bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of regulation of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase activity by low density lipoprotein in human lymphocytes
Authors: KRONE W. , BETTERIDGE D. J. , GALTON D. J. 
Published: March 2008

Abstract. The mechanism of action of low density lipoprotein (LDL) on the rate of sterol synthesis and on the activity of its rate‐determining enzyme 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase‐(HMG‐CoA reductase) was studied in lymphocytes freshly isolated from normal subjects and patients heterozygous for familial hypercholesterolaemia.Incubation of normal cells in lipid‐depleted serum led to a substantial rise in the rate of sterol synthesis from [14C]acetate. Addition of cycloheximide (20 μg/ml), a translational inhibitor, reduced sterol synthesis; addition of LDL (100 μg LDL‐cholesterol/ml) had a similar effect as cycloheximide in reducing sterol synthesis with a half‐life of about 3 h.Cordycepin (50 μg/ml) inhibited messenger RNA synthesis by more than 50% but had no inhibitory effect on the induction of sterol synthesis suggesting that the induction of the pathway is independent of newly synthesized messenger RNA.Lymphocytes from patients heterozygous for familial hypercholesterolaemia behaved similarly to cells from normal subjects in that cycloheximide reduced the incorporation of [14C]acetate into sterols, while cordycepin had no effect on the induction of sterol synthesis mediated by lipid‐depleted serum.Since sterol synthesis from [14C]acetate can be taken as a measure of HMG‐CoA reductase activity under our experimental conditions, the results suggest that: (i) the increase HMG‐CoA reductase activity in cells incubated in the presence of lipid‐depleted serum is due to increased de novo synthesis of the enzyme which can rapidly be inhibited by the addition of LDL, and (ii) in lymphocytes from normal subjects and patients heterozygous for familial hypercholesterolaemia the induction of HMG‐CoA reductase by lipid‐depleted serum and, by implication, the subsequent repression of the enzyme by LDL cannot be accounted for by a corresponding increase or decrease in the synthesis of messenger RNA.
Urinary bile acids during development of recurrent cholestasis of pregnancy
Authors: THOMASSEN PETER A. 
Published: March 2008

Abstract. The pregnancies of two patients with mild intrahepatic cholestasis of pregnancy (RCP) were followed with detailed analyses of bile acids in urine. About twenty‐five different bile acids were determined by GC/MS following separation according to mode of conjugation. The results were collated with the clinical course of the disease.The first detectable change in bile acid excretion was the appearance of tetrahydroxylated bile acids at about the 30th gestational week. Somewhat later and concomitant with the rise in urinary oestriol, the total bile acid excretion started to increase. In one of the patients, who had a maximum total excretion of 84 μmol/24 h, deoxycholic acid was a major constitutent, comprising about 40% of the total. The same patient had only slightly elevated levels of tetrahydroxylated bile acids and serum amino‐transferases. The possible effect of low‐fat diet on these results is discussed.Monohydroxylated bile acids were present throughout the pregnancies in small amounts and their role as aetiological factors is discussed. The care of RCP patients is outlined, and the need for simple, specific and quantitative methods for following the course of RCP is pointed out.
Urinary bile acids in late pregnancy and in recurrent cholestasis of pregnancy
Authors: THOMASSEN PETER A. 
Published: March 2008

Abstract. The metabolic profiles of urinary bile acids in pregnant women in the last trimester and patients with recurrent intrahepatic cholestasis of pregnancy (RCP) were studied. Following separation according to mode of conjugation, about thirty different bile acids were quantitatively analysed by gas chromatography‐mass spectrometry. In all patients the sulphate fraction comprised 50–90% of the total bile acids. In RCP a shift from glycine to taurine conjugation was noted together with a slight relative increase in sulphation.A ten‐ to hundred‐fold increase in cholic and chenodeoxycholic acids was seen in RCP, the increase being mainly in the sulphate fraction. Tetrahydroxylated bile acids, tentatively regarded as 1‐ and 6‐hydroxylated products of cholic acid, were quantitatively important in patients with RCP. The relative amounts of the secondary bile acids, deoxycholic and lithocholic acids, decreased with increasing cholestasis. Metabolites hydroxylated at C‐6 were common, and the excretion of hyocholic acid was positively correlated to that of chenodeoxycholic acid. An increase in the excretion of 5α‐configurated bile acids in RCP was noted.A positive correlation between the excretion of 3β‐hydroxy‐5‐cholenoic acid and 3β,12α‐dihydroxy‐5‐cholenoic acid indicates a metabolic relationship between the two compounds. Because of the relatively small amounts of lithocholic and 3β‐hydroxy‐5‐cholenoic acids in patients with RCP, these compounds do not seem to be of pathogenetic importance in this type of cholestasis.
Influence of meal frequency on diurnal lipid, glucose and insulin levels in normal subjects on a high fat diet; comparison with data obtained on a high carbohydrate diet
Authors: GENT C. M. VAN , MIRANI‐OOSTDIJK C. PAGANO , REINE P. H. VAN , FRÖLICH M. , HESSEL L. W. , TERPSTRA J. 
Published: March 2008

Abstract. Diurnal levels of serum triglyceride (TG) were measured in six normal persons consuming a fixed solid 65% fat diet under steady state conditions in a metabolic unit. The food was divided into either three or eight similar portions, differently spaced over the day and night.The diurnal TG‐profiles on this diet were practically identical to those found under comparable conditions on a 65% carbohydrate diet [1]. Mean diurnal TG values did not significantly differ with varying meal frequency. Free fatty acid levels, however, were significantly higher on a high fat diet.Post‐prandial glucose and insulin responses did not significantly differ whether a high fat diet or a high carbohydrate diet was consumed.We conclude that the composition of the diet is of little importance in determining diurnal TG patterns when the diet consists of normal food stuffs, but that these patterns are dependent on meal frequency and distribution.
Hereditary deficiency of triosephosphate isomerase in four unrelated families
Authors: EBER STEFAN W. , DÜNNWALD MANFRED , BELOHRADSKY BERND H. , BIDLINGMAIER FRANK , SCHIEVELBEIN HELMUT , WEINMANN HANS M. , KRIETSCH WOLFGANG K. G. 
Published: March 2008

Abstract. Triosephosphate isomerase deficiencies in erythrocytes and leucocytes were discovered in three unrelated families by a heterozygote screening of 3000 blood samples. In addition, a family found by Schröter et al. [not published] was studied. In these four families, only heterozygote carriers were found. In the family described by Freycon et al. with hetero‐ and homozygote carriers of triosephosphate isomerase deficiency, the heterozygotes were reinvestigated. There was 51% of normal enzyme activity in three of the families. In the other two families the enzyme activity was 64% and 71% of normal. Two of the eleven heterozygotes, both children, were diseased, but it seems unlikely that the disorders resulted from the deficiencies.The activities of thirteen enzymes, the Km of triosephosphate isomerase for glyceraldehyde phosphate and the concentrations of metabolites were normal. Antibody titration showed normal specific activities in four families and 50% of normal in one family. No electrophoretic variant was detected.From the proved heredity, a heterozygous frequency of at least 1/1000 is indicated. A maximal frequency of 5/1000 is estimated by using further instances of triosephosphate isomerase deficiency where heredity has not yet been investigated. An explanation for the small number of known cases is that this enzyme is not routinely assayed.
Uraemic sympathetic neuropathy after haemodialysis and transplantation
Authors: RÖCKEL A. , HENNEMANN H. , STERNAGEL‐HAASE A. , HEIDLAND A. 
Published: March 2008

Abstract. Autonomic function in patients with uraemia treated conservatively, by haemodialysis, and by transplantation was evaluated by the pupillary reaction to tyramine, the Valsalva manoeuvre and a postural tolerance test.The pupillary reaction to tyramine is diminished in haemodialysis patients compared with control subjects. Renal transplantation improves, but does not correct the pupillary reaction to tyramine. The frequency of the diminished response roughly correlates with the degree of renal insufficiency, with results of a Valsalva manoeuvre, and with postural tolerance tests. Our data show that uraemic autonomic dysfunction is improved by successful renal transplantation, but not by adequate haemodialysis.
Effects of chlorpromazine hydrochloride on bile salt synthesis, bile formation and biliary lipid secretion in the Rhesus monkey: a model for chlorpromazine‐induced cholestasis
Authors: ROS EMILIO , SMALL DONALD M. , CAREY MARTIN C. 
Published: March 2008

Abstract. We studied the acute effects of intravenous infusions of chlorpromazine hydrochloride on bile salt synthesis, bile formation and biliary lipid secretion in the alert female Rhesus monkey prepared with a total biliary fistula and in a steady bile salt secretory state. In twelve studies (three animals), five doses of radio‐labelled chlorpromazine hydrochloride (1–10 mg = 2.8–28 μmol/kg) were infused intravenously for 1 h in random order. Cholestasis was induced within minutes in all experiments. The radiolabel appeared rapidly in bile, with similar recoveries in bile and urine and a 90% total cumulative output in 4 days. Both bile flow, bile salt and other biliary lipid outputs were inhibited in a dose related and reversible manner. The apparent bile salt independent bile flow was consistently abolished, and a prompt return to basal values occurred when biliary concentrations of the drug and metabolites fell below 1–2 mM. When chlorpromazine hydrochloride was infused at three doses (2.5, 5.0 and 10.0 mg = 7–28 μmol/kg) during constant intravenous infusion of 14C sodium taurocholate (300 μmol/h), bile flow, total bile salt output and 14C taurocholate output decreased within minutes. This was accompanied by a progressive rise in the serum 14C taurocholate concentration. After 90 min the taurocholate specific activity in bile increased significantly indicating that bile salt synthesis was inhibited. Secretion of retained bile salts and reversal of inhibition of bile salt synthesis occurred with time: the course of both events was correlated with the dose of the drug.Thus, in monkeys, chlorpromazine hydrochloride induces reversible, dose related cholestasis involving suppression of the bile salt dependent and independent flow, inhibition of bile salt synthesis and impairment of biliary lipid secretion. We suggest that these effects are due to both bile salt‐chlorpromazine interactions and the effect of the latter on canalicular and other membranes.
Polymyalgia arteritica: a clinical review
Authors: DOUGLAS J. G. , FORD M. J. , INNES J. A. , MUNRO J. F. 
Published: March 2008

Abstract. In a series of thirty‐seven consecutive patients with polymyalgia arteritica, twenty‐five had polymyalgia rheumatica and twelve had cranial arteritis. Some failed to respond promptly to low doses of prednisolone and it is recommended that the initial dose should be in the order of 40 mg daily. An ESR above 40 mm in the first hour was present in four patients 3 months after admission; three were found to have rheumatoid disease and one pulmonary tuberculosis.Symptomatic relapses occurred in fourteen patients on twenty‐one occasions and all responded to an increase in the daily dose of maintenance prednisolone. Most occurred in the first year and were attributable to an excessively rapid reduction in steroid therapy. Relapses occurring in patients on a stable dose of prednisolone were commonly associated with the development of rheumatoid disease. In elderly patients who have relapsed, or who have had arteritic complications, life‐long prednisolone therapy appears justifiable.
Intestinal solubilization, absorption, pharmacokinetics and bioavailability of chenodeoxycholic acid*
Authors: LEON MAURIZIO PONZ DE , LORIA P. , CARULLI N. , MURPHY G. M. , DOWLING R. HERMON 
Published: March 2008

Abstract. Little is known about the physical state, intestinal solubilization, absorption and bioavailability of chenodeoxycholic acid used in the medical treatment of gallstones. Therefore the concentrations of unconjugated chenodeoxycholic acid were measured in the supernatant and precipitate phases of intestinal contents aspirated from stomach, duodenum and jejunum of nine control subjects who took 500 mg chenodeoxycholic acid (4 times 125 mg gelatin‐coated capsules) either fasting or together with a standard liquid meal. Chenodeoxycholic acid solubility was markedly influenced by luminal pH but was little affected by endogenous conjugated bile acids when their concentrations were > 1–2 mmol/1.Systemic bioavailability of 250, 500 and 750 doses of chenodeoxycholic acid was measured in five subjects by comparing areas under 4 h serum concentration‐time curves after giving the bile acid first as a bolus intraduodenal aqueous infusion of 3H‐labelled chenodeoxycholic acid containing either 14C‐polyethylene glycol or bromsulphthalein as non‐absorbable markers, and then as gelatin‐coated capsules by mouth.Absorption was assessed by measuring the ratio of marker: bile acid in intestinal contents aspirated for 2 h from sites 60 and 120 cm distal to the duodenal infusion port and in three subjects quantitative recovery of marker was measured proximal to an occluding intestinal balloon. Absorption of duodenally‐infused chenodeoxycholic acid was 96–99% complete and bioavailability was complete with the 250 and 500 mg doses but fell to 81% with the 750 mg dose.
The effect of cigarette smoke condensate on a,‐antitrypsin, antileukoprotease and granulocyte elastase
Authors: OHLSSON KJELL , FRYKSMARK ULLA , TEGNER HANS 
Published: March 2008

Abstract. Unfractionated cigarette smoke condensate was found to affect α1‐antitrypsin and antileukoprotease, which are the dominating enzyme inhibitors in the respiratory tract. The electrophoretic and crossed immunoelectrophoretic precipitate patterns of these inhibitors were grossly altered and their inhibiting capacity reduced in both a dose and time dependent way. Other plasma proteins were also affected by cigarette smoke condensate, which in high concentrations caused precipitation of most serum proteins.Human granulocyte elastase was reduced in functional activity by similar concentrations of the smoke condensate as the inhibitors. Although the elastolytic activity was markedly reduced, the esterolytic activity was reduced to a lesser degree.
Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man
Authors: FITZGERALD G. A. , BARNES P. , HAMILTON C. A. , DOLLERY C. T. 
Published: March 2008

Abstract. Six normotensive volunteers were infused with L‐adrenaline at 001, 003, 005, 0075 and 010 μg/kg‐1 min‐1, each increment lasted 10 min. Plasma adrenaline rose from 0–27 to 4–61 nmol/1, and there were dose‐related increases in plasma renin activity, blood glucose, plasma cyclic AMP and plasma free fatty acids, but not in plasma noradrenaline and cyclic GMP. Levels of circulating adrenaline previously noted in essential hypertensives had minimal cardiovascular effects. The secretion rate of adrenaline and its rate of clearance from the circulation were calculated from plasma samples taken during an hour‐long infusion (0–083 ± 0006 μg kg‐1 min‐1) of L‐adrenaline in the same individuals. The secretion rate ranged from 1 40 to 601 nmol/min with a mean (±SEM, 6) of 2–82 ±0–76 nmol/min. Mean clearance (±SEM, 6) was 9–41 ± 1 ‐37 1/min and ranged from 4–86 to 14.611/min. The decline of plasma adrenaline following the infusion was biexponential.Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation.
Enhanced pulmonary and intestinal activation of procarcinogens and mutagens after chronic ethanol consumption in the rat
Authors: SEITZ HELMUT K. , GARRO ANTHONY J. , LIEBER CHARLES S. 
Published: March 2008

Abstract. Recent epidemiological surveys have indicated that alcoholics exhibit increased incidences of a variety of cancers. We have investigated, as a possible contributing factor to carcinogenesis in this population, the effect of chronic ethanol consumption on metabolic activation of procarcinogens by microsomes isolated from lungs and small intestine. These tissues are major sites through which procarcinogens enter the body and are also potential sites of procarcinogen metabolism.Rat litter‐mates were pair‐fed nutritionally adequate liquid diets which contained either ethanol as 36% of total energy or an equivalent energy content of carbohydrates in place of ethanol. Chronic ethanol consumption produced significant increases in pulmonary microsomal cytochrome P‐450 and microsomal ethanol oxidation. The ethanol diet also enhanced the capacity of pulmonary microsomes to activate compounds present in tobacco pyrolyzates to mutagens detectable in the Ames Salmonella auxotroph reversion assay. The ethanol diet did not alter the capacity of pulmonary microsomes to hydroxylate benzo(a)pyrene (BaP) or to activate BaP to a mutagen. In contrast, microsomes from the upper small intestine of ethanol‐fed rats did exhibit both higher levels of BaP hydroxylase activity and enhanced activation of BaP to a mutagen. The ethanol feeding also enhanced the capacity of the intestinal microsomes to activate to mutagens both tryptophan pyrolyzate and 2‐aminofluorene but did not influence the metabolic activation of these promutagens by pulmonary microsomes. Chronic ethanol consumption thus influences carcinogen metabolism in the intestine and lung in a manner which varies with respect to both carcinogen and tissue.
Familial apolipoprotein CII deficiency: plasma lipoproteins and apolipoproteins in heterozygous and homozygous subjects and the effects of plasma infusion
Authors: MILLER N. E. , RAO S. N. , ALAUPOVIC P. , NOBLE N. , SLACK J. , BRUNZELL J. D. , LEWIS B. 
Published: March 2008

Abstract. Plasma lipoproteins and apolipoproteins have been studied in a kindred with familial apolipoprotein CII (apo CII) deficiency. As in two other recently documented pedigrees, apo CII deficiency appeared to be transmitted as an autosomal recessive trait. The homozygous state was characterized by gross fasting hypertriglyceridaemia, complete absence of apo CII from plasma and failure of plasma to activate lipoprotein lipase. Post‐heparin plasma hepatic triglyceride lipase activity was normal. Hypertriglyceridaemia reflected chylomicronaemia and elevated Sf 100–400 and Sf 20–100 lipoprotein concentrations; lipoproteins of Sf 12–20 (LDL1), Sf 0–12 (LDL2), F1.23.5–9 (HDL2) and F1.20–3.5 (HDL3) were greatly reduced in concentration. Low density lipoproteins (1.006–1.063 g/ml), isolated by preparative ultracentrifugation, and high density lipoproteins, isolated by heparin/Mn++, were triglyceride‐enriched. Electroimmunoassays revealed additionally low plasma concentrations of apolipoproteins AI, AII and B and very high concentrations of apolipoproteins CIII and E in the homozygote. The parents of the proband (heterozygotes) were normotriglyceridaemic, and had normal lipoprotein lipid concentrations and normal apolipoprotein AI, AII, B, CIII and E concentrations, in spite of having low apo CII concentrations.Activation of lipoprotein lipase in the homozygote by intravenous infusion of 200 ml fresh‐frozen plasma rapidly reduced the plasma concentrations of chylomicrons and very low density lipoproteins (VLDL). Within VLDL, the decrease in concentration occurred sequentially in the Sf 100–400 and Sf 20–100 subclasses. These changes were associated during a 4‐day study period with reciprocal increases in LDL1, LDL2, HDL2 and HDL3. The plasma concentrations of apo AI and apo B also increased, associated with a less marked fall in that of apo CIII; the apo AII and apo E concentrations were unchanged.These observations support other evidence that apo CII is a cofactor for the catabolism of chylomicrons and both major subfractions of VLDL by lipoprotein lipase in man, and that human LDL1 and LDL2 are derived, at least in part, from triglyceride‐rich lipoprotein catabolism. They also suggest that both major subfractions of HDL acquire additional components during triglyceride‐rich lipoprotein catabolism. In normal subjects the plasma apo CII concentration appears to be greatly in excess of that required for adequate activation of lipoprotein lipase.
Effect of angiotensin‐ll blockade on systemic and hepatic haemodynamics and on the renin‐angiotensin‐aldosterone system in cirrhosis with ascites
Authors: ARROYO V. , BOSCH J. , MAURI M. , RIBERA F. , NAVARRO‐LÓPEZ F. , RODÉS J. 
Published: March 2008

Abstract. We have studied the effect of angiotensin‐II blockade with saralasin on the cardiovascular and hepatic haemodynamics and on the renin‐angioten‐sin‐aldosterone system in fourteen patients with cirrhosis and ascites. Control measurements showed that most of the patients had a low mean arterial pressure, high plasma volume, normal or high cardiac index, low peripheral resistance and high plasma renin activity and aldosterone concentration. The wedged hepatic venous pressure was increased in each patient and the estimated hepatic blood flow was normal in most of them.Overall, saralasin induced a significant reduction of the mean arterial pressure, cardiac index and peripheral resistance. The decrease of the peripheral resistance was greater than that of the cardiac index. Six of the patients developped a marked reduction of the mean arterial pressure with low doses of saralasin (1–2.5 μg/kg/min), and they had significantly higher plasma renin activity and lower mean arterial pressure than the remaining eight patients who showed a slight or no hypotensive response in spite of infusing saralasin up to a dose of 10 μg/kg/min. Overall, the decrease of the mean arterial pressure correlated directly with the baseline values of plasma renin activity.Angiotensin‐II blockade induced a significant reduction of the wedged hepatic venous pressure. The hepatic blood flow did not show any significant change. The decrease of the wedged hepatic venous pressure was directly related to the reduction of the mean arterial pressure and also to the control plasma renin activity.Our study indicates that in most patients with cirrhosis, ascites and high plasma renin activity, arterial pressure is maintained by the effect of endogenous angiotensin II on the peripheral vasculature, and we suggest that a pre‐existing arterial hypotension secondary to an arteriolar vasodilatation is the cause of renin release in these patients. Our results also show that angiotensin‐II blockade is accompanied by a reduction of the post‐sinusoidal hepatic vascular resistance.