bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of recombinant tumour necrosis factor (rTNF‐α) in cancer. Observations on the acute phase protein reaction and immunoglobulin synthesis after high dose recombinant TNF‐α administration in isolated limb perfusions in cancer patients
Authors: SWAAK A. J. G. , LIENARD D. , KOOPS H. SCHRAFFORDT , LEJEUNE F. J. , EGGERMONT A. M. M.
Published: March 2008

Abstract. To obtain insight in the effect of TNF on the synthesis of acute phase proteins like CRP, αl‐antitrypsine, αl‐acidglycoprotein, C3 and C4 and the immunoglobulins (IgG‐M‐A), nine cancer patients who were treated with an isolated limb perfusion (ILP) with high dose recombinant TNF‐α (rTNF‐α) were investigated during a 7–day period after the end of the perfusion. Resorption of rTNF‐α from out of these limbs into the circulation after the ILP induced within 30 min to 6 h in all patients elevated serum levels of IL‐6. At the same time C‐reactive protein became detectable in serum. The highest serum levels were obtained at 48 h after ILP. The serum levels of the other acute phase proteins (α l–acidglycoprotein, αl‐antitrypsine, C3, C4), rose more slowly and the highest serum levels were found at the third day. All investigated proteins declined after they had reached their peak levels. Levels of α1‐‐acidglycoprotein and a,‐anti‐trypsin α1‐‐acid declined slower than both complement component. In regard to the immunoglobulin levels a nearly continuous increase in the serum level of specifically IgM was observed. This study clearly shows the interrelationship between TNF‐α and IL‐6 in regard to the synthesis of the different acute phase proteins; and moreover also a striking effect on IgM synthesis.
Spontaneous bacterial peritonitis is associated with high levels of interleukin‐6 and its secondary mediators in ascitic fluid
Authors: PROPST T. , PROPST A. , HEROLD M. , SCHAUER G. , JUDMAIER G. , BRAUNSTEINER H. , STÖFFLER G. , VOGEL W.
Published: March 2008

Abstract. We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin‐6, as well as acute phase reactants a‐l‐antitrypsin and C‐reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF‐α), neopterin, interleukin 2–receptor and granu‐locyte‐macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin‐2 and interleukin‐1 levels. In addition, interleukin‐6, TNF‐α and neopterin levels were found to correlate significantly with the outcome of the disease. These findings show that acute phase reaction occurs in the ascitic compartment in correlation with the development of spontaneous bacterial peritonitis.
Influence of insulin on glucose metabolism and lipolysis in adipose tissue in situ in patients with liver cirrhosis
Authors: JOHANSSON U. , ARNER P. , BOLINDER J. , HAGSTROM‐TOFT E. , UNGERSTEDT U. , ERIKSSON L. S.
Published: March 2008

Abstract. The influence of insulin on lipolysis and glucose metabolism in abdominal adipose tissue was studied in situ with the microdialysis technique during a euglycaemic insulin clamp (1 mUkg‐1 min‐1)in nine cirrhotic patients and 10 controls. The cirrhotic patients displayed a 50% decrease in glucose utilization rate during the clamp (P< 0.001). Dialysate glucose levels decreased similarly by 20–30%, in patients and controls, which in the presence of unchanged local blood flow in the adipose tissue in response to insulin, is at hand with a glucose uptake into the adipocytes of similar magnitude in both groups. Before and during the clamp, the arterial and dialysate levels of glycerol were higher in the patients than in the control subjects (anova P=0.001 and 0.048 in arterial blood and dialysate, respectively). In relative terms, however, insulin induced a 70% reduction of arterial and dialysate glycerol in both groups. The concentrations of lactate and pyruvate in the dialysate and blood increased in a similar way in both groups during hyperinsulinaemia. The results suggest an increased rate of lipolysis in cirrhotic patients. Insulin cannot lower it to normal, although it is still capable of achieving a relative reduction. No explanation was found in the adipose tissue to the insulin resistance to whole‐body glucose utilization that was noted in the patients with cirrhosis.
Lack of relationship between hip and spine bone mineral density and oral contraceptive use
Authors: MURPHY S. , KHAW K.‐T. , COMPSTON J. E.
Published: March 2008

Abstract. The aim of this study was to examine the relationships between oral contraceptive use and bone mineral density at the hip and spine.

Community based women aged 41–76 years (n = 841) were recruited from four general practices in Cambridge. Each subject completed a health questionnaire. Spine (L2‐L4, n= 841) and hip (n= 833) bone mineral density were measured by dual energy X‐ray absorptiometry using the Hologic QDR‐1000.

After adjustment for age, there was no significant difference in regional bone mineral density between ever and never users of oral contraceptives. Similar results were obtained after stratifying for potential confounding factors including menopausal status, parity, smoking, hormone replacement therapy use, and body mass index. There was no relationship between duration of oral contraceptive use and bone mineral density.

These results suggest that there is no relationship between oral contraceptive use and bone mineral density at the hip and spine in middle‐aged women.
Reverse cholesterol transport: relationship between free cholesterol uptake and HDL3 in normolipidaemic and hyperlipidaemic subjects
Authors: CABEZAS M. CASTRO , HEUSDEN G. P. H. VAN , BRUIN T. W. A. DE , BECKHOVEN J. R. C. M. VAN , KOCK L. A. W. , WTRTZ K. W. A. , ERKELENS D. W.
Published: March 2008

Abstract. High density lipoproteins (HDL) are responsible for the Reverse Cholesterol Transport (RCT). The role of the composition of the HDL particle in RCT, involving free cholesterol (chol) uptake from cell membranes, is not completely understood. We have therefore studied the uptake capacity from subjects with a wide variety of plasma HDL cholesterol concentrations in an HDL‐receptor free model consisting of bovine heart mitochondrial membranes labeled with [14C]cholesterol. HDL were isolated by molecular sieve chromatography from fresh plasma samples of eight subjects with low plasma HDL chol concentrations (≤ 1.0 mmol L‐1) and 15 subjects with normal HDL chol concentrations. The latter were subdivided into an intermediate (HDL chol: 1.0–1.4 mmol L‐1; n= 9) and a high HDL chol group (>1.4 mmol L‐1; n= 6). In the HDL fractions isolated by chromatography (cHDL), total chol and apolipopro‐tein (apo) A1 were measured. Free chol uptake was significantly decreased by 32% in the tertile with the lowest plasma HDL chol (49 1 ± 15.8 arbitrary units; mean ± SD), compared to the tertile with high HDL chol (72.1 ± 16.6 au). Linear regression analysis showed a positive correlation between the free choi uptake and plasma HDL3 concentrations (r= 0.61; P<0.01), HDL chol (r= 0.56; P<0.01), HDL associated apo A1 (r = 0.46; P<0.05), cHDL apo AT (r = 0.56; P<0.05) and cHDL chol (r = 0.46; P<0.05) in all subjects combined. Stepwise multiple‐regression analysis confirmed the association of [14C]cholesterol uptake with plasma HDL3 concentrations (β, 061; P= 0.004). No correlations were found between free chol uptake and total plasma apoAI (r = 0.26; ns) or HDL2 (r = 0.27; ns). After an oral fat load in four FCH patients, free chol uptake parallelled the changes in plasma HDL3 chol concentrations. We conclude that HDL3 is involved in the early steps of RCT and low HDL3 levels may result in less efficient RCT in hypertriglyceridemia.
Human CD5‐positive B Cells in lymphoid malignancy and connective tissue diseases
Authors: YOUINOU P. , MACKENZIE L. E. , LAMOUR A. , MAGEED R. A. , LYDYARD P. M.
Published: March 2008

Abstract. The current literature on human CD5‐positive B cells (CD5 + B cells) has been analysed, with a special emphasis on non organ‐specific auto‐immune diseases. Malignant cells of most of the chronic lymphoid leukaemias of the B cell lineage express the CD5 molecule. Antibodies of the IgM class produced by leukaemic B cells are multispecific auto‐antibodies. The CD5 + B cell subset may be expanded in non organ‐specific autoimmune diseases, such as rheumatoid arthritis, primary Sjogren's syndrome, systemic lupus erythematosus. This holds true for various conditions, including organ‐specific auto‐immune diseases. Since auto‐immune features are common in lymphoproliferative disorders, and the latter be a complication in non organ‐specific auto‐immune diseases, CD5 + B cells may represent an intermediatary between these auto‐immune diseases and B cell lym‐phoproliferations. Studies on the regulation of CDS + B cell production and function are likely to shed light on the aetiology of, and pathogenetic mechanisms operating in the different disease states.
Effect of glucagon immunoneutralization on the increase in urea synthesis after hysterectomy in rats
Authors: HEINDORFF H. , HOLST J. J. , ALMDAL T. , VILSTRUP H.
Published: March 2008

Abstract. To study the effect of glucagon immunoneutralization on postoperative changes of urea synthesis, hysterectomized rats were given one injection of a specific high titre antibody against pancreatic glucagon 24 h before operation raising the plasma glucagon binding capacity to values 10–20 times higher than the plasma glucagon concentration in control animals. Earlier studies have shown that the spontaneous rate of urea‐N synthesis (UNSR) doubles 3 h after operation, and that the Vmax of the process, the capacity of urea‐N synthesis (CUNS) is 50% higher than normal values 24 h after operation. Therefore, the effect of glucagon on UNSR and CUNS were investigated 3 and 24 h postoperatively, respectively. Control animals were given non immune rabbit serum. Glucagon immunoneutralization partly normalized the early increase in UNSR 3 h postoperatively (control: 4.7 ± 0.3, hysterectomy + serum: 6.7 ± 0.4, hysterectomy + Gluc‐Ab: 5.5 ± 0.4 μmol (min.100 g BW)‐1), but had no effect on the increase of CUNS 24 h postoperatively (control: 7.9 ± 0.3, hysterectomy + serum: 9.5 ± 0.3, hysterectomy + Gluc ‐ Ab: 9.8 ± 0.5 μmol (min‐100 g BW)‐1).

This shows that glucagon is important for the early postoperative increase in the efficacy of urea synthesis, whereas the late increase in capacity seems not to depend on hyperglucagonemia.
Binding of cyclosporine by erythrocytes: influence on cell shape and deformability
Authors: REINHART W. H.
Published: March 2008

Abstract. Cyclosporine is a widely used immunosup‐pressive drug with a high affinity for erythrocytes. It was hypothesized that the hydrophobic agent would interact with the erythrocyte membrane, which could cause a shape change and alter cell deformability. Administration of 300 mg cyclosporine in vivo and incubation of erythrocytes with concentrations up to 100 mg 1‐‐1in vitro at room temperature showed that cyclosporine is found in the cytoplasm, but not in the membrane of erythrocytes and that cell shape or deformability were not affected. Incubation of erythrocytes with the highest cyclosporine concentration (100 mg 1‐‐1) at 37°C lead to a time‐dependent, slight stomatocytic shape transformation, indicating that the drug is intercalated preferentially into the inner hemileaflet of the membrane under these conditions. Cyclosporine metabolites had no effect on the cell shape. The shape of erythrocyte ghosts was neither affected by cyclosporine nor by its metabolites. It is concluded that cyclosporine is bound in the erythrocyte cytoplasm and does not affect the cell membrane and cell deformability at therapeutic concentrations. These results may contribute to a better understanding of the interactions of cyclosporine with cells.
Effect of ageing on postprandial conjugated and unconjugated serum bile acid levels in healthy subjects
Authors: SALEMANS J. M. J. I. , NAGENGAST F. M. , TANGERMAN A. , SCHAIK A. VAN , HOPMAN W. P. M. , HAAN A. F. J. DE , JANSEN J. B. M. J.
Published: March 2008

Abstract. Colorectal cancer is a disease of elderly subjects. A decreased ileal absorption of bile acids in elderly subjects may lead to an increased exposure of the colonic mucosa to secondary bile acids. This may contribute to an enhanced risk of colorectal cancer. In this study fasting and postprandial conjugated and unconjugated serum levels of cholic, chenodeoxycho‐lic, and deoxycholic acid in 12 elderly and 12 younger subjects were investigated. Intestinal transit time, gallbladder emptying and jejunal bacterial flora were also studied in both age groups. Fasting levels of conjugated and unconjugated serum bile acids were similar in both age groups. Postprandial levels of all individual conjugated bile acids increased to a significantly higher extent in the younger subjects. Postprandial unconjugated serum bile acid levels did not differ significantly between both age groups, although unconjugated deoxycholic levels tended to increase to higher levels in the elderly. Results of jejunal bacterial counts, gallbladder emptying and intestinal transit time were similar in both groups. These data suggest that conjugated bile acids are reabsorbed less effectively in elderly subjects.
Adipose tissue and muscle volume determination by computed tomography in acromegaly, before and I year after adenomectomy
Authors: BRUMMER R.‐J. M. , LÖNNS L. , KVIST H. , GRANGÅRD U. , BENGTSSON B.‐A. , SJÖSTRÖM L.
Published: March 2008

Abstract. The adipose tissue volume, skeletal muscle and skin volume and visceral organ volume were determined using the multiscan CT (computed tomography) technique in 15 patients with acromegaly. The examinations were performed before treatment and 1 year after transsphenoidal adenectomy.

The mean body weight did not change significantly after treatment; 91–3 kg and 92–3 kg pre and postoperatively in men and 66.7 kg and 65.9 kg in women respectively. The total adipose tissue volume increased by 7.1 1 (59.2%, P<0.01) in the male group and 3.9 1 (20.39%, P< 0.05) in the female group. Muscle and skin mass and visceral organ mass decreased significantly after treatment. The muscle and skin mass decreased by 3.6 1 (‐7.4%, P<0.01) in males and by 3.2 1 in females (‐11.5%, P<0.02). The corresponding decrease in visceral organ mass was 1.5 1 (‐17.0%, P<0.01) in males and 1.0 1 (15.4%, P<0.05) in females respectively.

On average, the fractions of adipose tissue in the subcutaneous trunk and the intra‐abdominal depots increased after treatment, while the fractions of adipose tissue in the limbs and the head and neck region decreased. The change in adipose tissue distribution pattern reached significance (P<0.005) in men only.
A comparison of three diuretic regimens in heart failure
Authors: ANDREASEN F. , ERIKSEN U. H. , GUUL S.‐J. , NIELSEN L. P. , BECH O. M. , DIAMANT B. , KAHR O. , BRUUN P. , HARTLING O. J. , HVIDT S.
Published: March 2008

Abstract. Eight patients with mild heart failure were treated in random order for 1 week with 2 mg bumethanide at 0800 and 1200 (treatment I) h, 1 mg bumethanide at 0800, 1200, 1800, 2200 (treatment 2) and 5 mg bendroflumethiazide at 0800 and 1800 (treatment 3) h. The ‘quality of life’ did not differ significantly between the three treatment periods. At the presumed trough of the diuretic effect the circulating blood volume was largest during treatment 1; it was 6.3% smaller during treatment 2 (P<0.02) and 6.7%) lower during treatment 3 (P<0.05). In comparison with treatment 1, the maximal increase in rate‐pressure product during physical exercise was 24.6% higher in treatment 3. Compared with treatment 1 the area under the curve (AUC) for plasma lactate during physical exercise was 14% lower during treatment 2 (P<0.05) and 18% lower during treatment 3 (P<0.01). These findings suggest that the type of program for diuretic therapy influences the magnitude of inevitable diurnal fluctuations in body fluids, the ability of the heart to work and the ability of the body to adjust to the oxygen demand.
Apolipoprotein(a) polymorphism predicts the increase of Lp(a) by pravastatin in patients with familial hypercholesterolaemia treated with bile acid sequestration
Authors: KLAUSEN I. C. , GERDES L. U. , MEINERTZ H. , HANSEN F. A. , FAERGEMAN O.
Published: March 2008

Abstract. HMG‐CoA reductase inhibitors effectively reduce the concentration of low density lipoproteins (LDL) in plasma. Lipoprotein(a) [Lp(a)] may be as atherogenic as LDL. A few studies, only one of which was placebo controlled, suggest that the HMG CoA reductase inhibitors either do not affect Lp(a) or they increase Lp(a). The response of Lp(a) to HMG‐CoA reductase inhibition has not been related to apolipo‐protein(a) phenotypes in previous studies. We conducted a double‐blind, placebo controlled study of pravastatin in 51 patients with familial hypercholester‐olemia (FH) (n= 43) or probable FH (n= 8). All patients had LDL‐cholesterol concentrations above 4.1 mmol 1‐1 despite treatment with diet and bile acid sequestration. In patients assigned to pravastatin (n= 34), the mean concentrations of total cholesterol and LDL cholesterol fell significantly (P<0.01) when compared to placebo. Lp(a) increased (P<0.01) from a mean (±SD) of 33.6 ± 40.8 mgdl‐1 to 411 ± 46.1 mg dl‐1 on pravastatin but was unchanged during placebo treatment. The percentage increase in Lp(a) was the same in patients with different apo(a) phenotypes, and hence the absolute increase in Lp(a) was greatest in patients with the low molecular weight apo(a) phenotypes.
Glucose‐induced water movement from the intracellular to the extracellular space and its influence on calculations of glucose metabolism
Authors: PETERSEN K.‐G. , KHALAF A.‐N. , BÖCKER J. , KERP L.
Published: March 2008

Abstract. The osmotic effect of intravenous glucose was investigated in eight healthy volunteers. Increases in plasma glucose can induce water movement from the intracellular to the extracellular space. Serum choline esterase was used as an endogenous marker of serum dilution. Intravenous tests with 5, 15, 30 and 35 g of glucose showed that the water shift was proportional to the amount infused. The respective dilutions of choline esterase were 1.3 ± 0.7%, 3.3 ± 0.9%, 6.3 ± 0.8% and 7.8 ± 0.5%. The effect on extracellular water was maintained when plasma glucose remained elevated (inhibition of insulin secretion with a soma‐tostatin analogue). In comparison to glucose, infusion of 10 g of a mixture of amino acids produced a less pronounced effect than expected. The acute water shift after intravenous glucose dilutes serum components including glucose (8% of total extracellular glucose at 35 g). This can be misinterpreted as glucose clearance when calculating metabolic rates. For estimated amounts a proportional correction should be made (3.5% per 5 mmol 1‐1 increase). A measured plasma glucose of 22.2 mmol 1‐1 should be corrected to 24.8 mmol 1‐1, while a plasma glucose value of 5.0 mmol 1‐1 needs no correction.
Investigations into the haemorheological significance of postprandial and fasting hypertriglyceridaemia
Authors: SCHÜTZ E. , SCHUFF‐WERNER P. , GÜTTNER Y. , SCHULZ S. , ARMSTRONG V. W.
Published: March 2008

Abstract. Two study designs were conceived to evaluate the rheological significance of hypertriglyceridaemia. We first investigated the course of serum‐ (SV) and plasma viscosity (PV) and erythrocyte aggregation in serum (SEA) and plasma (PEA) of healthy normoli‐pidaemic individuals over 4 h after a fatty rich meal, in native material and after removal of triglyceride rich lipoproteins by centrifugation. Secondly, blood from patients with untreated hypertriglyceridaemia was investigated under fasting conditions. PEA and SEA increased in parallel with postprandial triglycerides (+135 mg dl‐1), but the effect on PEA was more pronounced (+ 0.8 abs% increase; 2 h after the meal) as compared to SEA (+ 0.4 abs% increase). PV and SV increased in parallel to the same extent (+ 0.05 mPas). In the triglyceride poor infranatant no significant changes occurred. In fasting plasma PEA and PV were significantly lower (1.1abs% and PV 0.04 mPas respectively) in infranatant than in native plasma, while only small differences in triglyceride (mostly VLDL) were observed. This phenomenon was barely detectable in serum samples.

We conclude that triglyceride rich lipoproteins have a profound influence on haemorheological parameters, and that fibrinogen in particular, potentiates the effect of large fasting VLDL on plasma viscosity and erythrocyte aggregation.
Decreased in vitro oxidizability of low‐density lipoprotein in hypercholesterolaemic patients treated with 3‐hydroxy‐3‐methyIgIutaryl‐CoA reductase inhibitors
Authors: KLEINVELD H. A. , DEMACKER P. N. M. , HAAN A. F. J. DE , STALENHOEF A. F. H.
Published: March 2008

Abstract. We studied the effects of the 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) reductase inhibitors simvastatin and pravastatin on the in vitro susceptibility of low‐density lipoprotein (LDL) to oxidation. Twenty‐three hypercholesterolaemic patients (mean serum cholesterol 9.7 mmol 1‐1) were treated with increasing doses of either simvastatin or pravastatin for 18 weeks. No significant differences in effect on lipid levels between the two drugs were found. Treatment resulted in lowering of total cholesterol and LDL‐cholesterol by maximally 30% and 34%, respectively. Chemical composition analysis showed that LDL particles contained relatively more protein and less free cholesterol and cholesteryl‐ester after treatment. The LDL cholesterol/protein ratio decreased from 1.24 ± 0.21 to 0.97 ± 0.23 (n = 20). By continuous monitoring of in vitro oxidation it appeared that LDL was less susceptible to oxidation after drug treatment. Maximal rate of diene production was significantly decreased from 19.7 ± 3.1 to 18.5 ± 3.3 nmol min‐1 mg‐1 LDL; total diene production decreased significantly from 420.3 ± 67.6 to 380.5 ± 49.1 nmol mg‐1 LDL; the lag time was unchanged throughout the study. These studies show that HMG‐CoA reductase inhibitors reduce the oxidizability of LDL by altering its composition.
Postabsorptive retinyl palmitate removal is retarded in lecithin‐cholesterol acyltransferase deficiency
Authors: GYLLING H. , MIETTINEN T. A.
Published: March 2008

Abstract. Postabsorption fat clearance of intestinal lipoproteins indicated by retinyl palmitate was studied in two siblings with the classical lecithin‐cholesterol acyltransferase (LCAT) deficiency and in a control group of 21 healthy subjects with similar apoprotein E 3/3 phenotype. Relatively high pre‐ and postabsorptive cholesterol esterification percentage of chylomi‐crons suggested that acyl coenzyme A:cholesterol acyltransferase activity was not inhibited. Postabsorptive levels of plasma lipids increased and decreased roughly similarly in the cases and controls with the postabsorptive peak values at about 4 h. Plasma total and chylomicron levels of retinyl palmitate were not affected by LCAT deficiency, while the removal of the vitamin from very low and intermediate density lipoproteins was clearly reduced so that the peak concentrations, values under the response curves and the time of the peak concentrations were markedly higher than in the controls. The long‐lasting circulation of chylomicron remnants of density < 1.006–1.019 g ml‐1 may have some clinical significance because postabsorptive lipoproteins are suspected to have atherogenic potentiality.
High density lipoprotein subfractions, apolipoprotein A‐I containing lipoproteins, lipoprotein (a), and cholesteryl ester transfer protein activity in alcoholic women before and after ethanol withdrawal
Authors: VÄLIMÄKI M. , KAHRI J. , LAITINEN K. , LAHDENPERÄ S. , KUUSI T. , EHNHOLM C. , JAUHIAINEN M. , BARD J. M. , FRUCHART J. C. , TASKINEN M.‐R.
Published: March 2008

Abstract. We studied 11 female alcoholics before and after ethanol withdrawal of 2 weeks and 10 healthy normolipidaemic, nonalcoholic women of similar age. In alcoholic women the HDL2 mass was increased by 63% (P<0.01) on admission and normalized (P<0.01) during abstention. The concentrations of HDL3 cholesterol and its mass remained unchanged throughout the study. Consistently with the fall of HDL2 gradient gel electrophoresis analyses also demonstrated decrease of the cholesterol concentration of HDL2b and HDL2a (P<0.05) during alcohol withdrawal. On admission the apo A‐II concentration was increased by 48% (P < 0.01) and it was normalized (P< 0.001) during abstention. Among apo A‐I containing lipoproteins the most prominent change occurred in Lp A‐1: A‐11, which fell by 32% (P<0.01) during 1 week's alcohol withdrawal. During abstention the lipoprotein (a) concentration increased in 10 out of 11 women. In patients cholesteryl ester transfer (CETP) activity increased by 35% (P<0.01) during 1 week of ethanol withdrawal. On admission post‐heparin plasma lipoprotein (LPL) and hepatic lipase activities were increased by 25% (P = NS); during 1 week's abstention they both returned to the control level (P < 0.05–< 0.01). In conclusion, chronic alcoholic women display multiple changes of lipoprotein metabolism which are rapidly reversed during abstinence. In contrast to alcoholic men, studied previously by us using the same study design and methods, there was no significant elevation of HDL3 cholesterol and apo A‐I. The data suggest that alcohol interferes with several regulatory steps of HDL metabolism which are partly gender dependent.
Monocyte adherence to endothelial cells in patients with atherosclerosis: relationships with risk factors
Authors: DUPLÀA C. , COUFFINHAL T. , LABAT L. , FAWAZ J. , MOREAU C. , BTETZ I. , BONNET J.
Published: March 2008

Abstract. Monocyte adhesion to endothelium appearing determinant in atherosclerosis, the possibility that circulating monocytes have an increase of their adherence on endothelial cells were investigated in patients with atherosclerosis. The adherence of circulating monocytes on endothelial cell monolayers was determined in 26 patients with atherosclerosis (age 59 ± 4), and 25 healthy individuals (age 55 ± 4). No difference of monocyte adherence was observed between the two groups (18.8±13.8% vs 19.2±13.4%), or following atherosclerosis severity. However monocyte adherence appeared positively correlated to smoking habits (r = 0–34, P<0.02) and fibrinogen level (r = 0.31, P<0.03), and negatively to the degree of plasmatic LDL oxidation (r=‐0.28, P<0.05). These results suggest that the adherence of monocytes to endothelial cells is not increased in atherosclerosis, but enhanced by risk factors. A weak plasmatic LDL oxydation could inhibit monocyte adhesion.
Effect of duodenal juice on bombesin‐stimulated cholecystokinin release during loxigIumide administration in man
Authors: JEBBINK M. C. W. , JANSEN J. B. M. J. , KLEIJ F. G. H. VAN DER , MOOY D. M. , ROVATIT L. C. , LAMERS C. B. H. W.
Published: March 2008

Abstract. Stimulation of cholecystokinin release by bombesin is augmented by cholecystokinin receptor blockade with loxiglumide. We hypothesize that this augmented cholecystokinin release results from inhibition of the pancreatico‐biliary response to bombesin during cholecystokinin receptor blockade. To test this hypothesis, we infused bombesin for 180 min in six healthy subjects Three bombesin‐infusion experiments were performed in each subject in random order on different days. In two of these experiments loxiglumide was co‐infused with bombesin, while in the third experiment saline was co‐infused with bombesin. In one of the loxiglumide experiments, duodenal juice, collected on the previous day during infusion of cholecystokinin‐GIH, was reperfused intraduodenally during the second hour of bombesin infusion.

In the saline experiment, the integrated cholecystokinin response during the first hour of bombesin‐infusion (262 ± 63 pmol 60 min‐1) was significantly (P < 0.01) higher than during the second (88 ± 26 pmol 60 min‐1) and third (87 ± 31 pmol 60 min‐l) hour of bombesin‐infusion. Loxiglumide augmented bombesin‐stimulated cholecystokinin secretion from 262 ± 63 pmol 60 min‐1 to 453 ± 63 pmol 60 min‐1 in the first hour of bombesin infusion (P < O.01). Integrated cholecystokinin values in the second (489 ± 90 pmol 60 min‐1) and third (450 ± 74 pmol 60 min‐1) hour of the loxiglumide experiment, were significantly (P < 0.01) higher than in the saline experiment. Duodenal juice significantly (P<0.05) suppressed cholecystokinin responses from 489 ± 90 to 401 ± 69 pmol 60 min‐1 in the first hour of reperfusion, and from 450 ± 74 to 300 ±85 pmol 60 min‐1 in the hour after reperfusion (P<0.05). However, during and after reperfusion of duodenal juice, cholecystokinin concentrations were still distinctly (P<0.01) higher than in the BBS without loxiglumide experiment.

Since the presence of bombesin‐like immunoreac‐tivity in the mucosa of the small intestine permits a role for this neuropeptide in the regulation of cholecystokinin release under physiological conditions, and since the present study demonstrates that pancreatico‐biliary outputs suppress the augmented cholecystokinin response to bombesin during specific blockade of CCK‐receptors, this study supports the concept that pancreatico‐biliary components in the duodenum may be involved in a feedback regulation between pancreatico‐biliary products and cholecystokinin release in man.
Composition of ascitic fluid in liver cirrhosis: bile acid and lipid content
Authors: SALVIOLI G. , TATA C. , PANINI R. , PELLATI M. , LUGLI R. , GAETTI E.
Published: March 2008

Abstract. The concentrations of lipids, bile acids and proteins were evaluated in the ascitic fluid and plasma of 23 cirrhotics. Ascitic fluid density was highly correlated with its protein content, represented mostly by low molecular weight proteins. The ratio of plasma to ascitic fluid concentrations of nine examined proteins increased with molecular weight, indicating a selective ultrafiltration of the peritoneal transudate. Low density lipoproteins in ascitic fluid had modified electrophoretic mobility. Total cholesterol had a higher plasma to ascitic fluid ratio than high density lipoprotein cholesterol, whereas bile acids and proteins had similar plasma to ascitic fluid ratios. Indeed, bile acids strongly bind to circulating albumin: consequently ascitic fluid contains more cholic acid (less hydrophobic) than other bile acids. Analysis of both plasma and ascitic fluid composition in cirrhotics provides useful information on processes regulating passage of blood components into the peritoneal cavity.
Decreased clearance of uraemic and mildly carbamylated low‐density lipoprotein
Authors: HÖRKKÖ S. , HUTTUNEN K. , KERVINEN K. , KESÄNIEMI Y. ANTERO
Published: March 2008

Abstract. Low‐density lipoprotein (LDL) was in vitro carbamylated with potassium cyanate and the clearance was studied in man. A minor carbamylation of LDL decreased the clearance of LDL by 41% (94% of amino groups free) and by 18% (90% of amino groups free). When LDL was extensively carbamylated its clearance was substantially accelerated. Moreover, the clearance of LDL isolated from 14 haemodialysis patients (uremic‐LDL) was studied in rabbits. Uraemic‐LDL, injected into rabbits simultaneously with the LDL of a healthy control subject, was cleared more slowly than the control‐LDL (difference in fractional catabolic rate –6·5%, P= 0·02). We also examined the lipid peroxidation of the carbamylated LDL by measuring the amount of thiobarbituric‐acid reactive substances (TBARS) and formation of conjugated dienes during exposure of carbamylated LDL to 5 μM Cu2+. The carbamylated and native LDL had similar lipid peroxidation and propensity for oxidation. In summary, both the uraemic‐LDL and minimally carbamylated LDL had a decreased clearance in vivo, which may contribute to the accelerated atherosclerosis in uraemic patients.
The diagnosis of pulmonary tuberculosis by gaschromatographic detection of tuberculostearic acid using flame ionisation detectors
Authors: HERZ A. , LEICHSENRING M. , FELTEN M. , OOSTHUIZEN O. J. , MAYATEPEK E. , HAAS W. , BREMER H. J.
Published: March 2008

Abstract. It has been shown that the detection of tuberculostearic acid (TBSA) with gas chromatography‐massspectrometry provides a highly specific, sensitive and rapid method for the diagnosis of various forms of tuberculosis. However, the need for complex and expensive equipment prevented the more widespread use of this method. We report on the application of conventional gas chromatography with flame ionization detectors in the detection of TBSA in sputum samples. TBSA was detected in all patients with proven pulmonary tuberculosis before treatment or under treatment for less than 4 weeks (n= 18). Six of these patients (33%) had a negative microscopy result at the time of the study. Sputum samples from patients under therapy for longer than 4 weeks (n= 20) were TBSA‐positive in 15 cases (75%). Only in two cases was the diagnosis by microscopy and/or cultur not met by TBSA‐detection. All sputa of 20 control patients with lung diseases other than tuberculosis were TBSA negative. Additional analysis of patients' data showed a significant relationship (P <0·005) between the relative amounts of TBSA detectable in the sputum samples and the duration of therapy. It is concluded that conventional capillary gaschromatography may be sensitive and specific enough to be used for the detection of TBSA in sputum of patients with pulmonary tuberculosis.
Plasma fibrinogen in relation to serum insulin, smoking habits and adipose tissue fatty acids in healthy men
Authors: CIGOLINI M. , TARGHER G. , SANDRE G. DE , MUGGEO M. , SEIDELL J. C.
Published: March 2008

Abstract. Recent prospective studies have reported an independent association between fibrinogen plasma levels and risk of cardiovascular events. Aim of this study was to investigate the relationships between fibrinogen level and conventional cardiovascular risk factors in a random sample of 38 year‐old apparently healthy men (n= 94), and to verify whether the fatty acid composition of the diet might influence those relations. Anthropometric measurements, serum lipids, blood pressure, and smoking habits were evaluated. In addition, fasting and after glucose‐load serum glucose and insulin concentrations were measured. The most significant difference in fibrinogen level was found among the tertiles of fasting serum insulin (Fanova= 4·5; P < 0·01) with the highest plasma fibrinogen values in the third insulin tertile, whereas body mass index (BMI), waist/hip circumference ratio (WHR) and serum triglycerides were more weakly related. The current smokers had substantially higher levels of fibrinogen than subjects who never smoked (P < 0·001). A multivariate regression analysis showed that, among the above reported variables, only serum insulin and smoking were independently associated with plasma fibrinogen. Furthermore, as the possible association between fatty acid composition of the diet and fibrinogen level regards, we have examined the fatty acid composition of adipose tissue, as a good and objective index of quality of the dietary fat intake. It was found that, fibrinogen level was not associated with any adipose tissue fatty acid. In conclusion, this study performed in a random sample of healthy men indicates an independent relationship of fasting insulin and smoking to fibrinogen plasma level.
Alpha‐subunit and human chorionic gonadotropin‐β immunoreactivity in patients with malignant endocrine gastroenteropancreatic tumours
Authors: GROSSMANN M. , TRAUTMANN M. E. , POERTL S. , HOERMANN R. , BERGER P. , ARNOLD R. , MANN K.
Published: March 2008

Abstract. In the serum of patients with malignant endocrine gastroenteropancreatic (GEP) tumours, both α‐subunit (α‐SU), common to all glycoprotein hormones, as well as free β‐subunit of human chorionic gonadotropin (hCG‐β) have been reported to be elevated in a substantial fraction. Both have been discussed as markers of malignancy in these neoplasms. In the present study we evaluated the diagnostic significance of α‐SU and hCG‐β as serum markers in patients with malignant endocrine gastroenteropancreatic tumours.

The study group consisted of 52 patients with endocrine GEP‐malignancies (24 nonfunctioning, 23 carcinoid syndromes, four gastrinoma, one glucagonoma), located in the small intestine (n= 29), pancreas (n= 17), colon or rectum (n= 3), retroperitoneum (n= 2) and stomach (n= 1). α‐SU and hCG‐β immunoreactivity was also assessed in the serum of patients with benign GEP‐tumors (five insulinoma, and three gastrinoma).

Concentrations of α‐SU and hCG‐β were determined using two highly sensitive and specific immunoradiometric assays employing two monoclonal antibodies each. In 19 of 52 patients (37%), either α‐SU (n= 9), hCG‐β (n= 7) or both subunits (n= 3) were elevated. In the subgroup of 24 patients with nonfunctioning GEP‐tumours, increased concentrations of either α‐SU (n= 6) or hCG‐β (n= 3) or both subunits (n= 1) were found in 10 of 24 patients (42%). In four of 23 patients with carcinoid syndrome (17%), either α‐SU (n= 2), hCG‐β (n= 1) or both subunits (n= 1) were above the normal range. Of five patients with functionally active endocrine pancreatic islet cell tumours, all had an elevation of at least one of the two substances. In contrast, in the serum of all eight patients with benign GEP‐tumours, α‐SU and hCG‐β were within normal limits. In summary, our data show a high frequency of elevated α‐SU or hCG‐β immunoreac tivity in the serum of patients with malignant endocrine gastroenteropancreatic tumours. Since immunoreactivity is mostly discordantly elevated, the two markers are well suited to supplement each other. Absolute values had a similar range in the subgroups analysed. The prevalence was highest for functionally active endocrine pancreatic islet cell cancers, but nonfunctioning endocrine GEP‐malignancies also exhibited a high frequency of predominantly α‐SU immunoreactivity. This is important since this subgroup of endocrine GEP‐tumours usually lacks hormonal markers. In patients with carcinoid syndrome, however, increased serum levels of α‐SU or hCG‐β appear to be rare and of no diagnostic value.
Studies on the effects of growth hormone administration in vivo on the rates of glucose transport and utilization in rat skeletal muscle
Authors: DIMITRIADIS G. , PARRY‐BILLINGS M. , LEIGHTON B. , PIVA T. , DUNGER D. , CALDER P. , BOND J. , NEWSHOLME E.
Published: March 2008

Abstract. The effects of growth hormone (GH) administration to rats in vivo on the sensitivity of the rate of glucose utilization to insulin were studied in soleus muscles isolated from these rats. A single injection of GH did not increase the rate of glucose transport within 1–2 h. However, 12 h after, the rate of glucose transport was increased at 10 mU insulin l‐1 and was accompanied by a similar increase in the rate of lactate formation but no change in the rate of glycogen synthesis. Prolonged treatment with GH decreased the rate of glucose transport and glycogen synthesis and increased the content of glucose 6‐phosphate at physiological levels of insulin but did not affect the rate of lactate formation. These results suggest that: (a) GH does not increase the rate of glucose transport acutely; however, after several hours, the sensitivity of glucose transport and glycolysis to insulin are increased; (b) prolonged elevations of the level of GH in plasma decrease the sensitivity of the rate of glucose transport and glycogen synthesis to insulin. However, redirection of glucose residues away from the pathway of glycogen synthesis towards that of glycolysis and a possible increase in the rate of glycogenolysis maintain a normal rate of lactate formation, although the rate of glucose transport is decreased.
Na+/H+ antiporter activity in peripheral blood lymphocytes of obese and type 2 diabetic patients is increased only in the presence of arterial hypertension
Authors: GHIGO D. , ALESSIO P. , BURZACCA S. , COSTAMAGNA C. , ANFOSSI G. , CAVALOT F. , BOSIA A. , TROVATI M.
Published: March 2008

Abstract. The aim of this work is to evaluate whether type 2 diabetes mellitus, obesity and arterial hypertension, three conditions characterized by the presence of insulin resistance, share some common genetic markers. A potential candidate is the Na+/H+ anti‐porter, the increased activity of which is considered a marker of essential hypertension. This ion exchanger seems to be related to the Na+/Li+ countertransport, that is considered a marker of insulin resistance in essential hypertension and in type 1 diabetes mellitus. In this study we wished to clarify whether the activity of the Na+/H+ antiporter is increased not only in hypertensive subjects, but also in obese and type 2 diabetic patients, both in the presence and in the absence of arterial hypertension. The activity of the ion exchanger was measured in peripheral blood lymphocytes (PBL) by clamping intracellular pH (pHi) at 5·8–6·2 and then detecting the rate of the proton efflux after sodium addition. In the absence of arterial hypertension, no significant difference in this parameter was observed in obese and type 2 diabetic patients in comparison with normal subjects. In the presence of arterial hypertension, there was a significant increase in the Na+‐induced H+ efflux at the internal pH (pHi) values of 5·8 and 6·2 both in hypertensive controls and in hypertensive obese and type 2 diabetic patients (P= 0·05–0·0001 vs. normotensive subjects and patients). In particular, H+ efflux at pH 5·8 (mmol l‐1 min‐1) was 35·36 ± 2·48 in normotensive and 42·77 ± 1·63 in hypertensive control subjects (P= 0·045), 33·06 ± 1·88 in normotensive and 50·40 ± 5·21 in hypertensive obese patients (P= 0·009), 31·16 ± 1·84 in normotensive and 55·54 ± 5·83 in hypertensive type 2 diabetic patients (P= 0·0001). H+ efflux showed a significant correlation with both systolic (at pHi 5·8, r = 0·473, P= 0·001; at pHi 6·2, r = 0·357, P= 0·016) and diastolic blood pressure (at pHi 5·8, r = 0·600, P= 0·0001; at pHi 6·2, r = 0·555, P= 0·0001). Therefore, our study demonstrates that the hyperactivity of the Na+/H+ exchanger in peripheral blood lymphocytes is also a marker of arterial hypertension in obesity and in type 2 diabetes mellitus, and that the exchanger activity is not increased in these two conditions in the absence of arterial hypertension.
Altered body composition and fuel metabolism in stable kidney transplant patients on immuno‐suppressive monotherapy with cyclosporine A
Authors: MATHIEU R. L. , CASEZ J. P. , JAEGER Ph. , MONTANDON A. , PEHEIM E. , HORBER F. F.
Published: March 2008

Abstract. Glucocorticoid associated altered body fat distribution and muscle wasting are well known following kidney grafting. Whether an immunosuppressive regimen after glucocorticoid withdrawal (i.e. monotherapy with cyclosporine A (CsA)) is associated with normalization of altered body fat distribution and muscle mass remains to be determined. Therefore 18 renal transplant patients (nine males and nine females, 64 ± 5 (mean ± SEM) months since transplantation; CsA‐monotherapy: 38 ± 7 months) and 18 age, sex and body mass index matched healthy volunteers were investigated using indirect calorimetry and dual energy X‐ray absorptiometry. Lean body mass (LBM) was decreased in patients mostly due to loss of striated muscle in the legs (P<0·01), Compared to healthy controls, fat mass was increased in head and trunk (P<0·01) and similar in extremities. Resting energy expenditure expressed per kg LBM was increased by more than 10% (P<0·05) in patients vs. controls. Plasma insulin and glucose concentrations, total serum cholesterol (C), triglyceride levels and the ratio of LDL‐C to HDL‐C were all elevated (P<0·01) in patients as compared with controls. In summary, renal transplant patients on immunosuppressive mono therapy with CsA demonstrate decreased muscle mass despite discontinuation of prednisone therapy. The increased upper body fat might account, at least in part, for peripheral hyperinsulinaemia and dyslipidaemia observed in kidney transplant patients even years after successful transplantation.
Platelets in ulcerative colitis and Crohn's disease express functional interleukin‐1 and interleukin‐8 receptors
Authors: SCHAUFELBERGER H. D. , UHR M. R. , McGUCKIN C. , LOGAN R. P. H. , MISIEWICZ J. J. , GORDON‐SMITH E. C. , BEGLINGER C.
Published: March 2008

Abstract Tissue and plasma concentrations of several cytokines are increased in patients with inflammatory bowel disease (IBD). Platelets play an important role in inflammation and circulate in an activated state in patients with IBD. This study assesses the expression of IL‐8 and IL‐1 receptors on the surface of platelets from patients with IBD using phycoerythrin (PE)‐labelled recombinant human rhIL‐1β and rhIL‐8 and flow cytometry. The percentage IL‐1R expressing platelets (median and interquartile range IQR) in the IBD group was 8·7% (5·5–18·2) compared to 4·2% (2·3–6·1) in controls (P= 0·02). The percentage IL‐8R expressing platelets in the IBD group was 22·5% (16·5–27·9) and 9·2% (4·3–9·6) in controls (P < 0·001). Furthermore, platelet IL‐1R expression in patients with IBD was inversely related to the total daily dose of steroids (r=–0·71, P < 0·01 linear regression analysis). Finally, platelet rich plasma from healthy controls was stimulated with rhIL‐1β and rhIL‐8 and assessed for activation dependent expression of platelet aGPIIb/IIIa and CD62 (p‐selectin, GMP‐140). IL‐1β and IL‐8 in vitro significantly and specifically activated the platelets. The surface membrane of platelets is able to express functional IL‐1R and IL‐8R, the expression of which is signficantly increased in IBD. Interleukin‐1β and IL‐8 modulate platelet activation in vitro indicating a target role for platelet function in inflammation.
Postprandial apolipoprotein B100 and B48 metabolism in familial combined hyperlipidaemia before and after reduction of fasting plasma triglycerides*
Authors: CABEZAS M. CASTRO , ERKELENS D. W. , KOCK L. A. W. , BRUIN T. W. A. DE
Published: March 2008

Abstract Hepatic VLDL overproduction in familial combined hyperlipidaemia (FCH) may delay the clearance of atherogenic apolipoprotein (apo) B containing particles. We investigated if normalization of fasting plasma triglycerides (TG) by hypolipidaemic treatment results in improved metabolism of apo B48 and apo B100 in six male subjects with FCH and compared them to six normolipidaemic controls. The FCH patients were studied before (TG, 5·2±1·2 mmoll‐1; mean ± SEM) and after therapy (TG, 2·1±0·3 mmoll‐1) with either simvastatin (n= 4) or combined therapy with gemfibrozil (n= 2). The post‐prandial changes of apo B100 and apo B48 were studied after a single oral fat meal (24h; 50 gram fatm‐2). Changes in triglyceride rich particles (TRP; d < 1·006 gml‐1) and remnant fractions (REM; d: 1·006–1·019g ml‐1) of apo B were quantitated by scanning silverstained SDS‐PAGE (4–15%). Apo B48 in fasting TRP in untreated and treated FCH was 15% and 14% of total apo B, and 6% in controls (P < 0·05). In controls, postprandial B48 increased maximally at 4h by 81% in TRP and by 137% in REM compared to baseline. In treated FCH, the post‐prandial apo B48 pattern normalized in TRP compared to the untreated state. Postprandial apo B100 in controls decreased in TRP and REM by 33% and 18% (P < 0·05). In untreated and treated FCH, postprandial apo B100 remained unchanged vs. baseline in TRP and in REM suggesting hypersecretion of VLDL. The elimination of B100—assessed as area under the curve—in TRP (32·5±3·6 au.h; mean±SEM) and REM fractions (33·2±3·1 au.h), improved significantly after treatment (21·0±2·8 and 20·4±3·3 au.h, respectively). The apo B48 clearance in TRP fractions was improved after treatment (4·3±1·4 au.h vs. 2·9±1·2 au.h; P= 0·06), but not in REM fractions (2·8±1·0 au.h vs. 1·8±0·5 au.h; NS). In conclusion, in FCH subjects with apo B100 hypersecretion and increased fasting plasma apo B48 levels, reduction of fasting plasma TG improved, but did not normalize, TRP apo B48 and B100 metabolism. However, therapy normalized postprandial apo B100 remnant metabolism. Impaired postprandial apo B metabolism may be instrumental in the development of premature atherosclerosis in FCH subjects.