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Effect of form of nitrogen on growth of ruminal microbes in continuous culture.

A study was conducted to determine the effect of various forms of N on the growth of ruminal microbes in a continuous culture system with solids and liquid dilution rates comparable to those of a high-producing dairy cow. Nitrogen forms were isolated soy protein, soy peptides, individual amino acids (AA) blended to profile soy protein, and urea, which were fed alone and in combinations so that the total N provided was 1.6% of the diet DM. The 100% soy protein treatment resulted in reduced digestion of N and nonstructural carbohydrate compared with other N forms, and outflow of bacterial N/24 h was less than when peptides were fed. This suggested that proteolysis rather than peptide uptake was the rate-limiting step in N utilization in this study. Non-urea N forms increased ADF digestion, total VFA production and the molar percentages of isobutyrate, isovalerate, and valerate compared to urea, which reflected the contribution of carbon skeletons of AA. When combinations of N forms were used, each form contributed an equal quantity of N, 50% of the total treatment, which was .8% of the diet DM. Combinations of N forms did not enhance, and in most cases reduced, ADF and NDF digestion when compared with individual N forms, and no combinations increased microbial growth over that of the individual forms. These results confirm that N forms other than ammonia are needed not only for maximum microbial growth, and they further demonstrate a need for non-protein N for the fiber digestion. In addition, results of this study suggest a requirement for a minimum level of peptide or AA N, which was met only when individual N forms were fed.

Amino Acids↗

Effects of volatile fatty acids on propionate metabolism and gluconeogenesis in caprine hepatocytes.

Isolated caprine hepatocytes were incubated with fatty acids of various chain lengths. Short-chain fatty acids effects on rates of gluconeogenesis and oxidation from [2-14C]propionate were determined. Additions of glucose (2.5 mM) had no effect on hepatic [2-14C]propionate metabolism in the presence and absence of amino acids. A complete mixture of amino acids increased label incorporation from [2-14C]propionate into [14C]glucose by 22%. Butyrate inhibited [2-14C]propionate metabolism and increased the apparent Michaelis constant for [2-14C]propionate incorporation into [14C]glucose from 2.4 +/- 1.5 to 5.6 +/- .9 mM. Butyrate's effects on propionate were similar in the presence and absence of L-carnitine (1 mM). Isobutyrate, 2-methylbutyrate, and valerate (1.25 mM) had no effect on [14C]glucose production but decreased 14CO2 production to 57, 61, and 54% of the control [2-14C]propionate (1.25 mM). This inhibition on 14CO2 production was not competitive. Isovalerate had no effect on either [2-14C]propionate incorporation into glucose or CO2. An increase in ratio of [14C]glucose to 14CO2 from [2-14C]propionate demonstrated that short-chain fatty acids other than butyrate do not inhibit gluconeogenesis from propionate. In addition, fatty acids that generate a net synthesis of intracellular oxaloacetate may partition propionate carbons toward gluconeogenic rather than oxidative pathways in goat hepatocytes.

Animals↗

Volatile fatty acid uptake and propionate metabolism in ruminant hepatocytes.

Previous reports have demonstrated that butyrate inhibits metabolism of propionate by liver cells isolated from sheep and goats. Our objectives were to examine some possible mechanisms for this inhibition and to test for this inhibition in the bovine animal. Incorporation of label from 2.5 mM [2-(14)C]propionate into glucose (nmol propionate/mg cell DM/h) in the presence of 0, 1.25, and 2.5 mM butyrate was 107, 66, and 62 by goat hepatocytes and 79, 25, and 29 by calf hepatocytes; therefore, butyrate inhibited propionate metabolism at least as effectively in calves as in goats. In goat hepatocytes 1.25 mM butyrate reduced 1.25 mM propionate uptake to 46% of control, and 1.25 mM [2-(14)C] propionate incorporation into glucose to 44% of control. Propionate had no effect on butyrate uptake. Isovalerate and valerate tended to be cleared from the media to a greater extent than butyrate but had no effect on propionate uptake. Therefore, inhibition of propionate conversion to glucose by butyrate is specific and is not due to a general competition among VFA for metabolism. Butyrate inhibits hepatic propionate utilization generally, not specifically propionate conversion to glucose. Butyrate also inhibited propionate utilization by goat liver homogenates, indicating that butyrate inhibits propionate metabolism at a step subsequent to propionate transport across the hepatocyte plasma membrane.

Animals↗

The effect of selenium or vitamin E supplementation on volatile fatty acid content of rumen liquor in sheep fed a purified diet.

Twelve crossbred wethers, four per diet, were allotted at random as follows: (1) purified control diet; (2) purified diet plus a weekly oral dose of 1 mg sodium selenite per sheep; (3) purified diet plus a weekly oral dose of 1000 l.U. vitamin E. The wethers were maintained on the diets for six months. Weight gains during the initial 140 days of the experiment were significantly greater in selenium (Se)-supplemental sheep than in the others. The rumem liquor from the untreated sheep contained lower proportions (molar %) of acetic acid than from the Se or vitamin E-supplemented sheep and had higher butyric acid concentration than the Se-supplemented sheep. Concentrations of acetate, butyrate and valerate were higher in vitamin E than in Se-supplemented sheep. In addition, the concentration and molar percent of isovaleric acid was significantly higher in Se-supplemented sheep than in the other sheep.

Acetates↗

Neuropathy target esterase.

Neuropathy target esterase (NTE) is an integral membrane protein present in all neurons and in some non-neural-cell types of vertebrates. Recent data indicate that NTE is involved in a cell-signalling pathway controlling interactions between neurons and accessory glial cells in the developing nervous system. NTE has serine esterase activity and efficiently catalyses the hydrolysis of phenyl valerate (PV) in vitro, but its physiological substrate is unknown. By sequence analysis NTE has been found to be related neither to the major serine esterase family, which includes acetylcholinesterase, nor to any other known serine hydrolases. NTE comprises at least two functional domains: an N-terminal putative regulatory domain and a C-terminal effector domain which contains the esterase activity and is, in part, conserved in proteins found in bacteria, yeast, nematodes and insects. NTE's effector domain contains three predicted transmembrane segments, and the active-site serine residue lies at the centre of one of these segments. The isolated recombinant domain shows PV hydrolase activity only when incorporated into phospholipid liposomes. NTE's esterase activity appears to be largely redundant in adult vertebrates, but organophosphates which react with NTE in vivo initiate unknown events which lead, after a delay of 1-3 weeks, to a neuropathy with degeneration of long axons. These neuropathic organophosphates leave a negatively charged group covalently attached to the active-site serine residue, and it is suggested that this may cause a toxic gain of function in NTE.

Amino Acid Sequence↗

Controlled double-blind comparative trial with fluprednylidene acetate cream and its base.

The effect of combined therapy with fluprednylidene acetate cream applied once daily plus cream base of the same formulation twice daily was tested in controlled double-blind contralateral investigations carried out on 31 in-patients with skin diseases which react to corticoids. Comparison with the 3 times daily application of the cream containing fluprednylidene and the 3 times daily application of a cream containing betamethasone 17-valerate did not show any differences in the result of treatment which was good to very good in each case within a 15-day trial period. No side effects were determined. The combined treatment with fluprednylidene acetate cream (once daily) and the cream base of the same formulation means that by economising on the use of the corticoid the risk involved in treatment is reduced and a therapeutic concept can be propounded which is suitable for all individual circumstances because the cream base used is kept constant.

Acetates↗

Portal recovery of short-chain fatty acids infused into the temporarily-isolated and washed reticulo-rumen of sheep.

The present study was undertaken to study the metabolism of short-chain fatty acids (SCFA) by the reticulo-ruminal epithelium and the portal-drained viscera (PDV) under in vivo conditions with no interference from the metabolism of the rumen microbes. The technique of temporary isolation of the reticulo-rumen was applied to wethers implanted with catheters in a mesenteric artery, the hepatic portal vein and the right ruminal vein. Portal blood flow was measured by downstream dilution of p-aminohippuric acid; the PDV uptake of arterial acetate, as well as the whole-body irreversible loss rate (ILR) of acetate, was estimated by [2-(13)C]acetate infusion into the right ruminal vein. The sheep were maintained with a bicarbonate-buffered solution of SCFA in the reticulo-rumen along with continuous intraruminal infusion of SCFA for 4 h. The portal appearance of SCFA of non-reticulo-ruminal origin was estimated before and after the infusion protocol. Of the acetate absorbed by the sheep, 89 (SE 5), 109 (SE 7) and 101 (SE 7)% was recovered as portal net appearance of acetate, portal net appearance of acetate corrected for PDV uptake of arterial acetate and increase in the ILR of acetate respectively. Of the propionate, isobutyrate, butyrate, isovalerate and valerate absorbed by the sheep, 95 (SE 7), 102 (SE 9), 23 (SE 3), 48 (SE 5) and 32 (SE 4)% respectively was recovered as portal net appearance. In contrast to current concepts, the present study showed that the reticulo-ruminal epithelium metabolizes none (or only a small proportion) of the acetate and propionate absorbed from the rumen. This observation could lead to the more efficient use of results obtained with multi-catheterized animals to quantify the net metabolite output of the rumen microbes.

Acetates↗

[Pharmacological study on 9 alpha-fluoro-11 beta, 17,21-trihydroxy-16 beta-methyl pregna-1, 4-diene-3,20-dione-17-benzoate(betamethasone-17-benzoate, MS-1112), a local anti-inflammatory agent. (2). Its action of delayed hypersensitivity dermatitis].

The anti-inflammatory activity of MS-1112, a new steroid compound, after topical application and systemical administration was examined by means of delayed-type hypersensitivity in mice and compared with other glucocorticoid analogues, betamethasone-17-valerate (Val), dexamethasone (Dexa) and betamethasone (Beta). In the case of pretreatment and therapeutic effect, topically applied MS-1112 was most active in inhibiting the delayed-type hypersensitivity induced by picryl chloride. The order of those inhibitory activities of MS-1112 and Val was ointment greater than cream greater than gel. In contrast to MS-1112 and Val, inhibitory action of Dexa was slow in onset after the topical application. It appears that esterification of the 17-hydroxyl group increases the anti-inflammatory activity after topical application. While systemically administered, MS-1112 was more potent than Val, and similarly potent to Beta, but less active than Dexa. From the above results, it may be considered that topically applied MS-1112 is superior to other glucocorticoids in the percutaneous penetration and retention in the skin. MS-1112 is thus considered to be a very potent agent as a dermatocorticoid.

Administration, Topical↗

Depigmenting action of corticosteroids. Experimental study on guinea pigs.

The depigmenting action of corticosteroids was studied on the black skin of the guinea-pig by cutaneous applications followed by repeated histological sections. These experiments demonstrated the depigmenting action of triamcinolone acetonide and betamethasone 17-valerate. The results of this study show the influence of concentration and chemical formula of the corticosteroids on the process of depigmentation. The histological study did not reveal any particular morphological aspect of melanocytes capable of suggesting a mechanism of action by these chemical compounds at the cellular level.

Adrenal Cortex Hormones↗

[Clinical experiences with a new topical steroid].

44 patients have been treated in a double-blind trial with Desoximetason (0.25%) and with Betamethasone-valerate (0.1%). It was a randomised left-right comparative trial, and Desoximetason was significantly better than the comparative drug in all observation periods (except the period 1-2 days). Desoximetason has also been tested on 280 patients in an open trial, showing good efficacy and good tolerance.

Adolescent↗

Polyhydroxyalkanoate form and polyphosphate regulation: keys to biological phosphorus and glycogen transformations?

Experimental studies with both synthetic and real domestic wastewater showed that poly-3-hydroxy-butyrate (3HB) and poly-3-hydroxy-valerate (3HV) formed in direct proportion to the acetate/propionate (Ace/Pro) ratio of the influent wastewater during Enhanced Biological Phosphorus Removal (EBPR). Acetic acid resulted in higher anaerobic phosphorus (P) release, polyhydroxyalkanoate (PHA) yield, 3HB content, and glycogen (CH) degradation. Linear regression showed that anaerobic P release (Prel) and CH degradation (CHdeg) were both a function of Ace-->3HB, but not of Pro-->3HV. Aerobic P uptake (Pup) correlated best with preceding Prel, rather than PHA (but note Prel correlated with Ace-->3HB). Aerobic CH formation (CHform) correlated best with CHdeg and 3HB. The results imply the acetate/propionate content of influent has a major influence on PHA, CH, and P transformations. Short-term increases in acetic or propionic acid increased Prel, but were always offset by corresponding changes in Pup to yield the same net P removal as the control reactor. Thus net P removal, and EBPR process performance, was probably a function of the population selected (i.e. XPAO fraction) during long-term cultivation.

Bacteria, Anaerobic↗

[Lymphocyte phenylvaleric acid hydroxylase activity (L-PVH), a new marker of peripheral neurotoxicity].

A reduction in the level of a new enzymatic assay--a phenyl valerate hydrolase (PVH)--has been found during the clinical evolution of toxic neuropathies (as almitrine-bismetilate ones) as well as alcoholic or diabetic neuropathies. The substrate and the enzymatic function are different from those used by M.K. Johnson for NTE. The method follows procedures comparable to NTE (differential determination after inhibition by paraoxon and by paraoxon plus mipafox or DFP). It may be useful to test possible neurotoxicity of drugs and chemicals.

Adult↗

[Comparative studies on Bi-Nerisona cream (diflucortolone valerinate + chlorquinaldol) and on a combination preparation (betamethasone valerinate + gentamicin + tolnaftate + clioquinol) in a double-blind trial].

Bi-Nerisone cream and a control preparation, also in the form of a cream, have been clinically tested on 343 patients by means of a double blind study. Equilvalent results were obtained without registering any significant statistical differences, a finding, however, proving to be of great importance as Bi-Nerisone only contains two active substances (Diflucortolone valerat + Chlorquinaldol), whereas the control preparation contains a total of four (Betamethasone valerate + Gentamycin + Tolnaftate + Clioquinol).

Betamethasone Valerate↗

Solitary mastocytoma successfully treated with a moderate potency topical steroid.

We report a case of solitary mastocytoma in a child which was successfully treated with a topical steroid of moderate potency. The patient was an 18-month-old girl who presented with localized oval shape yellowish to hyperpigmented lesion on the medial aspect of her right forearm noticed accidentally by the parents since the age of 6 months. The lesion was observed to get urticated mainly after bathing, toweling, and scratching of the area, associated with reddening and itching confined to the lesion (Figure 1). No other area of the body was affected with any similar lesion. Examination of the skin revealed a yellow-tan oval shape patch 1 x 3 cm in diameter which was firm to the touch with intact overlying skin. The lesion became swollen and itchy when it was rubbed vigorously (positive Darier's sign). Systemic examination was unremarkable. The patient investigations including complete blood count, routine biochemical data, plasma histamine level, and urinalysis were within normal levels. Skin biopsy was cancelled because the parents refused, so our clinical diagnosis was solitary mastocytoma even though it was not confirmed histologically. We started the patient on a moderate potency corticosteroid (betamethasone valerate 0.1% cream) twice a day for six weeks after which the lesion became softer with a weak Darier's sign. This treatment was continued for another four months which led to resolution of the lesion with residual hyperpigmentation, negative Darier's sign, and no signs of atrophy (Figure 2). Follow up of the patient for another 8 weeks without treatment did not reveal any recurrence of the lesion.

Betamethasone Valerate↗

Comparison of Psoralen ultraviolet A (PUVA) photochemotherapy plus topical corticosteroids with PUVA plus bland emollients in the treatment of psoriasis.

BACKGROUND: Psoralen Ultraviolet A (PUVA) therapy is a well-established treatment of psoriasis. The objective of the study was to compare the clinical improvement in psoriasis with PUVA photochemotherapy + topical corticosteroids and PUVA + bland emollients. METHODS: Forty patients with chronic plaque type of psoriasis were divided into two equal groups each having 20 patients. PUVA therapy was given thrice weekly. In addition, patients of group-A were allowed to apply topical betamethasone 17-valerate 0.1% diluted 1 into 2 parts with plain vaseline twice daily. Patients of group-B were allowed to apply only plain vaseline over lesions twice daily. Clinical improvement in lesions was observed by decrease in the severity of erythema, scaling and plaque elevation. RESULTS: Clearance of psoriasis was achieved in 95%, of the patients treated with PUVA plus topical corticosteroids while clearance was achieved in 80% of patients treated with PUVA plus bland emollients (P = 0.0758). Median numbers of exposures for group-A were 16 & for group-B were 17.5 (p = 0.1029). Similarly, median cumulative dose in group-A was 64.5 J/cm2 & in group-B was 70.7 J/cm2 (p = 0.372). CONCLUSION: There is no significant difference in clinical improvement in psoriasis treated either by PUVA plus topical steroids or PUVA plus bland emollients.

Adult↗

Topical application of potent glucocorticoids augments epidermal beta-adrenergic adenylate cyclase response in vivo.

The effects of topical application of glucocorticoids on the epidermal beta-adrenergic adenylate cyclase response were investigated. A significant increase in this receptor response was observed 24 h following topical application of potent glucocorticoid ointments (0.12% betamethasone-17-valerate, 0.05% clobetasol-17-propionate). The application of a relatively weak glucocorticoid, hydrocortisone-17-butyrate, revealed no augmentation effect. There was no significant difference in other adenylate cyclase responses (adenosine-, and histamine-) between control and glucocorticoid-treated epidermis. UVB irradiation is known to augment the beta-adrenergic response of epidermis. Comparison of the effects revealed that topical glucocorticoid treatment had less effect than UVB irradiation, and when the UVB irradiation was combined with glucocorticoid treatment, the beta-adrenergic augmentation effect was not enhanced. Cyclic AMP phosphodiesterase activities were not significantly altered by the glucocorticoid-, UVB-, or combined treatments. Our data indicate that epidermal beta-adrenergic adenylate cyclase response is affected by topical application of 'potent' glucocorticoids in vivo. Although the effect is weaker than that induced by UVB irradiation, we believe the system might be a useful tool for dissecting the glucocorticoidal potency of topical preparations using the epidermal keratinocyte response in vivo.

Adenylyl Cyclases↗

Plasminogen activation in psoriasis.

Plasminogen activation is a widely documented physiological phenomenon in which plasminogen activators (mainly urokinase and tissue type plasminogen activator) transform the zymogen plasminogen into the wide-spectrum proteinase plasmin. We show here that psoriatic epidermis is provided with abnormal plasminogen activator activity, mainly dependent on the activity of tissue type plasminogen activator and that this abnormal activity can be reversed with common topical treatments (i.e. anthralin, and 0.1% betamethasone valerate cream). We also report abnormal immunohistochemical localization of plasminogen, urokinase and tissue type plasminogen activator in psoriatic epidermis which returned to normal after the topical treatments. These data suggest a major role of plasminogen activation in the pathogenesis of psoriasis.

Adult↗

Adrenocortical suppression by topically applied corticosteroids in healthy dogs.

Three corticosteroid products (triamcinolone acetonide, fluocinonide, betamethasone valerate) and a control product composed of water, petrolatum, mineral oil, cetyl alcohol, steryl alcohol, sodium lauryl sulfate, cholesterol, and methylparaben each were applied topically to healthy dogs (5 dogs/product) once daily for 5 consecutive days. Plasma concentrations of immunoreactive adrenocorticotropic hormone (iACTH) and cortisol were determined before 1 microgram of ACTH/kg of body weight was given intravenously (pre-ACTH values) and cortisol was again measured 60 minutes after ACTH was given (post-ACTH values). Cortisol and iACTH concentrations were determined in each dog before, during, and after administration of the corticosteroid products. All 3 corticosteroids caused prompt and sustained pituitary-adrenocortical suppression. Compared with control applications, the application of corticosteroids resulted in significant reduction of plasma cortisol and iACTH concentrations by day 2 of treatment, and the lower concentrations continued to day 5. One week after the last application of the corticosteroids, plasma iACTH concentrations in the corticosteroid-treated dogs had returned to the range of values for the control dogs; however, pre- and post-ACTH cortisol concentrations remained suppressed in all corticosteroid-treated dogs. Two weeks after the last treatment, the pre-ACTH plasma cortisol concentrations of corticosteroid-treated dogs returned to those of the control dogs, but the post-ACTH plasma cortisol concentrations remained suppressed. By 3 weeks after the last treatment, post-ACTH plasma cortisol concentrations of dogs treated with triamcinolone acetonide had returned to the range of values for the control dogs, but remained suppressed in the other 2 groups of dogs. All indices of pituitary-adrenocortical activity were within the control range by 4 weeks after the last treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗