Modification of the relationship between cerebral metabolism, blood flow, and electroencephalogram by stimulation during anesthesia in the dog.
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Anesthesia, General↗
Biomedical subjects
T Kuramoto
Publications and source records attributed to T Kuramoto.
Comparative biochemical studies of bile acids and bile alcohols XI. Synthesis of 5 alpha-cholestane-3 alpha, 7 alpha, 12 alpha, 25, 26, 27-hexol.
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Cholestanols↗
Chemical synthesis of 5beta-cholestane-3alpha, 7alpha, 24, 25-tetrol and its metabolism in the perfused rabbit liver.
5beta-[G-3H]Cholestane-3alpha, 7alpha, 24xi, 25-tetrol (IV) was synthesized via dehydration and peroxidation of 5beta-[G-3H]cholestane-3alpha, 7alpha, 25-triol. Following perfusion of the labeled compound in the isolated rabbit liver, the bile alcohol and bile acid metabolites secreted into the bile were identified by a combination of thin layer chromatography, gas-liquid chromatography, and gas-liquid chromatography/mass spectrometry. The following bile alcohols were tentatively identified: 5beta-cholest-23-ene-3alpha, 7alpha, 25-triol, 5beta-cholest-25-ene-3alpha, 7alpha, 12alpha, 24xi-tetrol, and 5beta-cholestane-3alpha, 7alpha, 12alpha, 24xi, 25-pentol. The amount of administered tetrol recovered unchanged ranged from 1 to 88%. Cholic acid was the major product, but limited amounts of chemodeoxycholic acid were also formed. The 24-hydroxyl group in the steroid side chain did not prevent 12alpha-hydroxylation.
Animals↗
Identification of bile alcohols in normal rabbit bile.
Rabbit bile was examined for bile alcohols. Using combined gas chromatography-mass spectrometry, 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25,26-pentol, 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25--tetrol, 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,24 beta-tetrol, 24-methyl-25-homo-5 beta-cholane-3 alpha, 7 alpha, 12 alpha, 24-tetrol, and 5 alpha-cholestane-3 alpha, 7 alpha, 12 alpha, 24 beta-tetrol were identified as the minor constituents of normal rabbit bile.
Animals↗
Identifications of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23 beta-tetrol, 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24 alpha-tetrol, and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24 beta-tetrol in cerebrotendinous xanthomatosis.
The bile alcohols present in the feces of a patient with cerebrotendinous xanthomatosis were studied. Three bile alcohols which are different from any known natural bile alcohol were isolated as minor components of the fecal bile alcohol fraction. The structures of these compounds were established as 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23 beta-tetrol, 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24 alpha-tetrol, and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24 beta-tetrol by comparison with synthetic samples.
Adult↗
Cerebral effects of nitrous oxide in the dog.
The cerebral effects of nitrous oxide, 60 per cent, were examined in 27 dogs. During administration of halothane, 0.2 per cent, nitrous oxide increased cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMR02) to a maximum of 203 and 121 per cent of control, respectively. Cerebrospinal fluid pressure paralleled the change in CBF. The electroencephalogram (EEG) showed low-voltage slow-wave activity. With halothane, 0.8 per cent, nitrous oxide increased CBF and CMR02 to maximum values of 164 and 108 per cent of control, respectively. After administration of thiamylal, 8 mg/kg, intravenously, nitrous oxide did not increase CBF or CMR02 for the first 30-min period, but thereafter, CMR02 increased to 11 per cent above control. Pretreatment with reserpine, 0.5 mg/kg, intramuscularly, for two days did not modify the cerebral circulator and metabolic responses to nitrous oxide. These results indicate that nitrous oxide causes cerebral metabolic stimulation accompanied by an increase in CBF and slowing of the EEG. Sympathoadrenal stimulation would appear not to be the mechanism for the increases in CBF and CMR02. The cerebral effects of nitrous oxide are modified by the background anesthesia.
Animals↗
Metabolism of bile alcohols in the perfused rabbit liver - C26 bile alcohols.
The metabolism of a C26 bile alcohol (I, 24-nor-5beta-cho-lestane-3alpha, 7alpha,25-triol) was studied in the isolated perfused rabbit liver. The new bile alcohol and bile acid metabolites secreted into the bile were isolated and identified by a combination of TLC, GLC and GLC-MS. The following bile alcohols were found: II, 24-nor-5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol, III, 24-nor-5beta-cholestane-3alpha,7alpha,12alpha,25,26-pentol; IV, 24-nor-5beta-cholest-23-ene-3alpha,7alpha,12alpha-triol; and V, 24-nor-5beta-cholest-23-ene-3alpha,7alpha-diol. In the bile acid fraction, 24-nor-cholic acid and 3alpha,7alpha,12alpha-trihydroxy-24-nor-5beta-cholest-23-en-26-oic acid were present. The perfused nor-triol was not resistant to 12alpha-hydroxylation.
Animals↗
Cell cycle in mouse intestinal crypts during halothane or nitrous oxide anaesthesia.
The effects of inspired air, halothane 0.5% and nitrous oxide 64% on the cell cycle were examined by autoradiography in the duodenal and jejunal crypts of mice. The length of cell cycle phases was calculated from the rate of transition of the labelled cells from the DNA-synthetic to the mitotic phase, using a computer program based on a mathematical model of the cell cycle. The computer analysis showed that halothane 0.5% prolonged the post-mitotic gap by 57% in the duodenum and by 60% in the jejunum. The DNA-synthetic time was prolonged by 23% in the duodenum and 30% in the jejunum and the mitotic time by 33% in the duodenum and 46% in the jejunum, when compared with the control animals breathing air. Nitrous oxide 64% had no effect on the cell cycle.
Anesthesia, Inhalation↗
Metabolism of bile acids. IV. Absorption, distribution, excretion and metabolism of orally administered ursodeoxycholic acid in rats.
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Administration, Oral↗
Metabolism of bile acids. V . Metabolism of ursodeoxycholic acid in rhesus monkey.
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Animals↗
Quantitative aspects of the conversion of 5 beta-cholestane intermediates to bile acids in man.
The in vivo conversion of several 5 beta-cholestane intermediates to primary bile acids was investigated in three patients with total biliary diversion. The following compounds were administered intravenously: 5 beta-[G-3H]-cholestane-3 alpha, 7 alpha-diol, 5 beta-[G-3H]cholestane-3 alpha, 7alpha, 26-triol, and 5 beta-[24-14C]cholestane-3 alpha, 7 alpha-25-triol. Bile was then collected quantitatively at frequent intervals for the next 21 to 28 h. The administered 5 beta-[G-3H]cholestane-3alpha, 7alpha, 26-triol was found to be efficiently converted to cholic and chenodeoxycholic acids in two patients; 61 and 75% of the administered label was found in primary bile acids. The proportion of labeled cholic to chenodeoxycholic acid was 1.20 and 1.02 in the bile of these patients, indicating that the C-26 triol was efficiently converted to cholic acid. The ratio of cholic to chenodeoxycholic acid (mass) in the bile of these patients was 1.23 and 2.32. The 5 beta-cholestane-3alpha, 7alpha-diol intermediate was also efficiently converted (71%) to both primary bile acids. The cholic to chenodeoxycholic acid ratios by mass and label were similar (2.97 versus 2.23). By contrast, the 5beta-cholestane-3alpha, 7alpha, 25-triol was poorly converted to bile acids in three patients. Following the administration of this compound almost all of the administered radioactivity found in the bile acid fraction was in cholic acid (5 to 19%) and very little (less than 5%) was found in chenodeoxycholic acid. These findings indicate that ring hydroxylation at position 12 is not materially hindered by the presence of a hydroxyl group on the side chain at C-26 in patients with biliary diversion. The labeled C-26-triol which was efficiently converted to both primary bile acids in a proportion similar to that which was observed for the bile acids synthesized by the liver suggests that this 5beta-cholestane derivative may be a major intermediate in the synthesis of both cholic and chenodeoxycholic acids.
Bile Acids and Salts↗
Metabolism of bile alcohols in the perfused rabbit liver.
The mechanism and sequence of side chain hydroxylation of cholesterol in bile acid synthesis was studied in the isolated perfused rabbit liver. A comparison was made between the importance of 26- and 25-hydroxylation in cholic acid biosynthesis in the rabbit. The formation of [G-3H]cholic acid was observed when the liver was perfused with 5beta-[G-3H]cholestane-3alpha, 7alpha-diol, 5beta-[G-3H]cholestane-3alpha, 7alpha-12alpha-triol, and 5beta-[G-3H]cholestane-3alpha, 7alpha, 26-triol. No [G-3H]chenodeoxycholic acid was detected in the bile. These findings indicate that potential precursors of chenodeoxycholic acid were hydroxylated at position 12alpha either subsequent to or before hydroxylation of the cholesterol side chain. In addition, no other intermediates (tetrahydroxy or pentahydroxy bile alcohols) were found in the bile when these compounds were perfused in the liver. Bile acid precursors were detected in bile when the rabbit liver was perfused with 5beta-[24-14C]cholestane-3alpha, 7alpha, 25-triol. The 5beta-[24-14C]cholestane-3alpha, 7alpha, 25-triol was hydroxylated in the liver at the 12alpha position to yield the corresponding 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol. The tetrol was further metabolized to a series of pentols (5beta-cholestane-3alpha, 7alpha, 12alpha, 22, 25-pentol; 5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentol; 5beta-cholestane-3alpha, 7alpha, 12alpha, 24, 25-pentol; and 5beta-cholestane-3alpha, 7alpha, 12alpha, 25, 26-pentol). The major bile acid obtained from the perfusion of the 5beta-cholestane-3alpha, 7alpha, 25-triol was cholic acid. The experiments indicated that in the rabbit liver 12alpha-hydroxylation can occur after hydroxylation of the cholesterol side chain at either C-25 (5 beta-cholestane-3alpha, 7alpha, 25-triol) or C-26 (5beta-cholestane-3alpha, 7alpha-26-triol). Apparently, the rabbit can form cholic acid via the classical 26-hydroxylation pathway as well as via 25-hydroxylated intermediates.
Animals↗
New bile alcohols - synthesis of (22R)- and (22S)-5beta-cholestane-3alpha,7alpha,12alpha,22,25-pentols.
The synthesis of (22R)- and (22S)-5beta-cholestane-3alpha,7alpha,12alpha,22,25-pentols is described. Bisnorcholyl aldehyde was prepared from cholic acid and converted into the cholestane-pentols by a Grignard reaction with 3-methyl-3-(tetrahydropyran-2-yloxy)-butynylmagnesium bromide followed by hydrogenation and acid hydrolysis. One of the synthetic pentols, the 22R-isomer was identical with a metabolite of 5beta-cholestane-3alpha,7alpha,25-triol formed in the rabbit.
Animals↗
Isolation, quantitation, and identification of bile alcohols.
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Alcohols↗
Identification of (23S)-5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentol in cerebrotendinous xanthomatosis.
The synthesis of (23R)- and (23S)-5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentols is described. Norcholyl aldehyde was converted into the cholestanepentols by a Reformatsky reaction with ethyl bromoacetate followed by a Grignard reaction with methylmagnesium iodide. One of the synthetic pentols, the 23S epimer was identical with a bile alcohol isolated from patients with cerebrotendinous xanthomatosis.
Brain Diseases↗
Cerebral responses to the addition of nitrous oxide to halothane in man.
Cerebral responses to the substitution of 60% nitrous oxide for nitrogen during halothane anaesthesia (0.84%, end-tidal) were studied in four patients during surgery. The mean (+/-SEM) cerebral blood flow equivalent and internal jugular venous oxygen tension during halothane anaesthesia, 17+/-3 ml blood/ml oxygen and 41+/-2 mm Hg respectively, increased significantly to 45+/-3 ml blood/ml oxygen and 54+/-3 mm Hg following the introduction of nitrous oxide. On the withdrawal of nitrous oxide, the mean cerebral blood flow equivalent and internal jugular venous oxygen tension returned gradually to the control values. Cerebral perfusion pressure and blood-gas values, other than the internal jugular venous oxygen tension, did not change significantly. Marked slowing of the e.e.g. was observed following the addition of nitrous oxide to halothane, Upon the withdrawal of nitrous oxide the e.e.g. returned to the control pattern. These results indicate that cerebral blood flow was in excess of oxygen demand during nitrous oxide/halothane anesthesia in man.
Anesthesia↗
Isolation of new C26 bile alcohols from bullfrog bile.
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Animals↗
New bile alcohols--synthesis of 5beta-cholestane-3alpha, 7alpha, 25-triol and 5beta-cholestane-3alpha, 7alpha, 25-24 (14C)-triol.
5beta-Cholestane-3alpha, 7alpha, 25-triol and 5beta-cholestane-3alpha, 7alpha, 25-24(14-C)-triol were synthesized from 3alpha, 7alpha-dihydroxy-5beta-cholanoic acid (chenodeoxycholic acid). Chenodeoxycholic acid was converted to the diformoxy derivative (II) using formic acid. Reaction of II with thionyl chloride yielded the acid chloride which was treated with diazomethane (CH-2-N-2 or 14-CH-2-N-2) to produce 3alpha, 7alpha-diformoxy-24-oxo-25-diazo-25-homocholane (III, A or B). 25-Homochenodeoxycholic acid (IV, A or B) was formed from III by means of the Wolff rearrangement of the Arndt-Eistert synthesis. The methyl ester of V (A or B) was treated with methyl magnesium iodidi in ether to provide the desired triol, VI (A and B). The triol was identified by mass spectrometry and elemental analysis and was characterized by thin-layer and gas-liquid chromatography. The 3alpha, 7alpha, 25-triol is of possible significance as an intermediate in the pathway of bile acid formation from cholesterol.
Bile↗