, dimethylamine N-demethylation, glucuronidation, and sulfate conjugation. The major drug-related component in the plasma was sulfinylarbidol (M6-1), followed by unmetabolized arbidol, N-demethylsulfinylarbidol (M5), and sulfonylarbidol (M8). The exposures of M5, M6-1, and M8, as determined by the metabolite-to-parent area under the plasma concentration-time curve from 0 to t (AUC0-t) ratio, were 0.9 ± 0.3, 11.5 ± 3.6, and 0.5 ± 0.2, respectively. In human urine, glucuronide and sulfate conjugates were detected as the major metabolites, accounting for 6.3% of the dose excreted within 0 to 96 h after drug administration. The fecal specimens mainly contained the unchanged arbidol, accounting for 32.4% of the dose. Microsomal incubation experiments demonstrated that the liver and intestines were the major organs that metabolize arbidol in humans. CYP3A4 was the major isoform involved in arbidol metabolism, whereas the other P450s and flavin-containing monooxygenases (FMOs) played minor roles. These results indicated possible drug interactions between arbidol and CYP3A4 inhibitors and inducers. Further investigations are needed to understand the importance of M6-1 in the efficacy and safety of arbidol, because of its high plasma exposure and long elimination half-life (25.0 h). PMID:23357765
Yu, Lei-Min; Zhao, Ke-Jia; Wang, Shuang-Shuang; Wang, Xi; Lu, Bin
2018-01-01
AIM To study the role of microbial metabolites in the modulation of biochemical and physiological processes in irritable bowel syndrome (IBS). METHODS In the current study, using a metabolomic approach, we analyzed the key metabolites differentially excreted in the feces of control mice and mice with IBS, with or without Clostridium butyricum (C. butyricum) treatment. C57BL/6 mice were divided into control, IBS, and IBS + C. butyricum groups. In the IBS and IBS + C. butyricum groups, the mice were subjected to water avoidance stress (WAS) for 1 h/d for ten days. Gas chromatography/mass spectrometry (GC-MS) together with multivariate analysis was employed to compare the fecal samples between groups. RESULTS WAS exposure established an appropriate model of IBS in mice, with symptoms of visceral hyperalgesia and diarrhea. The differences in the metabolite profiles between the control group and IBS group significantly changed with the progression of IBS (days 0, 5, 10, and 17). A total of 14 differentially excreted metabolites were identified between the control and IBS groups, and phenylethylamine was a major metabolite induced by stress. In addition, phenylalanine metabolism was found to be the most relevant metabolic pathway. Between the IBS group and IBS + C. butyricum group, 10 differentially excreted metabolites were identified. Among these, pantothenate and coenzyme A (CoA) biosynthesis metabolites, as well as steroid hormone biosynthesis metabolites were identified as significantly relevant metabolic pathways. CONCLUSION The metabolic profile of IBS mice is significantly altered compared to control mice. Supplementation with C. butyricum to IBS mice may provide a considerable benefit by modulating host metabolism. PMID:29491683
Hypercholesterolemia Impairs Exercise Capacity in Mice
Maxwell, Andrew J.; Niebauer, Josef; Lin, Patrick S.; Tsao, Philip S.; Bernstein, Daniel; Cooke, John P.
2011-01-01
Objective We previously reported an attenuation of both exercise hyperemia and measures of aerobic capacity in hypercholesterolemic mice. In this study we expanded upon the previous findings by examining the temporal and quantitative relationship of hypercholesterolemia to aerobic and anaerobic capacity and by exploring several potential mechanisms of dysfunction. Methods Eight-week old wild type (n=123) and apoE knockout (n=79) C57BL/6J mice were divided into groups with distinct cholesterol levels by feeding regular or high fat diets. At various ages the mice underwent treadmill ergospirometry. To explore mechanisms, aortic ring vasodilator function and nitrate (NOx) activity, urinary excretion of NOx, running muscle microvascular density and citrate synthase activity, as well as myocardial mass and histologic evidence of ischemia were measured. Results At 8 weeks of age, all mice had similar measures of exercise capacity. All indices of aerobic exercise capacity progressively declined at 12 and 20 weeks of age in the hypercholesterolemic mice as cholesterol levels increased while indices of anaerobic capacity remained unaffected. Across the 4 cholesterol groups, the degree of aerobic dysfunction was related to serum cholesterol levels; a relationship that was maintained after correcting for confounding factors. Associated with the deterioration in exercise capacity was a decline in measures of nitric oxide-mediated vascular function while there was no evidence of aberrations in functional or oxidative capacities or in other components of transport capacity. Conclusion Aerobic exercise dysfunction is observed in murine models of genetic and diet-induced hypercholesterolemia and is associated with a reduction in vascular nitric oxide production. PMID:19651675
Guo, Shou-Dong; Cui, Ying-Jie; Wang, Ren-Zhong; Wang, Ren-Yuan; Wu, Wen-Xue; Ma, Teng
2014-09-01
The authors designed to separate, purify and determine the monosaccharide composition of the polysaccharide from Cordyceps militaris, and study its effect on reverse cholesterol transport in vivo by isotope tracing assay. Polysaccharides were separate and purify by ion exchange column Q-sepharose Fast Flow and size exclusion column Sephacryl S200HR; the molecular weight and monosaccharide composition of the polysaccharides were determined by high performance gel permeation chromatography and high performance liquid chromatography coming with pre-column derivation, respectively. Finally, three purified polysaccharides CMBW1, CMBW2 and CMYW1 were obtained, their total carbohydrate contents were 87%, 89%, 95%, respectively; their protein contents were 6.5%, 1.3%, 2.8%, respectively; their molecular weights were 772.1, 20.9, 13.2 kDa, respectively; CMBW1 was composed of mannose, glucosamine, rhamnose, glucuronic acid, glucose, galactose and arabinose with a molar ratio of 7.25: 0.17: 1.29: 0.23: 6.30: 11.08: 0.79; CMBW2 was composed of mannose, glucosamine, galactose and arabinose with a molar ratio of 2.40: 0.16: 2.92: 0.24; CMYW1 was composed of mannose, glucosamine, glucuronic acid and glucose with a molar ratio of 0.59: 0.57: 0.45: 25.61. Polysaccharide at 50 mg x kg(-1) could significantly improve the transport of 3H- cholesterol to blood and excretion from feces. All of the three purified polysaccharides CMBW1, CMBW2 and CMYW1 were heteropolysaccharide; and they could improve reverse cholesterol transport in vivo, the underlying mechanisms are being studied.
Koenig, K M; Beauchemin, K A
2013-05-01
The objectives were to characterize the effects of supplemental CP concentration and ruminal degradability in barley-based finishing diets on microbial protein synthesis, ruminal fermentation and nutrient digestion, and route and chemical form of N excretion in beef cattle. Four Angus heifers (564 ± 18 kg BW) with ruminal and duodenal cannulas were used in an experiment designed as a 4 × 4 Latin square with four 28-d periods (9 d for diet adaptation and 19 d for measurements). The basal diet consisted of 9% barley silage and 91% barley-based concentrate (DM basis). Dietary treatments included the basal diet with no added protein (13% CP) or diets containing 14.5% CP by supplementation with urea (UREA), urea and canola meal (UREA+CM), or urea, corn gluten meal, and xylose-treated soybean meal (UREA+CGM+xSBM). Nutrient digestion was determined using Yb as a digesta flow marker and purine N as a microbial marker with the collection of ruminal, duodenal, and fecal samples over 5 d. The next week, total collections of feces and urine were performed for 5 d to quantify route and chemical form of N excretion. Feed offered was restricted (95% of ad libitum) and there was no effect of the dietary treatments on DMI (P = 0.55); therefore, N intake was less (P < 0.05) in heifers fed the 13% CP diets than the 14.5% CP diets. Supplemental RDP and RUP had no effect on ruminal NH3-N (P = 0.17), peptide N (P = 0.46), and VFA (P = 0.62) concentrations, flow of microbial (P = 0.69) and feed (P = 0.22) N, and ruminal and total tract nutrient digestibility (P ≥ 0.18). Nutrient digestion in the rumen and total tract averaged 75.4 ± 3.8% and 84.6 ± 0.9% for OM, 80.8 ± 3.6% and 95.8 ± 0.8% for starch, and 41.2 ± 7.9% and 60.4 ± 3.3% of intake for NDF, respectively. Daily output of N in feces (P = 0.91) and urine (P = 0.14) were not affected by the dietary treatments. Fecal N output averaged 19.9 ± 1.9% (P = 0.30) and urine N output averaged 44.1 ± 2.8% (P = 0.63) of N intake. Urea N output, however, was greater (P < 0.05) in heifers fed the 14.5% CP than the 13% CP diets and was the major form of N in urine (68.3% in heifers fed the 13% CP diet and 78.7 ± 2.9% in heifers fed the 14.5% CP diets; P < 0.10). Beef cattle fed barley-based finishing diets containing 13% CP do not require additional RDP or RUP to meet microbial or host N requirements. Barley-based finishing diets with no supplemental CP minimized urea N excretion and the potential loss of N from the system.
Higham, James P; Ross, Caroline; Warren, Ymke; Heistermann, Michael; MacLarnon, Ann M
2007-09-01
Several authors have suggested that the consumption of plant compounds may have direct effects on wild primate reproductive biology, but no studies have presented physiological evidence of such effects. Here, for two troops of olive baboons (Papio hamadryas anubis) at Gashaka-Gumti National Park, Nigeria, we show major seasonal increases in levels of fecal progesterone metabolites in females, and provide evidence that this is linked to the consumption of natural plant compounds. Increases in fecal progestogen excretion occurred seasonally in all females, in all reproductive states, including lactation. Detailed feeding data on the study animals showed that only one food species is consumed by both troops at the time of observed progestogen peaks, and at no other times of the year: the African black plum, Vitex doniana. Laboratory tests demonstrated the presence of high concentrations of progestogen-like compounds in V. doniana. Together with published findings linking the consumption of a related Vitex species (Vitex agnus castus) to increased progestogen levels in humans, our data suggest that natural consumption of V. doniana was a likely cause of the observed increases in progestogens. Levels of progestogen excretion in the study baboons during periods of V. doniana consumption are higher than those found during pregnancy, and prevent the expression of the sexual swelling, which is associated with ovulatory activity. As consortship and copulatory activity in baboons occur almost exclusively in the presence of a sexual swelling, V. doniana appears to act on cycling females as both a physiological contraceptive (simulating pregnancy in a similar way to some forms of the human contraceptive pill) and a social contraceptive (preventing sexual swelling, thus reducing association and copulation with males). The negative effects of V. doniana on reproduction may be counter-balanced by the wide-range of medicinal properties attributed to plants in this genus. This is the first time that physiological evidence has been presented of direct effects of plant consumption on the reproductive biology of wild primates.
Baghdasaryan, Anna; Fuchs, Claudia D; Österreicher, Christoph H; Lemberger, Ursula J; Halilbasic, Emina; Påhlman, Ingrid; Graffner, Hans; Krones, Elisabeth; Fickert, Peter; Wahlström, Annika; Ståhlman, Marcus; Paumgartner, Gustav; Marschall, Hanns-Ulrich; Trauner, Michael
2016-03-01
Approximately 95% of bile acids (BAs) excreted into bile are reabsorbed in the gut and circulate back to the liver for further biliary secretion. Therefore, pharmacological inhibition of the ileal apical sodium-dependent BA transporter (ASBT/SLC10A2) may protect against BA-mediated cholestatic liver and bile duct injury. Eight week old Mdr2(-/-) (Abcb4(-/-)) mice (model of cholestatic liver injury and sclerosing cholangitis) received either a diet supplemented with A4250 (0.01% w/w) - a highly potent and selective ASBT inhibitor - or a chow diet. Liver injury was assessed biochemically and histologically after 4weeks of A4250 treatment. Expression profiles of genes involved in BA homeostasis, inflammation and fibrosis were assessed via RT-PCR from liver and ileum homogenates. Intestinal inflammation was assessed by RNA expression profiling and immunohistochemistry. Bile flow and composition, as well as biliary and fecal BA profiles were analyzed after 1week of ASBT inhibitor feeding. A4250 improved sclerosing cholangitis in Mdr2(-/-) mice and significantly reduced serum alanine aminotransferase, alkaline phosphatase and BAs levels, hepatic expression of pro-inflammatory (Tnf-α, Vcam1, Mcp-1) and pro-fibrogenic (Col1a1, Col1a2) genes and bile duct proliferation (mRNA and immunohistochemistry for cytokeratin 19 (CK19)). Furthermore, A4250 significantly reduced bile flow and biliary BA output, which correlated with reduced Bsep transcription, while Ntcp and Cyp7a1 were induced. Importantly A4250 significantly reduced biliary BA secretion but preserved HCO3(-) and biliary phospholipid secretion resulting in an increased HCO3(-)/BA and PL/BA ratio. In addition, A4250 profoundly increased fecal BA excretion without causing diarrhea and altered BA pool composition, resulting in diminished concentrations of primary BAs tauro-β-muricholic acid and taurocholic acid. Pharmacological ASBT inhibition attenuates cholestatic liver and bile duct injury by reducing biliary BA concentrations in mice. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
A randomized physiotherapy trial in patients with fecal incontinence: design of the PhysioFIT-study
Bols, Esther MJ; Berghmans, Bary CM; Hendriks, Erik JM; de Bie, Rob A; Melenhorst, Jarno; van Gemert, Wim G; Baeten, Cor GMI
2007-01-01
Background Fecal incontinence (FI) is defined as the recurrent involuntary excretion of feces in inappropriate places or at inappropriate times. It is a major and highly embarrassing health care problem which affects about 2 to 24% of the adult population. The prevalence increases with age in both men and women. Physiotherapy interventions are often considered a first-line approach due to its safe and non-invasive nature when dietary and pharmaceutical treatment fails or in addition to this treatment regime. Two physiotherapy interventions, rectal balloon training (RBT) and pelvic floor muscle training (PFMT) are widely used in the management of FI. However, their effectiveness remains uncertain since well-designed trials on the effectiveness of RBT and PFMT versus PFMT alone in FI have never been published. Methods/Design A two-armed randomized controlled clinical trial will be conducted. One hundred and six patients are randomized to receive either PFMT combined with RBT or PFMT alone. Physicians in the University Hospital Maastricht include eligible participants. Inclusion criteria are (1) adults (aged ≥ 18 years), (2) with fecal incontinence complaints due to different etiologies persisting for at least six months, (3) having a Vaizey incontinence score of at least 12, (4) and failure of conservative treatment (including dietary adaptations and pharmacological agents). Baseline measurements consist of the Vaizey incontinence score, medical history, physical examination, medication use, anorectal manometry, rectal capacity measurement, anorectal sensation, anal endosonography, defecography, symptom diary, Fecal Incontinence Quality of Life scale (FIQL) and the PREFAB-score. Follow-up measurements are scheduled at three, six and 12 months after inclusion. Skilled and registered physiotherapists experienced in women's health perform physiotherapy treatment. Twelve sessions are administered during three months according to a standardized protocol. Discussion This section discusses the decision to publish a trial protocol, the actions taken to minimize bias and confounding in the design, explains the choice for two treatment groups, discusses the secondary goals of this study and indicates the impact of this trial on clinical practice. Trial registration The Netherlands Trial Register ISRCTN78640169. PMID:18096041
Identification of volatiles from the secretions and excretions of African wild dogs (Lycaon pictus).
Apps, Peter; Mmualefe, Lesego; McNutt, J Weldon
2012-11-01
Gas chromatography/mass spectrometry was used to identify 103 organic compounds from urine, feces, anal glands, and preputial glands of free-ranging African wild dogs, Lycaon pictus. Aliphatic acids were the dominant class of compound in all materials. In addition to aliphatic acids, urine contained dimethyl sulfone, 1,3-propanediol, benzoic acid, 1-methyl-2,4-imidazolidinedione, and squalene as major components: feces contained indole and cholesterol; and both contained 2-piperidone, phenol, 4-methyl phenol, benzeneacetic acid, and benzenepropanoic acid and other compounds. Anal gland secretion was particularly rich in cholesterol and fatty acids, and preputial gland secretion rich in squalene. A large majority of the identified compounds have been reported from other mammals, including species sympatric with African wild dogs. Eleven of the African wild dog components have not been reported previously from mammals and have not been found in sympatric species; one component, 1-methylimidazole-5-carboxaldehyde has not been reported previously as a natural product. In the chemical profiles of their urine, feces, and anal gland secretion African wild dogs differ markedly from other canids.
Patel, Vishal; Joharapurkar, Amit; Kshirsagar, Samadhan; Sutariya, Brijesh; Patel, Maulik; Pandey, Dheerendra; Patel, Hiren; Ranvir, Ramchandra; Kadam, Shekhar; Patel, Dipam; Bahekar, Rajesh; Jain, Mukul
2018-02-25
Dyslipidemia enhances progression of atherosclerosis. Coagonist of GLP-1 and glucagon are under clinical investigation for the treatment of obesity and diabetes. Earlier, we have observed that coagonist reduced circulating and hepatic lipids, independent of its anorexic effects. Here, we investigated the role of coagonist of GLP-1 and glucagon receptors in complications of diet-induced dyslipidemia in hamsters and humanized double transgenic mice. Hamsters fed on high fat high cholesterol diet were treated for 8 weeks with coagonist of GLP-1 and glucagon receptors (75 and 150 μg/kg). Pair-fed control was maintained. Cholesterol fed transgenic mice overexpressing hApoB100 and hCETP with coagonist (300 μg/kg) for 4 weeks. After the completion of treatment, biochemical estimations were done. Coagonist treatment reduced triglycerides in plasma, liver and aorta, plasma cholesterol and hepatic triglyceride secretion rate. Expressions of HMG-CoA reductase and SBREBP-1C were reduced and expressions of LDLR, CYP7A1, ABCA1 and ABCB11 were increased in liver, due to coagonist treatment. Coagonist treatment increased bile flow rate and biliary cholesterol excretion. IL-6 and TNF-α were reduced in plasma and expression of TNF-α, MCP-1, MMP-9 and TIMP-1 decreased in liver. Treatment with coagonist reduced oxidative stress in liver and aorta. Energy expenditure was increased and respiratory quotient was reduced by coagonist treatment. These changes were correlated with reduced hepatic inflammation and lipids in liver and aorta in coagonist treated hamsters. Coagonist treatment also reduced lipids in cholesterol-fed transgenic mice. These changes were independent of glycaemia and anorexia observed after coagonist treatment. Long term treatment with coagonist of GLP-1 and glucagon receptor ameliorated diet-induced dyslipidemia and atherosclerosis by regulating bile homeostasis, liver inflammation and energy expenditure. Copyright © 2018 Elsevier B.V. All rights reserved.
Marcovecchio, M Loredana; Tossavainen, Paivi H; Heywood, James Jn; Dalton, R Neil; Dunger, David B
2012-09-01
Genetic factors modulate lipid levels and an intrafamilial aggregation of abnormal lipid profiles has been reported in the general population. As dyslipidemia is common among people with diabetes and has been related to diabetic nephropathy, we investigated whether parental lipid levels were related to lipids and albumin excretion in young offspring with childhood-onset type 1 diabetes (T1D). Non-fasting blood samples were collected from 895 offspring, 808 mothers and 582 fathers. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and non-HDL-C were measured. Three early morning urinary albumin-creatinine ratios (ACR), hemoglobin A1C (HbA1c) and anthropometric parameters were also assessed. The offspring's mean age (±SD) was 14.5 ± 2.2 yr, mean diabetes duration 5.5 ± 3.7 yr; the fathers' age was 45.7 ± 6.1 yr and the mothers' age was 42.8 ± 5.5 yr. After adjusting for the offspring age, gender, body mass index, HbA1c, maternal (TC: β = 0.242; TG: β = 0.152; HDL-C: β = 0.285; LDL-C: β = 0.278; non-HDL-C: β = 0.253; all p < 0.001) and paternal lipid levels (TC: β = 0.188; TG: β = 0.108; HDL-C: β = 0.253; LDL-C: β = 0.187; non-HDL-C: β = 0.173; all p < 0.001) were significantly associated with the offspring's lipid parameters. In contrast, no significant association was found between parental lipid levels and the offspring's ACR. In the present study, parental lipid levels were independently associated with the same traits in the offspring, suggesting a role of genetic influences and/or shared environmental factors in modulating the metabolic profile of adolescents with T1D. In contrast, there was no significant association between parental lipid levels and the offspring's albumin excretion. © 2012 John Wiley & Sons A/S.
Pölönen, I J; Partanen, K H; Jalava, T K; Toivonen, V F
2000-04-01
Three 2 x 4 factorial experiments were carried out from August to September with 30 juvenile male mink, 24 raccoon dogs, and 24 blue foxes to investigate the effect of dietary glycine supply (low or high) on the efficiency of these species to excrete hippuric acid with incremental benzoate intake (0, 1, 2, or 4 mmol/kg BW). For mink, two additional treatments with 1 or 2 mmol/kg BW of ethyl benzoate were included. A basal low-glycine diet was formulated to meet the minimum protein requirements of fur animals (30% of ME). This diet was supplemented with 0 or 3 g/kg of glycine, or with 0, 1.0, 2.07, or 4.15 g/kg of sodium benzoate for mink and blue foxes, and with 0 or 4.5 g/kg of glycine and 0, 1.58, 3.17, or 6.34 g/kg of sodium benzoate for raccoon dogs, respectively. Two additional diets with .76 or 1.53 g/kg of ethyl benzoate were made for mink. Fecal and urinary benzoic and hippuric acid excretion were measured for 3 d. The 24-h recovery of [14C]benzoic acid injected intraperitoneally was measured from urine, the liver, and the kidneys. All animals appeared healthy and no clinical signs of benzoate overdose were observed. Dietary benzoate level did not affect ADFI or ADG in any species. Glycine supplementation lowered ADFI in mink. The majority of ingested benzoates were absorbed from the gut (over 95%), except in blue foxes, which excreted 6 to 15% of ingested benzoates in feces with incremental increases in benzoate intake. Urinary free benzoic acid excretion accounted for 10% of the ingested benzoates in blue foxes but less than 5% in mink and raccoon dogs. When benzoate intake was 1 mmol/kg BW, mink, blue foxes, and raccoon dogs excreted 71, 77, and 34% of ingested benzoates as hippuric acid in urine, respectively. With higher benzoate intakes, urinary hippuric acid excretion decreased quadratically with mink to 20%, and linearly with blue foxes and raccoon dogs to 45 and 16%, respectively. The hippuric acid pathway appears to be the principal route of benzoate elimination in the mink and blue fox, whereas, in the raccoon dog, other pathways appear to be more important. In mink, the elimination of ethyl benzoate did not differ from that of sodium benzoate. Because glycine conjugation is the primary route of benzoate elimination, it is recommended that benzoate content in fur animal feeds should not exceed 1 g/kg feed on an as-fed basis.