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PubMed1991

Oncolytic effects of fatty acids in mice and rats.

Intrahepatic implants of M114 carcinoma in B6D2F1/J mice were treated by intraperitoneal injection of 30 mg sodium caprylate (octanoate), and implants of Nb2 lymphoma in Nb rats were treated with 300 mg tricaprylin orally. After 4-11 h extensive damage to tumor cells was evident microscopically whereas liver cells were unaffected. Tumors in mice treated once daily from the fourth to eighth day after implantation were obliterated. Subcutaneous implants of hepatoma Nb10L in Nb rats treated transdermally with a caprylic acid preparation underwent similar damage. Fatty acids can cause lysis of tumor cells with little damage to normal tissue in certain situations. This action is not related to mitotic activity and represents a novel mode of antitumor action.

Animals↗
PubMed1996

Intestinal synthesis and lymphatic secretion of apolipoprotein A-IV vary with chain length of intestinally infused fatty acids in rats.

To evaluate the hypothesis that stimulation of intestinal apolipoprotein (apo) A-IV by dietary fat depends upon assembly and transport of chylomicrons, we examined the effect of duodenal infusion of fatty acids of graded chain length on mucosal synthesis and lymphatic output of lipid and apo A-IV. Rats with duodenal cannulas and mesenteric lymph fistulas were given 8-h duodenal infusions of lipid emulsions containing either butyric (4:0), caprylic (8:0), lauric (12:0), myristic (14:0), stearic (18:0), oleic (18:1), linoleic (18:2) or arachidonic (20:4) acids, or tributyrin, tricaprylin or triolein. Lymph outputs of triglyceride, phospholipid and apo A-IV were measured at 0, 2, 4, 5, 6, 7 and 8 h after the start of lipid infusion. Significant increases in lymph lipid (triglyceride, phospholipid) and apo A-IV output were observed in response to long-chain fatty acids (14:0, 18:0, 18:1, 18:2, 20:4) or triolein; short- or medium-chain fatty acids (4:0, 8:0, 12:0) or tributyrin or tricaprylin produced no significant increase in lymph lipid output above basal levels. Similarly, increased jejunal mucosal synthesis of apo A-IV was observed in response to duodenal infusion of oleic acid but not butyric or caprylic acid. These results provide direct support for the hypothesis that stimulation of apo A-IV by dietary fat depends upon transport of absorbed lipid via chylomicrons in lymph.

Animals↗
PubMed2000

Tricaproin, tricaprin and trilaurin are utilized more efficiently than tricaprylin by carp (Cyprinus carpio L.) larvae.

We investigated the effect of chain length of dietary medium-chain fatty acids (MCFA) on growth performance and fatty acid composition of first-feeding carp larvae. In a first trial, five semi-purified isolipidic (23-24 g/100 g of dry matter) diets were formulated to contain either 10 g/100 g triolein (control diet) or 5 g/100 g triolein and 5 g/100 g medium-chain triacylglycerols (MCT) supplied as tricaproin, tricaprylin, tricaprin or trilaurin. After 21 d, survival and growth rates were significantly greater in larvae fed diets containing triolein, tricaproin, tricaprin and trilaurin (final survival: 92 +/- 7% and mean larval weight: 42 +/- 15 mg) than in larvae fed tricaprylin (final survival: 56 +/- 12% and mean larval weight: 15 +/- 1 mg). The recovered levels of the fed MCFA in larval total lipids were respectively 0, 1.3, 7.3 and 8.1 g/100 g of total fatty acids. In a second trial, two isolipidic (18 g/100 g) diets containing 10 g/100 g triolein or tricaprylin were tested. High amounts of capric acid (up to 25 g/100 g of total fatty acids) were found in neutral lipids of carp larvae fed tricaprylin for 11 d, suggesting an unusual elongation of caprylic acid. This study underlines the peculiarity of tricaprylin among other MCT which seem well utilized up to 20-30 g/100 g of total dietary fatty acids. The exception of tricaprylin raises the question of the metabolic pathways followed by this MCT, especially for the suggested direct elongation of caprylic acid into capric acid.

Animal Feed↗
PubMed2001

Jejunal or portal vein infusions of lipids increase hepatic vagal afferent activity.

Jejunal infusions of linoleic acid, corn oil, or caprylic acid significantly increased hepatic vagal afferent activity, whereas saline infusions were ineffective. The magnitude of response was greatest with either linoleic acid or corn oil. Hepatic portal infusions of linoleic acid, Liposyn II, or caprylic acid significantly increased hepatic vagal afferent activity, whereas 5% albumin/phosphate buffer vehicle was ineffective. The magnitude of response was greatest with either linoleic acid or Liposyn II. These data show that either jejunal or portal infusions of lipids increase activity of hepatic vagal afferents and could potentially serve as a complementary and/or alternative substrate to celiac vagal afferents in mediating the effects of jejunal infusions of lipids in suppressing food intake.

Action Potentials↗
PubMed2004

Inactivation of West Nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma-derived products.

BACKGROUND AND OBJECTIVES: Human plasma is the source of a wide variety of therapeutic proteins, yet it is also a potential source of viral contamination. Recent outbreaks of emergent viral pathogens, such as West Nile virus, and the use of live vaccinia virus as a vaccine have prompted a reassessment of the viral safety of plasma-derived products. The purpose of this study was to evaluate the efficacy of current viral inactivation methods for West Nile and vaccinia viruses and to reassess the use of model viruses to predict inactivation of similar viral pathogens. MATERIALS AND METHODS: Virus-spiked product intermediates were processed using a downscaled representation of various manufacturing procedures. Virus infectivity was measured before and after processing to determine virus inactivation. RESULTS: The results demonstrated effective inactivation of West Nile virus, vaccinia virus and a model virus, bovine viral diarrhoea virus, during pasteurization, solvent/detergent treatment and caprylate treatment. Caprylate provided rapid and effective inactivation of West Nile virus, vaccinia virus, duck hepatitis B virus and Sindbis virus. Inactivation of West Nile virus was similar to that of bovine viral diarrhoea virus. CONCLUSIONS: This study demonstrates that procedures used to inactivate enveloped viruses in manufacturing processes can achieve inactivation of West Nile virus and vaccinia virus. In addition, the data support the use of model viruses to predict the inactivation of similar emergent viral pathogens.

Animals↗
PubMed1962

Importance of calcium in the actions of some drugs that stimulate the isolated hypodynamic frog heart.

Eight drugs that stimulate the isolated hypodynamic frog heart have been tested for their ability to stimulate hearts freshly perfused in calcium-free Ringer solution. Ouabain and digitoxigenin regularly caused stimulation, veratridine did so occasionally. Hydrogen peroxide, tannic acid, paullinia tannin (from Paullinia pinnata, Linn.), sodium oleate and sodium caprylate did not stimulate. The stimulant action of ouabain could be prevented or greatly reduced by prior perfusion with either of the two tannins or with hydrogen peroxide. Hearts perfused for 3 to 4 hr with calcium-free Ringer solution, or hearts perfused for shorter periods of time with calcium-free Ringer solution containing the disodium salt of ethylenediaminetetra-acetic acid, behave unusually in that when perfusion with low-calcium Ringer solution is resumed twitch tension does not return for periods ranging from 10 to 90 min. Ouabain is unable to stimulate these "calcium-depleted" hearts. It is suggested that hydrogen peroxide, the two tannins, oleate and caprylate stimulate by causing the heart to increase the uptake of calcium from the perfusion fluid to a superficial site where calcium is necessary for the propagation of excitation from the cell membrane inwards. A special feature of the action of cardiac glycosides may be their ability to enable the heart to utilize in a similar way the intracellular stores of calcium.

Animals↗
PubMed1982

Comparison between two preparations of human serum albumin in treatment of neonatal hyperbilirubinaemia.

Thirty-six newborn infants with normal birth weights and with uncomplicated hyperbilirubinaemia, treated with light, were studied. At onset of phototherapy the infants received intravenously 1 g human serum albumin (HSA) per kg body weight as a 9% solution. Two different preparations of HAS were used and compared. One of these, HSAI, contained sodium caprylate and N-acetyltryptophan, 5 mmol/l of each, as stabilizers. HSAII contained only caprylate, 5 mmol/l. Nineteen infants received HSAI and seventeen infants HSAII. The reserve albumin for binding of bilirubin, measured by the [14C] MADDS method, was low in both preparations in vitro. During the infusion, the serum concentrations of albumin and reserve albumin increased and the serum unconjugated bilirubin concentration decreased, resulting in a fall in the index of plasma bilirubin toxicity in all infants. After completion of the infusion, the serum concentrations of albumin and reserve albumin declined, and a slight rise in index occurred. The increase in the serum reserve albumin concentration was markedly higher during infusion of HSAII than of HSAI. It is concluded that infusion of both HSA preparations during phototherapy provides an immediate protection against bilirubin encephalopathy. HSAI is inferior to HSAII, probably due to its content of N-acetyltryptophan.

Bilirubin↗
PubMed1984

Effects of acetylcholine and short-chain fatty acids on acinar cells of the exocrine pancreas in sheep.

In order to investigate the actions of acetylcholine and short-chain fatty acids on acinar cells of the exocrine pancreas of sheep, measurements of amylase release and 45Ca efflux from superfused segments, as well as changes in membrane potential, input resistance and equilibrium potential in the acinar cells, were carried out in vitro. The application of acetylcholine or short-chain fatty acids caused a dose-dependent increase in amylase release from the superfused tissue segments. The amylase release evoked by 10(-3) M-short-chain fatty acids containing 2-8 carbon atoms increased with increasing carbon number, up to 5 (i.e. it was maximum with iso-valerate, which has 5 carbon atoms). The amylase release stimulated by acetylcholine (5.5 X 10(-6) M) or caprylate (10(-3) was accompanied by an increase in 45Ca efflux, and was significantly reduced by the removal of extracellular Ca2+. The stimulating effect of caprylate (10(-3) M) on amylase secretion was also observed in superfused segments of the guinea-pig, but not in those of the mouse, rabbit or hamster. The resting membrane potential and input resistance of acinar cells of sheep pancreas were -31.1 +/- 1.6 mV and 2.7 +/- 0.7 M omega (means +/- S.E. of means), respectively. The application of acetylcholine or short-chain fatty acids always depolarized the cell membrane and reduced the input resistance. The effect of short-chain fatty acids was observed in the presence of atropine (1.4 X 10(-6) M). The equilibrium potentials for acetylcholine and butyrate were -15.0 +/- 0.8 and -16.0 +/- 1.1 mV, respectively. It is concluded that the cellular secretory process evoked by acetylcholine is qualitatively similar to that of short-chain fatty acids, and that Ca2+ ions might be an important mediator for these secretagogues in the acinar cells of the pancreas of sheep.

Acetylcholine↗
PubMed1991

Short chain fatty acids in the terminal ileum accelerate stomach to caecum transit time in the rat.

We have previously shown that infusion of triglycerides and long chain fatty acids into the ileum of humans and rats delays small bowel transit time. The present studies have investigated the effect on the stomach to caecum transit time of a baked bean meal of the ileal infusion of 20 mM, 50 mM, and 100 mM acetic, butyric, hexenoic, and caprylic acids in rats. After an 18 hour fast either a control or a short chain fatty acid (SCFA) solution (pH 6.5) was infused into the ileum for 30 minutes (0.3 ml/hour). A test meal was given by gavage and the infusion continued for a further 150 minutes. The arrival of the meal in the colon was signalled by a rise in the exhaled hydrogen concentration. Acetic acid (20 mM, 50 mM, 100 mM), butyric acid (100 mM), and caprylic acid (100 mM) produced a significant acceleration of transit which was inversely proportional to SCFA chain length. In a separate experiment, infusion of 100 mM acetic acid, the most potent SCFA, into an isolated ileal Thirty-Vella loop failed to accelerate transit of the test meal. Our results suggest that SCFAs accelerate transit via a local enteric reflex.

Acetates↗
PubMed1993

Regulation of prothymosin alpha mRNA levels in rat pituitary tumor cells.

Prothymosin alpha (PTA) mRNA and histone H4 (H4) mRNA levels were studied in various experimental conditions that affected GH1 pituitary tumor cell proliferation. Cell proliferation and progression through the cell cycle was assessed by counting cells, 3H-thymidine incorporation and flow cytometry. PTA mRNA levels were decreased in a time-dependent fashion following serum deprivation; when the cells were induced to grow by serum refeeding, PTA mRNA expression was greatly stimulated. Interestingly, after caprylic acid treatment (2.5 mM for 24 h) that arrested cells in the G0/G1 phase of the cell cycle, PTA mRNA and H4 mRNA levels were almost undetectable; conversely, following caprylic acid withdrawal, PTA mRNA and H4 mRNA expression were greatly stimulated. Furthermore, cells cultured in T3-deprived serum, which was found to decrease GH1 cell proliferation, had low levels of PTA and H4 mRNAs. This effect was reversed by the addition of nanomolar concentrations of T3 to the culture. On the other hand, IGF-1 addition to the culture did not substantially modify PTA mRNA levels. The present data clearly indicate that PTA mRNA expression is tied to the proliferating activity of GH1 cells and, thus, could be used as a marker of the action that various agents have on GH1 cell proliferation.

Actins↗
PubMed1995

Pressor effects of portal venous oleate infusion. A proposed mechanism for obesity hypertension.

Increased visceral fat accumulation is a strong predictor of arterial hypertension. In this study, we explored the hypothesis that increased hepatic portal venous free fatty acid delivery results in increased blood pressure. Such an effect might explain the link between visceral obesity and hypertension. In nine conscious, instrumented rats, we studied the effects of 1-hour infusions of sodium oleate solution into the portal and femoral veins and infusions of sodium caprylate solution into the portal vein on 3 separate days. Basal blood pressure was not significantly different on the 3 study days. Mean arterial pressure increased 29 +/- 4 mm Hg during portal oleate infusion and 13 +/- 2 mm Hg during femoral oleate infusion (both significant increases over basal, P < .001). Mean arterial pressure did not change during portal caprylate infusion. The increase during portal oleate infusion was greater than that during femoral oleate infusion (P = .028). Heart rate rose during all three infusions; the increase was greatest during portal oleate infusion (334 +/- 4 to 412 +/- 2 beats per minute). During portal venous oleate infusion in five rats, plasma norepinephrine rose from 2.17 +/- 0.34 to 3.58 +/- 0.50 nmol/L, epinephrine rose from 0.79 +/- 0.28 to 1.84 +/- 0.44 nmol/L, and corticosterone rose from 147 +/- 55 to 1130 +/- 289 nmol/L. Three rats given portal venous oleate infusions for 1 week had increased blood pressure compared with baseline (mean increase, 16 +/- 4 mm Hg). These studies indicate that increases in portal venous fatty acid concentrations have significant pressor effects, perhaps mediated by increased sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed2005

Negative interference in cardiac troponin I immunoassays by circulating troponin autoantibodies.

BACKGROUND: There are numerous potential sources of interference in immunoassays. Our aim was to identify the blood component that causes negative interference in cardiac troponin I (cTnI) immunoassays based on antibodies against the central part of cTnI. METHODS: We isolated an interfering factor (IF) from a sample with low recovery of added cTnI, using several consecutive purification steps: caprylic acid precipitation, ammonium sulfate precipitation, and purification on Cibacron Blue gel and protein G columns. Purified IF was identified by gel electrophoresis and mass spectrometric analysis of protein bands. For the direct detection of human antibodies to cardiac troponin in serum samples, we developed immunoassays using three different anti-human immunoglobulin antibodies and measured troponin antibodies in samples with low and normal cTnI recovery. RESULTS: Treatment with caprylic acid did not precipitate IF, but IF precipitated at 40% ammonium sulfate saturation. IF bound to a Cibacron Blue gel column, from which it was eluted with a linear salt gradient; it also bound to protein G. Gel electrophoresis of purified IF showed two major bands with molecular masses corresponding to the heavy (approximately 50 kDa) and light chains (approximately 25 kDa) of immunoglobulin, and their identities were confirmed by mass spectrometry. The presence of troponin-specific autoantibodies was confirmed in samples with low recoveries of cTnI by three different immunoassays. The median signals were significantly higher in 10 samples with low recovery than in 10 samples with normal recovery of cTnI (P < or = 0.007). CONCLUSIONS: Circulating autoantibodies to cTnI or other proteins of the troponin complex can be a source of negative interference in cTnI immunoassays.

Ammonium Sulfate↗
PubMed1993

Effects of free fatty acids on somatostatin secretion, content and mRNA levels in cortical and hypothalamic fetal rat neurones in monolayer culture.

The effects of free fatty acids on somatostatin secretion, content and mRNA levels in fetal rat hypothalamic and cortical cell cultures were investigated. Somatostatin secretion and content were quantified by radioimmunoassay. Somatostatin mRNA levels were measured by Northern blot hybridization using a cRNA probe. Treatment with either caprylic acid (5 x 10(-3) M) or oleic acid (5 x 10(-5) M) for 90 min inhibited basal somatostatin secretion in both hypothalamic and cortical cell cultures. In addition, the increase in somatostatin secretion induced by incubation with veratridine (10(-4) M) or carbachol (10(-4) M) for 90 min was significantly reduced by the addition of caprylic acid, but somatostatin release stimulated by 5.6 x 10(-2) M KCl was not affected. Furthermore, treatment with these free fatty acids for 90 min markedly decreased somatostatin mRNA levels in both types of neurone culture. These inhibitory effects were transient, being observed after 90 min, but not after 5 h. These results support the probability that there is a role for free fatty acids in the regulation of somatostatin mRNA levels and somatostatin secretion in both hypothalamic and cortical cell cultures.

Animals↗
PubMed2004

Inactivation of Enterobacter sakazakii in reconstituted infant formula by monocaprylin.

Enterobacter sakazakii is an emerging pathogen that causes meningitis, bacteremia, sepsis, and necrotizing enterocolitis in neonates and children, with a mortality rate of 14%. Epidemiological studies have implicated dried infant formula as the principal source of the pathogen. Caprylic acid is a natural eight-carbon fatty acid present in breast milk and bovine milk and is approved as generally recognizable as safe by the U.S. Food and Drug Administration. The objective of this study was to determine the antibacterial effect of monocaprylin (monoglyceride ester of caprylic acid) on E. sakazakii in reconstituted infant formula. A five-strain mixture of E. sakazakii was inoculated into 10-ml samples of reconstituted infant formula (at 6.0 log CFU/ml) followed by 0, 25, or 50 mM (1%) monocaprylin. The samples were incubated at 37 or 23 degrees C for 0, 1, 6, and 24 h and at 8 or 4 degrees C for 0, 6, 24, and 48 h, and the surviving populations of E. sakazakii at each sampling time were counted. The treatments containing monocaprylin significantly reduced the population of E. sakazakii (P < 0.05) compared with the controls. Monocaprylin (50 mM) reduced the pathogen by >5 log CFU/ml by 1 h of incubation at 37 or 23 degrees C and by 24 h of incubation at 8 or 4 degrees C. Results indicate that monocaprylin could potentially be used to inactivate E. sakazakii in reconstituted infant formula; however, sensory studies are warranted before its use can be recommended.

Anti-Bacterial Agents↗
PubMed2006

[Effects of absorption enhancers on intestinal absorption of lumbrokinase].

AIM: To explore the intestinal absorption characteristics of lumbrokinase (YJM-I) in the absence or presence of various absorption enhancers and to find the optimum intestinal site for YJM-I absorption. METHODS: The absorption kinetics and absorption intestinal sites for YJM-I absorption were investigated with the method of diffusion cell in vitro, duodenum bolus injection, recirculating perfusion and in situ duodenum perfusion in vivo. RESULTS: YJM-I could be transported into blood and kept its biological activity across intestinal endothelial membrane after administration via duodenum site, whereas with lower bioavailability. Some of the absorption enhancers were shown good enhancement effects on intestinal absorption of YJM-I in vitro and in situ experiments. The order of enhanced efficiencies of various enhancers on duodenum, ileum and jejunum in vitro permeation experiments were shown as follows: 1% chitosan > 1% SDCh > 1% Na2EDTA > 1% SDS > 1% sodium caprylate > 1% poloxamer > 1% HP-beta-CD. The order of enhanced efficiencies of various enhancers on duodenum absorption of YJM-I in vivo were as follows: 2.5% SDCh > 2.5% Na2EDTA > 2.0% chitosan > 2.5% SDS > 2.5% sodium caprylate > 2.5% Poloxamer > 2.5% HP-beta-CD. CONCLUSION: The results indicated that the absorption of YJM-I could be enhanced by various enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore, bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I absorption.

Administration, Oral↗
PubMedDate not supplied

Effect of medium-chain fatty acid salts on penetration of a hydrophilic compound and a macromolecular compound across rabbit corneas.

The effects of sodium salts of medium-chain fatty acids, caprylate and caprate, on the penetration of a hydrophilic compound and a macromolecular compound across rabbit corneas in vitro were examined. Sodium caprylate (0.5 and 1% 2/v) marginally increased the corneal penetration of 6-carboxyfluorescein, a hydrophilic compound. However, it did not change the corneal penetration of FITC-dextran (mol.wt 4000). Sodium caprate (0.5 and 1% w/v) markedly increased the corneal penetration of these compounds.

Animals↗
PubMed1986

Interfacial reaction dynamics and acyl-enzyme mechanism for lipoprotein lipase-catalyzed hydrolysis of lipid p-nitrophenyl esters.

The fatty acyl (lipid) p-nitrophenyl esters p-nitrophenyl caprylate, p-nitrophenyl laurate and p-nitrophenyl palmitate that are incorporated at a few mol % into mixed micelles with Triton X-100 are substrates for bovine milk lipoprotein lipase. When the concentration of components of the mixed micelles is approximately equal to or greater than the critical micelle concentration, time courses for lipoprotein lipase-catalyzed hydrolysis of the esters are described by the integrated form of the Michaelis-Menten equation. Least square fitting to the integrated equation therefore allows calculation of the interfacial kinetic parameters Km and Vmax from single runs. The computational methodology used to determine the interfacial kinetic parameters is described in this paper and is used to determine the intrinsic substrate fatty acyl specificity of lipoprotein lipase catalysis, which is reflected in the magnitude of kcat/Km and kcat. The results for interfacial lipoprotein lipase catalysis, along with previously determined kinetic parameters for the water-soluble esters p-nitrophenyl acetate and p-nitrophenyl butyrate, indicate that lipoprotein lipase has highest specificity for the substrates that have fatty acyl chains of intermediate length (i.e. p-nitrophenyl butyrate and p-nitrophenyl caprylate). The fatty acid products do not cause product inhibition during lipoprotein lipase-catalyzed hydrolysis of lipid p-nitrophenyl esters that are contained in Triton X-100 micelles. The effects of the nucleophiles hydroxylamine, hydrazine, and ethylenediamine on Km and Vmax for lipoprotein lipase catalyzed hydrolysis of p-nitrophenyl laurate are consistent with trapping of a lauryl-lipoprotein lipase intermediate. This mechanism is confirmed by analysis of the product lauryl hydroxamate when hydroxylamine is the nucleophile. Hence, lipoprotein lipase-catalyzed hydrolysis of lipid p-nitrophenyl esters that are contained in Triton X-100 micelles occurs via an interfacial acyl-lipoprotein lipase mechanism that is rate-limited by hydrolysis of the acyl-enzyme intermediate.

Animals↗
PubMed1985

Effects of secretagogues on membrane potential and input resistance of pancreatic acinar cells of sheep.

The effects of acetylcholine, short-chain fatty acids and peptide hormones on membrane potential and input resistance of the pancreatic acinar cells of sheep were investigated using intracellular glass microelectrodes. The resting membrane potential and input resistance were -28.0 +/- 4.3 mV (mean +/- SD, inside negative, n = 23) and 2.4 +/- 1.7 M omega, respectively. The application of acetylcholine, short-chain fatty acids (acetate, butyrate and caprylate) and peptide hormones (caerulein and bombesin) always caused depolarisation accompanied by a marked reduction in input resistance. The equilibrium potentials of acetylcholine and caprylate were -13.5 and -12.8 mV, respectively.

Acetates↗