bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for a particular binding capacity of rat peritoneal macrophages to rat glomerular mesangial cells in vitro
Authors: DUBOIS CHRISTINE H. , GOFFINET GÉRARD , FOIDART JACQUELINE B. , DECHENNE CHARLES A. , FOIDART JEAN M. , MAHIEU PHILIPPE R.
Published: March 2008

Abstract. The adhesion of normal rat peritoneal macrophages to normal rat glomerular epithelial or mesangial cells has been studied in vitro after a 60 min incubation at 37°C. After washing, the cell preparations were examined by phase contrast or scanning electron microscopy. Quantitative studies were also performed using macrophages labelled with 99mTc tin colloids. Peritoneal macrophages predominantly adhered to the cultured mesangial cells. The percentage of labelled macrophages adhering to these cells was about 10 times higher than that of labelled macrophages adhering to the cultured epithelial cells. This percentage increased proportionally to the number of labelled macrophages added, and was strongly reduced by the prior incubation of macrophagic cells with aggregated IgG, with anti‐fibronectin IgG, or with F(ab)2 fragments of anti‐fibronectin IgG. Furthermore, the macrophage‐mesangial cell interaction was significantly reduced by the prior incubation of mesangial cells with anti‐fibronectin IgG or with F(ab)2 fragments of anti‐fibronectin IgG. The data demonstrate that normal rat peritoneal macrophages preferentially adhere in vitro to normal rat glomerular mesangial cells, and that this binding may be modulated, at least, by: (a) the Fc receptor binding activity of macrophages; (b) the fibronectin molecules available at the surface of macrophages and of mesangial cells.
The individual variation in pharmacokinetics and pharmacodynamics of furosemide in young normal male subjects
Authors: ANDREASEN F. , CHRISTENSEN C. KJELDAHL , JACOBSEN F. KJAER , JANSEN J. , MOGENSEN C. E. , PEDERSEN O. LEDERBALLE
Published: March 2008

Abstract. Following a 24 h control period in the ward 80 mg furosemide was injected intravenously to ten young healthy, male volunteers. The serum clearance of furosemide (Cls) was between 140 and 201 ml min‐1 and on the average the renal clearance was 66% of Cls. During the initial 30 min period a maximum additional excretion rate of sodium of 3·3 mmol min‐1 was reached at an excretion rate of 0·8 mg furosemide min‐1. A marked initial drop in creatinine clearance (Clcr) was noted and Clcr(24 h) showed an average decrease of 12% after the drug administration. The serum concentration of potassium was decreased at 1 and 2 h after the injection and of sodium from 2 h and on. The concentration of albumin in serum increased by 3% (P < 0·05) already after 5 min. After 2 h a maximum increase of 14% was reached. After 8 min diastolic blood pressure was increased by 13% (P < 0·05), whereas systolic blood pressure reached a significant decrease gradually (7% after 3 h).
Diurnal metabolic profiles in hyperthyroidism
Authors: McCULLOCH A. J. , JOHNSTON D. G. , BURRIN J. M. , HODSON A. W. , CLARK F. , WAUGH C. , ALBERTI K. G. M. M.
Published: March 2008

Abstract. Hormone and metabolite profiles during a 12 h period of normal meals and activity were examined in nine hyperthyroid subjects with Graves' disease and sixteen matched controls. Six hyperthyroid subjects were restudied when euthyroid on carbimazole and thyroxine. Thyrotoxic patients had mild fasting hyperglycaemia (mean pL SEM blood glucose, 5·5 pL 0·2 v. 4·8 pL 0·1 mmol/l, P < 0·01), elevated blood glycerol (0·15 pL 0·02 v. 0·08 pL 0·01 mmol/l, P < 0·001) and elevated plasma non‐esterified fatty acid (NEFA) concentrations (0·91 pL 0·06 v. 0·58 pL 0·03 mmol/l, P < 0·001) when compared to controls. Fasting blood concentrations of the gluconeogenic precursors lactate, pyruvate and alanine, blood ketone body concentrations and circulating insulin and growth hormone levels were similar in hyperthyroid and control subjects. Blood glucose responses to meals were exaggerated and the mean 12 h blood glucose was increased (6·1 pL 0·1 v. 5·5 pL 0·1 mmol/l, P < 0·01) in hyperthyroidism. Similarly, hyperlactataemia and hyperpyruvicaemia were observed after meals. Blood ketone body, blood glycerol and plasma NEFA levels showed exaggerated pre‐prandial peaks and the mean 12 h values for blood glycerol (0·12 pL 0·01 v. 0·08 pL 0·01 mmol/l, P < 0·01) and plasma NEFA (0·71 pL 0·03 v. 0·53 pL 0·04 mmol/l, P < 0·01) were increased. Concentrations of insulin and growth hormone remained similar to control values throughout the study period. Blocking therapy with carbimazole and thyroid hormone replacement with thyroxine for 5–10 months suppressed blood glycerol, plasma NEFA and blood ketone body levels to normal or subnormal values but had no effect on the elevated blood glucose, blood lactate or blood pyruvate profiles.

Graves' disease with hyperthyroidism is thus associated with abnormalities of carbohydrate metabolism which are not restored to normal by 5–10 months oral antithyroid therapy. The changes in lipid metabolism in hyperthyroidism are normalized by this treatment.
The effect of respiratory and metabolic acid‐base changes on ionized calcium concentration: in vivo and in vitro experiments in man and rat
Authors: OBERLEITHNER HANS , GREGER RAINER , LANG FLORIAN
Published: March 2008

Abstract. Correlation of ionized calcium concentration, [Ca2+] and blood pH has long been recognized. So far no distinction of the acid‐base changes, i.e. respiratory changes or metabolic changes seemed necessary. The present study, with the use of a recently developed system for in vivo analysis of [Ca2+], and with in vitro experiments reinvestigates this question.

In a first series respiratory and metabolic changes were induced in rats. Changes of [Ca2+] (Δ[Ca2+]) and of plasma pH (ΔpH) were recorded continuously in vivo, plasma bicarbonate, [HCO‐3] was measured in vitro. In a second series respiratory and metabolic changes were induced in sixteen volunteers and, separately, in vitro in plasma and modified Ringer solution, and the same parameters were determined.

In all experiments Δ[Ca2+] correlates negatively with ΔpH. However, the correlation in respiratory changes was significantly less as compared to that in metabolic changes. As expected, Δ[HCO‐3] correlates positively with pH in metabolic and negatively in respiratory changes. We conclude from these experiments that in metabolic changes the effects of calciumalbumin interaction and calcium complexation with bicarbonate are additive, whereas both effects oppose each other in respiratory changes. This might explain the blunted effect of pH changes on [Ca2+] in respiratory changes.
The pharmacokinetics of porcine glucose‐dependent insulinotropic polypeptide (GIP) in man
Authors: SARSON DAVID L. , HAYTER ROGER C. , BLOOM STEPHEN R.
Published: March 2008

Abstract. The pharmacokinetics of porcine glucose‐dependent insulinotropic polypeptide were investigated in six healthy volunteers. At the maximum infusion dose (0·5 pmol kg‐1 min‐1) a plateau concentration of 115 ± 5·0 pmol/l plasma was obtained. On discontinuation of the infusion, the half‐time of disappearance was calculated to be 20·3 ± 1·2 min. The metabolic clearance rate was 2·6 ± 0·1 ml kg‐1 min‐1 and the apparent space of distribution was 75·8 ± 5·7 ml kg‐1. Blood glucose, pancreatic and gastrointestinal hormones remained at basal concentrations throughout. No side effects were noted by any of the subjects studied.
Effect of catecholamines on sterol synthesis in human mononuclear cells
Authors: KRONE W. , HILDEBRANDT F. , GRETEN H.
Published: March 2008

Abstract. The effect of adrenaline, noradrenaline, isoproterenol and dibutyryl cyclic AMP on the rate of sterol synthesis was studied in freshly isolated human mononuclear cells.

Incubation of cells in a medium containing lipid depleted serum led to a two‐fold rise in the rate of sterol synthesis from [14C]acetate. Adrenaline, noradrenaline and isoproterenol added in a concentration of 2 × 10‐5 mol/l at zero‐time resulted in an inhibition of 30% of this increase in sterol synthesis after 4 h, but had no effect when the hormones were given at 4 h. This indicates that the catecholamines require some time to exert their inhibitory action on sterol synthesis.

The action of catecholamines on the incorporation of [14C]acetate into sterols could be mimicked by dibutyryl cyclic AMP. Propranolol added in increasing concentrations to the incubation medium diminished or totally prevented the inhibitory effect of adrenaline, noradrenaline and isoproterenol on sterol synthesis.

The results indicate that cholesterol synthesis in extrahepatic human cells, regulated predominantly by low density lipoprotein derived from plasma, is under additional control of catecholamines which may act via cyclic AMP.
Adrenergic regulation of fat‐cell lipolysis in multiple symmetric lipomatosis
Authors: KATHER HORST , SCHRÖDER FRIEDHELM
Published: March 2008

Abstract. The responsiveness towards catecholamines of normal and lipomatous fat cells of two male subjects suffering from multiple symmetric lipomatosis has been studied by means of a newly developed bioluminescent method for microdetermination of glycerol.

In contrast to previous findings, lipomatous fat cells displayed normal α2– and β‐adrenergic responsiveness in both subjects studied. The apparent discrepancies between the results of the present study and those reported by others therefore support the contention that multiple symmetric lipomatosis is a symptom with various underlying causes rather than a nosological entity.
Metabolic clearance rate of immunoreactive vasopressin in man
Authors: BENMANSOUR MUSTAPHA , RAINFRAY MURIEL , PAILLARD FRANÇOISE , ARDAILLOU RAYMOND
Published: March 2008

Abstract. Metabolic clearance of synthetic arginine vasopressin (AVP) has been measured in sixteen healthy subjects and ten uraemic patients on maintenance haemodialysis. Plasma AVP was measured using a specific radioimmunoassay at different intervals after a single injection of 2 μg AVP. The theoretical curve which fitted best with the disappearance curve was the sum of two exponentials in twenty‐two subjects and of three exponentials in the other four. Metabolic clearance rate and the volume of fast initial distribution were 287·1 ml min‐1 (m2)‐1 and 219·3 ml/kg b.w., respectively, in normal subjects. Metabolic clearance rate was considerably lower in the uraemic group. This emphasizes the role of kidneys in the degradation of AVP and may account, at least in part, for the higher basal plasma value of this hormone observed in uraemic patients.
Effect of vitamin B6 administration on elevated plasma oxalic acid levels in haemodialysed patients
Authors: BALCKE P. , SCHMIDT P. , ZAZGORNIK J. , KOPSA H. , DEUTSCH E.
Published: March 2008

Abstract. Accumulation of oxalic acid resulting in elevated plasma levels is a common finding in uraemic patients. Since vitamin B6 is an important coenzyme in oxalic acid metabolism the influence of vitamin B6 administration on plasma oxalic acid levels was investigated.

Vitamin B6 was administered to eight chronic haemodialysis patients with secondary hyperoxalaemia. Mean plasma oxalic acid concentration decreased from 149·5 ± 67 μmol/l to 99·0 ± 36·4 μmol/l within 2 weeks and to 93·8 ± 33·1 μmol/l after 4 weeks of pyridoxine treatment (P<0·01) the mean reduction being 46% (32·0–56·1%). The decrease in plasma oxalic acid levels was most pronounced in patients with the highest pretreatment values. Two patients who received pyridoxine therapy prior to the beginning of the study had low initial values of plasma oxalic acid concentrations and showed no further decline.
Relationship between muscle morphology and metabolism in obese women: the effects of long‐term physical training
Authors: KROTKIEWSKI M. , BYLUND‐FALLENIUS A‐C. , HOLM J. , BJÖRNTORP P. , GRIMBY G. , MANDROUKAS K.
Published: March 2008

Abstract. To evaluate the relationships between changes in muscle morphology and metabolic adaptation to physical training in obesity, twenty obese women were subjected to a physical training pro‐gramme with three sessions a week for 3 months. Physical training resulted in lowering of plasma insulin and improved glucose tolerance. Neither body weight nor body fat changed. With physical training the percentage distribution of fast twitch oxidative (FTa) muscle fibres (m vastus lateralis) increased (from 30.3±5.1% to 35.2±4.8%, P < 0.05) and that of fast twitch glycolytic fibres decreased (from 18.3±6.6 to 5.8±4.8%, P <0.05). The number of capillaries increased, mainly around slow twitch (ST) fibres (from 4.5±0.6 to 5.8±0.8, P < 0.01) and fast twitch oxidative (FTa) fibres (from 3.9±0.7 to 4.7±0.8, P <0.01). The activities of oxidative enzymes (cytochrome‐c‐oxidase and citrate synthase) increased (P<0.05) while those of glycolytic enzymes (phosphofructokinase and hexokinase) decreased after physical training (P<0.01).

Significant negative correlations between plasma insulin and number of capillaries in contact with ST fibres (r=0.80, P<0.001) and FTa fibres (r= 0.62, P<0.001) were found before training. The capillary density around those fibres could predict 80% of the explained variance of plasma insulin levels (P<0.001). The changes of glucose concentration after training could be predicted by observed changes in enzyme activities. The strong associations between muscle morphology and capillarization and enzyme activities and glucose and insulin concentrations and their changes after training suggest an important regulatory role of muscle which warrants further studies.
The urinary excretion of prostaglandins E2 and F2α in essential hypertension
Authors: RATHAUS MAURO , KORZETS ZEEV , BERNHEIM JACQUES
Published: March 2008

Abstract. The 24 h urinary excretions of prostaglandins E2 (E2/d) and F2α (F2α/d) were measured in twenty‐five normal subjects and in thirty‐five patients with essential hypertension [seventeen with low renin (LRH) and eighteen with normal renin (NRH) hypertension].

E2/d was lower in patients with LRH than in normal subjects (P<0.01), whereas no difference was found between patients with NRH and the controls. F2α/d was similar in patients with LRH and in the normal subjects, but was significantly greater in patients with NRH (P<0.02). The ratio of prostaglandin E2 to prostaglandin F2α was decreased in hypertensive patients (P < 0.02), although in the NRH subgroup the difference was not statistically significant.

It appears that LRH is associated with impaired production of prostaglandin E2, while a deranged relationship between the two prostaglandins exists in all the patients with essential hypertension. These changes in prostaglandin production could possibly contribute to the pathogenesis of hypertension, by increasing renal vascular resistance and decreasing sodium excretion. Alternatively, they might be a secondary phenomenon, reflecting changes in renal prostaglandin metabolism induced by the hypertensive state.
Study of micturition parameters in healthy young adults using a uroflowmetric method
Authors: MEUNIER PATRICK
Published: March 2008

Abstract. Using the 21 F 01 DISA Mictiograph, the instant urine flow curves of fifty normal males and thirty‐three females (aged from 18 to 35 years) were analysed. A total of 363 micturitions was obtained (146 in the female group, 217 in the male group). Ten parameters were derived from each of the urine flow curves. These parameters were: the voided volume, the micturition time, the average‐flow rate, the flow at 2 s, the maximum flow‐rate, the percentage of difference between the maximum flow rate and the average‐flow rate, the duration until the maximum flow rate, the initial slope of the curve, the slope at the time from micturition initiation of voiding to maximum flow, and the difference between the two slopes. This study demonstrated that the urine flowmeter allowed, even at very low voided volume, a complete interpretation of micturition flow curves, a finding which might be useful in paediatric patients. It was also shown that the flow parameters were significantly more favourable in females than in males, and consequently that better hydrodynamics conditions for micturition exist in women compared to men.
Peripheral blood cell changes in response to acute hypoglycaemia in man
Authors: FRIER B. M. , CORRALL R. J. M. , DAVIDSON N. McD. , WEBBER R. G. , DEWAR A. , FRENCH E. B.
Published: March 2008

Abstract. Peripheral white and red blood cell changes were studied in response to acute insulin‐induced hypoglycaemia in six normal, six splenectomized and five sympathectomized (tetraplegic) subjects. The normal subjects were restudied during beta (propranolol) and beta1‐selective (metoprolol) adrenergic blockade.

In the normal subjects a lymphocytosis immediately followed the acute hypoglycaemic reaction (R) with a neutrophilia 2 h later. The early lymphocytosis was absent in sympathectomized subjects (P<0.01) and reduced under beta blockade (P<0.02) in normal subjects, indicating mediation via an adrenergic mechanism. The later neutrophilia from R + 60 min was not abolished by adrenergic blockade or preceding sympathectomy; the enhanced response with propranolol was associated with an elevated plasma Cortisol.

Haemoglobin, packed cell volume and total erythrocyte count rose maximally at R in all groups except the sympathectomized subjects in whom all parameters declined progressively from basal values. These peripheral erythrocyte changes appear to be mediated via an adrenergic mechanism which is unaffected by beta adrenergic blockade and which does not involve splenic contraction.
Cell attachment, growth characteristics and surface morphology of human upper‐respiratory tract epithelium cultured on extracellular matrix
Authors: WIESEL JOCHANAN M. , GAMIEL HAIM , VLODAVSKY ISRAEL , GAY ISSAC , BEN‐BASSAT HANNAH
Published: March 2008

Abstract. The advantageous utilization of nasal polypoid tissue as a source for human epithelial cells and the dramatic effect of extracellular matrix on growth and differentiation of these cells were demonstrated. Plating on extracellular matrix induced rapid, firm, cell attachment and flattening of the explants, promoted cell outgrowth as well as long‐term survival of epithelial cells in primary cultures. Prominent ciliary activity was observed on the cells of the explant and on the cells in the outgrowth. These cells could be maintained on the extracellular matrix coated dishes for prolonged periods even after removal of the explant, with the cells in the outgrowth covering the region occupied by the removed explant. Prominent ciliary activity, which is considered one of the main criteria for cell viability and differentiation, continued also in the absence of the explant.

The present system for cultivation of human upper respiratory tract epithelial cells on extracellular matrix might prove of value in analysing effects of chemother‐apeutic agents that influence normal differentiation as well as the effects of viral and chemical carcinogens on these cells in human respiratory disease.
The identification of urinary bile alcohols by gas chromatography–mass spectrometry in patients with liver disease and in healthy individuals
Authors: LUDWIG‐KÖHN HELGA , HENNING H. V. , SZIEDAT ASTRID , MATTHAEI D. , SPITELLER G. , REINER J. , EGGER H.‐J.
Published: March 2008

Abstract. The neutral steroid fractions in the urine of eleven patients suffering from various forms of liver disease with cholestasis and of ten healthy individuals were studied by glass capillary gas chromatography‐mass spectrometry. The steroid conjugates in urine were enzymatically solvolysed, the liberated steroids extracted and transformed into the trimethylsilylether for measurements.

The excretion rates of androstane and pregnane metabolites of patients with liver disease were far lower than those of healthy persons. The main compounds in the urine of the former were the bile alcohols 27 ‐ nor ‐3α, 7α, 12α, 24, 25 ‐ pentahydroxy ‐ 5β ‐ cholestane and 3α, 7α, 12α, 25, 26 ‐ pentahydroxy ‐ 5β ‐ cholestane. Our data suggest a correlation between the excretion rates of these bile alcohols and the serum levels of bilirubin. While the excretion rate of the two bile alcohols in the urine of healthy individuals was approximately 0.24 mg/24 h (0.6 μmol/24 h) a patient with a serum bilirubin of 841 μmol/1 excreted 4 mg/24 h (9 μmol/24 h). The accumulation of bile alcohols described in this study possibly indicates alternative pathways of cholic acid formation in liver disease.
Faecal excretion of bile acids and neutral steroids on diets differing in type and amount of dietary fat in young healthy persons
Authors: BRUSSAARD J. H. , KATAN M. B. , HAUTVAST J. G. A. J.
Published: March 2008

Abstract. The effect of different amounts and types of dietary fat on faecal steroid excretion in healthy volunteers was examined. In the first experiment with sixty volunteers four diets which differed in type and amount of dietary fat only were compared during a test‐period of 5 weeks. Faeces were collected during 7 days before and at the end of the test period and analysed individually. In the second experiment with thirty‐five volunteers, a low fat diet containing 22% of energy as total fat (4% as polyunsaturated fatty acids) was compared with a moderate fat diet (30% of energy as total fat; 11% as polyunsaturated fatty acids) during 13 weeks. Faeces were collected during the first 7 days of the test period and during 7 consecutive days near the end of the test period and pooled per dietary group.

Excretion of faecal neutral steroids and bile acids was not significantly influenced by amounts of total fat ranging from 22% to 40% of daily energy or by differences in polyunsaturated to saturated fatty acids ratio from 0.2 to 1.7. The only exception was the excretion of bile acids in the second experiment which was 0.19 mmol/24 h (75 mg/24 h) higher on the low fat diet than on the moderate fat, high polyunsaturated fat diet (P < 0.01).
Clinical significance of serum hydroxyproline‐containing peptides with special reference to hyproprotein
Authors: YAMADA SADAKO , HIRAYAMA CHISATO
Published: March 2008

Abstract. Serum hydroxyproline‐containing peptides were separated into three fractions, i.e. large protein, polypeptide and smaller peptides, by gel filtration on Sephadex G‐200. The large protein was presumed to be the Clq subunit of the first component of complement by an immunological analysis. The polypeptide had an electrophoretic mobility corresponding to β‐globulin and its molecular weight was estimated between 35 000 and 45 000 by gel filtration analysis. The polypeptide might well be defined as hyproprotein. The molecular weight of smaller peptides was estimated between 1400 and 3000.

As compared with the control value, hyproprotein levels were significantly increased in rheumatoid arthritis, systemic lupus erythematosus and chronic liver disease. Clq levels were slightly lowered in rheumatoid arthritis and systemic lupus erythematosus, and were slightly increased in chronic liver disease but were not significant. In all patient groups smaller peptides levels remained in the normal range. These results suggest that serum hyproprotein levels are raised in some fibroproliferative disorders, probably reflecting collagen metabolism.
Normal and low molecular weight heparins: interaction with human platelets
Authors: FABRIS F. , FUSSI F. , CASONATO A. , VISENTIN L. , RANDI M. , SMITH M. R. , GIROLAMI A.
Published: March 2008

Abstract. Porcine mucosal heparin was chemically depolymerized. The depolymerization was stopped at different steps to obtain two low molecular weight (LMW) heparins with a molecular weight of 10 000 and 6000, respectively. The LMW heparins were tested in vitro for anti‐clotting activities and for platelet serotonin release in different systems in comparison with normal heparins, dermatan and heparan sulphate.

After addition of various amounts of heparin preparations to washed platelets, no significant release was observed for all tested heparins. On the contrary, different heparins showed an inhibition of serotonin‐release induced by collagen in platelet rich plasma, whereas the ADP‐induced release was increased. The effect on the platelet release appears related to the molecular weight. In fact, it is significant only for normal heparins whereas it is not for LMW heparins. A good relation was observed, also, between anti‐activated factor X activity/antiglobal clotting activity (Xa/APTT) ratio of different heparins and the effect on platelet release.
Liver damage associated with occupational exposure to organic solvents in house painters
Authors: DØSSING MARTIN , ARLIEN‐SØBORG PETER , PETERSEN LISBETH MILLING , RANEK LEO
Published: March 2008

Abstract. Among 156 patients admitted to hospital because of suspected solvent intoxication or dementia following long‐term occupational exposure to organic solvents, twenty‐three had elevated aminotransferases in serum. In thirteen of these no particular cause of this elevation could be found and the chronic exposure to aliphatic and aromatic organic solvents is therefore likely to have played a pathogenetic role and a liver biopsy was performed.

Liver histology revealed significant steatosis in eleven patients and in six of these focal necroses were also observed. Moreover, six of the biopsies showed enlarged portal tracts with fibrosis. Necrosis was only observed in liver specimens from patients who recently had been exposed to solvents.

A causal relation between occupational exposure to aliphatic and aromatic organic solvents such as white spirit, xylene, toluene and styrene, and toxic liver injury is suggested by this descriptive study but needs confirmation.
Effect of diazoxide‐induced hypotension on cerebral blood flow in hypertensive rats
Authors: BARRY D. I. , STRANDGAARD S. , GRAHAM D. I. , BRAENDSTRUP O. , SVENDSEN U. G. , BOLWIG T. G.
Published: March 2008

Abstract. The effect on cerebral blood flow of acute diazoxide‐induced hypotension was studied in rats with renal and spontaneous hypertension. Diazoxide (5 mg/kg, i.v. bolus), caused arterial pressure to fall rapidly to that of normotensive rats, i.e. c. 75 mmHg. There was a concomitant fall in cerebral blood flow of about 35% (P< 0.01) in renal hypertensive rats and 25% (P < 0.05) in spontaneously hypertensive rats; the greater fall in flow in the former corresponded to a greater drop in pressure. Flow remained at these reduced levels during a 2 h observation period. Histological examination revealed small areas of is‐chaemic damage in the brains of five of the twelve animals. In control hypertensive rats not given diazoxide, cerebral blood flow and blood pressure were stable during a 2 1/2 h period and there was no evidence of ischaemic damage to the brains. The diazoxide‐induced reduction in cerebral blood flow was interpreted as being secondary to a blood pressure fall to below the lower limit of cerebral blood flow autoregu‐lation. No evidence was found of direct effects on the cerebral circulation such as seen with ganglionic blockers, alpha‐blockers and cerebral vasodilators.
Immune function during ageing in man: relation between serological abnormalities and cellular immune status
Authors: LOKHORST H. M. , LINDEN J. A. van der , SCHUURMAN H. J. , MEYLING F. H. J. GMELIG , BAST E. J. E. G. , GAST G. C. de
Published: March 2008

Abstract. In a group of 176 apparently healthy aged people living at home (age range 62–86 years) the prevalences of monoclonal immunoglobulin and of autoantibodies did not differ from those found in other studies, but remarkably 38% of the people studied had cold lymphocytotoxic antibodies. The occurrence of serological abnormalities showed no age dependency.

The participants were grouped according to serological abnormalities. The various groups showed no differences in peripheral blood mononuclear cell composition (concentration of B lymphocytes and T lymphocytes or of T lymphocyte subsets with OKT 4 and OKT 8 phenotype) or function (lymphocyte stimulation with phytohaemagglutinin, concanavalin A, pokeweed mitogen and antigen cocktail). Compared with a control group of young blood donors, the lymphocyte stimulation responses tended to be lower in the old age groups. It is concluded that, as measured in this study, humoral abnormalities during ageing are not associated with changes in B and T lymphocyte subsets or function.
Raised plasma levels of thromboxane B2 in systemic mastocytosis
Authors: OUWENDIJK R. J. T. , ZIJLSTRA F. J. , WILSON J. H. P. , BONTA I. L. , VINCENT J. E. , STOLZ E.
Published: March 2008

Abstract. Plasma levels of thromboxane B2 and 6‐keto‐prostaglandin F1α were measured in six patients with systemic mastocytosis. Patients with systemic mastocytosis had significantly higher plasma thromboxane B2 levels (530 ± 105 pg/ml, mean ± SEM) than controls (118 ± 8.2 pg/ml, P < 0.001) and significantly lower 6‐keto‐prostaglandin F1α levels (40 ± 3.1 pg/ml, mean ± SEM) than controls (49 ± 1.6 pg/ml, P < 0.05).

The mechanism of the raised plasma thromboxane B2 levels is not clear. One possible explanation is that the high thromboxane levels are secondary to an increased production of leukotrienes C and D, which are constituents of slow reacting substances of anaphylaxis.
Effects of retrograde luminal perfusion of the canine jejunum on intestinal absorption and myoelectrical activity
Authors: MITCHELL ANDREW , COLLIN JACK , DENTON TERENCE G.
Published: March 2008

Abstract. The effects of retrograde luminal perfusion of a 75 cm jejunal segment on absorption, transit time and myoelectrical activity were studied in four dogs. Retrograde perfusion increased jejunal absorption of water (0.016–0.021 ml cm intestinal length‐1 min‐1; P < 0.001) together with sodium (1.15‐1.82 μmol cm‐1 min‐1; P < 0.001) and glucose (1.98‐2.27 μmol cm‐1 min‐1; P < 0.01). Mean jejunal transit time was prolonged (9.2–13.9 min; P < 0.001) and jejunal spike activity was reduced compared with antegrade perfusion (14.5—4% of slow wave frequency; P < 0.01).

These results suggest that the reversal of small bowel segments in the treatment of the short bowel syndrome can result in an increase in absorption from the reversed segment itself in addition to any effect from delayed transit in the proximal bowel.
Local fibrinolytic activity and its structural basis in experimental gastric ulcers
Authors: STENBERG BJÖRN , BYLOCK ANDERS , RISBERG BO
Published: March 2008

Abstract. The stomach contains plasminogen activators localized to submucosal vessels and to the mucosa. To study the release of plasminogen activators from mucosal cells, we induced mucosal damage by pyloric ligature and instillation of 0.5 mol/l HCl in rats. After 4 h, all rats developed focal necrotic lesions and a diffuse mucosal damage, as studied both by light microscopy and by scanning electron microscopy. Diffuse mucosal damage was accompanied by significant increase (P < 0.001) in mucosal fibrinolytic activity based on plasminogen activators. This activity was probably derived from injured mucosal cells since focal necrotic lesions (erosions and ulcers) with total denudation of the mucosal epithelium lacked fibrinolytic activity. The results obtained in this study support the hypothesis that plasminogen activators are released during cellular degeneration.
Radionuclide quantification of mitral and aortic regurgitation
Authors: FOLMER S. C. C. REINDERS , KOSTER R. W. , RIVIÈRE A. V. LA , DUNNING A. J.
Published: March 2008

Abstract. Gated equilibrium bloodpool scintigraphy was used to obtain the ratio of left and right ventricular stroke counts (end‐diastolic minus end‐systolic counts within ventricular areas of interest), the radionuclide equivalent of stroke volumes. This ratio or stroke count index (SCI) should be unity in normal subjects and increased in patients with aortic or mitral regurgitation, when left ventricular stroke output rises to compensate for regurgitant flow.

Results of this non‐invasive method were compared with semiquantitative angiographic grading of mitral (1 to 4+) or aortic (1 to 3+) regurgitation in ninety‐seven patients. We found a SCI of 1.15 ± 0.18 (SD) in thirty‐six control subjects without evidence of mitral or aortic regurgitation at cardiac catheterization. Subsequently, a ratio of 1.50 was chosen as the upper limit of normal for the analysis of thirty‐seven patients with mitral regurgitation and twenty‐four patients with aortic regurgitation. Clearly, elevated SCI values were obtained in the presence of grade 3 and 4 mitral regurgitation (eighteen out of twenty patients) and of grade 2 and 3 aortic regurgitation (seventeen out of eighteen patients). Only two out of seventeen subjects with grade 1 or 2 mitral incompetence had an elevated SCI, while none of six subjects with grade I aortic regurgitation had an abnormal SCI. If these lesser degrees of valvular incompetence are considered of minor significance, overall sensitivity of the radionuclide method in our patient population was 92%, specificity 95%. Occasional discrepancies between SCI and angiographic severity of left‐sided valvular regurgitation are probably a result of methodological limitations. We could not demonstrate any relation with global left ventricular function as measured from the radionuclide ejection fraction.

We conclude that the SCI may be used as a non‐invasive tool for diagnosis and management of patients with valvular heart disease, both before and after interventions.
Effects of induced hypotension on breathing pattern in halothane‐anaesthetized man
Authors: HANNHART BERNARD , BERTRAND DOMINIQUE , PESLIN RENÉ , BOHADANA ABRAHAM
Published: March 2008

Abstract. The effects of hypotension induced by trimetaphan on ventilatory control were assessed in sixteen normal subjects under halothane anaesthesia. The breathing pattern, mouth occlusion pressures, lung mechanics, acid‐base balance, and arterial blood gases were analysed before and during trimetaphan infusion. During induced hypotension, the only significant change in the ventilatory variables was an increase in the ratio of inspiratory duration to total cycle duration from 0.39 ± 0.05 (SD) to 0.42 ± 0.03; P < 0.01. The average minute ventilation remained unchanged. No modification in lung mechanics was observed, but all subjects developed a slight but significant hypocapnic alkalosis: PaCO2 was reduced from 5.5 ± 0.4 to 5.2 ± 0.4 kPa (P± 0.001) and pH increased from 7.34 to 7.36 (P < 0.05), without change in standard bicarbonate concentration.

Our data indicate that the reduction in sympathetic nervous system activity induced by trimetaphan infusion in spontaneously breathing man causes only a minor alveolar hyperventilation. The weak respiratory response to hypotension suggests that changing peripheral afferent activity has little influence on the typically rapid breathing pattern induced by halothane.
Increased tight junction permeability: a possible mechanism of oestrogen cholestasis
Authors: ELIAS ELWYN , IQBAL SAJIDA , KNUTTON STUART , HICKEY ANTHONY , COLEMAN ROGER
Published: March 2008

Abstract. Ethinyl oestradiol increased rat biliary permeability for 3H‐inulin and 14C‐sucrose, and significantly raised serum concentrations of bile acids after 3 and 7 days' treatment (P < 0.0005) and bilirubin after 7 days (P < 0.005) but not after 3 days. Following intravenous infusion of bromsulphthalein or phenolphthalein, ethinyl oestradiol‐treated rats had elevated plasma concentrations of the three bile constituents, bromsulphthalein (P < 0.0005 after 3 and 7 days), bromsulphthalein‐glutathione conjugate (P < 0.005 after 3 days; P 0.0005 after 7 days) and phenolphthalein glucuronide (P < 0.005 after 3 days; P < 0.0005 after 7 days), but the plasma concentration of unconjugated phenolphthalein, which was undetectable in bile, was unchanged. Similar changes followed partial biliary obstruction produced by bile cannula elevation. This pattern suggests that biliary constituents are refluxing from bile to plasma via the paracellular pathway, a concept further supported by structural changes in tight junction morphology in the oestrogen‐treated rats. ‘Leakiness’ of canalicular tight junctions may explain the pathophysiology of oestrogen‐induced cholestasis.
Endothelial cell dysfunction in homocystinuria
Authors: GROOT PHILIP G. DE , WILLEMS CHARLES , BOERS GODFRIED H. J. , GONSALVES MERVIN D. , AKEN WILLEM G. VAN , MOURIK JAN A. VAN
Published: March 2008

Abstract. This report describes the isolation and culture of venous endothelial cells from the umbilical cord of an obligate heterozygote for homocystinuria. The effect of different sulphur‐containing amino acids on the viability and function of these cells was studied and compared with cultured normal endothelial cells. When endothelial cells were cultured in the presence of methionine (10 mmol/l) or homocystine (10 mmol/l), differences occurred between the viability and function of the heterozygote and normal cells in terms of 51Cr release and ability to prevent platelet adherence. The Cr release corrected for spontaneous release increases for the heterozygote cells after incubation for 21 h in the presence of methionine to 81.3% (control cells, range: 0–23.3%, n= 5) and in the presence of homocystine to 141% (control cells, range: 13.5–55.2%, n= 5). The total number of platelets that adhere to confluent monolayers increases for heterozygote cells cultured in the presence of methionine to 0.98 ± 107 platelets cm‐2 (normal cells, range: 0.56–0.72 ± 107 platelets cm‐2) and in the presence of homocystine to 1.41 ± 107 platelets cm‐2 (normal cells, range: 0.94–1±06 ± 107 platelets cm‐2). Both normal and control cells were sensitive to homocysteine. This study indicates for the first time what vascular endothelial cells, derived from an obligate heterozygote, are (partly) deficient in cysthathionine synthase and are more susceptible to methionine‐ and homocystine‐mediated injury than normal endothelial cells. Consequently, in homocystinuria, due to dysfunction of the endothelial cells, toxic sulphur‐containing amino acids may accumulate in these cells, causing injury of these cells.
The effect of high‐resistance training on the strength and cross‐sectional area of the human quadriceps
Authors: YOUNG A. , STOKES M. , ROUND J. M. , EDWARDS R. H. T.
Published: March 2008

Abstract. Seventeen volunteers performed unilateral strength‐training of the quadriceps with high‐resistance, low‐repetition, dynamic exercise, thrice weekly for an average of 5 weeks. Both before and after the training period, bilateral measurements were made of isometric quadriceps strength, quadriceps cross‐sectional area (by ultrasound scanning), and thigh circumference.

There were no significant changes in the untrained thighs. The trained quadriceps increased their isometric strength by more than they changed their cross‐sectional area (mean increments = 15% and 6% respectively). Quadriceps hypertrophy was underestimated by measurements of thigh circumference and could not be predicted from them.

We conclude that studies of localized muscle growth require direct measurements of the size of the muscle(s) concerned. Nevertheless, these may still underestimate the improvements in strength produced by high‐resistance training.
Portal‐systemic spill‐over of bile acids: a study of mechanisms using ursodeoxycholic acid
Authors: MIESCHER G. , PAUMGARTNER G. , PREISIG R.
Published: March 2008

Abstract. Portal‐systemic spill‐over of unconjugated ursodeoxycholic acid (UDCA) was assessed in ten healthy subjects, six patients with mild chronic liver disease and eight patients with cirrhosis. Following oral administration of UDCA (1·5 mg/kg body weight), serum concentrations of unconjugated UDCA were measured during 2 h using a capillary gas‐liquid chromatographic method. Peak time of UDCA varied from 15 to 30 min, but was not significantly different in the three groups studied. Peak concentration was increased up to two‐fold in patients with mild, and up to three‐fold in patients with cirrhotic liver disease. Since, in addition, plasma disappearance rate (k) was markedly impaired in cirrhotics (1·7 ± SD 0·5 %/min, compared to 2·8 ± 0·6 in healthy controls), the calculated area under the curve (AUC) was on the average five‐fold that in controls. In two healthy and four cirrhotic subjects, the data obtained after oral administration were compared with those after i.v. loading with the same UDCA dose. The k‐values after the two routes of administration were practically identical. Calculated systemic availability was 50% in normals, 78–87% in cirrhotics, 90 and 136% in two patients with surgical porta‐caval shunt. It is concluded that the portal‐systemic spill‐over of UDCA in patients with liver disease is increased primarily due to portal‐systemic shunting. Since in the normal liver hepatic extraction of conjugated, endogenous bile acids is greater than 80%, diminished first‐pass elimination is expected to augment systemic concentrations even more, particularly when measured after a meal.
Phenytoin modulates the pharmacokinetics of prednisolone and the pharmacodynamics of prednisolone as assessed by the inhibition of the mixed lymphocyte reaction in humans
Authors: FREY BRIGITTE M. , FREY FELIX J.
Published: March 2008

Abstract. Following induction of the microsomal liver enzymes, lower total prednisolone concentrations in plasma and an altered pattern of the prednisolone metabolites generated were observed. The purpose of the present study was to establish whether—as a consequence of an enhanced clearance—lower unbound concentrations of prednisolone in plasma are detectable after enzyme induction and to determine if the altered prednisolone metabolism modulates the biological effect.

Before and during phenytoin dosage in ten volunteers, the mean (±SD) total body clearance (ml min‐1 kg‐1) of both total and unbound prednisolone increased from 2·74±0·47 to 3·94±0·66 (P<0·001) and from 10·76±2·68 to 16·00±3·17 (P<0·001), respectively. These increments were due to increased non‐renal clearances. The immunosuppressive activity as a function of time in plasma determined as the percent inhibition of the mixed lymphocyte reaction decreased by one third after phenytoin dosing, while the EC50 values of unbound prednisolone were unaffected. Thus enzyme induction decreases both the unbound prednisolone concentration and the steroid efficacy.
Serum lipids and apolipoproteins A‐I, A‐II and B in primary hypothyroidism before and during treatment
Authors: MULS ERIK , ROSSENEU MARYVONNE , BLATON VICTOR , LESAFFRE EMMANUEL , LAMBERIGTS GERARD , MOOR PIETER DE
Published: March 2008

Abstract. Serum lipids and apolipoproteins (apo) A‐I, A‐II, and B were measured in twenty‐four patients with severe primary hypothyroidism (Thyrotropin above 40 mU/l), before and during l‐thyroxine treatment. Apo A‐I, A‐II, and B were assayed by immunonephelometry, using monospecific antisera.

The serum levels of total cholesterol (TC), of low‐density lipoprotein cholesterol (LDLc), and of the major LDL apoprotein, apo B, were markedly increased in the untreated hypothyroid patients compared to the values during therapy (TC: mean±SD, 8·87±2·9 v. 5·48±1·6 mmol/l; LDLc: 6·66±2·6 v. 3·78±1·4 mmol/l; apo B: 1·66±0·48 v. 1·14±0·37 g/l; P<0·00001 for all variables). High‐density lipoprotein cholesterol (HDLc) was slightly higher before than during therapy (1·58±0·7 v. 1·31±0·4 mmol/l; P<0·05), while the main HDL apoprotein, apo A‐I, was significantly elevated (1·49±0·42 v. 1·13±0·27 g/l; P<0·0002). The increase of the second major HDL apoprotein, apo A‐II, was less pronounced (0·33±0·1 v. 0·30±0·08 g/l; P<0·022). The apo A‐I to apo A‐II ratio, which reflects the relative concentrations of the HDL subfractions HDL2 and HDL3, was significantly higher before than during treatment (P<0·0006). Serum triglyceride levels were moderately elevated in the untreated hypothyroid patients (1·34±0·6 v. 0·95±0·4 mmol/l; P<0·002). The small decrease in body weight during therapy did not correlate with the changes of the various lipid and apoprotein parameters.

These data indicate that severe hypothyroidism has a differential influence on the serum concentrations of the major HDL apoproteins, A‐I and A‐II, and suggest that hypothyroidism is associated with an increase of HDL2 relative to HDL3.
Bile lipid composition and haemostatic variables in a case of high density lipoprotein deficiency (Tangier disease)
Authors: VERGANI CARLO G. , PLANCHER ANGELO C. , ZUIN MASSIMO , CATTANEO MARCO , TRAMALONI CASIMIRO , MACCARI SERGIO , ROMA PAOLA , CATAPANO ALBERICO L.
Published: March 2008

Abstract. A 62‐year‐old man with clinical and biochemical findings consistent with homozygous Tangier disease is presented. Widespread atherosclerosis was present. Bile lipid analysis showed a low molar percentage of cholesterol with a low saturation index. The data suggest that high density lipoprotein cholesterol may act as a preferential precursor of bilary cholesterol. Coagulation and platelet studies indicated that the patient's platelets were hyper‐responsive to aggregating agents and produced an increased amount of thromboxane B2. A platelet storage pool deficiency was also found.
Effects of methylprednisolone on the Fc‐receptor function of human reticuloendothelial system in vivo
Authors: HOYOUX CLAIRE , FOIDART JACQUELINE , RIGO PIERRE , MAHIEU PHILIPPE , GEUBELLE FERNAND
Published: March 2008

Abstract. To determine whether the Fc‐receptor function of reticuloendothelial system (RES) is modified by corticosteroid administration, we studied the spleen to liver uptake ratios of autologous, 99Tc‐labelled heatdamaged or IgG‐coated erythrocytes, injected intravenously into 10 normal volunteers, 4 h after receiving a single dose of 32 mg of methylprednisolone by mouth.

In standard conditions, quantitative scans indicated that the spleen to liver uptake ratios, calculated per unit area 40 min after the injection of labelled erythrocytes, were 13·4 ± 0·6 and 31·2 ± 1·5 (mean values ± ‐SEM), for the heat‐damaged (n= 7) and IgG‐coated red cells (n= 5) respectively. Four hours after corticosteroid administration, the spleen to liver uptake ratios were significantly reduced in five of ten volunteers. Abnormal ratios correlated with the Fc‐receptor function of monocytes measured in vitro using IgG‐coated erythrocytes. Indeed, 2–6 h after methylprednisolone was given, the Fc‐receptor binding activity of monocytes isolated from the same five subjects was reduced by at least 50%, spontaneously returning to a rather normal value 4–6 h later. The C3‐receptor binding activity of these monocytes remained normal, after otherwise identical experimental conditions.

These results show a transient, specific impairment of the Fc‐receptor function of RES after methylprednisolone administration, and may therefore explain, in part, the infectious complications occurring in some patients treated by corticosteroids.
Adenylate cyclase in the maturing human reticulocyte: selective loss of the catalytic unit, but not of the receptor‐cyclase coupling protein
Authors: FARFEL ZVI , COHEN ZOHARA
Published: March 2008

Abstract. Hormone sensitive adenylate cyclase consists of at least three components; hormone receptor, a catalytic unit, and the N‐protein, which couples the receptor to the catalytic unit. Human erythrocytes have very low adenylate cyclase activity, but do have N‐protein activity. We have investigated the fate of the catalytic unit and the N protein during maturation of human reticulocytes. We compared red blood cell membranes derived from nine patients with reticulocytosis averaging 12% to erythrocyte membranes from eight normal subjects. The catalytic unit was assayed by stimulation of adenylate cyclase with forskolin, and the N‐protein activity by an in vitro complementation assay. Forskolin stimulated adenylate cyclase activity was ten times higher in membranes derived from patients with reticulocytosis as compared with those of normal subjects. N‐protein activity was only slightly (12%) and insignificantly (P= 0·08) higher in the reticulocytosis patients membranes. We conclude that during maturation of the human erythrocyte there is a differential loss of the catalytic unit of adenylate cyclase.