bluuebunny/crossref_metadata_2025 huggingface dataset:
New form of dual porphyria:coexistent acute intermittent porphyria and porphyria cutanea tarda*
Authors: DOSS M. O.
Published: March 2008

Abstract. A previously unrecognized form of dual porphyria has been identified in four patients. One male and one female with acute symptoms were diagnosed as having acute intermittent porphyria (AIP), and two males with cutaneous and acute symptoms were diagnosed as having porphyria cutanea tarda (PCT). Biochemically, the excretion of haem precursors showed a complex constellation, with signs characteristic of both AIP and PCT. In one male, a clinical course with both overt PCT and acute manifestations of AIP was observed. Enzyme studies of haem biosynthesis in erythrocytes revealed a dual deficiency, with decreased activity of both porphobilinogen deaminase, as seen in AIP, and uroporphyrinogen decarboxylase, as seen in PCT. A family study showed that the two disorders do not consistently segregate together.

These findings suggest that the dual porphyria reflects a double heterozygous condition of coexistent AIP and PCT genes in the same subject.
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.
Analysis of cysteinyl leukotrienes in human urine:enhanced excretion in patients with liver cirrhosis and hepatorenal syndrome*
Authors: HUBER M. , KÄSTNER S. , SCHöLMERICH J. , GEROK W. , KEPPLER D.
Published: March 2008

Abstract. The cysteinyl leukotrienes, comprising leuk‐otriene C4 and its metabolites, are biologically most active mediators, eliminated from the blood circulation by the liver and the kidneys. The urine of normal subjects and of patients with hepatic and/or renal failure was analysed for endogenous cysteinyl leukotrienes. The leukotriene metabolites were separated by reversed‐phase high‐performance liquid chromatography and subsequently quantified by radioimmunoassay.

Leukotreine E4 was detected in all urine samples analysed. Its mean concentration increased from 0.3 nmol I‐1 in healthy subjects to 0.8 nmol 1‐1in patients with liver cirrhosis. In patients with hepatorenal syndrome leukotriene E4 averaged 7.8 nmol I‐1; in addition, N‐acetyl‐leukotriene E4 was detected in an average amount of 1.5 nmol ‐1. The mean leukotriene E4/creatinine ratio in urine increased from 0.02 in healthy subjects to 0.11 in patients with liver cirrhosis and to 1.2 µmol leukotriene E4 mol‐1 creatinine in patients with hepatorenal syndrome. These results indicate that cysteinyl leukotrienes may play an important role in the mediator network responsible for the development of the hepatorenal syndrome in patients with severe liver disease.
Proposed mechanism of induction of gastric carcinoids: the gastrin hypothesis
Authors: HÅKANSON R. , SUNDLER F.
Published: March 2008

Abstract. Novel, powerful and long‐acting inhibitors of gastric acid secretion include second generation H2‐blockers and so‐called proton pump inhibitors, such as omeprazole. Gastric carcinoids were found to develop in experimental animals as a consequence of continuous long‐term administration of several of these highly effective anti secretory drugs. This unwanted side effect is now thought to reflect the fact (1) that pharmacological blockade of acid secretion results in hypergastrinaemia, and (2) that long‐standing hyper‐gastrinaemia gives rise to hyperplasia of certain endocrine cells, the so‐called ECL cells, in the gastric mucosa. The carcinoids that develop in the rat stomach after lifelong treatment with antisecretagogues arise from the ECL cells. The proposed sequence of events is acid blockade—hypergastrinaemia—ECL cell hyperplasia—carcinoid. This concept, referred to as the gastrin hypothesis, maintains that the ECL cell hyperplasia (and possibly the carcinoids) is a consequence of long‐term continuous hypergastrinaemia.
Evaluation of a euglycaemic clamp procedure as a diagnostic test in insulinoma patients
Authors: NAUCK M. , STÖCKMANN F. , CREUTZFELDT W.
Published: March 2008

Abstract. In 15 patients with insulinoma, six patients after successful removal of this tumour, two patients with previous pancreas resection because of hypogly‐caemia elsewhere, and 10 control subjects, the diagnostic usefulness of euglycaemic clamp procedures (without exogenous insulin) was assessed in comparison with prolonged starvation. Only insulinoma patients developed sustained hypoglycaemia (≤2.3 mmol 1−1) within 2–44 h without caloric intake, because of inappropriately elevated immunoreactive insulin (IR‐insulin) concentrations. IR‐proinsulin values were elevated in most (7 out of 10), but not in all insulinoma patients. The steady‐state glucose infusion rate necessary to maintain a stable plasma glucose concentration of 4.4–5.0 mmol I−1 was significantly (P ≤0.001) higher in insulinoma patients (2.5 ±0.6 mg kg−1 min−1) than in pancreas resected patients (0.6 ± 0.2 mg kg−1 min−1), or in control subjects (0.5 ±0.1 mg kg−1 min−1). Due to a considerable degree of ovelap, sensitivity (0.44) and specificity (0.95) were too low for such a procedure to qualify as a diagnostic test. There was no correlation of glucose infusion rates to IR‐insulin values (r = 0.024, p = 0.461). One reason for this was the development of insulin resistance in some, but not in all insulinoma patients. When, in analogy to insulin/glucose ratios, a diagnostic index was derived by multiplying the steady state glucose infusion rate by the steady state IR‐insulin concentration, the diagnostic accuracy was greatly increased (sensitivity and specificity 0.94, respectively), but still lower than that of ‘amended’ insulin/glucose ratios in fasting plasma or at the time of discontinuation of prolonged fasts (1.00). Somatostatin infusions inhibited insulin secretion (IR‐C‐peptide plasma concentrations) by 52–88% in subjects without insulinoma and in those insulinoma patients whose tumour cells ultrastructurally contained plenty of normal secretory granules, and to a lesser degree when only abnormal or virtually no secretory granules were present, i.e. in more de‐differentiated tumours. In contrast to this significant (P=0.036) association, malignancy, i.e. the presence of metastases, could not be predicted from whether or not insulin secretion was resistant to the inhibitory action of somatostatin. In conclusion, euglycaemic clamp experiments are less reliable for detecting or excluding a functioning insulinoma than the relation of glucose and insulin values during starvation. The inhibition of insulin secretion by somatostatin depends on the presence of normal β‐granules, and does not distinguish adenomas from carcinomas.
Increased hepatic efficacy of urea synthesis from alanine in insulin‐dependent diabetes mellitus
Authors: ALMDAL T. P. , JENSEN T. , VILSTRUP H.
Published: March 2008

Abstract. The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and in 18 patients with insulin‐dependent diabetes mellitus (HbAlc = 8.4±1.0% (mean±SD)).

Following an overnight fast alanine was infused at 2 mmol h−1 kg−1 body weight. The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water and intestinal hydrolysis. The functional hepatic nitrogen clearance, i.e. the relation of urea synthesis rate to blood alanine concentration, was calculated as the slope of linear regression of urea synthesis rates on blood alanine concentrations.

Fasting glucagon concentrations were 85 + 26 ng 1−1 in controls and 161 ±35 ng 1−1 (P<0.01) in patients.

The functional hepatic nitrogen clearances were 21.8 ± 4.4 1 h−1 in controls and 44.7±12.41 h−1 (P<0.001) in patients.

By multiple step‐wise linear regression analysis the functional hepatic nitrogen clearance was found to correlate independently to fasting glucagon concentration, duration of diabetes, change in blood glucose and insulin following alanine infusion (r2 = 0.74). In a simple linear regression analysis the functional hepatic nitrogen clearance correlated strongly to fasting glucagon concentration (r2 = 0.54).

In conclusion the kinetics of urea synthesis in insulin‐dependent diabetes is changed in favour of increased conversion of alanine‐N to urea‐N at any blood amino acid concentration. The increased FHNC correlates strongly with hyperglucagonaemia.
The role of lipids in the pathogenesis of glomerulosclerosis in the rat following subtotal nephrectomy
Authors: RAYNER H. C. , ROSS‐GILBERTSON V. L. , WALLS J.
Published: March 2008

Abstract. Similarities between atherosclerosis and glomerulosclerosis suggest that hyperlipidaemia may contribute to glomerular injury. Dietary supplementation with 4% cholesterol +1% cholic acid was administered to rats 4 weeks after 1 1/3 nephrectomy and continued for 7 weeks. There was a significant increase in serum cholesterol (peak= 11.52 ±1.09 mmol 1−1 vs. 4.73 ± 0.31 on control diet, < 0.001) and triglyceride concentrations (peak = 2.31 ± 0.27 mmol 1−1 vs. 1.41 ±0.29, <0.05) and a marked increase in βmigrating lipoproteins. The severity of hypercholester‐olaemia was significantly correlated with proteinuria (control diet: r = 0.600, cholesterol diet: r = 0.672, < 0.0001) as was hypertriglyceridaemia (control diet: r = 0.544, cholesterol diet: r = 0.678, <0.0001). The percentage of glomeruli containing lipid deposits was increased from 21% to 60% (<0.05). The kidney total cholesterol content was increased from 29.2 ±0.8 to 47.7 ± 3.3 μmols g−1 dry weight (<0.0001), with esterified cholesterol increasing from 7.5 ± 0.4% to 14.5 ± 2.1% of total (<0.01). Serum cholesterol concentration was significantly correlated with both glomerular lipid deposition (rs = 0.7195, <0.0001) and tissue total cholesterol content (rs = 0.6053, <0.001). Lipid vacuolation was prominent in the paramesangium and within mesangial cells. Despite these changes hypertension, uraemia, proteinuria and glomerulosclerosis were not significantly increased on the cholesterol diet. Cholesterol deposition in the glomeruli occurs secondary to hyperlipidaemia in rats following subtotal nephrectomy but over 7 weeks no exacerbation of glomerulosclerosis is detectable.
Lipoprotein‐induced modulation of cyclosporine‐A‐mediated immunosuppression
Authors: RÖDL S. , FUCHS G. , KHOSHSORUR G. , IBERER F. , TSCHELIESSNIGG K. H.
Published: March 2008

Abstract. Human serum lipoproteins form complexes with cyclosporine‐A and act as a carrier of cyclospor‐ine‐A in vivo. We compared the immunosuppressive effects of free cyclosporine‐A, a complex composed of cyclosporine‐A and lipoproteins, free cyclosporine‐A in the presence of each unbound lipoprotein, and each lipoprotein without cyclosporine‐A with one another at concentrations comparable with in vivo conditions on PHA‐stimulated peripheral blood mononuclear cells.

Free cyclosporine‐A reduced the proliferation of the PHA‐stimulated mononuclear cells to 50% at a concentration of 300 ng ml‐1 (SD±30, n= 12) lipopro‐tein‐deficient medium.

Cyclosporine‐A loaded into VLDL showed a 50% proliferation rate reduction at 60 μg VLDL ml‐1 (SD± 10, n= 12) and 180 ng cyclosporine‐A ml‐1. In the presence of 100 ng ml‐1 cyclosporine‐A 180 μg ml‐1 VLDL (SD μ 25,n= 12) showed a proliferation rate reduction of 50%. In the same way VLDL without cyclosporine‐A induced a reduction to 50% at 740 μg ml‐1 (SD ± 30, n=12).

Cyclosporine‐A loaded into LDL showed a 50% proliferation rate reduction at 27 μg ml‐1 LDL (SD ± 5, n= 12) with 80 ng ml‐1 cyclosporine‐A. In the presence of 100 ng ml‐1, cyclosporine‐A 150 μg ml‐1 LDL (SD±25, n=12) showed a proliferation rate reduction of 50%. In the same way, LDL without cyclosporine‐A induced a reduction to 50% at 950 μg ml‐1 (SD ± 50, n=12).

HDL stimulates prolferation at concentrations of 32 to 1000 μg HDL ml‐1. Concentrations higher than 1000 μg HDL ml‐1 are inhibitory. Comparing the activity of each lipoprotein in the presence of free cyclosporine‐A with each lipoprotein‐cyclosporine‐A complex, we found that the cyclosporine‐A‐VLDL complex yields a reduced lymphocyte proliferation activity, the cyclosporine‐A‐HDL complex produces nearly the same activity and the cyclosporine‐A‐LDL complex induces a higher activity in comparison with the unlinked cyclosporine‐A.

Therefore, we suggest that lipoproteins may play an important role in the cyclosporine‐A‐mediated immunosuppression as the cyclosporine‐A‐LDL complex augments the cyclosporine‐A immunosuppressive power.
Influence of leucine infusion on intracellular amino acids in humans
Authors: ALVESTRAND A. , HAGENFELDT L. , MERLI M. , OURESHI A. , ERIKSSON L. S.
Published: March 2008

Abstract. A continuous intravenous infusion of L‐leucine (300 μmol min‐1) was given to 12 healthy females over a 2 1/2 h period. Arterial plasma concentrations of amino acids and the keto acids of the branched‐chain amino acids (BCAA) were measured. In six subjects muscle biopsies were taken before and at the end of the infusion for determination of intracellular (i.c.) free amino acid concentrations, and leg exchange of amino acids was measured. During infusion the plasma level of leucine rose sixfold. Approximately 40% of the infused amount was taken up by muscle. Of this, half was accumulated intracellularly, where the free leucine concentration increased from basal 190 ± 22 to 580 ± 110 μmol 1‐1 ICW (intracellular water) at the end of infusion. The concentrations of most other amino acids, above all the other BCAA and the aromatic amino acids, decreased, by 17–48% in the i.c. pool and by 17–79% in plasma. The plasma level of ketoisocaproic acid (KIC), the keto acid of leucine, increased in parallel with that of leucine. The concentration of keto valine, ketoisovaleric acid (KIV), decreased by 75%, whereas the keto acid of isoleucine, ketomethylvaleric acid (KMV), was unchanged. Leg release of alanine decreased significantly, whereas the exchange of other amino acids were unchanged. Taken together, decreased i.c. and plasma concentrations but unchanged leg exchange of tyrosine and phenylalanine suggest i.c. accumulation of protein. It can be calculated that approximately 40% of the leucine taken up by muscle was accumulated in the intracellular free pool, some 20% could have been incorporated into protein and 40% was probably oxidized.
Smoking depresses adipose lipoprotein lipase response to oral glucose
Authors: CHAJEK‐SHAUL T. , BERRY E. M. , ZIV E. , FRIEDMAN G. , STEIN O. , SCHERER G. , STEIN Y.
Published: March 2008

Abstract. Adipose tissue lipoprotein lipase was studied in smokers (n= 17) aged 18–47 years and compared with enzyme activity in non‐smokers of comparable age (n= 8) and a second time in some of the subjects 5–9 weeks after cessation of smoking (n= 7). Serum cotinine levels served to validate the smoking status of the subjects. Fasting enzyme activity was similar in smokers and non‐smokers, when expressed per 106 cells, but was significantly increased when normalized for cell size. When lipoprotein lipase was determined in the same individual 4 h after an oral glucose load, a significant decrease (P< 0.002) occurred in the smokers, while enzyme activity rose in the non‐smokers (P<0.02). A tendency for enzyme activity to rise after oral glucose was seen in ex‐smokers, which did not reach statistical significance. Even though the mean serum insulin and glucose levels did not differ in the three groups of subjects, the per cent decrease in lipoprotein lipase after oral glucose in smokers was negatively correlated with insulin release into serum in the same subject, i.e., the greater the insulin release, the less the decrease in lipoprotein lipase activity. We would like to propose that the lower body weight in smokers is related to the paradoxical response of adipose tissue lipoprotein lipase to carbohydrate and that the reversal of this behaviour contributes to the weight gain often observed after cessation of smoking.
A circadian rhythm of serum osteocalcin levels in postmenopausal osteoporosis
Authors: PIETSCHMANN P. , RESCH H. , WOLOSZCZUK W. , WILLVONSEDER R.
Published: March 2008

Abstract. The serum levels of osteocalcin, a 49 amino acid bone matrix protein, have been found to be a specific biochemical parameter of bone formation. The aim of our study was to assess the variability of serum osteocalcin and parathyroid hormone levels in postmenopausal osteoporosis. In 16 patients with postmenopausal osteoporosis, serum levels of osteocalcin and parathyroid hormone were determined in 4‐hourly intervals by radioimmunoassay. Whereas the serum parathyroid hormone levels were similar throughout the day, the serum osteocalcin levels showed a circadian rhythm, with lowest levels in the morning and maximal levels during the night. These findings might suggest a circadian variation of bone formation in patients with postmenopausal osteoporosis.
Platelet P1, P4‐Di (adenosine‐51) tetraphosphate (AP4A) in migraine patients before and during β‐adrenoceptor blockade
Authors: WINTHER K. , HEDMAN C. , FLODGAARD H.
Published: March 2008

Abstract. P1, P4‐Di(adenosine‐51) tetraphosphate (AP4A) is a metabolically inactive nucleotide which can be released from platelet dense granules. This study was designed firstly, to investigate whether platelet content of AP4A was decreased in patients with classical migraine and secondly, whether the content of AP4A was changed by β‐adrenoceptor blockade.

No significant difference in platelet dense granule content of AP4A, was observed between 10 migraine patients and 10 normal controls. Both metoprolol, a β1‐selective blocker and propranolol, a non‐selective beta‐blocker significantly decreased the migraine attack rate. However, while propranolol significantly reduced the platelet content of AP4A, metoprolol did not.

Therefore, the present data suggest that platelet dense granule release, as estimated by the content of AP4A is not of major importance in migraine.
Dexamethasone increases preproparathyroid hormone messenger RNA in human hyperplastic parathyroid cells in vitro
Authors: PERALDI M.‐N. , RONDEAU E. , JOUSSET V. , M'SELMI A. EL , LACAVE R. , DELARUE F. , GAREL J.‐M. , SRAER J.‐D.
Published: March 2008

Abstract. To determine if parathyroid hormone release in man is directly stimulated by glucocorticoids, dispersed human parathyroid cells from hyperplastic glands obtained from eight renal transplant recipients were studied in vitro. Dexamethasone (10‐11 to 10‐6 mol 1‐1) increased PTH release in a time‐ and dose‐dependent manner. A plateau was reached at 10‐8 mol 1‐1 (1015pM 149 vs. 230pM27 pg 10‐4 cells for control value, after 24 h incubation; P < 0.0001). An interaction with a glucocorticoid receptor was suggested since 10‐6 mol 1‐1 RU 486 blunted the dexamethasone‐induced PTH release. By Northern blot analysis, dexamethasone was found to increase the amount of preproPTH mRNA in these cells. The effect of dexamethasone was probably at the gene level since (1) 1,25 dihydroxy vitamin D3 inhibited both iPTH and pre‐proPTH mRNA increases induced by dexamethasone and (2) alpha‐amanitin (1,25 μg ml‐1) also completely suppressed the dexamethasone‐induced PTH release. Thus, for the first time, we demonstrate that dexamethasone induces an increase of PTH synthesis, probably by increasing PTH gene transcription. This effect may play an important pathogenic role in persisting hyper‐parathyroidism and steroid‐induced bone complications in renal transplant recipients.,
Plasma concentrations of endothelin in man: arterio‐venous differences and release during venous stasis
Authors: WAGNER O. F. , NOWOTNY P. , VIERHAPPER H. , WALDHÄUSL W.
Published: March 2008

Abstract. Endothelin‐1 is a recently described endothe‐lium‐derived vasoconstricting peptide. Plasma concentrations of immunoreactive (IR‐) endothelin were investigated in six healthy young men applying a radioimmunoassay after extraction of endothelin from plasma. In venous plasma a mean concentration of 1.3 pM; 0.4 pmol 1‐1 was found, whereas the mean concentration in arterial plasma was 0.9 pM; 0.4 pmol 1‐1 (p< 0.005). During venous stasis for 10 min the mean plasma concentration of IR‐endothelin increased about twofold, from basal 1.1pM;0.3 pmol l‐1 to 2.1pM;0.3 pmol 1‐1 (p<0.01). This manoeuvre may prove helpful to investigate the control of endothelin in vivo under a variety of pathological conditions.
Antibodies to cytoskeletal proteins in patients with Crohn's disease
Authors: MAYET W. J. , PRESS A. G. , HERMANN E. , MOLL R. , MANNS M. , EEW K. , MEYER ZUM BÜSCHENFELDE K. H.
Published: March 2008

Abstract. The immunologic basis of inflammatory bowel disease has been the focus of interest of a series of studies on Crohn's disease and the process of immune sensitization at the gastrointestinal mucosal level is functionally poorly understood. To date only few contradictory reports concerning the incidence of autoantibodies in patients with this disease exist. The aim of this study was to investigate the sera drawn from 60 patients suffering from biopsy‐proven Crohn's disease to evaluate the prevalence of autoantibodies against nuclear antigens and cytoskeletal proteins. Using standard methods, no anti‐nuclear antibodies or antibodies to extractable nuclear antigens could be detected. All sera were also negative for antibodies to double‐stranded DNA, anti‐mitochondrial antibodies, and antibodies to gastric parietal cells. Using sensitive enzyme‐linked immunosorbent assays with purified antigens and Western blotting with cytoskeletal proteins of human intestinal cells, the following antibodies could be demonstrated: cytokeratin 18 autoantibodies (IgG 20.0%; IgM 6.7%; IgA 13.3%), actin antibodies (IgG 36.7%; IgM 48.3%, IgA 26.7%), desmin antibodies (IgG 6.7%; IgM 15.08%; IgA 50%), vimentin antibodies (IgG 3.3%; IgM 16.7%; IgA 10.0%) and tropomyosin antibodies (IgG 3.3%; IgM 3.3%, IgA 5.0%). Statistically significant correlations could be found for levels of cytokeratin 18 antibodies (IgM‐type) and the BEST index of activity, and for levels of desmin antibodies (IgM‐type) and the van HEES index of activity. Highest levels could be measured for actin antibodies (IgG‐type) in patients with isolated disease manifestation in the colon. The mechanism of induction of autoantibodies against cytoskeletal components in Crohn's disease still remains obscure. Unmasking of hidden antigens after cell injury during the inflammatory process of disease might lead to sensitization and antibody production. The pattern of antibodies in patients with Crohn's disease seems to be different compared with that of connective tissue diseases.
Effect of synthetic human glucose‐dependent insulinotropic polypeptide (hGIP) on the release of insulin in man
Authors: FÜESSL H. S. , YIANGOU Y. , GHATEI M. A. , GOEBEL F. D. , BLOOM S. R.
Published: March 2008

Abstract. During an oral glucose tolerance test (oGTT) and an isoglycaemic intravenous glucose infusion, blood glucose and the responses of insulin and glucose‐dependent insulinotropic polypeptide (GIP) were measured in six healthy volunteers. On a subsequent occasion a constant infusion of human synthetic GIP (2 pmol kg‐1 min‐1 for 30 min and 0.5 pmol kg‐1 min‐1 for another 30 min was given to each subject, again with a simultaneous infusion of glucose to maintain isoglycaemia to the oGTT. During the oGTT, plasma GIP concentrations rose from 92pM18 pmol 1‐1 to 257 pM42 pmol 1‐1 60 min after ingestion of glucose (meanpMSEM). When glucose was administered intravenously plasma GIP levels did not rise significantly over basal. The infusion of hGIP mimicked the physiological plasma GIP response after oral glucose during the first 60 min of the study. Plasma insulin concentrations were significantly lower between 45 and 60 min than during the oGTT (438 pM 67 vs. 200pM48 pmol l‐1p<0.02; 465pM96 vs. 207pM48 pmol 1‐1;p<0.01). However, the total and incremental integrated insulin responses during the first 60 min of the study were, though lower, not significantly different from the oGTT experiment when glucose and hGIP were infused simultaneously. Thus, in the presence of mild physiological hypergly‐caemia, human GIP is able to enhance the initial insulin response almost equivalently to the stimulus provided by oral glucose. Decreased insulin concentrations during porcine GIP infusions in previous experiments might be due to sequence differences between human and porcine GIP. In humans, GIP must be considered as an important factor in the enteroinsular axis.
Chemotaxis of the peritoneal cells and the detection of a chemo‐attractant in the effluent from peritoneal dialysis patients
Authors: BOS H. J. , BOORSMA D. M. , TUK C. W. , VELD J. C. DE , MUYSENBERG A. J. C. VAN DER , HELMERHORST T. J. M. , STRUIJK D. G. , BRONSWIJK H. VAN , BEELEN R. H. J.
Published: March 2008

Abstract. The migration of peritoneal cells from 25 continuous ambulatory peritoneal dialysis patients and eight healthy women undergoing laparoscopy were studied. Peritoneal cells of continuous ambulatory peritoneal dialysis patients migrated to commonly used chemoattractants, like N‐formyl‐methionyl‐leu‐cyl‐phenyl‐alanine‐methyl‐ester and casein, but they also migrated to high concentrations of recombinant interleukin‐1 α and to endotoxin (lipopolysaccharide). In the peritoneal effluent from continuous ambulatory peritoneal dialysis patients a rather heat stable chemo‐attractant was found with a molecular weight of 40–200 kDa with an optimal activity at approximately 125 kDa. The chemoattractant is a protein and is not complement factor 5a or interleukin‐1 and was only found in peritoneal effluent from continuous ambulatory peritoneal dialysis patients, but not in peritoneal fluid from healthy women undergoing laparoscopy. Therefore, peritoneal dialysis might induce the generation of a chemoattractant. The optimal chemotactic response of peritoneal cells from continuous ambulatory peritoneal dialysis patients to N‐formyl‐methionyl‐leucyl‐phenyl‐alanine‐methyl‐ester in medium could be enhanced by replacing the medium by peritoneal effluent. So the chemotaxis of peritoneal cells to the factor in the peritoneal effluent is caused by another mechanism, which might involve different cell surface receptor populations, than the chemotactic response to N‐formyl‐methionyl‐leucyl‐phenyl‐alanine‐methyl‐ester.
Role of excretory graft function for erythropoietin formation after renal transplantation
Authors: ECKARDT K.‐U. , FREI U. , KLIEM V. , BAUER C. , KOCH K. M. , KURTZ A.
Published: March 2008

Abstract. To examine the role of renal excretory function for erythropoietin (EPO) formation we have determined the kinetics of plasma immunoreactive EPO (irEPO) in patients with end‐stage renal disease undergoing renal allotransplantation (RTX).

In 13 patients with immediate excretory graft function (imGF) and stable haemoglobin (Hb) concentrations (median Hb9–5gdl‐1and median irEPO 18 mU ml‐1before RTX) irEPO increased significantly on day 4 after RTX to a median value of 29 mU ml‐1and 2 days later reached a plateau of 34.4±3.3 mU ml‐1(mean ± SD of daily median values during days 6–20). In patients with imGF having acute blood loss and subsequently receiving transfusions, irEPO responded in an inverse fashion to changes in Hb concentrations.

In 12 patients with delayed graft function (dGF) (median Hb 8.8 gdl‐1and median irEPO 15 mU ml‐1before RTX) irEPO levels during the period of excretory failure remained either unchanged or displayed marked variations with peak values greatly exceeding those of patients with imGF. These variations were not related to changes in Hb concentrations and irEPO levels did not change following alterations in Hb concentrations. Upon recovery of excretory function irEPO approached the values found in patients with imGF.

The results suggest that an intact excretory renal function is not a prerequisite for the capability to produce EPO, but correlates with the oxygen‐dependent regulation of EPO formation.
The activity of cholesteryl ester transfer protein is decreased in hypothyroidism: a possible contribution to alterations in high‐density lipoproteins
Authors: DULLAART R. P. F. , HOOGENBERG K. , GROENER J. E. M. , DIKKESCHEO L. D. , ERKELENS D. W. , DOORENBOS H.
Published: March 2008

Abstract. The activity of cholesteryl ester transfer protein is instrumental in the distribution of cholesteryl ester between lipoproteins in plasma. We measured the activity of cholesteryl ester transfer protein in plasma, designated cholesteryl ester transfer activity, as the rate of cholesteryl ester transfer between exogenous radiolabelled low‐density and high‐density lipoproteins. The effect of hypothyroidism on cholesteryl ester transfer activity was investigated in 13 athyreotic patients who were studied in the hypothyroid condition and in the euthyroid state, after they had received triiodothyronine supplementation for 33 to 67 days.

During hypothyroidism plasma total cholesterol, very‐low‐ plus low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, plasma triacylglycerol, apolipoprotein A1 and B were significantly higher than in the euthyroid state. Cholesteryl ester transfer activity was 15% lower during hypothyroidism (P < 0.02), and an effect of treatment duration was observed. The changes in high‐density lipoprotein total cholesterol (P < 0.02), free cholesterol (P < 0.001), triacylglycerol (P < 0.05) and the free cholesterol/cholesteryl ester molar ratio in high‐density lipoproteins (P < 0.01) were inversely related to the changes in cholesteryl ester transfer activity.

We concluded that thyroid hormone is involved in the regulation of cholesteryl ester transfer protein activity, and that cholesteryl ester transfer protein activity may play a role in the alterations in high‐density lipoprotein lipids observed in hypothyroidism.
The effect of high‐fibre diet on plasma lipoproteins and hormones in genetically obese Zucker rats
Authors: MAZUR A. , REMESY C. , DEMIGNE C.
Published: March 2008

Abstract. The effects of prolonged substitution of readily digested carbohydrates (wheat starch) for poorly digested carbohydrates (mixture of various fibres and crude potato starch) on plasma lipids, lipoproteins and hormones were investigated in Zucker, genetically obese rats. Lean rats were also studied in parallel. Usually, plasma lipid and insulin levels and insulin/glucose ratio were higher in obese rats vs. their lean littermates. High‐fibre diet intake led to weight loss in both obese and lean rats. With a high‐fibre diet, plasma lipid, insulin and glucose postprandial levels in both groups were reduced when compared with their respective control animals. Dietary fibre modified the lipoprotein profile. Triglycerides and cholesterol were reduced in all studied lipoprotein fractions. The study of high density lipoprotein (HDL) fraction in rats fed a high‐fibre diet demonstrated a decrease in the HDL1 subpopulation and in the apolipoprotein (apo)E proportion. The findings show that a high‐fibre diet modulates plasma lipid, insulin and glucose levels and modifies the plasma lipoprotein distribution and composition in normolipaemic, lean rats as well as in hyperlipaemic, genetically obese rats.
Cystic fibrosis patients' B‐lymphocyte response is resistant to the in vitro enhancing effect of corticosteroids
Authors: EMILIE D. , CREVON M. C. , CHICHEPORTICHE R. , AUFFREDOU M. T. , BAROT‐CIORBARU R. , LENOIR G. , DAYER J. M. , GALANAUD P.
Published: March 2008

Abstract. Cystic fibrosis is associated with an cAMP‐regulated channel defect, which has been evidenced in many cell types including B lymphocytes. To document a B‐cell dysfunction potentially related to this defect, we studied the in vitro IgG production by lymphocytes from 11 cystic fibrosis patients. B lymphocytes were co‐cultured with autologous monocytes and stimulated with Staphylococcus aureus Cowan or with Nocardia‐delipidated cell mitogen in the presence of low concentrations of IL2. Cystic fibrosis patients' cells produced amounts of IgG comparable with that of normal and control patients' cells. However, dexamethasone (10‐7 mol l‐1) had no effect on the response of cystic fibrosis patients' cells, whereas it enhanced that of the latter two groups. This resistance of cystic fibrosis cells was true with concentrations of dexamethasone up to 10‐6 mol l‐1, whereas this agent induced a dose‐related enhancement from 10‐8 to 10‐6 mol l‐1 in cultures of normal cells. Co‐culture experiments showed that cystic fibrosis B lymphocytes themselves are resistant to the effect of dexamethasone. In contrast dexamethasone normally suppressed the anti‐CD3 antibody‐induced response of cystic fibrosis T cells in the presence of IL2 and the IL1 α‐ or β‐induced collagenase production of cystic fibrosis fibroblast cell lines. Thus cystic fibrosis B lymphocytes exhibit a selective defect which may interfere with the normal interactions between the hormonal and immune systems and may participate in the sensitivity of cystic fibrosis patients to bacterial bronchopulmonary infections.
Thrombin—antithrombin III complex in fulminant hepatic failure: evidence for disseminated intravascular coagulation and relationship to outcome
Authors: LANGLEY P. G. , FORBES A. , HUGHES R. D. , WILLIAMS ROGER
Published: March 2008

Abstract. Indirect evidence has suggested that intravascular coagulation may occur in patients with fulminant hepatic failure (FHF), the most severe form of acute liver disease. Thrombin is inhibited in circulation by antithrombin III, and measurement of the thrombin‐antithrombin III complex (TAT) is a direct measure of thrombin formation. Using a new rapid enzyme‐linked immunosorbent assay we have measured TAT in 54 patients on admission, with fulminant hepatic failure. TAT was significantly increased in patients with FHF compared with control subjects (25.8 pM 2.7 μg l‐1) compared with 2.6 pM 0.2 μg l‐1; n=10: P < 0.001). Patients who survived had significantly lower TAT levels than those who did not (17.2 pM 2.7 μg l‐1; n= 27 compared with 34.0 pM 4.2 μg l‐1; n= 27: P < 0.005) and patients with FHF caused by viral hepatitis had significantly lower TAT levels than those with FHF due to paracetamol overdose (14.6 pM 4.7 μg l‐1; n= 9 compared with 280 pM 3.1 μg l‐1; n= 45: P < 0.05). Levels of TAT correlated significantly with prothrombin time (r= 0.36, P < 0.01) and inversely with fibrinogen (r= ‐ 0.51, P < 0.001). There was no significant correlation with antithrombin III concentration. Thus, using a simple and rapid technique, we have been able to demonstrate increased levels of TAT complex in patients with FHF. This provides more direct evidence of intravascular coagulation and thrombin generation in these patients. These results confirm that the coagulation system is activated in FHF.
Exercise‐induced hyperkalaemia can be reduced in human subjects by moderate training without change in skeletal muscle Na, K‐ATPase concentration
Authors: KJELDSEN K. , NØRGAARD A. , HAU C.
Published: March 2008

Abstract. In 15 conscripts, venous plasma potassium was followed during exercise on a training bicycle before and after 10 weeks of moderate physical training and a putative relationship with skeletal muscle Na, K‐ATPase was evaluated. Peak plasma potassium concentration obtained at exhaustion was 61 pM 0.2 and 5.6 pM 0.2 mmol l‐1 (mean pM SEM, n= 14, P < 0.05) before and after training, respectively. Throughout the exercise period and within the first minutes of rest plasma potassium concentration was 0.2–0.5 mmol l‐1 higher before than after training. Neither peak values nor peak rises in plasma potassium concentration before nor after training were correlated to the 3H‐ouabain binding site (Na, K‐ATPase) concentration in vastus lateralis muscle. The results indicate that net loss of potassium from the skeletal muscle pool during exercise is reduced after training, that the heart during exercise may be exposed to a smaller rise in plasma potassium concentration after training than before, and that moderate improvement of capacity to clear extracellular potassium during exercise may be due to increased activity of existing Na, K‐pumps in resting skeletal muscle fibres. This may reduce muscle fatigue, increase physical performance and explain the paradoxical observation that, despite an increased catecholamine response, there is a reduced risk of cardiac events after training.
Plasma concentrations of endothelin in man: arterio‐venous differences and release during venous stasis
Authors: WAGNER O. F. , NOWOTNYy P. , VIERHAPPER H. , WALDHÄUSL W.
Published: March 2008

Abstract. Endothelin‐1 is a recently described endothe‐lium‐derived vasoconstricting peptide. Plasma concentrations of immunoreactive (IR‐) endothelin were investigated in six healthy young men applying a radioimmunoassay after extraction of endothelin from plasma. In venous plasma a mean concentration of 1.3 pM; 0.4 pmol 1‐1 was found, whereas the mean concentration in arterial plasma was 0.9 pM; 0.4 pmol 1‐1 (p< 0.005). During venous stasis for 10 min the mean plasma concentration of IR‐endothelin increased about twofold, from basal 1.1pM;0.3 pmol l‐1 to 2.1pM;0.3 pmol 1‐1 (p<0.01). This manoeuvre may prove helpful to investigate the control of endothelin in vivo under a variety of pathological conditions.
Preservation of the porcine pancreas with HTK and Euro‐Collins solution: studies in a reperfusion system
Authors: LEONHARDT U. , BARTHEL M. , TYTKO A. , DRÖGE M. , SIEGEL E. G. , NEBENDAHL K. , KÖHLER H. , CREUTZFELDT W.
Published: March 2008

Abstract. The present study compares the preservation of the porcine pancreas by the standard Euro‐Collins solution or the cardioplegic histidine‐trypto‐phan‐ketoglutarate solution (HTK). The explanted pancreas was stored at 4°C for 6 and 24 h respectively, following which organ quality was assessed in a reperfusion chamber measuring physiological and biomedical parameters. After 6 h ischaemia, the amount of lactate was significantly lower when HTK was used for protection. Other parameters like insulin release, amylase release, vascular resistance and oxygen consumption of the pancreas did not indicate a significant difference. Protection with HTK significantly improved pancreas preservation after 24 h ischaemia: lactate content in the reperfusate was lower (HTK: 64.0±7.2μmol 50 ml‐1 n= 8, v. EC: 114.2pM1–7 μmol 50 ml‐1, n= 6), the arteriovenous flow rate was higher (HTK: 5.7pM0.91 ml min‐1 v. EC: 3.0pM0.26 ml min‐1), and the pancreatic oxygen consumption was increased (HTK: 2.15pM0.22 μl O2 min‐1 g‐1 v. 0.47pM0.08 μl O2 min‐1 g‐1). We conclude that pancreas preservation can be improved in vitro by protection with HTK solution.
Role of excretory graft function for erythropoietin formation after renal transplantation
Authors: ECKARDT K.‐U. , FREI U. , KLIEM V. , BAUER C. , KOCH K. M. , KURTZ A.
Published: March 2008

Abstract. To examine the role of renal excretory function for erythropoietin (EPO) formation we have determined the kinetics of plasma immunoreactive EPO (irEPO) in patients with end‐stage renal disease undergoing renal allotransplantation (RTX).

In 13 patients with immediate excretory graft function (imGF) and stable haemoglobin (Hb) concentrations (median Hb9–5gdl‐1 and median irEPO 18 mU ml‐1 before RTX) irEPO increased significantly on day 4 after RTX to a median value of 29 mU ml‐1and 2 days later reached a plateau of 34.4±3.3 mU ml‐1 (mean ± SD of daily median values during days 6–20). In patients with imGF having acute blood loss and subsequently receiving transfusions, irEPO responded in an inverse fashion to changes in Hb concentrations.

In 12 patients with delayed graft function (dGF) (median Hb 8.8 gdl‐1 and median irEPO 15 mU ml‐1 before RTX) irEPO levels during the period of excretory failure remained either unchanged or displayed marked variations with peak values greatly exceeding those of patients with imGF. These variations were not related to changes in Hb concentrations and irEPO levels did not change following alterations in Hb concentrations. Upon recovery of excretory function irEPO approached the values found in patients with imGF.

The results suggest that an intact excretory renal function is not a prerequisite for the capability to produce EPO, but correlates with the oxygen‐dependent regulation of EPO formation.
Increased insulin‐stimulated glucose uptake by exercised human muscles one day after prolonged physical exercise
Authors: ANNUZZI G. , RICCARDI G. , CAPALDO B. , KAUSER L.
Published: March 2008

Abstract. We evaluated whether the increased peripheral insulin sensitivity often reported after physical exercise is generalized or limited to the active musculature. Substrate exchange in leg (previously active) and forearm (previously inactive) were measured by catheterization technique basally and during a hyperinsulinaemic euglycaemic clamp (2 mU insulin kg–1 BW min–1) in nine healthy men before and 1 day after 3‐h exercise (50%Vo2max). One day after exercise basal glucose uptake was unchanged in the leg, while it was decreased in the forearm (–61%, p < 0.01) compared with the pre‐exercise condition. Glucose uptake during hyperinsulinaemia was increased in the leg (+ 31%, p < 0.05), but not in the forearm. Basal lactate release by the leg was increased by the exercise, while lactate release by the forearm was decreased, significantly only during the clamp. These results indicate that local and not systemic factors are responsible for the changes in insulin sensitivity observed in the recovery from physical exercise.
Thermogenic responses to noradrenaline are unaltered following energy supplementation in chronically energy‐deficient human subjects
Authors: VAZ M. , KULKARNI R.N. , SOARES M.J. , KURPAD A.V. , SHETTY P.S.
Published: March 2008

Abstract. A group of chronically undernourished labourers underwent a period of controlled supplementary feeding (3.35 MJ per day) over a period of 12 weeks. Thermogenic responses to Noradrenaline (NA) (0.15 μg kg–1 fat‐free mass per min) were assessed (1) before supplementation (2) during the 12th week of supplementation and (3) 12–16 weeks following the cessation of supplementation. There were significant changes in anthropometric indices and basal metabolic rates (BMR) during the three stages of the study; however, these were not accompanied by significant changes in the thermogenic responses to NA.
n‐3 fatty acids and acute‐phase proteins
Authors: ERNST E. , SARADETH T. , ACHHAMMER G.
Published: March 2008

Abstract. The aim of this study was to determine the effects of n‐3 fatty acids on acute‐phase proteins and response. Healthy male volunteers were submitted to standard bicycle ergometry once without supplementation and a second time after 3‐weeks supplementation with highly purified n‐3 fatty acids (1.75 g eicosapentaenoic acid and 1.05 g docosahexaenoic acid per day). Acute‐phase proteins (immunoglobulin M, complement C4, haptoglobin, C‐reactive protein, a2‐macroglobulin, coerulopasmin, fibrinogen, α1‐glycoprotein) were measured before, immediately after, 24 and 72 h after exercise. There were significantly lower values of immunoglobulin M (pre‐exercise and at 72 h) and α2‐macroglobulin (pre‐exercise) when cross‐sectionally comparing the baseline data with and without n‐3 supplementation. Longitudinal comparisons show that the ergometric test induced a discrete acute‐phase reaction, which is evident with and without n‐3 fatty acids. Yet the kinetics of the response seem to be altered by n‐3 supplementation. The relative increase of most acute‐phase proteins is numerically larger and the rise persists longer, which is particularly evident for fibrinogen and α1‐glycoprotein. The findings suggest that n‐3 fatty acids lower acute‐phase proteins at baseline and alter the pattern of change following acute exercise.
The influence of gestational age on bilirubin conjugation in newborns
Authors: ULLRICH D. , FEVERY J. , SIEG A. , TISCHLER T. , BIRCHER J.
Published: March 2008

Abstract. Unconjugated, mono‐ and diconjugated bilirubin levels were determined in serum soon after birth, and followed up for several days. Fourteen preterm neonates were studied with a gestational age below 33 weeks (n= 7) or between 34 and 37 weeks (n= 7), respectively, as well as 19 full‐term newborns either untreated (n= 9) or treated by phototherapy (n= 10). Bilirubin and its derivatives were analysed by alkaline methanolysis and spectrometry after separation by thin‐layer chromatography.

In normal full‐term neonates total and unconjugated bilirubin reached peak levels at days 2–4. Thereafter, a decline of 11 % per day was detectable. Monoconjugates in serum amounted to 3.1 ± 1.1% of total pigment and remained at that level. The relative amount of diconjugates increased from 0.55 ± 0.25% (2–4th postnatal day) to 1.62 ± 0.99% (9–13th day of life). The rapid decline of unconjugated bilirubin paralleled by an increase of diconjugates are an expression of the maturation process for bilirubin conjugation.

The premature neonates with less than 33 weeks gestation exhibited an increase of unconjugated serum bilirubin up to the 4–5th postnatal day, the decline thereafter amounted 2% per day. The fraction of 2.3 ± 1.1% monoconjugates was small and exhibited only a moderate increase in the follow up. In contrast diconjugates were undetectable or very low and remained at this level. These results suggest the presence of a more severe immaturity as well as a slower maturation process of bilirubin conjugation in preterm newborns.

A subgroup of full‐term neonates treated by phototherapy showed highest serum bilirubin levels at the first days of life and the lowest monoconjugate fraction (1.2 ± 1±1%). In the follow up the monoconjugates rose slightly, whereas the diconjugate fraction remained very low. These findings in this subgroup of full‐term newborns might indicate a more severe conjugation defect for bilirubin as well as a bilirubin overload in respect to a limited bilirubin glucuronidation capacity.

Analysis of bilirubin pattern in serum seems to allow prediction of the severity and the maturation rate of bilirubin conjugation.
Antibodies against acetaldehyde‐modified epitopes: an elevated IgA response in alcoholics
Authors: WORRALL S. , DE JERSEY J. , SHANLEY B.C. , WILCE P.A.
Published: March 2008

Abstract. Several recent reports have shown that antibodies reactive with acetaldehyde (AcH)‐modified epitopes are present in alcoholics. However, similar antibodies have also been found in patients with nonalcoholic liver disease and control subjects. In each of these studies total immunoglobulin binding to the AcH‐modified proteins was measured, with no attempt being made to identify the classes of immunoglobulin involved. In the present study we employed an enzyme‐linked immunosorbent assay (ELISA) to assess the classes of immunoglobulin involved in this response, using plasma samples from 97 alcoholics with varying degrees of liver disease, 35 patients with non‐alcoholic liver disease and 33 control subjects. All three groups exhibited a large IgM response and a negligible IgG response. However, the alcoholics exhibited a significantly higher IgA response than either of the other groups. This suggests that the measurement of the IgA response to AcH‐modified epitopes may be a specific marker of ethanol abuse.