bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholestyramine treatment of type IIa hypercholesterolaemia normalizes platelet reactivity against prostacyclin
Authors: LÖBEL PETRA , STEINHAGEN‐THIESSEN ELISABETH , SCHRÖR KARSTEN
Published: March 2008

Abstract. The effect of lowering total plasma and low density lipoprotein (LDL) cholesterol in heterozygous familial hypercholesterolaemia type IIa (FH) on platelet function, thromboxane (TX) formation and platelet sensitivity against iloprost, a stable prostacyclin mimetic, was studied in platelet‐rich plasma ex vivo. Seven FH patients were treated with cholestyramine (12 g day‐1) for 8–11 months and were compared with eight untreated FH patients and 11 healthy control subjects. In comparison with platelets from healthy controls, platelets from untreated FH patients exhibited a significantly increased aggregation response and TX formation, and a reduced reactivity against inhibition of platelet aggregation by prostacyclin. Treatment with cholestyramine for 8–11 months resulted in a 21% reduction in total serum and LDL‐cholesterol. This was not accompanied by any change in platelet hyperreactivity or TX formation. However, cholestyramine treatment normalized the platelet reactivity of FH patients against iloprost, being no more different from healthy controls. It is concluded that reduction in plasma cholesterol by cholestyramine results in normalization of the reduced platelet sensitivity against prostacyclin. This might contribute to beneficial effects of cholestyramine treatment in preventing thrombembolic complications of atherosclerosis.
Interindividual variability in biliary excretion of ceftriaxone: effects on biliary lipid metabolism and on intestinal microflora
Authors: ARVIDSSON ANNIE , LEIJD BARBRO , NORD C. E. , ANGELIN B.
Published: March 2008

Abstract. Ceftriaxone is a broad spectrum parenteral cephalosporin that is eliminated through renal as well as biliary excretion. In order to characterize factors influencing the biliary excretion of ceftriaxone, and possible effects of this organic anion on biliary lipid transport, we studied six healthy volunteers before and during ceftriaxone infusion. The biliary secretion rates of cholesterol, bile acids, phospholipids and ceftriaxone were determined using a duodenal perfusion technique, and the biliary lipid composition and cholesterol saturation of stimulated hepatic bile were determined. Changes in the intestinal microflora induced by ceftriaxone treatment were also analysed. There was a three‐fold interindividual variation in biliary excretion of ceftriaxone, and this was correlated with the secretion rate of bile acids (rs=0·83, P=0·05). During ceftriaxone infusion, the secretion rate of cholesterol was reduced by 32% (P<0·05), which resulted in a reduction of cholesterol saturation of bile, from 107±11 to 75±12% (SEM, P<0·05). The suppression of intestinal Escherichia coli and Bacteroides, and the proliferation of enterococci and lactobacilli were related to the biliary excretion of ceftriaxone. We conclude (i) that biliary excretion of ceftriaxone is of major importance for its effects on intestinal microflora, (ii) that secretion of this organic anion into bile is largely dependent on bile acid secretion, and (iii) that ceftriaxone inhibits the biliary secretion of cholesterol.
Inhibition of human neutrophil migration by supernatants from Hodgkin's disease‐derived cell lines
Authors: SCHELL‐FREDERICK E. , RADTKE H. , SOMMER H. , HELBING I. , BURRICHTER H. , SCHAADT M. , DIEHL V.
Published: March 2008

Abstract. The contribution of defective neutrophil function to the increased susceptibility to infection observed in patients with Hodgkin's disease is unclear. We describe cell‐directed inhibition of normal human neutrophil migration by serum‐free culture supernatants of the Hodgkin‐derived cell line L428 KSA, tentatively termed Hodgkin‐derived leucocyte factor (HDLF). This factor inhibits both random migration and migration toward different chemoattractants, appears to bind to the cell surface and is stable at 56°C but destroyed at 100°C. Hodgkin‐derived leucocyte factor also stimulates basal neutrophil superoxide production but the cells remain fully responsive to n‐formyl‐methionylleucylphenylalanine. Get filtration chromatography shows a single peak of migration‐inhibitory and superoxide‐stimulatory activity at approximately 70000 g mol‐1, Hodgkin‐derived leucocyte factor migration inhibition persists in neutro‐phils from a patient with chronic granulomatous disease. Activity of HDLF is completely destroyed by trypsin but unaffected by the protease inhibitor phenyl‐methylsulphonylfluoride. Hodgkin's factor appears to be different from previously described neutrophil migration inhibitory factors.
Role of alpha‐adrenoceptor subtypes mediating sympathetic vasoconstriction in human digits
Authors: COFFMAN J. D. , COHEN R. A.
Published: March 2008

Abstract. The effects of intra‐arterial administration of alpha‐1 and alpha‐2 adrenoceptor agonists and antagonists on human digital blood flow were studied before and during reflex sympathetic vasoconstriction in normal subjects. Total finger flow was measured by venous occlusion air plethysmography and capillary flow by the disappearance rate of a radioisotope from a local injection in a fingerpad. Intra‐arterial phenylephrine (0·2–1·3 μg min‐1) and clonidine (0·12–0·48 μg min‐1) produced dose‐related decreases in finger blood flow and increases in vascular resistance. Clonidine was the more potent vasoconstrictor. Prazosin (0·48 μg min‐1) effectively blocked the vasoconstrictor effect of phenylephrine but not clonidine, while yohimbine (30–70 μg min‐1) blocked the effect of clonidine but not phenylephrine. In a 20°C room, prazosin (0·4–13·2 μg min‐1) caused no significant changes in finger blood flow (7·7 ± 2·1 to 11·7 ± 3·3 ml min‐1) 100 ml‐1) or vascular resistance (30·9 ± 8·8 to 28·1 ± 8·7 mmHg ml‐1 min‐1 100 ml‐1). In the 20°C room, yohimbine (30–70 μg min‐1) produced a significant increase in finger blood flow (7·8 ± 2·8 to 23·4 ± 6·8 ml, P>0·01) and decrease in vascular resistance (20·5 ± 5·7 to 6·0 ± 2·2 units, P>0·01). No significant changes occurred in finger capillary flow with prazosin or yohimbine infusions. It is concluded that alpha‐1 and alpha‐2 adrenoceptors are present in human digital vasculature and that alpha‐2 adrenoceptors are more important than alpha‐1 adrenoceptors in sympathetic neural vasoconstriction. Since capillary blood flow was unaffected by yohimbine infusions during reflex sympathetic vasoconstriction, the alpha‐2 adrenoceptors predominantly influence arteriovenous shunts in the finger.
Copper distribution among serum proteins in paediatric liver disorders and malignancies
Authors: BARROW L. , TANNER M. S.
Published: March 2008

Abstract. Fractionation of normal serum on Sephadex G‐150, followed by determination of copper, caeruloplasmin and albumin concentrations, indicated that only approximately 71% of total serum copper was associated with caeruloplasmin; less than previously reported values. Seven per cent was associated with a high molecular weight protein, designated ‘transcuprein’, 19% with albumin and 2% with amino acids. Compared with adult serum the concentrations of caeruloplasmin and of copper associated with caeruloplasmin were low both in serum from neonates and in serum from patients with symptomatic Wilson's disease. However, in contrast to the neonate, Wilson's disease patients exhibited a raised total serum copper and raised non‐caeruloplasmin‐copper. In Indian Childhood Cirrhosis serum caeruloplasmin and caeruloplasmin‐copper levels were normal, whilst the non‐caeruloplasmin‐copper was raised. Elevated non‐caeruloplasmin‐copper in Wilson's disease and Indian Childhood Cirrhosis may therefore represent an overspill into the serum from a copper‐laden liver. Children with malignancy showed increased serum concentrations of copper and caeruloplasmin. Both caeruloplasmin‐bound and non‐caeruloplasmin‐bound copper concentrations were elevated. It remains to be determined whether increased ‘transcuprein’‐ and albumin‐bound copper result from a sequestering of copper released from peripherally utilized caeruloplasmin, or are associated with increased rates of caeruloplasmin synthesis.
Low dose heparin versus low molecular weight heparin (Kabi 2165, Fragmin®) in the prophylaxis of thromboembolic complications of abdominal oncological surgery
Authors: FRICKER J.‐P. , VERGNES Y. , SCHACH R. , HEITZ A. , EBER M. , GRUNEBAUM L. , WIESEL M.‐L. , KHER A. , BARBIER P. , CAZENAVE J.‐P.
Published: March 2008

Abstract. Eighty patients undergoing pelvic or abdominal surgery for cancer were randomized in two groups for prevention of postoperative thromboembolism: 40 patients received a 15 000 IU day‐1 Calciparine® prophylaxis and 40 patients a 5000 anti‐Xa U/d Fragmin® prophylaxis for 10 days. In the Calciparine group, two patients (5%) developed postoperative pulmonary embolism but none developed it in the Fragmin group. Two patients in the Fragmin group (5%) developed isotopic DVT, which was not confirmed by phlebography. There was no deep vein thrombosis of the lower limbs in the two groups. Important postoperative bleeding (one patient in the Calciparine group and two patients in the Fragmin group) was similar in both groups. Moderate and minor bleeding were significantly lower in the Fragmin group. Haemoglobin and haematocrit changes, total blood loss and transfusion requirements were not different in both groups. It is concluded that, over a 10‐day period, one daily 5000 U Fragmin prophylaxis was as effective and safe as three daily 5000 IU Calciparine injections.
Atrial natriuretic factor enhances vasopressin‐induced bradycardia in normotensive (WKY) but not in spontaneously hypertensive (SHR) rats
Authors: LAPIŃSKI M. , STEPNIAKOWSKI K. , JANUSZEWICZ A. , NOSZCZYK B. , SZCZEPAŃSKA‐SADOWSKA EWA
Published: March 2008

Abstract. Effect of elevation of blood atrial natriuretic peptide (rat 1–28 ANF) level on pressor responses and bradycardia elicited by vasopressin (AVP) was compared in conscious normotensive (WKY) and spontaneously hypertensive (SHR) rats 14–16 weeks old, instrumented with arterial and venous catheters 1–2 days prior to the experiment. Blood pressure and heart rate were determined before and after i.v. injection of 2·5, 5·0 and 10·0 ng of AVP under control conditions (infusion of saline) and during infusion of ANF at a rate of 0·3 μg kg‐1 min‐1. Administration of ANF did not influence pressor responsiveness to AVP (determined as a maximum increase of systolic blood pressure) neither in WKY nor in SHR, however, it elongated the pressor response to the lowest dose of AVP in WKY. Atrial natriuretic factor significantly enhanced bradycardic responsiveness to AVP (determined as a maximum decrease of HR) in WKY but not in SHR. Reduction of heart rate in relation to the corresponding elevation of the systolic pressure (ΔHR/ΔSP) was also significantly greater in WKY but not in SHR. This effect was significant when blood pressure increases elicited by AVP did not exceed 40 mmHg. The results suggest that ANF potentiates reflex bradycardia elicited by AVP. This action may be a mechanism buffering blood pressure increases in response to AVP. Absence of this effect in SHR may be related to the impairment of the reflex control of blood pressure in this strain.
Adipocyte insulin receptor binding and lipogenesis at term in normal pregnancy
Authors: ANDERSEN O. , KÜHL C.
Published: March 2008

Abstract. Lipogenesis in subcutaneous abdominal adipocytes during late human pregnancy was investigated by studying insulin receptor binding, 3‐O‐methyl‐(14C‐(U))‐glucose flux and incorporation of (14C(U))‐glucose into CO2 (oxidation) and total lipids (lipogenesis) in adipocytes from 18 healthy pregnant women undergoing Caesarean section at term, and 19 non‐pregnant women undergoing gynaecological surgery. The cell diameter and fasting insulin were increased in the pregnant women, compared with controls (P < 0·01 and P < 0·05, respectively). The insulin receptor binding, 3‐O‐methyl‐glucose flux, and basal oxidation were similar in both groups. Basal lipogenesis was higher in adipocytes from pregnant women than from controls (P < 0·05), but the maximally stimulated increment was similar in both groups. Basal and maximally stimulated lipogenesis correlated positively with the cell diameter (P < 0·001 and P < 0·05, respectively). The findings indicate that lipogenesis in subcutaneous abdominal adipocytes from pregnant women is increased due to post‐receptor events and that adipocytes do not contribute to the insulin resistance in late pregnancy.
Polymorphism at the 5‘ end flanking region of the insulin gene is associated with reduced insulin secretion in healthy individuals
Authors: COCOZZA S. , RICCARDI G. , MONTICELLI ANTONELLA , CAPALDO BRUNELLA , GENOVESE S. , KROGH V. , CELENTANO E. , FARINARO E. , VARRONE S. , AVVEDIMENTO V. E.
Published: March 2008

Abstract. Sixty‐four unrelated healthy subjects were studied for the detection of a DNA polymorphism at the 5′ end of the insulin gene. No significant difference between the groups was found in blood glucose values at fasting and after an oral glucose load. A significant association was found between fasting (P < 0·05) and after load plasma C‐peptide levels (P < 0·01) and the presence of a 1·6 Kb insertion at the 5′ end of the insulin gene. A gene dose‐dependent effect was noted, class 3/3 individuals having the lowest after‐load C‐peptide concentration and class 1/3 an intermediate level (F for the linear trend: P=0·007). This might suggest that insulin gene polymorphism affects insulin secretion in healthy individuals. In order to confirm this, a subgroup of six class 3/3 and eight class 1/1 individuals subsequently underwent a hyperglycaemic clamp. The tissue sensitivity to insulin was similar in the two groups but glucose‐stimulated insulin secretion was markedly impaired in homozygotes for the class 3 allele. In this group, insulin secretion was, on average, only one‐third of that in class 1/1 individuals (P < 0·02). Similarly impaired in class 3/3 persons was the glucose+arginine‐stimulated insulin secretion (P < 0·05). We conclude that the polymorphism at the 5′ end of the insulin gene is associated with variations in insulin secretion in healthy humans.
Plasminogen activators and plasminogen activator inhibitor in malignant and non‐malignant ascitic fluid
Authors: HUBER K. , WOJTA J. , KIRCHHEIMER J. C. , ERMLER D. , BINDER B. R.
Published: March 2008

Abstract. Ascitic fluid from tumour patients (hepatoma, gastric cancer, gallbladder cancer, colorectal cancer, ovarian cancer) and from non‐malignant diseases (liver cirrhosis, congestive heart failure) were compared with respect to their content of determinants of the fibrinolytic system, tissue‐type plasminogen activator antigen (t‐PAag) and activity (t‐PAact), urokinase‐type plasminogen activator antigen (u‐PA) and plasminogen activator inhibitor activity (PAI). Furthermore, SDS‐polyacrylamide slab‐gel electrophoresis (SDS‐PAGE) was performed to evaluate molecular weight distribution of the detectable fibrinolytic parameters. In malignant ascites, PAI activity was three to four times higher, and increased complex formation of PAI with t‐PA could be demonstrated, compared with non‐malignant ascitic fluid. Tissue‐type plasminogen activator antigen and activity showed a similar concentration in ascites of both study groups. Urokinase‐type plasminogen activator antigen was detectable neither in ascites of malignant nor in ascites of non‐malignant origin. It is concluded that t‐PA is the physiological plasminogen activator in ascites and that increased PAI levels followed by increased complex formation between t‐PA and PAI might reflect a reaction of the peritoneum.
Differences in individual responsiveness of serum cholesterol to fat‐modified diets in man
Authors: KATAN M. B. , VAN GASTEL A. C. , DE ROVER C. M. , VAN MONTFORT M. A. J. , KNUIMAN J. T.
Published: March 2008

Abstract. In the period 1963–1974, 82 monks and 48 nuns from five Dutch and Belgian Trappist monasteries each participated in two or more out of nine different trials designed to test the effect of 58 different fat‐modified diets on serum cholesterol. We analysed these data to quantify the extentto which healthy, normolipaemic subjects differ in the responsiveness of their serum cholesterol to a change in dietary fatty acid composition. Statistically significant between‐person variance components (SD2ρp) were found in the serum cholesterol responses for the whole group (SD2ρp= [0·20 mmol l‐1]2), for the men (SD2ρp= [0·24 mmol l‐1]2) and for those women who participated in three or more trials (SD2ρp= [0·14 mmol l‐1]2). The between‐person variation (expressed as SD) was on average only half as large as the within‐person variation in response when the same subject was challenged repeatedly. It is concluded that medically significant differences in responsiveness to fat‐modified diets exist in both men and women. However, few subjects fail entirely to respond to a change in dietary fatty acid composition. In addition, the large within‐subject variability makes it difficult to identify hypo‐ and hyperresponders.
Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin‐induced extracorporeal LDL precipitation (HELP)*
Authors: SCHUFF‐WERNER P. , SCHÜTZ E. , SEYDE W. C. , EISENHAUER TH. , JANNING G. , ARMSTRONG V. W. , SEIDEL D.
Published: March 2008

Abstract. Heparin‐induced Extracorporeal LDL‐Pre‐cipitation (HELP) is an effective procedure for the elimination of both plasma LDL and fibrinogen.

In 10 adult patients with severe type II hyperlipoproteinemia, a single HELP treatment of 3 1 plasma led to an acute decrease in the average plasma viscosity (PV) from 1.30 to 1.1 mPas. At the same time, an even more marked decrease in the mean erythrocyte aggregation rate from a pathological value of 7.9% to a value of 3.7% (normal range <5%) was observed. Long‐term studies on five patients demonstrated a lasting improvement in these two haemorheological variables. The acute rheological changes were also accompanied by an improvement in polarographically determined muscle oxygen tension. Mean oxygen tension values measured in both the m.biceps brachii and the m.tibia‐lis anterior in five patients before and after a single HELP treatment increased from 30.4 to 37.7 mmHg and from 27.2 to 31.3 mmHg respectively.

These results may provide an explanation for the rapid improvement in patients' clinical symptoms such as angina pectoris and in stress electrocardiogram which have been observed during HELP therapy.
Modifications induced by diabetes on the physicochemical and functional properties of erythrocyte plasma membrane
Authors: MAZZANTI L. , RABINI R. A. , TESTA I. , BERTOLI E.
Published: March 2008

Abstract. Increasing evidence suggests that in experimental diabetes an impairment in Na+, K+–ATPase activity plays a central role in the pathophysiology of diabetic complications, while only a few data are available with regard to human subjects. We studied the erythrocyte membrane Na+, K+‐ATPase activity and membrane fluidity in insulin‐dependent and non‐insulin‐dependent diabetic subjects. A significant decrease in the enzyme activity and in fluorescence polarization values was found in both groups compared with normal subjects. Neither Na+, K+‐ATPase activity nor membrane fluidity was found to be related to metabolic control, assessed by means of fasting blood glucose levels and HbA1c. On the contrary, a significant correlation was observed between Na+, K+‐ATPase activity and membrane fluidity in both insulin‐dependent and non‐insulin‐dependent diabetic subjects. The present work provides evidence that a reduction in the Na+, K+‐ATPase activity is present in the plasma membranes of insulin‐dependent and non‐insulin‐dependent diabetics. Furthermore, it suggests that the change in enzyme activity might be related to modifications in membrane fluidity.
Erythrocyte sodium‐lithium countertransport in primary and renal hypertension: relation to family history
Authors: CARR S. J. , THOMAS T. H. , WILKINSON R.
Published: March 2008

Abstract. Sodium‐lithium countertransport (Na‐Li CT) has been reported to be increased in essential hypertension (EHT) but the nature and degree of distinction from normal controls is unclear. Of 44 unselected patients with EHT in the hospital hypertension clinic 36% had Na‐Li CT greater than the normal control range and 70% of these had a family history of hypertension. Almost all the patients with normal Na‐Li CT had no family history of hypertension. Analysis of variance showed that raised Na‐Li CT was related to both a family history of hypertension and a family history of a cardiovascular event. Of 23 patients with hypertension secondary to renal disease, 43% had Na‐Li CT greater than the normal control range and raised Na‐Li CT was related to both a family history of hypertension and a family history of cardiovascular event in the same way as EHT. Raised Na‐Li CT was not characteristic of EHT but identified a subgroup of patients with EHT and a family history of hypertension, some of whom also had renal disease.
Effect of hyperosmolality on basal and hormone‐stimulated hepatic glucose metabolism in vitro
Authors: KOMJATI M. , KASTNER G. , WALDHÄUSL W. , BRATUSCH‐MARRAIN P.
Published: March 2008

Abstract. To understand better impairment of glucose utilization in diabetics during a hyperosmolal state, in vitro models were established to evaluate the effects of hyperosmolality on basal glucose uptake as well as glucagon dependent glucose release by isolated hepatocytes. In these studies simulating a hyperglycaemic (40 mmol glucose) and hyperosmolal (up to 500 mosm kg‐1, NaCl as added solute) state basal hepatic glucose uptake was reversibly suppressed by 19% when osmolality was increased by as little as 10 mosm kg‐1. No such effects on glucose uptake by isolated hepatocytes could be attained when the incubation's fluid osmolality was augmented by the addition of urea or mannitol. Estimations of the transport rates of 3‐O‐methyl‐glucose and uptake of 2‐deoxyglucose at 400 vs. 300 mosm kg‐1 revealed that impaired intracellular enzymatic activity but not the transport rate of glucose into the cell were responsible for the hyperosmolal defect as uptake was more reduced (P< 0.025) by increased osmolality for 2‐deoxyglucose (16%) than for 3‐O‐methylglucose (13%). Glucagon dependent glucose release from isolated hepatocytes was diminished by 17.8% when the osmolality was raised to 400 mosm kg‐1 by NaCl as added solute. These data obtained in vitro support the clinical contention that a hyperosmolal state, which corresponds to a loss of fluid in excess of solutes, is able to impair basal hepatic glucose uptake as well as glycogenolytic glucagon action on the liver.
Hypertension in chronic idiopathic glomerulonephritis: analysis of 311 biopsied patients
Authors: RAMBAUSEK M. , RHEIN CHRISTINE , WALDHERR R. , GOETZ R. , HEIDLAND A. , RITZ E.
Published: March 2008

Abstract. Prevalence of hypertension and relation of hypertension to renal function, type of glomerulonephritis or histological features were evaluated in 311 patients with idiopathic chronic glomerulonephritis. The overall prevalence of hypertension was 49 8%. At least in women, prevalence of hypertension was increased even at serum creatinine levels < 1.1 mg dl‐1 compared with the local general population. Prevalence of hypertension was 2.12 and 8.6‐fold higher at serum creatinine 1.1–1.4 mg dl‐1 in males and females respectively. In patients with untreated hypertension, a relation was found between mean blood pressure and subsequent decline of estimated GFR.

Furthermore, in patients with arterial sclerosis, but not in patients without, a significant relation was found between blood pressure and subsequent increase in serum creatinine.
Isoforms of creatine kinase: MM in the study of skeletal muscle damage
Authors: PAGE S. , JACKSON M. J. , COAKLEY J. , EDWARDS R. H. T.
Published: March 2008

Abstract. Isoforms of creatine kinase (CK) MM have been analysed in plasma from normal subjects and patients with muscular dystrophy using isoelectric focusing techniques. Most plasma samples analysed contained three isoforms of CK‐MM of isoelectric points 7.26 (MMI), 6.85 (MMII) and 6.45 (MMIII) although in some plasma samples two additional isoforms of isoelectric points 7.12 and 6.65 were seen. Patients with muscular dystrophy were found to have a generally higher proportion of CK‐MMI in their plasma than normal subjects and this was relatively unaffected by large variations in the total creatine kinase activity. By comparison eccentric exercise in normal subjects was found to result in a large increase in total plasma CK activity which then declined to normal over a period of approximately 6 days. CK‐MMI was found to increase initially followed by CK‐MMII and CK‐MMIII. Analysis of the isoforms in biopsy samples of human muscle revealed the presence of two of the bands found in plasma (CK‐MMI and MMII) and a third muscle specific isoform, while incubation of muscle homogenates in plasma induced the formation of CK‐MMIII and the two isoforms of pi 7.12 and 6.65.

It is concluded that analyses of CK‐MM isoforms in human plasma can provide useful information on the extent and relative time course following an episode of muscle damage but that in patients with muscular dystrophy the large variations in plasma CK activity are not reflected in the proportion of CK found in each isoform. This implies that even during the large falls of total CK activity seen in plasma of patients with muscular dystrophy substantial muscle damage is still occurring.
Effect of pyridoxine supplementation on plasma oxalate concentrations in patients receiving dialysis
Authors: TOMSON C. R. V. , CHANNON SUSAN M. , PARKINSON I. S. , SHELDON W. S. , WARD M. K. , LAKER M. K.
Published: March 2008

Abstract. Plasma oxalate and erythrocyte glutamic oxaloacetate transaminase activity (EGOT) (an indicator of nutritional status with respect to pyridoxine) were measured in 21 patients maintained on regular continuous ambulatory peritoneal dialysis or haemodialysis before and after a 4‐month period of supplementation with pyridoxine, 100 mg day‐1. Prior to supplementation 10/21 patients showed subnormal EGOT activity, although the increment in activity on addition of pyridoxal‐5‐phosphate in vitro was within the normal range in all cases. Mean plasma oxalate was 31.5 μmol 1‐1 (SEM 2.9) prior to supplementation and did not change significantly with supplementation, despite normalization of EGOT activity in all but 2/21 patients. We conclude that pyridoxine deficiency does not contribute significantly to hyperoxalaemia in patients receiving dialysis and that 100 mg of pyridoxine daily is insufficient to reduce oxalate generation by a pharmacological action on glycine transamination.
Effects of therapeutic percutaneous electrical stimulation of atrophic human quadriceps on muscle composition, protein synthesis and contractile properties
Authors: GIBSON J. N. A. , MORRISON W. L. , SCRIMGEOUR C. M. , SMITH K. , STOWARD P. J. , RENNIE M. J.
Published: March 2008

Abstract. The effects of percutaneous electrical stimulation (70 V, 300 μs pulses at 30 Hz) on muscle composition and rate of protein synthesis were studied in seven patients with quadriceps atrophy secondary to unilateral osteoarthritis of the knee (stimulated group). Quadriceps were stimulated on the affected side for 1 h per day. The results were compared to those from seven patients who did not use a muscle stimulator (control group); in whom muscle biopsy at surgery provided evidence of wasting of tissue protein on the side of osteoarthritis (normal leg 608 ± 266 μg protein μg‐1 DNA, affected leg 256 ± 100 μg protein μg‐1 DNA, means ± SD, P<0.05; type I fibre diameters: normal 53.2 ± 6.7 μm, affected 43.8 ± 4.0 μm, P<0.05). In patients who had received stimulation there was no residual difference between the legs in either muscle protein concentration (normal 411 ± 168 μg protein μg‐1 DNA, affected 373 ± 112 μg protein μg‐1 DNA) or fibre diameter (type I diameters: normal 56.1 ± 7.8 μm, affected 58.0 ± 10.7 μm). Stimulation did not influence the ratios of muscle force elicited by acute stimulation at 20 and 50 Hz (normal 75 ± 15%, affected 79 ± 15%), or rates of muscle relaxation (percentage losses of tetanic force 10 ms‐1: normal 7.66 ± 1.2%, affected 8.67 ± 2.2%). In control (not stimulated) patients there was a higher rate of muscle protein synthesis (ks) on the side of knee osteoarthritis (normal 0043 ± 0.028% h‐1, affected 0.068 ± 0.044% h‐1, P<0.05). In patients stimulated on the affected side ks was certainly maintained (0.052 ± 0.02% h‐1 normal, 0.056 ± 0.02% h‐1 affected). The calculated rate of increase in muscle fibre volume induced by stimulation (0.055% h‐1) required to balance the discrepancy in volume between the legs of patients in the control group was similar to the rate of muscle protein synthesis measured in quadriceps after stimulation, suggesting that muscle protein breakdown had fallen to a level approaching zero. The results suggest possible therapeutic benefits of electrical stimulation in patients awaiting knee surgery.
Mobilizable lead in patients with chronic renal failure
Authors: KOSTER J. , ERHARDT A. , STOEPPLER M. , MOHL C. , RITZ E.
Published: March 2008

Abstract. Blood lead (Pb) and urinary Pb before and after i.v. infusion of 1 g of Na2Ca EDTA were determined (atomic absorption) in 46 control subjects and 91 patients with various stages of renal failure (median serum creatinine 2.5 mg dl‐1). Under baseline conditions, patients with renal failure had higher blood Pb levels (112 ng ml‐1, range 44–272 vs. 76; 36–187 in controls; P<0.001) and lower urinary Pb (16.2 nmol 24 h‐1 1.73 m‐2, 4.86–66.8 vs. 33; 11–91 in controls; P= 0.001). The increment in urinary Pb after EDTA infusion (mobilizable Pb) was higher (795 nmol 4 days‐1 1.73 m‐2, range 155–5611 vs. 307; 131–1587 in controls; P= 0.001). In 12 patients with renal failure (13%) mobilizable Pb was above the highest value in controls. Mobilizable urinary Pb correlated (r= 0.68) significantly (P= 0.001) with blood Pb, but only marginally with serum creatinine (r= 0.32; P < 0.007). Mobilizable Pb was higher in patients with renal failure and a history of smoking or occupational Pb exposure and tended to be higher in patients with alcoholism. Ten of 91 patients had gout; increased mobilizable Pb was present in three of the 10.

The data confirm relatively high prevalence of elevated body Pb burden in European patients with chronic renal failure. The question is unresolved whether Pb plays a role in the progression of renal failure.
Intravenous atrial natriuretic peptide does not affect water and ion transport in the human small intestine
Authors: PETRITSCH W. , HOLZER‐PETSCHE U. , HINTERLEITNER T. , KREJS G. J.
Published: March 2008

Abstract. Atrial natriuretic peptide (ANP) increases renal sodium and water excretion in several species including man. In rats ANP was also found to influence water and electrolyte transport in the small intestine. In the present study we investigated whether ANP can alter transport in the jejunum and ileum of healthy volunteers using a triple‐lumen perfusion technique. The small intestine was perfused under steady‐state conditions with a plasma‐like electrolyte solution using polyethylene glycol as a nonabsorbable volume marker. After an initial control period with intravenous saline infusion ANP was administered intravenously at a dose of 400 pmol kg‐1 h‐1. This dose led to a significant (P<0.05) increase in the plasma levels of ANP (up to 22‐fold) and cGMP (up to 15‐fold), and of urine volume. Intestinal water and electrolyte transport were, however, not affected by ANP. Our results suggest that circulating ANP does not play a role in the regulation of mucosal water and ion transport in the human small intestine.
Protection of the rat gastric mucosa against aspirin injury by arachidonic acid: a dietary prostaglandin precursor fatty acid
Authors: TARNAWSKI A. , HOLLANDER D. , STACHURA J. , KRAUSE W. J. , GERGELY HELLA
Published: March 2008

Abstract. We studied aspirin‐induced injury to the gastric mucosa in control rats pretreated with a solubilizer, pluronic F‐68 (PL), and in rats pretreated with solubilized arachidonic acid (AA). Fasted male rats were pretreated intragastrically with 1 ml of either pluronic or AA and 1 h later acidified ASA (1 ml suspension of 200 mg kg‐1 body weight) was administered intragastrically. Grossly apparent mucosal lesions developed 1 h after aspirin in pluronic‐pre‐treated rats, but were significantly reduced in AA‐pretreated rats. Histology, scanning and transmission electron microscopy demonstrated that AA pretreatment did not prevent aspirin‐induced initial damage to the surface epithelium but did significantly reduce extent of aspirin‐induced deep mucosal necrosis at 1,4 and 18 h after aspirin. Initial aspirin‐induced surface epithelial damage was rapidly restituted by two distinct types of re‐epithelialization ‐ vertical and horizontal. While the vertical type of re‐epithelialization has been reported previously as the first stage of mucosal repair following injury by various noxious agents such as concentrated ethanol, the horizontal type of re‐epithelialization, which is described for the first time in this paper, seems to be specific for the repair of aspirin‐induced gastric mucosal injury. These studies suggest that dietary factors such as essential fatty acids may play a role in gastric mucosal protection against aspirin injury.
Effects of four orally administered analogues of prostaglandin E1 and E2 on glucose tolerance and on the secretion of pancreatic and gastrointestinal hormones in man
Authors: NAUCK M. , HÄRTER S. , EBERT R. , CREUTZFELDT W.
Published: March 2008

Abstract. Oral glucose tolerance tests (75 g, 300 ml) were performed in 12 healthy volunteers, with prior administration of placebo, misoprostol (400 μg), rioprostil (300 μg), enprostil (70 μg), or nocloprost (200 μg), in a double‐blind, randomized manner. None of the drugs significantly affected glucose tolerance, although with misoprostal some volunteers displayed an impaired glucose tolerance. Nocloprost was without effect on gastric inhibitory polypeptide (GIP) and did not influence insulin or C‐peptide concentrations. Misoprostol and rioprostil reduced integrated incremental responses of GIP by 57% (P± 0.001) and 45% (P± 0.01), respectively, and both gave rise to an initial (˜10 min) delay of insulin and C‐peptide responses, without a significant overall reduction in integrated incremental responses. Enprostil almost totally inhibited the GIP response (by 94%; P± 0.001), delayed initial insulin and C‐peptide responses, but reduced the integrated incremental C‐peptide response (which corresponds to the overall release of insulin) by only 14% (P± 0.05). Enprostil more substantially reduced the integrated incremental response of insulin by 36% (P± 0.01), and also reduced the ratio of insulin and C‐peptide incremental responses (P± 0.001). In conclusion, prostaglandin E analogues which caused a reduction in GIP responses, and thereby disrupting the enteroinsular axis to varying degrees, delayed the time‐course of insulin secretion without a significant impact on glucose tolerance. Only enprostil, moderately, reduced overall insulin secretion, and, furthermore, reduced insulin in the peripheral circulation relative to the amount of insulin (C‐peptide) secreted. This phenomenon is most likely explained by an increased insulin clearance from the circulation under the influence of enprostil.
Efficacy and pharmacokinetics of piretanide in patients with congestive heart failure
Authors: MARONE C. , RIVERA B. , ZWAHLEN H. , LAHN W. , FREY F.
Published: March 2008

Abstract. The efficacy and pharmacokinetics of the diuretic piretanide were studied in two groups of six patients hospitalized for congestive heart failure. A dosage of 2 times 6 mg day‐1 to 2 times 12 mg day‐1 of intravenous piretanide for 7 days was sufficient to abrogate most symptoms of cardiac insufficiency. When compared with another group of healthy volunteers, patients with congestive heart failure had reduced total body clearance of piretanide of about 50% which was attributable to a diminished renal but not non‐renal clearance. The analysis of the interrelationship between urinary piretanide excretion and diuresis by means of a linearized Emax‐model revealed a maximal diuresis of 231 ml h‐1 and a urinary piretanide excretion to induce half‐maximal diuresis of 245 μg h‐1. Thus patients with congestive heart failure exhibit a decreased renal clearance of piretanide and a good response to this high ceiling diuretic after intravenous dosing.
Risk factors for coronary artery disease: a study comparing hypercholesterolaemia and hypertriglyceridaemia in angiographically characterized patients
Authors: BREIER CH. , PATSCH J. R. , MÜHLBERGER V. , DREXEL H. , KNAPP E. , BRAUNSTEINER H.
Published: March 2008

Abstract. Fifty‐two male patients undergoing coronary angiography were allocated to four groups each consisting of 13 subjects: group I had normal coronary arteries and patients in groups II‐IV exhibited coronary artery disease. In group II, plasma cholesterol was below 250 mg dl‐1 and triglycerides below 160 mg dl‐1; in group III, cholesterol was above 270 mg dl‐1 and triglycerides under 160 mg dl‐1; and in group IV, cholesterol was under 270 mg dl‐1 and triglycerides above 180mgdl‐1.

The hypertriglyceridaemic group IV had the highest coronary score. In addition, it had lowest lipoprotein lipase activity, lowest HDL‐cholesterol and lowest high‐density lipoproteins‐2 (HDL‐2) levels, suggesting that this type of hypertriglyceridaemia is caused—at least, in part—by lipoprotein lipase deficiency with impaired removal of the triglyceride‐rich lipoproteins and increased catabolism of HDL‐2. Our findings point towards a type of hypertriglyceridaemia strongly associated with coronary artery disease which should therefore be treated accordingly.
Defective enzyme protein in lipoprotein lipase deficiency
Authors: AUWERX J. H. , BABIRAK S. P. , FUJIMOTO W. Y. , IVERIUS P.‐H. , BRUNZELL J. D.
Published: March 2008

Abstract. A monoclonal antibody to lipoprotein lipase (LPL) has been used in an enzyme‐linked immunosorbent assay (ELISA) for LPL protein mass. Measurement of LPL immunoreactive mass in pre‐ and postheparin plasma distinguished three classes of abnormalities in patients with classical deficiency of lipoprotein lipase activity. The class I defect consisted of the absence of LPL immunoreactive homodimer in pre‐ and postheparin plasma compatible with a potential ‘null allele’. Patients with a class II defect had almost no LPL immunoreactive mass in preheparin plasma but showed an increase in their LPL mass of 68 ± 23 ng ml‐1 (mean ± SD) after heparin. Patients with the class III defect had considerable amounts of LPL immunoreactive material in preheparin plasma (159 ± 190 ng ml‐1). Heparin administration, however, caused very little additional release of LPL into the plasma (16 ± 51 ng ml‐1). Thus although both class II and class III patients had an LPL protein with abnormal catalytic activity, class III patients also appeared to have a defect in heparin binding of LPL. To test this hypothesis, postheparin plasma of classes II and III patients was analysed by heparin‐Sepharose chromatography. In contrast to class II patients, the LPL immunoreactive mass of class III patients did not show affinity for the heparin and eluted in the column void volume, suggesting the class III defect is also associated with a defect in heparin binding.
Role of the gastric phase in fat‐induced gallbladder contraction and cholecystokinin secretion in humans
Authors: MASCLEE A. A. M. , JANSEN J. B. M. J. , DRIESSEN W. M. M. , GEUSKENS L. M. , LAMERS C. B. H. W.
Published: March 2008

Abstract. The present study was undertaken to investigate the role of the gastric phase of fat‐induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra‐intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P < 0.05) later increase in plasma CCK levels (20 ± 2 min) compared to intraintestinal fat (5 ± 1 min). Similarly, the onset of gallbladder emptying was significantly (P < 0.05) delayed after intragastric fat (20±2 min) compared to intestinal fat (10±1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P < 0.005‐P < 0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 ± 1 min) and the onset of gallbladder emptying (15 ± 2 min) were in the same range after intra‐intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated. The main role of the stomach in the regulation of gallbladder contraction is by regulating the delivery of the stimulus to the intestine.
Ornithine decarboxylase and polyamines in cholecystokinin‐induced pancreatic growth in rats: effects of α‐difluoromethylornithine and the CCK receptor antagonist L‐364,718
Authors: LÖSER CHR. , FÖLSCH U. R. , SAHELIJO‐KROHN P. , CREUTZFELDT W.
Published: March 2008

Abstract. Acute and long‐term changes of ornithine decarboxylase and polyamines during pancreatic adaptation in response to cholecystokinin administration (1 μg kg‐1 body wt every 8 h) were studied in rats. α‐difluoromethylornithine, an irreversible and specific inhibitor of ornithine decarboxylase, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. In the cholecystokinin‐treated animals ornithine decarboxylase activity was increased after 2 h, reached a maximum after 8 h (444.6 pmol 14CO2 h.‐1 mg‐1 DNA, about 65‐fold greater than controls, P< 0.001) followed by a significant increase of putrescine after 6 h and spermidine after 24 h while spermine remained unchanged. The trophic parameters increased in the following time sequence: thymidine kinase (12 h), DNA polymerase (24 h), pancreatic weight (2 days), protein (2 days) and DNA (5 days), α‐difluoromethylornithine significantly delayed the increase in ornithine decarboxylase, putrescine and spermidine as well as all trophic parameters. Increases in ornithine decarboxylase, polyamines and all trophic parameters were completely inhibited by simultaneous application of the CCK receptor antagonist L‐364,718. These data indicate an important role for ornithine decarboxylase and polyamines in cholecystokinin‐induced pancreatic growth in rats.
Report from the 2nd workshop on quantitative evaluation of metabolism in the intact liver
Authors: KEIDING SUSANNE
Published: March 2008

Around 35 participants took part in one‐and‐a‐halfday's presentations and discussions of on‐going research.
Essential hypertension and insulin resistance in non‐insulin‐dependent diabetes
Authors: LAAKSO M. , SARLUND H. , MYKKÄNEN L.
Published: March 2008

Abstract. A recent study has shown that young, lean, hypertensive subjects are more insulin resistant than corresponding normotensive subjects. Whether this finding can also be demonstrated in the presence of non‐insulin‐dependent diabetes mellitus (NIDDM) is not known. Therefore, the degree of insulin resistance was studied in 26 middle‐aged hypertensive patients with NIDDM (11 men, 15 women) and 14 normotensive patients with NIDDM (eight men, six women) matched for age, metabolic control and the duration of diabetes, utilizing the glucose clamp technique. Non‐obese NIDD patients (body mass index <27.0 kg m‐2) with hypertension (n= 11) had significantly lower glucose disposal rates (GDRs) during the last 60 min of euglycaemic (5.5 mmol 1‐1) and hyperinsulinaemic (600 pmol 1‐1) clamp studies than NIDD patients without hypertension (n=6) (782.94 vs. 1418±97 μmol m‐2 min‐1, P<0.05). In contrast, GDRs were similar in obese NIDD patients with (n=15) and without (n= 8) hypertension (802 ± 90 vs. 849 ± 90 μmol m‐2/min‐1, respectively, P=NS). Basal hepatic glucose output, suppression of hepatic glucose production during hyperinsulinaemia and insulin secretion capacity did not differ between hypertensive and normotensive subjects. In a 2‐h oral glucose‐tolerance test non‐obese hypertensive NIDD subjects had higher fasting (P<0.01), 1‐h and 2‐h insulin levels (P<0.05) and areas under the insulin curve (P<0.05) than nonobese normotensive NIDD subjects, although no difference in fasting, 1‐h or 2‐h glucose concentrations between these groups were observed.
The diagnostic value of several immunological tests for anti‐nuclear antibody in predicting the development of connective tissue disease in patients presenting with Raynaud's phenomenon
Authors: WOLLERSHEIM H. , THIEN TH. , HOET M. H. , VENROOY W. J. VAN
Published: March 2008

Abstract. One‐hundred‐and‐one patients referred because of Raynaud's phenomenon (RP) were prospectively followed for a mean period of 42 months. At presentation they were screened for signs and symptoms of connective tissue disease (CTD) according to a detailed protocol. At presentation 37 patients had primary RP (PRP), nine had RP in combination with vascular occlusive disease (RP‐VOD), 25 had one symptom of a CTD (questionable PRP), 13 had two or more symptoms (undifferentiated CTD, UCTD) and 17 had definite CTD. Progression from one of these groups to another was seen in 24 patients and from PRP, RP‐VOD or questionable PRP towards a (U)CTD was seen in 19 patients. Patients with one sign of CTD showed a high tendency (56%) to develop CTD. The presence of ANA as detected by immunofluorescence and by immunoblotting at the start of the study was associated with the future development of symptoms of CTD; positive predictive value 65% and 71% and negative predictive value 93% and 83%, respectively. ANA‐testing by immunoblotting was of special help in predicting the development of scleroderma, the CREST syndrome and mixed connective tissue disease. In conclusion, testing for ANA by indirect immunofluorescence helps to discriminate between patients with persisting PRP and those who will develop a CTD, while testing for ANA by the immunoblotting technique helps to predict the development of a specific CTD.
Modulation of cytochrome P450 isozymes in human liver, by ethanol and drug intake
Authors: PERROT N. , NALPAS B. , YANG C. S. , BEAUNE P. H.
Published: March 2008

Abstract. Cytochromes P450 (P450) are a family of isozymes which play an important role in xenobiotic metabolism. The concentration of three P450 isozymes, namely P450‐IIEl(Alc),‐HIA(NF) and ‐IIC8‐10(MP) has been measured in human liver biopsies of patients with different alcohol and drug intake status. All these three P450s were expressed in all subjects. Ethanol intake increased P450‐IIEl(Alc) content with no effect on the content of the two other P450s. Drug intake (barbiturates) increased both P450‐IIIA(NF) and ‐IIC8‐10(MP) content without any effect on P450‐IIEl(Alc). This paper brought, at protein level, further evidence of the importance of environmental conditions on P450 isozyme pattern, and therefore, on drug metabolizing capacity of human liver.