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PubMed1992

Stimulatory effect of free fatty acids on growth hormone releasing hormone secretion by fetal rat neurons in monolayer culture.

The effects of free fatty acids (FFAs) on growth hormone releasing hormone (GHRH) secretion by fetal rat cortical and hypothalamic neurons in monolayer culture have been investigated. Treatment with caprylic or oleic acids for 90 min, induced a dose-dependent increase in GHRH secretion. The stimulatory effect of caprylic acid was time-dependent, being present after 90 min and 5 h but not after 24 h. Finally, GHRH release induced by 56 mM KCl or by the calcium ionophore A23187 was not modified by 5 x 10(-3) M caprylic acid. These data support a role for FFAs on GHRH secretion.

Animals↗
PubMed2004

Saturated fatty acids suppress adrenocorticotropic hormone (ACTH) release from rat anterior pituitary cells in vitro.

We studied whether fatty acids modify adrenocorticotropic hormone (ACTH) release induced by stimulation with corticotropin-releasing hormone (CRH) from rat anterior pituitary cells. Stimulation with CRH (0.01-100 nmol/l) significantly and concentration-dependently increased ACTH release, which was synergistically enhanced by the simultaneous stimulation with 1 nmol/l arginine-vasopressin. Addition of saturated fatty acids (butyrate, caprylate, laurate, palmitate and stearate) in a medium at 1 mmol/l, despite effects on the basal release, significantly reduced the ACTH release induced by CRH (1 nmol/l) stimulation. Caprylate suppressed ACTH release in a concentration-dependent manner. However, unsaturated C18 and C20 fatty acids (oleate, linolate, linolenate and arachidonate) at 1 mmol/l significantly increased the basal release, but none of them suppressed CRH (1 nmol/l)-induced ACTH release. In the presence of caprylate (1 mmol/l), CRH (1 nmol/l)-stimulated increase in cellular calcium ion concentration was diminished. From these results we conclude that saturated fatty acids have a suppressing effect on CRH-induced ACTH increase in primary cultured rat anterior pituitary cells.

Adrenocorticotropic Hormone↗
PubMed2002

In vitro evaluation of nimodipine permeation through human epidermis using response surface methodology.

An optimization technique (response surface method) was used in order to investigate the effect of the combination of two enhancers, namely caprylic acid and cineol on nimodipine's permeation through human cadaver epidermis. Using this quadratic model it was found that at 24 h the increase of the permeation of nimodipine it was mainly due to the effect of caprylic acid. On the contrary, it was shown that at 48 and 72 h the combination of the two enhancers contributed to the increase of the permeation. The greater Q(gel)/Q(control) values, at all time intervals (24, 48 and 72 h), were obtained when the concentration of cineol and caprylic acid range from 3.0 to 5.0% (v/v) and 8.0 to 9.5% (v/v), respectively.

Algorithms↗
PubMedDate not supplied

[The effect of carbohydrate metabolic changes during pregnancy on the capacity of liver mitochondria in rat progeny to oxidize the lipid intermediate].

Respiration rate, respiration control and ADP of liver mitochondria were studies in one-, ten-, and twenty-day-old rats born of females who had received subcutaneous insulin injections (0.25 U/100 g body weight) on days 5-7, 11-13 and 19-21 of pregnancy or glucose (1 g/100 g body weight, in the morning before feeding). Caprylate, an intermediate of the lipid metabolism, was used as the substrate for oxidation. In the control, caprylate oxidation in one-day old rats occurred at a low rate without providing for synthesis of ATP from ADP and phosphate. Insulin administration and alimentary hyperglycemia in females on days 5-7 of pregnancy had no significant effect on respiration rate of liver mitochondria in progeny of all ages tested. Administration of the above preparations on days 11-13 and 19-21 of pregnancy improved caprylate oxidation in mitochondria of the newborn rats. In other series the difference between experiments and the control was insignificant. Metabolic changes in the newborns are shown to be related to hyperinsulinemia in pregnant females.

Animals↗
PubMed2003

[Study on pulmonary delivery of peptide drugs in rats: effects of absorption enhancers on cellular membrane fluidity].

AIM: To study the relationship between cellular membrane fluidity and relative bioavailability (Fr) of protein and peptide drugs combined with absorption enhancers after pulmonary administration in rats. METHODS: A series of model drug salmon calcitonin (sCT) solutions with 6 absorption enhancers (Brij78, sodium cholate, sodium caprylate, 2-hydroxypropyl-beta-cyclodextrin, lecithin and chitosan) were prepared and then delivered to rats by pulmonary route. Serum drug concentration was determined by radioimmunoassay method. Using the techniques of electron spin resonance and fluorescence polarography, the effects of enhancers on pulmonary cellular membrane fluidity were investigated. RESULTS: Fr values of sCT solution with some absorption enhancers (Brij78, sodium cholate, sodium caprylate, lecithin and chitosan) were significantly higher than those without enhancers. Brij78, lecithin and sodium caprylate, not only increased membrane lipid fluidity but also loosed the constitution of membrane protein. The effect of sodium cholate on membrane protein was low. Lipid fluidity was reduced and protein constitution was changed markedly, after pulmonary cellular membrane was treated by 0.5% chitosan solution. This result showed that the absorption enhancing of chitosan mainly came from its effects on membrane protein. Corresponded with lower Fr after pulmonary administration, 2-hydroxypropyl-beta-cyclodextrin (0.5% and 3%) had not significant effects on both lipid fluidity and protein constitution. CONCLUSION: The effects of enhancers on pulmonary absorption of peptide drugs in vivo might be investigated on the grounds of determination of cellular membrane fluidity in vitro.

Absorption↗
PubMed1989

Resolution and binding site determination of D,L-thyronine by high-performance liquid chromatography using immobilized albumin as chiral stationary phase. Determination of the optical purity of thyroxine in tablets.

Human and bovine serum albumin bound to silica or aminopropyl silica were used as chiral stationary phases (CSPs). D,L-Thyronine, D,L-tryptophan, N-benzoyl-D,L-phenylalanine, D,L-warfarin and D,L-benzoin could be resolved on these CSPs using a mobile phase of 0.05 M phosphate buffer, pH 7.0. The capacity factor of D-thyronine was higher than that of L-thyronine. The resolution of D,L-thyronine was completely lost by the presence of bilirubin in the mobile phase, but only little affected by caprylate. By contrast, the resolution of D,L-tryptophan was not affected by bilirubin, but lost by the presence of caprylate. These results are consistent with binding of D-thyronine to the bilirubin binding site and L-tryptophan to the caprylate binding site in albumin, respectively, and suggests that such "displacement chromatography" can be used for the determination of binding sites. The optical purity of D-thyroxine in tablets was determined indirectly after de-iodination by catalytic hydrogenation.

Amino Acid Oxidoreductases↗
PubMed2006

Protease and esterase activity of staphylococci.

The aim of this work was to characterize protease and esterase activities of staphylococci in order to establish if they could contribute to the release of amino acids and short-chain fatty acids during ripening of fermented sausages. Eighteen Staphylococcus strains belonging to the species Staphylococcus xylosus (5), S. saprophyticus (3), S. equorum (4), S. carnosus (4) and S. simulans (2), previously isolated from different types of Southern Italian fermented sausages, were screened for proteinase, aminopeptidase and esterase activities. Most of the staphylococci strains lacked detectable levels of proteinase activity against casein-fluorescein isothiocynate. In the active strains, this activity was extracellular or cell-envelope associated. The studied staphylococci strains also showed low levels of aminopeptidase activities, which preferentially hydrolysed substrates containing L-methionine, L-leucine and L-phenylalanine as N-terminal residue. In contrast, all staphylococcal strains possessed significant activity against short-chain fatty acid esters. The maximum esterase activities were detected in whole-cell suspensions and cell-free extracts and to a lesser extent in the extracellular medium. The substrates preferentially hydrolysed were rho-nitrophenyl (rho-NP) butyrate and rho-NP caprylate and, secondly, rho-NP palmitate. The extracellular extracts of most of the strains were only active against rho-NP butyrate except for those of S. equorum (SI3, SI4) and S. simulans (Ssm12, Ssm21), which also hydrolysed rho-NP caprylate and rho-NP palmitate. The cell-free extracts and whole cells were mainly active against rho-NP butyrate and rho-NP caprylate, showing activity levels from 1760 U/mg of proteins to 54 U/mg of proteins and from 12,200 U/mg of proteins to 133 U/mg of proteins respectively. These activities were especially high in the strains that belonged to S. xylosus and S. equorum species. The diversity of the studied metabolic properties and, especially, the esterase activities in different staphylococcal species and even strains of the same species emphasize the relevance of these in vitro characterization studies for a rational selection of new starter cultures.

Aminopeptidases↗
PubMed2001

Synthesis of structured lipids by transesterification of trilinolein catalyzed by Lipozyme IM60.

Structured lipids (SL) containing caprylic, stearic, and linoleic acids were synthesized by enzymatic transesterification using Lipozyme IM60. Pure trilinolein and free fatty acids were used as substrates. Incorporation of stearic acid was higher than that of caprylic acid in all parameters. Highest incorporations of both acids were achieved at 32 h, mole ratio of 1:4:4 (trilinolein/caprylic/stearic acids), water content of 1% (wt %), temperature of 55 degrees C, and 10% (wt %) enzyme load. The maximal incorporations of caprylic and stearic acids were 23.73 and 62.46 mol %, respectively. Reaction time, water content, and enzyme load had major influences on the reaction, whereas substrate mole ratio and temperature showed less influence. Lipozyme showed good stability over six reuses. Differential scanning calorimetric analysis of SL gave a melting profile with a very low melting peak of 0-3.3 degrees C and a solid fat content of 25.21% at 0 degrees C. The melting profile and solid fat content of SL were compared with those of fats extracted from commercially available solid and liquid margarine products. The data suggest that enzymatically produced SL could be used in liquid margarine products.

Calorimetry, Differential Scanning↗
PubMed2004

Transdermal delivery of ketorolac tromethamine: effects of vehicles and penetration enhancers.

The effects of vehicles and penetration enhancers on the in vitro permeation of ketorolac tromethamine (KT) across excised hairless mouse skins were investigated. Among pure vehicles examined, propylene glycol monolaurate (PGML) showed the highest permeation flux, which was 94.3 +/- 17.3 microg/cm2/h. Even though propylene glycol monocaprylate (PGMC) alone did not show high permeation rate, the skin permeability of KT was markedly increased by the addition of diethylene glycol monoethyl ether (DGME); the enhancement factors were 19.0 and 17.1 at 20% and 40% of DGME, respectively. When DGME was added to PGML, the permeation fluxes were almost two times at 20-60% of DGME compared to PGML alone. In the cosolvent system consisting of propylene glycol (PG)-oleyl alcohol, the permeation rate increased as the ratio of PG increased. In the study to investigate the effect of drug concentration on the permeation rate of KT, the permeation rates increased as the drug concentration increased in all vehicles used, and the dramatic increase in permeation rate was obtained when the drug concentration was higher than its solubility. For the effects of fatty acids on the permeation of KT, five fatty acids were added to PG at concentrations of 1%-, 3%-, 5%- and 10%- caprylic acid, capric acid, lauric acid, oleic acid, and linoleic acid. The enhancing effects of fatty acids were different, depending on the concentration as well as the sort of fatty acids. The highest enhancing effect was attained with 10% caprylic acid in PG; the permeation flux was 113.6 +/- 17.5 microg/cm2/h. The lag time of KT was reduced as the concentration of fatty acids increased except for caprylic acid.

Adjuvants, Pharmaceutic↗
PubMed2000

[Production, characterization and purification of monoclonal antibodies against antigens of Mycobacterium tuberculosis H37Rv strain].

OBJECTIVE: Using monoclonal antibody (McAb) technique to analyze polypeptide antigens of Mycobacterium strains and try to find out the best method for purification of McAb. METHODS: McAbs against H37Rv strain were produced by routine procedure. McAb-producing hybridomas were detected by ELISA and immunoblots technique. 24 strains of mycobacterium were grown on Loewenstein-Jensen medium for 1 to 3 weeks at 37 degrees C. H37Rv strain were grown on Loewenstein-Jensen medium or Sauton liquid medium. Ammonium sulfate, caprylic acid precipitation and ion exchange chromatography methods were used to purify McAbs against antigens of H37Rv strain. RESULTS: 14 McAb-produing hybridomas were obtained. C2 McAb reacted with all 24 strains of mycobacterium and 7C12 only reacted with H37Rv, H37Ra, M. bovis, BCG strains, C2 and 7C12 reacted with secreted proteins of H37Rv strain. 40,000/38,000 antigen of H37Rv strain was expressed differently in Loewenstein-Jensen medium and Sauton liquid medium. Relative activity of all McAbs was between 10(-4)-10(-7). The results of purified McAb showed that ammonium sulfate precipitation method could have the highest rate of recovery. Ion exchange chromatography method could have the highest purity. Caprylic acid method can remove albumin effectively and the purification of McAbs in ascific fluid was simple and easy to perform. CONCLUSIONS: Polypeptide antigens of H37Rv against by C2, 7C12 McAb were the secreted proteins. For purification of McAb, the results suggested that ion exchange chromatography method can be applied for analysis and caprylic acid method for a very large volume of ascitic fluid.

Antibodies, Monoclonal↗
PubMed1988

Toxicity and character of the effect of some zinc compounds.

Investigation of the parameters of toxicity of 8 zinc compounds revealed some differences in the degree of their risk for persons working with them. The following TSELs (tentative safe exposure levels of harmful substances) have been determined: 0.5 mg/m3 for zinc nitrate and hydrogen and dihydrogen zinc phosphates, 2 mg/m3 for zinc carbonate and zinc selenide, as well as MAC (maximum allowable concentration) for zinc sulphide equal to 5 mg/m3. No TSEL have been set for zinc caprylate and zinc stearate, but intratracheal administration of 50 mg caprylate caused 100%, of stearate 50% death of experimental animals due to pulmonary edema. Maximum tolerable doses were 10 and 1 mg, respectively. Zinc nitrate shows an expressed irritative effect on the skin and a highly expressed effect on the conjunctiva. Zinc phosphates, zinc caprylate and zinc stearate are resorbed by the skin. In all cases, working persons must be protected from the effect of the compounds under study because even though the toxicity of a compound may be rather low, highly noxious compounds may develop in the course of the technological process, e.g., in mechanical treatment of zinc selenide and zinc sulphide monocrystals, hydrogen selenide and hydrogen sulphide, respectively, can be isolated.

Administration, Cutaneous↗
PubMed1963

THE INTERACTION OF SOME STIMULANT AND DEPRESSANT DRUGS ON THE FROG HEART.

THE ACTIVITY OF FROG ISOLATED HEARTS WAS DEPRESSED BY ALTERING THE PERFUSING RINGER SOLUTION IN FIVE DIFFERENT WAYS: by reducing the calcium content, by increasing the potassium content, and by adding ether, thiopentone or acetylcholine. Depressed hearts were perfused with Ringer solution containing the following stimulant drugs: paullinia tannin, tannic acid, hydrogen peroxide, sodium oleate, sodium caprylate and ouabain. All these stimulant drugs had similar actions on hearts depressed by calcium lack, ether and thiopentone; hearts depressed by acetylcholine were, however, only weakly stimulated. Hearts depressed by potassium were readily stimulated by oleate, caprylate and paullinia tannin; ouabain and hydrogen peroxide had weak stimulant actions on hearts depressed by potassium, and tannic acid had a negative inotropic action. The differing actions on hearts depressed by potassium are probably related to differences in the degrees of fixation of the stimulant drugs. The mode of action of ouabain and the functional lesion in hearts depressed by narcotics are discussed.

Acetylcholine↗
PubMed1987

A simple, non-chromatographic procedure to purify immunoglobulins from serum and ascites fluid.

A simple, two-step procedure to purify the immunoglobulin G (IgG) fraction from mammalian sera and ascites fluid is described. In the first step, albumin and other non-IgG proteins are precipitated with caprylic acid (octanoic acid). In the second, the IgG fraction is precipitated with ammonium sulfate. Factors influencing the precipitation of serum proteins by caprylic acid are described, as are procedural modifications to purify the IgG fraction from sera with a high lipid content. The procedure can be used to purify the IgG fraction of serum from rabbit, sheep, goat, horse, rat and mouse, as well as monoclonal antibodies from mouse ascites fluid. Greater than 80% of the IgG in rabbit serum could be isolated by this procedure, with a purity equal to rabbit IgG purified by anion-exchange chromatography. In addition to its simplicity and low cost, the procedure described offers several advantages over other methods to purify IgG.

Ammonium Sulfate↗
PubMed1995

Inclusion/exclusion of fatty acids in amylose complexes as a function of the fatty acid chain length.

Structural models are proposed for amylose-fatty acid complexes depending on the respective chain lengths of their constituents. The three studied fatty acids induce the Vh amylose crystalline type. However, in contrast to lauric and palmitic acids, caprylic acid is not present in crystals. On the basis of the relative amounts of amylose and fatty acid determined in complexes and previous results of molecular modelling, inclusion of lauric and palmitic acids inside the amylose helices is proposed; the acyl chains are included in crystalline areas and the carboxylic groups in amorphous areas. The absence of caprylic acid in crystals could be due to the solubility of this compound in the crystallization medium.

Amylose↗
PubMed2006

Comparative study of the anti-inflammatory effect of two intravenous immunoglobulin preparations manufactured by different processes.

Intravenous immunoglobulin (IVIG) is increasingly used in the treatment of diverse immune-mediated disorders. Since several preparations of IVIG are available for therapy, it is possible that different manufacturing processes might influence clinical efficacy of IVIG. An insight into the mechanisms of action of such different IVIG preparations is therefore necessary that will provide further guidelines for the utility of IVIG preparations in autoimmune and inflammatory diseases. Since endothelial cells (EC) influence the inflammatory process via production of cytokines, chemokines and expression of adhesive molecules, we analyzed the anti-inflammatory effect on EC of two IVIG preparations: caprylated IVIG (IVIG-C) versus solvent/detergent-treated IVIG (IVIG-SD) preparation. We found that both IVIG preparations inhibit in an equivalent manner, the expression of different pro-inflammatory factors such as IL-6, IL-8, GM-CSF, IL-1beta and TNF-alpha and the adhesion molecules ICAM-1 and VCAM-1. Our results thus suggest that the caprylate while inactivating the virus and enhancing the yield of IgG during IVIG formulation, does not modulate the immunomodulatory properties of IVIG at EC level and that the two preparations show similar anti-inflammatory effects.

Caprylates↗
PubMed2001

Separation of glyceride positional isomers by silver ion chromatography.

Separation of triglyceride and diglyceride positional isomers by silver ion high-performance liquid chromatography coupled with an evaporative light-scattering detector is described. The triglyceride isomers had a fatty acid composition of CLC and CCL, where C and L were caprylic acid and linoleic acid, respectively. Diglyceride isomers, 1,2(2,3)-diglyceride and 1,3-diglyceride, which contained caprylic acid were separated too. A solvent system based on n-hexane, 2-propanol, ethyl acetate, and acetonitrile with a flow-rate of 0.8 ml/min was developed. Calibration curves of CLC and CCL were achieved with triolein as internal standard. Using this method, the incorporation of linoleic acid onto specific a position of glycerol backbone can be monitored.

Caprylates↗
PubMed2003

Pharmacokinetics and tolerability of a new intravenous immunoglobulin preparation, IGIV-C, 10% (Gamunex, 10%).

BACKGROUND AND OBJECTIVES: A new intravenous immunoglobulin (IGIV) process has been developed that integrates efficient inactivation of enveloped virus, using caprylate, with immunoglobulin G (IgG) purification and caprylate removal by column chromatography. Two clinical studies were conducted to compare the pharmacokinetics of the new product, IGIV-C, 10% (Gamunex, 10%), formulated with glycine, with the licensed solvent-detergent (SD)-treated intravenous immunoglobulin IGIV-SD, 10% (Gamimune N, 10%), formulated with glycine, and IGIV-C, 5%, formulated with 10% maltose. MATERIALS AND METHODS: Both studies were randomized, multicentre crossover trials of 18 and 20 (respectively) adult patients with primary humoral immune deficiency in which patients received one IGIV product for three consecutive periods (3-4 weeks) before crossing over to the other product. Pharmacokinetic parameters were determined after the third infusion of each product. RESULTS: IGIV-C, 10% was bioequivalent to IGIV-SD, 10%, with half-lives (t1/2) of 35 and 34 days, respectively. IGIV-C, 5%, was bioequivalent to IGIV-C, 10%, with t1/2 of 35 and 36 days, respectively. The products had comparable safety profiles. CONCLUSIONS: The pharmacokinetic profiles observed in these trials indicate that IGIV-C, 10% may replace, and be administered in a manner similar to, IGIV-SD, 10%.

Adult↗
PubMed2000

Gel catalysts that switch on and off.

We report development of a polymer gel with a catalytic activity that can be switched on and off when the solvent composition is changed. The gel consists of two species of monomers. The major component, N-isopropylacrylamide, makes the gel swell and shrink in response to a change in composition of ethanol/water mixtures. The minor component, vinylimidazole, which is capable of catalysis, is copolymerized into the gel network. The reaction rate for catalytic hydrolysis of p-nitrophenyl caprylate was small when the gel was swollen. In contrast, when the gel was shrunken, the reaction rate increased 5 times. The activity changes discontinuously as a function of solvent composition, thus the catalysis can be switched on and off by an infinitesimal change in solvent composition. The kinetics of catalysis by the gel in the shrunken state is well described by the Michaelis-Menten formula, indicating that the absorption of the substrate by the hydrophobic environment created by the N-isopropylacrylamide polymer in the shrunken gel is responsible for enhancement of catalytic activity. In the swollen state, the rate vs. active site concentration is linear, indicating that the substrate absorption is not a primary factor determining the kinetics. Catalytic activity of the gel is studied for substrates with various alkyl chain lengths; of those studied the switching effect is most pronounced for p-nitrophenyl caprylate.

Acrylamides↗