bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in norepinephrine content and beta adrenoceptor regulation in myocardium bordering aneurysm in human heart: their possible role in the genesis of ventricular tachycardia
Authors: BEVILACQUA M. , NORBIATO G. , VAGO T. , MERONI R. , DAGANI R. , RAGIG U. , FRIGENI G. , SANTOLI C.
Published: March 2008

Abstract. On the assumption that alterations in the adrenergic system may play a role in generating ventricular tachycardia in patients with myocardial post‐infarction apical aneurysm, we evaluated norepinephrine concentration, number and affinity of both beta 1 and beta 2 adrenoceptors in perianeurysmatic tissue in twelve patients operated upon for congestive heart failure and recurrent sustained ventricular tachycardia. Concentration of norepinephrine in perianeurysmatic tissue was 0·1 ± 0·05 μg g‐1 tissue (n= 8), this value being much lower than that found in papillary muscle (n= 10) from patients with mitral valve stenosis (0·8 ± 0·02 μg g‐1 tissue) (P < 0·01). The total number of beta adrenoceptors (71·4 ± 7·8 v. 48·0 ± 5·1 fmol mg‐1 protein; P < 0·01) and the percentage of beta 1 subtype were found to be higher in perianeurysmatic tissue (˜90%) than in papillary muscle (˜68%). Out of twelve patients with aneurysm, beta 2 adrenoceptors had considerably decreased in three patients and were absent in the remaining nine. Decrease in the neuronally released norepinephrine associated with contrasting behaviours of beta 1 and beta 2 adrenoceptors suggests the presence of a profound alteration in the sympathetic innervation of the perianeurysmatic myocardial tissue that may contribute to the genesis of sustained ventricular tachycardia in patients with post‐infarction apical aneurysm.
Ursodeoxycholic acid treatment in humans: effects on plasma and biliary lipid metabolism with special reference to very low density lipoprotein triglyceride and bile acid kinetics*
Authors: ANGELIN BO , NILSELL KLAS , EINARSSON KURT
Published: March 2008

Abstract. Ursodeoxycholic acid reduces biliary saturation with cholesterol and may induce dissolution of cholesterol gallstones in man. In order to characterize the effects of this potentially useful bile acid on plasma lipid metabolism, we determined lipoprotein levels and very low density lipoprotein (VLDL) triglyceride kinetics in six hypertriglyceridaemic and three normo‐lipidaemic subjects before and after 4–6 weeks of ursodeoxycholic acid treatment at a daily dose of 15 mg kg‐1 body weight. The plasma levels of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were not significantly affected by therapy. Nor were the plasma level and apparent formation of VLDL triglycerides changed. In five subjects, the effects of a low dose (7·5 mg kg‐1 body weight day‐1 for 4–6 weeks) of ursodeoxycholic acid on biliary lipid composition and kinetics of cholic acid and chenodeoxycholic acid were determined. The relative concentration of cholesterol in bile was reduced to the same level as during treatment with a high dose of ursodeoxycholic acid. The synthesis rates of bile acids were not suppressed with ursodeoxycholic acid. It is concluded that, unlike chenodeoxycholic acid, ursodeoxycholic acid does not suppress endogenous bile acid production. The efficiency at lower doses, and the lack of effects on plasma lipid metabolism, may make ursodeoxycholic acid a more attractive alternative for clinical attempts of gallstone dissolution.
Haematological findings in chronic alcoholics after heavy drinking with special reference to haemolysis
Authors: KRISTENSSON‐AAS AUD , WALLERSTEDT SVEN , ALLING CHRISTER , CEDERBLAD GITTEN , MAGNUSSON BENGT
Published: March 2008

Abstract. Haematological abnormalities are frequently found in heavy‐drinking chronic alcoholics, but anaemia is generally a rare complication. When present, haemolysis is considered to be one of the most common causes. However, little is known about mild haemolysis without anaemia. The present report on eighteen male chronic alcoholics with a recent heavy debauche but without signs of severe liver disease gave support for the occurrence of a reversible low‐degree haemolysis without concomitant gross changes of the erythrocytes. Thus the bone marrow showed an increased erythropoiesis in the absence of iron deficiency and known blood losses. Further, increased reticulocyte counts and low levels of haemopexin were noted in the early abstinence. Finally, during the withdrawal phase haptoglobin and haemopexin increased concomitantly with diminishing values of unconjugated bilirubin. The most likely cause of the proposed diminished red cell survival before the withdrawal is supposed to be a reduced membrane stability.
Generation of superoxide anion and hydrogen peroxide by erythrocytes from individuals with sickle trait or normal haemoglobin
Authors: SCHACTER L. P.
Published: March 2008

Abstract. To test the hypothesis that the resistance of sickle trait (AS Hgb) erythrocytes (rbcs) to malaria may be mediated by increased production of activated oxygen species, the production of superoxide anion (O2–) and hydrogen peroxide (H2O2) by AS rbcs and normal (AA Hgb) rbcs was measured under defined conditions. Formation of O2– and H2O2 was time, temperature and oxygen saturation dependent. Reproducible measurement of O2– formation required the presence of 0·2 mmol l‐1 KCN to inhibit a cytochrome oxidase activity found in the cytochrome C preparation used. There was an inverse relationship between cell concentration and O2– and H2O2 formation. Use of the inhibitor of superoxide dismutase (SOD), diethyldithiocarbamic acid, increased the amount of O2– measured. When rbcs from blacks with AS Hgb and with AA Hgb were incubated under standardized conditions, significantly (P < 0·05) more O2– was formed by AS than AA cells (24·3 v. 14·5 mmol per mol Hgb). These findings show that AS rbcs can generate more O2– than AA rbcs. The increased formation of O2– by rbcs containing AS Hgb may contribute to the resistance of AS rbcs to malarial parasitism.
Circulating endogenous vasoactive intestinal polypeptide (VIP) in patients with uraemia and liver cirrhosis
Authors: HENRIKSEN J. H. , STAUN‐OLSEN P. , MOGENSEN N. BORG , FAHRENKRUG J.
Published: March 2008

Abstract. The concentration of vasoactive intestinal polypeptide (VIP) in peripheral venous plasma was median 6·0 pmol l‐1 (range 0–20) in 112 normal subjects. In fifty‐three patients with decreased kidney function plasma VIP was significantly increased (median 15·0 pmol l‐1, range 0·5–70, P < 0·0001) and positively correlated to serum creatinine concentration (r= 0·51, P < 0·001). In 133 patients with liver cirrhosis peripheral venous VIP was slightly elevated (median 7·0 pmol l‐1 range 0–86, P < 0·01). Samples obtained during a central venous catheterization showed significant renal extraction of circulating VIP in control subjects (median extraction fraction 23%, P < 0·05, n= 6) and in patients with cirrhosis (median 60%, P < 0·02, n= 8), but not in uraemic patients (median 0%, NS n= 5). In control subjects and patients with cirrhosis the concentration of VIP in the hepatic vein was significantly below that of systemic plasma (–42%, P < 0·05, n= 6 and –45%, P < 0·01, n= 10, respectively). On the contrary, in uraemic patients hepatic venous VIP was almost similar to systemic VIP (–4%, NS, n= 7). The results indicate that in normal subjects and patients with cirrhosis both the liver and kidneys are involved in the biodegradation of VIP. The elevated level of circulating VIP in uraemic patients may in part be due to decreased renal and hepatic biodegradation but increased neuronal release of VIP, especially in the splanchnic system, may also contribute to the increased plasma VIP in this condition.
Insulin receptor binding to monocytes and erythrocytes during normal human pregnancy
Authors: ANDERSEN O. , KUHL C.
Published: March 2008

Abstract. In normal human pregnancy glucose tolerance deteriorates gradually in spite of a steady increase in plasma insulin levels. To see whether this change in insulin resistance is accompanied by changes in insulin receptor binding, insulin binding to monocytes and erythrocytes was measured serially during pregnancy and again post‐partum in fifteen normal women. Insulin binding to monocytes increased from week 12 to week 24 of gestation (P < 0·001) and it decreased from week 32 to week 36 (P < 0·05). After delivery a new increase in insulin binding to monocytes was seen (P < 0·05). Insulin binding to erythrocytes increased from week 30–32 to week 36 (P < 0·05), decreased from week 36 to delivery (P < 0·01) and decreased further post‐partum (P < 0·001). Insulin receptor binding was not significantly correlated to plasma insulin, estradiol, estriol, progesterone or cortisol. The insulin receptor binding to monocytes, but not to erythrocytes, paralleled the insulin resistance found in human pregnancy.
Inducing efficacy of ethanol on hepatic drug metabolizing enzymes in patients
Authors: HOENSCH H. P. , SCHREIER I. , OHNHAUS E. E.
Published: March 2008

Abstract. In liver biopsy material of eighty‐nine patients with suspected liver disease the drug‐metabolizing function was investigated. The capacity of the liver to oxidatively metabolize drugs was assessed by determination of cytochrome P‐450 dependent monooxygenase activity in vitro. The biotransformational function of these microsomal enzymes was tested with compounds representing the activity of oxidative drug metabolism (7‐ethoxycoumarin, p‐nitroanisol and cytochrome c). From the eighty‐nine patients sixty‐one had various liver diseases not related to ethanol and twenty‐eight abused ethanol. When both groups were matched for age, sex, smoking, treatment with sedatives, drugs and degree of liver damage the alcoholic group had significantly higher activities of 7‐ethoxycoumarin O‐deethylase (EOD: 76·9±31·1 pmol min‐1 mg‐1 protein, x̄± SD) than the non‐alcoholic liver disease group (42·7±14·1). The inducing effect of ethanol was most striking on the EOD activity, less for the O‐demethylation of p‐nitroanisol (PNA) and not present for the NADPH‐cytochrome c reductase. The induced patients were analysed in detail to find out which factors were responsible for the observed scatter of enzyme activities within the alcoholic group. Alcoholics with fatty liver (n= 7) had the highest EOD activities (108·9 ± 25·0), patients with alcoholic hepatitis (n= 10) had significantly less activity (66·0 ± 1·9) than the former group. However, alcoholics without liver damage (n= 6) had activities not significantly different (46·0±15·8) from controls (39·4±9·1). These subgroups among the alcoholics were comparable in terms of sex, age, smoking and drinking habits. Our results show that alcoholism when associated with fatty liver and hepatitis leads to an induction of the hepatic monooxygenase activity in humans.
Enzymatic determination of urinary chondroitin sulphate: applications in renal stone disease and acromegaly
Authors: FELLSTRÖM B. , DANIELSON B. G. , LIND E. , LJUNGHALL S. , WIKSTRÖM B.
Published: March 2008

Abstract. A method was developed for the determination of urinary chondroitin sulphate (CS), including dermatan sulphate and chondroitin 4 and 6‐sulphates, using an enzymatic degradation with chondroitinase‐ABC followed by precipitation with Alcian blue, whereby CS was determined as the difference between undigested and chondroitinase digested material. The method was linear in the range 0–100 mg l‐1 with a detection limit of 1 mg l‐1 and allowed determinations on small urine volumes without pretreatment of the urine. It could be demonstrated that males excreted more CS than females, and growing children had the highest urinary content of CS. Renal calcium stone formers did not differ from healthy controls in urinary CS. Patients with acromegaly had a higher excretion of CS compared with controls. There was also, in these patients, a positive correlation between the serum growth hormone levels and the urinary CS, indicating that CS‐excretion may be an estimate of the activity of the pituitary disorder.
Effect of oral prostaglandin E2 on DNA turnover in gastric and intestinal epithelia of the rat
Authors: JOHANSSON C. , URIBE A. , RUBIO C. , ISENBERG J. I. , Unit G.I.
Published: March 2008

Abstract. The mucosal incorporation and clearance of a DNA precursor was examined in the rat stomach and intestine following oral treatment with natural prostaglandin E2 (PGE2) or 15(R) 15 methyl prostaglandin E2 (Me PGE2). Control groups received vehicle or pentagastrin. After five days of treatment animals were labelled with methyl‐3H‐thymidine. Groups of rats were killed at 0·75, 24, 72,96 and 120 h after labelling. Treatments continued until killed. Mucosal scrapings were analysed for radioactivity and DNA. Morphometric measurements were performed and plasma levels of gastrin and somatostatin determined.

PGE2 and its stable analogue produced hyperplasia within one week of treatment, in particular of the gastric antrum and changed the incorporation and clearance of radioactive thymidine from gastric and intestinal epithelia. The most consistent finding was a delayed elimination of thymidine from the mucosa, indicating a slowing of the DNA turnover. The DNA synthesis was differently affected along the gastrointestinal tract, being unchanged or reduced in the stomach and moderately increased in the intestine.

Prostaglandin treatment was associated with a three‐ to ten‐fold increase of the gastric acid contents and with elevated plasma levels of gastrin and somatostatin. It is concluded that E2 prostaglandins produce hyperplasia of gastric and intestinal epithelia in the rat by prolonging the cell survival time rather than by increasing new cell production. Hypergastrinemia is not a likely mediator of trophic actions of E2 prostaglandins, which develop despite elevated plasma levels of somatostatin.
Why do dyspeptic patients prefer one liquid antacid to another?
Authors: BLUM A. L.
Published: March 2008

Abstract. The motives of dyspeptic patients for preferring one treatment over another were examined. In a conventional double‐blind study, no difference with respect to the effectiveness of two liquid antacid preparations in symptomatic relief of dyspeptic symptoms was found. In a double‐blind randomized self‐controlled crossover ‘preference study’, the two preparations were given in coloured bags. The patients were asked to switch from one type of bag to another until they had a preference. Most patients finally preferred bags displaying the colour which they had initially chosen. The reasons given for preferring one of the drugs were better effectiveness on symptoms, less side effects and better taste. Colour of the bags was not given as a reason. Thus, the patients may prefer drugs on the basis of the external appearance of the wrapping without being aware of the true reason for their choice.
Captopril enhances insulin responsiveness of forearm muscle tissue in non‐insulin‐dependent diabetes mellitus
Authors: JAUCH K.‐W. , HARTL W. , GUENTHER B. , WICKLMAYR M. , RETT K. , DIETZE G.
Published: March 2008

Abstract. Bradykinin infusion has been shown to improve glucose metabolism in non‐insulin‐dependent diabetic subjects (NIDD). Therefore, we tested the following hypothesis: inhibition of Kininase II, the bradykinin (BK) degrading enzyme, by captopril may also improve glucose metabolism in NIDD. Immediate effects of captopril on total body and peripheral glucose disposal were examined in five normotensive, normal weight NIDD and compared with five NIDD control subjects, well matched for age, weight and degree of fasting hyperglycaemia. The euglycaemic insulin clamp technique was employed in combination with the forearm catheter technique. After 90 min of insulin infusion a single dose of 25 mg captopril was administered orally, whereas in the control group a placebo was given. Captopril lead to a significant rise in total body glucose disposal and forearm glucose uptake, while in the control group no change was observed. Simultaneously, captopril lead to reduction in muscular release of lactate and pyruvate. We conclude that these results demonstrate the stimulatory effect of captopril on insulin‐induced glucose disposal of the whole body, which appears to be a result of increased glucose utilization by peripheral tissues. Because of the described insulin‐like activity of bradykinin, the concomitant accumulation of local kinins by captopril‐induced inhibition of kininase II may represent an attractive hypothesis to explain the generated data sufficiently.
Natural killer cell activity during cortisol and adrenaline infusion in healthy volunteers
Authors: TØNNESEN E. , CHRISTENSEN N. J. , BRINKLØV M. M.
Published: March 2008

Abstract. The effects of cortisol and adrenaline on natural killer (NK) cell activity and the distribution of circulating lymphocyte subpopulations were studied in twenty volunteers, using a continuous intravenous infusion pattern to simulate some of the hormonal changes induced by major surgery. The participants were allocated to receive either cortisol for 5 h, adrenaline for 1 h, cortisol for 5 h with simultaneous adrenaline during the last hour, or placebo for 5 h. Cortisol induced leucocytosis, neutrophilia, and lymphopenia with marked reduction in the number of T‐lymphocyte subsets (OKT3+, OKT4+, and OKT8+ cells). No changes were induced in the activity or number of NK (Leu 11+) cells. Adrenaline produced an instantaneous increase in NK‐cell activity accompanied by a selective increase in circulating NK cells. Significant leucocytosis, lymphocytosis and neutrophilia occurred. All measurements returned to preinfusion levels within 15 min after completing infusion. The effects of simultaneous infusion of cortisol and adrenaline were equal to the additive response to the hormones administered separately, except for the leucocytosis, which clearly exceeded this. In the placebo group all measurements remained unchanged. The results confirm the role of adrenaline as a potent stimulator/inducer of NK‐cell activity. Adrenaline may be responsible for the increase in NK‐cell activity during anaesthesia and major surgery.
Effect of dietary cholesterol on production of lipoproteins and apolipoproteins by perfused livers from Japanese monkeys (Macaca fuscata)
Authors: TERAMOTO T. , KATO H. , HASHIMOTO Y. , KINOSHITA M. , WATANABE T. , OKA H. , NAITO C.
Published: March 2008

Abstract. Isolated livers from Japanese monkeys were perfused for the purpose of characterizing low density lipoprotein (LDL) secreted directly by the liver, and for determining whether cholesterol feeding affects the hepatic production of LDL. Perfusate containing [3H]leucine was recirculated for 60 min, followed by perfusion with fresh perfusate for two additional 2‐h periods. Radiolabelled lipoproteins, which are isolated by ultracentrifugation as very low density lipoprotein (VLDL), LDL, and high density lipoprotein were 0·87 ± 0·74, 1·83 ± 1·47, and 0·44 ± 0·33%, respectively, of total radiolabelled protein in the medium of the last 2‐h period. Subfractionation of perfusate LDL by high performance liquid chromatography, and by concanavalin A sepharose chromatography, revealed that the newly synthesized LDL were secreted as apo E‐rich particles. Cholesterol feeding resulted in a fourfold increase in hepatic secretion of newly synthesized VLDL, but not of the LDL. The distribution of radioactivity among VLDL apolipoproteins was not affected by cholesterol feeding. Incorporation of radioactivity into apo B100 of LDL decreased significantly, but that into apo E did not change. These results suggested that (i) the elevation of serum LDL in cholesterol‐fed monkeys is not due to enhanced hepatic production of LDL, but probably results from intravascular metabolism of VLDL, which is of hepatic origin, and (ii) cholesterol feeding affects the hepatic apo B100 synthesis and/or release but not apo E.
Abnormal regulation of LDL receptor activity and abnormal cellular metabolism of hypertriglyceridaemic low density lipoprotein: normalization with bezafibrate therapy
Authors: KLEINMAN Y. , OSCHRY Y. , EISENBERG S.
Published: March 2008

Abstract. The regulation of LDL (B, E) receptor activity and of cellular LDL protein metabolism by hypertriglyceridaemic (HTG) low density lipoprotein before and during hypolipidaemic therapy (with bezafibrate (BZ)) were determined in cultured human skin fibroblasts. Defective binding and subnormal capacity to regulate LDL receptor activity was found for HTG‐LDL. Binding affinity (Kd) of HTG‐LDL to the receptor was 4·97 times 10‐8 M and of N‐LDL, 1·74 times 10‐8 M. When assayed with normal 125I‐LDL, the capacity of HTG‐LDL to down‐regulate receptor activity was 46–68% less than N‐LDL. Both abnormalities reverted towards normal during treatment. The cellular metabolism of HTG‐, BZ‐ and N‐LDL in cells grown for 48 h with the respective lipoproteins was determined. In spite of their defective binding to the receptor, the metabolism of HTG‐LDL in the regulated cells was accelerated in comparison to N‐LDL, and equal to that of BZ‐LDL. That observation is explained by the inefficient ability of HTG‐LDL to depress LDL receptor activities in the cells.
Insulin sensitivity and beta‐cell function assessed by C‐peptide in young adults with cystic fibrosis
Authors: DAVIS T. M. E. , BATTEN J. C. , RUDENSKI A. S. , TURNER R. C.
Published: March 2008

Abstract. Eight patients with cystic fibrosis (CF) aged 18–34 who had normal random plasma glucose levels were studied with a continuous infusion of glucose with model assessment (CIGMA) and plasma C‐peptide to assess beta‐cell function, and plasma insulin to assess insulin sensitivity. Two had impaired glucose tolerance, two had impaired beta‐cell function and all had normal insulin sensitivity. The results of previous studies suggesting that glucose intolerance is common in CF may reflect the inability of an impaired liver to handle a large oral glucose load. The few CF patients who become diabetic may be those who have a preexisting diabetic trait.
Production of 5‐lipoxygenase pathway metabolites by peripheral leucocytes in capillary leak syndrome (Clarkson disease)
Authors: RONDEAU E. , SRAER J. , BENS M. , DOLERIS L. MOULONGUET , LACAVE R. , SRAER J. D.
Published: March 2008

Abstract. Periodic systemic capillary leak syndrome (Clarkson disease) is characterized by unexplained attacks of a marked increase in capillary permeability. As leukotrienes, derived from arachidonic acid via the 5‐lipoxygenase pathway, enhance capillary permeability, we studied arachidonate metabolism in leucocytes of a patient with capillary leak syndrome. Leucocyte‐platelet suspensions, prepared from blood collected from the patient during asymptomatic periods (n= 11) produced greater amounts of 5‐hydroxyeicosatetraenoic acid (5‐HETE) than control suspensions (P < 0·05). Peripheral leucocytes, collected during attacks (n= 3) and studied without addition of A23187 released LTB4 in vitro but not sulphidopeptides leukotrienes. This result was never observed with leucocytes from control subjects or from the patient out of a crisis. These results suggest that in the patient, peripheral leucocytes could be stimulated by an unknown, as yet to be determined, endogeneous factor to produce more 5‐HETE and LTB4. Whether LTB4 plays a pathogenic role in the capillary leakage remains to be determined.
Role of alpha‐adrenoceptors for adipocyte size in man
Authors: ARNER P. , MARCUS C. , KARPE B. , SONNENFELD T. , BLOME P.
Published: March 2008

Abstract. Catecholamines have dual effects on lipid mobilization in man. Lipolysis is stimulated via beta‐adrenoceptors and inhibited via alpha2‐adrenoceptors. The relationship between fat‐cell size and catecholamine‐induced lipolysis (expressed per cell surface area) was investigated in vitro in subcutaneous adipocytes of thirty‐five non‐obese subjects between 1 month and 45 years of age. Fat‐cell volume showed a positive correlation with noradrenaline‐induced lipolysis (r= 0·7). Furthermore, fat‐cell size showed a negative correlation with the alpha2‐effect of noradrenaline (r= 0·8) but no correlation with the beta‐effect of the hormone (r < 0·1). Although age showed a positive correlation with noradrenaline‐induced rate of lipolysis (r= 0·6) it did not contribute to the relationship between cell size and the catecholamine effect. There was no relationship between adipocyte size and the basal (unstimulated) rate of lipolysis (r < 0·1). In conclusion, ageing in non‐obese subjects is associated with enlargement of fat‐cell size and enhancement of the lipolytic effect of catecholamines. The latter is due to diminished alpha2‐anti‐lipolytic effect of the hormones. This modulation of the alpha2‐adrenoceptor activity may be of importance for the regulation of adipocyte size in man.
Inhibition of muscular amino acid release by lipid infusion in man
Authors: WICKLMAYR M. , RETT K. , SCHWIEGELSHOHN BETTINA , WOLFRAM G. , HAILER SUSANNE , DIETZE G.
Published: March 2008

Abstract. Amino acid balances of healthy postabsorptive volunteers were investigated with the forearm technique under the influence of an intravenous infusion of triglyceride emulsions (MCT; LCT/MCT). A decrease of the basal muscular release of most of the amino acids, resulted in an increase of pre‐existant uptake rates. In parallel, arterial concentrations of these amino acids declined. With constant insulin levels and substantially unchanged blood glucose levels, this inhibition of muscular proteolysis and/or stimulation of proteosynthesis is most probably due to the increased level of free fatty acids.
Xenopsin‐ and neurotensin‐like peptides in gastric juice from patients with duodenal ulcers
Authors: SHAW C. , STÖCKMANN F. , CONLON J. M.
Published: March 2008

Abstract. Using an anti‐serum directed against the COOH‐terminal region of neurotensin and an antiserum raised xenopsin in radioimmunoassays, the presence of neurotensin‐ and xenopsin‐like immunoreactivity in Sep‐pak extracts of human gastric juice was demonstrated. An anti‐serum directed against the NH2‐terminal to central residues of neurotensin and an anti‐serum directed against a conformation, present only in the intact peptide, did not detect immunoreactivity in the juice. Infusions of pentagastrin at doses of 0·75 μg kg‐1 h‐1 and 1·5 μg kg‐1 h‐1 resulted in significant (P<0·05) increases in the total amount of xenopsin‐like, but not neurotensin‐like, immunoreactivity released in the juice compared with basal release. No significant differences in the release of xenopsin‐ or neurotensin‐like immunoreactive were observed between patients with selective proximal vagotomy and patients without operation. Analysis by gel permeation chromatography and high performance liquid chromatography demonstrated that both the neurotensin‐ and xenopsin‐like immunoreactivity was heterogeneous and an increase in molecular complexity on pentagastrin‐stimulation was observed. As both neurotensin and xenopsin inhibit gastric exocrine activity, the presence of immunochemically related substances in gastric juice may have physiological relevance.
Time‐course of alterations of high density lipoproteins (HDL) during thyroxine administration to hypothyroid women
Authors: VERDUGO CECILIA , PERROT L. , PONSIN G. , VALENTIN CATHERINE , BERTHEZENE FRANÇOIS
Published: March 2008

Abstract. Serum HDL cholesterol, apolipoproteins AI and All and post heparin lipolytic activities (PHLA) have been measured in a group of fourteen hypothyroid women without ovarian oestrogen secretion before and during a 2‐month thyroxine treatment. The more rapid and consistent observed event was a decrease in apo Al levels (164 ± 5 vs. 149±5 mg dl‐1, mean ± SEM, P<0·05) correlated (r=0·79, P<0·05) to a slight increment of PHLA. A slight decrease in apo All concentration was seen only after 5 days (25 ± 2 vs. 22 ± 2 mg dl‐1, P < 0·05) and in HDL cholesterol only after 60 days (1·3±0·6 vs. 1·1±0·5 mmol l‐1, P<0·05).

Apo AI, HDL2 and HDL3 cholesterol were measured in another group of seven hypothyroid post‐menopausal women before and after a 2‐month thyroxine treatment. We observed a decrease in HDL2 cholesterol (1·69 ± 0·20 vs. 1·17±0·09 mmol l‐1, P<0·02) with no changes in HDL3 cholesterol (0·88±0·09 vs. 0·99±0·06 mmol l‐1, NS). The decrease in HDL2 cholesterol correlated (r= 0·72, P= 0·05) with that for apo AI.

The differential influence of thyroxine (T4) administration on the major HDL components might reflect changes in HDL composition due to the multiple effects of thyroid hormones on lipid metabolism. It can be hypothesized that the decrease in apo AI and HDL2 cholesterol concentrations are due, at least in part, to the increase in hepatic lipase activity.
Prognostic value of serum lactic dehydrogenase (S‐LDH) in multiple myeloma
Authors: SIMONSSON B. , BRENNING G. , KÄLLANDER C. , ÅHRE A.
Published: March 2008

Abstract. Serum lactic dehydrogenase (S‐LDH) was analysed at diagnosis in ninety‐three patients with multiple myeloma. The patients were then followed up after a mean observation period of 39 months (SD 29). Serum lactic dehydrogenase was elevated in twenty‐seven out of ninety‐three patients and found to correlate with the serum concentrations of β2‐microglobuline, creatinine, and thymidine kinase. In discriminant analysis of pretreatment S‐LDH levels in relation to survival, the best discrimination level was 7·0 μkat l‐1. Patients with values below 7 μkat l‐1 had a median survival time of 45 months compared to 14 months for those with levels above 7 μkat l‐1 (P<0·001). Serum lactic dehydrogenase at diagnosis, thus, has prognostic information in multiple myeloma.
Analysis of liver‐specific protein LSP using murine monoclonal antibodies
Authors: PORALLA T. , MANNS M. , DIENES H. P. , DIPPOLD W. , HÜTTEROTH T. H. , BÜSCHENFELDE K.‐H. MEYER ZUM
Published: March 2008

Abstract. We describe twenty murine monoclonal antibodies directed against different antigenic determinants of human and rabbit liver‐specific protein LSP. Among them, nine were directed against liver‐specific epitopes as judged from immunohistological studies. Immunoelectronmicroscopy revealed that seven of these monoclonals recognized membrane determinants differing in staining of distinct areas of the hepatocellular surface. Eleven antibodies were directed against intracellular structures. Western blot analysis showed that the epitopes detected were displayed on either single or multiple protein bands with apparent molecular weights between 24 000 and 60 000. Further differences were observed with respect to the species specificity and (among the non‐organspecific antibodies) pattern of tissue cross‐reactivity. Our results demonstrate the presence of several liver‐specific determinants and membrane components within LSP. There are, however, a very much greater number of non‐organ‐specific epitopes and numerous determinants displayed on intracellular structures. This emphasizes the remarkable heterogeneity of the antigen preparation named LSP and warrants the use of clearly defined antigens in further studies dealing with auto‐immune phenomena in liver diseases.
Effects of posture and saline infusion on atrial natriuretic peptide and haemodynamics in patients with Bartter's syndrome and healthy controls
Authors: DOORENBOS C. J. , DAHA M. R. , BÜHLER F. R. , BRUMMELEN P. VAN
Published: March 2008

Abstract In order to explore the role of atrial natriuretic peptide (ANP) in Bartter's syndrome, five patients and five healthy controls matched for age and sex were studied. The study was designed to stimulate and suppress ANP secretion by manipulation of right atrial pressure with different body positions and mild volume expansion with saline. Other vasoactive hormones were also measured, and heart rate and blood pressure were recorded at 5‐min intervals. Plasma ANP levels increased after head‐down tilt and returned to baseline in the upright position. Infusion of saline failed to increase plasma ANP both in the control group and in four of the patients. No significant differences were found in plasma atrial natriuretic peptide concentrations between both groups. In view of previously reported elevated plasma ANP levels, Bartter's syndrome may be heterogeneous in this respect. Plasma renin activity was higher in the patients, but plasma aldosterone, adrenaline and noradrenaline were similar in both groups. Mean arterial blood pressure was similar in both groups, but rose significantly in the upright position in the control group only, while changes in heart rate were similar in both groups. We conclude that atrial natriuretic peptide does not seem to play a causal role in our patients with Bartter's syndrome.
Granulocyte activation during haemodialysis in the absence of complement activation: inhibition by calcium channel blockers
Authors: HAAG‐WEBER MARIANNE , SCHOLLMEYER P. , HÖRLy W. H.
Published: March 2008

Abstract The effect of the calcium channel blockers nifedipine (9 and 18 μg kg‐1h‐1), diltiazem (100 and 200 μg kg‐1h‐1) and verapamil (19 μg kg‐1h‐1) continuously infused during haemodialysis on granulocyte and complement activation was investigated. Plasma levels of lactoferrin, elastase in complex with α1‐proteinase inhibitor (E‐α1PI) and C3a were measured in patients dialysed with dialysers made of cuprophane, polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN). Calcium channel blockers caused no change of blood pressure during haemodialysis in all patients. There was no effect of nifedipine, diltiazem or verapamil on plasma lactoferrin, E‐α1PI or C3a levels in patients dialysed with cuprophane. However, plasma lactoferrin and E‐α1PI values were significantly reduced by all calcium channel blockers in patients dialysed with PMMA, and also by nifedipine and verapamil in patients dialysed with PAN. Our data indicate that calcium channel blockers inhibit granulocyte activation occurring in dialysers with very little anaphylatoxin formation. These drugs, however, are ineffective in patients dialysed with cuprophane where complement activation takes place. Therefore, granulocyte activation during haemodialysis in the absence of complement activation seems to be mediated by calcium ions.
Occurrence of cholesterol monohydrate crystals in gallbladder and hepatic bile in man: influence of bile acid treatment
Authors: SAHLIN S. , AHLBERG J. , ANGELIN B. , EWERTH S. , NILSELL K. , REIHNÉR E. , EINARSSON K.
Published: March 2008

Abstract The occurrence of cholesterol monohydrate crystals was examined and related to the degree of cholesterol saturation in gallbladder bile and hepatic bile of gallstone (GS) patients (n= 34), gallstone‐free (GSF) subjects (n= 33) and GS patients treated with chenodeoxycholic acid (CDCA (n= 7) or ursodeoxycholic acid (UDCA) (n= 11) for 3 weeks prior to cholecystectomy. Twenty‐five untreated GS patients (74%) and four UDCA‐treated patients (40%) displayed cholesterol crystals in the gallbladder bile. Only two GSF subjects (6%) and none of the CDCA‐treated patients had crystals. Half of the patients with crystals in the gallbladder bile had crystals also in the hepatic bile. Cholesterol saturation of the gallbladder bile was higher in GS (142 ± 15%, mean ± SEM) than in GSF patients (74 ± 5%). Saturation was also higher in GS patients with crystals (157 ± 20%) than in those without crystals (99 ± 12%). Gallblader bile was unsaturated in all CDCA‐ and UDCA‐treated patients. The results underline the importance of the degree of cholesterol saturation for the formation of cholesterol crystals. The data also give further support to the concept that the mechanism for inducing gallstone dissolution is different for CDCA and UDCA.
Intraplatelet serotonin in patients with diabetes mellitus and peripheral vascular disease
Authors: BARRADAS M. A. , GILL D. S. , FONSECA V. A. , MIKHAILIDIS D. P. , DANDONA P.
Published: March 2008

AbstractIntraplatelet serotonin (5‐HT) content was determined in 23 patients with type I (insulin‐dependent) diabetes mellitus (IDDM), 23 patients with type II (non‐insulin‐dependent) diabetes mellitus (NIDDM), 29 patients with peripheral vascular disease (PVD) and 34 age‐matched normal subjects. Intraplatelet 5‐HT content in normal subjects showed an age‐related decline (r=–0·45;P< 0·008), as has been previously demonstrated. The median 5‐HT content in platelets of the young normal subjects was 4·36 (range: 3·62–6·79) nmol 10‐9platelets, while that in the elderly normal subjects was 3·87 (range: 2·8–6·0) nmol 10‐9platelets and that in young+elderly subjects was 4·05 (range: 2·8–6·8) nmol 10‐9platelets. The median intraplatelet 5‐HT content was significantly lower (P< 0·002) in IDDM patients: 3·0 (range 1·3–6·3), NIDDM patients: 2·5 (range 1·7–5·8), PVD patients: 2·42 (range 0·94–4·98) nmol 10‐9platelets than that in all young+elderly healthy subjects. The presence of hypertension in DM patients caused a small but significant (P< 0·05) decrease in intraplatelet 5‐HT content, whilst its presence had no effect in PVD patients. In a smaller study, it was established that NIDDM and PVD patients have significantly (P< 0·002) greater plasma 5‐HT concentrations than controls. Insulin‐dependent diabetes mellitus patients had greater plasma 5‐HT concentrations but this did not achieve statistical significance despite a 66% increment in its value. We conclude that the diminished 5‐HT content in platelets and the increased plasma levels may reflect enhanced release of 5‐HT by hyperactive platelets. This increase in plasma 5‐HT may contribute to the pathogenesis of atherosclerosis and vasospasm.
The TSH, T4, T3 and prolactin responses to consecutive infusions of a potent and stabilized thyrotrophin releasing hormone analogue, RX77368, in man
Authors: ECKLAND D. J. A. , LIGHTMAN S. L.
Published: March 2008

Abstract The endocrine manifestations of a stabilized thyrotrophin releasing hormone (TRH) analogue, RX77368, have been investigated in six male volunteers. Infusions were given on two occasions, with a 5‐day interval between infusions. On the second exposure to RX77368, there was a significant reduction in the TSH response, despite normal basal T3 and T4 levels, while the response of prolactin to RX77368 was unaltered. Domperidone administered during the infusion of RX77368 caused a further elevation of prolactin levels, whilst TSH levels were unchanged. This study shows the differential regulation of thyrotrophs and lactotrophs in response to stimulation by a TRH analogue, and shows, for the first time, down‐regulation of the TSH response in vivo, in the presence of normal peripheral thyroid hormone levels. The T3 response to infusions of RX77368 was less than to a bolus injection of TRH, despite a greater TSH response to the analogue, suggesting impaired biological activity of TSH released in reponse to an infusion of the analogue.
Decreased prostacyclin sensitivity of platelets in patients with Behçet's syndrome
Authors: WILSON A. P. , EFTHIMIOU J. , BETTERIDGE D. J.
Published: March 2008

Abstract Patients with Behçet's syndrome have an increased risk of arterial and venous thrombosis, and abnormal platelet function has been implicated. Platelet function was studied in nine patients with Behçet's syndrome and in nine age‐ and sex‐matched healthy volunteers. Platelet aggregation in response to ADP was measured, and the threshold concentration required to produce irreversible aggregation determined. Sensitivity of platelets to the inhibitory effect of prostacyclin was also determined. In addition, plasma levels of the platelet‐specific proteins, β‐thromboglobulin and platelet factor 4, and stimulated platelet thromboxane B2 production, were measured. Platelets from patients with Behçet's syndrome showed normal aggregation in response to ADP, irrespective of disease activity. Platelet sensitivity to prostacyclin was, however, decreased compared with controls—with a mean prostacyclin ID50 of 5·5 ± 1·3 ng ml‐1(mean ± SEM) and 1·9 ± 0·3 ng ml‐1, respectively (P < 0·01). This reduction in platelet sensitivity to prostacyclin was greatest in patients with the most active disease. These results suggest that Behçet's syndrome may be associated with altered platelet function, and this may have important consequences with regard to the increased risk of thrombosis associated with this condition.
Effect of exercise on plasma atrial natriuretic factor and cardiac function in men and women
Authors: DONCKIER J. E. , COSTER P. M. DE , BUYSSCHAERT M. , LEVECQUE P. , CAUWE F. M. , BRICHANT C. M. , BERBINSCHI A. C. , KETELSLEGERS J.‐M.
Published: March 2008

Abstract In order to provide an integrated view of the physiology of atrial natriuretic factor (ANF) during exercise, we studied changes of its plasma concentrations in 13 normal subjects (seven males, six females) during three graded exercise levels and two periods of recovery (5 and 30 min), concomitantly with an assessment of cardiac function and ventricular volumes by multigated radionuclide angiography. Mean ANF levels (± SEM) increased in all patients at the second (P < 0·002) and third (P < 0·002) exercise levels, and after 5‐min recovery (P < 0·01): in males from 16 ± 7 to 30 ± 11 pg ml‐1at the third level, in females from 27 ± 12 to 61 ± 33 pg ml‐1. Normal values were observed after 30‐min recovery. Even if mean ANF levels were all higher in females, this difference did not reach statistical significance (P= 0·06). Significant decreases of ventricular volumes, as well as increases of ejection fraction and rate pressure product, were noted during exercise and were similar in both sexes. The kinetics of plasma ANF concentrations, compared with the increase of rate pressure product, was characterized by a latency and a remanence in recovery. This remanence, also present in the changes of ventricular volumes, supports the hypothesis that other factor(s) like catecholamines might still exert their influence after the exercise stops.
Transcutaneous oxygen pressure measurements in type I diabetic patients for early detection of functional diabetic microangiopathy
Authors: BREUER H.‐W. M. , BREUER J. , BERGER M.
Published: March 2008

AbstractSeventy‐six type I diabetic patients free of peripheral artery disease and 82 age‐matched healthy volunteers were studied by means of transcutaneous oxygen pressure measurements. Two transcutaneous probes were attached to the skin at the subclavian region and at the supramalleolar region. Basal transcutaneous oxygen pressure values and values during breathing of 5 and 10 1 O2min‐1, the rate of rise of oxygen pressure and the time required from the beginning of the oxygen pressure increase to the achievement of its maximum were recorded, and a regional perfusion index was calculated.

Nearly all the measured transcutaneous oxygen parameters showed significant differences between diabetic and control subjects. The differences were most pronounced with the transcutaneous oxygen pressure values during oxygen breathing. Even patients with a diabetes duration of less than 1 year and free of any detectable microangiopathic complication, differed significantly from control subjects. These findings may indicate a microcirculatory disturbance in diabetic patients, which might be considered as the manifestation of a functional diabetic microangiopathy preceeding any morphological alterations of the vasculature in diabetes mellitus.
Methodological limitations of the use of intrinsic hepatic clearance of ICG as a measure of liver cell function
Authors: KEIDING S. , SKAK C.
Published: March 2008

Abstract Negligible extra‐hepatic elimination of indocyanine green (ICG) makes it well suited as a liver test substance. The liver blood flow rate (Q) is estimated from concentration measurements in peripheral (A) and hepatic venous (V) blood during a constant ICG infusion rate (Inf), as Q= Inf/(A – V). Intrinsic hepatic clearance of ICG, Cli = Inf/((A – V)/In(A/V)), is interesting because it should give a flow‐independent quantitative estimate of liver cell function, utilizing the same concentration measurements. The present study was aimed to investigate possible limitations involved in the estimation and use of Cli of ICG in 41 liver patients and 20 controls. Time‐dependence was studied by means of two successive 40‐min infusion periods (with no significant change in Q). Cli of ICG decreased 6% per hour ± 3% (mean ± SD, n= 6, P < 0·01) due to a small but significant increase of the concentrations during the infusion period. Flow‐dependence was studied by measurements before and after an increment of flow of on average 51%, induced by the intake of a meal. This caused no significant change in Cli of ICG (P > 0·5, n= 5, Student's paired t‐test). The intrinsic hepatic clearance of ICG was on average 0·75 ± 0·26 1 plasma min‐1 (± SD, n= 20) in controls and 0·39 ± 0·18 1 plasma min‐1 in liver patients (n= 41), P < 0·001. It was positively correlated to the galactose elimination capacity, although the scatter was large (P < 0·05, n= 56). This might be due to the fact that Cli depends both on liver cell function and on intra‐hepatic vascular shunting of blood.
Serum type III procollagen peptide levels in coronary artery disease (a marker of atherosclerosis)
Authors: BONNET J. , GARDERES P. E. , AUMAILLEY M. , MOREAU C. , GOUVERNEUR G. , BENCHIMOL D. , CROCKETT R. , LARRUE J. , BRICAUD H.
Published: March 2008

Abstract. The known shift in collagen synthesis from procollagen type I to type III in patients with atherosclerosis, suggested measurement of serum procollagen III peptide (PIIIP) levels in patients with coronary artery disease (CAD). Two groups of patients were studied: group I—thirty‐six patients with CAD (male, mean age 56·9 ± 7·5 years, hospitalized for coronary angiography. Risk factors included 16 patients with high blood pressure, four diabetics, 31 smokers and 15 with hypercholesterolaemia. Five patients had no significant lesions, seven had one vessel with over 50% stenosis, 10 had two vessels and 14 had three vessels. Group II—35 patients (male, mean age 39·4 ± 13·3 years), with normal physical examination and ECG according to WHO criteria, formed the control group: the risk factors included nine patients with high blood pressure, 14 smokers and one with hypercholesterolaemia. Procollagen III peptide levels were determined by radioimmunoassay. In group I, PIIIP levels were 26·8 ± 16 ng ml‐1 vs. 10·4 ± 3·2 for group II. Sixty‐one per cent of group I had pathological levels of PIIIP with an absence of correlation with the severity of atherosclerosis or risk factors. Only 2·8% of patients in group II had pathological levels. Procollagen III peptide determination would appear to be a sensitive, specific and predictive test for atherosclerosis in patients with CAD.
Hyperlactataemia, hyperkalaemia and heart block in acute iron overload: the fatal role of the hepatic iron‐incorporation rate in rats on ferric citrate infusions
Authors: ROSENMUND A. , BRAND B. , STRAUB P. WERNER
Published: March 2008

Abstract. An animal model is presented that provides constant and controllable conditions for approaching gradually, and within reasonable time, different stages of iron overload and, probably, an iron‐induced mitochondrial disorder. Thirty‐five rats were infused with ferric citrate, sodium citrate and saline at constant rates for 6–24 h. In the 200–3200 μg Fe h‐1 loading range, the iron‐incorporation capacity of the liver was not saturable and the fractional iron uptake by the liver remained at ˜ 30% even at a loading rate of 3200 μg Fe h‐1. Up to a loading rate of 200 μg Fe h‐1, iron storage was not associated with toxic effects. Beyond this loading rate, however, the liver was no longer able to prevent a massive plasma iron increase on one side and hyperlactaemia on the other. These signs most probably represent hepatocellular decompensation with respect to a critical iron‐storage rate. The product of plasma iron x exposition time was significantly correlated with increased plasma lactate levels (r= 0·89, P<0·005), whereas increased plasma iron levels per se were not. Hyperlactataemia was associated with hyperkalaemia and progressive cardiac conduction defects leading to cardiac arrest at lactate concentration of 9·1 ± 4·3 mmol l‐1. The hypothesis is discussed that toxicity in acute iron overload may entirely be due to hepatocellular (mitochondrial) damage, and not to multiple organ iron overload.