Conversion of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine to 1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine. A novel pathway for the metabolism of ether-linked phosphoglycerides.
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Madin Darby canine kidney (MDCK) cells convert 1-O-[3H]alkyl-2-acyl-sn-glycero-3-phosphocholine [( 3H]alkylacylGPC) to a product tentatively identified as an ethanolamine-containing phosphoglyceride (PE) (Daniel, L. W., Waite, B. M., and Wykle, R. L. (1986) J. Biol. Chem. 261, 9128-9132). In the present study, analysis of the radiolabeled phosphoglycerides as diradylglycerobenzoate derivatives indicated that [3H] alkylacylGPC was initially converted to 1-O-[3H]alkyl-2-acyl-sn-glycero-3-phosphoethanolamine [( 3H]alkylacylGPE) which was subsequently desaturated to 1-O-[3H]alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine [( 3H]alkenylacylGPE). The conversion of [3H]/[32P]alkyl-lysoGPC to [3H]alkenylacylGPE indicated that base exchange enzymes were not involved in this pathway. A phosphono analog of alkyl-lysoGPC, resistant to phospholipase D hydrolysis and radiolabeled in the 1-O-alkyl chain was readily incorporated, acylated, and subsequently metabolized to [3H]alkylacylGPC and [3H]alkenylacylGPE. Therefore, the involvement of phospholipase D in the conversion pathway was ruled out. The conversion of [3H]alkylacylGPC or its phosphono analog to [3H]alkenylacylGPE was significantly enhanced by the addition of 100 microM ethanolamine to the culture media, suggesting that [3H]alkylacylglycerol is an intermediate in the cytidine-dependent pathway of PE synthesis. MDCK cell cytosol and microsomes contained no detectable phospholipase C activity. However, incubation of microsomes with CMP resulted in the degradation of [3H]alkylacylGPC and accumulation of [3H]alkylacylglycerol. Furthermore, the addition of CDP-ethanolamine to microsomes following preincubation with CMP, resulted in a decrease in [3H]alkylacylglycerol with a concomitant increase in [3H]alkenylacylGPE. Overall, these results suggest that the reverse reaction of choline phosphotransferase may be responsible for the conversion of alkylacylGPC to alkylacylGPE. (+info)
In vitro effects of the ionophore lysocellin on ruminal fermentation and microbial populations.
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Batch and continuous culture techniques were used to evaluate the effect of the ionophore lysocellin on ruminal fermentation and microbial populations. In batch culture, .5 and 1 ppm (of the fluid) lysocellin markedly decreased (P less than .01) the acetate:propionate ratio without affecting fiber digestion, ammonia concentration, or culture pH. Greater concentrations of lysocellin had negative effects (P less than .05) on fiber digestion and increased (P less than .05) culture pH. In continuous culture, a low level of lysocellin (33 ppm of the diet DM or about .7 ppm of the fluid) decreased pH (P less than .05) and methane (P less than .05) production but had no effect on fiber digestion. Lysocellin tended to increase (P less than .05) OM digestion in corn-based diets but decreased OM digestion in barley-based diets (starch source x lysocellin interaction, P less than .05). In addition, the molar proportion of propionate was increased more in barley- than in corn-based diets. Total anaerobes and amylolytic and lactate-utilizing microorganisms were not affected by the ionophore. In continuous culture, cellulolytic and lactate-producing organisms were insensitive to lysocellin, but, in lysocellin-treated media, cellulolytic organisms were resistant, whereas lactic acid producers were sensitive to lysocellin at 4 ppm. In summary, the ionophore lysocellin alters ruminal fermentation by decreasing ruminal methane production and increasing the molar proportion of propionate; however, effects varied depending on whether corn or barley served as the primary starch source. (+info)
Trifluoroethylvinyl ether (fluoromar); a preliminary report on clinical experience and animal experiment.
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In observations of 80 cases in which Fluoromar was used for inhalation anesthesia it was noted that induction was rapid; maintenance although labile, was usually smooth; and recovery of reflexes was rapid. Anesthetic complications were minimal, and postanesthetic complications were limited to nausea and vomiting in no greater incidence than that expected to follow the use of most inhalation anesthetic agents. Fluoromar produces rapid, and not particularly unpleasant, loss of consciousness, and will produce complete anesthesia without supplement. However, the muscular relaxation afforded by Fluoromar is not complete, and delayed recovery from anesthesia may follow attempts to produce relaxation by deepening too greatly the level of anesthesia. The inflammability of Fluoromar is less than that of other inhalation agents. (+info)
General anesthetics and regional hypoxic pulmonary vasoconstriction.
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Administration of N2O, fluroxene and isoflurane to the left lower lobe (LLL) of dogs anesthetized with pentobarbital was previously shown to inhibit LLL hypoxic pulmonary vasoconstriction (HPV). Using the same experimental model, the present study examined the effect of whole-lung administration of N2O, fluroxene, isoflurane, halothane, and enflurane on left-lower-lobe HPV. Selective ventilation of the LLL with N2 alone caused blood flow to the lobe to decrease 53.3 +/- 3.0 per cent. Responses to LLL hypoxia were remeasured during administration of inhalation anesthetics at 1 and 2 MAC to both the LLL and the rest of the lung. Isoflurane and fluroxene progressively inhibited and at 2 MAC halved lobar HPV. N2O (one third MAC) caused slight but significant inhibition, while halothane and enflurane caused slight and nonsignificant changes in lobar HPV. These effects of whole-lung administration of anesthetics on HPV were almost identical to those obtained when the administration was confined to the test lobe alone. It is concluded that N2O, isoflurane, and fluroxene locally inhibit regional HPV and via this mechanism increase total venous admixture, while halothane and enflurane do not have this effect. (+info)
Anaesthesia in new-born animals.
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Pentobarbitone was more toxic to new-born than to adult rabbits and rats, produced a longer loss of righting reflex in new-born animals but did not anaesthetize them effectively in less than toxic doses. Urethane did not anaesthetize new-born animals in doses which anaesthetized adults. Ether produced loss of righting reflex at lower concentrations for new-born than for adults, but the new-born animals became anaesthetized more slowly. (+info)
Noradrenaline content in the heart and spleen of the mouse under normal conditions and after administration of some drugs.
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The noradrenaline content of the heart and spleen was investigated in normal mice and in mice treated with drugs. A modification of the methods of Bertler, Carlsson & Rosengren (1958) was used for extraction, and of v. Euler & Floding (1955) for fluorimetric estimation of the amine. In normal mice the mean noradrenaline content of the heart was 0.55 mug/g and that of the spleen 0.26 mug/g fresh tissue. Iproniazid (100 mg/kg), nicotine (0.1 mg/kg) and histamine (0.5 mg/kg), given 1 and 3 hr before killing the mice, did not significantly change the concentration of noradrenaline in the heart. Neither did nicotine and histamine, administered 1 hr before death, significantly alter the noradrenaline content of the spleen. The rapid changes in the catechol amine content of mouse tissues reported with these drugs by De Schaepdryver & Preziosi (1959) were not observed. In contrast, reserpine (2.5 mg/kg), methyl reserpate methyl ether (1 mg/kg), and methyl 18-epireserpate methyl ether (2 mg/kg) caused severe depletion of noradrenaline from the heart and spleen of the mice. (+info)
STIMULANT ACTIONS OF VOLATILE ANAESTHETICS ON SMOOTH MUSCLE.
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A number of volatile anaesthetics, and some compounds synthesized in the search for new anaesthetics, have been tested on guinea-pig intestinal smooth muscle in vitro. All the compounds produced a contractile response. This effect did not correlate well with convulsant activity in vivo among the compounds tested. Two kinds of stimulant effect were distinguishable: (1) Rapid, transient contractions, abolished by cocaine or lachesine; most of the anaesthetics in clinical use had this action. (2) Slow, sustained contractions, unaffected by cocaine or lachesine; this effect predominated among the fluorinated ring compounds. Hexamethonium and mepyramine did not affect the contractile response to any of the compounds. The first type of effect presumably represents excitation of postganglionic nerve cells, while the second type is a direct action on the muscle cell. The action of perfluorobenzene, which is of the latter kind, was studied further. Adrenaline and lack of calcium diminished the contraction in parallel with the contraction to histamine, which suggests that the cell membrane was the site of action; in contrast to the stimulant action of histamine or acetylcholine, the effect was highly temperature-sensitive, being almost abolished by cooling to 32 degrees C, and enhanced at 40 degrees C. The depressant action of anaesthetics on smooth muscle is affected very little by temperature changes. These findings are discussed in relation to other observations which suggest a stimulant action of volatile anaesthetics on excitable tissues. Protein denaturation is tentatively suggested as a mechanism of action. (+info)
CP-72,588, a semisynthetic analog of the polyether ionophore UK-58,582 with increased anticoccidial potency.
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We have employed semisynthesis to enhance the anticoccidial potency of a polyether ionophore. CP-72,588 is the alpha-methyl analog of the fermentation-derived polyether ionophore UK-58,852. The parent ionophore required a dose of 15 ppm to achieve anticoccidial efficacy in chickens equivalent to that of salinomycin at 60 ppm. CP-72,588 demonstrated substantially improved potency, with efficacy at 5 to 7.5 ppm. The intrinsic antimicrobial potencies of the two ionophores are similar; however, CP-72,588 was found in chicken tissues at higher levels than those of the parent ionophore when each was administered at the same dose (8 ppm). The enhanced potency of CP-72,588 may be partially due to enhanced uptake into tissues. (+info)