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At least 1,153 records · Page 64Linked to original sources
PubMed1980

A possible rôle for acid phosphatase in gamma-amino-n-butyrate uptake in Aspergillus nidulans.

Previously published work from another laboratory has shown that the mutation pacC-5 in the ascomycete Aspergillus nidulans leads to loss of an acid phosphatase (EC 3.1.3.2) activity and is probably located in the structural gene for this enzyme. Here, we show that, pleiotropically, pacC-5 considerably reduces gamma-amino-n-butyrate transport levels as shown both by direct uptake measurements and two kinds of growth tests. A reduction in expression of the permease specified by the gabA gene is almost certainly responsible for the gamma-amino-n-butyrate uptake defect in pacC-5 strains. pacC-5 does not reduce L-proline uptake, mainly mediated by the prnB permease, or beta-alanine uptake. This work and our previously published results suggest that, although it does not uniquely reduce gamma-amino-n-butyrate uptake, pacC-5 is highly selective in its effects on transport processes. It is therefore probable that the acid phosphatase specified by the pacC gene plays some rôle in the synthesis, membrane integration or functioning of a particular class of permeases. A rôle for acid phosphatases in membrane processes casts an intriguing new light on the fact that these enzymes are periplasmic and extracellular in many micro-organisms including A. nidulans.

Acid Phosphatase↗
PubMed2003

Clinical and pharmacologic study of tributyrin: an oral butyrate prodrug.

PURPOSE: Butyrate is a small polar compound able to produce terminal differentiation and apoptosis in a variety of in vitro models at levels above 50-100 microM. Previously our group demonstrated that daily oral administration of the prodrug, tributyrin, is able to briefly achieve levels >100 microM. Given in vitro data that differentiating activity requires continuous butyrate exposure, the short t1/2 of the drug and a desire to mimic the effects of an intravenous infusion, we evaluated a three times daily schedule. PATIENTS AND METHODS: Enrolled in this study were 20 patients with advanced solid tumors for whom no other therapy was available, had life expectancy greater than 12 weeks, and normal organ function. They were treated with tributyrin at doses from 150 to 200 mg/kg three times daily. Blood was sampled for pharmacokinetic analysis prior to dosing and at 15 and 30 min and 1, 1.5, 2, 2.5, 3, 3.5 and 4 h thereafter. RESULTS: The patients entered comprised 15 men and 5 women with a median age of 61 years (range 30-74 years). Prior therapy regimens included: chemotherapy (median two prior regimens, range none to five), radiation therapy (one), no prior therapy (one). There was no dose-limiting toxicity. Escalation was halted at the 200 mg/kg three times daily level due to the number of capsules required. A median butyrate concentration of 52 microM was obtained but there was considerable interpatient variability. No objective responses were seen. There were four patients with prolonged disease stabilization ranging from 3 to 23 months; median progression-free survival was 55 days. Two patients with chemotherapy-refractory non-small-cell lung cancer had survived for >1 year at the time of this report without evidence of progression. CONCLUSION: Tributyrin is well tolerated and levels associated with in vitro activity are achieved with three times daily dosing.

Administration, Oral↗
PubMed1979

Changes in amniotic fluid glucose, beta-hydroxy-butyrate, glycerol, and lactate concentration in diabetic pregnancy.

Amniotic fluid glucose, beta OH butyrate, glycerol, and lactate concentrations were measured in 75 samples collected in the third trimester of pregnancy from 50 diabetic patients, all but four of whom required insulin. Increases in maternal fasting plasma sugar were accompanied by corresponding increases in amniotic fluid glucose and on occasion increases in amniotic fluid beta OH butyrate. These data correspond to previous reports of placental glucose transfer and in addition, provide statistically significant evidence of placental betaOH butyrate transfer since the hyperglycemic, hyperinsulinemic fetus of a diabetic mother would be a poor primary source for ketogenesis. Relatively poor correlation of elevated fluid levels of these solutes to fetal outcome probably reflects a low incidence of maternal hyperglycemia, ketogenesis. Relatively poor correlation of elevated fluid levels of these solutes to fetal outcome probably reflects a low incidence of maternal hyperglycemia, ketoacidosis, and over-all reduced neonatal morbidity-mortality rates in this group of metabolically well-controlled, predominantly insulin-requiring diabetic patients managed in a regional high-risk perinatal center.

Adult↗
PubMedDate not supplied

Effects of spermine and sodium butyrate on the in vitro phosphorylation of HMG non-histone proteins of the liver of young and old rats.

The in vitro phosphorylation of high mobility group (HMG) proteins and its modulation by spermine and sodium butyrate were studied in the liver of young (15 week) and old (138 week) male rats. Except HMG 1 which remained unchanged, the phosphorylation of other proteins (HMG 2, 14 and 17) decreased drastically in old age. Spermine stimulated the phosphorylation of HMG 1 and 17 in young but HMG 1, 2 and 14 in old rats. The incorporation of (32)P into total HMG proteins was enhanced by butyrate in the liver of both ages. However, the degree of stimulation was higher in young rats. Particularly, the HMG 1 and 17 of young and HMG 2 and 17 of old rats showed increased phosphorylation. Furthermore, butyrate also inhibited the phosphorylation of HMG 2 in young and HMG 1 and 14 in old rats. Such alteration in the phosphorylation of major HMG proteins modulates their interaction with DNA and other components of chromatin. This may account for changes in the higher order organization of chromatin and expression of genes during aging.

Journal Article↗
PubMed2004

Beta-hydroxy-butyrate alters the extracellular content of S100B in astrocyte cultures.

Astrocytes have a variety of roles in maintaining neural tissue physiology, including energetic support, uptake and metabolism of glutamate and secretion of neurotrophic factors. Glutamate toxicity has been implicated in neurodegenerative disorders associated with conditions related to energy failure, and to elevation of glutamate extracellular levels in brain. Glucose is the main energetic substrate for brain cells but, in some circumstances, the ketone bodies are used as a supplementary source and have been suggested to be neuroprotective agents against seizure disorders. Here, we investigate some possible biochemical changes in astrocyte cultures induced by beta-hydroxy-butyrate, the predominant blood ketone body. Its effect upon S100B secretion, astrocyte morphology and glutamate uptake was particularly investigated. S100B, a calcium-binding protein expressed and secreted by astrocytes, has neurotrophic activity and a possible role in epileptogenesis. Cell morphology was investigated by phase-contrast microscopy and immunocytochemistry for actin, GFAP and S100B. Our data show that beta-hydroxy-butyrate induces dramatic changes in astrocyte morphology and, independent of this, causes changes in the extracellular content of S100B. We observed an increment in S100B 1 h after beta-hydroxy-butyrate addition and a decrease 24 h later. No changes were observed in glutamate uptake. These astrocytic modifications may be associated with reduced neuronal excitability observed in the ketogenic condition.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

Heritability estimates for octyl acetate and octyl butyrate in the mature fruit of the wild parsnip.

The aliphatic esters octyl acetate and octyl butyrate occur as major components of essential oils in the vittae, or oil tubes, of the wild parsnip (Pastinaca sativa). We determined phenotypic variation and narrow-sense heritabilities of these octyl esters in wild parsnip fruits from 30 maternal families. The mean octyl acetate content was 1.56 microg/mg dry fruit (0.08-5.51 microg/mg dry fruit) and the mean octyl butyrate content was 4.28 microg/mg dry fruit (1.28-14.22 microg/ mg dry fruit). Narrow-sense heritabilities for each ester's content were calculated by analysis of half-sib families (HS) and parent-offspring regression (OP). Heritabilities were 0.389 (HS) and 0.654 (OP) for octyl acetate and 0.670 (HS) and 0.626 (OP) for octyl butyrate. The amounts of the esters were phenotypically correlated with each other and with the linear furanocoumarins bergapten and xanthotoxin, phototoxic compounds that co-occur in the vittae with the esters. Ester amounts were not genetically correlated, indicating that these compounds could respond independently to selection pressures. These octyl esters may serve as carrier solvents that enhance penetration of these furanocoumarins into herbivore integuments and gut walls.

Acetates↗
PubMed1976

The effect of clobetasone butyrate and other topical steroids on skin thickness of the domestic pig.

A new glucocorticoid, clobetasone butyrate, has been shown in patients to have good topical anti-inflammatory activity and a minimal effect on hypothalamic-pituitary-adrenal function. Among a group of topically active corticosteroids, compared in a controlled study in the domestic pig, clobetasone butyrate is shown to cause less epidermal thinning than any of the others except only 1% hydrocortisone. This evidence of a lesser atrophogenic effect may indicate further dissociation of unwanted from wanted properties in clobetasone butyrate.

Administration, Topical↗
PubMed1981

A clinical comparison of topical clobetasone butyrate and sodium cromoglycate in allergic conjunctivitis.

Clobetasone butyrate (0.1%), a new topical corticosteroid eye preparation for the treatment of ocular inflammation, has been compared with sodium cromoglycate (2%) eye drops in thirty-nine patients experiencing allergic conjunctivitis during the hay fever season. In this double-blind, within-patient comparative study both preparations were effective in relieving the patients' symptoms of conjunctivitis. However, clobetasone butyrate was clinically more effective than sodium cromoglycate as determined by symptom score card analysis (P less than 0.01) and the patients' overall assessment of treatment (P less than 0.05). Patients' preference for the treatment of seasonal allergic conjunctivitis was markedly in favour of clobetasone butyrate (P less than 0.001).

Adolescent↗
PubMed1984

Alclometasone dipropionate cream 0.05% versus clobetasone butyrate cream 0.05%. A controlled clinical comparison in the treatment of atopic dermatitis in children.

A randomized, double-blind, parallel-group study was conducted comparing the efficacy and safety of alclometasone dipropionate cream 0.05% and clobetasone butyrate cream 0.05% in the treatment of atopic dermatitis in 43 children. The medications were applied to study areas as a thin layer of cream twice daily for 2 weeks. Efficacy was assessed by evaluation of three disease signs (erythema, induration, and pruritus) and by mean of a physician's global evaluation following treatment. Safety was evaluated through patient-reported and clinically observed adverse experiences. Both treatments were effective. At the end of the trial, average reduction in disease signs was 85% for alclometasone dipropionate-treated patients and 86% in the clobetasone butyrate-treated group. In the global evaluation, the physician rated symptoms as cleared in 9 of 22 alclometasone dipropionate-treated patients and in 10 of 21 clobetasone butyrate-treated patients.

Administration, Topical↗
PubMed1981

Formation of N,N-Dimethylglycine, Acetic Acid, and Butyric Acid from Betaine by Eubacterium limosum.

Two bacterial strains that grow anaerobically on betaine were isolated from enrichment cultures and identified as strains of Eubacterium limosum. In a mineral medium supplemented with yeast extract and Casitone, the doubling time of E. limosum strain 11A on betaine was 6 h at 37 degrees C. The molar growth yield amounted to 9 g of dry cell mass per mol. Betaine was fermented in accordance with the following equation: 7 betaine + 2 CO(2) --> 7 N,N-dimethylglycine + 1.5 acetate + 1.5 butyrate. E. limosum also grew on methanol and choline. The former was converted to acetate and butyrate, and the latter was converted to N,N-dimethylethanolamine, acetate, and butyrate. The conditions for the quantitative determination of N,N-dimethylglycine by capillary tube isotachophoresis have been determined.

Journal Article↗
PubMed1986

Quantitative influences of butyrate or propionate on thermophilic production of methane from biomass.

Sodium butyrate and sodium propionate were continuously infused into separate 4-liter thermophilic digesters. These digesters were operated at 55 degrees C, had a retention time of 20 days, and had a pH of 7.8. Infusion rates were started at 10 mM day and were increased incrementally when new stable external organic acid pool sizes and new stable gas production rates were observed. Stable conditions were obtained in both digesters at an infusion rate of 15 mM day, with methanogenesis elevated over that of control digesters. Calculations based on expected CH(4) at this infusion rate and measured CH(4) production in the treated and control digesters, however, showed an approximately 25% inhibition of methanogenesis in both digesters. A digester infused with sodium chloride showed little or no inhibition at this infusion rate, but was totally inhibited when its infusion rate was increased to 20 mM day, and cumulative added NaCl reached 0.38 M. The butyrate and propionate-amended digesters tolerated addition rates of 20 mM day, but both failed when they were increased to 25 mM day. These results indicate that the thermophilic digesters could function stably at higher external pool sizes of butyrate or propionate than routinely observed.

Journal Article↗
PubMed1993

Inhibition of Butyrate Oxidation by Formate during Methanogenesis.

A mixed methanogenic culture fed with glucose was perturbed with butyrate and formate to investigate the role of formate in the acetogenesis of butyrate. A free energy analysis suggests that formate rather than H(2) was the interspecies electron carrier for butyrate conversion into acetate for the culture studied.

Journal Article↗
PubMed1981

Clinical evaluation of clobetasone butyrate eye drops in the treatment of anterior uveitis and its effects on intraocular pressure.

Clobetasone butyrate has been formulated as a new steroid preparation of use in ophthalmology and has been compared with prednisolone phosphate and betamethasone phosphate in the treatment of anterior uveitis. The results from 4 double-blind, between-patient studies have shown that all 3 treatments are effective in reducing the signs and symptoms of this intraocular disease. 87% of those patients receiving clobetasone butyrate had a good or satisfactory response, but no differences in therapeutic efficacy were observed between these 3 steroid treatments. Clobetasone butyrate had little effect on intraocular pressure when compared with dexamethasone or hydrocortisone, both of which cause a significant rise in intraocular pressure.

Adolescent↗
PubMed1983

Concentration of clobetasone butyrate in aqueous humour.

The concentrations of clobetasone butyrate and betamethasone were measured in aqueous humour of patients undergoing cataract extraction 12.5 to 18.5 hours after application into the lower conjunctival sac of an ointment containing 0.1% of the steroid. Samples were assayed from 10 patients receiving clobetasone butyrate and 13 patients receiving betamethasone phosphate. There were measurable concentrations in only 2 samples in the former group, and both were 0.1 ng/ml. In the betamethasone group measurable concentrations were found in 11 samples, and the concentrations ranged from 0.5 to 20.3 ng/ml, with the highest concentrations between 12.5 and 13.5 hours after application. The concentration of betamethasone in the aqueous humour decreased by about 90% in the 6 hours from 12.5 to 18.5 hours after application. It is speculative as to whether it is these differences in pharmacokinetic behaviour, or other differences in biological or physicochemical properties, which are responsible for the minimal effect on intraocular pressure induced by clobetasone butyrate compared with betamethasone.

Aged↗
PubMed1975

Clobetasone butyrate, a new topical corticosteroid: clinical activity and effects on pituitary-adrenal axis function and model of epidermal atrophy.

Clobetasone butyrate is a new corticosteroid, selected for study because of its combination of good activity in the vasoconstriction test and low systemic activity in animals. Formulated as an 0.05% ointment and cream (Molivate) it was clinically effective in patients with eczema, its activity being significantly greater than that of hydrocortisone 1% or fluocortolone 0.2% (Ultradil). Under conditions that predispose to maximal percutaneous absorption clobetasone butyrate ointment had minimal effect on hypothalamic-pituitary-adrenal function. In an animal model of cutaneous atrophy it caused less thinning of the epidermis than steroids other than hydrocortisone. Clobetasone butyrate 0.05% ointment and cream gave every indication of offering clinically effective topical anti-inflammatory activity with a wide margin of safety.

Administration, Topical↗
PubMed1987

Domoprednate, a new nonhalogenated topical steroid: comparison to hydrocortisone butyrate.

Thirty-nine patients with mainly psoriasis vulgaris and atopic dermatitis were treated for 4 weeks with 0.1% domoprednate and hydrocortisone butyrate ointment according to a right-left, randomized design. Various assessments of efficacy only revealed marginal, but statistically insignificant differences. Patients' preferences for one of the two treatment favored domoprednate in 20 cases and hydrocortisone butyrate in 12 cases; 6 cases were ties (p greater than 0.2). The efficacy of domoprednate, a new, nonhalogenated topical steroid, is evidently at least of the same order as that of the hydrocortisone butyrate, and the tolerance of the two ointments is equally good.

Administration, Topical↗
PubMed1976

Effect of hydrocortisone 17-butyrate on the percutaneous absorption of antibiotics.

Abrption of antibiotics from combined preparations containing oxytetracycline, chlortetracycline, doxycycline or gentamicin and hydrocortisone 17-butyrate into the skin of rats was examined. The penetration of antibiotics from the ointment into the skin was inhibited by 0.2% hydrocortisone 17-butyrate to a significant degree. It is suggested that this effect of hydrocortisone 17-butyrate is the consequence of its vasoconstrictor action.

Administration, Topical↗
PubMed1997

Pyrrole butyric acid derivatives as inhibitors of steroid 5 alpha-reductase.

A series of pyrrole butyric acid derivatives was synthesized and evaluated for inhibitory activity on human and rat steroid 5 alpha-reductase in vitro and ex vivo. 3-Benzoyl-4-alkylpyrrole-1-butyric acids and 1-methyl-2-alkyl-3-benzoylpyrrole-5-butyric acid derivatives were effective inhibitors. Structure activity relationships were evaluated among the 37 compounds synthesized. Compound 37 (HQL-1069) shows potent inhibitory activities against both rat and human 5 alpha-reductase.

5-alpha Reductase Inhibitors↗