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PubMed1986

Antagonistic effect of butyrate on hexamethylene bisacetamide induced differentiation of murine erythroleukemia cells.

Butyrate, at concentrations greater than 0.75 mM, induces hemoglobin accumulation in murine erythroleukemia cells (MELC). At concentrations below 0.75 mM, butyrate inhibits hemoglobin accumulation induced by hexamethylene bisacetamide (HMBA) as well as HMBA induced commitment to terminal cell division. The blocking of HMBA induced differentiation does not result from growth inhibition. When cells were exposed to HMBA and butyrate for 4 days and then both inducers were removed, the cells did not terminally divide. On the other hand, cells exposed to HMBA for 4 days, with subsequent removal of HMBA, did go on to terminally divide. Thus, butyrate blocks the ability of HMBA to accumulate the intracellular signals for terminal cell division. A 48-h pretreatment of cells with butyrate did not inhibit the ability of subsequent HMBA treatment, after butyrate removal, to induce terminal cell division. These results might suggest that cells do not generate a memory of exposure to HMBA in the presence of butyrate or a memory of exposure to butyrate when used as a pretreatment under these conditions. HMBA, at concentrations below 1.0 mM, does not induce MELC differentiation, but such concentrations actually enhance dimethyl sulfoxide induced differentiation of MELC. Equimolar concentrations of short chain fatty acids (1 to 7 carbons) were tested for their ability to block HMBA induced differentiation of MELC. Butyrate and valerate (4 and 5 carbons, respectively) had blocking activities similar to each other, whereas the other fatty acids exhibited little or no blocking of HMBA induced differentiation.

Acetamides↗
PubMed2006

Action of topical thyroid hormone analogues on glucocorticoid-induced skin atrophy in mice.

Previously we demonstrated the stimulation of collagen synthesis in triiodothyroacetic acid (TRIAC)-topically treated human and mice. In the present study, we have evaluated the dose response effect of thyroid hormone (TH) analogues and tretinoin on glucocorticoid-induced skin atrophy in a haired mouse model. For this investigation, we treated haired mice twice daily for 7 days with various topically administered doses of TRIAC, triiodothyronine-sodium salt (T(3)-Na), diiodothyroacetic acid (DIAC), 3,5-diiodothyropropionic acid (DITPA), and tretinoin with 0.2 mM betamethasone17-valerate (BM), or with the vehicle as a control group. We also investigated a combination of commercial betamethasone dipropionate (BD) 0.05% cream and various doses of TRIAC on mouse skin. TRIAC was able to reverse the skin atrophy by 25% in a daily dose of 1 nmol/cm(2) in the presence of 0.2 mM BM (p < 0.05). Neither other TH analogues nor TRIAC in lower and higher concentrations had a significant inhibitory effect on dermal atrophy (p > 0.05). A combination of 0.2 mM BM and 10 nmol/cm(2) TRIAC was able to prevent dermal atrophy by 18%. The addition of TRIAC to 0.05% BD cream in a final concentration of 0.1% was able partially to reverse the dermal atrophy by 15% (p < 0.05). TRIAC alone in a concentration of 1,000 nmol/cm(2) stimulated dermal proliferation by 34% (p < 0.05). Other TH analogues alone had no stimulatory effect on dermal proliferation. Tretinoin 0.8 mM was able to inhibit dermal atrophy by 20% (p < 0.05) and had an effect on dermal thickness of 85% (p < 0.05). However, severe side effects with edema, erythema, and scaling were commonly observed in all tretinoin-treated mouse skin, which could partly explain the increase in dermal thickness. In contrast, no skin side effects were observed after treatment with TRIAC. This study indicates that TRIAC may have a therapeutic effect on BM-induced dermal atrophy in mouse skin and a direct stimulatory effect on dermal proliferation when given alone.

Acetates↗
PubMed1988

[Anti-inflammatory activity of the dry distillation tar of delipidated soybean (Glyteer) (2)].

The anti-inflammatory effects of Glyteer (GL) were investigated by its local administration using the CMC-pouch method in rats, and the effects were compared with those of betamethasone 17-valerate (BV, 1 mg), phenylbutazone (PB, 10 mg), flufenamic acid (FA, 10 mg), bufexamac (BM, 10 and 20 mg), bendazac (BZ, 10 and 20 mg), icthammol (IT, 10 mg) and pine tar (PT, 10 mg). At three hours after CMC-treatment, GL (10 mg) significantly inhibited not only the protein exudation, but also the leucocyte migration. The inhibitory activity of GL on the leucocyte migration had the same potency as that of FA, but was stronger than those of PB, BV, BM, BZ, IT and PT. Furthermore, in relation to the leucocyte migration, GL markedly inhibited not only the neutrophil, but also the macrophage migration. At three hours after CMC-treatment, the inhibitory activity of GL on the neutrophil migration had the same potency as those of PB and FA, but was stronger than those of BV, BM, BZ, IT and PT. On the other hand, GL, BM, BZ, FA, IT and PT had an inhibitory activity on the macrophage migration, and the activity was more potent in GL, FA and IT. From these results, it is suggested that the inhibition of GL on increased vascular permeability and leucocyte migration is one of the mechanisms of its anti-inflammatory action.

Administration, Topical↗
PubMed1984

Odd-carbon fatty acid metabolism in hepatocytes from starved rats.

The metabolism of odd-chain fatty acids was investigated in hepatocytes from 24 h-starved rats. Rates of glucose and 14CO2 production from [1-14C]propionate, [1-14C]valerate and [1-14C]nonanoate were maximal at 0.1 mM. Glucose production was greater with propionate as substrate than with valerate or nonanoate. Ketone body, lactate and pyruvate release were not affected by addition of the odd carbon fatty acids. It is concluded that hepatic odd-chain fatty acid metabolism in starvation is partly oxidative and partly gluconeogenic. Vasopressin and angiotensin II stimulated 14CO2 production from [1-14C] valerate and [1-14C]nonanoate but not from [1-14C]propionate and [1-14C]oleate in hepatocytes from starved rats. Nonanoate and valerate generate acetyl-CoA and propionyl-CoA, whereas oleate or propionate produce acetyl CoA and propionyl-CoA respectively. Given this stoichiometry, it is inferred that in hepatocytes from starved rats there must be an input of a tricarboxylic acid cycle intermediate to permit expression of the hormonal sensitivity.

Angiotensin II↗
PubMed1988

[The use of a partly-hydrolysed straw meal in the feeding of weaned piglets. 2. Concentration and production of volatile fatty acids in the large intestine by the use of test rations with various portions of straw].

The ad libitum influence of various quotas of partly hydrolysed straw meal (PHSM) on the fermentation and production of volatile fatty acids (VFA) in the colon in the measuring periods 2nd and 8th weeks of keeping was checked within a feeding experiment with weaned piglets of the country species (42nd-98th day of life; 1st-8th week of keeping). The straw hydrolysis product was fed in a parallel experiment without or after neutralization with CaCO3 in quotas of, 5, 10 and 15% related to dry matter in comparison to the feeding of sole concentrate feed. The measuring in the 2nd week of keeping (adaptation phase) was blurred by the diarrhea in the groups with regard to the concentration, production and molar proportion of VFA. The concentration and production quota of VFA was diminished and the C2:C3 relation as well as the molar quota of branched-chain fatty acids increased in the comparison of the groups above all under the feeding conditions of the sole use of concentrate and--less distinctly--of quotas of 5% PHSM (insufficient dietetic effect) in the feed mixture. Measuring in the 8th week, in which diarrhea did not play a role in any of the groups, showed a significant, ration specific influence on the fermentation pattern of VFA. With the increasing quota of PHSM in the feed mixture (x) a significantly positive relation with the molar acetate quota (y) could be calculated (y = 52.6 + 0.36x;r = 0.50). The C2:C3 relation after sole concentrate feeding rose to 2.6:1 at a 15% PHSM integration. In this, the molar increase of acetate was predominantly linked with a decrease of the butyrate and valerate quotas. A falling tendency of the molar iso-acid quota in the colon digesta was registered with the growing straw quota in the feed mixture. The daily production quota of VFA varied in the measuring period in the 8th week of keeping between 400 and 800 mmol/animal.d without an ascertainable influence of the crude fibre quota of the straw. In comparative calculations with other test results, however, a significant positive correlation between the daily intake of digestible organic matter and the production of VFA in the large intestine could be proved.

Animal Feed↗
PubMed1979

Effects of estrogen to alter amino acid transport in R3230AC mammary carcinomas and its relationship to insulin action.

The effects of estrogens on transport and incorporation of amino acids into the R3230AC mammary adenocarcinoma were studied in vivo and in vitro. Dissociated tumor cells from ovariectomized rats, like those from diabetic rats, displayed elevated transport of proline, representing entry by the A system; transport of phenylalanine (L system) was unaltered, as was glucose transport and its utilization. Administration of estradiol valerate decreased the entry of proline into tumor cells from intact, diabetic, or ovariectomized animals; the response to the steroid hormone was greater in ovariectomized or diabetic rats compared to intact animals. The time course of the effects of estrogen treatment was examined in diabetic rats. By 72 hr, transport of both proline and leucine was significantly decreased; incorporation of leucine into proteins and uridine into RNA was significantly reduced by 24 hr after injection of estradiol valerate. The effects of estrogen in vivo to reduce transport of amino acids and their incorporation into proteins appeared to correlate with the reduced tumor growth observed. Experiments were performed to examine the effects of 17 beta-estradiol in vitro on amino acid transport into dissociated cells from ovariectomized or diabetic rats. Under these experimental conditions, 17 beta-estradiol (10(-6)M) inhibited proline transport with little or no effect on leucine transport in cells from ovariectomized rats; in cells from diabetic rats, proline transport and leucine incorporation were significantly reduced by estradiol, whereas phenylalanine transport was slightly inhibited (approximately 20%). The effect of estradiol in vitro was also manifest in tumor cells obtained from diabetic rats treated in vivo with estradiol valerate; estradiol in vitro caused a further reduction in proline transport but not in leucine transport, results that imply some specificity to the action of estrogen on the A system. Since we had earlier shown that insulin action on transport in these tumor cells were directed towards the A system, we examined the effects of insulin, estradiol, and their combination in vitro on proline and leucine transport. Insulin (10(-8) M) stimulated proline transport; 17 beta-estradiol, at a selected lower level of 10(-8) M, inhibited proline transport. When both were added in vitro, estradiol (10(-8 M) was capable of significantly reducing the insulin (10(-8) M)-induced increase in proline transport. Leucine transport was not altered in any of these experiments. Together, these data suggest that estrogens are capable of inhibiting amino acid transport into the R3230AC mammary carcinoma, an effect that is compatible with reduced tumor growth. The possible relationship of estrogen and insulin at the level of amino acid transport remains to be elucidated.

Adenocarcinoma↗
PubMed1991

Acid profile in carious dentin.

Organic acids in carious dentin from 69 permanent teeth were analyzed by gas chromatography. Lactate, acetate, propionate, and butyrate were detected in most samples, and limited amounts of isobutyrate, valerate, isovalerate, caproate, and isocaproate were occasionally detected. Lactate, acetate, and propionate were major acids and altogether accounted for about 90% of total acid in most samples of carious dentin. However, the proportion of these three acids varied among the samples. Some samples contained over 85% lactate, while others contained mainly acetate and propionate. A high percentage of acetate was usually accompanied by an appreciable amount of propionate. All seven samples in carious dentin under fillings or restorations had little lactate, but a high percentage of acetate plus propionate. The differences in acid profiles of carious dentin may reflect differences in the microbial ecology of carious dentin, and a stage of progress of dentin caries or a type of dentin caries.

Acetates↗
PubMed1989

Coenzyme A transferase from Clostridium acetobutylicum ATCC 824 and its role in the uptake of acids.

Coenzyme A (CoA) transferase from Clostridium acetobutylicum ATCC 824 was purified 81-fold to homogeneity. This enzyme was stable in the presence of 0.5 M ammonium sulfate and 20% (vol/vol) glycerol, whereas activity was rapidly lost in the absence of these stabilizers. The kinetic binding mechanism was Ping Pong Bi Bi, and the Km values at pH 7.5 and 30 degrees C for acetate, propionate, and butyrate were, respectively, 1,200, 1,000, and 660 mM, while the Km value for acetoacetyl-CoA ranged from about 7 to 56 microM, depending on the acid substrate. The Km values for butyrate and acetate were high relative to the intracellular concentrations of these species; consequently, in vivo enzyme activity is expected to be sensitive to changes in those concentrations. In addition to the carboxylic acids listed above, this CoA transferase was able to convert valerate, isobutyrate, and crotonate; however, the conversion of formate, n-caproate, and isovalerate was not detected. The acetate and butyrate conversion reactions in vitro were inhibited by physiological levels of acetone and butanol, and this may be another factor in the in vivo regulation of enzyme activity. The optimum pH of acetate conversion was broad, with at least 80% of maximal activity from pH 5.9 to greater than 7.8. The purified enzyme was a heterotetramer with subunit molecular weights of about 23,000 and 25,000.

Biological Transport↗
PubMed2005

Corn grain endosperm type and brown midrib 3 corn silage: ruminal fermentation and N partitioning in lactating cows.

Interactions of endosperm type of corn grain and the brown midrib 3 mutation (bm3) in corn silage on ruminal fermentation and microbial efficiency of lactating dairy cows were evaluated. Eight ruminally and duodenally cannulated cows (72 +/- 8 d in milk; mean +/- SD) were used in a duplicated 4 x 4 Latin square design experiment with a 2 x 2 factorial arrangement of treatments. Treatments were corn grain endosperm type (floury or vitreous) and corn silage type (bm3 or isogenic normal). Diets contained 26% neutral detergent fiber and 30% starch. Increasing ruminal starch digestibility by replacing vitreous corn grain with floury grain reduced mean and minimum ruminal pH. Brown midrib 3 corn silage reduced mean and minimum ruminal pH and increased total volatile fatty acid concentration. Ruminal pH was positively associated with rate of valerate absorption. Although floury endosperm reduced acetate:propionate ratio in both control and bm3 corn silage diets, it had a greater effect on reducing acetate:propionate ratio for control silage compared with bm3 corn silage. Nonammonia N flow to the duodenum did not differ among treatments and no effects of treatment were detected for microbial N and nonammonia, nonmicrobial N flow. Although treatment effects on ruminal fermentation and ruminal pH were observed, few interactions of treatment were detected and treatments did not affect flow of N fractions to the intestines.

Animals↗
PubMed1985

Pharmacokinetics and biotransformation of estradiol valerate in ovariectomized women.

Estradiol valerate is well suited for treatment of the characteristic symptoms accompanying menopause in women. The pharmacokinetics and biotransformation of estradiol valerate were studied in women following intravenous, intramuscular and oral administration. Intravenously given, estradiol valerate is split by enzymatic hydrolysis into 17 beta-estradiol and the fatty acid. The estrogen arising in vivo from the steroid ester is subject to intermediate metabolism. The metabolites are eliminated at a nearly constant rate mainly in urine. The biotransformation of estradiol valerate was not different following intravenous or intramuscular injection. Orally given estradiol valerate is subject to an extensive first pass metabolism. Daily repeated oral administration does not result in accumulation of 17 beta-estradiol and its metabolites.

Administration, Oral↗
PubMed1999

Interaction of tallow and hay particle size on ruminal parameters.

Four nonlactating ruminally cannulated Holstein cows were used in a 4 x 4 Latin square experiment with 4 21-d periods to determine if the effects of dietary fat would be affected by hay particle length. Treatments consisted of two levels of tallow (0 and 5%) and two hay particle lengths (short-cut and long-cut) in a 2 x 2 factorial. Diets contained alfalfa hay, corn silage, and concentrate [1:1:2, dry matter (DM) basis] fed as a total mixed ration (TMR) once per day. Samples of the 0 and 5% tallow TMR were ground and incubated in situ in polyester bags for 24 and 48 h. Ruminal samples were taken on day 21 at 0800 h and at 2-h intervals until 1600 h. The total tract digestibilities of acid detergent fiber (ADF) and neutral detergent fiber (NDF) were not affected by tallow or by hay by tallow interactions. There was a trend for tallow to improve total tract digestibility of crude protein (CP) (70.2 vs. 74.7%). After 48 h of ruminal incubation, tallow significantly decreased the digestibilities of DM, ADF, and NDF. No hay length by tallow interactions for DM, NDF, ADF or CP digestibilities occurred after 24 or 48 h. Tallow increased concentrations of propionate and decreased concentrations of acetate and valerate and the acetate-to-propionate ratio. Total volatile fatty acids increased when tallow was added to diets with short-cut hay, which suggests that when unprotected fat is added to diets with a high level of hay, a short-cut hay length may be advantageous. This result may be due to shorter rumen retention time of feed particles, which reduces the time for fatty acids to exert antimicrobial effects. Or, it may because the increased surface area of the hay particle provides more area for microbial attachment and increased fermentation.

Adipose Tissue↗
PubMed1993

Failure of a tryptophan-free amino acid mixture to modify sexual behavior in the female rat.

Female Wistar rats, weekly injected with estradiol valerate after ovariectomy, were trained to cause a sexual contact with a potent male by operating a lever. Contact-response latencies, which vary according to the nature of the sexual contact, were measured as an index of the female's sexual motivation. In these experimental conditions the administration of a tryptophan-free amino acid mixture, which has been proved to decrease brain serotonin and to enhance male mounting behavior, failed to modify the sexual motivation of the female rats.

Amino Acids↗
PubMed1982

Ruminal VFA production with steers fed whole or ground corn grain.

Ruminal production and interchange rates of volatile fatty acids (VFA) were measured for steers fed corn grain in the whole or ground form. Liquid turnover rate was 29% greater (P less than .10) with steers fed the corn in the whole form. On a molar basis (mol/100 mol), ruminal concentrations of propionate were lower while those of butyrate, 3-methyl butyrate, valerate and caproate were greater with whole than with ground corn diets. Acid production differences followed similar trends with de novo production of butyrate being seven times greater and irreversible butyrate loss three times greater with whole than with ground corn diets. Conversion of acetate to butyrate was about 70% greater with whole than with ground corn diets. This conversion far exceeded other VFA exchange rates. Outflow of VFA to the omasum was calculated to equal 20, 25 and 12% of the irreversible loss of acetate, propionate and butyrate, respectively. Ruminal output of energy as VFA from the rumen equaled 60 and 43% of consumed energy with the whole and ground grain diets, respectively. Production rates of VFA were poorly correlated with ruminal concentrations except for butyrate. Less than 10% of the labeled carbon from acetate and butyrate was detected in plasma glucose, but the transfer coefficient from propionate uncorrected for crossover of label was 59%. Gluconeogenesis from propionate alone exceeded literature estimates for basal glucose requirements of nonlactating ruminants.

Acetates↗
PubMed1987

Changes in oxidation reduction potentials and volatile fatty acid production by rumen bacteria when methane synthesis is inhibited.

Rumen inoculum was cultured in specially designed fermenters that allowed simultaneous measurement of pH, oxidation-reduction potentials, and gas production. The cultures were maintained at pH 6.8 by addition of 1 M NaHCO3 and continuous infusion of artificial saliva. Gas flow was maintained at 20.0 ml/min with a stream of O2-free N2. Monensin at 7.0 micrograms/ml inhibited CH4 production 49% below control concentrations. The sodium salt of 2-bromoethanesulfonic acid added at an initial concentration of 5 x 10(-5) M inhibited CH4 production by 86% and increased H2 production from less than .5 mumol/min in the control to 24.5 mumol/min in the inhibited fermenter. The redox potentials in the control fermenter remained above -.20 V and did not change with the addition of monensin. Bromoethanesulfonic acid rapidly decreased the redox potential in the fermenter to -.33 V. Volatile fatty acid production was not significantly altered by the addition of 2-bromoethanesulfonic acid. The addition of monensin gave the expected decrease in acetate:propionate ratios, decreased acetate and butyrate production, and increased valerate (but not propionate) production.

Alkanesulfonates↗
PubMed1994

Topical glucocorticosteroids modulate the expression of CRABP I and II in human skin differently.

Epidermal cells express two retinotic acid-binding proteins (CRABP I and II). Because CRABP II protein is strongly induced by topical retinoic acid, the respective roles of the two proteins in the pharmacological activity and toxicity of topical retinoids deserve particular attention. Since topical steroids diminish the irritation induced by retinoic acid (RA), whereas retinoic acid may counteract the atrophogenic effects of steroids, the possible interplay of both compounds in the expression of CRABP I and II appeared worth studying. We have analyzed the effects of topical application of triamcinolone acetonide (TA) on the retinoic acid-induced altered expression of CRABP I and II in normal human skin, at the protein and mRNA levels. We found that CRABP II protein and mRNA were strongly increased upon retinoic acid application: this induction was significantly inhibited by concomitant application of triamcinolone acetonide; a more potent steroid, difluocortolone valerate, was also found to diminish normal endogenous expression of CRABP II. In contrast, CRABP I protein was decreased by topical retinoic acid, and the down modulating effect of retinoic acid was counteracted by triamcinolone acetonide.

Administration, Topical↗
PubMed1977

Essential fatty acid deficient hairless mouse: a model of chronic epidermal hyperproliferation.

Epidermal DNA synthesis has been shown to be increased approximately three-fold in hairless mice that were fed a diet deficient in essential fatty acids (EFA deficient) for 65 days, compared with animals fed a standard diet. Autoradiographic labelling indices showed a 330% increase in the EFA deficient mice over controls. The animals developed evidence of a diffuse thickening, scalping and loss of elasticity of the skin after 40 days on the EFA deficient diet. Histologically, the epiderma of the EFA deficient animals showed acanthosis, hypergranulosis, hyperkeratosis and increased intracellular epidermal spaces. Increased mitotic indices were found with Feulgen staining. This is further evidence that deficiencies of essential fatty acids are associated with disturbance of normal epidermal cell proliferation and control of keratinization. A single application of topical 0.1% betamethasone valerate to EFA deficient mice reduced the epidermal DNA synthesis to that of normal diet mice. Ten percent linoleic acid topically over 2 weeks also returned epidermal DNA synthesis to normal levels.

Animals↗
PubMed1982

Organic acidurias: approach, results and clinical relevance.

More than twenty-five inherited organic acidurias have been identified during the last fifteen years. This remarkable development is due mainly to the introduction of gas chromatography, and gas chromatography combined with mass spectrometry, in paediatric laboratories for metabolic disease. The chemical approach is determined mainly by physical properties of the acid, such as their extractability and volatility. Most progress has been made with extractable acids. The techniques used for derivatization are mentioned, such as trimethylsilylation, methylation and the preparation of asymmetric derivatives for the separation of optical enantiomers. Metabolite patterns may be so characteristic that the underlying enzyme defect can be deduced. Examples are the leucine degradation defects, all encountered in the authors' laboratory: branched-chain ketoaciduria; isovaleric acidaemia; 3-methylcrotonylglycinuria; 3-methylglutaconic aciduria; and 3-hydroxy-3-methylglutaric aciduria. These abnormalities are discussed. D-glyceric aciduria is shown as an example of a not yet fully understood organic aciduria. The clinical approach varies. Metabolic acidosis is an indication for organic acid analysis in urine and plasma, but in many defects there is no acidosis, or only a transient one caused by secondary metabolites, such as lactic and 3-hydroxybutyric acids. Gas chromatography is an obligatory routine investigation in screening programmes for inborn errors of metabolism, especially for the examination of acutely ill neonates and premature babies.

Child↗