bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of calcium intake on serum levels of 25‐hydroxyvitamin D3
Authors: BERLIN T. , BJÖRKHEM I.
Published: March 2008

Abstract. The effects of high calcium intake on vitamin D metabolism were investigated. To the normal diet of 14 healthy men, 2 g calcium were added daily for 6–7 weeks. The mean serum concentration of 25‐hydroxyvitamin D3 increased from 73 ± 7 to 94 ± 6 nmol l‐1 (P<0·05, Student's unpaired t‐test; P<0·01, paired t‐test) in the subjects receiving calcium, whereas there was only a minimal increase, from 67 ± 5 to 71 ± 4 nmol l‐1 in a control group on a normal diet. At the end of the study the difference between the test group and the controls was highly significant (P<0·005). The calcium loading caused a statistically significant depression of the serum levels of 1,25‐dihydroxyvitamin D. The results obtained are in agreement with previous studies in rats and indicate that calcium intake is of some importance for the serum level of 25‐hydroxyvitamin D3. The findings are discussed in relation to our previous finding that there is a relationship between high 25‐hydroxyvitamin D3 levels and hypercalciuria in renal‐stone formers.
Determinants of kallikrein proteolysis of apolipoprotein B‐100 in human blood plasma
Authors: GUSTAFSON A. , KANE J. P. , HAVEL R. J.
Published: March 2008

Abstract. The formation of apolipoprotein B‐74, a fragment of apolipoprotein B‐100, in blood plasma in vitro is shown to occur only at temperatures below 15°C, and is promoted by exposure to glass and other surfaces known to activate factor XII. Removal of C‐I esterase inhibitor from plasma permits formation of apolipoprotein B‐74 at room temperature. These observations are consistent with conversion of prekallikrein to kallikrein by factor XII, and with evidence that kallikrein proteolysis in vitro is activated in the cold by alteration of its binding to C‐I esterase inhibitor. Since the two proteolytic fragments of apolipoprotein B‐100 produced by kallikrein digestion are identical to apolipoproteins B‐74 and B‐26, it is concluded that apolipoproteins B‐74 and B‐26 are in‐vitro products produced in low density lipoproteins of normal plasma in the cold by kallikrein.
Tamm Horsfall glycoprotein interferes with bacterial adherence to human kidney cells
Authors: DULAWA J. , JANN K. , THOMSEN M. , RAMBAUSEK M. , RITZ E.
Published: March 2008

Abstract. The effect of Tamm Horsfall protein (THP) of 18 healthy subjects and 14 diabetics on adherence of Escherichia coli (06:K13) 2699 strain to human kidney cells (HUK) was studied. Adhesion of bacteria (without additions: 100 bacteria per cell) was reduced dose‐dependently by THP, half maximal inhibition occurring with 250 μg THP ml‐1. Maximal inhibition (– 84% at 1000 μg ml‐1) exceeded inhibition by alphamethyl‐mannoside (36% at 50 mM), was specific (not reproduced by other glycoproteins, e.g. ovalbumin, mucin or thyroglobulin) and reversible (abolished by washing THP off HUK cells). Anti‐adherence property of THP was not abolished by neuraminidase treatment. No significant difference of anti‐adherence activity of THP was found between controls and diabetics, despite altered carbohydrate composition of THP in diabetes.
Insulin stimulates the uptake of chylomicron remnants in cultured rat hepatocytes
Authors: JENSEN E. , FLORÉN C.‐H. , NILSSON Å.
Published: March 2008

Abstract. The effects of insulin (10–1000 μU ml‐1) on chylomicron remnant uptake and degradation were studied in hepatocyte monolayer cultures. Both uptake and degradation were stimulated by insulin. The degree of stimulation was influenced by cell density, being most pronounced in sparse cultures. The uptake was stimulated in a dose‐dependent fashion and was noticed already at a physiological insulin level (100 μU ml‐1). At this insulin concentration uptake was stimulated by approximately 50% (range 26–84%). As suggested by the increase in Vmax for the remnant uptake, the number of lipoprotein receptors on the hepatocytes was increased by 100 μU ml‐1 of insulin. Apolipoprotein‐E‐free low density lipoproteins (LDL) competed much less efficiently for the uptake of radioactive remnants than did unlabelled remnant particles. About half of the stimulatory effect of insulin on the remnant uptake could, however, be abolished by adding an excess of LDL, indicating that at least part of the stimulation by insulin was due to increased activity of the LDL receptor. This study thus shows that physiological insulin levels increase chylomicron remnant uptake in hepatocyte monolayer cultures. It is assumed that the effect of insulin is to increase the number of lipoprotein receptors at the cell surface, and at least part of the stimulation is due to an increase in LDL receptor activity.
Cytokine production in patients with newly diagnosed insulin‐dependent (type I) diabetes mellitus
Authors: LUGER A. , SCHERNTHANER G. , URBANSKI AGATHA , LUGER T. A.
Published: March 2008

Abstract. There is ample evidence that cell‐mediated immune mechanisms are crucial in the initiation of insulin‐dependent diabetes mellitus (IDDM). Therefore, the role of cytokines in the pathogenesis of IDDM was investigated in 51 patients with IDDM, in comparison with 20 normal controls. The patients were divided into three groups, group 1 consisting of 31 newly diagnosed type 1 diabetics, in group 2 IDDM had been diagnosed for between 2 months and 2 years, and in group 3 onset had occurred 2–20 years before. Interleukin 1 (IL 1) activity was measured by the thymocyte co‐stimulator assay, and interleukin 2 (IL 2) using IL 2 dependent cell lines. Peripheral blood monocyte IL 1 production was not altered under basal conditions. However, silica‐stimulated IL 1 release was normal in patients with newly diagnosed or short‐term disease, but was significantly decreased in long‐term diabetics. Peripheral blood T‐lymphocyte IL 2 production at onset of IDDM was normal under basal conditions, and upon optimal stimulation with concanavalin A (ConA) and phorbol myristate acetate (PMA). However, in the two groups with longer standing diabetes, basal and stimulated IL 2 release was decreased. We conclude that monocytes and T‐lymphocytes from patients with diabetes mellitus have a diminished capacity to release IL 1 and IL 2 only later in the course of the disease. At the time of manifestation of disease, IL 1 and IL 2 production is normal in type‐I diabetes mellitus.
Feedback regulation of stimulated pancreatic enzyme secretion during intraduodenal perfusion of trypsin in man
Authors: DLUGOSZ J. , FÖLSCH U. R. , CZAJKOWSKI A. , GABRYELEWICZ A.
Published: March 2008

Abstract. The pancreatic enzyme secretion in several species is controlled by a negative feedback mechanism induced by the presence of active proteases in the duodenum. The existence of this mechanism in man is controversial. The purpose of the present study was to evaluate the effect of tryptic activity in the duodenum on phenylalanine‐stimulated pancreatic enzyme secretion in healthy volunteers. A double‐balloon, multilumen tube was used for the collection of duodenal juice containing pancreatic enzymes. The continuous infusion of phenylalanine (100 mM) into the duodenum evoked an almost constant secretion of trypsin, amylase and lipase for 160 min. The infusion of trypsin (150 mg h‐1; 1·25 g l‐1) caused a reduction of phenylalanine‐stimulated amylase and lipase output by 25%. The subsequent infusion of aprotinin at a dose of 1·5 × 106 KIU for 30 min led to an almost complete inhibiton of trypsin. Simultaneously, the amylase and lipase output returned to the values seen before trypsin perfusion. Infusion of a higher dose of trypsin (300 mg h‐1; 2·5 g l‐1) caused a more pronounced decrease in phenylalanine‐stimulated amylase and lipase output by 45%. These data indicate that active trypsin in the duodenum is responsible for the inhibition of phenylalanine‐stimulated pancreatic enzyme secretion in man in a dose‐dependent fashion, thus confirming the existence of a feedback control of pancreatic secretion regulated by the amount of proteases in the gut.
Renal lithium handling during water loading and subsequent d‐DAVP‐induced anti‐diuresis
Authors: BOER W. H. , KOOMANS H. A. , MEES E. J. DORHOUT
Published: March 2008

Abstract. Assuming that lithium is exclusively reabsorbed in the proximal tubules pari passu with sodium (Na), the lithium clearance (CLi) has been advanced as an index of filtrate delivery from the proximal tubules. In order to determine whether water loads in a range commonly given during clearance studies affect CLi, we studied nine normal subjects (Na intake 150 mmol day‐1) on three water loads resulting in stable urine flow rates of 2·2 ± 0·9, 6·1 ± 0·7 and 11·7 ± 3·0 ml min‐1, respectively. We also studied the effect of acute anti‐diuresis (urine flow <1 ml min‐1) induced by d‐DAVP given i.v. at the end of all studies. Water loading up to induction of maximum water diuresis did not significantly affect absolute or fractional CLi‐Sodium and chloride excretion were reduced at the highest water intake level. Administration of d‐DAVP caused a 50% reduction in fractional Na excretion and a small but significant rise in fractional lithium reabsorption from 75·5 ± 3·9 to 77·5 ± 3·6%. We conclude that CLi is hardly affected over a wide range of water intakes and urine flow rates, despite concomitant changes in Na excretion. The finding that d‐DAVP, which probably enhances Na reabsorption in the thick ascending limb of Henle's loop, also enhanced lithium reabsorption, suggests that lithium may be partly reabsorbed in this nephron segment. Thus, lithium may not be the exact, quantitative marker of Na reabsorption in the proximal tubules that it is purported to be.
Lithium clearance during variations in sodium intake in man: effects of sodium restriction and amiloride
Authors: BOER W. H. , KOOMANS H. A. , MEES E. J. DORHOUT , GAILLARD C. A. , RABELINK A. J.
Published: March 2008

Abstract. Assuming that lithium is exclusively reabsorbed in the proximal tubules in proportion to sodium and water, the lithium clearance (CLi) has been advanced as an index of filtrate delivery from the proximal tubules. However, studies in the rat and dog showed that CLi drops sharply at fractional sodium excretion rates (FELi) below 0·4% due to lithium reabsorption in the amiloride‐sensitive segment of the distal nephron, which disqualified CLi as an index of distal filtrate delivery during sodium restriction in these animals. In order to investigate whether this phenomenon also occurs in man, we studied CLi in 103 normal subjects at varying sodium intakes, including marked sodium restriction. In contrast to findings in the rat and dog, no sharp drop but a gradual fall in CLi was observed at decreasing FENa values down to 0·02%. Maximum urine flow, another index of filtrate delivery from the proximal tubules, decreased proportionally, suggesting that the fall in CLi was due to enhanced proximal and not distal lithium reabsorption. Amiloride (15 mg p.o.) did not affect CLi despite unequivocal effects in the distal nephron in eight normal subjects at a mean FENa of 0·1%. In conclusion, a low FENa due to severe sodium restriction in man is not accompanied by strongly enhanced distal lithium reabsorption sensitive to amiloride. Thus, in contrast to the rat and dog, a low FENa forms no objection to use CLi as an index of sodium and filtrate delivery from the proximal tubules in humans.
Skin microvascular circulation in the sympathetic dystrophies evaluated by videophotometric capillaroscopy and laser Doppler fluxmetry
Authors: ROSÉN L. , ÖSTERGREN J. , FAGRELL B. , STRANDEN E.
Published: March 2008

Abstract. Finger‐skin microcirculation and its reactions to sympathetic stimuli were investigated in 12 patients with sympathetic dystrophies, secondary to trauma or other diseases. Nailfold‐skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy. Laser Doppler fluxmetry was used to provide an index of skin circulation in vessels in addition to the superficial capillaries. Both CBV and laser Doppler flux (LDF) values were significantly lower in the patients, compared with the healthy controls (P<0·05), despite the fact that skin temperature was the same in both groups. During cooling of the contralateral hand, CBV and LDF decreased markedly (22–60%) in the control group but not in the patients (0–13%). The decrease in skin perfusion normally seen upon lowering of the hand was also impaired in the patient group (7%) compared with controls (42%) (P<0·05). These impaired vasomotor reflex responses are consistent with sympathetic dysfunction and may well explain some of the typical features of the syndrome, e.g. limb oedema.
Value of autopsy in internal medicine: a 1 ‐year prospective study of hospital deaths
Authors: BOERS M. , KRUSEMAN A. C. NIEUWENHUYZEN , EULDERINK F. , HERMANS J. , THOMPSON J.
Published: March 2008

Abstract. In a university Department of Internal Medicine, we compared the clinical information, as written down immediately post mortem, with the demand for autopsy and with the autopsy findings during one complete year. Autopsies were performed in 143 of 306 consecutive deaths. In autopsied patients clinicians had recorded more diagnoses per patient, but with less certainty than in non‐autopsied patients. Patients with a diagnosis of a solid tumour were autopsied less often, and patients with infections or gastrointestinal disease more often than the average patient. These findings indicate selection of cases for autopsy. In 41% of patients erroneous diagnoses were detected that might have influenced management of the patient. In 28% of patients autopsy offered no additional information about one or more diagnoses. Both the proportion of errors and the proportion of uninformative autopsies increased with decreasing clinical certainty about the diagnosis. We conclude that autopsy offers useful information in most cases, and that selection of cases for autopsy is probably not justified.
α2‐Antagonist compounds and lipid mobilization: evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers
Authors: GALITZKY J. , TAOUIS M. , BERLAN M. , RIVIÈRE D. , GARRIGUES M. , LAFONTAN M.
Published: March 2008

Abstract. Investigations were carried out to analyse the interactions of α2‐antagonists (yohimbine, idazoxan, SK & F‐86,466) with human fat cell α2‐adrenoceptors. All the α2‐antagonists enhanced the lipolytic potencies of epinephrine with an order of potency: yohimbine > idazoxan > SK & F‐86,466; the same order was also found in 3H‐yohimbine competition studies on human fat cell membranes. The most potent agent, yohimbine, was administered orally in humans to define the conditions of appearance and the time‐course of a putative lipid‐mobilizing action. Oral yohimbine administration (0·2 mg kg‐1) elevated plasma glycerol and non‐esterified fatty acids in fasting healthy subjects without significant action on heart rate or blood pressure during the time‐course of the experiment. The lipid‐mobilizing action of yohimbine was reinforced during physical exercise, completely suppressed after a meal and partially blocked by administration of propranolol (0·5 mg kg‐1; 60 min before yohimbine). Plasma norepinephrine concentrations were increased (40–50%) after oral yohimbine administration. The rise in plasma catecholamine concentration elicited by yohimbine was not modified by propranolol treatment. The lipid‐mobilizing effect of yohimbine could be attributable to: (i) the increase in synaptic norepinephrine with a resultant increment in lipolysis by β‐adrenergic agonism; (ii) a decrease in α2‐adrenoceptor stimulation of human fat cell α2‐adrenoceptors; (iii) a blockade of presynaptic α2‐adrenoceptors. The use of highly selective α2‐antagonists will allow investigations into α2‐adrenoceptors, which may represent a novel locus for pharmacological intervention in lipid‐mobilization strategies. It is questioned whether α2‐antagonists would be useful in treatment or catecholamine‐refractoriness and obesity.
Positive inotropic effects in isolated ventricular myocardium from non‐failing and terminally failing human hearts
Authors: NÄBAUER M. , BÖHM M. , BROWN L. , DIET F. , EICHHORN M. , KEMKES B. , PIESKE B. , ERDMANN E.
Published: March 2008

Abstract. The positive inotropic responses to isoprenaline, dobutamine, histamine, forskolin, isobutylmethylxanthine (IBMX), dibutyryl‐cyclic adenosine monophosphate (db‐cAMP), ouabain and calcium were studied in isolated, electrically driven papillary muscle strips from either terminally failing human hearts or non‐failing donor myocardium. The positive inotropic effect of calcium has been taken to evaluate the maximal force of contraction of each individual muscle strip (‘contractile reserve’). In the non‐failing heart, the maximal positive inotropic effect of isoprenaline, dobutamine, IBMX, ouabain and calcium were not significantly different, but were significantly greater than histamine. In terminally failing hearts, the positive inotropic effects of agents stimulating the adenylate cyclase by a receptor‐dependent mechanism (isoprenaline, dobutamine and histamine) and the phosphodiesterase inhibitor IBMX are less than in the normal heart. Furthermore, these compounds gave a markedly reduced inotropic effect compared with forskolin, db‐cAMP and ouabain, which gave maximal responses similar to calcium in the failing hearts. The data did not differ when the increase of force of contraction was related to the diameter of each preparation. These results indicate that a defect in adenylate cyclase occurs in the failing human heart, presumably located at the regulatory stimulatory subunit (Gs) of the adenylate cyclase since effects through stimulatory receptors were reduced. Responses from activation of the catalytic subunit or through cAMP‐dependent protein kinases were less affected. Since the positive inotropic effect of IBMX is also impaired, it is suggested that the basal rate of cAMP production is also reduced in heart failure. Therefore, compounds directly activating the catalytic subunit of the adenylate cyclase or cAMP‐dependent protein kinases or the (Na+, K+)‐ATPase should be effective positive inotropic agents even in severe heart failure.
Insulin resistance in Graves' disease: a quantitativein‐vivoevaluation
Authors: CAVALLO‐PERIN P. , BRUNO A. , BOINE LAURA , CASSADER M. , LENTI G. , PAGANO G.
Published: March 2008

Abstract.Hyperthyroidism is considered to be an insulin‐resistant state, but a quantitative evaluation of some action of insulin is still lacking. We performed euglycaemic clamp at about 350 and 7000 pmol l‐1plasma insulin concentration in combination with the 3H‐glucose infusion in 12 patients with Graves' disease and in 12 matched controls. Fasting plasma insulin (126±6·5 vs. 77·5±5·7 pmol l‐1;P<0·001), C‐peptide (502±36 vs. 363±41 pmol l‐1;P<0·001) and glucagon (47±3·3 vs. 33·3±3 pmol l‐1;P>0·01) were significantly higher in hyperthyroids than in euthyroids. Basal hepatic glucose production was significantly higher in hyperthyroids than in euthyroids (18·3±1·4 vs. 9·2±0·5 μmol l‐1;P<0·0001), and its suppression during physiological hyperinsulinaemia was only 50% in hyperthyroids. Glucose utilization and suppression of lipolysis were normally stimulated by insulin. All parameters altered during hyperthyroidism were normalized during methimazole‐induced euthyroidism. We conclude that insulin resistance involves mainly glucose rather than lipid and is selective at the hepatic level.
Retention of haematoporphyrin in the aorta of hypertensive rats: in‐vivo and in‐vitro studies
Authors: SCANNAPIECO G. , PAULETTO P. , PAGNAN A. , MATTIELLO A. , JORI G. , DAL PALU C.
Published: March 2008

Abstract. Porphyrins are known to be accumulated and retained by tumours and atherosclerotic plaques. This property has been used for a new therapeutic approach called photodynamic therapy. In this study we assessed whether the presence of arterial hypertension could modify porphyrin turnover in the vascular wall. At various times after intravenous injection, haematoporphyrin concentration was assessed by a spectrophotofluorimetric method in the aortas of normotensive and hypertensive rats. Moreover, we studied the binding of haematoporphyrin to cultured smooth muscle cells obtained from normotensive and hypertensive rats. Larger amounts of haematoporphyrin were accumulated by the aorta of hypertensive rats and cleared at a slower rate, compared with normotensive rats. As for in‐vitro experiments, cultured smooth muscle cells from hypertensive rats bound larger amounts of haematoporphyrin than cells from normotensive rats.
Serum amyloid A and high density lipoproteins during the acute phase response
Authors: BAUSSERMAN LINDA L. , BERNIER D. N. , McADAM K. P. W. J. , HERBERT P. N.
Published: March 2008

Abstract. Serum amyloid A and high density lipoprotein (HDL) interrelationships were evaluated in 11 normal men during an acute phase response induced by the inflammatory steroid etiocholanolone. Compared with baseline, HDL‐cholesterol levels were significantly elevated at 30 h but not at 50 h (P < 0·05) after etiocholanolone. A‐apoprotein concentrations were unchanged at 30 h but were reduced at 54 h (P < 0·01). Four subjects were sampled every 6–8 h for 5 days. Two men had peak SAA concentrations of 30 and 33 mg dl‐1. Their A‐apoprotein levels declined as SAA rose and remained low even after SAA levels had returned to baseline. High density lipoprotein cholesterol levels did not fall, however, when SAA was increasing, and fell only after SAA levels declined. No changes in HDL‐cholesterol or protein were observed in two subjects whose peak SAA concentrations were 10 and 12 mg dl‐1. These observations suggest that a threshold level of acute phase response is required before HDL reductions occur. Column chromatography of SAA‐rich plasma did not demonstrate the presence of either SAA or A‐apoproteins that were unassociated with lipoproteins. Serum amyloid A, moreover, demonstrated little capacity to displace A‐proteins from HDL at SAA concentrations typically observed during the acute phase response. We infer from these studies that SAA may substitute for the A‐apoproteins and temporarily maintain HDL‐cholesterol levels; but that low HDL levels during the acute phase response are likely due to reduced A‐protein synthesis rather than displacement by SAA.
Differences between premenopausal women and young men in the transamination pathway of methionine catabolism, and the protection against vascular disease
Authors: BLOM H. J. , BOERS G. H. J. , VAN DEN ELZEN J. P. A. M. , VAN ROESSEL J. J. M. , TRIJBELS J. M. F. , TANGERMAN A.
Published: March 2008

Abstract. Catabolism of methionine is supposed to proceed via two known pathways: transsulphuration and transamination. In 10 premenopausal women and 13 young men we measured methionine, the transsulphuration metabolite homocysteine, and the transamination metabolites 4‐methylthio‐2‐oxo‐butryate and methanethiol mixed disulphides in the fasting state as well as after oral administration of 0·1 g L‐methionine kg‐1 body weight. Both in the fasting state and after methionine loading the concentrations of homocysteine in serum were significantly lower in premenopausal women than in young men. Since there is evidence that even a moderate homocysteinaemia may be a risk factor in the development of vascular disease, the low homocysteine levels could be an additional factor contributing to the lower incidence of vascular disease in premenopausal women. After oral methionine these women showed significantly higher concentrations both in serum and urine of the transamination metabolites than the group of men. This higher methionine transamination in premenopausal women may contribute to keeping the homocysteine levels low and may therefore have an impact on the protection of these women against vascular disease.
Relationships between plasma isotope enrichments of leucine and α‐ketoisocaproic acid during continuous infusion of labelled leucine
Authors: THOMPSON G. N. , PACY P. J. , FORD G. C. , MERRITT H. , HALLIDAY D.
Published: March 2008

Abstract. The ratio at steady‐state of α‐ketoisocaproic acid (KIC) to leucine 13C enrichments in plasma during continuous infusion of [13C]leucine was examined in 58 studies under a variety of conditions. The ratio was lower (P < 0·001) in ‘arterialized’ venous plasma (mean±SD 0·85±0·09) than in deep venous plasma (0·95±0·08), the sampling site enrichment differences being greater for leucine than for KIC. Variation in the ratio between the various conditions studied was largely explained by analytical variation. Three normal subjects were given an intravenous bolus dose of L‐[1‐13C, 15N]leucine. Both [13C]KIC and [13C]leucine appeared quantitatively in plasma within 10 min, indicating that both transamination of leucine and KIC, and their equilibration between intracellular fluid and plasma, is rapid. This study suggests that changes in sampling site, rather than in study conditions, are more likely to lead to variation in the KIC: leucine enrichment ratio. The lesser variation for KIC, and the rapid equilibration of the [13C]leucine bolus, favour KIC as tracee for [13C]leucine protein turnover studies.
Characterization of stereomicroscopically identified preneoplastic lesions during dimethylhydrazine‐induced colonic carcinogenesis
Authors: SANDFORTH F. , HEIMPEL S. , BALZER T. , GUTSCHMIDT S. , RIECKEN E. O.
Published: March 2008

Abstract. Preneoplastic mucosal changes were studied at six different time‐points during dimethylhydrazine (DMH)‐induced colorectal carcinogenesis in the rat. After 40 weeks of treatment, seven of 10 animals were bearing a total of 11 colorectal adenocarcinomas. The crypt cell production rate in the normal mucosa of DMH‐treated animals was greatly increased in the left colon and rectum and further rose with the duration of the experiment. Focal disturbances of the mucosal architecture could be detected as early as 4 weeks after the initiation of DMH‐treatment using a stereomicroscope. Their incidence was greatest in the left colon and rectum and increased strongly with the duration of carcinogen exposure. Characterization of these mucosal alterations, by means of conventional histology, morphometry after microdissection, cell kinetics, mucin histochemistry and quantitative enzyme histo‐chemistry performed with serial sections, revealed mild epithelial dysplasia, a considerable elongation and dilatation of the crypts and a marked increase of the crypt cell production, including a shift of the main proliferative compartment from the basal to the medial crypt segment as well as the occurrence of mitotic figures in the luminal epithelium. In affected crypts, the goblet cells completely lacked sulphomucins and exclusively contained sialomucins. The activities of the enzymes diaminopeptidase IV (brush‐border), succinate dehydrogenase (mitochondria) and acid β‐galactosidase (lysosomes) were markedly reduced. We conclude that these early mucosal alterations are indeed preneoplastic lesions and indicate the existence of the adenoma‐carcinoma sequence in this animal model. The easy detection of these microadenomas under the stereomicroscope and the existence of similar findings in man suggest possible clinical applications.
Monocyte C1‐inhibitor synthesis in patients with C1‐inhibitor deficiency
Authors: LAPPIN D. F. , McPHADEN A. R. , YAP PENG‐LEE , CARTER P. E. , BIRNIE G. D. , FOTHERGILL J. E. , WHALEY K.
Published: March 2008

Abstract. Monocytes of seven out of eight patients with type 1 C1‐inhibitor (C1‐inh) deficiency (HAE) produced 40% as much C1‐inh as monocytes from normal donors (controls). In contrast, monocytes from three patients with type 2 and three patients with acquired C1‐inh deficiency produced similar amounts of Cl‐inh as controls. Recombinant γ‐interferon (γ ‐interferon 10 ng/ml) stimulated C1‐inh production of C1‐inh (eight‐10‐fold) by control and patients' monocytes. Monocytes from patients with type 1 HAE contained 40% the level of C1‐inh messenger ribonucleic acid (mRNA) found in control monocytes, γ ‐interferon increased the abundance of Cl‐inh mRNA by the same extent in both control and patients' monocytes. C1‐inh protein and mRNA were undetectable in the monocytes of one patient, unless stimulated by γ‐interferon. Under these conditions, his monocytes produced comparable amounts of C1‐inh (protein and mRNA) as γ‐interferon‐stimulated monocytes of the other type 1 HAE patients.

The data suggest that in most type 2 HAE patients there is a lesion in the C1‐inh gene such that mRNA is transcribed by a single allele.
Analysis of cysteinyl leukotrienes in human urine: enhanced excretion in patients with liver cirrhosis and hepatorenal syndrome*
Authors: HUBER M. , KÄSTNER S. , SCHÖLMERICH J. , GEROK W. , KEPPLER D.
Published: March 2008

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

Leukotreine E4 was detected in all urine samples analysed. Its mean concentration increased from 0.3 nmol I‐1 in healthy subjects to 0.8 nmol 1‐1in patients with liver cirrhosis. In patients with hepatorenal syndrome leukotriene E4 averaged 7.8 nmol I‐1; in addition, N‐acetyl‐leukotriene E4 was detected in an average amount of 1.5 nmol ‐1. The mean leukotriene E4/creatinine ratio in urine increased from 0.02 in healthy subjects to 0.11 in patients with liver cirrhosis and to 1.2 μmol leukotriene E4 mol‐1 creatinine in patients with hepatorenal syndrome. These results indicate that cysteinyl leukotrienes may play an important role in the mediator network responsible for the development of the hepatorenal syndrome in patients with severe liver disease.
Adenosine receptor mediated stimulation of ventilation in man
Authors: JONZON B. , SYLVÉN C. , BEERMANN B. , BRANDT R.
Published: March 2008

Abstract. We wanted to examine how adenosine stimulates ventilation in man. Bolus doses of adenosine were given i.v. in an antebrachial vein in multiples of 2.65 mg. The minute ventilation was increased by adenosine 5.3 to 15.9 mg (median values) from control 12.6 ± 1.9 1 min‐1 to 42.5 ± 4.7 1 min‐1 in a dose‐dependent manner. The adenosine receptor antagonist theophylline, 58.3 ± 3.3 (mean±SEM) μniol 1‐1 plasma, inhibited the response by approximately 25%. Dipyridamole 10 mg, an adenosine uptake blocker, enhanced the effect of adenosine by approximately 60%. The ventilation was not affected by metoprolol, atropine, naloxone or cromolyn sodium but was attenuated by hyperventilation.

The respiratory stimulation started before chest pain and cardiovascular effects such as AV‐block were encountered. It is concluded that this respiratory stimulation shows characteristics of adenosine receptor mediated responses but the location of such adenosine receptors is uncertain. The findings are compatible with a stimulatory or facilitating effect of adenosine on afferent pathways.
Increased number of ouabain binding sites in lymphocytes from borderline hypertensives
Authors: NIELSEN J. ROKKEDAL , PEDERSEN K. E. , KLITGAARD N. A. , JOHANSEN T.
Published: March 2008

Abstract. Lymphocytes were used as a cellular model for the in vitro measurements of maximal ouabain binding sites in order to assess any changes in young men at increased risk of developing essential hypertension, and to analyse whether any such changes were associated to borderline hypertension and/or heredity.

Four groups were evaluated; 28 normotensive (NTO) and 20 borderline hypertensive (BHO) offspring of hypertensives. Twelve borderline hypertensives (BH) and 28 normotensive subjects (NT) with normotensive parents.

The number of ouabain binding sites were significantly increased in the borderline hypertensives irrespective of heredity.

The borderline hypertensives were heavier than the normotensives. A stepwise multiple regression model was therefore used in order to control confoundings by body mass index (BMI) and other factors such as age, gamma glutamyl transferase, 24 h sodium excretion, serum triglyceride, and serum cholesterole, which may influence the number of ouabain binding sites. Only BMI entered the stepwise model.

These results indicate the presence of an increased number of sodium‐potassium pumps in lymphocytes from borderline hypertensives. This difference may be attributed to the blood pressure disease or increased body mass.
Low protein alimentation normalizes renal haemodynamic response to acute protein ingestion in type 1 diabetic children
Authors: CASTELLINO P. , SANTO N. G. DE , CAPASSO G. , ANASTASIO P. , COPPOLA S. , CAPODICASA G. , PERNA A. , TORELLA R. , SALVATORE T. , GIORDANO C.
Published: March 2008

Abstract. The effect of an acute protein load (2 g kg‐1bodyweight [BW]) was studied in nine type 1 diabetic children. Patients were maintained on two different dietary regimens. In study one, patients were on a high protein diet providing from 2.7 to 1.8 g of protein/kg of BW per day. In study two, patients were reevaluated after three weeks of a diet providing from 1.0 to 1.2 g kg‐1 of BW per day of protein. In study one (High Protein Diet), we failed to observe any rise in GFR and RPF following the protein meal (137 ± 21 basal vs. 110±14 and 472±93 basal vs. 494±93 ml/1.73 m2 of SA min‐1 at 60 min.

This is in contrast with results from seven age matched controls consuming a free diet, which showed a significant rise in both GFR and RPF.

In study two (low protein diet), basal GFR was significantly reduced. However after the protein load, both GFR (92±11 vs. 126±18 ml/1.73 m2 of SA min‐1) and RPF (467±83 vs. 705±102 ml/1±73 m2 min‐1) rose significantly (P<0.05 vs. basal). The data indicate that:

1 short term protein restriction reduces significantly GFR in type 1 diabetic children;

2 diabetic children maintained on an high protein intake show an altered haemodynamic response to protein ingestion;

3 a normal response to protein ingestion can be restored by short term dietary protein restriction.
Antithrombin III activity, von Willebrand factor antigen and platelet function in young diabetic patients treated with multiple insulin injections versus insulin pump treatment
Authors: HUSTED S. E. , NIELSEN H. K. , BAK J. F. , BECK‐NIELSEN H.
Published: March 2008

Abstract. In a prospective study with cross‐over design 20 patients with insulin‐dependent diabetes mellitus of more than 2 years duration were treated for 6 months with continuous subcutaneous insulin infusion (CSII) and multiple insulin injections (MII).

Metabolic control, platelet aggregability, thromboxane B2 levels in serum and plasma as well as antithrombin III (ATIII) activity and von Willebrand factor antigen were evaluated. A good metabolic control was obtained by both intensified regimens. No difference could be demonstrated between either platelet function tests or serum level of von Willebrand factor antigen during treatment with CSII and MII. However, the plasma level of ATIII activity was significantly higher (P < 0.01) during MII treatment as compared to CSII treatment. There was no correlation between ATIII activity and daily insulin requirement or serum fructosamine.

In conclusion, long‐term metabolic control with MII has a favourable effect on ATIII activity in plasma. This may be important for a delay in onset and progression of diabetic vascular complications.
Abnormal glomerular and tubular function during angiotensin converting enzyme inhibition in renovascular hypertension evaluated by the lithium clearance method
Authors: PEDERSEN E.B. , SØRENSEN S. S. , AMDISEN A. , DANIELSEN H. , EISKJÆR H. , HANSEN H. H. , JENSEN F.T. , JESPERSEN B. , MADSEN B. , NIELSEN H. K.
Published: March 2008

Abstract. Glomerular filtration rate (GFR) and tubular function were measured by means of the lithium clearance technique in 14 patients with renovascular hypertension (RVH) and eight patients with essential hypertension (EH) before and after oral administration of captopril 25 mg.

In RVH captopril reduced 51‐Cr‐EDTA clearance (67.3 (median) to 47.5 ml min‐1, P<0.01), proximal absolute reabsorption of fluid (53.9 to 41.5 ml min‐1, P<0.01) and distal absolute reabsorption of sodium (2195 to 1402 μmol min‐1, P<0.01), whereas proximal fractional reabsorption increased slightly (77.5 to 80.2%, P<0.02). In EH, however, these parameters were practically unaffected by captopril. In both RVH and EH plasma concentrations of angiotensin II and aldosterone were reduced after captopril, but atrial natriuretic peptide in plasma and urinary excretion rate of prostaglandin E2 were unchanged. Blood pressure decreased after captopril in both groups, but the maximum fall in systolic BP was more pronounced in RVH (22%) than EH (13%).

It is concluded that angiotensin converting enzyme inhibition markedly reduced absolute reabsorption in both the proximal and distal tubules in RVH, in contrast to EH, predominantly due to fall in the GFR, and that the slight increase in proximal fractional reabsorption may be attributed to a reduction in the hydrostatic pressure in the peritubular vessels.
Platelet‐derived growth factor (PDGF) in type 1 diabetes mellitus
Authors: GUILLAUSSEAU P. J. , DUPUY E. , BRYCKAERT M. C. , TIMSIT J. , CHANSON P. , TOBELEM G. , CAEN J. P. , LUBETZKI J.
Published: March 2008

Abstract. In 10 patients with type 1 diabetes mellitus, platelet‐derived growth factor (PDGF) was assessed using an in vitro assay based on the stimulation of DNA synthesis in the 3T3 mouse fibroblast cell line. β‐Thromboglobulin (β‐TG) was used as an index for platelet α‐granules content. Platelet β‐TG content and PDGF were markedly decreased in diabetic patients while plasma β‐TG was increased as compared with control subjects. In diabetic patients, a significant negative correlation was found between plasma β‐TG level and β‐TG total platelet content, associated with a significant positive correlation between platelet β‐TG content and PDGF. These results suggest that PDGF release might be increased in diabetic subjects. This may account in part for the cell proliferation observed in diabetic angiopathy.
The optimal therapeutic range for oral anticoagulant treatment as suggested by fibrinopeptide A (FpA) levels in patients with heart valve prostheses
Authors: PENGO V. , PERUZZI P. , BACA M. , MARZARI A. , ZANON F. , SCHIVAPAPPA L. , VOLTA S. DALLA
Published: March 2008

Abstract. Fibrinopeptide A is a good marker of in vivo thrombin formation. The aim of oral anticoagulants (OA) is to lower in vivo thrombin formation. We therefore assessed FpA levels on several occasions in 38 patients receiving OA for artificial heart valve prostheses and in 20 patients receiving OA for biological heart valve prostheses. The mean FpA level, 1 82 ng ml‐1 (SEM 0.14, n= 176), in patients with artificial valves was significantly higher than the mean, 1.02 ng ml‐1 (SEM 0.4), obtained in 41 healthy subjects (P=0.01). FpA mean value for biological valves was 1.41 ng ml‐1 (SEM 0.14, n=76), which was not significantly higher than controls (P=0.08). A decrease in FpA levels, for both artificial and biological heart valve prostheses, was associated with a parallel increase in the intensity of anticoagulation. When considering FpA values obtained in the optimal therapeutic range for oral anticoagulant treatment, (International Normalized Ratio [INR] between 3 and 4.5), the mean level for artificial valves, 1.87 ng ml‐1 (SEM 0.18, n=102), was significantly higher than the mean value, 1.25 ng ml‐1 (SEM 0.16, n=55), obtained for biological valves. From a biological point of view, this indicates that artificial valves should be kept at a higher intensity of anticoagulation.
Platelet noradrenaline release in patients with familial hypercholesterolaemia
Authors: SMITH C. C. T. , WILSON A. P. , PRICHARD B. N. C. , BETTERIDGE D. J.
Published: March 2008

Abstract. We have examined resting and thrombin (0.3 units ml‐1) induced release of noradrenaline by washed platelets from 15 normal subjects and eight patients with heterozygous familial hypercholesterolaemia.

Platelets from both normal and hypercholesterolaemic subjects showed irreversible aggregation with 0.3 units ml‐1 thrombin. Extents of aggregation were 76.3% and 90.8% respectively, platelets from hypercholesterolaemic patients being significantly more sensitive (P < 0.002).

Under resting conditions platelet noradrenaline release was 136% greater (P<0.02) in hypercholesterolaemic patients than in normal subjects. Thrombin‐stimulated release of noradrenaline was also higher (73%, P<0.05) in hypercholesterolaemics than in normals. The differences between resting and thrombin‐stimulated release were greater for hypercholesterolaemic patients than normal subjects (P<0.05).

Under resting conditions total platelet noradrenaline levels (sum of supernatant and platelet pellet concentrations) were similar in preparations from the two groups. However, following thrombin stimulation total noradrenaline concentrations were substantially greater (86%) in platelets from hypercholesterolaemics than normals (P<0.02). In hypercholesterolaemic patients thrombin stimulation was associated with an 101% increase (over resting levels) in total platelet noradrenaline (P<0.01), no increases being observed with normal subjects.

We suggest that platelet membranes may be more permeable in patients with familial hypercholesterolaemia leading to increased non‐specific release of catecholamines. Platelets from patients with familial hypercholesterolaemia may also be more responsive to stimulation with respect to catecholamine release. The results obtained on calculation of total platelet noradrenaline levels may indicate that abnormalities of platelet dense granules occur in familial hypercholesterolaemia. In this context the relative proportions of free and conjugated catecholamine may be of relevance.

The importance of lipoprotein‐platelet interactions has been emphasized as regards the development of atherosclerosis. Platelet thrombus formation is also of undoubted importance in myocardial infarction. The platelet abnormalities described in this paper may contribute to the increased risk of premature vascular disease in patients with familial hypercholesterolaemia.
The mechanism of the hypocholesterolaemic effect of activated charcoal
Authors: NEUVONEN P. J. , KUUSISTO P. , MANNINEN V. , VAPAATALO H. , MIETTINEN T. A.
Published: March 2008

Abstract. The hypocholesterolaemic mechanism of activated charcoal was studied in seven patients with primary hypercholesterolaemia. The reduction of serum cholesterol was correlated with the serum concentrations of cholesterol precursors and of two plant sterols. Activated charcoal, 8 g t.i.d. for 4 weeks, reduced serum concentration of total cholesterol by 27% (P<0.01). The effect was accompanied by a moderate elevation (P<0.05) in serum squalene and desmosterol concentrations and by a marked increase (up to 300–700%) in serum lathosterol and Δ8 latho‐sterol concentrations. The levels of two plant sterols, campesterol and β‐sitosterol, were unchanged or only slightly decreased by the use of activated charcoal. The decrease of serum cholesterol concentration had significant negative correlations with serum lathosterol and Δ8 lathosterol, and significant positive correlations with serum cholestanol and β‐sitosterol. These observations suggest an increased cholesterol synthesis upon treatment with activated charcoal, probably caused by the interference with the enterohepatic circulation of bile acids.
Xbal restriction fragment length polymorphism of apolipoprotein B in Swedish myocardial infarction patients
Authors: WIKLUND OLOV , DARNFORS CATARINA , BJURSELL G. , NILSSON JEANETTE , LINDE'N T. , OLOFSSON S. O. , WILHELMSEN L. , BONDJERS G.
Published: March 2008

Abstract. Apolipoprotein B (apoB) is a major importance to the metabolism of lipoproteins, and there is also evidence which suggests that apoB plays a central role in atherogenesis. In order to study whether there is a link between one of the mutations of the apoB gene and premature coronary heart disease, the frequency of the XbaI RFLP for the apoB gene was analysed in 52 male myocardial infarction patients. These were compared with a control group matched for age and sex (n= 52), and a random population sample of middle‐aged men (n= 106).

Two alleles were identified by the presence (X2) or the absence (X1) of an XbaI cleavage site.

A somewhat higher frequency of the X2 allele was seen among the patients, however there was no significant difference between patients and controls regarding the genotypes or allele frequencies.

This observation does not confirm one earlier report where a higher frequency of the X1 allele was seen in myocardial infarction patients. Differences between the studied populations or epidemiological designs of the studies might explain the diverging results. Further studies are evidently needed to fully resolve the relation between the XbaI RFLP and risk of atherosclerotic disease or lipoprotein metabolism.
Lipolysis of polyenoic fatty acid esters of human chylomicrons by lipoprotein lipase
Authors: EKSTRÖM B. , NILSSON Å. , ÅKESSON B.
Published: March 2008

Abstract. Human chylomicrons, obtained from chylous pleural fluid of a patient with mesothelioma, were incubated with bovine milk lipoprotein lipase. No difference in the release of different C16–C18 fatty acids as unesterified fatty acids, or in their appearance in diacylglycerols, was observed. The rate of lipolysis of arachidonic (20:4), and eicosapentaenoic (20:5) acid ester bonds of chylomicron triacylglycerols was slower, and a larger proportion of these fatty acids accumulated in mono‐ and diacylglycerols. The hydrolysis pattern for docosahexaenoic acid (22:6) was intermediary between that of the C16–C18 fatty acids and that of 20:4 and 20:5. The data suggest that the presence of a double bond at position 5 in the eicosanoid precursors may be important for the rate of lipolysis. The relative resistance of the 20:4‐ and 20:5‐esters of chylomicrons to lipoprotein lipase may be important for the tissue distribution of these fatty acids.
Gastrointestinal transit of (indigestible solids measured by metal detector EAS II
Authors: EWE K. , PRESS A. G. , DEDERER W.
Published: March 2008

Abstract. A new method was developed to measure gastrointestinal transit: a metal particle is followed on its way through the gastrointestinal tract by means of a portable metal detector. Deviation of measured localization of the metal particle from the exact site was 0.5–1.0 cm depending on its size and distance from the search probe. A metal sphere of 6 mm diameter can be located accurately in the body at a distance of 2–12 cm from the abdominal surface.

Emptying of a metal particle from the stomach, its arrival at the caecal area and its passage through the colon into the rectum can be registered and hence, gastric residence time, small intestinal transit and transit through different parts of the colon were determined.

Gastric residence time at the interdigestive phase was (mean ± SD) 67 ± 52 min in 20 persons with a range of 9–185 min. When gastric emptying was recorded by pH sensitive radiotelemetering capsule in 10 persons, correlation of both methods was r= 0.99.

Small intestinal transit averaged 110 ± 56 min in six healthy volunteers when breakfast was eaten after the marker had left the stomach. It was delayed to 218 ± 34 min (P<0.01) whan fasting was continued.

Large intestinal transit of the metal marker was compared to whole body transit of radio‐opaque (‘Hinton’) markers. In nine normal persons, 70% of the Hinton markers were excreted together with the metal particle.

It is concluded that this new method is suitable for studying a large variety of physiological, pathophysiological and pharmacological questions concerning gastrointestinal transit. It is inexpensive and easily performed, does not cause radiation exposure, and allows measurements under everyday life conditions.