bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of Effect of Cholestyramine on the Pharmacokinetics of Clofibrate in Man
Authors: Sedaghat A. , Ahrens E. H.
Published: March 2008

Abstract. This study was undertaken to determine whether cholestyramine (16 g daily) interfered with clofibrate absorption when the two drugs were given together. Fifteen patients taking I g of clofibrate twice daily (for 2 to 416 weeks) participated in the study. Clofibrate (as the acid, p‐chlorophenoxyisobutyric acid, CPIB) was quantified by thin‐layer and gas‐liquid chromatography. In patients taking clofibrate only, mean plasma CPIB concentration before the morning dose of clofibrate was 123 μg/ml. Peak levels were reached 3. 5 hours after drug intake, the mean peak plasma CPIB concentration being 193 μg/ml. Absorption of CPIB exceeded 99%. Ninety‐eight percent of the daily CPIB‐intake was excreted in the urine, 61 % being conjugated. In vivo degradation of CPIB did not occur. Free and conjugated CPIB was present in bile (mean fasting level being 55 μg/ml). The decay of radioactive CPIB in plasma was not log‐linear: the mean t 1/2 of the first exponential was 0. 45 hours, and of the second 15. 1 hours. The pool size in 3 patients 3 hours after the morning dose of clofibrate was 1054 mg. CPIB was not detectable in adipose tissue, and kinetic data gave no hint of drug accumulation in patients on long‐term therapy. In 6 patients given cholestyramine together with clofibrate, there was no significant alteration in fasting plasma CPIB levels, 24‐hour urinary and faecal excretion of CPIB or in the half‐life and pool size of the drug. A short delay in reaching peak plasma CPIB levels was the only consistent finding.
Discrepancy between the Measurement of Thyroxine‐Binding Prealbumin Plasma Level and Binding Capacity in Protein‐Calorie Malnutrition
Authors: Ingenbleek Y. , Nayer Ph. De , Visscher M. De
Published: March 2008

Abstract. The measurement of thyroxine‐bindung prealbumin (TBPA) in protein‐calorie malnutrition by two different techniques leads to the recognition of an unexpected discrepancy. Whereas TBPA plasma levels as measured by immunodiffusion are markedly decreased to 29. 3 % of the normal, those recorded by maximal binding capacity (TBPAcap) are characterized by a wide dispersion. In the control group, the ratio between TBPA and TBPA plasma level is 9. 1. In the malnourished group on admission, the same ratio is
Deoxyribonucleoside Triphosphates in Human Cells: Changes in Disease and Following Exposure to Drugs
Authors: Tattersall M. H. N. , Lavoie A. , Ganeshaguru K. , Tripp E. , Hoffbrand A. V.
Published: March 2008

Abstract. Deoxyribonucleic acid synthesis requires adequate cellular concentrations of the four deoxyribonucleoside triphosphates. Using a sensitive enzymic assay, we have measured the concentrations (pools) of these compounds in human bone marrow cells and in lymphocytes. The mean concentrations (pmol/106 cells) in normal human bone marrow cells were: deoxyadenosine triphosphate (dATP) 1. 5; deoxyguanosine triphosphate (dGTP) 0.4; thymidine triphosphate (dTTP) 1. 4 and deoxycytidine triphosphate (dCTP) 0.6; and in normal phytohaemagglutinin (PHA)‐stimulated lymphocytes (72 h cultures); dATP 3. 7; dGTP 1. 9; dTTP 9. 4 and dCTP 2. 9. The deoxyribonucleoside triphosphate concentrations were increased approximately threefold in the nucleated marrow cells from patients with leukaemia and myeloproliferative diseases. PHA‐stimulation of lymphocytes caused a marked increase of the deoxyribonucleoside triphosphate concentrations, particularly of dTTP, between 24 and 48 h of culture. In PHA‐stimulated lymphocytes, the antifolate drugs methotrexate, pyrimethamine and trimethoprim, all produced a fall in dTTP and a rise in dATP concentrations within 1 h. These effects could be reversed by folinic acid. 5‐Fluorouracil caused a fall in dTTP and in dCTP but no consistent changes in dATP; hydroxyurea caused a fall in dATP with a rise in dTTP. BCNU caused a significant fall in dATP and dCTP. Dibutyryl cyclic 3′, 5′ adenosine monophosphate and theophylline had no consistent effect on the deoxyribonucleoside triphosphate concentrations. 6‐Mercaptopurine caused a fall in dATP and dGTP, the fall in dATP being marked after 4 h incubation.

It is concluded that measurement of the deoxyribonucleoside triphosphates in human cells provides a new method of studying DNA synthesis in human disease states and of analysing the action of antimetabolite drugs on normal and diseased cells.
Granulocyte Collagenase, Elastase and Plasma Protease Inhibitors in Purulent Sputum
Authors: Ohlsson Kjell , Tegner Hans
Published: March 2008

Abstract. Sputum was collected from patients with purulent chronic bronchitis. Immuno‐chemical techniques using rabbit antiserum against human granulocyte collagenase and elastase showed the presence of both enzymes. Also the serum protease inhibitors α1‐antitrypsin and α2‐macroglobulin were demonstrated. Their protease inhibiting capacity was saturated. Granulocyte elastase and collagenase occurred not only in complexes with the inhibitors, but also as free enzymes. All sputa showed free proteolytiC., elastolytic and collagenolytic activity. The concentration of collagenase was equal in the sol phase and in the gel phase of the sputa, but most of the elastase was bound to the gel phase.
Defective Thyroglobulin Endocytosis and Hydrolysis in Thyroid Cold Nodules1
Authors: van den Hove‐Vandenbroucke M. F. , Couvreur‐Eppe M. , Visscher M. De
Published: March 2008

Abstract. The catabolic phase of thyroid secretion has been studied by incubating thyroid slices with 0.1%125I thyroglobulin (Tg) in the following cases: 11 follicular adenomas (FA), 8 hyerplastic nodules in multinodular glands (NM), 3 carcinomas (follicular or papillary, FC., PC) and normal (N) or micronodular tissue (M). Tg pinocytosis is severely impaired in all cold nodules (25 to 60 % reduction). In the follicular tumours (FA, FC), Tg hydrolysis is more affected than would be expected based only on reduced Tg endocytosis: the hydrolysis products remain in the phagolysosomes instead of being secreted. As far as the acid hydrolases are concerned these enzymatic activities are increased in nearly all nodules, in particular in follicular adenomas and carcinomas.
Turnover of a Prostaglandin Precursor, Arachidonic Acid, in Rheumatoid Arthritis
Authors: Hagenfeldt Lars , Wennmalm Åke
Published: March 2008

Abstract. The plasma concentration and the turnover of free arachidonic and oleic acids were determined in patients with rheumatoid arthritis and in control subjects. The plasma level of free arachidonic acid, but not of oleic acid, was significantly decreased in male rheumatoid patients. Female patients did not differ from healthy subjects in this respect. Following treatment with indomethacin, a significant increase in the plasma concentration of free arachidonic acid was observed in rheumatoid patients of both sexes. It is suggested that the findings in the rheumatoid patients reflect a partial exhaustion of the pool of arachidonic acid serving as precursor in the synthesis of prostaglandin.
The Glucose‐Induced Gastrointestinal Stimulation of Insulin Secretion in Man: Relation to Age and to Gastrin Release
Authors: Rehfeld J. F. , Stadil F.
Published: March 2008

Abstract. An oral 50 g glucose tolerance test and a simple intravenous glucose infusion test were performed in 20 young (20–32 years), 20 middle‐aged (42–55 years), and 20 old (65–81 years) normal subjects. Blood glucose, serum insulin, and serum gastrin concentrations were measured during all tests. The intravenous glucose infusion duplicated the oral blood glucose curve in young, middle‐aged, and half of the old subjects. In the remaining old subjects the intravenous blood glucose curve was below the oral blood glucose curve. Glucose and insulin concentrations were of similar magnitude in all groups, but maximum concentrations were reached later in the old subjects. Glucose per os induced a rapid rise in serum gastrin concentrations of the order of 10 pmol/1 and a subsequent decrease of about 20 pmol/1 in all groups. The intravenous glucose infusion induced no significant changes in serum gastrin concentrations. The non‐glycaemic (i. e. enteral) stimulation of insulin secretion was expressed as the difference between the integrated incremental areas of the oral and intravenous insulin curves in subjects with identical glucose curves during the two tests. This stimulation was of similar magnitude in all age groups, and it was not correlated to variations in gastrin concentrations. However, in the young subjects the enteral stimulation was greater during the first 30 minutes and smaller during the two last hours when compared to the old subjects.

The results suggest that: 1. A simple intravenous glucose infusion test can be used to copy the oral blood glucose curve. 2. The size of the enteral stimulation of insulin secretion during the whole test is independent of age. 3. The action of the glucose‐induced enteral stimulation is delayed with age, and closely linked to the dynamics of the glycaemic stimulus. 4. The glucose‐induced gastrin release is probably too small to affect insulin secretion significantly.
Is Phlorizin or Its Aglycon the Inhibitor of Intestinal Glucose Transport?
Authors: Blum A. L. , Haemmerli U. P. , Lorenz‐Meyer H.
Published: March 2008

Abstract. Inhibition of glucose transport by phlorizin was examined in man by perfusion of an isolated small bowel segment. Inhibition was similar in normal and lactase deficient subjects. Since the small bowel of lactase deficient subjects contains only very small amounts of phlorizin hydrolase, phlorizin and not a product of enzymatic cleavage is the inhibitor of the small intestinal glucose carrier.
The Growth Hormone Response to Insulin Induced Hypoglycemia in Anorexia Nervosa and Control Underweight or Normal Subjects
Authors: Brauman H. , Gregoire F.
Published: March 2008

Summary. Hypoglycaemic stimulation of growth hormone (GH) secretion has been measured in 12 anorexia nervosa patients, 11 adolescents approximately matched for weight and age, 14 underweight adults with no history of anorexia nervosa and 27 normal patients. The results showed a high proportion of blunted growth hormone responses among the anorexia nervosa patients as compared to normal subjects, underweight adolescents or adults. In the group of underweight adults, diminished growth hormone responses were most frequently seen in patients with depressive illness. The complex pathogenesis of the diminished growth hormone response in anorexia nervosa involves many factors; undernutrition itself, possible hypothalamic insufficiency related to the psychopathological background and other endocrine abnormalities like hypogonadism, relative hypercorticism and hypothyroidism. The interference of the nutritional, psychological and endocrine factors could not be dissociated in our investigation or from the review of the literature on this subject. It is suggested that hypothalamic insufficiency plays a prominent role in the growth hormone hyporesponsiveness in anorexia nervosa. Although diminished, the stimulated growth hormone response remains higher in anorexia nervosa than in true hypopituitarism. This phenomenon coupled to a preserved or even increased suprarenal function enables one to differentiate cachexia resulting from anorexia nervosa and hypopituitarism leading eventually to cachexia.
Radioimmunoassay of Prostaglandins Fα, E1 and E2 in Human Plasma
Authors: Dray F. , Charbonnel B. , Maclouf J.
Published: March 2008

Abstract. Antibodies against prostaglandins (PG)F2α, E1 and E2 were obtained in rabbits immunized with respectively PG F2α, PG E1 and PG E2 conjugated to bovine serum albumin by carbodiimide. A radioimmunoassay capable of measuring 7 pg of PG Fα, 2 pg of PG E2 and 14 pg of PG Ej in human peripheral plasma is described. Plasma samples (pH 3, citric acid) are extracted with cyclohexane: ethyl acetate, 1:1 and then chromatographed on silicic acid columns to separate the prostaglandins into three fractions: fraction I, PG A, PG B and some unknown immunoraactive compounds; fraction II, PG E and fraction III PG Fα. The recovery is 80 %± 6. 2. Mean plasma levels iu adults of PG Fa and PG E, expressed in pg/ml: ‐PG Fα 12 ± 2. 8 (n = 25 men), 8 ± 2. 3 (n = 18 women, follicular phase), 7 ± 1. 4 (n = 18 women, luteal phase). ‐PG E1 40. 5 + 7. 6 (n = 13 men), 38 + 17. 1 (n = 10 women). ‐PG E2 4. 5 ± 1 (n = 12 adult subjects).

The major characteristics of the method described herein are the following: ‐ a large volume of plasma has to be processed (10 ml or more for PG Fa and PG E1, 5 ml or more for PG E2). ‐ a chromatographic step is necessary to separate the different prostaglandins which makes it possible to circumvent problems of immunological cross reactivity and interference with unknown immunoreactive compounds. ‐ great care has been taken in collection of blood samples, especially to insure complete removal of blood cells namely platelets.
Effects of Burn Injury on Insulin Secretion and on Sensitivity to Insulin in the Rat in vivo
Authors: Frayn K. N.
Published: March 2008

Abstract. Both insulin resistance and impairment of insulin secretion are know to occur in man after injury. The relative importance of these effects was studied in rats 2 h after a non‐lethal 20 % dorsal scald. No impairment of insulin secretion was found after this injury. Concentrations of both blood glucose and plasma insulin were elevated in scalded rats. Scalded rats responded to intravenous glucose injection (1. 0 g/kg) with a further rise in plasma insulin concentration, which remained normal for the prevailing blood glucose concentration. However, marked impairment of glucose tolerance was observed, indicating the presence of insulin resistance. After intravenous insulin injection (1. 0 U/kg) the initial rate coefficient for fall of blood glucose concentration was significantly lower (p < 0–02) in scalded (mean 3. 9 % min. ‐1) than in control rats (mean 6–3 % min. ‐1). The minimum in blood glucose concentration after insulin injection was reached at 10 min. in control rats, but not until 60 min. after injection in scalded rats. This difference was due to a delay in compensation for the hypoglycaemia in the scalded rats, since the rate of disappearance of insulin measured by injection of a tracer of 25i‐labelled bovine insulin was not decreased after this injury. It was concluded that the impairment of glucose utilization in scalded rats (Heath and Corney, 1973) is due to decreased sensitivity to insulin rather than to suppression of insulin release.
Conversion of Type III Hyperlipoproteinaemia to Type IV Hyperlipoproteinaemia by a Fat‐Free, Carbohydrate Rich Diet
Authors: Vessby B. , Carlson L. A.
Published: March 2008

Abstract. Hyperlipoproteinaemia type III has been considered a clear cut clinical entity characterized by the presence of cholesterol rich “floating” beta very low density lipoproteins (VLDL) after ultracentri‐fugation. Carbohydrate inducibility is pronounced in type III. This study was undertaken to elucidate the effect of a high carbohydrate diet in type III as an effort to clarify a suggested association between type III and IV hyperlipoproteinaemia. On an isocaloric fat free carbohydrate rich diet the lipoprotein pattern changed as the VLDL triglycerides increased 31 per cent on average and LDL and HDL cholesterol decreased by 40 and 22 per cent. The high ratio cholesterol/triglycerides in VLDL was normalized. The lipoprotein levels in serum after carbohydrate induction showed all characteristics of a type IV with high VLDL triglycerides, normal cholesterol/triglyceride ratio in VLDL, subnormal cholesterol levels in LDL and HDL with changed relation between LDL1 and LDL2. On electrophoresis the floating beta band disappeared. It is probable that depending on the nutritional situation, the metabolic defect in type III may be expressed either as a type III or a type IV. An explanation of the effects of the carbohydrate rich diet on the lipoprotein pattern is suggested.
Observations on the Effect of CO2 and Temperature on the Sickling Phenomenon
Authors: Rampling M. W.
Published: March 2008

Abstract. The explanation of the effect of CO2 on the sickling phenomenon has, in the past, been based solely on the alteration of the oxygen affinity of haemoglobin induced by the CO2, and hence solely on the oxygen saturation of the haemoglobin. A re‐investigation of this phenomenon, reported here, shows that this explanation is inadequate; rather, a full explanation requires the use of Perutz's hypothesis that the haemoglobin molecule can exist in various conformationally distinct states, the relative concentrations of which are dependent not only on the oxygen saturation of the molecules but also on other factors such as pH and 2, 3‐diphosphoglycerate (DPG) concentration. The effect of temperature on the sickling phenomenon is explained in a similar fashion. Low temperature is found to have no effect on the morphology of irreversibly sickled cells.
Plasma Catecholamines and Blood Substrate Concentrations: Studies in Insulin Induced Hypoglycaemia and after Adrenaline Infusions
Authors: Christensen N. J. , Alberti K. G. M. M. , Brandsborg O.
Published: March 2008

Abstract. Plasma adrenaline‐blood glucose interrelationships in insulin‐induced hypoglycaemia in man have been studied using a sensitive double‐isotope derivative method for adrenaline estimation. Plasma adrena‐i‐line reached a peak of 1. 24 ng/ml at 45 minutes after insulin while blood glucose reached a nadir of 22 mg/ 100 ml at 30 minutes. There was a strong correlation both between the rise in adrenaline and the degree of hypoglycaemia and between the rise in adrenaline and the post‐hypoglycaemic rise in glucose. Plasma noradrenaline rose from 0. 29 to 0. 59 ng/ml, the rise correlating with the rise in adrenaline. Changes in pulse rate preceded and were unrelated to changes in plasma catecholamines. Fuel mobilisation in response to adrenaline infusion (6 μg/min. for 20 min.) in normoglycaemic man was also studied. Plasma adrenaline concentration rose from a mean of 0. 02 ng/ml to 0. 71 ng/ml while plasma noradrenaline concentration was unchanged. Blood glucose rose from 71 to 98 mg/100 ml while plasma insulin decreased from 11 to 8 yU/ml. Blood lactate rose by 0. 85 mM while pyruvate concentration remained unchanged. Blood glycerol concentration rose twofold and ketone body concentration threefold but there was little change in the concentrations of the glucogenic amino acids, alanine, glutamate and glutamine. Both the 3‐hydroxybutyrate/acetoacetate ratio and the lactate/pyruvate ratio rose implying a more reduced intracellular state due presumably to increased hepatic fatty acid oxidation. It is concluded that adrenaline enhances the recycling of lactate and spares glucose through the mobilitsation of lipids but that amino acids are little affected.
Effect of Fasting on Two Postheparin Plasma Triglyceride Lipases and Triglyceride Removal in Obese Subjects
Authors: Huttunen J. K. , Ehnholm C. , Nikkilä E. A. , Ohta M.
Published: March 2008

Abstract. A new method was used for selective measurement of lipoprotein lipase and hepatic lipase in human postheparin plasma. Hepatic lipase was assayed in 1. 0 M NaCl without addition of serum, and the activity of lipoprotein lipase was determined in 0. 1 M NaCl after immunoprecipitation of hepatic lipase with specific antiserum. The activity of both these enzymes and the total lipolytic activity were measured in plasma samples taken during a 4‐h infusion of heparin. Each of the activities was related to basal serum triglyceride concentration and to the fractional removal constant (K) of Intralipid in 13 obese subjects before and after prolonged fasting. During a normal isocalqric diet the lipolytic activities showed a biphasic response to heparin infusion in all subjects. A peak activity was reached within 30 minutes (“early response”) and thereafter the lipase activities decreased to a constant level maintained during the rest of the heparin infusion (“late response”). The early response of lipoprotein lipase showed a significant inverse correlation with the basal serum triglyceride level (r – 0. 85) and a significant positive correlation with the fractional removal rate of Intralipid (r + 0. 84). The late response of lipoprotein lipase was not related to either of these parameters. The early response of hepatic lipase was not correlated with basal triglyceride concentration or Intralipid removal, whereas the late response of this enzyme showed a significant negative correlation with the removal rate of Intralipid (r = ‐ 0. 82). After fasting for several days the acute response of all lipolytic activities to heparin was markedly decreased or totally abolished, but the magnitude of the late response was similar to that seen in the fed state. The fractional removal rate of Intralipid was slightly increased by starvation. All correlations between postheparin plasma lipases and serum triglyceride concentration and removal disappeared in fasting subjects. It is concluded that the rapidly releasable lipoprotein lipase probably reflects the activity of the tissue enzyme(s) which is responsible for the primary removal of very low density lipoprotein (VLDL) triglycerides and chylomicrons. It is probable that this component of the postheparin plasma lipolytic activity is derived from the endothelial lipoprotein lipase pool. This enzyme plays a key role in the efflux of plasma triglycerides under normal conditions, and it is thus one determinant of plasma triglyceride level. Prolonged fasting obviously changes the triglyceride removal sites and mechanism but does not impair the removal efficiency.
The Response of Thyrotropin and Triiodothyronine to Various Doses of Thyrotropin Releasing Hormone in Normal Man
Authors: Weeke J.
Published: March 2008

Abstract. The relationship between serum thyrotropin (TSH) and serum triiodothyronine (T3) before and after injection of different doses of thyrotropin releasing hormone (TRH), given as single injections or as multiple injections with short intervals, was investigated in normal men. A positive correlation between prestimulated serum TSH and serum T3 levels and between the increase in the serum TSH and the serum T3 levels after TRH was found when repeated tests were performed in the same individual. There was a dose dependent TSH and T3 response to TRH. The smallest dose that produced a maximal response of both TSH and T3 was only 30 ug TRH. After six injections of 30 ug TRH with an interval of 30 minutes the increase in TSH was two times and the increase in T3 was three times as high as the maximal increase after single injections of TRH. This test with multiple injections of TRH may prove to be of clinical value in the measurement of both pituitary and thyroid function in selected patients. The close positive correlation between the serum TSH and serum T3 levels in basal conditions, demonstrated in four normal subjects in this study, probably reflects the steady state level determined by the hypothalamus from which the feedback control of TSH secretion operates.
Alteration of Drug Metabolism During Cholestasis in Man*
Authors: Carulli N. , Manenti F. , de Leon M. Ponz , Ferrari A. , Salvioli G. , Gallo M.
Published: March 2008

Abstract. The morphological and functional alterations of the smooth endoplasmic reticulum of the liver cell related to biliary stasis have brought attention to drug biotransformation during cholestasis. The metabolism of meprobamate, pentobarbital and tolbutamide was assessed in subjects with intrahepatic recurrent cholestasis (3), cholestatic hepatitis (6), extrahepatic biliary obstruction (7) and normal controls (16). In the patients with recurrent intrahepatic cholestasis no differences in drug metabolism were noted as compared to the control group. In cholestatic hepatitis the plasma half‐lives of meprobamate (828 ± 422 min.) and pentobarbital (39 ±6. 5 hours) were significantly longer than in controls (444 ± 37 and 25. 4 ± 1. 1 respectively). Tolbutamide plasma half‐life appeared unchanged. The most striking variations were observed in the patients with extrahepatic biliary obstruction. In such cases while meprobamate half‐life was unchanged, pentobarbital half‐life was significantly prolonged (31. 2 + 2. 5) and the in vitro metabolism of the drug, using liver preparations, was decreased to less than 50 % of the control value. In contrast the metabolism of tolbutamide was accelerated as evidenced by a significant decrease of plasma half‐life (165 ± 48 min. versus 384 ± 76 of the controls) and an enhanced urinary excretion of the drug's metabolites. However the metabolism of tolbutamide in vitro did not show any difference between normal and cholestatic liver. Whatever the mechanism of the peculiar behaviour of tolbutamide in extrahepatic biliary obstruction it seems to be related to the increased bile salt concentration during cholestasis. In fact the low values of plasma half‐life increase significantly either relieving the biliary obstruction or producing a bile salt depletion with cholestyramine. Preliminary results in vitro suggest the bile salt could displace tolbutamide from albumin binding thus increasing the amount of free drug available for biotransformation by the liver. In conclusion cholestasis may affect drug metabolism depending on the degree of biliary stasis, liver cell injury and the type of drug tested. The mechanism could be that of an impaired biotransformation in the smooth endoplasmic reticulum or could involve extrahepatic factors.
Fatty Acid Pattern of Lipids in Normal and Dystrophic Human Muscle
Authors: Kunze D. , Reichmann G. , Egger E. , Olthoff D. , Döhler K.
Published: March 2008

Abstract. The fatty acid distribution of the main lipid fractions: triglycerides (TG), phosphatidylcholine (PCh), phosphatidylethanolamine (PE), and sphingomyelin (Sph) of muscle from 6 patients with progressive muscular dystrophy (p. m. d.), Duchenne, 8 to 12 years old was estimated and compared with normal controls of different age. In view of the results of several authors about varied fatty acid distribution in immature muscle a third group comprising samples of neonatal muscle was studied. 1. The fatty acid pattern of the lipid fractions TG, Sph, and PE from muscle of patients with p. m. d. shows no important variation in comparison to normal controls. In contrast to this the fatty acid distribution in PCh is extremely varied: the percentage of 18:2 is decreased and correspondingly the content of 18:1 is increased. In view of the high percentage (nearly 10 %) in which linoleic acid is substituted by oleic acid in PCh, effects on the plasma membrane are to be expected. 2. The fatty acid pattern in neonatal muscle shows in nearly all positions of the fractions TG, Sph, PE, and PCh a different distribution from normal or dystrophic muscle. In view of the most important variation in dystrophic muscle it must be stated that generally 18:2 is decreased. This deficit was replaced by an increase of all other fatty acids (not only at a substitution by 18:1 as given in p. m. d.). Therefore the diminished content of linoleic acid in PCh of neonatal and dystrophic muscle cannot be interpreted as expression of a corresponding or similar lipid metabolism in both tissues. The results were seen as signs of significant qualitative alterations especially of PCh in p. m. d. They were discussed as proof of our thesis that the basic defect in p. m. d. concerns the specific acylation of PCh with linoleic acid.
Interaction of Secretin and Insulin on Human Forearm Metabolism
Authors: Chisholm D. J. , Klassen G. A. , Dupre J. , Pozefsky T.
Published: March 2008

Abstract. The effect of secretin on forearm metabolism (muscle compartment) was examined in the presence of low and high concentrations of insulin. Continuous infusions (30 min. duration) of secretin 12 ng/min. (SEC), insulin 160 ng/min. (INS) or these doses of insulin and secretin together (INS + SEC) were delivered into the brachial arteries of normal volunteers. SEC alone was without significant effect on forearm metabolism. INS as previously reported, stimulated glucose and potassium uptake and inhibited the output of some amino acids from the deep venous bed. The two hormones together (INS + SEC) increased maximum lactate (p < 0. 025) and alanine output (p < 0. 005) beyond that observed with INS alone. A marked calcium output occurred (p < 0. 001) with the combined infusion which was not observed with either hormone alone. Potassium metabolism with INS + SEC was similar to that observed with INS alone. These results suggest that these two hormones, acting in concert, stimulate glycolysis and net calcium efflux. This joint action of insulin and secretin may have a physiological role in the immediate postprandial period.
Colchicine Administration to Mice: A Metabolic and Ultrastructural Study
Authors: Singh A. , Marchand Y. Le , Orci L. , Jeanrenaud B.
Published: March 2008

Abstract. A single injection of colchicine has been administered to normal albino mice, and the metabolic effects as well as the hepatic ultrastructural changes resulting from this treatment have been studied at various time intervals. A marked decrease in circulating triglyceride levels was evident 4 hours after colchicine injection and was maximum after 11 hours. It coincided with a marked increase in hepatic triglyceride content. Twenty hours after colchicine administration, plasma triglyceride levels and hepatic triglyceride content had returned to normal values. Similar changes in the levels of circulating proteins were observed although their magnitude was less than that observed for triglycerides. Ultrastructurally, colchicine treatment resulted in the virtual disappearance of the microtubules from the hepatocytes, and in the appearance of many clusters of vesicles containing very low density lipoprotein‐like particles which eventually transformed into lipid droplets. These ultra‐structural alterations were also completely reversible, the reversibility coinciding with the morphological reappearance of microtubules. Finally, colchicine treatment resulted in marked metabolic changes that are interpreted as representing an attempt, by the organism, to keep adequate energy sources during the period of lack of circulating triglycerides.
Ischaemic Heart Disease and Associated Risk Factors in 40 Year Old Men in Edinburgh and Stockholm
Authors: Oliver M. F. , Nimmo I. A. , Cooke Margaret , Carlson L. A. , Olsson A. G.
Published: March 2008

Abstract. The incidence of ischaemic heart disease in men in their early forties is approximately three times greater in Edinburgh than in Stockholm. To gain more information about some of the possible reasons for this striking difference, a random sample of apparently healthy men aged 40 was selected from each city. Identical clinical and biochemical measurements were made and interlaboratory variations were eliminated by making each analysis in the same laboratory. Serum triglycerides were higher in Edinburgh men than in Stockholm men, and the shapes of the‐distribution curves were significantly different. Serum cholesterol concentrations were similar in the two cities. Fasting plasma glucose concentrations were the same in the two cities. After a standardised glucose load, the mean plasma glucose decreased in men in both cities and significantly more in Edinburgh. There were significantly more men in Edinburgh with high insulin values. There were significantly more cigarette smokers in Edinburgh. This is possibly the most clear‐cut difference between the cities. Edinburgh men were shorter than Stockholm men. Analysis of the distributions of high risk characteristics showed that Edinburgh had more putative high risk individuals for ischaemic heart disease. This study is exploratory in nature and the differences found cannot by themselves explain the greater incidence of ischaemic heart disease in Edinburgh compared with Stockholm. Nor are they likely to be independent of such influences as diet, physical activity and ethnic origin. The fact that such marked differences can be found emphasises the potential value of studying in this way populations with dissimilar incidence of disease.
Effect of Lipids on Insulin, Growth Hormone and Exocrine Pancreatic Secretion in Man *
Authors: Raptis S. , Dollinger H. C. , von Berger L. , Kissing J. , Schröder K. E. , Klör U. , Pfeiffer E. F.
Published: March 2008

Abstract. Influences of fat on release of insulin, growth hormone and pancreatic enzyme secretion were studied in 35 metabolically healthy subjects. A fat solution containing 40 g of soy bean oil was administered, I. V., orally and intraduodenally. In all cases there was a similar increase of insulin but the rise in serum insulin after oral or intraduodenal fat administration was not related to the changes in plasma free fatty acids, free glycerol and triglyceride levels. Blood sugar responded according to insulin secretion. The route of fat administration may possibly influence growth hormone secretion. Following intraduodenal fat administration volume and bicarbonate contents of the duodenal juice rose slightly whereas trypsin and bilirubin content increased considerably. These results suggest that insulin secretion after oral or intraduodenal administration of fat is influenced by intestinal factors. Cholecystokinin‐pancreozymin and gastric inhibitory polypeptide are qualified to serve as such factors.
Phenazone Metabolism in Patients with Liver Disease
Authors: Andreasen P.B. , Greisen G.
Published: March 2008

Phenazone metabolism was studied in 14 patients with liver disease and six normal volunteers. The plasma and renal clearance of phenazone and the 4‐hydroxyphenazone excretion in urine was significantly decreased in the patients with liver disease. The urinary excretion of 4‐hydroxyphenazone was significantly correlated to the plasma clearance of phenazone (r =+ 0.95, P < 0.001), to quantitative liver function as measured by the galactose elimination capacity (r =+ 0.95, P < 0.001), and to the prothrombin values (r =+ 0.82, P < 0.001). The determination of the 4‐hydroxyphenazone excretion in urine may be used as an easy and non‐invasive test of quantitative liver function.
Myofibrillar AlPase, DNA and Hydroxyproline Content of Human Hypertrophied Heart
Authors: Leclercq J.F. , Swynghedauw B. , Bouveret P. , Faucomprez C. , Piguet V.
Published: March 2008

70 human hearts were studied less than 36 hours after death. The apex, and in some cases other parts of the myocardium were homogenized, DNA, hydroxyproline content, myofibrillar Ca2+ and Mg2+ ATPase were measured. In normal hearts the DNA and collagen content were 372 ± 9 mg and 36 ± 7 mg. Ca2+ and Mg2+ ATPase of the myofibrils prepared from these hearts have shown the same specific activity (35 ± 5 and 34 ± 6 nmol/min./mg) as those from fresh biopsies taken during open‐chest surgery. The heart weight correlates with the DNA content (r =+ 0.58 ‐ p < 0.01) and with the myofibrillar ATPase (r = ‐ 0.33 ‐ p < 0.02) but not with the DNA concentration nor with the collagen content or concentration. The main result of this study was the presence of a negative correlation between the DNA content of the heart and the Mg2+ or Ca2+ myofibrillar ATPase (r = ‐ 0.31, p < 0.05 ‐ r = ‐ 0.45, p < 0.01). This correlation was analysed with reference to the histological and biochemical studies published by several authors in human or experimental heart hypertrophy and it was suggested that in human heart hypertrophy the decrease of the myofibrillar or myosin ATPase is a direct consequence of the high degree of polyploidy of the muscular cells observed in this condition.
Human Adipose Tissue in Culture
Authors: Smith U. , Isaksson O. , Nyberg G. , Sjöström L.
Published: March 2008

Abstract. Explants of human adipose tissue were cultured for several days with noradrenaline (NA). After the culture period the explants were carefully washed, preincubated and then incubated for 2 h by a technique analogous to those generally used to study adipose tissue metabolism. The results show that explants cultured with NA were considerably less responsive to the acute lipolytic effect of catecholamines than explants not previously exposed to NA. The diminished responsiveness could not be reversed by the addition of phentolamine or by preincubating the explants with a prostaglandin antagonist and it was dependent upon the concentration of noradrenaline used in the culture medium as well as upon the period of time that the explants were exposed to the hormone. The cyclic AMP (cAMP) levels did not increase in response to NA in these explants. Addition of theophylline or dibutyryl cAMP elicited a lipolytic response. However, the phosphodiesterase levels were not increased in the explants cultured with noradrenaline. When freshly excised tissue specimens were incubated in the culture medium which had previously contained NA the acute lipolytic effect of catecholamines was blunted. The results indicate that an antagonist is formed during the incubation with NA which inhibits the responsiveness to catecholamines. The effect of the antagonist seems to be exerted at a step prior to the formation of cAMP.
Diabetes Mellitus in Gonadal Dysgenesis: Studies of Insulin and Growth Hormone Secretion
Authors: Rasio E. , Antaki A. , Van Campenhout J.
Published: March 2008

Abstract. On the basis of results obtained from an oral glucose tolerance test (OGTT), twenty patients with gonadal dysgenesis were classified as normal (N = 8) and diabetic (N = 12). The two groups of patients were further tested by a rapid intravenous glucose injection, a tolbutamide test, an insulin sensitivity test and an oral amino acid load. Fasting levels of plasma growth hormone (GH) were normal in all subjects but one. Approximately 1/3 of the GH responses during testing periods were abnormal, being either absent during hypoglycaemia or following amino acid ingestion, or paradoxically increased during hyperglycaemia. No correlation was found between the degree of carbohydrate intolerance and the levels of plasma GH. There was no gross alteration of tissue sensitivity to exogenous insulin. The g‐cell response to tolbutamide, amino acid and intravenous glucose were comparable in patients with a normal or a diabetic OGTT. In both groups, the rates of decrease of blood glucose following tolbutamide or intravenous glucose were also similar and within the normal range. During OGTT, the diabetic group had a delayed insulin release and a low insulinogenic index. It is concluded that in gonadal dysgenesis the intolerance to an oral carbohydrate load is frequently associated with, but unrelated to, anomalies of the GH secretion. In diabetic subjects, the process of insulin secretion loses its normal sensitivity to the oral glucose stimulus while remaining unaltered and similar to that of non‐diabetic subjects in response to tolbutamide, amino acid and intravenous glucose.
Bile Salt Glucuronides: Identification and Quantitative Analysis in the Urine of Patients with Cholestasis
Authors: Fröhling W.
Published: March 2008

Abstract. Glucuronides of lithocholate, chenodeoxycholate and cholate were synthesized enzymatically and characterized by thin layer chromatography, column chromatography and specific enzymatic hydrolysis. Bile salt glucuronides were quantitatively analysed in the urine of patients with intra‐ and extra‐hepatic cholestasis and were found to be present in 19 out of 20 patients studied. Our patients with intrahepatic cholestasis excreted 8.9 mg non‐sulphated and non‐glucuronidated bile salts, 18.2 mg sulphated bile salts and 7.2 mg glucuronidated bile salts. The patients with extrahepatic cholestasis excreted 14.7 mg non‐sulphated and non‐glucuronidated bile salts, 20.7 mg sulphated bile salts and 4.7 mg glucuronidated bile salts. These findings indicate that glucuronidation of bile salts occurs in man and represents a metabolic pathway in patients with cholestasis.
Sodium Balance and Renal Tubular Sensitivity to Aldosterone During Total Fast and Carbohydrate Refeeding in the Obese1)
Authors: Kolanowski J. , Desmecht P. , Crabbé J.
Published: March 2008

Abstract. In man the first days of fasting are characterized by enhanced natriuresis despite an increase in aldosterone secretion. Therefore the possibility of a decreased renal tubular sensitivity to this hormone was considered. The response to aldosterone infused before a fast and again on day 4 of fasting was evaluated in 12 starving obese women in terms of urinary sodium, chloride and potassium excretion. The data were compared to those obtained from 20 untreated starving obese women. In addition, salivary flow and sodium output were measured before and after aldosterone infusion in 4 out of the 12 patients treated. The involvement of aldosterone in the mechanism of fasting natriuresis and glucose‐induced sodium retention was evaluated by means of spironolactone treatment (Aldactone A; 300 mg/day p.o.) on days 6 to 8 of the fast, with an oral glucose load (100 g) on day 7. Aldosterone infused on day 4 of the fast caused on average only 40 % of the antinatriuretic effect it achieved before the fast. On the other hand even before aldosterone infusion, salivary sodium output was markedly reduced during the fast to levels comparable to those observed after aldosterone treatment in the pre‐fast period. Furthermore, spironolactone administration on day 6 of the fast was associated with a prompt and marked increase in natriuresis. These 3 sets of facts indicate a definite biological activity of aldosterone during the initial phase of fasting with factor(s) interfering at the renal level with the normal expression of the hormonal action on sodium balance. There was still a distinct antinatiuretic effect of glucose in the presence of spironolactone, but less pronounced than when glucose was administered alone. The well‐documented hyperaldosteronism of a total fast may represent a compensatory mechanism to decrease sodium loss at the end of a week‐long fast. In addition a marked sodium‐retaining effect of glucose can be demonstrated after aldosterone action is blocked by spironolactone. This provides another indication that glucose stimulates sodium retention through mechanism(s) which do not involve aldosterone.
Action of H1 and H2 Inhibitors on the Response of Histamine Sensitive Adenylyl Cyclase from Guinea‐Pig Mucosa1
Authors: Perrier C. V. , Griessen M.
Published: March 2008

Abstract. In the guinea‐pig, it has been shown that homogenates of mucosa from the fundus contain an adenylyl cyclase system that is activated by histamine as well as by prostaglandins PGE] and PGAj. The effects of burimamide, an H2‐inhibitor, and mepyramine and chlorpheniramine, both Hj‐inhibitors, were tested. Both H) and H2 inhibitors behaved kinetically as competitive inhibitors of histamine, but the Km derived for burimamide (2.5 ‐ 4.1 10‐5) was significantly lower than that for either chlorpheniramine (0.9 ‐ 1.9 10‐4) or mepyramine (1.3 ‐ 1.4 10‐4). On the other hand none of the three inhibitors influenced the cyclase activation by PGE1 and PGA1. These results suggest that there are at least two types of receptors in the preparation studied, one responsive to histamine and the other to the prostaglandins, and that the specificity of H1‐ and H‐2receptors is not absolute in the broken cell preparation.
The Effect of Fructose Infusions on the Oxygen Transport System of Human Blood
Authors: Standl E. , Kolb H.J.
Published: March 2008

Abstract. In 9 healthy subjects the erythrocyte 2,3‐diphosphoglycerate (2,3‐DPG) concentration, which modifies the oxygen affinity of haemoglobin, decreased by more than 25 per cent within 60 minutes of the beginning of a fructose infusion (0.5 g.kg body weight‐1.h‐1). In contrast erythrocyte adenosine triphosphate (AIP) concentration was unchanged. In spite of the diminished 2,3‐DPG concentrations the oxygen affinity of whole blood actually measured remained unaltered. However, at the same time both the arterial and the venous blood pH had fallen by 0.05 or more, in vitro experiments indicated that this fall of erythrocyte 2,3‐DPG was not due to a direct effect of fructose on the intra‐erythrocytic regulation of 2,3‐DPG or to changes indirectly related to the intravenous administration of fructose in vivo, i.e. an increase of the blood lactate/pyruvate ratio or a decrease of plasma inorganic phosphate. It is suggested that two opposing effects on the oxygen transport system of blood are induced by fructose infusions: 1) a displacement of the oxygen dissociation curve to the right due to the Bohr effect 2) a virtually counterbalancing shift of the oxygen dissociation curve to the left due to decreased erythrocyte 2,3‐DPG concentrations.
Metabolism of Very Low Density Lipoproteins in Hyperlipidaemia: Studies of Apolipoprotein B Kinetics in Man
Authors: Sigurdsson G. , Nicoll A. , Lewis B.
Published: March 2008

The metabolism of very low density lipoprotein‐B (VLDL‐B) peptide was studied in nineteen subjects with endogenous hypertrigylceridaemia (Types V, IV and lib), three patients with heterozygous familial hyperbetalipoproteinaemia (Type Ila) and eight healthy subjects, by reinjecting autologous radioiodinated VLDL. The kinetics of VLDL‐B peptide were followed. The mean turnover rate of VLDL‐B peptide was significantly higher in the hypertriglyceridaemic group than in the control group but a considerable overlap in turnover rate was found between these groups. The patients with heterozygous familial hyperbetalipoproteinaemia had a normal turnover rate of VLDL‐B peptide. A significant positive correlation was found between the turnover rate of VLDL‐B peptide and VLDL‐triglyceride concentration in the whole series.

It is concluded that the underlying defect in endogenous hypertriglyceridaemia is heterogeneous. Overproduction of VLDL is a major determining factor in seme patients whereas a reduced clearance is the determining factor in others.
Triglyceride Metabolism in Acute Starvation: The Role of Secretin and Glucagon
Authors: Stout R.W. , Henry R.W. , Buchanan K.D.
Published: March 2008

Plasma lipid and hormone levels have been measured during 72 hours total starvation in nine healthy subjects, to assess the relative importance of hormones and substrates in human triglyceride metabolism. Plasma free fatty acid and glycerol concentrations rose steadily on each day of starvation. Plasma triglyceride concentrations rose on the second and third days, from a control level of 649 ± 67 mg/1 to a maximum of 1001 ± 66 mg/1. Plasma cholesterol concentrations remained unchanged while glucose concentrations fell and insulin did not change. Plasma glucagon (C‐GLI) levels doubled while secretin levels, reported previously, rose threefold. It is suggested that during acute starvation the rise in triglyceride concentration results from the increased availability of free fatty acids, and that elevated secretin and glucagon levels enhance lipolysis and hence provide substrates for triglyceride synthesis.