bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormalities in left ventricular diastolic function in male patients with rheumatoid arthritis without clinically evident cardiovascular disease
Authors: MUSTONEN J. , LAAKSO M. , HIRVONEN T. , MUTRU O. , PIRNES M. , VAINIO P. , KUIKKA J. T. , RAUTIO P. , LÄNSIMIES E.
Published: March 2008

Abstract. Epidemiological studies have suggested that patients with rheumatoid arthritis (RA) have increased mortality due to cardiovascular disease. We studied cardiac performance in 12 asymptomatic male patients with RA and 14 control subjects to elucidate early disturbances in cardiac function. In echocardiography, isovolumic relaxation time was longer (64 ± 6 vs. 49 ± 3 ms, mean ± SEM, P = 0.010) and peak filling rate (134 ± 10 vs. 159 ± 6 mm s‐1, P = 0.015) lower in patients with RA than in control subjects, reflecting an impairment in left ventricular diastolic function. Left ventricular systolic function assessed by radionuclide angiocardiography at rest and during exercise was similar in both groups. There were no differences between the patients with RA and control subjects in the heart rate, systolic blood pressure and oxygen uptake during peak exercise. Left ventricular diastolic function is impaired in spite of normal left ventricular systolic function in patients with R A without clinically evident cardiovascular disease and this may contribute to the excess of cardiovascular mortality in patients with RA.
Gemfibrozil increases apolipoprotein A‐I and cholesterol concentrations in human peripheral lymph
Authors: REICHL D. , MILLER N. E. , STERCHI J. M.
Published: March 2008

Abstract. Peripheral lymph lipoproteins were studied in four hyperlipidaemic men before and after 6 weeks of treatment with gemfibrozil, a drug which is known to increase the fractional catabolic rate of very low density lipoproteins (VLDL) by raising lipoprotein lipase activity in peripheral tissues. Decreases in plasma triglycerides of 18–60% (mean, 45%) were accompanied by increases in lymph apolipoprotein (apo) A‐I concentration of 30–108% (mean, 66%; P<0.01), and in lymph cholesterol concentration of 35–100% (mean, 59%; P<0.05). The additional lymph cholesterol was distributed over a broad range of lipoprotein particle sizes. Effects on plasma apo A‐I concentration (mean, +7%) and plasma total cholesterol concentration (‐ 7%)) were not statistically significant. No changes were observed in four untreated control subjects. These findings are compatible with the hypothesis that lipolysis of VLDL at the blood‐endothelium interface increases the transfer of apo A‐I from plasma to interstitial fluids, and thereby promotes cholesterol efflux from cells.
Mechanisms of tubulo‐interstitiaI injury in progressive renal diseases
Authors: FINE L. G. , ONG A. C. M. , NORMAN J. T.
Published: March 2008

Abstract. A vast amount of evidence, based upon human renal biopsy material, indicates that the presence of tubular atrophy and interstitial fibrosis is a better indicator of outcome of renal function than is the extent of glomerular sclerosis. The pathophysiological basis for this surprising fact has not been adequately addressed. In this review we point out that the systemic hypertension which accompanies most forms of chronic renal disease could impact adversely upon the vasodilated interstitial vascular compartment which, together with a component of primary capillary injury related to the disease process, could cause progressive obliteration of particular capillaries. This would initiate a process of chronic tubular ischaemia ultimately leading to tubular atrophy. Since tubular cells have been shown to produce an array of cytokines and growth factors which modulate fibroblast proliferation, extracellular matrix production and chemo‐attracts for infiltrating cells, it is further proposed that it is the tubular injury which initiates the deleterious cascade of events. Tubular injury may be aggravated by the filtration of potentially ‘noxious’ molecules through the diseased glomerulus and by infiltrating cells. As the vascular bed into which glomerular blood flow empties is progressively obliterated, glomerular function declines and renal failure advances in relation to the degree of tubulo‐interstitial fibrosis.
Effects of the correction of renal anaemia by erythropoietin on physiological changes during exercise
Authors: LEWIS N. P. , MACDOUGALL I. C. , WILLIS N. , COLES G. A. , WILLIAMS J. D. , HENDERSON A. H.
Published: March 2008

Abstract. The effects of treating the anaemia of end‐stage renal failure with erythropoietin were studied in nine dialysis patients. The increase in haemoglobin concentration (by 59% from 7.0 ± 1.2 to 11.1 ± 1.1 g dl‐1) was associated with increases in exercise duration (by 41%) and maximum oxygen consumption (by 34%). Treatment reduced resting heart rate but did not significantly alter heart rate at maximum exercise, nor resting or exercise blood pressure. Resting arterial potassium concentrations were slightly increased after treatment, but they increased similarly in relation to minute ventilation during exercise. Lactic acidaemia developed during exercise at both levels of haemoglobin, and was accompanied by similar reductions in arterial pH and bicarbonate levels but constant Pao2 and Paco2. Ventilation was coupled to the metabolic rate of carbon dioxide production, ventilatory dead‐space and arterial Pco2 before and after treatment of anaemia, the ventilatory requirement for carbon dioxide elimination being unchanged. Treatment of anaemia did not alter resting arterial lactate concentration; the concentration of lactate at maximum exercise was increased slightly following treatment but this increase did not reach statistical significance. The rate of increase in arterial lactate concentration as a function of oxygen consumption, assessed both with respect to the ‘lactate threshold’ and ‘lactate slope index’, was significantly delayed by treatment. Treatment of anaemia also delayed the ‘anaerobic threshold’, and there was good correlation between lactate and anaerobic thresholds. Treatment of renal anaemia by erythropoietin thus results in improved tissue oxygen supply during exercise, reflected by delay in the onset of lactic acidaemia.
Affinity of anti‐GP41 antibody in patients infected with human immunodeficiency virus type I
Authors: RADKOWSKI M. , LASKUS T. , GOCH A. , SLUSARCZYK J.
Published: March 2008

Abstract. Anti‐gp41 antibody affinity was investigated prospectively in 25 patients with asymptomatic and symptomatic HIV‐1 infection for a period of 9–42 months. Major differences in the processs of immune response maturation towards gp41 were observed among individual subjects, however, antibody affinity increased with time in all examined persons including patients with AIDS. Anti‐gp41 affinity values were found to reflect both the duration and the clinical stage of HIV infection
Decreased ability of high density lipoproteins to transfer cholesterol esters in non‐insulin‐dependent diabetes mellitus
Authors: AHNADI C.‐E. , MASMOUDI T. , BERTHEZÈNE F. , PONSIN G.
Published: March 2008

Abstract. Esterified cholesterol transfer (ECT) from high density lipoproteins (HDL) to very low (VLDL) and low density lipoproteins (LDL) may be abnormal in situations at high risk for atherosclerosis. It has been shown to increase in insulin‐dependent diabetes and to decrease in non‐insulin‐dependent diabetes (NIDD). Since the net transfer of esterified cholesterol (EC) results from a bidirectional exchange between HDL and VLDL/LDL, we developed a transfer assay specifically designed to measure the unidirectional transfer of EC from HDL to lipid emulsions according to first‐order kinetics. Our results show that in NIDD the rate constant of HDL‐dependent ECT is decreased by 30% by comparison with control subjects. Analysis of HDL composition revealed that, in both groups, HDL‐dependent ECT was positively correlated with the free cholesterol/phospholipid ratio (r = 0.94; P < 0.001) and negatively correlated with the triglycer‐ide/EC ratio (r=‐0.85; P<0.001). It is concluded that, besides the known defect of acceptor lipoproteins, the abnormality of ECT in NIDD is also caused by a decreased ability of HDL to act as an EC donor, presumably because of a change in composition. In addition, our work shows that the amount of EC lost by HDL during the reaction transfer is counterbalanced by a reciprocal equimolar transfer of triglycer‐ides.
The effects of the menopause on insulin sensitivity, secretion and elimination in non‐obese, healthy women
Authors: WALTON C. , GODSLAND I. F. , PROUDLER A. J. , WYNN V. , STEVENSON J. C.
Published: March 2008

Abstract. We have carried out intravenous glucose tolerance tests with measurement of plasma glucose, insulin and C‐peptide concentrations on 66 premeno‐pausal and 92 postmenopausal non‐obese Caucasian women. After adjustment for the effects of a number of possible confounding variables, including age and body mass index, there was little difference between pre and postmenopausal women in glucose and insulin concentrations either fasting or in response to intravenous glucose. Mathematical modelling analysis of the resultant plasma concentration profiles was used to obtain measures of insulin sensitivity, secretion and elimination, and non‐insulin dependent glucose disposal. We found reciprocal differences in mean insulin sensitivity (increased by 50%) and non‐insulin dependent glucose disposal (decreased by 30%). Plasma C‐peptide response and pancreatic insulin secretion were markedly lower in the postmenopausal group (‐ 35% and ‐50% respectively). However, the rate constant for insulin elimination was also lower in these women. As a result, intravenous glucose tolerance test plasma insulin concentrations were not significantly different between the two groups. We conclude that, despite the occurrence of little or no variation in plasma glucose and insulin concentrations, the menopause is associated with significant changes in insulin metabolism.
Relationship of alcohol consumption to changes in HDL‐subfractions
Authors: SILLANAUKEE P. , KOIVULA T. , JOKELA H. , MYLLYHARJU H. , SEPPÄ K.
Published: March 2008

Abstract. Epidemiological studies have consistently shown an apparent protective effect of moderate alcohol consumption on coronary artery disease (CAD). This has been considered to be due to the rise in the high‐density cholesterol lipoprotein (HDL‐cholesterol). Since the response of the HDL‐subfractions to moderate or heavy dose of alcohol is less clear, we now compared the high‐density lipoprotein cholesterol status between groups consuming different amounts of alcohol. In this population‐based survey serum total high‐density lipoprotein cholesterol and its HDL2 and HDL3 subfractions were blindly compared between 264 consecutive middle‐aged men (37 teetotallers, 137 moderate drinkers, 90 heavy drinkers) participating in a voluntary health screening and 104 male alcoholics.

Alcohol consumption correlated significantly (P<0.001) with total HDL‐cholesterol, HDL2, HDL3 when all subjects (n= 368) were included but the correlation disappeared when alcoholics were excluded (n = 264). In comparison with teetotallers, alcoholics had significantly higher total HDL‐cholesterol, HDL2 and HDL3 values (P < 0.001). Moderate or heavy intake of alcohol had no effect on HDL2 but increased the HDL3‐‐fraction.

If the protective effect of moderate alcohol consumption is mediated by high‐density lipoprotein, it may not be accounted for by changes in the HDL2‐‐fraction. The observed increases in the concentration of the HDL3‐‐fraction, however, suggest that this subfraction may not be inert with respect to coronary disease and could possibly have a role in the protective effect.
The insulin‐like growth factor‐I/binding protein axis: physiology, pathophysiology and therapeutic manipulation
Authors: LANGFORD K. S. , MIELL J. P.
Published: March 2008

Abstract. Insulin‐like growth factor‐I (IGF‐I) is a single‐chain polypeptide which has multiple metabolic actions and effects on the differentiation and proliferation of a wide variety of cell types. IGF‐I has endocrine, paracrine and autocrine actions and is bound in the circulation to a complex system of binding proteins which alter its bioavailability and activity. Thus its physiology is complex and is altered in a number of pathological states. This review will discuss these states and the actual and proposed therapeutic applications of recombinant human IGF‐I (rhIGF‐I).
In vivo kinetics of lipoprotein(a) in homozygous Watanabe heritable hyperlipidaemic rabbits
Authors: LIU R. , SAKU K. , KOSTNER G. M. , HIRATA K. , ZHANG B. , SHIOMI M. , ARAKAWA K.
Published: March 2008

Abstract. In vivo kinetics of lipoprotein(a) [Lp(a)] were investigated in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits (an animal model of familial hypercholesterolemia (FH)), and in normo‐lipidemic Japanese White rabbits (controls). 1251‐labelled Lp(a) and 131I‐labelled LDL were simultaneously injected intravenously. Blood samples were then taken periodically. Kinetic parameters were cal culated from the plasma radioactivity decay curves. The fractional catabolic rates (FCRs) of both Lp(a) and LDL (1.355 ± 0.189 pools per day and 1.278 ± O.397 pools per day, respectively) in the WHHL rabbits were significantly (P<0.005) smaller than those in the control rabbits (2.008 ± 0.083 pools per day and 2.855 ± 0.759 pools per day, respectively). In WHHL rabbits, the FCRs of Lp(a) and LDL were similar. However, in control rabbits, the FCR of Lp(a) was significantly (P<0.01) smaller than that of LDL. In WHHL rabbit organs, the mean ratio of 125I‐Lp(a): 131I‐LDL, 48 h after injection, normalized to the corresponding isotope ratio in plasma, were 1.525, 1 020, 1.819 and 1.967, in liver, kidney, spleen and bile, respectively. These values were significantly higher than the corresponding values in control rabbits (0.590, 0.677, 0.862 and 0.766, respectively). Our data strongly suggest that Lp(a) clearance is not entirely dependent upon LDL receptors and may be mediated by some other mechanisms.
Non‐steady‐state kinetics of low density lipoproteins in man: studies after plasma exchange in healthy subjects and patients with familial hypercholesterolaemia
Authors: ERIKSSON M. , BERGLUND L. , GABRIELSSON J. , LANTZ B. , ANGELIN B.
Published: March 2008

Abstract. Five patients with heterozygous familial hypercholesterolaemia (FH), one patient with non‐familial hypercholesterolaemia, and four healthy normals were treated with plasma exchange (PE). In order to achieve a non‐steady‐state situation with low plasma cholesterol levels, PE was performed twice in each subject at an interval of 1–3 days. At each time, 1500 ml of plasma were removed and replaced with colloids and albumin. Lipoprotein analyses were performed daily in all subjects for a period of 14 days following PE. Kinetic calculation of LDL cholesterol data using a two‐compartment open model was performed, and rate constants, synthetic rate and apparent clearance of LDL were determined. A lower clearance and a tendency towards a higher synthesis of LDL were observed in the FH patients. In four of the subjects, LDL kinetics was also studied with the conventional 125I‐LDL turnover technique. The synthetic rates of LDL were compared using data derived from PE and 125I‐LDL kinetics. The two techniques showed a good correlation (r=+0.93) although synthetic rates in general were higher when calculated from the 125I‐LDL procedure (3.98 vs. 2.64 mmol d‐1 for LDL cholesterol synthesis). The results indicate that non‐steady‐state kinetics of LDL, as measured using the PE technique, is a useful method for analysis of LDL metabolism.
Pathogenesis of genetic haemochromatosis
Authors: STREMMEL W. , RIEDEL H. D. , NIEDERAU C. , STROHMEYER G.
Published: March 2008

Abstract. Genetic haemochromatosis is an autosomal recessive inherited iron overload disease. The genetic defect and the underlying metabolic error are not known. Several observations indicate that the 2–4‐fold increase of iron absorption is due to a regulatory defect of a membrane iron transport system in duodenal mucosal cells. The key pathophysiologic factor may be the increase of gut‐derived non‐transferrin bound iron liganded to low‐molecular mass organic molecules. A putative membrane carrier protein for nontransferrin bound iron was identified and preliminary data suggest its enrichment in plasma membranes of human mucosal cells as well as in liver and other organs which are affected in genetic haemochromatosis. Cellular accumulation of ionic iron leads to peroxidative decomposition of organelle membrane phospholipids with the consequence of cell degeneration and cell death. Impairment of organ function and structural alterations such as cirrhosis of the liver are clinical manifestations.
Tritium and 14C isotope effects using tracers of leucine and alpha‐ketoisocaproate
Authors: BENNET W. M. , GAN‐GAISANO M. C. , HAYMOND M. W.
Published: March 2008

Abstract. To test if different leucine tracers behave in an indistinguishable manner and, by implication, that their metabolism is identical to that of natural leucine, we measured whole body leucine turnover in dogs and humans and fibrinogen synthesis in dogs by simultaneously infusing either [1–14C]leucine or [4,5–3H]leucine or [I‐14C]α‐ketoisocaproate (KIC) and [4,5–3H]KIC. Whole body leucine fluxes calculated from the plasma specific activity of the transaminated product of the infused tracer (reciprocal pool model) were lower (dogs by 5.7%; humans by 6.4%, both P<0.02) when the plasma 'H specific activity compared to 14C specific activity were used with leucine tracers and were also lower (dogs by 4.4%, P<0.02; humans by 86%, P<0.06) using the KIC tracers. Using leucine or KIC tracers in dogs, the fractional rate of fibrinogen synthesis was 6.7% or 9.4% lower, respectively, (P<0.02) using the 3H versus the 14C tracer. The apparently lower incorporation of 3H into protein was only in part accounted for by detritiation (2.1%, P = 0.05) of [3H]leucine during acid hydrolysis of proteins. These results suggest that in vivo and/or in vitro differential isotope effects are small (˜5%), but should be considered when dual isotopes infusions are employed to partition amino acid metabolism.
Changes in biological activity and immunoreactive mass of lipoprotein lipase in congenital nephrosis: relationship to hypertriglyceridaemia
Authors: ANTIKAINEN M. , HOLMBERG C. , OLIVECRONA T. , BENGTSSON‐OLIVECRONA G. , LABEUR C. , ROSSENEU M. , TASKINEN M‐R
Published: March 2008

Abstract. The major lipid disturbance in children with congenital nephrosis of the Finnish type (CNF) is hypertriglyceridaemia. To determine whether or not hypertriglyceridaemia is caused by defective triglycer‐ide catabolism, we measured lipoprotein lipase (LPL) activities and masses at various stages of the disease. At age 3 months in CNF both LPL activity and mass were decreased, but a close positive correlation between these parameters similar to that in controls was observed. At age 9 months both LPL activity and mass were even lower. At that time a significant positive correlation (r = 0.72, P<0.05) between LPL activities and albumin concentrations and significant negative correlations between plasma free fatty acid (FFA) concentrations and LPL activities (r= ‐0.72, P<0.05) and between plasma FFA concentrations and serum albumin concentrations (r= ‐0.73, P < 0.05) were observed, suggesting that low albumin concentrations result in increase of FFA levels, which could interfere with a normal LPL function at the endothelial surface. On dialysis after nephrectomy, LPL activities and masses increased. At age 3 and 9 months apoprotein C‐II (apo C‐II) and apoprotein C‐III (apo C‐III) levels were not decreased although apoproteins were being lost into the urine. On dialysis the mean ratio of apo C‐II/C‐III was significantly lower than the mean in controls (P<0.001). We conclude that impaired function of LPL seems to be the major cause of hypertriglyceridaemia and disinte‐grity of the VLDL‐IDL‐LDL delipidation cascade in children with CNF.
Enhanced renal production of cyclic GMP and reduced free water clearance during sodium nitroprusside infusion in healthy man
Authors: NIELSEN C. B. , EISKJÆR H. , PEDERSEN E. B.
Published: March 2008

Abstract. A 90–min intravenous infusion of the direct vasodilator sodium nitroprusside (SNP) was compared with a placebo infusion in 32 healthy control subjects in order to study the acute effects of SNP on renal haemodynamics, tubular function evaluated by the lithium clearance technique, the plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo) and arginine vasopressin (AVP) and the tubular transport of cGMP (TcGMP). SNP infusion induced a significant reduction in mean arterial blood pressure (from 89.5 to 81.5 mmHg), urinary output (from 7.7 to 4.5 ml min‐1), free water clearance (from 4.0 to 1.3 ml min‐I) and ANP (from 3.3 to 2.5 pmoll‐1) and a significant increase in heart rate (from 57 to 64 beats min‐l), Ang II (from 11 to 18 pmoll‐1), Aldo (from 189 to 308 pmol L‐1) and in the tubular secretion of cGMP (TcgmP from 28.8 to 214.4 pmol min‐1), (all values are medians and changes from baseline to 90 min after infusion start). Glomerular filtration rate, renal plasma flow, urinary sodium excretion, lithium clearance and plasma level of AVP were not significantly changed. It is concluded that SNP infusion in healthy subjects decreases urinary output and free water clearance without any change in sodium excretion, indicating a dissociation between the salt and water retaining effects of SNP in the early phase of treatment, probably due to an enhanced distal tubular water reabsorption of water. It is suggested that this increase in reabsorption of water in the distal parts of the nephron during SNP infusion may be mediated by an increase of cGMP production in the kidney, as indicated by the increase in TcGMP during the SNP infusion.
Possible involvement of β‐PKC rather than that of α‐PKC in differentiation of 3T3–L1 cells to adipocytes
Authors: UEDA H. , ISHIDA Y. , TANIGUCHI H.
Published: March 2008

Abstract. The change of subspecies of protein kinase C (PKC) was studied in 3T3—L1 cells in terms of their differentiation to adipocytes. 3T3—L1 cells feasible to differentiate to adipocytes by exposure to 3–isobutyl‐1–methylxanthine (IBMX) and dexamethasone had both α‐ and β‐PKC. However, 3T3–Ll cells unfurnished with such feasibility had only α‐PKC. α‐PKC, therefore, seems to be more deeply involved in differentiation of 3T3–LI cells to adipocytes than α‐PKC.
Regulation of VLDL secretion in primary culture of rat hepatocytes: involvement of cAMP and cAMP‐dependent protein kinases
Authors: BJÖRNSSON Ó. G. , SPARKS J. D. , SPARKS C. E. , GIBBONS G. F.
Published: March 2008

Abstract. When hepatocytes were cultured for 24 h in the presence of forskolin (10‐4 mol l‐1) or isobutylmethylxanthine (IBMX, 10‐3 mol l‐1), the intracellular cAMP concentration peaked (320–380 pmol mg‐1 protein) after 10–20 min of culture. This increase was accompanied by a decrease in the secretion of triacylglycerol, cholesterol and apoprotein B associated with VLDL. After 4 h cAMP levels had returned almost to basal values but the inhibition of VLDL secretion persisted. There was a small intracellular accumulation of triacylglycerol but not of apoprotein B. Addition of forskolin and IBMX together led to a further increase in intracellular cAMP and a further suppression of VLDL output. Similar effects on the secretion of VLDL were also observed after addition of Bt2cAMP. Exposure of cell cultures to glucagon (10‐7 mol l‐1) for only 10 min raised cellular cAMP levels to > 200 pmol mg‐1 protein, and suppressed VLDL secretion during the next 24 h to < 40% of control. All of the substances tested inhibited de novo synthesis of fatty acids but had little or no effect on cholesterol synthesis and did not inhibit oleate esterification to triacylglycerol. The cAMP‐dependent protein kinase antagonist Rp‐cAMPS prevented suppression of VLDL triacylglycerol secretion induced by glucagon (10‐7 mol l‐1) and abolished glucagon‐induced ketogenesis. Rp‐cAMPS also inhibited Bt2cAMP (7·5 times 10‐6 mol l‐1)‐induced suppression of VLDL secretion and enhancement of ketogenesis. It is concluded that rat hepatic VLDL metabolism can be regulated by cAMP and cAMP‐dependent protein kinases, and that the initial transient rise in cellular cAMP levels induced by glucagon is sufficient to maintain a long‐term inhibitory effect on assembly and secretion of VLDL.
Zinc and magnesium in liver cirrhosis
Authors: ROCCHI E. , BORELLA P. , BORGHI A. , PAOLILLO F. , PRADELLI M. , FARINA F. , CASALGRANDI G.
Published: March 2008

Abstract. The Authors determined zinc (Zn) and magnesium (Mg) in the plasma, urine, erythrocytes (RBCs), mono‐ and polymorphonuclear cells (MNCs and PMNs) of patients with overt alcoholic and nonalcoholic liver cirrhosis. In order to obtain a clearer clinical picture, biochemical and nutritional parameters (retinol, tocopherol, six different carotenoids, creatinine‐height index and tricipital skinfold), as well as markers of portal hypertension (spleno‐portal size and platelet count) were also evaluated.

The plasma levels of Zn and Mg were found to be reduced, as were the urine levels of Mg. Urine Zn, on the other hand, was higher than normal. Plasma Zn correlated inversely, and urine Zn directly, with the severity of the disease, rather than with alcohol consumption or treatment with diuretics. Protein metabolism impairment would appear to affect the plasma transport of Zn rather than its overall availability in the organism; the opposite was found in the case of Mg, the availability of which appeared to be reduced. Determination of the two elements in RBCs, MNCs and PMNs suggested that a true nutritional deficit cannot be demonstrated. MNCs, rather than RBCs or PMNs seem better to reflect tissue status of trace elements.
Auditory brain‐stem responses (ABRs) in sleep respiratory disorders
Authors: PAQUEREAU J. , MEURICE J. C. , NEAU J. P. , INGRAND P. , PATTE F.
Published: March 2008

Abstract. Neurophysiological repercussions of sleep respiratory disorders (SRDs) are still unclear. It has been shown that SRDs induce disturbance on auditory event‐related potentials with a delayed latency of the cognitive P300 potentials. Since the Auditory Brainstem Responses (ABRs) explore the auditory brainstem structures and are independent on cognition, we evaluated the neurological impact of SDRs on central nervous system by ABRs in these patients. Four groups of patients were studied: snorers (S, 17 subjects), sleep apnoea syndrome (SAS, 48 subjects), apnoeic patients with respiratory insufficiency (SAI, 17 patients) and patients with respiratory insufficiency alone (RI, 12 subjects). A standard polysomnographic study was done in each patient with further quantitative analysis of sleep, respiratory events, and oxygen arterial saturation. ABRs were recorded before the study night and interpeak latencies (IPLs) between waves I, III and V were measured. Results were expressed as the mean of each group for all the different parameters. ABR IPL latencies (IPLI‐III, IPLIII‐V, IPLI‐V) of the four groups were within the normal range. However, comparing groups between themselves, there were significant differences (ANOVA) between groups. Longer IPLIII‐V and IPLI‐V (which explored the central conduction time) were observed in group SAI compared to group SAS. No evidence on the origin of this elongation was found; the level of hypoxia, in particular, was not related to IPL values. These results show that SAS alone do not affect lower brainstem auditory function, in contrast to the asscociation of SAS and RI.
The relationship of serum total sialic acid with serum acute phase proteins and lipoprotein (a) in patients with severe hypertriglyceridaemia
Authors: CROOK M. , HAQ S. , HAQ M. , TUTT P.
Published: March 2008

Abstract. Total serum sialic acid (TSA), recently shown to be a cardiovascular risk factor, was measured in 15 patients with severe hypertriglyceridaemia (fasting triglyceride > 2·3 mmol l‐1) and 15 age and sex matched normal control subjects.

To test the hypothesis that serum TSA is related in some way to serum acute phase proteins we also measured five acute phase proteins, namely alpha‐1‐antichymotrypsin (ACT), alpha‐1‐acid‐glycoprotein (AGP), alpha‐2‐macroglobulin (AMG), C‐reactive protein (CRP) and haptoglobin (HAP) in both groups.

Of note was the significantly elevated serum TSA in the severely hypertriglyceridaemic group as compared to normal subjects. Serum TSA being 71·9 ± 11·7 mg dl‐1 and 59·6 ± 10·2 mg dl‐1 respectively (P < 0·01 Mann‐Whitney test).

Serum CRP was significantly elevated in the type IV patients as compared to controls (6·4 ± 4·5 mg l‐1 vs. 3·3 ± 1·9 mg l‐1P<0·05 Mann Whitney test) as was serum AMG (2·1 ± 0·89 g l‐1 vs. 1·5 ± 0·53 g l‐1P < 0·05 Mann Whitney test).

There was no correlation between serum TSA and lipoprotein (a) in either the normal or severely hypertriglyceridaemic subjects. We suggest that serum TSA could in part be related to hypertriglyceridaemia and serum acute phase proteins but that its property as a cardiovascular risk factor is not related to serum lipoprotein (a) concentrations.
Sex‐ and age‐dependency of IgG auto‐antibodies against IL‐1α in healthy humans
Authors: HANSEN M. B. , SVENSON M. , ABELL K. , VARMING K. , NIELSEN H. P. , BERTELSEN A. , BENDTZEN K.
Published: March 2008

Abstract. Naturally occurring anti‐interleukin (IL)‐1α IgG antibodies (Ab‐IL‐1α) were measured in sera of 466 healthy Danish blood donors. Ab‐IL‐1α bound IL‐1α with exceptionally high affinity (Kd: 10‐11 M) and neutralized both cell‐associated and extracellular IL‐1α but not IL‐1β or IL‐1 receptor antagonist. More than 80% of the saturable binding of rIL‐1α to serum was to Ab‐IL‐1α, suggesting that these antibodies are the quantitatively most important IL‐1α‐binding components in serum. Judged by second antibody precipitation assay, the prevalence of Ab‐IL‐1α varied between 30% and 75% and correlated positively with age (P= 0·037). The binding capacity of serum also increased with age. Although men were more frequently positive than women (P < 0·001), there were no sex‐ or age‐dependent alterations in the average affinities of the antibodies. Free IL‐1α‐like molecules were generally not detected in these sera. However, acid treatment showed that 25% of Ab‐IL‐1α‐positive sera contained low amounts of IL‐1α‐Ab‐IL‐1α immune complexes. IgG4 represented the main IgG isotype, whereas IgG3 Ab‐IL‐1α were undetectable. The relative amounts of IgG4 Ab‐IL‐1α increased while IgG2‐and IgG1 Ab‐IL‐1α decreased in elderly individuals. The presence in normal individuals and the lack of affinity maturation with age suggest that Ab‐IL‐1α may be regulatory natural auto‐antibodies perhaps coded by germline genes.
Effect of 5‐hydroxytryptamine antagonists on cholera toxin‐induced secretion in the human jejunum
Authors: EHERER A. J. , HINTERLEITNER T. A. , PETRITSCH W. , HOLZER‐PETSCHE U. , BEUBLER E. , KREJS G. J.
Published: March 2008

Abstract In rats, the combined administration of the 5‐HT2 antagonist ketanserin and the 5‐HT3 antagonist tropisetron inhibits cholera toxin‐induced intestinal secretion. We investigated whether these agents and the 5‐HT3 antagonist ondansetron can inhibit cholera toxin‐induced secretion in the human jejunum using a segmental perfusion technique. In a first control period the subjects' jejunums were perfused continuously with a plasma‐like electrolyte solution. In a second control period they either received a combination of tropisetron plus ketanserin, or tropisetron or ondansetron alone. Cholera toxin 6·25 μg was then administered intrajejunally and the experiments were continued for 4 h. Net water movements during the 4th hour after CT administration minus net water movement during the first control period was used for further calculation and was referred to as net luminal gain. In perfusion studies with tropisetron plus ketanserin resp. ondansetron the net luminal gain of water (+161 ± 26 resp. 189 ± 28 ml 30 cm‐1 h‐1, mean ± SEM) was significantly higher compared to perfusion studies with cholera toxin alone (+94 ± 30). Treatment with tropisetron did not change the CT‐induced net luminal gain of water (+108 ± 41). Movements of sodium, chloride, bicarbonate and potassium paralleled the movement of water. In agreement with these observations we found a deterioration of clinical parameters after the end of the perfusion studies in four of five subjects treated with CT 25 μg plus ketanserin and tropisetron. Contrary to what has been observed in animal experiments the results in humans indicate enhancement rather than inhibition of CT‐induced secretion by administration of 5‐HT antagonists. Our results do not support the contention that the intravenous administration of ketanserin, tropisetron or ondansetron might be of potential therapeutic value in patients with Asiatic cholera.
Effect of experimental non‐insulin requiring diabetes on myocardial microcirculation during ischaemia in dogs
Authors: SEBBAG L. , FORRAT R. , CANET E. , WIERNSPERGER N. , DELAYE J. , RENAUD S. , LORGERIL M. DE
Published: March 2008

Abstract To examine whether chronic high blood glucose may influence myocardial microcirculation during acute myocardial ischaemia in the dog, a non‐insulin‐requiring diabetes was induced by the streptozotocin‐alloxan method. Seventy‐five days later, myocardial ischaemia was provoked by occluding the left anterior descending coronary artery for 2h and micro‐circulation regulation was assessed in the ischaemic and non‐ischaemic myocardium by the radioactive microsphere method. Diabetic dogs were compared with normal dogs. Diabetic dogs had higher blood glycated haemoglobin (2·66±0·4%) and fructosamine (397±62 μmol l‐1) than control dogs (0·66±0·2, P<0·004 and 229 ± 13, P<0·03, respectively). Haemodynamic data in the two groups were not different at any time. The size of the ischaemic zone was similar in both groups. During the 2h ischaemia in the ischaemic zone subendocardial (P= 0·22) and subepicardial (P<0·05) blood flow slightly increased in control dogs whereas there was a 63% (P<0·02) and 35% (P= 0·06) reduction respectively in diabetic dogs. In the non‐ischaemic zone, blood flow of controls tended to increase (P<0·006 in the subepicardium and P<0·06 in the subendocardium) whereas in diabetic dogs blood flow tended to decrease (P= 0·03 in the subendocardium and in the subepicardium). This first investigation on myocardial microcirculation in diabetic dogs during ischaemia suggests that one of the possible causes of increased mortality rate from ischaemic cardiac disease in diabetics might be related to a paradoxical and unfavourable pattern of myocardial blood flow during ischaemia.
Hepatic uptake and intestinal absorption of bile acids in the rabbit
Authors: ALDINI R. , RODA A. , MONTAGNANI M. , POLIMENI C. , LENZI P. L. , CERRE C. , GALLETTI G. , RODA E.
Published: March 2008

Abstract The existence of transporters for bile acids (BA) in liver and intestine has been well documented, but information is still needed as to their respective transport capacity. In the present investigation, we compared the hepatic and intestinal transport rates for BA, using perfused livers and intestines. The livers and intestines were separately perfused and dose‐response curves (0·25–10 mM) for tauroursodeoxycholate, taurocholate and taurodeoxycholate were obtained. The intestinal and mesenteric concentration and bile acid pattern were also evaluated in six non‐fasting rabbits. Taurocholic, tauroursodeoxy‐cholic and taurodeoxycholic acid ileal absorption showed saturation kinetics in the intestine as in the liver; the maximal uptake velocity for each bile acid in the liver was tenfold higher than the respective maximal transport velocity in the intestine; the Km values obtained in the liver were of the same order of magnitude, i.e. in the millimolar range. Taurocholic, tauroursodeoxycholic and taurodeoxycholic acid transport differences in the liver paralleled those in the intestine. Although the intestine was not homogeneously filled, the bile acid concentration in the ileal content fell into the range of the Km for the three studied bile acids, while the portal blood total bile acid concentration was inferior to the observed Kms of liver uptake. Therefore, both the hepatic and intestinal systems do not operate at their maximal transport rates at the prevailing concentrations in portal blood and luminal content, and the hepatic transport occurs at its highest efficiency (below the Km values) in physiological conditions.
Persistence of counter‐regulatory abnormalities in insulin‐dependent diabetes mellitus after pancreas transplantation
Authors: BATTEZZATI A. , LUZI L. , PERSEGHIN G. , BIANCHI E. , SPOTTI D. , SECCHI A. , VERGANI S. , CARLO V. DI , POZZA G.
Published: March 2008

Abstract Conventional insulin therapy does not correct the counter‐regulatory abnormalities of insulin‐dependent diabetes mellitus. Pancreas transplantation is an alternative therapy that restores the endogenous insulin secretion in diabetes. In this study, the effects of segmental pancreas transplantation on counter‐regulation to mild hypoglycaemia were evaluated. Glucose kinetics and the counter‐regulatory hormonal responses were assessed in eight insulin‐dependent diabetics with end‐stage renal failure who had received pancreas and kidney transplantation 1 year previously, seven diabetic uraemic subjects (candidates for combined transplantation), five patients with chronic uveitis on immunosuppressive therapy comparable to pancreas recipients and 10 normal subjects. Insulin (0·3 mU kg‐1 min‐1) was infused for 2h to induce mild hypoglycaemia (plasma glucose 3·2–3·5‐mmol l‐1) and exogenous glucose was infused as required to prevent any glucose decrease below 3·1 mmol l‐1. After transplantation, two of eight recipients had hypoglycaemic episodes reported in their medical records. During the study, hepatic glucose production was rapidly suppressed in the controls and in the patients on immunsuppression (–80 ± 7 and –54 ± 7%, P < 0·001 vs. basal), and rebounded to the baseline values within 1 h (–3 ± 1 and –6 ± 2%, P= NS vs. basal). The transplant recipients had similar suppression in the first hour (–88 ± 8%, P < 0·001 vs. basal), but the suppression persisted in the second hour (–69 ± 11%, P < 0·001 vs. basal) indicating a lack of glucose counter‐regulatory response. The uraemic‐diabetics had reduced suppression of hepatic glucose production (–45 ± 14%, P < 0·001 vs. basal) with respect to the recipients (P < 0·001), but had the same lack of response in the second hour (suppression: –39 ± 12%, P < 0·001 vs. basal). In addition, the response of glucagon to hypoglycaemia was blunted in both the recipients and in the diabetic subjects. In conclusion, the alterations in glucose counter‐regulation of insulin‐dependent diabetes persists after segmental pancreas transplantation. Specifically, the increased sensitivity of hepatic glucose production to the action of insulin renders this defect more evident after transplantation.
The effect of probucol and vitamin E treatment on the oxidation of low‐density lipoprotein and forearm vascular responses in humans
Authors: McDOWELL I. F. W. , BRENNAN G. M. , McENENY J. , YOUNG I. S. , NICHOLLS D. P. , McVEIGH G. E. , BRUCE I. , TRIMBLE E. R. , JOHNSTON G. D.
Published: March 2008

Abstract This study investigates the hypothesis that lipid soluble antioxidants may increase the resistance of low‐density lipoprotein (LDL) to oxidation and also enhance vascular endothelial responses in humans. In a double‐blind parallel group study, 24 hypercholesterolaemic patients, already on treatment with simvastatin (20mg day‐1), were randomized to supplementary treatment with probucol (500 mg bd), vitamin E (400 IU daily) or placebo for 8 weeks. Mean serum cholesterol before antioxidant treatment was 7·00 mmol l‐1. Resistance of LDL to oxidation by copper was increased by 830% in the probucol group and by 30% in the vitamin E group. However, thiobarbituric acid reacting substances in whole serum were not altered by either antioxidant. Probucol lowered HDL‐and LDL‐cholesterol levels and increased the QT interval. Forearm vascular responses, as measured by venous occlusion plethysmography, to acetylcholine, glyceryl trinitrate and NG‐monomethyl‐L‐arginine, were not significantly changed by antioxidant treatment. Probucol has a major, and vitamin E a minor, effect on LDL resistance to oxidation but neither compound appears to alter forearm vascular responses in vivo.
Inhibition of human vascular smooth muscle cell proliferation by lovastatin: the role of isoprenoid intermediates of cholesterol synthesis
Authors: MUNRO E. , PATEL M. , CHAN P. , BETTERIDGE L. , CLUNN G. , GALLAGHER K. , HUGHES A. , SCHACHTER M. , WOLFE J. , SEVER P.
Published: March 2008

Abstract Restenosis remains the largest single obstacle to the long‐term success of invasive vascular interventions. Lovastatin, an HMG‐CoA reductase inhibitor, has been shown to reduce myointimal hyperplasia in animal models of restenosis and in one clinical coronary restenosis trial. We have assessed the effect of lovastatin on the growth of cultured human vascular smooth muscle cells derived from saphenous vein and vascular graft stenoses. Lovastatin (2 μM) inhibited proliferation over 14 days in saphenous vein (and graft stenoses) derived vascular smooth muscle cells by 42% and 32%, respectively: this was not significantly different. Lovastatin (10 μM) reduced [methyl 3H]‐thymidine uptake by 51% in saphenous vein‐derived cells. These concentrations were significantly higher than those achieved in plasma during therapeutic dosage. Lovastatin‐induced inhibition of vascular smooth muscle cell proliferation and [methyl 3H]‐thymidine uptake was completely reversed by adding mevalonate (100 μM) but cholesterol (10–40 μl‐1) had no effect. Isopentenyl adenine (25–50 μM) did not affect the inhibition of [methyl 3H]‐thymidine uptake by lovastatin (10 μM), but farnesol (20 μM), another isoprenoid precursor of cholesterol synthesis, reversed the antiproliferative effect.
Influence of weight reduction on platelet volume: different effects of a hypocaloric diet and a very low calorie diet
Authors: TOPLAK H. , WASCHER T. C.
Published: March 2008

Abstract Since platelet volume reflects platelet activity, the mean platelet volume (MPV) is proposed to be a further independent risk factor for cardiovascular disease (CVD). Even if it is well established that weight reduction reduces some of the risk factors of CVD in obese patients, an increase of MPV occurs during periods of weight loss. We therefore prospectively investigated the effects of different weight reduction therapies on platelet mass, platelet volume, body weight and serum lipid profile in patients undergoing an 8 week weight reduction therapy either by a hypocaloric diet (HD) or a nutritionally completed very low calorie diet (VLCD) with a subsequent maintenance period of 40 weeks. In both groups, MPV transiently increased during the 8 week diet period. After 48 weeks the MPV was decreased to initial values. The change in MPV was significantly (P < 0·05) smaller in the VLCD group. We therefore suggest that fasting might alter the control of platelet size with a possible impact on platelet activity. This might result in an increased risk for thromboembolic ischaemic events in atherosclerotic patients. Thus, we conclude that the use of a VLCD is potentially superior for weight reduction in patients with pre‐existing atherosclerosis.
Ascorbic acid reduces the endotoxin‐induced lung injury in awake sheep
Authors: DWENGER A. , PAPE H. C. , BANTEL C. , SCHWEITZER G. , KRUMM K. , GROTZ M. , LUEKEN B. , FUNCK M. , REGEL G.
Published: March 2008

Abstract Our aim was to investigate whether ascorbic acid can reduce reactive oxygen metabolite‐mediated acute lung injury.

The effects of intravenous administration of Escherichia coli endotoxin were studied, with and without ascorbic acid infusion, on haemodynamics, lung lymph flow, cardio‐respiratory and neutrophil function in chronically instrumented sheep. Paired experiments were performed on eight sheep in which they received either endotoxin alone (0·5 μg kg‐1 b.w.) (ET group) or in combination with an ascorbic acid infusion (1 g kg‐1 b.w. bolus injection followed by 0·2 g kg‐1 h‐1 continuous infusion) (ET + ASC group) in random order. Four of the animals also received ascorbic acid alone (ASC group).

As a result, for the ET + ASC group a general and mostly significant improvement (P < 0·05) in the early hypertensive phase (0·60 min, P values) and in the late permeability phase (2–4 h, *P values) of cardiorespiratory function (mean artery pressure: P/*P= 0·283/0·049; mean pulmonary artery pressure: P/*P= 0·0.0001; mean pulmonary artery wedge pressure: P/*P= 0·02/0·001; right ventricular stroke work index: P/*P= 0·02/0·0001; cardiac index: P/*P= 0·797/0·755; arterial oxygen saturation: P/*P= 0·0059/0·01; arterial‐venous difference of oxygen tension: P/*P= 0·011/0·0005), oxygen consumption: P/*P=0·013/0·035, lung lymph flow: P/*P=0·562/0·012, lymph/plasma protein ratio: P/*P= 0·304/0·008 and protein clearance: P/*P= 0·56/0·05 was observed in comparison with the ET group. The decrease of the neutrophil chemiluminescence response of the ET + ASC group in the late phase: P/*P= 0·419/0·026 was most likely due to ascorbic acid, whereas β‐N‐acetylglucosaminidase secretion was identical for both groups. In conclusion, we suggest that reactive oxygen metabolite scavenging by ascorbic acid is responsible for the improvement of endotoxin‐induced acute lung injury.
HLA‐DPB1 polymorphisms on the MHC‐extended haplotypes of families of patients with Graves' disease: two distinct HLA‐DR17 haplotypes
Authors: RATANACHAIYAVONG S. , McGREGOR A. M.
Published: March 2008

Abstract HLA‐DPB1 polymorphisms were investigated in 217 members of 21 multiplex families of patients with Graves' disease, who had previously been haplotyped, using in vitro enzymatic DNA amplification and hybridization with sequence‐specific oligonucleotide probes. Using the strategy of group‐specific amplification, we were able to assign 19 DPB1 alleles with the use of 13 sequence specific oligonucleotide probes. No recombination was found between HLA‐DPB1 and the HLA‐DR/DQ complex in 243 informative meioses. HLA‐DPB1*0401 was found to be the most common allele followed by DPB1*0101, *0201 and 0402 with allele frequencies of 0·4214, 0·1132, 0·1069 and 0·1006, respectively. Besides the strong linkage disequilibrium between HLA‐DPB1*0101 allele and the HLA‐B8, DR17/DQ2 haplotype; HLA‐DPB1*0202 and *1101 alleles were also found to be significantly associated with HLA‐B18 and DR7 with Pc < 0·001 and Pc < 0·009, respectively. HLA‐DR17/DQ2 was found to be more commonly associated with HLA‐DPB1*0101 on the Affected haplotypes (from family members affected with Graves' disease) while associated with DPB1*0401 on the Ab + ve haplotypes (deduced from thyroid autoantibody positive unaffected members). The differences in the frequency of this preferential association on the Affected and Ab + ve haplotypes was statistically significant (χ2= 10·18, df = 2, P < 0·007). Though it is rather unlikely that the HLA‐DPB1 polymorphism by itself could contribute a direct role towards the genetic susceptibility for the development of autoimmune thyroid disease, it could serve as a marker in identifying family members with the HLA‐DR17/DQ2 haplotype who are more likely to develop Graves' disease or thyroid autoantibodies.