bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclic AMP production in isolated colonic epithelial crypts: a highly sensitive model for the evaluation of vasoactive intestinal peptide action in human intestine
Authors: DUPONT C. , LABURTHE M. , BROYART J. P. , BATAILLE D. , ROSSELIN G.
Published: March 2008

Abstract. Epithelial cells of human colon were isolated in the form of entire epithelial crypts devoid of vasoactive intestinal peptide (VIP) as measured by radioimmunoassay. This preparation allowed the demonstration, in any conditions tested, of the considerable sensitivity of cyclic AMP accumulation in colonic epithelium to VIP. The magnitude of cyclic AMP accumulation in this preparation was dependent on temperature, time of incubation and concentration of phosphodiesterase inhibitor. At 37 C, in the presence 0–2 mM 3‐isobutyl‐l‐methylxanthine, a 4‐fold increase of cyclic AMP above basal was observed 5 min after addition of 10‐10 M VIP and a 16‐fold increase (maximal response) was obtained after 20 min by 10‐8 M VIP. The dose‐response curve was studied in conditions of equilibrium, i.e. a 60 min incubation at 15CC in the presence of 0–2 mM 3‐isobutyl‐l‐methylxanthine, and appeared to be monophasic with a half‐maximal stimulation at l‐2 times 10‐9 M VIP. Synthetic secretin, porcine intestinal histidine isoleucine amide (PIHI) and the other active substances (prostaglandins E and isoproterenol) were 2500, 600, and at least 100 times less potent than VIP, respectively. Adenylate cyclase of membranes prepared from epithelial crypts was stimulated by concentrations of VIP identical to those acting on cyclic AMP level in intact crypts. Plasmas from patients with the watery diarrhoea syndrome were able to induce a significant rise of cyclic AMP production in human colonic epithelial crypts. This effect was suppressed by previous exposure of the plasmas to a specific anti‐VIP immunserum.
The effect of beta‐adrenergic blockade on metabolic rate and peripheral thyroid metabolism in obesity
Authors: JUNG R. T. , SHETTY P. S. , JAMES W. P. T.
Published: March 2008

Abstract. The interactions of catecholamine and thyroid hormones in determining changes in metabolic rate were assessed in obese patients given propranolol, both on weight maintenance diet and during semistar‐vation. Propranolol reduced the resting metabolic rate by 8‐6% on a weight maintenance diet but had no effect during energy restriction. Since propranolol led to a similar fall in triiodothyronine (T3) and an increase in reverse T3 on both diets, the early fall in RMR on semi‐starvation may depend on catecholamine‐mediated mechanisms. Beta‐adrenergic blockade might promote energy retention on a normal energy intake but should not reduce the efficacy of slimming diets.
Increased plasma HDL‐cholesterol and apo A‐1 in sedentary middle‐aged men after physical conditioning
Authors: KIENS BENTE , JORGENSEN IDA , LEWIS STEVEN , JENSEN GORM , LITHELL HANS , VESSBY BENGT , HOE STEEN , SCHNOHR PETER
Published: March 2008

Abstract. Previous studies have demonstrated an inverse relationship between plasma high density lipoproteins (HDL) cholesterol and coronary heart disease risk. In the present study we investigated prospectively the effect of a moderate physical conditioning programme on plasma lipids and lipoproteins, especially HDL‐cholesterol and apolipoprotein A‐I (apo A‐I), the major apoprotein of HDL. Healthy, sedentary, middle‐aged men were randomly selected and assigned either to a training group (n= 24, age 40±3–4, mean ± SD) or to a control group (n= 13, age 39±50). Training consisted of various indoor and outdoor sports activities 45 min/day, 3 times/week for 12 weeks at an intensity of approximately 80% of measured maximal oxygen uptake (VO2 max). The trained subjects were studied at 4, 8 and 12 weeks. The training increased VO2 max by 12% (P < 0–01). Increases were observed in both apo A‐I (10%, P < 0 02) and HDL‐cholesterol (8%, P < 002) after training, with significant increases already after 4 and 8 weeks, respectively. Furthermore, decreases in total plasma cholesterol (5%, P < 0004) and plasma triglycerides (26%, P < 0 003) were found without changes in body weight, body composition, cigarette smoking, alcohol consumption or the percentage composition of dietary intake. Fasting serum‐insulin concentrations decreased significantly during training. No changes were noted in the control group. The present study demonstrates prospectively that moderate physical training can increase HDL.
Interaction of laxatives with enzymes of cyclic AM P metabolism from human colonic mucosa
Authors: SIMON BERND , KATHER HORST
Published: March 2008

Abstract. The mechanism by which laxatives such as dioctyl sodium sulfosuccinate and ricinoleic acid evoke colonic fluid secretion has been suggested to involve mucosal cyclic AMP. Ricinoleic acid and dioctyl sodium sulfosuccinate were tested for their capacity to modulate the key enzymes of cAMP‐metabolism‐ adenylate cyclase and cAMP‐phosphodiesterase‐in human colonic mucosa.

Both laxatives were ineffective stimuli of human colonic adenylate cyclase. In contrast to ricinoleic acid, dioctyl sodium sulfosuccinate was a competitive inhibitor of soluble cAMP‐phosphodiesterase activity. These experiments suggest that the cathartic properties of dioctyl sodium sulfosuccinate in human colonic mucosa might be mediated by cyclic AMP via inhibition of soluble phosphodiesterase activity.
Effects of pancreatic polypeptide on motilin and circulating metabolites in man
Authors: ADRIAN T. E. , GREENBERG G. R. , BARNES A. J. , CHRISTOFIDES N. D. , ALBERTI K. G. M. M. , BLOOM S. R.
Published: March 2008

Abstract. Pancreatic polypeptide was infused intravenously in healthy fasting subjects at 1 pmol kg‐1 (n= 7) and 4 pmol kg‐1 min‐1 (N= 10) producing plasma PP concentrations of 223±37 pmol/1 (mean ± SEM) and 891±64 pmol/1 respectively. These levels are similar to and four‐fold higher than those seen after a normal mixed breakfast in healthy young adults. In a separate study five healthy subjects ingested a small breakfast during infusion of PP on different days at 1 pmol kg‐1 min‐1 and 2 pmol kg‐1 min‐1 respectively. PP at 1 pmol kg‐1 min‐1 caused a marked reduction in fasting plasma motilin concentrations to 20% of the basal level (P < 0–001). There were, however, no significant changes in plasma concentrations of insulin, glucagon, gastrin, secretin, enteroglucagon, gastric inhibitory peptide or neurotensin.

Despite previous reports possibly implicating PP in metabolism, there were no significant effects on blood levels of glucose, alanine lactate, 3‐hydroxybutyrate, glycerol or non‐esterified fatty acids, either in the fasting state or after the ingestion of food. Although it seems unlikely that PP is a major hormonal regulator of intermediary metabolism in man, its ability to suppress motilin at physiological concentrations suggests the possibility of an indirect influence on digestive motor function.
Turnover in humans of β2‐microglobulin: the constant chain of HLA‐antigens
Authors: KARLSSON F. ANDERS , GROTH TORGNY , SEGE KARIN , WIBELL LARS , PETERSON PER A.
Published: March 2008

Abstract. The turnover of β2‐microglobulin, the common subunit of the HLA antigens, has been examined in normal subjects and in some patients with kidney disorders, multiple myeloma and rheumatoid arthritis. All patients displayed elevated serum levels of β2‐microglobulin. The plasma disappearance curve of 125I‐β2‐microglobulin demonstrated that the protein has a rapid turnover (11/2 = 21 h; range 1 1–2‐8 h) in normal persons and in patients with a normal glomerular filtration rate. In patients with kidney disorders the impaired renal filtration prolonged the turnover time and led to elevated serum levels of β2‐microglobulin.

Simultaneous measurements of 125‐β2‐microglobulin in serum and urine allowed estimations of the β2‐microglobulin net reabsorption in the renal tubuli. Two patients with renal disease reabsorbed 84% and 89%, respectively, of the β2‐microglobulin filtered in the glomeruli. In normal persons the net reabsorption is close to 100%.

In patients with normal kidney function increased serum levels of β2‐microglobulin seem to be due to an increased synthetic rate of the protein as the elimination rate is normal. HLA antigen heavy chains in serum are present in smaller amounts than β2‐microglobulin. The present data, therefore, suggest an imba‐lanced synthesis of the two chains.
Effects of jejuno‐ileal bypass on serum lipoproteins and glucose tolerance in severely obese patients
Authors: KRAL JOHN G. , SJÖSTRÖM L. , GUSTAFSON A.
Published: March 2008

Abstract. Plasma insulin and blood glucose during oral glucose tolerance tests (OGTT) and serial determinations of serum lipoprotein fractions before and after jejuno‐ileostomy in twenty severely obese (mean weight 137 kg) patients with a mean age of 29 years revealed statistically significant postoperative decreases in all parameters concomitant with a mean weight loss of 42 kg. Before the operation the patients were hyperinsulinaemic and had elevated blood glucose levels during OGTT though no patient had overt diabetes. Serum triglyceride and total cholesterol levels were normal but HDL cholesterol was significantly lower than in controls. During follow‐up at least until body weight had levelled off a mean 19 months postoperative, there were statistically significant reductions in blood glucose and plasma insulin as well as serum total cholesterol and lipoprotein fractions. There was no change in serum triglycerides. The low preoperative HDL levels decreased. In a subgroup of these patients we have earlier shown postoperative increases in arterial tissue cholesterol coincident with the present significant decreases in HDL as well as in LDL cholesterol.

Correlations between total cholesterol and lipoprotein cholesterol values in serum and blood glucose and plasma insulin at fast and during OGTT and changes in these parameters demonstrate interrelationships between lipid and carbohydrate metabolism. The bypass procedure most likely reduces the intestinal synthesis of HDL which in turn may increase hepatic cholesterol synthesis. Evidently there is a multifactorial aetiology for the low HDL levels in the severely obese both before and after jejuno‐ileostomy.
Plasma aspirin esterases in normal individuals, patients with alcoholic liver disease and rheumatoid arthritis: characterization and the importance of the enzymic components
Authors: RAINSFORD K. D. , FORD N. L. V. , BROOKS P. M. , WATSON H. M.
Published: March 2008

Abstract. Two enzymes in human plasma capable of hydrolysing aspirin (‘aspirin esterases’) were isolated (by ion exchange and gel chromatography) and characterized, since their activity has been reported to be important in certain disease/therapeutic situations. The optimum pH and calcium concentration for plasma aspirin esterases were 80 and 5 mmol/1 respectively.

The main enzymic activity (enzyme ‘C’) was associated with plasma cholinesterases. This component had a Km of 6‐5 mmol/1 for aspirin and a Kmax of 0–27 /imol salicylate/mg protein/min at pH 80 (Ca2+ present). It was not acetylated by aspirin but was inhibited by anti‐cholinesterase agents (eserine, echothiophate) and the neuromuscular blocking agent, decameth‐onium. The other enzymic component in plasma was albumin esterase.

The sex difference in aspirin esterase activity in normal individuals previously reported by Menguy and co‐workers [1] was re‐investigated since it appeared that they had employed non‐optimal assay conditions. No significant differences were observed between the sexes in either normal individuals or patients with rheumatoid arthritis when the enzyme was assayed at either pH 7‐4 or the optimal pH of 80 (with Ca2+ added). The plasma albumin esterase activity was, however, markedly depressed in patients with alcoholic liver cirrhosis when assayed at pH 7‐4 and 80. Plasma aspirin esterases were elevated in nine rheumatoid arthritic patients receiving gold salt or D(‐)penicil‐lamine. Aspirin esterase 'C activity was negatively correlated with pain score in the plasma of female but not male rheumatoid arthritics. Also the percentage activation by calcium of aspirin esterase was correlated with the concentration of plasma calcium indicating that small changes in plasma calcium concentration may markedly affect enzymic activity.

These results suggest that certain drugs (anti‐cholinesterase agents), disease states (e.g. alcoholic liver cirrhosis) or genetic deficiences (e.g. inactive pseudo‐cholinesterase) may be potentially important in the pharmacological and iatrogenic activities of aspirin.
Very low density lipoprotein overproduction in genetic forms of hypertriglyceridaemia
Authors: CHAIT ALAN , ALBERS JOHN J. , BRUNZELL JOHN D.
Published: March 2008

Abstract. Very low density lipoprotein kinetic parameters were compared in familial hypertriglyceridaemia and familial combined hyperlipidaemia, two distinct genetic forms of hypertriglyceridaemia. Very low density lipoprotein apoprotein B turnover rate was greater in hypertriglyceridaemic subjects with familial combined hyperlipidaemia (0.99 ± 0.27 mg/kg)/h; n = 5; P < 0.005) and also in familial hypertriglyceridaemia (0.74 ± 0.10; n = 6; P < 0.005) than in age and weight matched non‐hyperlipidaemic controls (0.54 ± 0.21; n = 6), suggesting that the hypertriglyceridaemia seen in both genetic disorders was due to very low density lipoprotein overproduction. Very low density lipoprotein apoprotein B turnover rate was greater in familial combined hyperlipidaemia than in familial hypertriglyceridaemia while plasma triglyceride turnover was higher in familial hypertriglyceridaemia. This disparity in the turnover rates of apoprotein B and triglyceride between these disorders was accompanied by a higher very low density lipoprotein triglyceride/apoprotein B ratio in familial hypertriglyceridaemia than in familial combined hyperlipidaemia (P < 0.001) and in normals (P < 0.005).

The findings suggest that the hypertriglyceridaemia of familial combined hyperlipidaemia is due to overproduction of very low density lipoprotein of normal composition, while that of familial hypertriglyceridaemia is due to oversecretion of triglyceride‐enriched very low density lipoprotein.
Acute ethanol ingestion and haem biosnthesis in health subjects
Authors: McCOLL KENNETH E. L. , THOMPSON GEORGE G. , MOORE MICHAEL R. , GOLDBERG ABRAHAM
Published: March 2008

Abstract. The effects of acute ethanol ingestion on the activities of the enzmes of haem biosnthesis in peripheral blood cells have been monitored in eight health subjects. The mitochondrial enzmes delta‐aminolaevulinic acid (ALA) snthase, coproporph‐rinogen oxidase and ferrochelatase were measured in leucoctes and the ctosolic enzmes ALA dehdratase, porphobilinogen (PBG) deaminase and uroporphrinogen decarboxlase in erthroctes. Ingestion of 1–316 mol ethanol resulted in increased activit of the rate‐controlling enzmes ALA snthase and PBG deaminase and decreased activit of the other four enzmes. There was also increased urinar excretion of coproporphrin. These observations ma be relevant to the biochemical mechanisms involved in the ethanol‐related conditions, sideroblastic anaemia, cutaneous hepatic porphria and hepatic siderosis.
Kinetic bases of the primar hperlipidaemias: studies of apolipoprotein B turnover in geneticall defined subjects
Authors: JANUS E. D. , NICOLL A. M. , TURNER P. R. , MAGILL P. , LEWIS B.
Published: March 2008

Abstract. Autologous 131I‐labelled ver low densit lipoprotein (VLDL) and 125I‐labelled low densit lipoprotein (LDL) were injected into seven normal subjects and into fort‐three hperlipidaemic patients, classified into groups on the basis of famil studies and clinical findings, to quantitate VLDL and LDL apolipoprotein B kinetics. In normal subjects, mean VLDL‐B peptide snthetic rate was 151 mg kg‐1 da‐1, mean LDL‐B peptide snthetic rate 7‐7 mg kg‐1 da‐1 and mean LDL‐B fractional catabolic rate (FCR) 0–31 da‐1.

In heterozgous familial hpercholesterolaemia (n= 14) VLDL‐B peptide production was normal in patients with normal triglceride levels; in those with high triglceride levels there was either VLDL overproduction or a catabolic defect. LDL‐B peptide snthetic rates ranged from high normal to increased (8‐5‐180 mg kg‐1 da‐1) and LDL‐B peptide FCR values were markedl reduced (0–14‐0‐28 da‐1) confirming the presence of a defect in LDL catabolism but indicating over‐production as well.

In familial combined hperlipidaemia (n= 11) VLDL‐B peptide production ranged from normal to elevated (13‐9‐44‐4 mg kg‐1 da‐1, mean 23‐8 mg kg‐1 da‐1) correlating with the VLDL triglceride level (i.e. with the phenotpic expression of the disorder). LDL‐B peptide production ranged from high normal to markedl increased (8–9‐19‐5 mg kg‐1 da‐1, mean 12‐2 mg kg‐1 da‐1) and correlated with LDL cholesterol levels (i.e. the phenotpe), (r=+ 0–66, P < 005).

Three patients with unclassified hpercholesterolaemia had increased LDL‐B peptide snthetic rates. One patient with remnant hperlipoproteinaemia (tpe III) had a high normal VLDL‐B peptide snthetic rate, 17‐3 mg kg‐1 da‐1, and a strikingl low FCR of VLDL‐B.

In familial hpertriglceridaemia (three patients)
Serum lipids, biliary lipid composition, and bile acid metabolism in vegetarians as compared to normal controls
Authors: HUIJBREGTS A. W. M. , SCHAIK A. VAN , BERGE‐HENEGOUWEN G. P. VAN , WERF S. D. J. VAN DER
Published: March 2008

Abstract. Since dietary factors have been implicated in various diseases, such as coronary heart disease, gallstone formation and colonic cancer, possibly by affecting cholesterol and bile acid metabolism, we studied serum lipid levels, biliary lipid composition, cholic acid and deoxycholic acid kinetics in a group of young healthy male vegetarians and in age, sex and weight matched control subjects. Daily intake of nutrients was higher with respect to polyunsaturated fatty acids, carbohydrates and dietary fibre in the vegetarian group. Although mean serum lipid levels in the vegetarian were 8–28% lower than in the control subjects, differences were not statistically significant. Biliary lipid and biliary bile acid composition were similar in both groups. Bile acid kinetics, measured after simultaneous injection of [3H] cholic acid and [14C]deoxycho‐lic acid, showed a slightly lower output of cholic acid and a slightly higher input of deoxycholic acid in the vegetarians, this causing a significantly (P < 0025) higher 7α‐dehydroxylation fraction (input deoxycholic acid divided by synthesis of cholic acid) in the vegetarians. Our results in young males suggest that bile acid conservation is associated with a vegetarian diet, but do not support the supposition that a vegetarian diet reduces deoxycholate formation.
Evaluation of the roles of lipoprotein lipase and hepatic lipase in lipoprotein metabolism: in vivo and in vitro studies in man
Authors: NICOLL ANNE , LEWIS BARRY
Published: March 2008

Abstract. The roles of lipoprotein lipase (LPL) and hepatic lipase in very low density lipoprotein (VLDL) and VLDL remnant metabolism were investigated by (1) in vivo studies where the kinetics of VLDL‐apo B removal were measured in patients with non‐functioning lipoprotein lipase systems, and (2) in vitro studies where the relative capacities of hepatic lipase and LPL to hydrolyse the triglyceride (TG) of different lipoprotein substrates was measured. The results indicated that VLDL‐apo B removal was not impaired in patients with non‐functional LPL, nor was there any apparent abnormality in the conversion of VLDL‐apo B to intermediate‐ (IDL) and low (LDL) density lipoprotein‐apo B. Post‐heparin plasma hepatic lipase activity against VLDL was normal in these subjects. Purified normal hepatic lipase had a similar Km for VLDL‐TG hydrolysis (1.57 mmol/l) to that of LPL (1.49 mmol/l). However, at equal lipoprotein TG concentration, hepatic lipase had increasing activity with lipoproteins of decreasing particle size, in the order chylomicrons ≪ VLDL of Sf 100–400 < VLDL of Sf 60–100 < VLDL of Sf 20–60 < IDL. The mean contribution of hepatic lipase to VLDL‐TG hydrolysis by post‐heparin plasma was 35% in normal controls, but the contribution to IDL‐TG hydrolysis was significantly higher (mean = 58%). It is concluded that hepatic lipase plays a significant role in VLDL and, especially, IDL metabolism, at least in patients with non‐functioning lipoprotein lipase.
Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein‐lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy
Authors: LITHELL HANS , BOBERG JONES , HELLSING KRISTOFFER , LJUNGHALL SVERKER , LUNDQVIST GUDMAR , VESSBY BENGT , WIDE LEIF
Published: March 2008

Abstract. Twenty‐one patients with increased, thyroid‐stimulating‐hormone (TSH) concentrations in the serum while fasting were studied before and after substitution with l‐thyroxine. Nine patients had TSH values < 40 mU/1 and an average serum‐thyroxine value of 64 nmol/1. Twelve patients with TSH‐values > 40 mU/1 had an average serum‐thyroxine value of 23 nmol/1. On treatment TSH and thyroxine normalized (reference limits < 8 mU/1 and 65–160 nmol/1 respectively) as did also the response to a load with thyroid‐releasing hormone (TRH).

In the group with severe thyroid dysfunction (TSH > 40 mU/1) the lipoprotein‐lipase activities in both adipose and skeletal‐muscle tissue were subnormal before therapy and increased during substitution treatment. This was also reflected in a significant increase of the post‐heparin, lipoprotein‐lipase activity in the plasma and of the fractional removal rate of an i.v. injected fat emulsion. Ten out of twelve patients showed a decrease of the triglyceride concentration in whole serum, which reflected changes of the triglyceride concentrations in low‐density lipoproteins (LDL) and high‐density lipoproteins (HDL) more than changes in very‐low‐density lipoproteins, in which the triglyceride concentration was unchanged during treatment. In LDL, both the cholesterol and triglyceride concentrations were elevated before therapy and decreased by 22% and 32% of the pretreatment values, respectively, during treatment. Furthermore, the serum‐apolipoprotein‐B concentration decreased by 16%. The serum‐apolipoprotein‐A‐I concentration was subnormal before treatment and the lipid composition of the HDL particle was changed towards an enrichment of triglycerides. During treatment, the HDL‐triglyceride concentration decreased, whereas that of HDL cholesterol was unchanged. The fasting serum‐insulin concentration increased significantly during the treatment period.

In the group with mild hypothyroidism (TSH < 40 mU/1), there were no significant changes similar to those found in severe hypothyroidism.
The effect of a single dose of propranolol on human erythrocytes in vivo
Authors: REINHART W. , STÄUBLI M. , STRAUB P. W.
Published: March 2008

Abstract. In vitro propranolol has a profound effect on erythrocytes as indicated by a decrease of the packed cell volume and a shift to the right of the oxygen dissociation curve. Because of the lack of satisfactory in vivo studies, the effect of 80 mg propranolol and placebo was compared in twelve volunteers in a double‐blind study. Although plasma propranolol concentrations varied greatly from individual to individual, all propranolol subjects demonstrated effective beta‐blockade. Packed cell volume, mean cellular volume, plasma trapping after haematocrit centrifugation, P 50, 2,3‐DPG, ATP, erythrocyte filterability and blood viscosity at different packed cell volumes (50% and 80%) and shear rates (11.5, 23, 46, 115 and 230 s‐1) did not change significantly following administration of either propranolol or placebo. These findings are of interest in view of the use of betablocking agents in critically ill patients.
The release of β‐ thromboglobulin and platelet factor 4 during extracorporeal circulation for open heart surgery
Authors: CELLA GIUSEPPE , VITTADELLO ORNELLA , GALLUCCI VINCENZO , GIROLAMI ANTONIO
Published: March 2008

Abstract. Cardiopulmonary bypass is extremely damaging to platelets and it causes a quantitative and qualitative alteration in their functions. We evaluated the release of two platelet‐specific proteins, β‐thromboglobulin (βTG) and platelet factor 4 (PF4), in patients who underwent extracorporeal circulation for open heart surgery. A parallel release (basal value βTG: 119.6 ng/ml, PF4 30 ng/ml) was present for both proteins in a time dependent fashion until the end of extracorporeal circulation. High average levels were observed in patients in whom the bypass was stopped after about 1 h (βTG 1606 ng/ml, PF4 745 ng/ml) and similarly in those in whom the bypass was stopped after about 2 h (βTG 1540 ng/ml, PF 4754 ng/ml). No correlation was found either between the level of PF4 and the additional heparin administered after the initial standard dose (r= 0.29, P>0.10) and between the level of PF4 and the amount of heparin consumed during the bypass (r= 0.05, P>0.5).
Fibronectin in synovial fluid and tissue in rheumatoid arthritis
Authors: VARTIO TAPIO , VAHERI ANTTI , ESSEN ROBERT VON , ISOMÄKI HEIKKI , STENMAN SVANTE
Published: March 2008

Abstract. Fibronectin is a glycoprotein found in body fluids, loose connective tissue matrix and in basement membranes. Fibronectin in rheumatoid arthritis synovial fluid was immunologically indistinguishable from the plasma form, as shown by double‐diffusion analysis. Fibronectin isolated from rheumatoid synovial fluid by affinity chromatography on gelatin‐Sepharose had a polypeptide pattern similar to that of plasma fibronectin in SDS‐polyacrylamide gel electrophor‐esis. In fifty‐one patients with rheumatoid arthritis and related diseases fibronectin concentrations in synovial fluid were 445 ±103 μg/ml (mean ±SD) and within normal range, 335±52 μg/ml, in plasma. Immuno‐fluorescence staining showed a prominent increase of fibronectin in the proliferating synovial connective tissue in rheumatoid arthritis as compared to normal synovial membrane. The results suggest an increased local production of fibronectin in rheumatoid synovial tissue.
Blood‐brain barrier permeability of L‐dopa in man
Authors: FRII M. L. , PAULSON O. B. , HERTZ M. M. , BOLWIG T. G.
Published: March 2008

Abstract. The permeability of L‐dopa across the blood‐brain barrier was studied in twelve patients by means of the indicator dilution method. The extraction of [l‐14C]L‐dopa and [3‐14C]L‐dopa was 11.7% and 10.4%, respectively. After pretreatment with carbi‐dopa the extraction was unchanged (13.5% and 11.6%). The permeability coefficient (P) was calculated to 0.9×10‐5 cm s‐1.
Intrapartum stress Sowers the concentration of high density lipoprotein cholesterol in cord plasma
Authors: MARTINSEN K. , EHNHOLM C. , HUTTUNEN J. K. , TERVILÄ L. , KOSTIAINEN E.
Published: March 2008

Abstract. The concentration of cord plasma triglycer‐ides, total cholesterol, high density lipoprotein (HDL) cholesterol, and apoprotein AI and All has been measured in acidotic and non‐acidotic full‐term neonates without chronic maternal‐fetal problems. The level of cord plasma triglycerides was significantly increased (P<005) and that of HDL cholesterol significantly decreased (P< 0–001) in the newborns belonging to the quintile class with the lowest blood PH (≤ No differences were present between the acidotic and non‐acidotic neonates in the plasma concentrations of total cholesterol or of apoprotein AI and All. The concentration of triglycerides was increased (<005) and that of HDL cholesterol was decreased (P<005) in the infants with the longest duration of labour. No correlation was observed between the concentrations of glycerol and lipids or lipoproproteins in cord plasma. The results suggest that intrapartum stress raises plasma triglycerides and induces qualitative and quantitative changes in the plasma high density lipoprotein fraction in the newborn.
Decreased arteriovenous flow resistance in the left gastric venous area in cirrhotic patients
Authors: KOYANAGI NOBUHIRO , INOKUCHI KIYOSHI , NAKAYAMA SHINICHI , SAKATA HISANOBU , BEPPU KAZUSHIGE
Published: March 2008

Abstract. To assess the relationship between the fluid mechanics in the left gastric venous area and the portal trunk, manometric measurements were made in patients with or without cirrhosis of the liver. In ten normal subjects, temporary portal vein occlusion produced comparable elevation in both the occluded left gastric venous pressure (OLGP) and the portal vein pressure (PVP); 152–4129 mm of water in OLGP and 115–452 mm of water in PVP. In sixty cirrhotic patients, however, the portal vein occlusion resulted in far less increase in OLGP than that in PVP; 281–365 mm of water in OLGP and 281–540 mm of water in PVP. In other words, regarding pressure measurements, the relationship was ‘separated’ in cirrhotics, but ‘continuous’ in normal subjects. Mathematical analysis of the data using a modification of Wheat‐stone bridge model suggested that the arteriovenous flow resistance in the left gastric venous area of cirrhotics was reduced to less than one fifth of that in the controls. It would appear that the increased flow capacity as a result of a reduced arteriovenous flow resistance is responsible for the functional ‘separation’ from the portal trunk.
Plasma lipids in kidney transplanted children and adolescents: influence of pubertal development, dietary intake and steroid therapy
Authors: BROYER MICHEL , TÉTE MARIE‐JOSEPHE , LAUDAT MARIE‐HÉLÉNE , BERTHELIER SONIA GOLDSTEIN with the technical assistance of MARTINE , DARTOIS ANNE‐MARIE , BERTHELIER MARTINE
Published: March 2008

Abstract. Plasma triglycerides and/or cholesterol were significantly increased in twenty‐four of thirty kidney transplanted children and adolescents with stable renal function, at least one year after the last rejection crisis who received low dose prednisone therapy. The cholesterol increment was related to both low density and high density lipoproteins. However, similar to findings in adult allograft recipients, these increases were very variable: six subjects had normal levels, eight had increased triglycerides, five increased triglycerides and cholesterol, and eleven increased cholesterol. No influence of renal function was found in this series of patients all of whom had plasma creatinine below 160 μmol/1. Subjects who had achieved sexual development had lower cholesterol values. An insignificant difference was observed between patients receiving daily and alternate‐day steroid therapy, but a significant negative correlation was found between plasma triglycerides and fractional urinary excretion of 17 OH corticosteroids in the first 6 h after an oral dose of prednisone. Finally, no correlation was found between energy intake and triglycerides; but a significant correlation was observed between protein intake and plasma cholesterol.

In conclusion, some patients show a high level of triglycerides and/or cholesterol after renal transplantation, possibly due to a different individual response to steroid therapy.
The stimulus‐secretion coupling of amino acid‐induced insulin release: insulinotropic action of branched‐chain amino acids at physiological concentrations of glucose and glutamine
Authors: SENER ABDULLAH , MALAISSE WILLY J.
Published: March 2008

Abstract. The stimulant action of branched‐chain amino acids upon insulin release was examined in rat pancreatic islets incubated at physiological concentrations of D‐glucose and L‐glutamine. In the presence of the latter nutrients, L‐leucine and L‐isoleucine used together at a physiological concentration (0.25 mmol/1 each) doubled insulin secretion rate. The effect of L‐leucine upon insulin release was dose‐related without any indication of a threshold phenomenon. The insulinotropic action of L‐leucine was mimicked, to a limited extent, by its nonmetabolized analogue, 2‐aminobicyclo[2,2,l] heptane‐2‐carboxylic acid, l‐Glutamine slightly inhibited glucose‐stimulated insulin release. It is concluded that, under close‐to‐physiological conditions, L‐leucine stimulates insulin release by acting in the islet cells both as a fuel and as an allosteric activator of glutamate dehydrogenase.
Quantitative liver functions after 70% hepatectomy
Authors: YILDIRIM S. I. , POULSEN H. E.
Published: March 2008

Abstract. Following 70% hepatectomy on rats the galactose elimination capacity, taken as a measure of the cytosolic liver function, was reduced from 2.55 ± 0.48 to 1.27 ± 019 (mean ± < SEM) μmol/min. Six hours later it was restored to control values. The prothrombin index, representing the function of the endoplasmic reticulum, was reduced from 1.13±0.02 to 0.34 ± 0.02 (arbitrary units) after 12 h, and it was restored after 96 h. The rapid normalization of the initial fall in the capacity to metabolize galactose reflects a two‐ to three‐fold increase of the galactose metabolizing capacity of the remaining liver.

This study demonstrates that liver functions are dissociated in time following 70% hepatectomy in the rat, and that the galactose elimination capacity is restored before regeneration can compensate for the loss in liver cell mass.
Persisting modification of dogs' basal exocrine pancreatic secretion after repeated intravenous calcium injections
Authors: NOEL‐JORAND M.C. , COLOMB E. , ASTIER J.P. , SARLES H.
Published: March 2008

Abstract. Biochemical, histological and crystallographic studies were carried out on the pure exocrine pancreatic juice of calcium treated dogs and of normal dogs.

The ionic equilibrium was changed leading to modifications of protein and calcium solubilities with formation of protein and calcium precipitates.

Plugs were further studied: three components were identified, (a) cells mostly of ductal origin, (b) calcium salt already crystallized in the plug on coming out of the duct, (c) protein material in the central part of the plug.

The importance of these data is in relation with pancreatic disorders by hypercalcaemia and hyperparathyroidism.
Platelet function in diabetes mellitus in relationship to complications, glycosylated haemoglobin and serum lipoproteins
Authors: BETTERIDGE D.J. , ZAHAVI J. , JONES N.A.G. , SHINE B. , KAKKAR V.V. , GALTON D. J.
Published: March 2008

Abstract. Mean levels of 8‐thromboglobulin and platelet factor 4 were highly significantly elevated in diabetes compared to controls (72.6 v. 36.3 ng/ml, P < 0.0005; 48.5 v. 16.5 ng/ml, P < 0.0005; respectively) as was malondialdehyde formation (12.4 v. 8.1 nmol/109 platelets, P< 0–0005). Diabetics with retinopathy had significantly higher levels of ß‐thromboglobulin than those without retinopathy (79 v. 70 ng/ml; P < 0.042). However, those diabetics without clinical evidence of vascular disease had levels of ß‐thromboglobulin and platelet factor 4 significantly higher than controls.

β‐Thromboglobulin did not correlate with glycosylated haemoglobin but did correlate significantly with individual lipid and lipoprotein levels (ß‐thromboglobulin v. total triglyceride, P < 0–029; u. VLDL triglyceride, P<0441; v. LDL cholesterol, P<O.042; v. HDL/total cholesterol ratio, P< 0.02).

Abnormal platelet function may contribute to the vascular complications of diabetes mellitus.
Intestinal obstruction in germ‐free dogs
Authors: HENEGHAN J. B. , ROBINSON J. W. L. , MENGE H. , WINISTÖRFER H.
Published: March 2008

Abstract. Mechanical occlusions were created in the intestines of four germ‐free dogs. At the time of the operation, a control loop of mid‐intestine was perfused in vivo and then excised for examinations in vitro, which included the determination of the equilibrium uptake of phenylalanine and of ß‐methyl‐glucoside, the influx kinetics of phenylalanine and morphometric analysis of the mucosa by microdissection and stereological techniques. Seven days after establishment of the occlusion the abdomen was reopened, and loops above and below the occlusion were perfused, and then excised for the same tests in vitro.

Unlike occluded loops of conventional dogs, the intestine of the germ‐free animal above the occlusion does not secrete water and electrolytes into the lumen. Its transport properties in vitro do not differ from those of the control loop, and the morphometric analyses reveal only slight changes in villus structure. The loop below the obstruction undergoes marked atrophy, as has been observed in conventional dogs.

The results suggest that the copious secretion that occurs above an intestinal obstruction in normal animals is due to the presence of an abundant bacterial population in the obstruction fluid.
Effect of parenteral hyperalimentation on serum lipoproteins and on lipoprotein lipase activity of adipose tissue and skeletal muscle
Authors: TASKINEN MARJA‐RIITTA , TULIKOURA ILKKA , NIKKILÄ ESKO A. , EHNHOLM CHRISTIAN
Published: March 2008

Abstract. This study reports on the effects of parenteral nutrition with glucose alone or in combination with Intralipidr̀ on heparin‐releasable lipoprotein lipase (LPL) activity of adipose tissue and skeletal muscle and on serum lipoproteins. Thirteen patients with postoperative hypercatabolism and nine patients with caloric malnutrition were studied. The average adipose tissue LPL activity increased 5‐fold during 4‐day glucose infusion (P < 0.001) and 7.4‐fold during Intralipidr̀ plus glucose infusion (P< 0.001). In contrast, no change occurred in the LPL activity of skeletal muscle. Glucose infusion caused a significant increase in VLDL and LDL triglyceride concentrations and the Intralipidr̀ plus glucose infusion was followed by a rise in LDL and HDL triglyceride concentrations. HDL cholesterol decreased by 26% (P < 0.01) during glucose and by 19% (P< 0.05) during Intralipidr̀ plus glucose. Apoprotein A I was very low already at the start of parenteral alimentation and it did not change during either nutrition. The HDL cholesterol and apoprotein A I and A II levels were each positively correlated with adipose tissue LPL activity before parenteral nutrition but not after it.
Lack of sensitivity and specificity of the renal clearance of amylase/clearance of inulin ratio in experimental acute rat pancreatitis with a study on the renal handling of amylase
Authors: GREUTER G. , WIDGREN S. , FAVRE H.
Published: March 2008

Abstract. As there are controversies about the specificity and the sensitivity of the amylase clearance/inulin clearance ratio (Cam/Cin) in the diagnosis of pancreatitis, this ratio has been calculated: (a) in rats with induced pancreatitis with histologically proven lesions; (b) in toxic induced tubulopathy rats with lesions demonstrated histologically and biologically (enzymuria). Hyperamylasaemia was found in 86% of the pancreatitis rats at 24 h, 50% at 48 h and 25% at 60 h. The ratio Cam/Cin was elevated above 2 SD of the control values among 14% of the rats at 24 h, 50% at 48 h and 25% at 60 h. There were no changes in enzyme elimination rates in the urine as compared to control values. Renal histology remained normal. Histological scores expressing a severe haemorrhagic pancreatitis were identical at 24, 48 and 60 h. In toxic induced tubulopathy rats, amylasaemia remained normal, but the Cam/Cin ratio only increased when the glomerular filtration rate was diminished by 90%.

The diagnosis could only be made by hyperamylasaemia in 50% of the histologically proven pancreatitis in the rat. The use of the ratio Cam/Cin does not increase the frequency of a correct diagnosis. Finally, amylase must be only filtered by the kidney as no tubular enzymes appeared in the urine of pancreatitis rats. Furthermore, this ratio is not specific for pancreatitis as it could be elevated in other pathologic states such as severe renal failure.
Platelets from diabetic subjects show diminished sensitivity to prostacyclin
Authors: BETTERIDGE D. J. , TAHIR K. E. H. EL , RECKLESS J. P. D. , WILLIAMS K. I.
Published: March 2008

Abstract. Prostacyclin, an unstable metabolite of arachidonic acid metabolism, has been shown to have potent platelet antiaggregatory and vasodilator activity. Available evidence suggests that arterial prostacyclin production is diminished in the diabetic state. In this study we have examined the sensitivity of platelets from diabetic subjects to the antiaggregatory effects of prostacyclin in vitro and report that platelets from some diabetic patients show diminished sensitivity to the antiaggregatory effects of prostacyclin. Thus diabetic subjects may not only have diminished prostacyclin production but also their platelets may be less sensitive to its effects. These findings may help to explain the increase in vascular disease observed in diabetic patients.
Inhibition of drug metabolism by cimetidine in man: dependence on pretreatment microsomal liver function
Authors: RÖLLINGHOFF WILHELM , PAUMGARTNER GUSTAV
Published: March 2008

Abstract. The effect of cimetidine on hepatic microsomal drug metabolism was studied in six patients with normal liver and eleven patients with chronic liver disease using the aminopyrine breath test. Before administration of cimetidine, the elimination rate constant of 14CO2 from breath (Kb) was 28·3±SD 1·3%/h in patients with normal liver and 13·5 ± 7·7%/h in patients with liver disease (P<0·001). After 7 days of cimetidine therapy (1 g/day) Kb decreased to 23·3±5·2%/h (19·0±13·8% decrease; P<0·05) and 7·4 ± 5·8%/h (50·5±14·4% decrease; P<0·001), respectively. Plasma levels of cimetidine were not significantly different (1·05 ± 0·14 μg/ml v. 0·88 ± 0·41; P> 0·05). The findings indicate that therapeutic doses of cimetidine lead to an inhibition of drug metabolism which is more pronounced in patients with impaired liver function than in liver normals. Therefore, patients with chronic liver disease may be at increased risk with respect to interactions between cimetidine and other drugs which are demethylated by the liver.
Lipoprotein lipase activity of adipose tissue, skeletal muscle and post‐heparin plasma in primary endogenous hypertriglyceridaemia: relation to lipoprotein pattern and to obesity
Authors: TASKINEN MARJA‐RIITTA , NIKKILÄ ESKO A. , KUUSI TIMO
Published: March 2008

Abstract. The lipoprotein lipase (LPL) activity was determined from heparin eluates of adipose tissue and skeletal muscle and from post‐heparin plasma of sixty‐five males with hypertriglyceridaemia and of seventy males with normal serum lipid levels. The patients were subgrouped by their lipoprotein concentrations into types 2b, 4 and 5. The mean LPL activity of adipose tissue (per tissue weight) of nonobese type 2b, 4 and 5 patients was reduced to 54%, 41 % and 13%, respectively, of the corresponding value of normolipidaemic men. On the other hand, among obese hyperglyceridaemic men only those with type 5 showed a decreased LPL activity in adipose tissue (44%). The mean skeletal muscle LPL was subnormal in nonobese type 4 (55%) and in type 5 patients (34%) but was normal in type 2b and in obese type 4 patients. The post‐heparin plasma LPL activity was significantly reduced in all nonobese hyperglyceridaemic groups but was normal in obese patients apart from cases with type 5 who had low values. One exceptional subject with type 5 had high post‐heparin plasma LPL activity.

It is concluded that a low LPL activity may be a crucial factor in the pathogenesis of hypertriglyceridaemia in nonobese subjects and in patients having type 5 disorder.
Noradrenaline release and clearance in relation to age and blood pressure in man
Authors: RUBIN PETER C. , SCOTT PETER J. W. , McLEAN KATHLEEN , REID JOHN L.
Published: March 2008

Abstract. Plasma noradrenaline concentration increases with age. This study was designed to investigate whether an increased rate of noradrenaline release into the circulation or a decrease in clearance is primarily responsible for this age related change in concentration. Sixteen healthy male subjects were studied, eight young (21–36 years) and eight old (65–78 years). Clearance was calculated from steady state noradrenaline concentrations during constant rate infusions of unlabelled noradrenaline. Clearance did not differ between the two groups: young 4.8 1/min (range 2.7–6.1), old 4.1 (range 2.6–8.2). The old subjects had significantly greater rates of release. Supine: young 10.3 nmol/min (range 5.3–17.6), old 19.7 (range 10.1–30), P<0.05. Standing: young 17.2 (range 11–36.4), old 29.2 (range 21.8–47.9), P<0.01. No significant relationship was found in either supine or standing position between rate of noradrenaline release and either systolic or diastolic blood pressure. These results indicate that plasma noradrenaline concentration rises with age because of an increased rate of release, but that this increased release is not responsible for the higher blood pressure seen in the elderly.
Alkaline phosphatase and acid lysosomal hydrolases in pancreatic juice and fibroblast cell cultures of patients with chronic calcifying pancreatitis
Authors: FIGARELLA C. , VOGT E. , HOSLI P.
Published: March 2008

Abstract. Nine lysosomal enzymes and alkaline phosphatase have been assayed in human pancreatic juice from controls and patients with chronic calcifying pancreatitis. Specific activities were evaluated by a non parametric test (Wilcoxon) with a probability of 2P.0.5. The values of acid phosphatase, α‐glucosidase, β‐glucosidase and α‐galactosidase are significantly higher in pathological juices; the values of α‐mannosidase and β‐glucuronidase are also increased in the same patients but at the limit of significance. Alkaline phosphatase, β‐hexosaminidase and α‐fucosidase follow the same trend but the values are not statistically significant between the two groups of patients. Studies on skin cultures of four patients with chronic calcifying pancreatitis demonstrate that the increased specific activities of lysosomal enzymes in the pathological juices do not correspond to a leakage of these enzymes into the extracellular space as described for cystic fibrosis.
Effects of haem infusion on biliary secretion of porphyrins, haem and bilirubin in man
Authors: McCORMACK LARRY R. , LIEM HENG H. , STRUM WILLIAMSON B. , GRUNDY SCOTT M. , MULLER‐EBERHARD URSULA
Published: March 2008

Abstract. Employing a continuous bile collection, we measured the bile secretion of porphyrins, haem (iron protoporphyrin IX regardless of oxidation state) and bilirubin in five healthy subjects. The baseline values for the flow of porphyrins in the bile were: 4·7 pL 1·9 nmol/h uroporphyrin, 27·3 pL 3·8 nmol/h coproporphyrin and 39·2 pL 11·7 nmol/h protoporphyrin. Bile haem flow was 59·7 pL 12·6 nmol/h, and that of bilirubin 23·8 pL 8·2 μmol/h. Following haem injection (6·4 μmol/kg) the flow of protoporphyrin but not of the other porphyrins was reduced, and the bile haem flow increased (232 pL 109·5 nmol/h), while the flow of bilirubin did not increase significantly. A few patients with representative porphyrias showed the expected increase in copro‐ and protoporphyrin in the bile. The patient with coproporphyria exhibited a bile flow of coproporphyrin of 1470 pL 133 nmol/h and of protoporphyrin of 334 pL 29 nmol/h; haem infusion significantly reduced the bile flow of both porphyrins (to 649 pL 101 for copro‐ and 215 pL 36 nmol/h for protoporphyrin). The patient with protoporphyria had an increased protoporphyrin flow, yet haem infusion caused no reduction in protoporphyrin flow (106 pL 7 after v. 81·4 pL 13 nmol/h before haem).

In conclusion, we found that haem and porphyrins are normal constituents of bile, and that injected haem appears in bile. Bile bilirubin did not rise within 12 h after haem infusion a finding which warrants further investigation.