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Simple and selective one-pot replacement of the N-methyl group of tertiary amines by quaternization and demethylation with sodium sulfide or potassium thioacetate: an application to the synthesis of pergolide
No full textThe paper describes a mild, selective, and rapid replacement of an N-methyl group of tertiary amines with other alkyl groups via a simple one-pot procedure. This transformation is easily achieved by preparation of the appropriate quaternary ammonium salt in sulfolane and in situ treatment with sodium sulfide or potassium thioacetate. The protocol is successfully applied to the transformation of dihydrolysergol, dextromethorphan and laudanosine (as models of ergot and opium N-methyl alkaloids) into various A-alkyl congeners
Cleavage of benzyloxycarbonyl-5-oxazolidinones to α-benzyloxycarbonylamino-α-alkyl esters by alcohols and sodium hydrogen carbonate
No full textThe reaction of benzyloxycarbonyl-5-oxazolidinones with alcohols and sodium hydrogen carbonate to afford the corresponding benzyloxycarbonyl esters is described
NO DOCUMENTABLE ROLE FOR XANTHINE-OXIDASE IN THE PATHOGENESIS OF HEPATIC IN-VIVO ISCHAEMIA/REPERFUSION INJURY
Full text linkAn investigation was made into the possible involvement of the enzyme xanthine oxidase (XO) (EC 1.1.3.22), both reversible (XOrev) and irreversible (XOirr), in damage observed after short-term in vivo hepatic ischaemia/reperfusion (60 or 120 min I and 15 min R) in fasted rats with: (i) a physiological content of XO (25%); and (ii) higher XO percentage (45%). In the latter the hepatic XO physiological percentage was increased by diethylmaleate treatment (300 mg kg(-1)) that depleted the cytosolic glutathione (GSH) to 14% of the controls. It was shown that, in animals with physiological content of XO, 60 and 120 min of hepatic ischaemia followed by 15 min reperfusion results in decreased GSH levels, and significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels, without any modification of either the percentages of XO (XOirr and XOrev) or the hepatic thiobarbituric acid reactive substances (TBARS). Sixty minutes of ischaemia/reperfusion in rats with the higher XO level and lower hepatic GSH content led to further conversion of XDH to XOrev, with no increase in XOirr. In addition, the ALT and AST serum levels in these animals rose to the same extent as in normal rats after 120 min ischaemia and 15 min reperfusion, this extent being observed to be associated with a moderate increase in thiobarbituric acid reactive substances (TBARS). However, the administration of allopurinol, at a dose of 50 mg kg(-1), which almost completely inhibits XO activity, did not lead to any decrease in liver damage or TBARS. These findings exclude any role of XO in liver damage in the short term following ischaemia/reperfusion events, also when marked GSH depletion could increase the enzymatic physiological XO level
Effects of alpha-lipoic acid administration on plasma glucose levels, total malondialdehyde values and withdrawal signs in rats treated with morphine or morphine plus naloxone
No full textMorphine (CAS 57-27-2) administration or its removal induces alterations in glucose levels and oxidative status or behaviour signs, which may be hypothetically closely related; if this is correct, controlling glucose changes may lead to modifications in peroxide levels and in behaviour profile. It therefore seems important to rind a drug able to control alterations of glucose metabolism, peroxide generation and behaviour symptoms in morphine or morphine withdrawal animals. This paper describes the effects of morphine or morphine plus naloxone (CAS 51481-60-8) on the plasma levels of glucose, malondialdehyde (MDA) (CAS 100683-54-3) and behavioural signs in rats treated or not with alpha-lipoic acid (CAS 1077-28-7), known to interfere with glucose and peroxide levels.The administration of morphine or its removal by naloxone alters plasma glucose levels, increases MDA values, and also affects signs such as pain threshold values, fecal excretion and jumping behaviour.The injection of alpha-lipoic acid decreases glycemia in rats treated with morphine or morphine plus naloxone. This result may be due to the capacity of alpha-lipoic acid to facilitate glucose transport and its utilization. The administration of alpha-lipoic acid to rats given morphine or morphine plus naloxone lowers total MDA levels because of its peroxide scavenging capacity. In animals injected with morphine plus naloxone, which show altered pain thresholds, high fecal excretion and jumping behaviour, treatment with alpha-lipoic acid increases latency times, decreases fecal excretion and reduces jumping. These effects can be attributed to the capacity of alpha-lipoic acid to interfere with mediators or peroxides involved in the modified behaviour. The glycemia levels, MDA values and behavioural signs seem to be interconnected in the reported experiments. The administration of alpha-lipoic acid is demonstrated to control the alterations in plasma glucose levels, peroxide values or behavioural profile in animals receiving morphine or morphine plus naloxone
A simple model for studies on the regulation of cholesterol synthesis using freshly isolated hepatocytes
No full textRat hepatocytes isolated by the procedure described here showed 3-hydroxy-3-methylglutaryl-CoA reductase activity in the range of that reported for rat liver at the maximum of the circadian cycle, even if they were taken from rats at the time of the minimum. The enzyme was present in cells as both its active dephosphorylated (20 +/- 8%) and the inactive phosphorylated forms. The enzyme activity and the ratio between the two forms were unaltered during 3 h of cell incubation. 25-Hydroxycholesterol (50 microM) induced about 50% inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase activity during 1 h incubation but the relative amount of the two forms was not modified by the sterol. Cells isolated by the described procedure may therefore be a useful tool in studies on the regulation of cholesterol neogenesis, both through the synthesis of the enzyme, which can be shown by measuring the activity after complete dephosphorylation of the enzyme, and via the rapid reversible shift of the inactive to the active form, resulting from the ratio between the two enzyme forms. The latter mechanism for the modulation of cholesterol synthesis cannot be tested in cell cultures because full activation of the enzyme occurs during hepatocyte plating
EFFECT OF GLUTATHIONE DEPLETION ON THE CONVERSION OF XANTHINE DEHYDROGENASE TO OXIDASE IN RAT-LIVER
No full textThe ability of endogenous glutathione (GSH) to modify the activity of the enzyme xanthine oxidase (XO) in rat liver was investigated. The effect of hepatic GSH depletion on the conversion of xanthine dehydrogenase (XDH) (EC 1.1.1.204) to XO (EC 1.1.3.22) was determined 10 min after i.p. administration of different amounts of diethylmaleate to fasted rats. After administration of 400 mg/kg, total hepatic non-protein GSH (reduced + oxidized GSH) decreased significantly to 14% of controls. In this condition the level of oxidized GSH was unchanged and no lipid peroxidation was observed, while a significant increase of reversible XO and a minor increase of the irreversible form of the enzyme was detected
β Oxidative cleavage of octanoyl and dodecanoyl CoA in rat liver cytoplasm
No full text[12 14C] Dodecanoyl CoA and [8 14C] octanoyl CoA were tested as substrates for shortening the chain by two carbon atoms using both the 105,000 x g soluble fraction and the sonicated mitochondrial fraction of rat liver homogenate as the enzyme source. Both substrates were metabolized by the cytoplasmic enzymes giving rise to the accumulation of intermediates of the β oxidation process without formation of two carbon units from the methyl carbon of the acyl residue. A new method is described which allows quantitative estimation of volatile fatty acids formed by β oxidation of dodecanoyl and octanoyl Coenzyme A
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