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PubMed1980

[Intracellular concentration of phenylalanine, tyrosine and alpha-amino butyric acid in 13 homozygotes and 19 heterozygotes for phenylketonuria (PKU) compared with 26 normals (author's transl)].

Intracellular concentrations for phenylalanine, tyrosine, alpha-amino butyric acid and 7 other amino acids (glycine, alanine, valin, cystin, methionine, iso-leucin, leucin) were measured in lymphocytes of 13 homozygotes and 19 heterozygotes for phenylketonuria as well as in lymphocytes of 26 normals. Intracellular concentrations for phenylalanine, tyrosine and alpha-amino butyric acid were significantly higher in homo- and heterozygotes than in normals (p less than 0,001--p less than 0,01). For the other 7 amino acids there were no or only questionable differences. Between homo- and heterozygotes there was no difference in any of the amino acids. Intracellular phenylalanine: tyrosine ratio was essentially the same in all three groups of individuals. There was no correlation between intracellular phenylalanine above or below 10 nmol/10(6) cells and IQ in heterozygotes. The same is true for phenylalanine: tyrosine ratio greater or smaller than 1. In Homozygotes there was no correlation between intracellular phenylalanine and age -- to whom DQ/IQ is correlated. There was no significant difference in intracellular phenylalanine between homozygotes with blood levels above and below 908 mumol/l (15 mg/100 ml) at the time of blood sampling and no correlation between intra- and extra-cellular phenylalanine concentrations. Among the 26 normals there were only 2 with intracellular phenylalanine above 10 nmol/10(6) cells, both showing phenylalanine loading test curves suspicious for heterozygosity. The results are discussed and important functions of the cell wall supposed. An abnormal unknown intracellular metabolite being the real noxious agent could explain the incomparably different degree of brain dysfunction in individuals with equal though elevated intracellular phenylalanine concentrations i.e. homozygotes and heterozygotes for PKU.

Aminobutyrates↗
PubMed1981

[Comparison of betamethasone and clobetasone butyrate eye drops and their effect on intraocular pressure (author's transl)].

The effect of clobetasone butyrate eye drops on ocular pressure was tested in 15 steroid responders suffering from different types of conjunctivitis and compared with betamethasone eye drops. Elevated intraocular pressure following application of 0.1% betamethasone eye drops decreased significantly within 2 weeks under medication with 0.1% clobetasone butyrate 4 times daily, whereas fellow eyes kept under treatment with betamethasone suffered further increases in IOP. The therapeutic effect and subjective compatibility of the two steroids were found to be approximately equal.

Betamethasone↗
PubMed2001

Eumovate (clobetasone butyrate) 0.05% cream with its moisturizing emollient base has better healing properties than hydrocortisone 1% cream: a study in nickel-induced contact dermatitis.

BACKGROUND: The emollient base of a topical corticosteroid, through its moisturizing properties, can be a useful treatment adjunct. OBJECTIVE: To compare the healing properties of Eumovate trade mark (clobetasone butyrate) 0.05% cream with its emollient base, hydrocortisone 1% cream and with no treatment. METHODS: A single-centre, double-blind, intra-individual, comparative study that involved 18 volunteers with nickel-induced contact dermatitis. Following a positive patch test to nickel, sub-therapeutic amounts (10 micro l = 3 mg cm(-2)) of each of the treatments were applied twice daily for seven days to each of the four test sites. RESULTS: In terms of the primary endpoint, a physician's global assessment after 7 days of treatment, clobetasone butyrate (CB) 0.05% cream showed a significantly better response than hydrocortisone (HC) 1% cream (78% vs 39%, difference -0.4, 95% CI -0.7 to -0.1; p = 0.046) or no treatment (78% vs 28%, difference -0.5, 95% CI -0.9 to -0.1; p = 0.016). CB 0.05% cream also showed a better response than its emollient base (78% vs 56%), though statistical significance was not achieved. In terms of moisturizing effects, there was no difference in transepidermal water loss (TEWL) between CB 0.05% cream and its emollient base. CB 0.05% cream treated sites did, however, have significantly lower values (i.e. were more moisturized) than untreated sites (difference -8.5, 95% CI -12.0 to -4.86; p < 0.001) or HC 1% treated sites (difference -7.1, 95% CI -11.0 to -3.4; p < 0.001). In terms of skin blanching activity, as expected the steroid-based creams achieved lower colorimetric values than the emollient base cream. CONCLUSIONS: These results from experimentally induced skin inflammation indicate that CB 0.05% (as Eumovate 0.05% cream) has both more effective anti-inflammatory activity and better moisturizing properties than hydrocortisone 1% cream and that these effects are in part due to its efficient emollient base.

Administration, Cutaneous↗
PubMed2003

Antisecretory factor peptide derivatives specifically inhibit [3H]-gamma-amino-butyric acid/36Cl- out-->in permeation across the isolated rabbit Deiters' neuronal membrane.

AIMS: Antisecretory factor (AF) is a 41-kDa protein, its main function being the regulation of intestinal ion/water transport, but it also inhibits chloride and gamma-amino-butyric acid transport across nerve cell membranes. The present experiments were designed to evaluate whether the same AF peptide sequence mediates the permeability effects seen at the nerve cell membrane and in the rat small intestine. METHODS: Four peptides were prepared by the solid phase technique with sequences derived from positions 1-51 of the full-length antisecretory factor AF and tested on nerve cell membranes isolated from rabbit Dieter cells. RESULTS: AF peptides containing the active 36-51 peptide exerted a blocking effect of the out-->in permeation of 36Cl- as well as of [3H]-gamma-amino-butyric acid. The minimal dose causing inhibition, however, varied between 10(-11) m (AF10) and 10(-7) m (AF13). The most potent peptides have been shown previously to be active in inhibiting experimental diarrhoea in vivo in small intestinal ligated loops in rats. The non-active sequence AF23-32 did not inhibit any of the two permeation markers in vitro, a result which supports the lack of activity found also in vivo. CONCLUSION: The results suggest that AF, or AF derivatives, counteract intestinal hypersecretion by blocking anion permeation across large anionic pores. Such a blocking effect could also influence the generation of action potentials in enteric nerve cells controlling the intestinal water and ion transport system.

Amino Acid Sequence↗
PubMed1981

Halogenation and topical corticosteroids: a comparison between the 17-butyrate esters of hydrocortisone and clobetasone in ointment bases.

Clobetasone butyrate 0.05% (Eumovate), a halogenated topical steroid, was compared with hydrocortison butyrate 0.1% (Locoid) which does not contain any halogen atoms. In the treatment of eczema there was not difference between the preparations, but in that of psoriasis the halogen-containing steriod was significantly more effective. Under normal circumstances neither preparation had any detectable effect on adrenal function, but with large doses under total-body polythene occlusion, circulating cortisol levels were reduced less by the halogenated than by the non-halogenated preparation. Corticosteroids which contain a halogen atom are often considered to cause more adverse effects than the non-halogenated preparations with similar clinical efficacy. This study shows that this cannot be assumed for their ability to suppress cortisol levels.

Administration, Topical↗
PubMed1981

Plasma alpha-amino-n-butyric acid/leucine ratio in alcoholics.

Fasting free amino acid concentrations in plasma of 20 control and 18 alcoholic subjects were compared in an attempt to validate previous reports that the molar ratio of alpha-amino-n-butyric acid/leucine (A/L ratio) is a marker for alcoholism. We were unable to confirm the observations of either altered alpha-amino-n-butyric acid or leucine concentrations or an increased A/L ratio in alcoholic subjects, and we conclude that the A/L ratio is not a biochemical marker for alcoholism.

Adult↗
PubMed1979

Contact allergy to hydrocortisone 17-butyrate.

Two female patients with stasis dermatitis developed allergic contact dermatitis to hydrocortisone 17-butyrate cream. Patch tests with hydrocortisone 17-butyrate were positive, but not with the vehicle. One patient was also allergic to two other commerical corticosteroids, but patch tests revealed positive reactions only to ingredients of the vehicles. Attention is drawn to the frequency of contact allergy to corticosteroids in patients with stasis dermatitis.

Dermatitis, Contact↗
PubMed1975

Oxidation of glucose and D-B-OH-butyrate by the early human fetal brain.

The isolated brains of 12 previable human fetuses obtained at 12 to 21 weeks' gestation, were perfused through the interval carotid artery with glucose (3 mM) and/or DL-B-OH-butyrate (DL-BOHB), 4.5 MM, plus tracer quantities of either glucose-6-14C (G6-14C) or beta-OH-butyrate-3-14C (BOHB3-14C). Oxidative metabolism was demonstrated by serial collection of gaseous 14CO2 from the closed perfusion system, and from the recirculating medium. Glucose and BOHB were utilized at physiological rates as indicated (mean plus or minus SEM): G6-14C at 0.10 plus or minus 0.01 mumoles/min g brain (n equal 7) or 17.5 plus or minus 1.9 mumoles/min kg fetus; and BOHB3-14C at 0.16 plus or minus 0.05 mumoles/min g (n equal to 5) or 27.3 plus or minus 7.4 mumoles/min kg. Based on fetal weight, glucose metabolism by brain apparently accounted for about 1/3 of basal glucose utilization in the fetus. On a molar basis BOHB3-14C was taken up at 1.47 times the rate of G6-14C. Both BOHB3-14C and G6 14C were converted to 14CO2. The rate of BOHB3-14C conversion to 14CO2 was equal to its rate of consumption, and exceeded the conversion of glucose to CO2 because 45% of the G6-14C was incorporated into lactate-14C. Accordingly, both substrates support oxidative metabolism by brain; and BOHB is a major potential alternate fuel which can replace glucose early in human development.

Blood Glucose↗
PubMed1981

Metabolic Activity of Fatty Acid-Oxidizing Bacteria and the Contribution of Acetate, Propionate, Butyrate, and CO(2) to Methanogenesis in Cattle Waste at 40 and 60 degrees C.

The quantitative contribution of fatty acids and CO(2) to methanogenesis was studied by using stirred, 3-liter bench-top digestors fed on a semicontinuous basis with cattle waste. The fermentations were carried out at 40 and 60 degrees C under identical loading conditions (6 g of volatile solids per liter of reactor volume per day, 10-day retention time). In the thermophilic digestor, acetate turnover increased from a prefeeding level of 16 muM/min to a peak (49 muM/min) 1 h after feeding and then gradually decreased. Acetate turnover in the mesophilic digestor increased from 15 to 40 muM/min. Propionate turnover ranged from 2 to 5.2 and 1.5 to 4.5 muM/min in the thermophilic and mesophilic digestors, respectively. Butyrate turnover (0.7 to 1.2 muM/min) was similar in both digestors. The proportion of CH(4) produced via the methyl group of acetate varied with time after feeding and ranged from 72 to 75% in the mesophilic digestor and 75 to 86% in the thermophilic digestor. The contribution from CO(2) reduction was 24 to 29% and 19 to 27%, respectively. Propionate and butyrate turnover accounted for 20% of the total CH(4) produced. Acetate synthesis from CO(2) was greatest shortly after feeding and was higher in the thermophilic digestor (0.5 to 2.4 muM/min) than the mesophilic digestor (0.3 to 0.5 muM/min). Counts of fatty acid-degrading bacteria were related to their turnover activity.

Journal Article↗
PubMed1995

Interspecies Electron Transfer during Propionate and Butyrate Degradation in Mesophilic, Granular Sludge.

Granules from a mesophilic upflow anaerobic sludge blanket reactor were disintegrated, and bacteria utilizing only hydrogen or formate or both hydrogen and formate were added to investigate the role of interspecies electron transfer during degradation of propionate and butyrate. The data indicate that the major electron transfer occurred via interspecies hydrogen transfer, while interspecies formate transfer may not be essential for interspecies electron transfer in this system during degradation of propionate and butyrate.

Journal Article↗
PubMed1988

Cloning and expression of Clostridium acetobutylicum phosphotransbutyrylase and butyrate kinase genes in Escherichia coli.

A 13.6-kilobase (kb) Sau3AI restriction endonuclease fragment of Clostridium acetobutylicum DNA cloned into pBR322 enabled Escherichia coli ato mutants to grow on butyrate as a sole carbon source (But+). Complementation of the ato defect by the recombinant plasmid pJC6 was due to expression of the genes for phosphotransbutyrylase (PTB) and butyrate kinase (BK). Both genes were efficiently expressed in E. coli, as their products were readily detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell extracts. PTB was found to have a polypeptide subunit molecular weight of approximately 31,000, while that of BK was approximately 39,000. Deletion analysis and Tn5 mutagenesis of plasmid pJC7 (a But+ subclone containing a 4.4-kb BamHI fragment from the insert of pJC6) localized the PTB and BK genes within a region spanning approximately 2.9 kb. Preliminary evidence suggests that the two genes may form an operon that is transcribed as a single unit from a promoter of clostridial origin within the 4.4-kb insert of pJC7.

Acetyltransferases↗
PubMed1988

Rapid identification of Branhamella catarrhalis with 4-methylumbelliferyl butyrate.

Branhamella catarrhalis can be distinguished from Neisseria spp. by the presence of butyrate esterase. This enzyme can be rapidly detected when 4-methylumbelliferyl butyrate is used as the substrate. All B. catarrhalis strains tested gave a positive fluorescence reaction within 5 min, while Neisseria spp. remained negative, even after 18 h of incubation.

Carboxylic Ester Hydrolases↗
PubMed1994

Comparison of three rapid methods, tributyrine, 4-methylumbelliferyl butyrate, and indoxyl acetate, for rapid identification of Moraxella catarrhalis.

Moraxella catarrhalis can easily be differentiated from other oxidase-positive, gram-negative cocci with tributyrine, 4-methylumbelliferyl butyrate, or indoxyl acetate. All M. catarrhalis give positive reactions, and all Neisseria spp. give negative reactions. The 4-methylumbelliferyl butyrate tube test and indoxyl acetate strip test provide same-day identification of M. catarrhalis isolates.

Acetylesterase↗
PubMed1980

Clinical evaluation of clobetasone butyrate: a comparative study of its effects in postoperative inflammation and on intraocular pressure.

Clobetasone butyrate, a new corticosteroid with a high topical activity, has been compared with prednisolone phosphate and a placebo in the treatment of inflammation following cataract extraction. These 2 steroids were more effective in relieving postoperative inflammation than placebo (P less than 0.05), though no obvious clinical differences between the 2 compounds emerged from this investigation. However, a single-blind comparative study against betamethasone phosphate in patients suspected of having steroid-induced glaucoma showed that, while betamethasone phosphate significantly raised intraocular pressure, clobetasone butyrate had only a minimal effect, and this difference was statistically significant (P less than 0.02).

Administration, Topical↗
PubMed1981

Clinical evaluation of clobetasone butyrate eye drops in episcleritis.

Thirty-nine patients took part in a double-blind, between-patient clinical trial to compare clobetasone butyrate, betamethasone phosphate, and placebo eye drops in the treatment of episcleritis. Although from the symptom scores the patients given placebo appeared to do as well as the other patients in the first week of treatment, they did significantly less well after this time. Clobetasone butyrate and betamethasone phosphate eye drops seemed to be equally effective in the treatment of this disease.

Anti-Inflammatory Agents↗
PubMed1981

The effect of the topical steroid clobetasone butyrate on coeliac mucosa maintained in organ culture.

The effect of the topical corticosteroid clobetasone butyrate on enzyme activity and morphology of duodenal mucosa was studied in 9 patients with coeliac disease and 10 controls using organ culture techniques. There was significant increase in mucosal alkaline phosphatase, lactase and maltase activities, but inclusion of a soluble extract of gluten reduced this effect. When clobetasone butyrate was also included in the culture medium significant elevations in enzymes were again observed. Enterocyte height was not affected by incorporation of gluten into the medium. Intra-epithelial lymphocyte counts fell significantly during the culture period. This improvement was also inhibited by gluten and overcome by addition of steroid.

Adult↗
PubMed1996

No effect of albumin on the dermal absorption rate of hydrocortisone 21-butyrate, permethrin or diflunisal in the isolated, single-pass perfused rabbit ear.

Rabbit ears were single-pass perfused with a buffer solution containing either 6% hetastarch or 5% bovine serum albumin. Hydrocortisone 21-butyrate (5 mM), diflunisal (17 mM) or permethrin (33 mM) was added to isopropyl myristate with 5% polyethylene, and applied to about 40% of the epithelial surface area of the ear. Hydrocortisone 21-butyrate or permethrin were not found in the effluent with hetastarch or albumin. Following cutaneous ester hydrolysis, the appearance rate of hydrocortisone was about 4 pmol/min per cm2 in the hetastarch- or the albumin-containing buffer solution. No hydrolysis of permethrin was detected; the appearance rate of 3-phenoxybenzyl alcohol with 3-phenoxybenzoic acid corresponded to the absorption rate of the substrate impurities. During ex vivo perfusion of intact skin, serum albumin in the perfusion fluid may not enhance the appearance rate of xenobiotics in the effluent following dermal application when the distribution coefficient n-octanol/water is > 2,000 or when the xenobiotic is ionized at physiological pH. In general, for all substances investigated with our perfusion model thus far, the appearance rates decreased with rising distribution coefficient (n-octanol/buffer pH 7.4). High lipophilicity hinders the release from isopropyl myristate and the penetration through the skin.

Administration, Cutaneous↗
PubMed1976

Systemic effects and percutaneous absorption of topically applied 0.1% hydrocortisone 17-butyrate.

The systemic effects of topically applied 0.1% hydrocortisone 17-butyrate during treatment with and without occlusion were measured in terms of the functions of the pituitary-adrenal axis. Corticosteroid levels in the blood were determined by the modified method of MURPHY, a competitive protein-binding radioassay. Circulating eosinophils were counted and the urinary 17-OHCS and 17-KS excretion were also determined. Percutaneous absorption following the topical application of 14C hydrocortisone 17-butyrate 1 (HC 17-B, Locoid) was measured by means of autoradiography. The application of the corticosteroid to the normal skin without occlusion did not induce systemic effects, whilst the application of the drug under occlusive dressing showed that systemic effects may possibly be induced. The number of circulating eosinophils, corticosteroid levels in the blood and urinary 17-OHCS excretion all decreased. However, these values returned to normal about 2 days after the withdrawal of the application, so we consider the systemic effect induced by the topical corticosteroid to be of a temporary nature. The percutaneous absorption of the corticosteroid was proved by an autoradiographic technique using 14C-labelled HC 17-B. At various intervals after the application, radioactive substances were observed as silver grains in the horny layer of the epidermis and skin appendages, and the density of the silver grains gradually increased with the course of time. It may be surmised that locally applied HC 17-B will be retained in the horny layer of the epidermis at a very early stage after the application and then absorbed in the blood via the epidermis and skin appendages. The reservoir of the corticosteroid in the skin was demonstrated 24 h after the withdrawal of the application.

17-Hydroxycorticosteroids↗