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PubMed1999

Effects of a Saccharomyces cerevisiae culture on in vitro mixed ruminal microorganism fermentation.

Previous research has shown that Saccharomyces cerevisiae culture increases lactate utilization and cellulose digestion by pure cultures of ruminal bacteria. Based on these pure culture results, in vitro mixed ruminal microorganism fermentations were conducted to determine the effects of 0.35 and 0.73 g/L of Sacc. cerevisiae culture on the fermentation of ground corn, maltose, alfalfa hay, bermudagrass hay, and lactate. In addition, experiments were performed to evaluate the effects of Sacc. cerevisiae culture and monensin on the mixed ruminal microorganism fermentation. In the presence of ground corn, both concentrations of Sacc. cerevisiae culture had little effect on final pH or fermentation products, except the 0.35 g/L treatment increased valerate concentration. Saccharomyces cerevisiae culture had little effect on final pH or fermentation products in maltose or lactate fermentations. When alfalfa hay was the substrate, 0.73 g/L of Sacc. cerevisiae culture increased propionate concentration and both treatments decreased the acetate to propionate ratio. In the case of Coastal bermudagrass hay, 0.73 g/L Sacc. cerevisiae culture increased concentrations of acetate, propionate, CH4, butyrate, isovalerate, valerate, and decreased the acetate to propionate ratio, whereas both treatments increased total volatile fatty acid concentrations. Similar to alfalfa hay, in vitro dry matter disappearance of Coastal bermudagrass hay was numerically increased in the presence of Sacc. cerevisiae culture. Monensin altered the fermentation by decreasing concentrations of CH4 and lactate and increasing concentrations of propionate. There was no interaction between Sacc. cerevisiae culture and monensin. In conclusion, the incorporation of Sacc. cerevisiae culture into mixed ruminal microorganism fermentations of ground corn, maltose, or lactate had little effect on final pH and fermentation products. However, in the presence of alfalfa hay or Coastal bermudagrass hay Sacc. cerevisiae culture increased concentrations of several fermentation products and numerically increased in vitro dry matter disappearance of forage fiber.

Acetates↗
PubMed1992

Topical glucocorticoids of the non-fluorinated double-ester type. Lack of atrophogenicity in normal skin as assessed by high-frequency ultrasound.

With the advent of non-fluorinated double esters the spectrum of topical dermatotherapy with glucocorticoids seems to have broadened to include safer congeners. To assess the atrophogenicity potential of glucocorticoids, high-frequency ultrasound has been proposed. In a comparative trial using the DUB 20 system, 24 healthy volunteers applied hydrocortisone aceponate, the corresponding vehicle, prednicarbate ointment and betamethasone-17-valerate ointment over a period of 6 weeks. While both hydrocortisone aceponate and prednicarbate ointment induced no significant reduction in skin thickness, the onset of epidermal-dermal thinning with betamethasone-17-valerate was early and the extent marked. These findings imply an increased therapeutic index with the non-fluorinated double esters.

Administration, Topical↗
PubMed1976

Serum concentrations of individual monocarboxylic short-chain fatty acids C2-C6 in underweight children.

The serum concentrations of individual short-chain fatty acids containing 2-6 carbon atoms were studied in 12 underweight children. Mean n-butyric and iso-valeric acid levels were significantly elevated in underweight children, while those of n-valeric and iso-caproic acids were not significantly higher than in the control group. The level of total free fatty acids was also increased in the underweight group. A reduced enzymatic activity in fatty acid synthesis is supposed to be the factor underlying the impaired lipogenesis.

Adolescent↗
PubMedDate not supplied

[Corticotherapy and mucocutaneous pathology].

The tremendous advances in treatment brought about by corticotherapy applied to cutaneo-mucosal pathology should not be allowed to obscure the fact that its action is merely palliative, that it should only be proceeded with after careful diagnosis and that it may trigger undesirable side-effects. General corticotherapy is definitely indicated in certain serious dermatoses (e.g. pemphigus vulgaris) in large doses at the beginning of the course of treatment which often has to be kept up indefinitely; it is in these patients that the most serious accidents occur. It is also indicated in other dermatoses (e.g. lichen planus) in smaller doses and in separate courses, generally triggering incidents and accidents of a less serious nature which to a certain extent seem to be attenuated by taking the drug on alternate days. It is counter-indicated in one particular condition: psoriasis. Corticotherapy by intra- and sub-lesional local injection is most useful in the treatment of certain localised skin lesions (e.g. cheloids) and of the oral mucosa (e.g. erosive lichen planus). Either a few drops are injected or a larger quantity in a suspension of microcrystals. Complications have sometimes been observed in the skin (leukoderma, dermoepidermatrophia and, particularly, amaurosis), but never so far after sub-mucosal injections. Local corticotherapy by external application, very widely used in the form of ointments, creams and lotions for numerous cutaneous conditions may cause various more or less serious local side-effects, the systemic effects with depression of the hypophyso-adrenal axis, only seem to occur to any extent with occlusive dressings. It can also be used in the treatment of some conditions of the oral mucosa (e.g. some forms of lichen planus, benign mucous membrane pemphigoid) by means of either a corticosteroid incorporated into a special excipient which adheres to the mucous membrane or in tablets of 17-betamethasone valerate which gradually break up in the saliva. With the usual posology of 10 tablets of 0.1 mg per day, even over several months, there are no systemic effects, 17-betamethasone valerate (unlike phosphate) having an action which is primarily topic and being practically unabsorbed as has been shown by assessment of plasmatic cortisol.

Administration, Topical↗
PubMed2000

Topical corticosteroid in foam vehicle offers comparable coverage compared with traditional vehicles.

BACKGROUND: A new preparation of betamethasone valerate in a novel foam vehicle is available for treatment of scalp dermatoses. The vehicle spreads between hair until it reaches the scalp, where it melts and delivers the active drug. Solids make up only a tiny fraction of the foam vehicle, leaving no apparent residue on the skin or hair. The uniqueness of this vehicle raises the question of how to compare it with other topical corticosteroid preparations. OBJECTIVE: The purpose of this study was to determine the equivalency of a given quantity of the foam product to quantities of drugs in conventional vehicles. METHODS: The number of fingertip units (FTUs) per gram and the area of coverage of an FTU of betamethasone valerate foam vehicle were determined and compared with those of cream, lotion, gel, and solution psoriasis treatments. RESULTS: The weight of an FTU of foam vehicle was 52.5 +/- 5.7 microg. There were 9 to 12 times as many FTUs in 100 g of vehicle foam as in 100 g of cream or gel and 2.3 to 2.8 times as many as in 100 g of lotion or solution. The area covered by an FTU of foam vehicle was less than the area covered by an FTU of cream or gel. CONCLUSION: The characteristics of foam vehicle are different from those of other vehicles. The greater number of FTUs in 100 g of foam vehicle made up for the lower coverage per FTU, such that total coverage area for 100 g of foam vehicle was comparable to the coverage area for 100 g of the drugs in traditional vehicles.

Administration, Topical↗
PubMedDate not supplied

In vivo inhibition of chicken brain acetylcholinesterase and neurotoxic esterase in relation to the delayed neurotoxicity of leptophos and cyanofenphos.

An equimolal single dose (1 mmole/kg) of leptophos or cyanofenphos was given orally to chickens to assay the clinical and biochemical neurotoxic effects of these two organophosphorus insecticides. Parathion and TOCP at 2 and 1000 mg/kg of chicken body weight were tested in the same manner as negative and positive neurotoxicants, respectively. Three birds of each of five groups tested were sacrificed 1,2,3,7,14,21 and 28 days after treatment and the brains were taken for the biochemical tests. Acetylcholinesterase (AChE) and neurotoxic esterase (NTE) activities were determined in the brain microsomal fractions. In addition, the AChE activity in the brain soluble fractions was measured. Clinical observations indicated that leptophos-, cyanofenphos- and parathion-treated chickens became acutely poisoned but recovered from the typical cholinergic signs in a day or two. However, about 10 to 15 days later leptophos- and cyanofenphos-treated chickens developed the characteristic leg weakness and unrecoverable ataxia seen in birds given TOCP. The biochemical results indicated that cyanofenphos followed by leptophos and parathion produced more in vivo AChE inhibition than that produced by TOCP in both chicken brain soluble and microsomal fractions. Results suggested that there are no correlations between the in vivo effect of TOCP, leptophos and cyanofenphos on AChE and phenyl valerate-total hydrolyzing activities and the ability of these chemicals to produce neuropathy in hens. The results obtained from this study of the in vivo effect of the tested compounds on chicken brain NTE activity present an acceptable correlation between the inhibition of this enzyme and the ability of these chemicals to induce neuropathy. The mechanism and explanation for this correlation are presented. The in vivo effect of the tested compounds on the chicken brain NTE activity was determined using the indirect and a new direct method. The data presented in this report suggested that the new direct technique of assaying NTE activity using 4-nitrophenyl valerate (4-NPV) as substrate, can be useful in the in vivo screening studies of organophosphates for their ability to induce neuropathy in hens.

Acetylcholinesterase↗
PubMed1977

Clinical investigation of halopredone acetate, a new topical steroid, in dermatology. Controlled study.

17,21-Bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate; Topicon) cream, a new synthetic corticosteroid for topical use, has been evaluated against betamethasone valerate by means of double-blind sequential study, where the patients, mainly affected with psoriasis, presented symmetrically located lesions which were treated with either the new drug or the reference cream so that each patient could serve as his own control. Activity and tolerability of the two preparations were equivalent. This equivalence is particularly significant when bearing in mind that the concentration of the active principle (0.01%) contained in the halopredone acetate cream is one of the lowest employed so far and 10 times lower than that of the reference steroid (betamethasone valerate 0.1%). A second open trial, made in 30 patients suffering from psoriasis, confirmed the positive anti-inflammatory properties which the new substance had already displayed during the previous pharmacological tests.

Administration, Topical↗
PubMed1978

Dose-dependent effect of topical corticosteroids on blood flow in human cutaneous tissue.

In seven healthy subjects the dorsum of the hand was treated with beta-methasone valerate cream in increasing concentrations, from 0.1 to 1.0%, and with hydrocortisone butyrate 0.1% with or without plastic occlusion. Under conditions of controlled room temperature, blood flow in treated, placebo-treated, and untreated cutaneous tissue was measured using the local 133Xenon wash-out technique. Placebo creams did not affect cutaneous blood flow, but beta-methasone valerate 0.1% reduced blood flow and 1.0% increased it. An increase in blood flow was also observed after use of hydrocortisone butyrate under plastic occlusion. The results indicate a dual effect of potent corticosteroids on cutaneous blood flow.

Administration, Topical↗
PubMed1993

Mometasone versus betamethasone creams: a trial in dermatoses.

AIM: To compare the efficacy and safety of mometasone furoate cream 0.1% applied daily versus betamethasone valerate cream 0.1% applied twice daily in a variety of dermatoses. METHODS: A 4 week study was undertaken of patients with at least moderately severe dermatoses as judged by scoring of a target lesion. Weekly global improvement was assessed, as well as change in target lesion scores. Local side effects were noted including observation of atrophy. RESULTS: Fifty eight patients in three centres completed the study, 30 in the betamethasone group and 28 in the mometasone. There was no difference in demographic variables or disease severity in each group or any difference between the three investigator gradings of initial severity. There was a rapid onset of improvement in both groups by day seven (scores being reduced by 72% in the betamethasone group and 65% in the mometasone group). By the fourth week visit there was 90% reduction in the betamethasone group score and 93% in the mometasone. There was no significant difference between the groups. CONCLUSION: Mometasone furoate cream 0.1% applied daily in dermatoses is as effective as betamethasone valerate 0.1% cream. Both creams had rapid onset of action and had no signs of atrophy. Better patient compliance could be expected with the convenience of mometasone cream being applied daily.

Administration, Cutaneous↗
PubMed2006

Rapid determination of short-chain fatty acids in colonic contents and faeces of humans and rats by acidified water-extraction and direct-injection gas chromatography.

Short-chain fatty acids (SCFAs) have attracted much attention recently because of their positive physiological effects. In this work, a rapid and reliable gas chromatographic method for determination of eight SCFAs, in colonic and faecal samples from rats and humans has been developed and validated. The methodology involves extraction of the SCFAs in water before a direct injection procedure on a FFAP capillary column. A stock standard solution containing acetic acid, propionic acid, n-butyric acid, i-butyric acid, n-valeric acid, i-valeric acid, n-caproic acid and n-heptanoic acid was prepared and used. A high linearity (r2 > 0.9990), low quantification limit (2.38-30.14 microm) and high recovery for most acids were obtained. Acidification of faecal samples was found to be crucial for quantitative determination of the SCFAs, and adjustment of pH to 2-3 was regarded as necessary. Glass wool inserted in the glass liner of the injection port proved effective in preventing the contamination of the column by non-volatiles, and 12% formic acid reduced the ghost peak that appeared gradually after several injections. After validation, the methodology was applied on two faecal samples from rats fed diets containing different amount of dietary fibre and one faecal sample from human fed a normal diet to test the accuracy of the developed method.

Adult↗
PubMed1994

Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products.

Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS)

Biodegradation, Environmental↗
PubMed1993

Tissue response and in vivo degradation of selected polyhydroxyacids: polylactides (PLA), poly(3-hydroxybutyrate) (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/VA).

The tissue response and in vivo molecular stability of injection-molded polyhydroxyacids--polylactides (PLA), poly(3-hydroxybutyrate) (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/VA, 5-22% VA content)--were studied. Polymers were implanted subcutaneously in mice and extirpated at 1, 3, and 6 months in order to study tissue response and polymer degradation. All polymers were well tolerated by the tissue. No acute inflammation, abscess formation, or tissue necrosis was observed in tissues adjacent to the implanted materials. Furthermore, no tissue reactivity or cellular mobilization was evident remote from the implant site. Mononuclear macrophages, proliferating fibroblasts, and mature vascularized fibrous capsules were typical of the tissue response. Degradation of the polymers was accompanied by an increase in collagen deposition. For the polylactide series, the inflammatory response after 1 month of implantation was less for materials containing the D-unit in the polymer chain, whereas in the case of the polyhydroxybutyrate/valerates, the number of inflammatory cells increased with increasing content of the valerate unit in the polymer chain. Between 1-3 months, there was slightly more tissue response to the PHB and PHB/VA polymers than to PLA. This response is attributed to the presence of leachable impurities and a low molecular weight soluble component in the polyhydroxybutyrate/valerates. At 6 months, the extent of tissue reaction was similar for both types of polymers. All polylactides degraded significantly (56-99%) by 6 months. For a poly(L-lactide) series, degradation rate in vivo decreased with increasing initial molecular weight of the injection-molded polymer. Several samples showed pronounced bimodal molecular weight distributions (MWD), which may be due to differences in degradation rate, resulting from variability in distribution of crystalline and amorphous regions within the samples. This may also be the result of two different mechanisms, i.e., nonenzymatic and enzymatic, which are involved in the degradation process, the latter being more extensive at the later stage of partially hydrolyzed polymer. The PHB and PHB/VA polymers degraded less (15-43%) than the polylactides following 6 months of implantation. Generally, the polymer with higher valerate content (19%, 22%) degraded most. The decrease in molecular weight was accompanied by a narrowing of the MWD for PHB and copolymers; there was no evidence of a bimodal MWD, possibly indicating that the critical molecular weight that would permit enzyme/polymer interaction had not been reached. Weight loss during implantation ranged from 0-50% for the polylactides, whereas for the PHB polymers weight loss ranged from 0-1.6%.

Absorption↗
PubMed1979

Corticosteroid determination in skin preparations by a reaction rate method.

A reaction rate method for the determination of beta-methasone, betamethasone valerate, triamcinolone acetonide, and fluocinolone acetonide is described. The method is based on a modification of the widely accepted blue tetrazolium reaction. Analysis times of 30--70 sec are required. Relative standard deviations of 0.3--1.9% are obtained, and the analytical working curves are linear. Analysis of pharmaceutical skin preparations by the new method gave results that correlated well with the time-consuming standard equilibrium method. Analysis of betamethasone and betamethasone valerate mixtures by measuring absorbance values at two different times was performed also.

Administration, Topical↗
PubMed1983

Effect of fatty acids on the membrane fluidity of cultured chick dorsal root ganglion measured by fluorescence photobleaching recovery.

The effect of fatty acids on the membrane fluidity in tissue cultured chick embryo dorsal root ganglion was studied by fluorescence recovery method. Lateral motion of the lipid was measured by observing the fluorescent probe, 5-(octadecylthiocarbamoylamino) fluorescence, F18. The effective lateral diffusion coefficient of the membrane was around 0.30 X 10(-8) cm2/sec in control cells, 0.42 X 10(-8) cm2/sec in 2-decenoic acid treated cells, and 0.35 X 10(-8) cm2/sec in valeric acid treated cells. From these results it is concluded that effective mobilities of the membrane complex increased about 40% by the external application of 2-decenoic acid, while valeric acid increased it only 12%. From the physiological results that 2-decenoic acid inhibits the Na-channel, it is suggested that this increase in the membrane fluidity might affect the Na-channel.

Animals↗
PubMed2004

Analysis of betamethasone, dexamethasone and related compounds by liquid chromatography/electrospray mass spectrometry.

A reversed-phase high-performance liquid chromatography/electrospray ionisation mass spectrometry (HPLC/ESI-MS) method has been developed to conclusively differentiate the epimers betamethasone and dexamethasone and various esterification products (betamethasone and dexamethasone 21-acetate, betamethasone and dexamethasone 21-phosphate, betamethasone 17-valerate, betamethasone 21-valerate and betamethasone 17,21-dipropionate) in counterfeit drugs. Good separation with baseline resolution of all epimers or isomers was obtained on a Zorbax Eclipse XDB or Luna C8 column, using a step gradient with mobile phases of 0.05 M ammonium acetate and acetonitrile. Betamethasones can also be distinguished by the relative abundance of their m/z 279 ion in the positive electrospray tandem mass spectra. The LC/MS or LC/MS/MS method developed was successfully applied to the analysis of drug product samples, i.e. creams and tablets.

Betamethasone↗
PubMed1994

The fate of the carboxyl oxygens during D-proline reduction by clostridial proline reductase.

D-Proline is converted to 5-amino valeric acid by D-proline reductase. This conversion involves the reductive cleavage of the alpha-carbon-nitrogen bond. We have examined the fate of the carboxyl oxygen atoms during conversion of D-proline to delta-NH2-valeric acid. 18O atoms from the carboxyl group of D-proline are not lost during conversion to product. In contrast, in the conversion of glycine to acetyl phosphate by glycine reductase a carboxyl oxygen atom is lost to solvent. An intermediate acyl-enzyme is found during the reduction of glycine. We conclude that the reduction of proline proceeds without the formation of an acyl enzyme intermediate.

Amino Acid Oxidoreductases↗
PubMed1997

The effects of betamethasone derivatives on endotoxin-induced uveitis in rats.

The anti-inflammatory effects of betamethasone and its derivatives (betamethasone 21-phosphate, betamethasone 21-acetate, betamethasone 17-valerate, clobetasol 17-propionate and betamethasone dipropionate) on endotoxin-induced uveitis (EIU) in rats was investigated. Among the compounds examined, betamethasone, betamethasone 21-phosphate, betamethasone 21-acetate and clobetasol 17-propionate strongly inhibited cell infiltration into the aqueous humor in the EIU by instillation into the eye in a dose-dependent manner (0.01-1.0%) and by systemic administration (1 mg kg-1). On the other hand, betamethasone 17-valerate and betamethasone dipropionate showed only weak inhibitory effects or enhancement of cell infiltration by instillation into the eye (0.01-1.0%) and by systemic administration (1 mg kg-1). Combined systemic administration of betamethasone dipropionate and betamethasone reduced the inhibitory effect of betamethasone on cell infiltration and gene expression of IL-1 beta. In an in vitro interleukin-8 (IL-8) release assay, betamethasone showed stronger inhibition of the IL-8 release from rat peritoneal exudate cells (PEC) than betamethasone dipropionate, and simultaneous addition of betamethasone dipropionate with betamethasone reduced the inhibitory effect of the latter. These results suggest that the betamethasone derivative betamethasone dipropionate might behave as an anti-glucocorticoid in rats.

Administration, Cutaneous↗
PubMed1983

Neurotoxic esterase. Identification of two isoenzymes in hen brain.

Two phenyl valerate hydrolyzing carboxylesterases (EC 3.1.1.1) of hen brain were identified as neurotoxic esterases (NTEA and NTEB) by kinetic analysis of organophosphorus inhibition curves. The activities of both NTE isoenzymes with phenyl valerate (PV) as substrate and their inhibition rate constants were determined in six different animals. In-vivo-application of a single oral dose of 500 mg/kg triorthocresyl phosphate (TOCP) caused 86% inhibition of NTEA and 93% inhibition of NTEB within 24 h. Total NTE activity (NTEA plus NTEB) determined by kinetic analysis shows an excellent correlation (r = 0.989) to NTE activity simultaneously tested with a differential NTE assay. The excellent sensitivity (97%) and high specificity (79%) of the NTE differential test is demonstrated.

Animals↗