bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclosporin‐A‐induced lipid peroxidation in human liver microsomes and its influence on cytochrome P‐450
Authors: INSELMANN G. , BARTH A. , ENGEMANN R. , HEIDEMANN H. TH.
Published: March 2008

Abstract. The present in vitro study using human liver tissue was performed to investigate the effect of cyclosporin A on lipid peroxidation and cytochrome P‐450 concentration in isolated liver microsomes. Incubations were either carried out with cyclosporin A concentrations of 10,30,100 and 300 μg ml‐1 for 1 h or for different time periods (15, 30, 60 and 90 min) with cyclosporin A 300 μg ml‐1. Lipid peroxidation was monitored measuring the amount of malondialdehyde. In additional experiments the effect of reduced and oxidized glutathione (1 mM) on cyclosporin‐A‐induced lipid peroxidation in human liver microsomes was studied.

Cyclosporin A caused a significant dose and time‐dependent increase of the lipid peroxidation product malondialdehyde. At the highest cyclosporin A concentration (300 μg ml‐1) malondialdehyde production increased 5‐fold in comparison to corresponding control values. Incubations for different time periods resulted in a 5‐fold net increase of malondialdehyde formation after 90 min.

In the presence of reduced glutathione, cyclosporin‐A‐induced lipid peroxidation was significantly inhibited. Furthermore, cyclosporin‐A‐induced microsomal lipid peroxidation was accompanied by a significant dose‐dependent decline of the microsomal cytochrome P‐450 content. At a cyclosporin A concentration of 300 μg ml‐1, cytochrome P‐450 content was decreased to 49% in comparison to control values. In the presence of reduced gluthathione, cyclosporin A decreased the cytochrome P‐450 concentration only to 79% (P<0·05). In contrast, oxidized glutathione had no effect.

In conclusion, the results of the present study demonstrate that cyclosporin A induces lipid peroxidation in human liver microsomes accompanied by a decrease of the microsomal cytochrome P‐450 content. Lipid peroxidation may therefore contribute to cyclosprin‐A‐induced hepatotoxicity.
The calcium binding protein tropomyosin in human platelets and cardiac tissue: elevation in hypertensive cardiac hypertrophy
Authors: CRABOS M. , YAMAKADO T. , HEIZMANN C. W. , CERLETTI N. , BÜHLER F. R. , ERNE P.
Published: March 2008

Abstract. Intracellular calcium transients play a major role in the control of cellular contraction and act through binding to target proteins and inducing subsequent conformational changes and activation of enzymes. Abnormalities of intracellular calcium handling are involved in the pathophysiology of essential hypertension and cardiac hypertrophy. In this study we report on the isolation, purification and calcium binding of a 33 kDa protein from human platelets and of a 38 kDa protein from cardiac tissue, both of which are identified as tropomyosin. The calcium binding properties of these human tropomyosin isoforms indicate a putative role for these proteins in the fine tuning of the cellular contraction. Elevated tropomyosin level is demonstrated in platelets from untreated essential hypertensive patients with left ventricular hypertrophy (tropomyosin/actin: 45·1 ± 3·5, n=12) relative to essential hypertensive patients without cardiac hypertrophy (tropomyosin/actin: 33·8 ± 2·3). These findings suggest an association between the enhanced expression of tropomyosin in platelets and the development of cardiac hypertrophy which may relate to the cellular calcium overload of this disease.
Relationships between local inflammation, interleukin‐6 concentration and the acute phase protein response in arthritis patients
Authors: HOLT I. , COOPER R. G. , HOPKINS S. J.
Published: March 2008

Abstract. Interleukin‐6 (IL‐6) concentrations in knee joint synovial fluids and paired plasma samples of arthritis patients were examined with respect to each other and parameters of the inflammatory response. Synovial fluid and plasma IL‐6 concentrations were significantly higher in patients with inflammatory arthritis than those detected in patients with osteoarthritis (P<0·001). The IL‐6 concentrations in synovial fluids were considerably higher than, but significantly correlated with (r=0·65; P<0·001), those of plasma. Furthermore, synovial fluid IL‐6 concentrations in bilaterally inflamed knees were significantly correlated (r=0·79; P<0·001) and there was a significant correlation with the extent of inflammatory cell infiltrate (r=0·75; P<0·001). In unselected rheumatoid arthritis patients there was only a weak correlation between IL‐6 and plasma C‐reactive protein (CRP) concentration, and no correlation between IL‐6 and erythrocyte sedimentation rate (ESR). However, both ESR and CRP concentration were highly correlated with plasma IL‐6 concentration in patients with other inflammatory arthritides, particularly psoriatic and HLA B27 positive spondyloarthritis (r=0·72‐0·94; p<0·005). These relationships suggest that IL‐6 production in inflamed knee joints can be a significant determinant of acute phase protein responses in arthritis patients, although the situation in patients with rheumatoid arthritis is more complex and may be influenced by other disease‐related factors.
Liquid crystal thermography as a screening test for deep vein thrombosis in patients with cerebral infarction
Authors: CAMERON E. W. , SACHDEV D. , GISHEN P. , MARTIN J. F.
Published: March 2008

Abstract. Pulmonary embolism secondary to deep vein thrombosis is a frequent cause of death in stroke patients. In a multicentre study of deep vein thrombosis prophylaxis, 112 patients with cerebral infarction and leg paresis were given aspirin 300 mg three times a day (t.d.s.) alone or with dipyridamole 100 mg t.d.s. To screen for deep vein thrombosis liquid crystal thermography of the legs was performed daily for 15 days on all patients. Those patients with positive thermography underwent immediate X‐ray venography of the appropriate limb as the definitive investigation for venous thrombosis.

Twenty‐two patients had positive thermograms, of whom 16 had confirmed deep vein thrombosis as demonstrated by X‐ray venography. Only 8 of the 22 had clinical signs of deep vein thrombosis and 2 of those had a negative venogram. Of the 14 patients with positive thermography but negative clinical signs 10 had positive venograms. Difference in the incidence of deep vein thrombosis in the two treatment groups was not demonstrated.

It is concluded that occult deep venous thrombosis is common after ischaemic stroke and it can occur without clinical signs. Liquid crystal thermography is a simple, rapid and cheap screening test that will allow the detection of clinically unrecognized thrombosis.
Retinyl esters in chylomicron remnants inhibit growth of myeloid and lymphoid leukaemic cells
Authors: SKREDE B. , BLOMHOFF H. K. , SMELAND E. B. , WATHNE K.‐O. , NORUM K. R. , BLOMHOFF R.
Published: March 2008

Abstract. We have studied the effects of retinyl esters in chylomicron remnants on cell growth and differentiation of myeloid and lymphoid leukaemic cells. Ten μmol l‐1 retinyl ester in chylomicron remnants effectively reduced proliferation of the myeloid leukaemic cell lines HL60, U937 and KG‐1, and induced differentiation of 68% and 53% of the HL60 and U937 cells, respectively, in 5 days. While no effect on cell growth of the lymphoid cell lines Daudi, Raji and SOS was observed, 10 μmol l‐1 retinyl esters in chylomicron remnants reduced the growth of the B lymphoid cell line Reh by more than 50%. Primary cell cultures from six patients with acute leukaemia (four non‐lymphocytic and two lymphocytic) were incubated with chylomicron remnant retinyl esters and proliferation was measured by means of thymidine incorporation. Among the myeloid leukaemic cells, the mono‐myelocytic, the two promyelocytic and the monoblastic leukaemic cells were growth inhibited. Chylomicron remnants had no effect on the growth of the c‐ALL primary culture, but reduced proliferation of the T‐ALL primary culture by approximately 20% after 48 h. These data suggest that high doses of retinol may be used in the treatment of some forms of acute leukaemia.
Effect of medium‐ and long‐chain triglyceride infusion on lipoprotein and hepatic lipase in healthy subjects
Authors: NORDENSTRÖM J. , NEESER G. , OLIVECRONA T. , WAHREN J.
Published: March 2008

Abstract. Plasma lipolytic activity and hydrolysis of intravenous fat were studied in six healthy subjects during infusion of a long‐chain triglyceride (LCT) fat emulsion (Intralipid 20%) or of a medium‐chain triglyceride (MCT)/LCT emulsion (Lipofundin MCT 20%).

The fat emulsions were infused continuously at a rate of 0·17 g triglyceride kg‐1 body weight (BW) h‐1 for 6 h in random order at 7‐day intervals. A continuous infusion of glucose (0·18 g kg‐1 BW h‐1) was administered for a period of 7h and was started 1h before the lipid infusion.

Infusions of both types of fat increased plasma triglyceride (TG), free fatty acid (FFA) and lipoprotein lipase (LPL) levels and steady‐state values were present during the 3rd to 5th h of infusion. MCT/LCT infusion resulted in higher plasma levels at steady‐state of TG (3·63±0·45 [SEM] vs 2·73±0·45 mmol l‐1; P < 0·05), FFA (1·05±0·08 vs 0·54±0·04 mmol l‐1; P < 0·01) and LPL (4·6±0·6 vs 2·6±0·5 mU m l‐1; P < 0·05) in comparison with LCT administration. There was a positive correlation between plasma LPL activity and TG concentration (r=0·77; P< 0·001) when data for the two infusions were combined.

Although the same amount of fat was infused on a weight basis, the molar infusion rate was 40% higher with MCT/LCT than with LCT infusion, due to differences in molecular weights (634 vs 885 Da). The increments in molar TG levels of both groups were comparable with differences in molar infusion rates, indicating that MCT/LCT and LCT fat were cleared at similar rates.

After 5h of lipid infusion 50 IU of heparin kg‐1 BW was injected as a bolus dose to release endothelial lipases into the circulating blood. LPL activity increased approximately 90 times and reached 343·38 mU ml‐1 during MCT/LCT and 226·22 mU ml‐1 during LCT infusion (P < 0·01).

It is concluded that the interaction between plasma TG and LPL activity is reciprocal. LPL activity is an important factor for regulating TG turnover and plasma TG affects LPL activity. On a molar basis, the two types (LCT and LCT/MCT) of fat emulsion were cleared at comparable rates.
Leukotriene B4 levels from stimulated neutrophils from healthy and allergic subjects: effect of platelets and exogenous arachidonic acid
Authors: HOSNI R. , CHABANNES B. , PACHECO Y. , MOLIERE P. , GROSCLAUDE M. , FAYOLLE M. PERRIN , LAGARDE M.
Published: March 2008

Abstract. Leukotriene B4 (LTB4) levels were measured in peripheral blood neutrophils from allergic and healthy donors after stimulation by calcium ionophore A 23187. This level was higher in neutrophils from allergic subjects than in neutrophils from healthy subjects in the presence as well as in the absence of exogenous arachidonic acid. Platelets from allergics increased LTB4 levels from neutrophils from allergics but not levels in those from healthy donors. Moreover, platelets from healthy subjects reduced LTB4 in neutrophils from both groups. These results suggest that biochemical differences exist in neutrophils and platelets from allergics which contribute to changes in arachidonic acid metabolism via the 5‐lipoxygenase pathway. In addition, they support the concept that platelets may play an important role in the regulation of neutrophil LTB4 levels, possibly by affecting the 5‐lipoxygenase activity during the course of allergic inflammatory reactions.
Lipoproteins of human peripheral lymph. Apolipoprotein AI‐containing lipoprotein with alpha‐2 electrophoretic mobility
Authors: REICHL D. , HATHAWAY C. B. , STERCHI J. M. , MILLER N. E.
Published: March 2008

Abstract. Evidence from diverse sources has implicated a central role of apolipoprotein AI (apo AI), the most abundant protein of plasma high‐density lipoproteins, in the transport of cholesterol from peripheral tissues to the liver (reverse cholesterol transport). Particles containing only apo AI appear to be more effective as cholesterol acceptors in tissue culture than do particles which also contain apo AII The apo AI‐containing lipoproteins of plasma have been extensively studied, but there is less information on those in tissue fluids, to which most peripheral cells are exposed. In the present study the heterogeneity of apo AI‐containing particles in human peripheral lymph, collected from the dorsum of the foot, has been examined by starch block electrophoresis, exclusion chromatography and immunoelectrophoresis.

The apo AI‐containing particles of lymph were found to be more variable in both electrophoretic mobility and size than those of plasma from the same subjects. Of particular interest was a subpopulation which migrated on electrophoresis with the same mobility as alpha‐2‐macroglobulin. This fraction accounted for approximately 7% (range: 4–12%; n= 5) of lymph apo AI, contained no immunodetectable apo AII, and by exclusion chromatography was composed of particles the size of, or smaller than, albumin. Such physicochemical properties suggest that these alpha‐2 migrating particles may function as the principal primary acceptors of cell cholesterol in the extracellular matrix of human peripheral tissues. By isoelectric focusing, lymph apo AI was found to contain a higher proportion of more negatively charged isoforms than the apo AI of plasma.
Decreased insulin secretory capacity and normal pancreatic B‐cell glucose sensitivity in non‐obese patients with NIDDM
Authors: HAEFTEN T. W. VAN , MAARSCHALKERWEERD W. W. A. VAN , GERICH J. E. , VEEN E. A. VAN DER
Published: March 2008

Abstract. We investigated the dose‐response characteristics of glucose‐induced insulin release and the influence of hyperglycaemia on arginine‐induced insulin secretion in eight non‐obese subjects with NIDDM and in eight non‐diabetic volunteers. Plasma C‐peptide levels, achieved during 60 min hyperglycaemic clamps with and without the infusion of a primed continuous infusion of arginine (infusion rate 15 mg kg‐1 min‐1) during the last 30 min, were analysed with a modified Michaelis‐Menten equation. The insulin secretory capacity (Vmax) for glucose‐stimulated insulin release snowed a trend towards a negative correlation with the fasting blood glucose in the NIDDM subjects (r=0.68, P=0.6); it was lower than the Vmax of non‐diabetic controls (2.2±0.2 vs 4.2±0.4 nmol 1‐1 respectively; P<0.001). The ED50 (half maximal stimulating blood glucose concentration) of the second‐phase glucose‐stimulated insulin release (determined from the plasma C‐peptide levels at 60 min) was not significantly different from the ED50 of the controls (11.9±0.8 vs 13.3±1.9 mmol 1‐1 respectively; P>0.2).

Combined glucose‐arginine stimulation significantly increased insulin release. The Vmax for both phases were significantly lower in NIDDM patients than in controls (2.3±0.2 vs 5.0±0.9 and 3.8±0.5 vs 8.5±0.9 nmol 1‐1 respectively; P<0.01). In both NIDDM patients and controls, the ED50 of the influence of glucose on first‐phase arginine‐induced insulin release was significantly lower than the ED50 for the second phase (8.2±0.8 vs 10.5±1.1 mmol 1‐1 (NIDDM) and 9.4±1.4 vs 11.6±0.9 mmol 1‐1 (non‐diabetic subjects) respectively; P<0.02). No differences in ED50 were seen between the two groups.

In NIDDM patients, the fasting blood glucose level was negatively correlated with the Vmax of the second phase of glucose‐arginine‐induced insulin release (r=‐0.70, P=0.05).

We conclude that (1) insulin secretory capacity is reduced in NIDDM both for stimulation with glucose and with arginine; (2) the B‐cell glucose sensitivity is normal in patients with NIDDM.
Increased removal of remnants of triglyceride‐rich lipoproteins on a diet rich in polyunsaturated fatty acids
Authors: DEMACKER P. N. M. , REIJNEN I. G. M. , KATAN M. B. , STUYT P. M. J. , STALENHOEF A. F. H.
Published: March 2008

Abstract. We studied the effect of two diets, one rich in polyunsaturated and the other in saturated fatty acids, on the postprandial processing of exogenous and endogenous triglyceride‐rich lipoproteins (chylomicrons, very‐low‐density lipoproteins, and their remnants).

For this purpose, 12 normolipidaemic young volunteers were fed, in a cross‐over design of 9 days on each diet, either a diet rich in saturated fat (21% of their daily energy intake from saturated fat, 12% from monounsaturated fat, and 3% from polyunsaturated fat) or a diet rich in polyunsaturated fat (10% saturated fat, 9% monounsaturated fat, and 18% polyunsaturated fat) (P/S ratios 0.14 and 1.8, respectively). On the last day of each dietary period blood samples were drawn six times over a 24‐h period for determination, by densitometric scanning of SDS gels, of the diurnal pattern of apoprotein B‐48 and B‐100 in the d<1.019 g ml‐1fractions, as estimates for the processing of chylomicrons and very‐low‐density lipoproteins.

In addition to the usual decrease in the fasting and diurnal concentrations of total serum cholesterol and of cholesterol in the low‐density lipoprotein fractions (between 15 and 21%), the diet rich in polyunsaturated fat resulted in 43% lower daily concentrations of chylomicrons and their remnants. This was due to differences in the clearance rate of chylomicrons and their remnants, rather than to differences in the absorption rate of exogenous fat. In addition, the concentrations of very low density lipoproteins and their remnants during the day were 20% lower on the diet rich in polyunsaturated fat.

As remnants, especially those from intestinal origin, are considered to be atherogenic, our observations provide an additional explanation why atherosclerosis is reduced on diets with a relatively high ratio of polyunsaturated to saturated fat.
Acute effects of HMG‐CoA reductase inhibitors on biliary lipids in patients with interrupted enterohepatic circulation
Authors: MURACA M. , BAGGIO G. , MICONI L. , VILEI M. T. , MARTINI S. , GABELLI C. , BELLUCO C. , LISE M. , CREPALDI G.
Published: March 2008

Abstract. HMG‐CoA reductase inhibitors decrease serum cholesterol by inhibiting hepatic cholesterol synthesis, but their influence on biliary lipids is not well characterized. In the present study Pravastatin (80 mg) was administered as a single oral dose to 10 patients with external bile fistula, after 1 week of interruption of the enterohepatic circulation, in order to assess the effect of inhibition of hepatic cholesterol synthesis on biliary lipids in conditions of stimulated bile acid synthesis. Bile was collected every hour for 12 h. On the day before, the same procedure was applied with a placebo, and collected bile used as control. Pravastatin decreased both bile acid and phospholipid concentration to about 60% of basal values; this change was still significant after 10 h. Cholesterol concentration was also decreased to about 70% of basal values, but this change was significant only from the 5th to the 7th h. The per cent of cholic and chenodeoxycholic acid was not affected by the drug, but the ratio of glyco‐ to tauroconjugated bile acids was decreased to about half the initial values. Bilirubin concentration exhibited a late increase, suggesting a reduction in the bile flow. These results suggest that, in patients with interrupted enterohepatic circulation, biliary excretion of bile acids can be largely dependent on hepatic cholesterol synthesis.
Predictability of low‐density lipoprotein levels during apheretic treatment of hypercholesterolemia
Authors: FRANCESCHINI G. , BUSNACH G. , CALABRESI L. , CHIESA G. , GIANFRANCESCHI G. , ZOPPI F. , MINETTI L. , SIRTORI C. R.
Published: March 2008

Abstract. The efficiency and efficacy of low‐density lipoprotein (LDL) apheresis performed with a dextran sulphate cellulose (DSC) regenerating unit were tested in five familial hypercholesterolaemic patients. LDL apheresis was repeated four times at both bi‐weekly and weekly intervals, processing one plasma volume each time. The efficiency of the procedure (i.e., the extent of lipoprotein removal) was nearly identical with both schedules. Efficacy parameters, i.e., decreases of plasma total and LDL cholesterol (TC and LDL‐C) and apo B, were highly correlated (r>0.96) with preapheresis levels, allowing an accurate prediction of the absolute lipid removal in the single individual. Plasma triglycerides, high‐density lipoprotein cholesterol, apo A‐I and apo A‐II recovered rather rapidly, reaching 91–96% of the pre‐apheresis values in 48 hours; the recovery of TC, LDL‐C and apo B was much slower, with a relatively rapid early phase (80% recovery after about 7 days) followed by a successive slower rise. This pattern was highly reproducible in the single patient, allowing the definition of a simple mathematical model for an accurate (error<20%) prediction of the individual process. Based on this model one can design the treatment schedule necessary to maintain lipid levels within the desired range in the single individual. The hypolipidaemic efficacy of DSC apheresis appears, otherwise, not to be dependent upon the procedure per se, but on other individual factors, e.g. the amount of removable lipoproteins and the rate of lipid recovery; both can be predicted with sufficient accuracy.
Late‐onset congenital adrenal hyperplasia in women with hirsutism
Authors: ARNAOUT M. A.
Published: March 2008

Abstract. Hirsutism in women is a clinical manifestation of excessive production of androgens. The source of the excess androgen may be either the ovaries or the adrenal glands, or increased peripheral conversion of weak androgenic hormones to more potent androgens. Late‐onset (non‐classic) congenital adrenal hyperplasia is a cause of hirsutism in adult women, but its frequency and the patterns of abnormalities in adrenal hormone secretion are not well understood. The frequency of non‐classical adrenal hyperplasia due to deficiencies of 3β‐hydroxy‐Δ5‐steroid dehydrogenase, 21‐hydroxylase, and 11β‐hydroxylase among 65 women with hirsutism were determined. All enzyme defects were identified by comparing the patients' hormonal responses to 0.25 mg intravenous bolus of α1–24‐ACTH with those of age‐matched normal women. The hormones measured in plasma during the ACTH stimulation tests were progesterone, 17‐hydroxypregnenolone, 17‐hydroxyprogesterone, DHEA‐sulfate, androstenedione, testosterone, 11‐deoxycortisol, and cortisol. Similarly these hormones were measured after overnight 1 mg oral dexamethasone.

Twelve women (18.5%) had 3β‐hydroxy‐Δ5‐steroid dehydrogenase deficiency, 24 (37%) 21‐hydroxylase deficiency, and 14 (21.5%) 1 lβ‐hydroxylase deficiency. Women with 21‐hydroxylase deficiency also had evidence of a partial deficiency in 11β‐hydroxylase activity (12 of the 24 patients). Similarly, most (11 of the 14) of the women with 11β‐hydroxylase deficiency also had evidence of a deficiency in 3β‐hydroxy‐δ5‐steroid dehydrogenase activity. Among the 15 patients with no adrenal biosynthetic defect, eight had high plasma androgen concentrations, and seven had normal concentrations. Elevated basal levels of hormones were not predictive of the individual response to ACTH. Polycystic ovary syndrome was present in all four groups, with an incidence of 35% in the adrenal biosynthetic defect groups. Paternal consanguinity, whether first degree or second degree, was present in 50% of patients with adrenal biosynthetic defect groups as compared to 20% in patients with no adrenal biosynthetic defects (P < 0.02).

In conclusion, a substantial proportion (77%) of women with hirsutism had defects in adrenal steroidogenesis, revealed by ACTH stimulation test, that are indicative of non‐classical congenital adrenal hyperplasia. Measurements of basal steroid levels are not helpful in differentiating among the causes of increased androgen production in women with hirsutism. Secondary adrenal biosynthetic defects were frequent in these women and were probably caused by intraadrenal androgen excess rather than by dual inherited enzymatic deficiencies.
In vitro immune modulation of polymorphonuclear leukocyte adhesiveness by sodium fluoride
Authors: GÓMEZ‐UBRIC J. L. , LIÉBANA J. , GUTIÉRREZ J. , CASTILLO A.
Published: March 2008

Abstract. We investigated the influence of sodium fluoride on polymorphonuclear leukocyte (PMN) adhesiveness in a healthy subject with low serum levels of fluoride. The PMN were separated from venous blood, and the percentages of adhered and unadhered cells were determined in vitro in plastic culture plates. The cells were cultured with five different fluoride concentrations ranging from 6.25 10‐2μM to 4.0 μM in the presence and absence of autologous serum.

PMN adhesiveness in both the presence and in the absence of autologous serum was 98.5%; the addition of fluoride had no effect on the results in the absence of serum. However, in the presence of autologous serum, PMN adhesiveness decreased significantly with the addition of fluoride (P < 0.05) from 0.5 μM. The decrease was smaller (1.1%) at a concentration of 0.125 μM, and larger at 12 times this concentration of fluoride (52.7%). We conclude that sodium fluoride reduces PMN adhesiveness in a dose‐dependent manner. The effect is not direct, but should be modulated by a seric factor.
MuIti‐frequency bioelectrical impedance augments the diagnosis and management of lymphoedema in post‐mastectomy patients
Authors: WARD L. C. , BUNCE I. H. , CORNISH B. H. , MIROLO B. R. , THOMAS B. J. , JONES L. C.
Published: March 2008

Abstract. The value of multiple frequency bioelectric impedence analysis (MFBIA) in the monitoring and management of post‐mastectomy lymphoedema of the arm was evaluated in 15 patients and controls. The technique was found to produce quantitative agreement with a clinical diagnosis of lymphoedema and with the currently‐used measure (limb volume calculated from circumferential measurements) of limb size. The significance of this finding lies in MFBIA being diagnostically informative: it indicates when an observed change in limb volume is directly, albeit theoretically, attributable to accumulation of extracellular fluid. MFBIA potentially offers the means for earlier definitive diagnosis and more‐accurate monitoring of extracellular fluid changes during and after treatment.
Can urinary pyridinium crosslinks and urinary oestrogens predict bone mass and rate of bone loss after the menopause?
Authors: MOLE P. A. , WALKINSHAW M. H. , ROBINS S. P. , PATERSON C. R.
Published: March 2008

Abstract. We measured urinary pyridinoline and deoxy‐pyridinoline by high performance liquid chromatography, and urinary oestrogens by radio‐immunoassay, in 68 healthy postmenopausal women to evaluate these assays for the prediction soon after the menopause of the risk of developing osteoporotic fractures in later life. Change in forearm bone mineral content was assessed by single photon absorptiometry over 4 years.

Although there was no significant correlation between the pyridinium crosslinks and urinary oestrogens, we found that up to 58% of the variation in the rate of loss of bone mineral content in women soon after the menopause could be explained by pyridinoline and oestradiol glucuronide assays together with body mass index. Measurement of the urinary pyridinium crosslinks and oestradiol glucuronide may make a significant contribution to a biochemical screening procedure for future osteoporotic fracture.
Effects of the new somatostatin analogue (BIM 23014) on blood glucose homeostasis in normal men
Authors: KUHN J. M. , BASIN C. , MOLLARD M. , ROUGE B. DE , SCHATZ B. , WOLF L. M.
Published: March 2008

Abstract. Changes in blood glucose homeostasis induced by the new somatostatin analogue BIM 23014 (BIM) were studied. Eight normal men (study 1) received either vehicle or 1000, 2000 and 3000 μg BIM as a 24 h s.c. infusion. Blood glucose, plasma insulin, C‐peptide, glucagon and growth hormone (GH) were measured before treatment and then hourly for 24 h. In five normal men (study 2) an oral glucose tolerance test (OGTT) was performed during vehicle infusion and then on days 1 and 7 of a continuous s.c. infusion of 2000 μg BIM daily for 7 days. The same biological parameters as in study 1 were measured before OGTT and then twice‐hourly for 5 h. Dose‐dependent and transient glucose intolerance was observed in the first half of study 1. Except for glucagon, BIM significantly (p<0.01) reduced plasma insulin, C‐peptide and GH levels. In study 2 BIM infusion induced glucose intolerance and a drop in plasma insulin and C‐peptide on day 1 which disappeared on day 7 of infusion. Higher on day 7 than on day 1, plasma GH secretion was significantly (p< 0.01) reduced throughout BIM infusion. In contrast plasma glucagon levels were not modified at any time. Side‐effects were abdominal cramps and diarrhoea which were observed in most subjects when increasing BIM daily dose. In conclusion, BIM infusion induced transient changes in glucose homeostasis and insulin secretion in normal men. By contrast, plasma GH levels remained reduced throughout the treatment. BIM appears to be a useful tool to selectively inhibit GH secretion.
Extra‐hepatic cholestasis determines a reversible increase of glycoproteic tumour markers in benign and malignant diseases
Authors: BASSO D. , MEGGIATO T. , FABRIS C. , PLEBANI M. , FOGAR P. , PANOZZO M. P. , FAVERO G. DEL
Published: March 2008

Abstract. This study was performed in order to assess the relative role of cholestasis in increasing some serum glycoproteic markers of malignancy (CA 19–9, TPA, CEA). 30 Patients with benign and 16 with malignant extra‐hepatic cholestasis were studied on admission (stage A) and after the operative or spontaneous resolution of the cholestatic picture (stage B). CA 19–9 and TPA were found to be lower in stage B than in stage A benign diseases. A similar behaviour was found in malignant diseases, although findings were significant only for CA 19.9. In neither of the patient groups was CEA found to present a significant trend. Extra‐hepatic cholestasis appears able to increase per se serum glycoproteic markers in benign diseases, with variations proportional to the severity of the clinical picture. The same considerations can apply to malignancies, even if in these situations the production of tumour markers by the neoplastic growth should also be considered. We should therefore be cautious in assessing the diagnostic usefulness of new tumour markers when cholestasis is present.
Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man
Authors: BEGLINGER C. , HILDEBRAND P. , ADLER G. , WERTH B. , LUO H. , DELCO F. , GYR K.
Published: March 2008

Abstract. To explore the interactions between chole‐cystokinin (CCK) and the cholinergic system, we compared the effect of cholinergic or peptidergic CCK blockade on gallbladder contraction and pancreatic enzyme secretion using atropine and loxiglumide (a specific CCK antagonist) as pharmacological tools. Gallbladder contraction was measured by sonography and pancreatic secretion by a marker perfusion and aspiration technique. Graded doses of exogenous CCK8 induced dose‐dependent contractions of the gallbladder and increasing enzyme outputs. Loxiglumide (10 mg kg‐1 h‐1) abolished the gallbladder response and prevented an increase in pancreatic enzyme secretion to CCK8. Atropine (5 μg kg‐1 h‐1), however, only reduced gallbladder contraction and enzyme output to CCK8.

Gallbladder volumes decreased maximally to 12±4% after oral food, whereas enzyme output and plasma CCK levels increased 6‐ to 8‐fold. Loxiglumide completely abolished gallbladder contraction and inhibited enzyme secretion by 30%. Atropine caused a small reduction in gallbladder volumes, but essentially blocked postprandial enzyme secretion.

The results indicate that CCK is the major regulator of gallbladder contraction with the cholinergic system modulating the response, while the exocrine pancreas is crucially dependent on a cholinergic background with CCK modulating the secretory response.
The human renal 25‐hydroxyvitamin D3‐1α‐hydroxylase: properties studied by isotope‐dilution mass spectrometry
Authors: HAGENFELDT Y. , BERLIN T.
Published: March 2008

Abstract. The renal 25‐hydroxyvitamin D3‐α‐hy‐droxylase activity has been measured in normal human kidney cortex, using a highly specific assay based on isotope‐dilution mass spectrometry. The cortex was obtained from kidneys removed due to renal tumours.

The subcellular distribution of 25‐hydroxyvitamin D3‐1α‐hydroxylase activity was studied. Enzyme activity was only observed in the mitochondrial fraction. Mitochondria from non‐tumourous kidney cortex had a Vmaxof 0.17 ±0.02 pmol min‐1 mg‐1 protein and the apparent Km was in the range 14 μmol l‐1.

There was a tendency to a higher 25‐hydroxyvitamin D3‐1α‐hydroxylase activity in preparations from male kidney (0.21±0.03 pmol min‐1 mg‐1 protein) than female (0.12±0.02, P<0.05).

A significant inverse correlation between serum phosphate and 25‐hydroxyvitamin D3‐1α‐hydroxylase activity was found. No correlation was observed between enzyme activity and serum levels of 1,25‐dihydroxyvitamin D (total and free index), PTH, total calcium or ionized calcium.

The results indicate that there is a sex difference in human 25‐hydroxyvitamin D3‐1α‐hydroxylase activity similar to the one observed in laboratory animals. Furthermore, the data support the hypothesis that serum phosphate is a major regulator of 1,25‐dihy‐droxyvitamin D3 production in man.
Identification in human urine of a natural growth inhibitor for cells derived from solid paediatric tumours
Authors: SCHWEIGERER L. , CHRISTELEIT K. , FLEISCHMANN G. , ADLERCREUTZ H. , WÄhÄlÄ K. , HASE T. , SCHWAB M. , LUDWIG R. , FOTSIS T.
Published: March 2008

Abstract. Partially purified urine of healthy human subjects contains several fractions able to inhibit the proliferation of cultured human neuroblastoma cells. One of the most active fractions was further analysed by gas chromatography‐mass spectrometry and shown to contain genistein, a substance formed in the human body from precursors obtained by diet. Synthetic genistein was able to inhibit the proliferation of human neuroblastoma cells with a half‐maximal effect at 5–10 μmol 1‐1 concentrations. Genistein displayed similar potencies in inhibiting the proliferation of cells derived from various other solid pediatric tumours. Our results suggest that genistein is a natural antineo‐plastic agent present in diet and that it could be useful for the therapy of paediatric tumours.
Effects of interferon alpha on insulin binding and glucose transport in human adipocytes
Authors: KOLACZYNSKI J. W. , TASKINEN M.‐R. , HILDEN H. , KIVILUOTO T. , CANTELL K. , KOIVISTO V. A.
Published: March 2008

Abstract. We have previously demonstrated that interferon administration impairs glucose tolerance and causes insulin resistance in healthy man. Whether this is a direct effect of interferon is not known. The present study was undertaken to examine directly the effect of interferon alpha on insulin binding and action on glucose transport in isolated human adipocytes. Different concentrations of interferon alpha (range 10‐3‐105 IU ml‐1) and different incubation times (0–5–24 h) with interferon were employed. Acute and 5‐h and 24‐h exposure of human adipocytes to 10‐2‐10 IU ml‐1 of interferon increased the high affinity binding of 125I‐insulin (P< 0.05). In contrast, human interferon alpha had no effect on insulin binding in rat adipocytes. In short‐term studies interferon had no effect on 14C‐glucose transport clearance. 24‐h preincubation of human adipocytes with 10‐2, 10, 104 IU ml‐1 interferon increased maximally‐insulin stimulated 14C‐glucose transport clearance (P<0.05) and glucose transport responsiveness to insulin was enhanced by 24% (P<0.05) in cells exposed to 10‐2 IU ml‐1 interferon. After 5 and 24‐h preincubations with interferon we observed modest changes in glucose transport sensitivity to moderate concentrations of insulin (50–100 pM) with upregulation in the presence of 10‐2— 10 IU ml‐1 interferon and downregulation in the presence of 104‐105 IUm ml‐1 interferon (P<0.05). The insulin sensitivity index (ED50) did not change. These results indicate that human interferon alpha at low (10‐2‐10 IU ml‐1) concentrations: (a) increases the high affinity binding of insulin to adipocytes; (b) this phenomenon is species specific, (c) after prolonged preincubations, interferon alpha may also modulate, in a complex way, the sensitivity and responsiveness of glucose transport system to insulin.
Connective tissue response to major surgery and postoperative infection
Authors: HAUKIPURO K. , MELKKO J. , RISTELI L. , KAIRALUOMA M. I. , RISTELI J.
Published: March 2008

Abstract. Type I and type III collagen are components of a healing wound, and major structural proteins. According to our previous study, wound fluid concentrations of the liberated propeptide extensions of procollagens can be used to monitor collagen synthesis in the wound. Serum concentrations of the carboxy‐terminal propeptide of type I procollagen (PICP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied here for up to half a year in 102 patients, admitted for major abdominal surgery. In a frequent follow‐up (n= 9), one minimum and two maxima were found for S‐PICP, occurring 1 day, 7 days, and 2 months after surgery, respectively. S‐PIIINP had a minimum at 1 day and a peak at 10 days. Relative changes (follow‐up result/pre‐operative concentration) of the propeptides in 50 uncomplicated patients were compared. The 1‐day minimum of S‐PICP was 0.60 (SD 0.18), and that of S‐PIIINP 0.89 (0.27), (P<0.0001, 95% CI for the mean difference 0.21 to 0.36). The 7‐day peak of S‐PICP was 1.4 (0.5), and that of S‐PIIINP 2.5 (1.2), (P< 0.0001, CI 0.81 to 1.42). The 2‐month‐peak of S‐PICP was 1.6 (0.3), and at the same time the relative S‐PIIINP was still 1.7 (0.3) without any separate peak. Major infectious (n= 8) and other (12) complications, exploratory procedures (22) and patients with abnormal pre‐operative propeptide levels (8) were studied separately. Two early deaths were excluded. Only major infection had a remarkable effect on the responses of S‐PICP (3/8) and S‐PIIINP (5/8). The results demonstrate the ability of extracellular matrix to adjust its turnover in response to major trauma and infection.
Cellular energetics in hypothyroid muscle
Authors: TAYLOR D. J. , RAJAGOPALAN B. , RADDA G. K.
Published: March 2008

Abstract. Skeletal muscle of seven hypothyroid patients was investigated in the resting state and during exercise and recovery using 31P magnetic resonance spectroscopy. The bioenergetics and intracellular pH of the hypothyroid muscle were thus evaluated and compared with results from normal muscle and muscle of patients with mitochondrial myopathy. In resting hypothyroid muscle there were significant elevations in the concentration ratios of phosphocreatine/ATP and inorganic phosphate/ATP, while phosphocreatine/inorganic phosphate and intracellular pH were lower than normal. In exercising hypothyroid muscle, energy stores were depleted more rapidly and acidification began later than in normal muscle. Recovery of phosphocreatine to the pre‐exercise value was normal, but intracellular pH recovered slowly. The data suggest that in the hypothyroid state, glycogen breakdown in skeletal muscle was delayed thereby limiting the substrate supply for both glycolytic and oxidative production of ATP at the beginning of exercise. There was no evidence for a decrease in the oxidative capacity of the muscle of our patients, but elevated ADP may have stimulated oxidative metabolism and helped to compensate for low mitochondrial content. The low intracellular pH in resting muscle and the slow pH recovery after exercise imply that proton handling was abnormal in the hypothyroid muscle.
Bone mass of spine and forearm in osteoporosis and in German normals: influences of sex, age and anthropometric parameters
Authors: WÜSTER C. , DUCKECK G. , UGUREL A. , LOJEN M. , MINNE H. W. , ZIEGLER R.
Published: March 2008

Abstract. We measured forearm bone mineral density (BMD) using single photon absorptiometry (SPA) and bone mineral content (BMC) and BMD of lumbar spine by dual photon absorptiometry (DPA). The population consisted of 463 bone healthy subjects, 346 females and 117 males aged 20–85 years. Any underlying bone disease or other diseases known to affect bone mass were excluded by physical examination, thoracic and lumbar radiographs and laboratory screening. Patients with osteoarthritis of lumbar spine were excluded as well as patients taking drugs known to affect bone mass. All bone mass values declined with age. Body height also declined with age by 1.2 cm and 1.8 cm per 10 years (— 0.7% and — 1 %) in females and males respectively. Main effects of age, body height, ‐surface, ‐weight and ‐mass index on bone mass were calculated using multiple regression models. In males and females lumbar BMC measured in gHA depended primarily on body height and secondarily on age. Spinal BMD as measured in g cm‐2 was primarily dependent on age and then on height. In females forearm BMD depended primarily on age and then on body surface, in males on body surface only.

Using receiver operating characteristic (ROC) analysis the ROC area increased from 0.81–0.85 (n.s.) including body height into spinal BMD values leading to a higher sensitivity of measurements of spinal bone mass in recognizing 58 patients with spinal postmeno‐pausal osteoporosis. Including body surface into forearm BMD measurements ROC area increased from 0.66–0.69 (P=0.055).

We conclude from these data that measurements of bone mass not only depend on age and sex, but on body height and surface. These anthropometric parameters and their changes over decades have to be taken into account when examining any effects on bone mass in cross‐sectional studies. Including these parameters into bone mass values may lead to higher sensitivity of the method.
Influence of clinical findings, positional manoeuvres, and systolic ankle arterial pressure on transcutaneous oxygen tension in peripheral arterial occlusive disease
Authors: SCHEFFLER A. , EGGERT S. , RIEGER H.
Published: March 2008

Abstract. The mutual effects of systolic ankle arterial pressures, positional manoeuvres, and calf artery occlusions on transcutaneous oxygen partial pressures (tcpO2) were studied in 388 legs of 258 patients with peripheral arterial occlusive disease (PAOD). The tcpO2‐vs‐perfusion pressure relationship could be satisfactorily fitted by a non‐linear regression model deduced from the tcpO2 theory. Flow‐insensitive ranges of tcpO2‐vs‐flow hyperbolas were reduced by both leg lowering and moving the electrode towards proximal measuring sites. Lower tcpO2 values were found in case of occluded compared to patent calf arteries at ankle arterial pressure indices below 0.4. The tcpO2 positional variability increased with worsening hemodynamic compensation and was most pronounced in critical limb ischaemia (ischaemic rest pain, non‐healing ulcerations). According to a retrospective analysis, a critical ischaemia could be assumed if supine and sitting tcpO2‐values exceed neither 10 nor 45 mmHg, respectively.
Antibodies to Cathepsin G in Crohn's disease
Authors: MAYET W. J. , HERMANN E. , FINSTERWALDER J. , RIEDER H. , PORALLA T. , MEYER K. H. , BÜSCHENFELDE ZUM
Published: March 2008

Abstract. Antibodies directed against antigens in human neutrophils have proved to be of great diagnostic value in certain systemic vasculitides. Recent reports have focused the attention on these antigens as targets of antibodies in sera of patients with inflammatory bowel disease. We investigated the sera drawn from 60 patients suffering from biopsy proven Crohn's disease and 15 patients with active ulcerative colitis. Using sensitive enzyme‐linked immunosorbent assays with purified antigens and Western blotting the following antibodies could be demonstrated: cathepsin G (cat‐G) antibodies IgG 38.3%, IgM 13.3%, IgA 23.3% and antibodies against human leucocyte elastase (HLE) IgG, IgA, IgM 3.3%. Low but significant correlations could be found for cat‐G antibodies (IgG) and the van HEES index of activity. 73.9% of the cat‐G (IgG) positive patients had colon involvement. In the sera of patients with ulcerative colitis no antibodies to cat‐G or HLE were detectable. Only 8.3% of the patients with Crohn's disease had antibodies against proteinase 3 (C‐ANCA). Our data indicate that cat‐G among other myeloid lysosomal enzymes seems to be an important target antigen of antibodies in sera of patients with Crohn's disease. Cat‐G antibodies might be helpful to distinguish Crohn's disease from ulcerative colitis.
Inheritance of monoclonal rheumatoid factor cross‐reactive idiotypes in primary Sjogren's syndrome (pSS). Comparative studies of a rabbit polyclonal anti‐idiotype and 17109 monoclonal anti‐idiotype
Authors: TZIOUFAS A. G. , BOUMBA D. S. , SKOPOULI F. N. , CARSON D. A. , MOUTSOPOULOS H. M.
Published: March 2008

Abstract. A comparison of the presence of two idiotypes, one identified by a rabbit polyclonal anti‐idiotypic antibody, first found on a cryoprecipitable IgM.± rheumatoid factor (RF) from an SS patient (3rd SS) and the 17109 idiotype, identified by a monoclonal antibody was performed in 106 sera and eight minor salivary gland biopsies of Sjögren's syndrome (SS) patients and 125 sera from age‐sex matched normal controls. Of 106 of SS patients' sera 36 had immuno‐globulins positive for the 3rd SS idiotype. 17109 activity was more prevalent in SS patients positive for the polyclonal anti‐idiotype 3rd SS, than those with negative idiotype (9/36 VS 2/70 times2= 12.53 P <0.005). Cross inhibition studies, however, revealed that the polyclonal anti‐idiotype binding was not inhibited by the 17109 moAb. 3rd SS and 17109 anti‐idiotypes were reacted with immunoglobulins in the serum of 3–5% and 1.7% of normal human sera respectively. Immu‐nohistologic studies demonstrated that 4/8 and 2/6 minor salivary gland biopsies had infiltrating plasma cells containing immunoglobulins bearing the 3rd SS and the 17109 idiotypes, respectively. The inheritance of both idiotypes was investigated in sera of 4 SS kindreds. In two kindreds with 3rd SS positive pro‐bands, the idiotype was detected in 3 first degree relatives of the same generation. 17109 activity was detected in the serum of a sister of the positive proband who had a high RF titer. These results suggest that the 17109 moAb recognizes a different epitope of that of the 3rd SS. The idiotypes of monoclonal RFs are not inherited and probably are produced by plasma cells infiltrating the labial minor salivary glands of SS patients.
Patients with anticardiolipin antibodies with and without antiphospholipid syndrome: their clinical features and β2‐glycoprotein‐l plasma levels
Authors: VLACHOYIANNOPOULOS P. G. , KRILIS S. A. , HUNT J. E. , MANOUSSAKIS M. N. , MOUTSOPOULOS H. M.
Published: March 2008

Abstract. The clinical and serological features of 38 aCL‐positive patients were compared to those of 45 aCL‐negative patients. A significantly higher incidence of thrombophlebitis and livedo reticularis was found in aCL‐positive patients. There were 13 aCL positive patients with thrombophlebitis and/or arterial thromboses and these 13 patients were designated as having the antiphospholipid syndrome (APS) while the remaining 70 patients were diagnosed as having Systemic Lupus Erythematosus (SLE). APS patients also had a high incidence of arterial occlusions, recurrent abortions and strokes compared to SLE patients. Patients with high levels of IgG‐aCL were more likely to have APS, while patients with low levels of IgG‐aCL or IgM‐aCL only were more likely to have SLE without the clinical features of APS. Since aCL antibodies have recently been shown to interact with a phospholipid‐binding plasma proteinβ2‐glycoprotein‐I (β2‐GPI), we measured the β2‐GPI levels in these patients and found thatβ2‐GPI levels are significantly higher in APS compared to SLE patients negative for aCL antibodies. Sinceβ2‐GPI is known to exert multiple effects on coagulation processes the interaction of aCL antibodies with this glycoprotein may play a pathogenic role in APS.