bluuebunny/crossref_metadata_2025 huggingface dataset:
Are leucocyte‐derived free radicals involved in ischaemia in human legs?
Authors: CIUFFETTI G. , MERCURI M. , MANNARINO E. , LOMBARDINI R. , PASQUALINI L. , OTT C. , LUPATTELLI G.
Published: March 2008

Abstract. Leucocyte‐derived free radicals were monitored in 30 stage II peripheral vascular disease (PVD) patients in an open placebo‐controlled study. Linked to a transcutaneous oxygen pressure (TcPo2) monitor, they performed two consecutive standard treadmill tests (5 min, 2 km h–1 12% slope) before and after 15‐days treatment with placebo or a leucocyte‐derived free radical scavenger (Piroxicam, 20 mg day–1), the second test being carried out at the TcPo2 half‐recovery time. Blood samples were collected at baseline, at the maximum walking times and the TcPo2 half recovery times. The total and differential leucocyte counts, the percentage of cells with pseudopodia or cytoplasmatic irregularities, the filterability rates (using a positive pressure Nuclepore filter system) of the main leucocyte subfractions and plasma oxidant activity were monitored. Compared with values before treatment and with the placebo‐treated group Piroxicam therapy significantly (P < 0.001) reduced the final half‐recovery time, the percentage of cells with pseudopodia and the level of plasma oxidant activity (P < 0.01) and kept the granulocyte filterability rate stable, showing leucocyte‐derived free radicals are involved in peripheral ischaemia.
Plasma concentrations of apolipoprotein A‐I containing particles in normolipidaemic young men
Authors: LUC G. , PARRA H.‐J. , ZYLBERBERG G. , FRUCHART J.‐C. , SERLIA  , INSERM
Published: March 2008

Abstract. Low levels of plasma high‐density lipoprotein (HDL)‐cholesterol and apolipoprotein (apo)‐A‐I are associated with premature coronary heart disease. However, particles in the density range of HDL are heterogeneous. Two main types of apo A‐I‐containing particles can be identified, one species containing both apo A‐I and apo A‐II (Lp A‐I: A‐II) and the other apo A‐I but no apo‐A‐II (Lp A‐I). This study was designed to measure HDL cholesterol, apo A‐I, and, using a new procedure, Lp A‐I in 233 healthy normolipidaemic young men (cholesterol < 250 mg dl–1 and triglycerides < 200 mg dl–1). Among these subjects, the composition of HDL was very variable as indicated by the 10th and the 90th percentiles of the HDL‐cholesterol/apo A‐I ratios which were 0.32 and 0.49, respectively. The 10th and 90th percentiles of apo A‐I and Lp A‐I: A‐II were 126 and 167 mg dl –1 and 83 and 116 mg dl–1, respectively. On the other hand, Lp A‐I showed a much larger variation, the 10th and 90th percentiles being at 33 and 62 mg dl–1, respectively. The distribution of individual values of Lp A‐I showed that this fraction of apo A‐I‐containing particles was very variable among subjects, the Lp A‐I/apo A‐I ratio extending from 0.18 to 0.58. Triglycerides, Lp A‐I and Lp A‐I:A‐II were correlated with HDL cholesterol, but no correlation between apo A‐I containing sub‐fractions and plasma triglycerides was noticed. Since preliminary results from angiographic and clinical studies show that Lp A‐I could exert a protective role for atherosclerosis, it would seem that the measurement of Lp A‐I might help in the future to characterize better the individual's risk for atherosclerosis.
Chloride‐depletion metabolic alkalosis induces ECF volume depletion via internal fluid shifts in nephrectomized dogs
Authors: GARELLA S. , COHEN J.J. , NORTHRUP T.E.
Published: March 2008

Abstract. We recently reported that chloride‐depletion metabolic alkalosis (CDMA) results in renal losses of Na, K, and water. In these studies we investigated whether CDMA (induced using a new model that avoids external changes in Na and water balance) was also associated with internal Na and water shifts out of the ECF. CDMA was induced using haemofiltration in functionally nephrectomized dogs. Plasma ultrafiltrate was substituted quantitatively with a solution duplicating each dog's plasma electrolyte composition in control animals, and with a solution containing HCO3 as the sole anion in CDMA animals. ECF volume was estimated as the space of distribution of [3H]‐mannitol. Plasma composition and [3H]‐mannitol distribution space were unchanged in control dogs. In CDMA dogs metabolic alkalosis developed; despite the absence of external changes in Na and water balance, the space of distribution of [3H]‐mannitol decreased by 335 ± 46 ml (equivalent to 8% of baseline ECF volume), calculated chloride space fell by 304 ± 50 ml, and haematocrit increased from 45.6 to 48.5 vol%. We conclude that CDMA causes an internal shift of fluid out of the ECF. The resulting ECF volume contraction appears to be an inherent feature of CDMA.
Serum hyaluronate and type III procollagen aminoterminal propeptide concentration in chronic liver disease. Relationship to cirrhosis and disease activity
Authors: RAMADORI G. , ZÖHRENS G. , MANNS M. , RIEDER H. , DIENES H.P. , HESS G. , ZUM BÜSCHENFELDE K.‐H.MEYER
Published: March 2008

Abstract. To analyse the relationship between the presence of liver cirrhosis and hepatic inflammation and the serum concentrations of the aminoterminal propeptide of procollagen type III (P‐III‐NP) and of hyaluronic acid (HA) in chronic liver disease, we measured P‐III‐NP and HA concentrations in paired serum samples from 133 patients with various chronic liver diseases, from 22 patients with acute hepatitis and from 50 healthy age‐matched controls. In 24 (of the 133) patients with autoimmune chronic liver disease, follow‐up determination was performed during therapeutic treatment with immunosuppressive drugs. Compared with controls P‐III‐NP concentrations (medians) were significantly elevated in 65% of patients with chronic active hepatitis (P=0.00097) and in 79% of patients with active liver cirrhosis (P=0.0126) but not in patients with chronic persistent hepatitis (P= 0.06). Serum concentrations (medians) of HA were increased (P= 0.0058) in 32% of patients with chronic active hepatitis and in 91% of patients with active cirrhosis (P < 6.10‐7). The difference of HA serum concentrations but not that of P‐III‐NP serum concentrations in patients with chronic active hepatitis and in patients with active cirrhosis was statistically significant. HA and P‐III‐NP serum concentrations were significantly elevated in 22 patients with acute hepatitis. Serum concentrations of P‐III‐NP in patients with autoimmune chronic liver disease significantly decreased during immunosuppressive therapy in patients with autoimmune chronic active hepatitis (P= 0.0001) and in patients with autoimmune active cirrhosis (P= 0.0039); HA serum concentration decreased to normal level in patients with autoimmune chronic active hepatitis (P= 0.0017); in contrast, when cirrhosis was present, serum HA levels decreased but remained elevated (P= 0.129).

It is concluded that determination of HA serum concentrations will help to differentiate chronic active hepatitis from active cirrhosis. While elevated P‐III‐NP serum concentrations mainly correlate with inflammatory activity, elevated HA serum concentrations seem to be an expression of mainly the reduced functional (clearance function) capacity of the liver in chronic liver diseases. Therefore determination of HA serum concentration is of greater diagnostic value, especially when inflammatory activity is low.
Arterial wall hypoxia following thrombosis of the vasa vasorum is an initial lesion in atherosclerosis
Authors: MARTIN J.F. , BOOTH R.F.G. , MONCADA S.
Published: March 2008

Abstract. Pressure on the outside of arteries can cause physical and biochemical changes in the vessel wall of rabbits which are characteristic of atherosclerosis. It is hypothesized that occlusion of the vasa vasorum causes ischaemia of the arterial media which results in smooth muscle cell proliferation and cellular accumulation of cholesteryl esters. Hypoxia increases mRNA for platelet‐derived growth factor in arterial wall cells and increases the activity of acyl Co A: cholesterol acyltransferase (ACAT). Such a mechanism may explain many of the anatomical, actuarial and environmental risk factors for atherosclerosis. Hypoperfusion may follow thrombosis of the vasa vasorum.
Insulin time‐dependent effects on the leg exchange of glucose and amino acids in man
Authors: LUNDGREN F. , EDÉN E. , ARFVIDSSON B. , LUNDHOLM K.
Published: March 2008

Abstract. Time‐dependent effects of insulin on the leg exchange of glucose, lactate, glycerol, free fatty acids (FFA) and amino acids were measured in relation to oxygen uptake (leg and whole body) and whole body glucose assimilation including oxidation. Seven healthy males (58 ± 3 years of age) were investigated before operation of uncomplicated inguinal hernia or varicose veins. Euglycaemic glucose clamp investigations with systemic hyperinsulinaemia between 100–120 mU 1‐1 were used. Metabolic measurements were performed before and during hyperinsulinaemia at 2 and 6 h following the start of glucose clamp to evaluate the time‐dependency of insulin actions.

Whole body glucose uptake increased continuously for up to 6 h (from 4·7 ± 0·7 to 8·0 ± 0·8 mg/kg/min, P<0·01) despite stable plasma concentrations of glucose and insulin. This was also true for glucose oxidation. Whole body oxygen uptake did not change significantly during the clamp while the leg exchange of oxygen uptake did (from 5·9 ± 0·86 μmol/100 g/min to 11·6 ± 2·4, P<0·01). Insulin effect on leg blood flow was time‐dependent and increased two‐fold (2·3 ± 0·4 ml/100 g/min to 4·4 ± 0·9, P<0·001) during clamp. The leg production of lactate increased continuously, accounting for approximately 15% of the glucose uptake across the leg, but the rise in arterial lactate did not reach the level of statistical significance. Plasma FFA concentrations decreased in a time‐dependent manner during clamp, while the leg exchange of FFA switched rapidly to a stable net uptake. Arterial concentrations of amino acids declined with time. The leg release of the sum of all amino acids decreased also in a time‐dependent manner and then switched to a net uptake, mainly depending on an increasing uptake of leucine, valine and methionine. The release of phenylalanine and tyrosine, which are not metabolized in peripheral tissues, were not significantly influenced by prolonged hyperinsulinaemia.

The results demonstrate that the euglycaemic glucose clamp procedure is not associated with steady‐state metabolism for glucose assimilation, oxygen uptake, lactate formation and amino acid exchange either measured across the whole body or peripheral tissues. The results also support a recent finding in our laboratory that insulin in itself does not inhibit net degradation in human peripheral tissues including the leg skeletal muscles.
The effects of low dose insulin infusions on the renin angiotensin and sympathetic nervous systems in normal man
Authors: ROONEY D. P. , EDGAR J. D. M. , SHERIDAN B. , ATKINSON A. B. , BELL P. M.
Published: March 2008

Abstract. To examine the effects of physiological insulin concentrations on the renin‐angiotensin and sympathetic nervous systems, healthy volunteers were studied by the euglycaemic glucose clamp technique with sequential 60 min 0·5 and 1·0 mU kg‐1min‐1 insulin infusions and, subsequently, by a control infusion simulating clamp conditions. Plasma renin activity increased from 0·8 ± 0·1 ng ml‐1h‐1 basally to 1·0 ± 0·2 ng ml‐1h‐1 during the 0·5 mU infusion to 1·4 ± 0·1 ng ml‐1h‐1 during the 1 mU infusion but did not change during control infusion (0·9 ± 0·3 ng ml‐1h‐1 to 0·9 ± 0·2 ng ml‐1h‐1 to 1·0 ± 0·1 ng ml‐1h‐l) (P<0·001 insulin vs. control by ANOVAR). Plasma angiotensin II increased during insulin (21·2 ± 1·8 to 25·2 ± 2·3 to 29·3 ± 2·4 pg ml‐1) but not during control infusion (24·0 ± 2·8 to 23·6 ± 2·6 to 23·5 ± 2·5 pg ml‐1) (P<0·001 insulin vs. control). Serum aldosterone did not change significantly during either infusion (insulin: 239 ± 89 pmol 1‐1 to 237 ± 50 pmol 1‐1 to 231 ± 97 pmol 1‐1, control: 222 ± 79 to 237 ± 50 to 213 ± 97 pmol 1‐1). Plasma noradrenaline increased to a greater extent during insulin (1·03 ± 0·2 to 1·14 ± 0·8 to 1·27 ± 0·17 nmol 1‐1) than control infusion (0·86 ± 0·09 to 0·97 ± 0·09 to 0·99 ± 0·09 nmol 1‐1 (P<0·01 insulin vs. control). Changes in mean systolic blood pressure during insulin infusion were significantly different from control (+3 vs.‐4 mmHg, P<0·001). In conclusion acute hyperinsulinaemia within the physiological range increases circulating hormones of the renin‐angiotensin and sympathetic nervous sytems and also increases systolic blood pressure.
Assessment of iron availability using stable54Fe
Authors: KALTWASSER J. P. , HANSEN Ch. , OEBIKE Y. , WERNER E.
Published: March 2008

Abstract.This paper describes a method of quantitatively assaying the bioavailability of orally administered iron in order to promote haemoglobin synthesis in iron deficiency anaemia. The non‐radioactive tracer substance54Fe was employed. An experimental iron deficiency model was tested in 18 healthy male volunteers. The trial design made it possible to assess intestinal absorption and efficacy of iron substitution. The iron deficiency was experimentally induced by weekly phlebotomy. Two commercially available iron preparations with different rates of iron release were investigated at a dosage of 150 and 160 mg Fe2+daily, respectively. In the first seven days of treatment, both preparations were administered in54Fe‐labelled form. Afterwards, iron substitution was given with the commercially available preparations. Measurements were made of erythrocyte utilization of54Fe and plasma iron tolerance curves at the beginning of the periods in which the54Fe‐labelled product and the commercially available preparation were administered, and of haemoglobin and serum ferritin concentration curves over three months. The mean utilization of the iron administered was virtually identical for the two preparations (23 and 22%, respectively). Likewise, there was no difference with respect to the average daily increase in haemoglobin concentration in the blood (1.5 g 1‐1). There was also no significant difference with respect to serum ferritin concentration curves. In contrast, the two preparations differed markedly with respect to the plasma iron tolerance curves. This suggests that evaluation of plasma iron tolerance curves alone is not suitable for comparative assessment of the therapeutic value of orally administered iron preparations.
Platelet response to the aggregatory effect of platelet activating factor (PAF) ex vivo in patients with acute myocardial infarction
Authors: TSELEPIS A. D. , TSOUKATOS D. , DROUDES C. , DONAS A. , EVANGELOU A.
Published: March 2008

Abstract. Platelets from patients with acute myocardial infarction exhibit an increased sensitivity to the aggregatory effect of PAF, in vitro, the first 48 h after the onset of the symptoms. This sensitivity, expressed as PAF EC50 values, seems to be transient after the 2 day period. Also, a remarkable decreased sensitivity to the inhibitory effect of PGI2 against the aggregation induced by PAF appears to the platelets of those patients the first hours after the onset of the symptoms, and persists for at least 14 days. Treatment of patients by drugs with a known inhibitory effect on platelet aggregation in vivo and in vitro (aspirin, nifedipine, indomethacin), does not influence the increase in platelet sensitivity to PAF, but inhibits the secondary aggregation induced by the released aggregating factors from the PAF activated platelets. The increase in platelet sensitivity to PAF is not unique to the AMI since it is also observed in patients with acute bacterial pneumonia. However, we cannot support the theory that it is a general phenomenon of acute tissue injury since it is general phenomenon of acute tissue injury since it is not observed in patients with acute muscular injury.
Serum neurone specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction
Authors: CUNNINGHAM R. T. , YOUNG I. S. , WINDER J. , O'KANE M. J. , McKINSTRY S. , JOHNSTON C. F. , DOLAN O. M. , HAWKINS S. A. , BUCHANAN K. D.
Published: March 2008

Abstract. A radioimmunoassay has been developed and used to measure serum neurone specific enolase (NSE) concentrations in 24 patients, following cerebral infarction. A significant correlation between cerebral infarct volume and maximum serum NSE concentration was observed (P= 0·047). Serum NSE was also assayed at times 24, 48, 72 and 96 h post ictus. At 72 h a significant correlation existed between serum NSE levels and infarct volume (P= 0·012), and levels appeared to be approaching statistical significance at 48 h (P=0·067). No correlation existed at 24 and 96 h. In addition serum concentrations of NSE were compared to clinical outcome as determined by the Glasgow Outcome Score. Using the Mann‐Whitney U test, there was no significant difference in maximum NSE level between patients graded 1–3 on the Glasgow Outcome Score and those graded 4 and 5. However, further studies are required on a larger population to more completely assess this. NSE may prove to be a useful marker of neuronal damage in the study of stroke, with particular application in the assessment of treatment.
Adrenergic regulation of lipolysis in human fat cells during exercise
Authors: WAHRENBERG H. , BOLINDER J. , ARNER P.
Published: March 2008

Abstract. The adrenergic regulation of lipolysis was studied, before and after 30 min of submaximal exercise, in isolated adipocytes removed from the abdominal and gluteal regions of healthy non‐obese men and women. Noradrenaline‐induced lipolysis was significantly enhanced in gluteal adipocytes from men but not in women after exercise. However, the pure beta‐adrenergic responsiveness was equally increased in gluteal adipocytes of both sexes after exercise, as judged by the effect of isoprenaline. Furthermore, the alpha2‐adrenergic anti‐lipolytic responsiveness was more apparent after exercise in females than in males thereby counter‐balancing the increase in the beta‐adrenergic effect in the gluteal region in the former. The increased beta‐adrenergic responsiveness induced by exercise in gluteal adipocytes of males could be mimicked by agents acting at the levels of adenylate cyclase, coupling proteins, phosphodiesterase, and protein kinase and seems to be due to an adaptive enhancement at the hormone‐sensitive‐lipase level. There was no change in the stoichiometric properties of beta‐adrenoceptors of gluteal adipocytes after exercise. Abdominal adipocytes of both sexes were four to five times more responsive to noradrenaline than gluteal ones. However, exercise induced no further enhancement of the catecholamine‐stimulated lipolysis rate in fat cells from this site.

Thus, the influence of exercise on catecholamine‐stimulated lipolysis is regional and sex dependent. Men, but not women, have a greater ability to adapt lipolysis to increasing energy demands during exercise that are due to an acute increase in the effectiveness of the hormone‐sensitive lipase complex. This effect was observed only in the gluteal region, whereas lipolysis in the abdominal region did not adapt to exercise. Women, in general, were more responsive than males to catecholamines in the abdominal region.
Response of sympathetic nervous system activity to exercise in patients with congestive heart failure
Authors: KINUGAWA T. , OGINO K. , KITAMURA H. , MIYAKODA H. , SAITOH M. , HASEGAWA J. , KOTAKE H. , MASHIBA H.
Published: March 2008

Abstract. To investigate the serial sympathetic nervous system response to exercise, plasma norepinephrine (NE) and epinephrine (E) concentrations were measured at rest, during each stage of treadmill exercise, and immediately and 5 minutes after exercise in 68 congestive heart failure (CHF) patients (NYHA functional class I 24, II 25, III 19) and 30 normal subjects. Circulatory responses of NYHA class II patients increased at early stages of exercise. Systolic blood pressure and double product at peak exercise were significantly lower in NYHA class III patients. Plasma NE response of NYHA class I patients was similar to that of normal subjects. However, plasma NE at rest, and during and after exercise were significantly higher in NYHA classes II and III patients than in normal subjects and NYHA class I patients (peak NE (pg ml‐1); Normals: 547±37, I: 535±53, II: 867±87, III: 1033±157). There was no significant difference in plasma E levels among the four groups. NE response to exercise was augmented according to the severity of heart failure, which suggested compensatory activation of sympathetic nervous system activity. Circulatory responses were reduced in NYHA class III patients despite the exaggerated compensatory activation of the sympathetic nervous system. Blunted circulatory responses to increased NE concentration in NYHA class III patients might relate to a decreased cardiac responsiveness to sympathetic activity in severe CHF patients.
Expression of transferrin receptors by monocytes and peritoneal macrophages from renal failure patients treated by continuous ambulatory peritoneal dialysis (CAPD)
Authors: MOUGHAL† N. A. , McGREGOR S. J. , BROCK J. H. , BRIGGS J. D. , JUNOR B. J. R.
Published: March 2008

Abstract. Approximately 20% of monocytes and peritoneal macrophages from renal failure patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were transferrin‐receptor (TfR) positive by immunofluorescence, whereas cells from normal controls were generally TfR negative, as were monocytes from rheumatoid arthritis patients and from renal failure patients treated by haemodialysis. There was a significant correlation between the length of time on CAPD and the proportion of TfR‐positive blood monocytes. CAPD peritoneal macrophages possessed 6·7–37·1 × 103 transferrin binding sites per cell, with a Ka of 3–25 × 107 mol l‐1. In culture, monocytes from CAPD patients showed a progressive decrease in TfR expression, while in contrast about 20% of monocytes from normal controls which were originally 100% TfR negative expressed TfR after 3 days in culture. These findings indicate that regulation of Tf R in monocytes/macrophages is complex, and that frequent removal of peritoneal cells during dialysate exchange may place a strain on the bone marrow, resulting in the release of an increasingly immature population of TfR positive monocytes to the circulation in CAPD patients.
Desogestrel in hormone replacement therapy: long‐term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding
Authors: MARSLEW U. , RIIS B. J. , CHRISTIANSEN C.
Published: March 2008

Abstract. Seventy‐three healthy, postmenopausal women, aged 45–54 years, were randomly assigned to one of three groups for 2 years of treatment: 17β‐oestradiol 1·5 mg on days 1–12 and 17β‐oestradiol 1·5 mg+desogestrel 150 μg on days 13–24 (E2/DG) or oestradiol valerate 2 mg on days 1–11 and oestradiol valerate 2 mg+medroxyprogesterone acetate 10 mg on days 12–21 (E2V/MPA) or placebo. Fifty‐seven women (78%) completed the study.

Bone mineral content of the distal regions of the forearms (measured by single photon absorptiometry, SPA) and bone mineral density of the spine (measured by dual energy X‐ray absorptiometry, DXA) showed increases of 0·5‐1% and 4–5%, respectively, in the hormone groups over 2 years. The placebo group exhibited a decrease in spinal bone density of 2% per year, and in the forearm of 2·5‐3·5% per year. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium) decreased significantly to premenopausal levels in the hormone groups but remained unchanged in the placebo group.

In both hormone groups total cholesterol decreased by about 9% (P < 0·001), whereas low density lipoprotein cholesterol decreased by 16% in the E2/DG group and 20% in the E2V/MPA group (P < 0·001). High density lipoprotein cholesterol showed only minor, insignificant changes in the hormone groups. The placebo group had virtually unchanged values.

Climacteric symptoms, including hot flushes, were significantly reduced in both hormone groups. Bleeding occurred regularly in about 80% of the women.

We conclude that both combinations of oestrogen and progestogens effectively prevent postmenopausal bone loss and are appropriate alternatives in hormone replacement therapy.
Effects of muscarinic blockade on insulin secretion and on glucose‐induced thermogenesis in lean and obese human subjects
Authors: SCHNEEBERGER D. , TAPPY L. , TEMLER E. , JEQUIER E.
Published: March 2008

Abstract. To determine whether hyperinsulinaemia of human obesity is dependent on the activity of the parasympathetic nervous system, and whether activation of the parasympathetic nervous system plays a role in glucose‐induced thermogenesis, the metabolic effect of a continuous intravenous glucose infusion [44·4 μmol kg‐1 body weight (bw) min‐1] with or without atropine infusion was assessed in 11 obese patients and 10 lean controls.

Compared with lean controls, obese patients had increased basal and glucose‐stimulated plasma insulin and C‐peptide concentrations and increased plasma glucose concentrations during glucose infusion. Glucose oxidation during i.v. glucose was lower in obese patients than in lean controls. Glucose‐induced thermogenesis was similar in obese patients and in lean controls.

Atropine infusion did not affect basal plasma glucose, insulin or free fatty acid concentrations nor glucose‐stimulated plasma glucose, insulin, C‐peptide, glucagon or free fatty acid concentrations in both groups of subjects. Glucose and lipid oxidation rates and glucose‐induced thermogenesis were also unaffected by atropine administration.

It is concluded that (1) glucose‐stimulated hyperinsulinaemia in human obesity is not dependent on a hyperactivity of the parasympathetic nervous system, which indicates that human obesity is different from most animal models of obesity; (2) glucose‐induced thermogenesis is similar in obese and lean subjects when a similar load of glucose is administered; (3) inhibition of the parasympathetic nervous system does not affect the thermic effect of i.v. glucose.
Blockade of glucocorticoid receptors prevents the increase in urea synthesis after hysterectomy in rats
Authors: HEINDORFF H. , ALMDAL T. P. , VILSTRUP H.
Published: March 2008

Abstract. The postoperative increase in hepatic conversion of amino nitrogen to urea nitrogen seems to be a primary cause of post‐surgical catabolism. The importance of glucocorticosteroids for the spontaneous urea nitrogen synthesis rate (UNSR) and for the maximally amino acid‐stimulated capacity of urea nitrogen synthesis (CUNS) was investigated 3 and 24 h postoperatively, respectively, in hysterectomized rats.

Corticosteroid effects were neutralized by gluco‐corticoid receptor blockade by the pharmacological analogue RU486.

Hysterectomy doubled UNSR from 3·16 ± 0·20 to 6·12 ± 0·27 μmol (per min per 100 g body weight) after 3 h (P < 0·01) and increased CUNS by 40% from 7·47 ± 0·30 to 10·29 ± 0·41 μmol (per min per 100 g body weight) after 24 h (P < 0·01). These changes were both normalized by the receptor blockade. Hysterectomy decreased total blood α‐amino nitrogen concentration by 25% from 3·4 ± 0·2 to 2·6 ± 0·2 mmol l‐1 (P < 0·05) 3 h after surgery, which was normalized by glucocorticoid receptor blockade. Hysterectomized rats lost 10 ± 1 g the first 24 h after surgery. The blockade reduced the weight loss to 6 ± 1 g body weight (P < 0·05) without changing food intake.

The results indicate that glucocorticoid action plays a major role in the postoperative increase in hepatic amino nitrogen conversion.
Fish oil reduces ethanol‐induced damage of the duodenal mucosa in humans
Authors: SCHEPP W. , PESKAR B. M. , TRAUTMANN M. , STOLTE M. , HAGENMÜLLER F. , SCHUSDZIARRA V. , CLASSEN M.
Published: March 2008

Abstract. Eight healthy volunteers were studied before and after 3 weeks of dietary supplementation with fish oil (10.5 g day‐1, 18% (1.9 g) eicosapentaenoic acid). Duodenal mucosal lesions were induced by instillation of 40 ml ethanol (40%). Mean endoscopic lesion score was lower after fish oil treatment (1.62±0.32; mean±M) than before (3.25±0.31; P<0.01). Histologic lesion score fell from 22.75±1.98 before treatment to 13.50±1.51 after fish oil (P<0.01). Basal and pentagastrin‐stimulated gastric acid output remained unaffected. Release of prostaglandin E2, 6‐keto‐prostaglandin F1α, and thromboxane B2 from biopsy specimens of the duodenal mucosa in vitro was not significantly altered after fish oil ingestion. In the same in vitro system calcium ionophore A23187‐induced release of total leukotriene C (LTC) increased from 10.6±1.5 ng g‐1mucosa 20 min before treatment to 30.4±3.2 ng after fish oil. High pressure liquid chromatography analysis showed that this increase was partly due to formation of LTC5 as after fish oil 28% of total LTC were identified as LTC5 whereas 72% were LTC4. We conclude that in humans fish oil reduces ethanol‐induced damage of the duodenal mucosa without inhibiting gastric acid secretion or stimulating prostaglandin formation. It remains to be clarified if the changes in leukotriene formation are relevant for the mucosaprotective fish oil effect.
Hereditary hepatic porphyria due to homozygous δ‐aminolevulinic acid dehydratase deficiency: studies in lymphocytes and erythrocytes
Authors: SASSA S. , FUJITA H. , DOSS M. , HASSOUN A. , VERSTRAETEN L. , MERCELIS R. , KAPPAS A.
Published: March 2008

Abstract. Activities of δ‐aminolevulinic acid (ALA) dehydratase and porphobilinogen (PBG) deaminase, and haem content were determined in EB‐virus transformed lymphocytes from two patients with homozygous ALA dehydratase deficiency, and their family members to determine the expression of the specific gene defect in this cell type. ALA dehydratase activity, but not PBG deaminase activity or haem content, was markedly decreased in lymphocyte preparations from both patients with homozygous enzyme deficiency, and moderately decreased in subjects heterozygous for enzyme deficiency. Immunochemical quantitation of erythrocyte ALA dehydratase suggested the presence of a cross‐reactive material in a patient with a late‐onset of acute hepatic porphyria due to the homozygous enzyme deficiency.
Mechanisms of protein conservation during xylitol infusion after burn injury in rats: isotope kinetics and indirect calorimetry
Authors: GEORGIEFF M. , PSCHEIDL E. , MOLDAWER L. L. , BISTRIAN B. R. , BLACKBURN G. L.
Published: March 2008

Abstract. In order to study the mechanisms by which nutrients influence post‐trauma metabolism, Sprague‐Dawley rats received a 25% full‐thickness burn and were randomly assigned to receive 12.5 g kg‐1bodyweight (BW) per day amino acids (AA) only, AA and 14.7 g hydrous glucose kg‐1BW per day or AA and 14.7 g hydrous xylitol kg‐1BW per day. After 4 days of hypocaloric feeding, rats receiving xylitol had a cumulative nitrogen balance of ± 213 ± 82 mg N, which was significantly (P < 0.001) better compared with either the AA with only —493±61 mg N or the AA and glucose group (P < 0.01) with – 160±101 mg N. During glucose infusion reduction of insulin‐mediated fat oxidation was partially compensated by an increase in glucose oxidation. Xylitol infusions resulted in increased glucose oxidation compared with the amino acid only group without simultaneously reduced fat oxidation. Although glucose and xylitol are calorically similar, their protein sparing properties and metabolic action after injury cannot be based entirely upon their caloric equivalent.
Supplementation with n‐3 fatty acids reduces triglycerides but increases PAI‐1 in non‐insulin‐dependent diabetes mellitus
Authors: BOBERG M. , POLLARE T. , SIEGBAHN A. , VESSBY B.
Published: March 2008

Abstract. The effects of dietary supplementation with n‐3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non‐insulin‐dependent diabetic patients who were given 10 g of MaxEPA (3 g n‐3 fatty acids) or placebo (olive oil) per day in a randomized double‐blind cross‐over study during two consecutive 8‐week periods. The serum triglyceride (TG) concentrations decreased by 27% (P < 0.01) after addition of MaxEPA with a reduction of VLDL TG by 36% (P < 0.05) while LDL cholesterol increased by 6% (P= 0.05). The fasting blood sugar and HbA1c. concentrations increased significantly after addition of MaxEPA but the changes were not significantly different from those during the placebo period. The highest glucose concentrations at fasting and after an i.v. glucose injection were seen after MaxEPA while the serum insulin concentrations were unchanged. The peripheral insulin sensitivity, as measured by a euglycaemic, hyperinsulinaemic clamp technique, did not change during the study. The mean plasminogen inhibitor‐1 (PAI‐1) activity of the patients was elevated compared with healthy controls. In spite of the reduction of the triglyceride concentrations and unchanged insulin levels, there was a significant increase of the activity of PAI‐1 (+ 21%, P < 0.01) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity. In many situations there seems to be a reduction of PAI‐1 when the triglycerides are lowered. In the diabetic patients given n‐3 fatty acids this was not the case.
Transforming growth factor alpha and atrial natriuretic peptide in white adipose tissue depots in rats
Authors: CRANDALL D. L. , GORDON G. , HERZLINGER H. E. , SAUNDERS B.D. , ZOLOTOR R. C. , CERVONI P. , KRAL J.G.
Published: March 2008

Abstract. To detect the presence in adipose tissue of peptides known to affect tissue growth and to investigate potential regional differences, epididymal and perirenal adipose tissue depots from male Sprague‐Dawley rats were separated into adipocyte and stroma‐vascular fractions by collagenase digestion, sequential centrifugation and filtration. Identity and integrity of the fractions were demonstrated by light and electron microscopy, while dose‐response curves for angiotensin‐converting enzyme (ACE) were performed, revealing maintained functional capacity of the stroma‐vascular fraction. ACE, atrial natriuretic peptide (ANP), and transforming growth factor‐alpha (TGF‐alpha) concentrations were significantly greater in epididymal than perirenal stroma‐vascular tissue. Adipocyte fractions from both depots contained significant concentrations of ANP and TGF‐alpha. There was no detectable ACE in the adipocyte fractions, indicating that no contaminating stromal‐vascular cells were present in these fractions. These data show significant concentrations of peptides with effects on growth in subfractions of adipose tissue and demonstrate regional differences in concentrations between fat depots.
The critical role of magnesium ions in osteoclastmatrix interaction: implications for divalent cations in the study of osteoclastic adhesion molecules and bone resorption
Authors: MAKGOBA M. W. , DATTA H. K.
Published: March 2008

Abstract. We have studied the adhesion and dissociation of isolated rat osteoclasts from plastic or bone matrix using time‐lapse videomicroscopy and adhesion assays, and find that Mg2+ and not Ca2+ is essential for cell attachment and that Ca2+ and not Mg2+ is critical for dissociation.
Surfactant protein A (SP‐A) is decreased in acute parenchymal lung injury associated with polytrauma*
Authors: PISON U. , OBERTACKE U. , SEEGER W. , HAWGOOD S.
Published: March 2008

Abstract. To further investigate if the pulmonary surfactant system is altered in acute parenchymal lung injury of adults following polytrauma we measured SP‐A level and phospholipid composition in 150 sequentially obtained lung lavage samples from poly‐traumatized patients (n= 19) beginning at the day of trauma and ending 18 days later or when the patient was extubated. Out of the 19 patients studied 10 had severe parenchymal lung injury (ARDS), nine had moderate lung injury. SP‐A was measured using a two‐monoclonal sandwich ELISA‐assay. Phospholipids were separated using high‐performance liquid chromatography and their composition was calculated by comparison with standard phospholipid mixtures. We found immunoreactive SP‐A concentrations ranging from 01 μg ml“‘ to 8–5 μg ml‐1 lung lavage fluid obtained from all patients. The mean SP‐A concentration in patients who had severe parenchymal lung injury (ARDS) was 1–06 ± 0.16 μg ml‐1 lavage fluid, the mean concentration in patients who had only moderate parenchymal lung injury was 1.92 ± 0.18 μg ml‐1 lavage fluid. Both concentrations were lower than in healthy controls (2.74 ± 0.3 μg ml‐1 lavage fluid; n = 12). In patients who had moderate lung injury the SP‐A level normalized, but in patients who had severe lung injury the SP‐A level remained low during the timespan examined. SP‐A alterations did not correlate to changes in phospholipid composition as determined in lung lavage samples of individual patients. We conclude that alveolar SP‐A concentrations decrease in polytraumatized patients who have acute parenchymal lung injury soon after the trauma occurs. In patients who have lung injury of low severity the SP‐A level normalizes with recovery, but with more severe parenchymal lung injury SP‐A levels remain low. We speculate that the metabolic regulation of individual surfactant components might differ during lung injury and repair.
Plasma lipids affect maximum velocity not sodium affinity of human sodium‐lithium countertransport: distinction from essential hypertension
Authors: RUTHERFORD P. A. , THOMAS T. H. , LAKER M. F. , WILKINSON R.
Published: March 2008

Abstract. Inheritance is a major determinant of increased sodium‐lithium countertransport (SLC) activity in hypertension. However, hyperlipidaemia can also cause increased SLC activity in some individuals and it is difficult to distinguish this effect from the effect of hypertension. Erythrocyte SLC activity and its kinetic determinants sodium affinity (km) and maximum velocity (Vmax) were measured in 25 hyperli‐pidaemic patients and 15 normal controls (NC). Increased SLC activity (0–31± SEM 003 mmol Li/ (hxl cells) vs. NC 0.20 ± 0.01, P< 0.01) in the hyperli‐pidaemic patients was associated with increased Vmax (0.59±0.07 vs. NC 0.41± 0.03, P<0.01) but normal km (median 120 range [40–324] mmol 1‐1. vs. 140 [108–260]. Lipid‐lowering therapy resulted in decreased SLC activity secondary to a fall in Vmax. Km remained constant despite the changes in lipids and Vmax. The mechanism of increased SLC activity in hyperlipidaemia is different from that in essential hypertension where increased sodium affinity is found. Measurement of the kinetic characteristics of SLC may discriminate between the independent influences of hypertension and hyperlipidaemia on the sodium‐lithium countertransporter.
Bile acid active and passive ileal transport in the rabbit: effect of luminal stirring
Authors: ALDINI R. , RODA A. , LENZI P. L. , USSIA G. , VACCARI M. C. , MAZZELLA G. , FESTI D. , BAZZOLI F. , GALLETTI G. , CASANOVA S. , MONTAGNANI M. , RODA E.
Published: March 2008

Abstract. The intestinal absorption of bile acids (BA) with different chemical structure has been evaluated in the rabbit, after intestinal infusion of different concentrations (025–30 mM) of BA, by mesenteric blood sampling. Cholic (CA), chenodeoxycholic (CDCA), ursodeoxycholic (UDCA) acid, free and taurine (T‐) conjugated, together with glycocholic (GCA) acid and deoxycholic acid (DCA) were studied.

The apparent uptake parameters were calculated. All conjugated BA showed active transport (T max, nmol min‐1 cm‐1 int.), with Tmax values in the following order: TCA > TUDCA > TCDCA; uncon‐jugated BA showed passive uptake, with values in the following order: DCA > CDCA > UDCA > CA. GCA and CA showed both passive uptake and active transport. For all BA studied the % uptake in the ileal segment considered was less than 10%, BA uptake being thus limited by transport and/or diffusion kinetics, rather than by flow velocity. The liquid resistance to BA radial diffusion inside the lumen was evaluated, and the infusate‐to‐blood uptake parameters corrected for it, in order to get the uptake parameters from the epithelium‐to‐liquid interface to mesenteric blood: the apparent Km decreased, passive uptake coefficient increased, while Tmax was unchanged.

The passive component of the uptake, corrected for the luminal resistance, correlated with the BA hydro‐phobicity (r = 0–963; P<0–01).

These studies show that: (a) the active transport for BA in the rabbit ileum is mediated by a saturable, high‐efficiency, low‐affinity carrier; (b) that passive transport is highly efficient for unconjugated BA, mainly for the most lipophilic ones; (c) that both systems are important in the intestinal absorption of BA.
Early diagnosis of the multiple endocrine neoplasia type 2 syndrome: consensus statement
Authors: CALMETTES C. , PONDER B. A. J. , FISCHER J. A. , RAUE F.
Published: March 2008

Abstract. The diagnosis of medullary thyroid carcinoma by biochemical and genetic testing is possible in families with multiple endocrine neoplasia type 2. At an early stage total thyroidectomy usually cures the patient. As the clinical penetrance of the autosomal dominant, transmitted, multiple endocrine neoplasia type 2 gene is not complete, family screening is indicated for every new patient who presents with apparently sporadic medullary thyroid carcinoma. Problems related to a screening programme and early diagnosis have led the members of the European Community Concerted Action: Medullary Thyroid Carcinoma group to formulate a consensus on biochemical and genetic screening. For biochemical screening, measurement of basal and pentagastrin and/or calcium stimulated serum levels ofcalcitonin by radioimmunoassay are essential starting at the age of three and continuing annually until 35 years of age. Furthermore, annual screening for pheochromocy‐toma by measuring the urinary excretion of catechol‐amines and for hyperparathyroidism by serum calcium determination is indicated. Genetic screening using linked markers can be done with a 95% accuracy in informative families when DNA is available from at least two family members proven to be affected. Biochemical screening can thus be reserved for gene carriers, while those at low risk can be reassured. Combined biochemical and genetic screening for multiple endocrine neoplasia type 2 is important and effective for the cure of medullary thyroid carcinoma.
Autoantibodies to insulin have similar affinity to that of antibodies to exogenous insulin but lower binding capacity
Authors: VÄHÄSALO P.
Published: March 2008

Abstract. The binding characteristics of insulin autoantibodies (IAA) were compared with those of antibodies to exogenous insulin (IBA) by analyzing the specific binding, binding capacity and affinity for insulin in 11 children (age range 1.5–13.0 years) with insulin‐dependent diabetes (IDDM) both at diagnosis and after 1 year of insulin treatment. Maximal specific insulin binding was 7.8 (1.5; SE) pmol‐1 for IAA and 28.1 (6.7) pmol 1‐1 for IBA (P<0.01), and the binding capacity of the high affinity class of IAA 0.01 (0.003) nmol l‐1, as compared with 0.19 (008) nmol 1‐1 for the corresponding IBA class (P< 0.01). With regard to the low‐affinity components the binding capacity was 0.11 (005) nmol l‐1 for IAA and 1.50 (0.95) nmol l‐1 for IBA (P< 0.01). No differences in the affinity constants could be observed between IAA and IBA. There was no correlation between the insulin binding of IAA and quantitative levels of islet cell antibodies (ICA) at the clinical presentation or subsequent IBA values. The specific insulin binding of IBA correlated negatively with serum C‐peptide concentrations and positively with HbA1 levels at 1 year. The present observations suggest that IAA developing before the diagnosis of IDDM are characterized by a reduced binding capacity as compared with antibodies to exogenous insulin, whereas they have a similar affinity for insulin. IAA seem to be quantitatively unrelated to ICA and postdiagnostic IBA levels. High IBA levels appear to be associated with reduced endogenous insulin secretion and poor metabolic control during the early clinical course of the disease.
Effect of intravenous polyunsaturated phosphatidylcholine infusion on insulin receptor processing and lipid composition of erythrocytes in patients with liver cirrhosis
Authors: CANTAFORA A. , MASELLA R. , ANGELICO M. , GANDIN C. , BLOUNT R. J. , PETERSON S. W.
Published: March 2008

Abstract. The aim of this study was to determine whether insulin receptor processing capabilities of human erythrocytes could be improved by changing the cell membrane lipid composition using an intravenous infusion of polyunsaturated phosphatidylcholine. Thirteen cirrhotics were submitted to the i.v. infusion of phosphatidylcholine (2 g day‐1 for 3 days). Both erythrocyte lipid composition and insulin receptor processing ability were examined at the beginning of the study and at 0, 3 and 11 days after the end of the treatment. This treatment decreased the erythrocyte cholesterol to phospholipid molar ratio and increased the proportion of polyunsaturated fatty acids (mainly linoleic acid) immediately after the end of the treatment. The proportion of arachidonic acid increased immediately in the phosphatidylserine class and, a few days later, also in phosphatidylethanolamine. The phospholipid class distribution did not show any relevant modification in the course of the study. Surface insulin receptors, which generally were up‐regulated in the untreated subject (— 7.1±20.4%), showed an improvement in down regulation capabilities that appeared to be well correlated with the changes in lipid composition of cell membranes induced by i.v. infusion of polyunsaturated phosphatidylcholine. The confirmation of these findings also in target cells for insulin may open new perspectives in the treatment of diabetes mellitus.
Anti‐neutrophil cytoplasm antibodies, anti‐GBM antibodies and anti‐dsDNA antibodies in glomerulonephritis
Authors: BYGREN P. , RASMUSSEN N. , ISAKSSON B. , WIESLANDER J.
Published: March 2008

Abstract. The diagnostic potential of assays detecting anti‐neutrophil cytoplasm antibodies (ANCA), anti‐GBM antibodies and anti‐dsDNA antibodies was evaluated by examining sera from time of admission in a consecutive series of 455 patients with biopsy verified primary or secondary glomerulonephritis (GN). ANCA were classified into c‐ and p‐ANCA by indirect immunofluorescence (IIF) and ELISAs using alfa‐granule extract, proteinase‐3, myeloperoxidase (MPO), elastase and lactoferrin. C‐ANCA was virtually confined to 64 patients with systemic small vessel vasculitis, 66–74% being c‐ANCA positive. P‐ANCA against MPO, seen in 47 patients, segregated through many diagnostic categories of primary and secondary severe GN. ANCA against lactoferrin and elastase were rare. Anti‐dsDNA positive patients constituted 57% of the 44 ANA‐positive patients with systemic lupus erythematosus.

It is concluded that the IIF and ELISAs for anti‐proteinase‐3, anti‐MPO, anti‐dsDNA and anti‐GBM have an acceptable performance and are useful in the primary diagnostic work‐up of patients suspected for secondary GN as the majority of such patients will be classified by these assays.