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An increase in histone acetylation and IL-2 antagonizing the immunoinhibitory effect are necessary for augmentation by butyrate of in vitro anti-TNP antibody production.

We investigated the role of histone acetylation in the promotion of antigen-specific antibody production in murine B cells induced by sodium butyrate (NaBu) plus interleukin 2 (IL-2). NaBu dose dependently increased the acetylation levels of histone H4 at concentrations which effectively enhanced anti-trinitrophenyl (TNP) antibody production in the presence of IL-2. Among other short-chain fatty acids and NaBu analogs, propionate, valerate and vinylacetate were effective in the presence of IL-2 in increasing both antibody production and the histone H4 acetylation level, but acetate, alpha-, beta- and gamma-hydroxybutyrates and alpha-, beta- and gamma-aminobutyrates were not effective, even in the presence of IL-2. The effect of the specific histone deacetylase inhibitor trichostatin A (TSA), which enhances anti-TNP antibody production without IL-2, was markedly inhibited by adding NaBu simultaneously. However, the effect of TSA was neither inhibited nor potentiated by NaBu in the presence of IL-2. Splenic B cells treated with NaBu, TSA and both together in the presence or absence of IL-2 showed almost the same increased acetylation level of histone H4. These results suggest that the NaBu-induced enhancement of anti-TNP antibody production in the presence of IL-2 is mediated through a moderate increase in the level of histone acetylation and that NaBu has both stimulating and inhibiting activities for anti-TNP antibody production, the latter of which is overcome by IL-2.

Acetylation↗

Effect of wheat and high-moisture sorghum grain fed singly and in combination on ruminal fermentation, solid and liquid flow, site and extent of digestion and feeding performance of cattle.

Two experiments were conducted to determine how varying the proportion of wheat (W) and high-moisture sorghum grain (SG) in 80% grain dies would affect ruminal fermentation, liquid and solid flow, site and extent of digestion (Exp. 1) and feeding performance of cattle (Exp. 2). In Exp. 1, three ruminal, duodenal and ileal cannulated steers (average weight 295 kg), fed at 1.54% of body weight, were used in a six-period crossover design. Treatments were: W, 50W:50SG (W:SG) and SG. Increasing wheat level decreased ruminal pH, molar proportion of acetate, and acetate:propionate ratio (P less than .05) and increased (P less than .05) L-lactate concentration, molar proportions of propionate and valerate and total volatile fatty acid concentration. Ruminal liquid dilution and outflow rates were faster (P less than .05) and retention time was shorter (P less than .05) for the W diet. Duodenal and ileal liquid flow increased (P less than .05), and solid flow decreased (P less than .05), as dietary level of wheat increased. Apparent ruminal digestion (% of intake) of dry matter (DM) and organic matter (OM) was greater (P less than .01) with the wheat-containing diets. Intestinal DM and OM digestion (percent of intake) was higher (P less than .05) with the SG and W:SG diets. Ruminal, small intestine, large intestine and total tract starch digestion (percent of intake) was 93.5, 5.6, .7, 99.8, 71.5, 20.4, 5.7, 97.6; and 48.0, 32.5, 10.5, 91.0 with the W, W:SG and SG diets, respectively. In Exp. 2, group-fed (24 pens) steers (avg initial weight 341 kg) were fed ad libitum once daily for 121 d. Treatments were: W, 67W:33SG, 33W:67SG and SG. Rates of gain (kg/d) with the W (1.32), 67W:37SG (1.33) and 33W:67SG (1.30) diets were similar (P greater than .05), but faster (P less than .05) than those with the SG diet (1.16). Feed intake was lower (P less than .01) with the W and 67W:33SG diets, but the wheat-containing diets were utilized more efficiently (P less than .01). Increasing the proportion of wheat in sorghum grain feedlot diets improved cattle performance by optimizing ruminal and post-ruminal digestion.

Animal Feed↗

Influence of ration form and nitrogen availability on ruminal fermentation patterns and plasma of growing bull calves.

Nine rations containing three forms (ground hay, .2 to 2 cm; chopped hay, 6 to 10 cm; or all concentrate) and three percents (30, 45, and 60%) of rumen degradable nitrogen were fed to 54 Holstein calves (3 X 3 factorial) between 8 and 20 wk of age. Rumen fluid samples were obtained at 8, 11, 14, 17, and 20 wk of age and plasma at 14 and 20 wk of age. Rumen fluid acetate concentration was greatest for ground hay and lowest for concentrate; propionate was greatest for concentrate and lowest for calves fed ground hay. Calves fed concentrate had highest valerate and total volatile fatty acid concentration, whereas lactate concentration and pH were least for concentrate. Ruminal ammonia nitrogen increased with increasing ruminally degradable protein feedstuffs in the ration. Plasma acetate was highest for chopped hay and lowest for concentrate, whereas calves fed concentrate and ground hay were comparable with higher propionate and glucose concentrations than calves fed chopped hay. Plasma urea nitrogen was highest for calves fed 60% ruminally degradable protein.

Animal Feed↗

Interleukin-8 stimulates the migration of human colonic epithelial cells in vitro.

The migration of colonic epithelial cells (restitution) is an important event in the repair of mucosal injuries. Interleukin-8 (IL-8) is a physiological initiator of the chemotactic migration of leucocytes. This study aimed to determine whether IL-8 had a similar effect on migration in an in vitro model of wounded colonic epithelium. Cell migration over 24 h was assessed in circular wounds made in confluent monolayers of the human colon cancer cell line LIM1215. This migration was stimulated in a concentration-dependent manner by IL-8, with maximal effects of approx. 1.75-fold above basal migration. The motogenic effect of IL-8 was mediated independently of effects on cell proliferation. In contrast, it was partially dependent upon gene transcription and protein synthesis and involved the activation of pertussis-toxin-sensitive G-proteins. The short-chain fatty acids, acetate, propionate, butyrate and valerate, the activator of protein kinase C (phorbol-12-myristate-13-acetate) and tumour necrosis factor-alpha (TNF-alpha) all stimulated the secretion of IL-8. However, only the motogenic effect of TNF-alpha was dependent upon IL-8. In conclusion, IL-8 stimulated cell migration in an in vitro model of colonic epithelium, whereas the motogenic effect of at least one physiologically relevant factor was dependent upon an increase in its endogenous levels. If IL-8 stimulates colonic epithelial restitution in vivo, this would have ramifications for the control of repair processes following wounding of the colonic mucosa.

Cell Division↗

The utility of changes in cardiac weight as an index of drug-induced cardiotoxicity.

The effects of toxic doses of various drugs and of food or water deprivation upon heart weights of mice were evaluated over a four day period to test the validity of the hypothesis that changes in cardiac weights are indicators of cardiotoxicity. Drugs included in the study were actinomycin-D, methotrexate, 5-fluorouracil, adriamycin, daunomycin, N-dimethyladriamycin, N-trifluoroacetyladriamycin-14-valerate, isoproterenol, atropine, and acetylsalicylic acid. Additional groups of mice served as vehicle controls, or were deprived of food or water for the duration of the experiment to control for the anorexia and dehydration accompanying treatment with antineoplastic drugs. Body weights were taken at the start of the experiment (day 0), day 2, and day 4 (just prior to sacrifice). Heart ventricle wet weights were determined immediately, and dry weights after thorough desiccation of the samples. Statistical evaluation of the weights revealed that there were no ventricular weight changes unique to any particular drug, and that decreases in heart weights correlated well with decreases in body weights, thereby reflecting the general toxicities of the drugs, including inanition, and not any specific cardiotoxicities.

Animals↗

Induction by short-chain fatty acids of alkaline phosphatase activity in cultured mammalian cells.

Short-chain fatty acids, such as propionic, n-butyric, n-butyric, n-valeric, isovaleric, n-caproic, and n-caprylic acids, induce alkaline phosphatase activity in cultured mammalian cells. Long-chain fatty acids have no similar effects. With B-6 cells (mouse X Chinese hamster cell hybrids), n-butyrate at 2 to 5 mM exhibits the greatest activity. Induction begins exponentially about 24 hours after addition of the fatty acid and continues over 48 hours. Studies on the inducing activity-structure relationship revealed the necessity of a carboxyl and an ethyl or longer alkyl group. n-Butyrate shows a marked synergistic action of induction when added along with other types of inducers: adenosine 3':5'-cyclic monophosphate (cAMP) or 5-bromodeoxyuridine (BrdU). Treatment of other cell lines with either n-buryrate, cAMP, or BrdU revealed a cell-type specific response pattern of alkaline phosphatase. The biological significance of this effect of short-chain fatty acids is discussed.

Acid Phosphatase↗

Exoenzymes of Propionibacterium acnes.

Thirty strains of Propionibacterium acnes were grown in basal salt medium containing lecithin as a lipid substrate and in other media. The cultures were assayed for production of lipase (measured as fatty acid esterase) and other exoenzymes. Lipase was assayed spectrophotometrically; other enzymes were assayed using the API ZYM system (Analytab Products Inc., Plainview, NY). Substance for lipase were alpha- and beta-naphthol esters of propionic, butyric, valeric, caprylic, lauric, myristic, and oleic acids. All strains showed fatty acid esterase activity. Using the API ZYM system 19 enzymes were detected, 8 of which were found frequently and had high activity in most strains. Acid and alkaline phosphatases, phosphoamidase, ester lipase, trypsin-chymotrypsin-like proteases, beta-glucuronidase (80%), beta-galactosidase (80%), and N-acetyl-beta-glucosaminidase were found. Many enzymes of P. acnes appear to be adaptive, dependent on the culture substrate.

Culture Media↗

Short-chain fatty acid fermentation products of plant fiber affect glucose metabolism of isolated rat hepatocytes.

Short-chain fatty acids (SCFA) produced during fermentation of plant fibers and absorbed from the colon may affect hepatic glucose metabolism. We examined the effects of different fatty acids on rates of glucose production and glycolysis in isolated rat hepatocytes. Acetate, butyrate, and long-chain fatty acids significantly increased glucose production from lactate. However, propionate and valerate significantly decreased glucose production from lactate. Whereas 5 mM butyrate increased the incorporation of [14C]lactate into [14C]glucose by 80%, 5 mM propionate produced a 67% decrease. Glycolysis was significantly decreased by acetate, butyrate, and long-chain fatty acids. However, propionate and valerate significantly increased glycolysis. Thus propionate, which inhibits hepatic acetate metabolism, acts to increase glucose use and decrease glucose production. Plant fibers may influence hepatic glucose metabolism via their SCFA metabolites.

Animals↗

Analysis of volatile fatty acids in wastewater collected from a pig farm by a solid phase microextraction method.

The main purpose of this study is to develop a reliable Solid Phase Microextraction (SPME) method for monitoring the concentration of volatile fatty acid (VFA) in the wastewater collected from pig farms. Ten volatile fatty acid species were spiked in 2 ml of swine wastewater and extracted with a carbowax coated extraction fiber to evaluate the accuracy and precision of the method. The fiber was introduced into a gas chromatography system by thermal desorption and detected by a mass spectrometer detector. The estimated method detection limits ranged from 11.5 mM/L for formic acid to 0.03 mM/L for heptanoic acid. The method is more sensitive than the sample direct injection method. The percentage recovery of analytes ranged from 77.3 for propanoic acid to 114.1 for formic acid at the spike level of 19.09 mM/L. The compound absorption rate varied significantly with the fiber absorption time for n-Valeric, isocaproic, n-caproic and heptanoic acids. An SPME method with twenty minutes fiber absorption and three minutes thermal desorption was tested in this study and resulted in good reproducibility for analyzing VFAs in swine wastewater. The method may be applied for scanning a wide spectrum of polar organic compounds in environmental samples.

Acrylic Resins↗

Urinary bile acids in women treated with contraceptive steroids. A study using computerized gas chromatography-mass spectrometry.

Twenty-five different bile acids were determined by gas chromatography-mass spectrometry in 24 hour urine specimens before and during treatment with a commercial contraceptive drug. Neither excretion pattern nor individual amounts of bile acids showed any change during treatment of 4 healthy women. One woman with a history of recurrent cholestasis of pregnancy showed a slight increase in the levels of S-ALAT and total amount of urinary bile acids one day before she stopped taking the pill because of generalized itching. Another patient had a normal pattern of urinary bile acids after one year with a daily intake of 10 mg of estradiol valerate.

Adult↗

Evidence for a lactate-anion exchanger in the rat jejunal basolateral membrane.

BACKGROUND/AIMS: The mechanism by which lactate, absorbed from the intestinal lumen or generated within the epithelium, crosses the basolateral membrane of the enterocyte and enters the bloodstream has not previously been characterized in detail. METHODS: L-lactate uptake into and efflux from isolated jejunal basolateral membrane vesicles was investigated at room temperature using rapid filtration techniques. RESULTS: Furosemide sensitive uptake of L-lactate was unaffected by cis sodium or proton gradients but could be stimulated by a trans gradient of bicarbonate and chloride. Kinetic analysis showed uptake to consist of a saturable component with a Michaelis constant (Km) of 3.2 mmol/L and a maximum velocity (Vmax) of 67 pmol.mg protein-1 x s-1 and a nonsaturable alpha-4-hydroxy-cinnamic acid insensitive component. Pyruvate, butyrate, acetate, valerate, and propionate competitively inhibited lactate uptake into the vesicles. Efflux of lactate from preloaded vesicles was furosemide sensitive and accelerated by a trans bicarbonate gradient as well as by 10 mmol/L acetate, butyrate, and pyruvate. CONCLUSIONS: It is concluded that there is a short chain-fatty acid carrier system in the intestinal basolateral membrane, which operates as an anion exchanger.

Animals↗

Double-blind clinical study reveals synergistic action between alpha-hydroxy acid and betamethasone lotions towards topical treatment of scalp psoriasis.

OBJECTIVE: A double-blind, single-site, split-face clinical study was organized and carried out in order to evaluate the efficacy, tolerability, and safety of a glycolic acid containing scalp lotion in conjunction with a betamethasone (as the 17-valerate) scalp application against conditions of psoriasis. BACKGROUND: Alpha-hydroxy acids (AHA) have been proposed as therapeutic modalities against skin exfoliative conditions such as ichthyosis, xeroderma, and psoriasis. AHAs are hereby clinically investigated as therapeutic modalities adjuvant to corticosteroids in order to diminish systemic and topical adverse side-effects most frequently associated with use of the latter. METHODS: Twenty patients suffering from scalp psoriasis and other psoriatic conditions were included in a double-blind, split-face clinical study, using combinations of a 10% (w/w) glycolic acid scalp lotion, placebo lotion (excipients only), and a 0.1% (w/w) betamethasone scalp application, applied twice daily without any bandage for a period of 8 weeks. Clinical assessments were carried out by highly experienced physician evaluations based on a four-grade scale, prior to treatment and after 2, 4, 6 and 8 weeks. RESULTS: Improvement was observed in all cases included in the study following treatment with the 10% glycolic acid lotion. However, when equal parts of the 0.1% betamethasone lotion were combined, most of the treated sites were healed. Moreover, the duration of treatment required for healing was in this case reduced to approximately half of that needed when the glycolic acid or the betamethasone lotions were used separately for treatment. CONCLUSIONS: The present clinical study demonstrates for the first time that the effective and well tolerated therapeutic efficacy of glycolic acid scalp lotions is enhanced when used in conjunction with a 0.1% betamethasone scalp application against scalp psoriasis. This potential offers the practising dermatologist with novel treatment modes against severe skin conditions by combining topical corticosteroid with exfoliative agent therapy.

Administration, Topical↗

Cytotoxicity of organic acids produced by anaerobic intestinal bacteria on cultured epithelial cells.

BACKGROUND: Anaerobic intestinal bacteria produce various organic acids. We identified the concentrations of various organic acids produced by intestinal bacteria needed to kill cultured cells. METHODS: Nine organic acids and their sodium salts were added to five epithelial cell lines and the cells were examined for cytotoxicity. To assess cytotoxicity, the colorimetric 3-(4,5-dimethyl-2-thiazoyl-2,5-diphenyl tetrazolium bromide (MTT) assay was performed. We calculated the lowest concentration that killed 50% of the cells by the MTT assay. Adherent and floating cells were collected 96 h after incubation for analysis of apoptosis by gel electrophoresis and flow cytometry. RESULTS: The minimum concentrations of the acids and sodium salts of n-butyric, propionic, isovaleric, and succinic acids capable of causing cytotoxicity were lower than the concentrations produced by intestinal bacteria. Apoptosis was found in all cell lines treated with the acids and the sodium salts of n-butyrate, isobutyrate, propionate, isovalerate, and n-valerate. However, no apoptosis was found in cells treated with the acid or sodium salts of formate and lactate. CONCLUSIONS: This study showed that acetate, butyrate, propionate, and valerate produced by intestinal bacteria could induce apoptosis at physiological concentrations. This cytotoxicity may contribute to the pathogenesis of colonic ulcers.

Apoptosis↗

Dietary magnesium oxide interactions with sodium bicarbonate on cows in early lactation.

Thirty-six Holstein cows were fed a diet of 50% concentrate and 50% corn silage (dry matter) for 12 wk postpartum. Treatments were 0, .4, and .8% magnesium oxide with or without .8% sodium bicarbonate in a 2 X 3 factorial arrangement. Dry matter intake was not different among treatments although the combined buffers had higher intake. Milk production was higher for the .4% magnesium oxide treatments either alone or with sodium bicarbonate as compared with either the 0 or .8% magnesium oxide treatments. Ruminal pH was increased with addition of sodium bicarbonate either alone or together with magnesium oxide. Dietary addition of .4% magnesium oxide either alone or with sodium bicarbonate increased total volatile fatty acid in ruminal fluid. Propionate and valerate were depressed in both of the combined buffered diets. Fecal pH was increased with magnesium oxide addition either alone or with sodium bicarbonate. Increasing magnesium oxide increased magnesium in plasma. No interactions in animal performance were significant for the two buffers.

Ammonia↗

Determination of organic acids, sugars, diacetyl, and acetoin in cheese by high-performance liquid chromatography.

Sugars (lactose, glucose, and galactose), nonvolatile acids (citric, orotic, piruvic, lactic, ossalic, and hippuric), some free fatty acids (formic, acetic, propionic, butyric, isobutyric, valeric, and isovaleric), diacetyl, and acetoin were separated on an Aminex HPX-87H column using a simple isocratic HPLC method and identified by retention times with ultraviolet and refractive index detectors. With the proposed technique it is possible to evaluate the development of microbial fermentations and, at the same time, degree of cheese ripening.

Acetoin↗