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PubMed2003

Selective optimization in thermophilic acidogenesis of cheese-whey wastewater to acetic and butyric acids: partial acidification and methanation.

For partial acidogenesis of cheese-whey wastewater, a set of experiments were carried out to produce short-chain volatile fatty acids (VFA) in laboratory-scale continuously stirred tank reactors (CSTR). The maximum rate of acetic and butyric acid production associated with simultaneous changes in hydraulic retention time (HRT), pH, and temperature was investigated, in which the degree of acidification of the whey to the short-chain VFAs was less than 20% of the influent chemical oxygen demand (COD) concentration. Response surface methodology was successfully applied to determine the optimum physiological conditions where the maximum rates of acetic and butyric acid production occurred. These were 0.40-day HRT, pH 6.0 at 54.1 degrees C and 0.22-day HRT, pH 6.5 at 51.9 degrees C, respectively. The optimum conditions for acetic acid production were selected for partial acidification of cheese-whey wastewater because of a higher rate in combined productions of acetic and butyric acids than that at optimum conditions for butyric acid production. A thermophilic two-phase process with the partial acidification followed by a methanation step was operated. Performance of the two-phase process was compared to the single-phase anaerobic system. The two-phase process clearly showed a better performance in management of cheese-whey wastewater over the single-phase system. Maximum rate of COD removal and the rate of methane production in the two-phase process were, respectively, 116% and 43% higher than those of the single-phase system.

Bacteria, Anaerobic↗
PubMed2003

Cellular interactions and degradation of aliphatic poly(ester amide)s derived from glycine and/or 4-amino butyric acid.

A series of poly(ester amide)s derived from amino acid (glycine or 4-amino butyric acid), diol (1,6-hexanediol or 1,4-butanediol) and sebacoyl chloride were prepared by interfacial polymerization. FT-IR analysis indicated that for poly(ester amide)s derived from glycine, only amide-amide hydrogen bonds and hydrogen-bonded C=O ester groups were established, whereas the poly(ester amide)s derived from 4-amino butyric acid contained amide-amide hydrogen bonds and amide-ester hydrogen bonds, including NH groups and C=O ester groups in free state. The biodegradability was estimated by weight residue of poly(ester amide) films in pH 6 buffer solution with papain at 37 degrees C. The poly(ester amide) films derived from glycine demonstrated significantly improved degradability compared to the poly(ester amide) films derived from 4-amino butyric acid. This difference of degradation rate could be explained by the bonding state in C=O ester groups. The cellular interaction of the poly(ester amide)s was studied by measuring the proliferation of human dermal fibroblasts on the polymer films. The cells proliferated significantly faster on poly(ester amide) films derived from 4-amino butyric acid than on poly(ester amide) films derived from glycine. These results suggest that the poly(ester amide) prepared in this study may serve as a potential cell-compatible biomedical material.

Absorbable Implants↗
PubMed2002

Modulatory effect of butyric acid-a product of dietary fiber fermentation in experimentally induced diabetic rats.

The effect of feeding of butyric acid on alleviation of diabetic status was studied. Diabetes was induced in rats using streptozotocin. Rats were fed with basal diet containing wheat bran (5%) as a source of insoluble dietary fiber and guar gum (2.5%) as a source of soluble dietary fiber. The experimental group received butyric acid at 250, 500 and 750 mg/kg body weight/day. The diabetic animals lost weight in spite of high diet consumption. The levels of water intake, urine output, urine sugar, fasting blood sugar increased during diabetic condition compared to control and these were reduced by nearly 20% in the fiber-fed diabetic group. Further supplementation of butyric acid at 500 mg/kg body weight/day ameliorated the diabetic status by nearly 40%. Urine sugar level during the diabetic state was reduced from 7.2 g/day to 3.6 g/day and fasting blood glucose from 270 mg/dl to 180 mg/dl. Butyric acid feeding at 500 mg/kg body weight/day was most effective in controlling the diabetic status.

Journal Article↗
PubMed1999

Induction of tissue transglutaminase expression by propionate and n-butyrate in colon cancer cell lines.

Short-chain fatty acids (SCFAs) have been demonstrated to induce differentiation and/or apoptosis in colon cancer cells. A close correlation between tissue transglutaminase (tTG) expression and differentiation and/or apoptosis has been suggested in many cell lineages. However, the effects of SCFAs on tTG expression in colon cancer cells have not yet been reported. In this report, the relationship between cytosolic tTG levels and differentiation state was investigated in six human colon cancer cell lines. Effects of four kinds of SCFAs (acetate, propionate, n-butyrate, and isobutyrate) on the expression of tTG then were investigated in association with their effects on apoptosis induction. High expression of tTG protein and mRNA were found in SW480 and WiDr cell lines, which exhibited well differentiated phenotypes. tTG expression was hardly detectable in the less differentiated cell lines COLO201, COLO320DM, and CW-2. However, n-butyrate and propionate significantly increased cytosolic tTG levels at concentrations above 0.5 mM in these less differentiated colon cancer cells. n-Butyrate and propionate induced growth suppression and apoptosis in these cell lines at concentrations that can induce tTG expression. Acetate and isobutyrate did not induce tTG expression or growth suppression at concentrations up to 8 mM. In conclusion, tTG induction by propionate and n-butyrate was suggested to be closely linked to their differentiation- and apoptosis-inducing effects in colon cancer cells. These findings may explain the mechanisms by which dietary fiber show preventive effects against colon carcinogenesis.

Journal Article↗
PubMed1971

An evaluation of 4-s-methyl-2-keto-butyric Acid as an intermediate in the biosynthesis of ethylene.

Stimulation of ethylene production by cauliflower (Brassica oleracea var. botrytis L.) tissue in buffer solution containing 4-S-methyl-2-keto-butyric acid is not due to activation of the natural in vivo system. Increased ethylene production derives from an extra-cellular ethylene-forming system, catalyzed by peroxidase and other factors, which leak from the cauliflower tissue and cause the degradation of 4-S-methyl-2-keto-butyric acid. This exogenous ethylene-forming system is similar to the ethylene-forming horseradish peroxidase system which utilizes methional or 4-S-methyl-2-keto-butyric acid as substrate. We conclude that 4-S-methyl-2-keto-butyric acid is probably not an intermediate in the biosynthetic pathway between methionine and ethylene.

Journal Article↗
PubMed1978

The effects on epidermal DNA synthesis of the butyrate esters of clobetasone and clobetasol, and the propionate ester of clobetasol.

An animal model for evaluating the effects of drugs on epidermal DNA synthesis has been used to determine the time of onset, period of maximum activity and duration of effect of two topically applied proprietary glucocorticosteroids, clobetasone butyrate and clobetasol propionate. Both drugs produced maximum inhibition of epidermal DNA synthesis by 24 h after application. Clobetasol propionate exhibited a significantly earlier onset (4 1/2 h) and longer duration (36 h) of activity than clobetasone butyrate (6 and 24 h respectively). A systemic effect was not observed at any time after the application of clobetasone butyrate but was observed for up to 24 h after the application of clobetasol propionate. Clobetasol butyrate was also assayed in this system and was found to be as potent as clobetasol propionate. It is concluded that the alcoholic, as opposed to the ketonic, grouping in the 11 positions of the steroid ring profoundly alters the potentials of this molecule for systemic activity.

Animals↗
PubMed1984

Intermediary Metabolism in Clostridium acetobutylicum: Levels of Enzymes Involved in the Formation of Acetate and Butyrate.

The levels of seven intermediary enzymes involved in acetate and butyrate formation from acetyl coenzyme A in the saccharolytic anaerobe Clostridium acetobutylicum were investigated as a function of time in solvent-producing batch fermentations. Phosphate acetyltransferase and acetate kinase, which are known to form acetate from acetyl coenzyme A, both showed a decrease in specific activity when the organism reached the solvent formation stage. The three consecutive enzymes thiolase, beta-hydroxybutyrylcoenzyme A dehydrogenase, and crotonase exhibited a coordinate expression and a maximal activity after growth had ceased. Only low levels of butyryl coenzyme A dehydrogenase activity were found. Phosphate butyryltransferase activity rapidly decreased after 20 h from 5 to 11 U/mg of protein to below the detection limit (1 mU/mg). Butyrate no longer can be formed, and the metabolic flux may be diverted to butanol. Butyrate kinase showed a 2.5- to 10-fold increase in specific activity after phosphate butyryltransferase activity no longer could be detected. These results suggest that the uptake of acetate and butyrate during solvent formation can not proceed via a complete reversal of the phosphate transferase and kinase reactions. The activities of all enzymes investigated as a function of time in vitro are much higher than the metabolic fluxes through them in vivo. This indicates that none of the maximal activities of the enzymes assayed is rate limiting in C. acetobutylicum.

Journal Article↗
PubMed1985

Interactions in syntrophic associations of endospore-forming, butyrate-degrading bacteria and h(2)-consuming bacteria.

Butyrate is an important intermediate in the anaerobic degradation of organic matter. In sulfate-depleted environments butyrate is oxidized to acetate and hydrogen by obligate proton reducers, in syntrophic association with hydrogen-consuming methanogens. This paper describes two enrichments of endospore-forming bacteria degrading butyrate in consortia with methanogens. The isolates are readily established in coculture with H(2)-consuming, sulfate-reducing bacteria by pasteurizing the culture. The two original enrichments differed in that one grew to an optically dense culture while the second grew in clumps. Examination by scanning electron microscopy showed that clumping resulted from the production of large amounts of extracellular polymer. Several H(2)-consuming methanogens were identified in the enrichments. Some of them grew closely associated to the butyrate degraders. This attachment to the hydrogen producer may permit some methanogens to compete for the growth substrate against other bacteria having higher substrate affinity.

Journal Article↗
PubMed1980

Study of the effects of hydrocortisone and hydrocortisone 17-butyrate ointments on plasma ACTH levels and Synacthen responses in children with eczema.

This study compares the effects on the hypothalamo-pituitary adrenal (HPA) axis of two dosage schedules of hydrocortisone 17-butyrate and hydrocortisone ointments in 20 children suffering from eczema. Children with moderately extensive eczema received either 30 g of 0.1% hydrocortisone 17-butyrate or 30 g of 1% hydrocortisone ointment weekly for 4 weeks without occlusion. Children with extensive eczema received either 60 g of hydrocortisone 17-butyrate or 60 g of hydrocortisone weekly for 4 weeks. All four groups showed some clinical improvement. Although many of the children appeared to have some impairment of adrenal function prior to entering the trial, no further significant depression of the HPA axis as reflected by the plasma ACTH levels and a 30-min Synacthen test was observed during the trial. On the basis of 4 weeks' treatment, hydrocortisone 17-butyrate did not have a significantly different effect on the HPA axis in children from that of hydrocortisone.

Administration, Topical↗
PubMed1983

Clinical comparison of alclometasone dipropionate cream 0.05% with hydrocortisone butyrate cream 0.1% in the treatment of atopic dermatitis in children.

Alclometasone dipropionate cream 0.05% was compared to hydrocortisone butyrate cream 0.1% in the treatment of atopic dermatitis in forty children, 5 to 11 years old. In this double-blind, parallel-group trial, the experimental creams were applied twice daily for 2 weeks, without occlusion, to the study areas. Efficacy was evaluated 1 and 2 weeks after the start of treatment. Both creams were effective treatments for atopic dermatitis; however, alclometasone dipropionate was judged slightly more efficacious. Improvement in erythema, induration, and pruritus averaged 76% for alclometasone dipropionate-treated patients and 70% for hydrocortisone butyrate-treated patients. At the end of treatment, the physician's global evaluation indicated nineteen of twenty patients in the alclometasone dipropionate group had between 51% and 100% improvement in disease signs and symptoms, compared with sixteen of twenty patients treated with hydrocortisone butyrate. Two patients in the alclometasone dipropionate-treated group and one in the hydrocortisone butyrate-treated group reported mild stinging.

Child↗
PubMed1976

Clinical evaluation of clobetasone butyrate in the treatment of children with atopic eczema, and its effect on plasma corticosteroid levels.

Studies were carried out to assess the effectiveness of clobetasone butyrate in treating eczema and psoriasis, and to determine if the compound had any effect on plasma cortisol levels. In the first trial, 71 children with bilateral symmetrical atopic eczema lesions were treated twice daily for 1 week, on one side with 0.05% clobetasone butyrate cream or ointment and on the other with 0.0125% flurandrenolone cream or ointment. Lesions improved or healed in the majority of the patients. Treatment preference showed a trend in favour of clobetasone butyrate but the difference was not statistically significant. In a second open trial, 29 adults with eczema or psoriasis were treated twice daily with clobetasone butyrate for 1 week: lesions in 10 patients remained static, 12 improved, and 7 were cleared. Plasma corticosteroid levels remained within the normal range at the end of the treatment period.

Adolescent↗
PubMed2000

Sodium butyrate-induced differentiation of human LIM2537 colon cancer cells decreases GSK-3beta activity and increases levels of both membrane-bound and Apc/axin/GSK-3beta complex-associated pools of beta-catenin.

Analysis of the glycogen synthase kinase-3beta (GSK-33) activity in several colon cancer cell lines suggested a correlation between comparatively low enzyme activity and moderate to high differentiation status. Treatment of LIM2537 cells, a poorly differentiated colon cancer cell line, with the potent differentiating agent sodium butyrate resulted in 34% reduction in GSK-3beta activity in the treated cells (P < 0.028, n = 3). Decreases in GSK-3beta activity were paralleled by stabilization of cytoplasmic beta-catenin, a hallmark of Wnt signaling. However, in contrast to Wnt signaling, expression of the beta-catenin/ TCF target genes c-myc and cyclin D1 did not appear to be increased in the sodium butyrate-treated cells. Interestingly, expression of membrane-bound beta-catenin was increased in the sodium butyrate-treated cells. This suggests that, in the context of cellular differentiation, increases in beta-catenin expression may be sequestered at the cell membrane and suggests that a possible role of sodium butyrate in promoting differentiation may be via increasing the levels of beta-catenin available for cell adhesion.

Alkaline Phosphatase↗
PubMed1987

Butyrate kinase from Clostridium acetobutylicum.

Crude extracts of Clostridium acetobutylicum contain a butyrate kinase of high specific activity (5.2 mumol/min/mg of protein). The enzyme has been purified 77-fold in a six-step procedure to a specific activity of 402 mumol/min/mg of protein. The purified butyrate kinase showed a single band with a molecular weight of 85,000 on nondenaturing polyacrylamide gradient gel electrophoresis. Separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the enzyme is a dimer of two apparently identical subunits with molecular weights of 39,000. The pH optimum for the reaction in the butyryl phosphate-forming direction is 7.5, and the pI of the kinase is 5.6. The amino acid composition of the enzyme is also reported. It contains no tryptophan and is low in sulfur-containing amino acids. The kinase has a broad substrate specificity and exhibits its highest relative activities with butyrate and valerate. Butyrate kinase is rapidly inactivated at 50 degrees C in the absence of a fatty acid substrate. Although a reducing agent was required for maximum activity, treatment with several sulfhydryl-modifying agents failed to inhibit the enzyme.

Amino Acids↗
PubMed1996

In vivo search for butyrate responsive sequences using transgenic mice carrying A gamma gene promoter mutants.

We describe an in vivo approach, in transgenic mice, aimed to identify promoter elements responsible for the induction of gamma globin expression by butyrate. Transgenic lines carrying human A gamma gene promoter truncations at position -141, -201, -382, and -730 A gamma were treated with alpha amino butyric acid (alpha ABA), and effects on gamma globin expression were analyzed at the messenger RNA level. No induction of gamma gene expression was observed in animals carrying promoters truncated at positions -141, -201, or -382 A gamma, suggesting either that butyrate response elements (BRE) are not located in the proximal gamma gene promoter or, if they were, they require the cooperation of upstream sequences for gamma gene induction. Two animals from one line carrying the -730 A gamma truncation responded to alpha ABA treatment with significant increases in gamma gene expression, indicating that a BRE is located between position -382 and -730 region of the A gamma gene promoter. Because the maximum induction by alpha ABA is observed in transgenic mice carrying a A gamma gene promoter extending to nucleotide -1350, it is likely that another butyrate responsive element is located between -730 and -1350 of the A gamma gene promoter. These results indicate that the transgenic mouse model can be used for identification of DNA regions that contain cis elements involved in gamma globin gene inducibility.

Aminobutyrates↗
PubMedDate not supplied

Effect of butyrate analogues on proliferation and differentiation in human neuroblastoma cell lines.

Butyric acid has been shown in vitro to produce cytodifferentiation of a wide variety of neoplastic cells. The potential clinical use of this compound as a therapeutic agent is limited by its rapid metabolism. This has led to the examination, as potential antineoplastic agents, of compounds structurally correlated to butyrate, with longer biological half lives. In this study we investigated the effect in vitro of two butyrate analogues, tributyrin and butyramide, on inducing growth inhibition and expression of morphological and immunophenotypic properties, in human neuroblastoma cell lines. Treatment with tributyrin resulted in a strong inhibition of cell proliferation and in induction of extensive differentiation; on the contrary butyramide was scarcely effective or quite ineffective. These results demonstrate that tributyrin retains the effectiveness of butyrate and suggest that this analogue could have utility for cytodifferentiation therapy.

Amides↗
PubMed1990

Butyrate induces expression of transfected human fetal and endogenous mouse embryonic globin genes in GM 979 erythroleukemia cells.

We have analyzed the expression of endogenous murine genes and of transfected human fetal A gamma globin gene in GM 979, a mouse erythroleukemia line which produces adult as well as embryonic globins. Optimal induction of the endogenous murine adult globin genes was obtained with DMSO or HMBA while the epsilon y and beta h1 embryonic genes were preferentially induced by butyrate. Similarly, the transferred human A gamma-globin gene was preferentially induced by butyrate. These results as well as previous observations in vivo or in erythroid cell cultures suggest that butyrate preferentially induces the expression of fetal globin genes.

Acetamides↗
PubMedDate not supplied

Differential effect of TPA and n-butyrate on induction of Ii and EBV antigens in the P3HR-1 lymphoblastoid cell line.

The aim of this study was to test whether EBV induction by TPA or n-butyrate was related directly to hyperexpression of Ii, an electrophoretically invariant, 35 000 dalton, HLA-DR antigen-associated glycoprotein which is abundantly detected in EBV freshly transformed cells and is enhanced by EBV superinfection of lymphoblastoid cell lines. P3HR-1 lymphoblasts were treated with n-butyrate or TPA in variable doses and durations. The augmented expression of Ii, EBV antigens (EA and VCA), DNA synthesis, and cell growth and viability were monitored. n-Butyrate induced hyperexpression of Ii at 2 days with a maximal effective dose of 4 mM, induced EBV antigens (EA and VCA) in 36 per cent of the cells at 2 days, inhibited DNA synthesis and cell growth, and was not cytolytic at 48 h when Ii induction was maximal. TPA did not induce hyperexpression of Ii, induced EBV antigens (EA) in 30 per cent of the cells at 4 days, did not inhibit DNA synthesis and cell growth, and was not cytolytic in the time course and doses studied. Ii expression, therefore, did not appear to be an obligatory consequence of EBV antigen induction. Ii induction might be related to an effect of EBV inducers on cellular DNA synthesis, or on control of the cell cycle, or directly upon Ii gene regulation.

Antigens, Neoplasm↗
PubMed1985

Butyrate enhances the synthesis of interphotoreceptor retinoid-binding protein (IRBP) by Y-79 human retinoblastoma cells.

The synthesis and secretion of interphotoreceptor retinoid-binding protein (IRBP) from Y-79 human retinoblastoma cells was investigated using immunocytochemistry and SDS-polyacrylamide gel electrophoresis. Indirect immunofluorescence of cells growing in monolayer culture for 11 and 13 days showed no significant IRBP staining although by SDS-polyacrylamide gel electrophoresis, a small amount of IRBP was detected in the culture medium, suggesting synthesis and extracellular secretion. Butyrate (2mM) treatment of cells starting on the eighth day of culture resulted in a dramatic increase of IRBP fluorescence 3-5 days after treatment. Treatment of cells in all conditions with 1 microM monensin for 3 h showed concentration of IRBP in the Golgi apparatus of about 10-20% of cells as proved by a double immunofluorescent technique, employing anti-IRBP antibody and wheat-germ agglutinin. Incubation of cells with either radiolabeled amino acids or glucosamine followed by analysis of cell cytosol and culture medium by SDS-polyacrylamide gel electrophoresis also confirmed that 1) IRBP is synthesized by the Y-79 cells and secreted into the medium and 2) its production is markedly increased by butyrate treatment. The enhancement of IRBP synthesis by butyrate suggests biochemical differentiation of Y-79 cells possibly into photoreceptor-like cells and offers a new system for studying the properties of this unique retinoid-binding protein and of factors that control its synthesis and secretion.

Amino Acids↗