bluuebunny/crossref_metadata_2025 huggingface dataset:
Biliary cholesterol saturation in non‐obese women and non‐obese men before and after puberty
Authors: BERGMANN K. VON , BECKER M. , LEISS O.
Published: March 2008

Abstract. The lipid composition of gallbladder bile was determined in forty‐seven normal, non‐obese subjects (twenty females and twenty‐seven males) without gallstones ranging in age from seven months to twenty‐nine years. Before puberty, bile was undersaturated with cholesterol in both sexes to the same extent. After puberty a marked increase in cholesterol saturation was observed in females but not in males (138%vs 88%; P<0·01). A significant correlation between age and cholesterol saturation could be observed in females (r=0·546; P<0·05) but not in males.

In addition a significant correlation between absolute weight and cholesterol saturation in all females (r=0·827; P<0·001) and those after puberty (r=0·659; P<0·05) could be demonstrated. In neither sex was saturation related to body mass index or ideal body weight. These findings suggest that saturation of bile raises in women during puberty but not in men, and this sex‐related difference in cholesterol saturation probably contributes to the more common occurrence of gallstones in women than in men.
Relationship between urinary prostaglandin E2 and F2α excretion and plasma arginine vasopressin during renal concentrating and diluting tests in renal transplant recipients
Authors: PEDERSEN E. B. , CHRISTENSEN P. , DANIELSEN H. , EISKJæR H. , JESPERSEN B. , KNUDSEN F. , KORNERUP H. J. , LEYSSAC P. P. , NIELSEN A. H. , SØRENSEN S. S.
Published: March 2008

Abstract. Urinary excretion of prostaglandin E2 (PGE2 and F2α (PGF2α) and plasma concentration of arginine vasopressin (AVP) were determined during urinary concentrating and diluting tests in renal transplant recipients and control subjects. During the concentrating test PGE2 and PGF2α remained unchanged in the renal transplant recipients, whereas both PGE2 and PGF2α were significantly reduced in the control subjects. During the diluting test PGE2 and PGF2α increased in both groups but, contrary to PGF2α, PGE2 was significantly higher in all periods in the transplant recipients compared to the controls. However, the prostaglandin excretion rates per kidney were significantly higher in the renal transplant recipients than control subjects, for all periods during both the concentrating and the diluting test. Arginine vasopressin was significantly higher in renal transplant recipients than control subjects during basal conditions, increased to a significantly higher level in the transplant recipients after thirst, but was reduced to the same levels in the two groups during the diluting test. It is concluded that the increased excretion of prostaglandins in renal transplant recipients may be a compensatory phenomenon representing an adaptation to a reduced renal mass in order to maintain adequate renal water excretion. Although a direct relationship between the prostaglandin excretions of PGE2 and PGF2α and AVP does not seem to exist, it is possible that the higher prostaglandin excretion in the renal transplant recipients may be a counterbalancing mechanism to the higher AVP level, which most likely is secondary to a decreased responsiveness to vasopressin of the renal collecting ducts in the transplanted kidney.
Alcohol impairs age‐dependent adaptation of human lymphocyte beta‐adrenergic receptors
Authors: PADOVANI A. , GOVONI S. , BATTAINI F. , MAGNONI MARIA SANDRA , CIVELLI L. , MAURI A. , PICOTTI G. B. , GALVA MARIA DONATA , TRABUCCHI M.
Published: March 2008

Abstract. Lymphocyte beta‐adrenergic receptor function and norepinephrine (NE) plasma concentration have been compared in normal subjects and in ethanoladdicted patients of different ages. Direct measurement of the density and properties of beta‐adrenoceptors in membrane fractions was performed using the radioligand 125I‐Iodocyanopindolol (ICYP). In normal subjects beta‐receptor density decreased and norepinephrine plasma concentration increased with age. There was a statistically significant negative correlation between plasma norepinephrine and beta‐receptor number. In ethanol‐addicted patients the agerelated modification in beta‐receptor number and the correlation between plasma norepinephrine and beta‐receptor density were lost, in spite of the fact that the increase of NE plasma concentration was still present. The ethanol‐induced effects in lymphocyte beta‐receptor may have consequences on immunological function and may be qualitatively similar to alterations in other tissues not routinely accessible in humans.
Bisphosphonate whole body retention test: relations to bone mineralization rate, renal function and bone mineral content in osteoporosis and metabolic bone disorders
Authors: MOSEKILDE L. , HASLING C. , CHARLES P. , JENSEN F. TÅGEHØJ
Published: March 2008

Abstract. The bisphosphonate whole body retention test (WBR) has been used to estimate bone mineralization rate (bone turnover). Bisphosphonates given i.v. are taken up by bone or excreted in urine. The aim of the present investigation was to test the efficacy of WBR in estimating bone mineralization rate (m) and to evaluate the influence of renal function (Clcr) and bone mass (forearm bone mineral content; BMC) on WBR. The 24‐h retention of 3–7 MBq 99mTc‐HMBP (1‐hydroxymethylene‐1,1 ‐bisphosphonate) (Osteoscan®) given i.v. was measured by a medium sensitive whole body counter in thirty‐one patients with hyperparathyroidisme (n= 14), hyperthyroidism (n= 8) or hypothyroidism (n= 9) (group 1) and in seventy‐six females with postmenopausal spinal crush fracture osteoporosis (group 2). In the same individuals m was calculated from a 7‐day 47Ca‐kinetic study using the expanding calcium pool model. Multiple regression analysis of WBR vs. m and Clcr in group 1 disclosed that WBR correlated positively to m [rp= 0·49, P<0·01 (rp= partial correlation coefficient)] and inversely to Clcr (rp=‐0·44, P<0·02). Inclusion of BMC in the analysis did not reveal any significant partial correlation between WBR and BMC (rp=‐0·33, 0·05 <P<0·10). In group 2 WBR correlated inversely to Clcr (rp= ‐0·48, P<0·001) but showed no significant relation to m (rp= 0·10, NS). WBR was not related to BMC (rp= 0·09, NS), WBR was slightly inferior to serum alkaline phosphatase and renal hydroxyproline excretion in estimating bone mineralization rate in group 1 and, contrary to the biochemical markers, inapplicable in group 2. A model was developed that took into account that bisphosphonate is either taken up by bone or excreted in the urine. The model, however, did not improve the efficacy by which m could be predicted from simultaneous measurements of WBR and Clcr, probably because of an increase in the method error.

We conclude that measurements of the whole body retention of HMBP is of no value in estimation bone turnover in the investigated metabolic states characterized by wide variations in bone turnover and no mineralization defects.
Prolonged administration of human atrial natriuretic peptide in healthy men: evanescent effect on diuresis in spite of simultaneous infusion of norepinephrine
Authors: VIERHAPPER H. , NOWOTNY P.
Published: March 2008

Abstract. In healthy, sodium and fluid replete men (n= 6) a transient increase in diuresis is seen during the prolonged infusion of human atrial natriuretic peptide (hANP: 50μg h‐1 for 6 h). In order to evaluate whether this evanescent diuretic effect of hANP is due to the peptide's hypotensive action, the latter was compensated for by the concomitant infusion of norepinephrine (NE: 50 ng kg‐1 min‐1). The decrease in hANP‐induced diuresis towards the end of the 6‐h infusion was not prevented by the additional infusion of norepinephrine, which also failed to influence hANP‐stimulated natriuresis. Plasma concentrations of hANP, which were continuously elevated to about double of basal concentrations during the infusion of hANP, were not affected by exogenous norepinephrine. These data demonstrate that the transient character of hANP‐induced diuresis cannot be offset by counterbalancing the peptide's hypotensive effect.
Acetaldehyde modification of low density lipoprotein accelerates its catabolism in man
Authors: KESÄNIEMI Y. A. , KERVINEN K. , MIETTINEN T. A.
Published: March 2008

Abstract. Acetaldehyde (AcA), the first metabolite in ethanol oxidation, is chemically highly reactive and binds covalently to the free amino groups of various proteins. In this study, we examined the metabolism of acetaldehyde‐modified LDL (AcA‐LDL) in man. LDL was isolated from human volunteers, radiolabelled with either 125I or 131I, incubated in various AcA concentrations (Aca‐LDL) and injected back into the donors simultaneously with LDL incubated in identical conditions but omitting AcA (C‐LDL). Acetaldehyde treatment did not change the chemical composition, electrophoretic mobility or the flotation characteristics of LDL. The proportion of free amino groups of AcA‐LDL, ranging from 97 to 54·5%, was negatively correlated with the final concentration of AcA used in the incubation medium (r=–0·99, P < 0·001). AcA modification of LDL accelerated its in vivo catabolism in man in such a way that the fractional catabolic rate (FCR) for AcA‐LDL was negatively correlated with the percentage of free amino groups in AcA‐LDL (r=–0·87, P < 0·01). The clearance of AcA‐LDL modified in 0·4, 2·0, 4·0 and 8·0 mM AcA was 0·9, 1·4, 2·5 and 3·7 times faster than the clearance of C‐LDL, respectively. If AcA‐LDL is formed in man after ethanol ingestion, its rapid clearance may be one possible mechanism for the low LDL levels observed in chronic alcohol users.
Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearanceof lithium and 51Cr‐EDTA
Authors: NIELSEN A. H. , KNUDSEN F. , DANIELSEN H. , PEDERSEN E. B. , FJELDBORG P. , MADSEN M. , BRØCHNER‐MORTENSEN J. , KORNERUP H. J.
Published: March 2008

Abstract. In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr‐EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.
Alterations in the peritoneal transport of water and solutes during peritonitis in continuous ambulatory peritoneal dialysis patients
Authors: KREDIET R. T. , ZUYDERHOUDT F. M. J. , BOESCHOTEN E. W. , ARISZ L.
Published: March 2008

Abstract. The in situ intraperitoneal volume and the mass transfer area coefficients (MTC) of urea, lactate, creatinine, glucose, kanamycin, inulin, β2‐microglobulin, albumin and IgG were studied in eight continuous ambulatory peritoneal dialysis (CAPD) patients. All patients were studied during a 4‐h dialysis dwell, first during peritonitis and subsequently after recovery from the infection. The maximal intraperitoneal volume was reached at 68 min during peritonitis and at 150 min in the study after recovery (P < 0·01), suggesting increased water transport during the infection. For all investigated solutes MTCs were higher in the presence of peritonitis than after recovery. This increase was most marked for the proteins (> 100%). The power curve relationships between MTCs and molecular weight indicated that peritoneal transport of the low‐ and middle‐molecular weight solutes was determined by free diffusion and that the infection‐induced rise was due to an increase in effective surface area. For protein transport restricted diffusion was found. The increase of this transport during peritonitis was probably caused by both a larger effective surface area and a higher vascular permeability.
Type 1 (insulin‐dependent) versus Type 2 (non‐insulin‐dependent) diabetes mellitus: characterization of serum lipoprotein alterations
Authors: WEISWEILER P. , SCHWANDT P.
Published: March 2008

Abstract. Serum lipoprotein lipids and apolipoproteins A‐I, B, and E were investigated in Type 1 (insulin‐dependent) diabetics, Type 2 (non‐insulin‐dependent) diabetics, and two control groups, twenty subjects each. Lipoproteins were separated and analysed by common methods, apolipoproteins were measured by endpoint immunonephelometry. Compared with controls, Type 2 diabetics had increased serum apolipo‐protein E levels (0·116 pL 0·020 vs. 0·079 pL 0·014 g l‐1, P < 0·01) together with an increased content of cholesteryl ester‐enriched very low‐density lipoproteins. Furthermore, Type 2 diabetics had higher apolipoprotein B concentrations (1·06 pL 0·21 vs. 0·85 pL 0·21 g l‐1P < 0·01), but lower high‐density lipoprotein cholesterol concentrations than the controls. Conversely, Type 1 diabetics had elevated serum apolipoprotein A‐I values vs. controls and Type 2 diabetics (1·70 pL 0·33 vs. 1·49 pL 0·22 and 1·43 pL 0·21 g l‐1, P < 0·01). It is concluded that Type 2 diabetics, like other groups at risk for atherosclerotic diseases, are characterized by an increased concentration of partly catabolized very low‐density lipoproteins. Sufficiently insulinized Type 1 diabetics have, on the other hand, an increased number of high‐density lipoprotein particles.
Seeking clues for a positive diagnosis of the irritable bowel syndrome
Authors: VERNIA P. , LATELLA G. , MAGLIOCCA F. M. , MANCUSO G. , LI R. CAPRIL
Published: March 2008

Abstract. Despite its high prevalence the irritable bowel syndrome (IBS) lacks acceptable pathophysio‐logical markers and its diagnosis largely depends on the exclusion of underlying organic disease. Systemic acid‐base balance, serum electrolytes and the composition of faecal water (electrolytes and organic anions), were studied in thirty‐eight diarrhoeal patients out of a series of ninety‐three consecutive IBS patients. Only patients with diarrhoea as the predominant symptom were included in the study to evaluate whether this subgroup could provide the clue for a positive diagnosis of the syndrome. Serum electrolytes and systemic acid–base balance were within the normal range. Faecal electrolytes were also normal (Na 26·6 pL 19·3 SD; K 66·8 pL 28·3; Cl 19·1 pL 15·2 mEq l‐1), despite the finding of a moderately increased 24‐h faecal output. The K: Na ratio was also within the normal range. These data are in agreement with the lack of systemic changes observed in IBS patients even with profuse or longstanding diarrhoea. Both faecal short chain fatty acids and lactic acid were increased in patients vs. controls, but a considerable overlap with normal values was observed (131·4 pL 62·6 SD vs. 108·5 pL 58·3 mEq l‐1). Only lactic acid concentration was significantly higher than in controls (1·3 pL 1·2 vs. 0·5 pL 0·2). Despite these findings it is concluded that the subgroup of IBS patients with diarrhoea also appears to lack a pathophysiological marker and does not provide clues for a positive diagnosis of this syndrome.
Effect of modulators on prostasome membrane‐bound ATPase in human seminal plasma
Authors: RONQUIST G.
Published: March 2008

Abstract. The Mg2+‐ and Ca2+‐dependent ATPase system in human seminal fluid is linked to membranes encasing small organelles denoted ‘prostasomes’. This activity was completely pelleted after ultracentrifugation at 105 000 x g, provided the seminal plasma was diluted 1:10. On the contrary, prostatic acid phosphatase activity remained in the supernatant and was inhibited to about 75% by tartrate (0·5 mmol l‐1) contrasting with the ATPase system that was not inhibited. Calmodulin, in the concentration interval 0·30–0·90 μmol l‐1, did not further activate the ATPase system. Calmidazolium, which is a highly lipophilic substance, was a competitive inhibitor of the Mg2+‐ and Ca2+‐dependent ATPase and half maximal inhibition was attained at 2–3 μmoll‐1 calmidazolium. This inhibition was antagonized to a moderate degree (25%, P < 0·02) by calmodulin, 0·60 μmol ‐1. Quercetin, at concentrations of 30–60 μmol l‐1, did not influence the prostasome membrane ATPase in any direction. Oleate was an inhibitor of the ATPase system at any concentration up to 50 μmol l‐1. This inhibition was not counteracted to an appreciable extent by calmodulin. These results displayed a pattern giving support to the view that the Mg2+‐ and Ca2+‐dependent ATPase of the prostasome membrane may be the molecular basis for vectorial transport of Ca2+ into prostasomes.
Effect of the composition of very low and low density lipoproteins on the rate of cholesterylester transfer from high density lipoproteins in man, studied in vitro
Authors: DULLAART R. P. F. , GROENER JOHANNA E. M. , ERKELENS D. W.
Published: March 2008

Abstract. The process of cholesterylester (CE) transfer is supposed to be a regulatory factor in the distribution of CE between lipoproteins. In addition to the activity of CE transfer protein, this process may be affected by acceptor lipoprotein characteristics. In this study the effect of the composition of different very low density lipoproteins (VLDL) and low density lipoproteins (LDL) on the ability to accept CE from HDL in vitro was investigated. [3H]‐CE high density lipoprotein (HDL) (100 nmol CE) from one batch was incubated with VLDL (75 nmol CE), isolated from fifteen subjects for 4 h and separately with LDL (250 nmol CE), isolated from thirteen subjects for 16 h, both in the presece of lipoprotein‐free plasma providing a source of cholesterylester transfer protein. The CE transfer rate to VLDL (range 1·34–2·84% [3H]‐CE transferred h‐1) was correlated to the triacylglycerol (TG):CE molar ratio (r: 0·63, P < 0·05), to the phospholipid (PL):CE molar ratio (r: 0·75, P < 0·01), to the protein (Pr):CE ratio (expressed in g nmol‐1) (r: 0·72, P < 0·01) and to the free cholesterol (FC):CE molar ratio (r: 0·69, P < 0·01), but not to the FC:PL molar ratio (r: ‐0·08, NS). The CE transfer rate to LDL (range 1·18–3·59 nmol CE h‐1) was correlated to the Pr:CE ratio (r: 0·72, P < 0·01) and inversely to the FRC:PL molar ratio (r: ‐0·88, P < 0·001), but not to the TG:CE molar ratio (r: 0·40, NS), nor to the FC:CE molar ratio (r: ‐0·37, NS). The correlation between CE transfer rate and PL:CE molar ratio almost reached significance (r: 0·54, 0·05 < P < 0·10). It is concluded that the ability of VLDL to accept CE is enhanced when it contains more TG and more surface constituent, relative to CE, while in LDL surface characteristics are involved in the process of CE transfer. An influence of VLDL and LDL composition and CE transport in human plasma is suggested.
Complete iodide trapping defect in two cases with congenital hypothyroidism: adaptation of thyroid to huge iodide supplementation
Authors: LEGER F. A. , DOUMITH R. , COURPOTIN C. , HELAL O. B. , DAVOUS N. , AURENGO A. , SAVOIE J. C.
Published: March 2008

Abstract. Two cases of congenital defect in iodide trapping mechanism are related. The absence of thyroid and gastric concentration of 99mTcO4 led to the diagnosis. The study of saliva and gastric: serum concentration ratios confirmed the complete defect. The kinetics of radioiodine studied by external detection showed an early simultaneous decay in the thyroid, the stomach and the left ventricle. Thyroid accumulation of 131I, demonstrated by camera imaging, was estimated to be 0·1% at 48 h. It probably originated from simple diffusion. Iodide supplementation was progressively increased to 4·5 g and 10 g day‐1 respectively. It resulted in a normalization of all parameters. Huge doses of iodide did not result in any evidence of hyperthyroidism as TSH rose normally after TRH. Intermittent iodide supplementation in one case could not maintain euthyroidism longer than a few weeks. Daily treatment, therefore, seems necessary.
Quinidine reduces biliary clearance of digoxin in man
Authors: ANGELIN B. , ARVIDSSON ANNIE , DAHLQVIST R. , HEDMAN ANN , SCHENCK‐GUSTAFSSON KARIN
Published: March 2008

Abstract. Quinidine is known to reduce the renal clearance of digoxin, but this effect does not completely explain the influence of quinidine on the total clearance of digoxin. We therefore studied the effect of quinidine administration on biliary clearance of digoxin in five patients with atrial fibrillation. Biliary clearance of digoxin under steady state conditions before and during treatment with quinidine was investigated using a duodenal‐marker‐perfusion technique. Quinidine caused an average 42% (range 21–65%, P < 0·02) reduction of the measured biliary clearance of digoxin. We conclude that the biliary effect adds to the previously demonstrated inhibitory effect of quinidine on the renal clearance of digoxin and helps to explain the decrease in total clearance of the drug. This is the first demonstration in man of a pharmacokinetic drug interaction at the level of biliary excretion.
Sodium balance as a determinant of prostacyclin production by isolated rat aorta
Authors: DÜSING R. , LANDSBERG G. , PIETSCH R. , SCHERHAG R. , SÖNTGERATH C. , KRAMER H. J.
Published: March 2008

Abstract. The present study investigates whether the synthesis of prostacyclin (PGI2) in isolated rat aorta is dependent on the state of sodium balance of the animals. Three groups of ten rats each were included into the study. Two of them were fed a diet low in NaCl for 10 days with group I receiving 0·9% saline and group II distilled water as drinking fluid. Group III received a regular rat chow containing approximately 0·8 mmol day‐1 of sodium, also for 10 days. At the end of the dietary protocol, systolic arterial blood pressure was significantly higher in group I (109·9 ± 2·4 mmHg) as compared to group II (101·0 ± 2·4 mm Hg; P < 0·05) and group III animals (102·2±1·6 mm Hg; P<0·05). Generation of PGI2‐like activity was determined in portions of the animals' isolated aorta using a platelet aggregation bioassay following incubation in 0·05 m Tris buffer (pH 9·3) for 12, 15, and 30 min, respectively. During these incubation times, generation of PGI2‐like activity averaged 48·6 ± 3·5, 57·8 ± 4·3 and 68·3 ± 3·2 pmol mg‐1 in group III animals, which had received the regular rat chow, with similar values in the low salt group II (50·2 ± 2·5, 57·7 ± 2·7 and 72·9 ±3·7 pmol mg‐1). Aortic generation of PGI2‐like material was significantly suppressed in the high salt group I (37·5 ± 2·8, 46·2 ± 3·2 and 61·3 ± 4·0 pmol mg‐1; P<0·01). When added directly into the incubation buffer, norepinephrine and the α‐receptor agonist phenylephrine (100 nm) induced a significant stimulation of the generation of PGI2‐like activity while the β‐receptor agonist isoproterenol had no effect. Our results show that the significantly increased arterial blood pressure during chronic NaCl loading is accompanied by suppressed vascular synthesis of PGI2. This may be mediated, at least in part, by changes in α‐adrenergic activity.
Enhanced biliary gamma‐glutamyltransferase excretion following prolonged alcohol consumption in rats
Authors: TESCHKE R. , KRUKENBERG S. , STREMMEL W. , NISHIMURA M.
Published: March 2008

Abstract. In order to study the question of whether chronic ethanol consumption may alter the biliary excretion of gamma‐glutamyltransferase (γ‐GT), female rats were pair‐fed nutritionally adequate liquid diets containing either ethanol (36% of total calories) or isocaloric carbohydrates for 24 days. Compared to pair‐fed controls, the administration of the alcohol‐containing diet resulted in an increased biliary excretion of γ‐GT (5·84±0·73 mU 6 h‐1 100 g‐1 b.w. vs. 8·82±0·79, P<0·001). This was associated with a corresponding enhanced biliary output of total bile acids. An apparent linear relation between the biliary output rates of γ‐GT and those of total bile acids was observed both in alcohol‐fed animals (r= 0·83) and in their pair‐fed controls (r= 0·95). In addition, there was a significant increase of gamma‐glutamyltransferase activities in the liver homogenate and in liver plasma membranes, both in fractions rich in bile canalicular and basolateral membranes and in those rich in blood sinusoidal site. Serum gamma‐glutamyltransferase activities as well as serum bile acid concentrations were also enhanced by 96·8% (P<0·001) and 233% (P<0·001), respectively. These data show that chronic alcohol consumption enhances hepatic γ‐GT activities, leading to an increased efflux of γ‐GT into the bile and possibly into the blood out of the liver cell. Furthermore, these data suggest the involvement of bile acids with their solubilizing properties for the biliary excretion of γ‐GT.
Calcium transport across the colon ascendens and the influence of 1,25‐dihydroxyvitamin D3 and dexamethasone
Authors: KARBACH U. , RUMMEL W.
Published: March 2008

Abstract. Concentration dependence of unidirectional calcium fluxes across the rat colon ascendens were measured in a modified Ussing chamber. Both the mucosa (m) to serosa (s) and the s to m calcium flux exhibited saturation kinetics. The maximum transport rates and the affinity to the transporter of calcium was higher in the m to s direction than that from s to m, resulting in a remarkable net calcium absorption. The results obtained from measurements of unidirectional calcium fluxes in dependence on clamped transepithelial potentials showed that: (i) calcium transport in both direction had a voltage‐independent component; (ii) the voltage‐independent, i.e. non diffusive fraction of the m to s calcium flux was 3·2 times greater than that in the opposite direction; (iii) the voltage dependent, i.e. diffusional fraction of the m to s calcium flux, was about two times greater than the voltage‐dependent fraction of the calcium flux in the s to m direction; and (iv) in the m to s direction 62%, and in the s to m direction 73%, of the total unidirectional flux was voltage‐dependent. Dexamethasone, known to enhance sodium and water absorption in the colon, had no significant influence on net calcium absorption but increased the unidirectional calcium fluxes in both directions. The increase in unidirectional calcium fluxes parallel to that of the extracellular marker mannitol suggests that dexamethasone has no influence on the transcellular calcium transport but increases the calcium flux along the paracellular way. Amiloride had no influence on the dexamethasone‐induced changes of the epithelial electrical parameters as distinguished from the colon descendens. The increase in calcium and mannitol fluxes after dexamethasone treatment was also unaffected by amiloride. 1,25(OH)2D3 had no influence on the kinetics of unidirectional calcium fluxes as distinguished from the colon descendens. The electrical parameters of the tissue and unidirectional mannitol fluxes were also unaffected by 1,25(OH)2D3. The mode of calcium transport found in the colon ascendens exhibits characteristics distinct from the transport properties reported for the colon descendens. The heterogeneity of both parts, with respect to the calcium transport, suggests that both colonic segments might have different functions in the final modulation of calcium balance by the intestine.
The gap junction: a channel for multiple functions?
Authors: BRUZZONE R. , MEDA P.
Published: March 2008

Abstract Gap junctions are specialized membrane structures that enable the intercytoplasmic exchange of small molecules and ions between contacting cells. During the past decade, biophysical and structural analyses of the junctional channel have considerably increased our understanding of the pharmacological properties and gating mechanisms of gap junctions. Despite this impressive amount of work, until recently the physiological role of these ubiquitous intercellular pathways has remained speculative in most tissues. This review summarizes the most recent information obtained on the structure of the gap junction by molecular cloning of the major protein components and emphasizes the growing evidence for their functional role in adult tissues formed by highly differentiated secretory cells. The relevance of cell‐to‐cell coupling for the co‐ordinated function of the exocrine and endocrine pancreas is discussed.
Monocytic production and plasma bioactivities of interleukin‐1 and tumour necrosis factor in human cancer
Authors: MOLDAWER L. L. , DROTT C. , LUNDHOLM K.
Published: March 2008

Abstract Plasma concentrations and in‐vitro production of interleukin‐1 and tumour necrosis factor were evaluated in 23 weight‐losing patients with cancer, six bacterially infected patients without cancer and six healthy controls. Bioactivity of interleukin‐1 was found in the plasma from five of six bacterially infected patients but only from one of 23 cancer patients. Tumour necrosis factor activity was not detected in the plasma of any patient. In four of 23 patients with cancer, in‐vitro stimulation of peripheral blood monocytes by either endotoxin or heat‐killed Staphylococcus albus resulted in no significant production of interleukin‐1. Such a defect was not seen in any of the bacterially infected or control patients. Tumour necrosis factor production by endotoxin‐stimulated blood monocytes was unaffected by the presence of cancer or bacterial infections and was normal in the four individuals with defective interleukin‐1 production. We can therefore conclude that interleukin‐1 bioactivity is not generally found in the plasma of weight‐losing cancer patients. Furthermore, in a fraction of such cancer patients, monocytic production of interleukin‐1 is markedly down‐regulated. However, this defect appears to be specific for interleukin‐1 since in‐vitro tumour necrosis factor production is normal.
Rates of bone loss in normal women: evidence of accelerated trabecular bone loss after the menopause
Authors: NILAS L. , CHRISTIANSEN C.
Published: March 2008

Abstract We have followed the changes in bone mass over 2 years in 42 premenopausal, seven perimenopausal and 76 postmenopausal women. The latter had passed a natural menopause between 6 months and 7 years previously. Bone mass was measured every 3 months at the proximal and distal forearm sites by single photon absorptiometry, and every 6 and 12 months in the lumbar spine and whole body by dual photon absorptiometry. The relative content of trabecular bone is approximately 15, 50, 60 and 20% at these four sites. Before the menopause there was a significantly low rate of bone loss from the two forearm sites and the whole body, whereas the spinal loss was insignificant. The rate of loss was five‐ to tenfold higher at all sites after the menopause (P < 0·001). With increasing menopausal duration the rate of loss declined at the two forearm sites and whole body (P < 0·01). The distal forearm loss was larger than the proximal, both before and after the menopause (P < 0·01). From the forearm results we thus conclude that a slightly larger loss of trabecular than cortical bone takes place both before and immediately after the menopause. The loss of both types of bone is, however, much larger after the menopause and this rapid bone loss seems to take place throughout the skeleton.
Ammonia and glutamine metabolism in human liver slices: new aspects on the pathogenesis of hyperammonaemia in chronic liver disease
Authors: KAISER S. , & W. GEROK , HÄUSSINGER D.
Published: March 2008

Abstract Ammonia and glutamine metabolism was studied in slices from normal, fatty and cirrhotic human livers. The liver disease was evaluated by histological examination. With respect to ammonia removal, urea and glutamine synthesis in human liver represent low and high affinity systems with k0·5(NH4+) values of 3·6 and 0·11 mM, respectively. Compared with normal control livers, cirrhotic livers showed a decreased glutamine synthesis from NH4Cl by about 80%. The same was true for urea synthesis. Conversely, flux through hepatic glutaminase was increased in cirrhosis 4–6‐fold. These changes in hepatic glutamine and ammonia metabolism were observed regardless of whether reference was made to liver wet weight, DNA or protein content. Acetazolamide inhibited urea synthesis in cirrhotic liver slices by about 50%, indicating that mitochondrial carbonic anhydrase is required for urea synthesis also in cirrhosis. There was a significant correlation between the in‐vitro determined capacity for urea synthesis from NH4Cl and the in‐vivo determined plasma bicarbonate concentration. The data suggest that (i) pathogenesis of hyperammonaemia in chronic liver disease involves the impairment of the perivenous ammonia scavenger cells capable of glutamine synthesis; (ii) the increased flux through glutaminase observed in cirrhosis increases the ammonia input into the urea cycle and acts as a compensatory mechanism for maintenance of a life‐compatible urea cycle flux despite the decreased urea cycle enzyme activities; (iii) intramitochondrial bicarbonate provision for carbamoylphosphate synthetase by carbonic anhydrase may become rate‐controlling also in liver cirrhosis; and (iv) hyperbicarbonataemia in chronic liver disease may, amongst other effects, be due to an impaired hepatic HCO3‐ removal by urea synthesis, in line with the concept of a role of the liver in systemic acid–base homeostasis.
Platelet and vessel associated prostacyclin and thromboxane A2/prostaglandin endoperoxide receptors
Authors: JASCHONEK K. , MULLER C. P.
Published: March 2008

Abstract. Synthetic stable analogues of thromboxane A2 (TXA2), cyclic endoperoxides (PGH2) and prostacyclin (PGI2) opened up new opportunities for investigating the mechanisms of action of these compounds. They proved to be useful pharmacological probes for characterizing PGI2 and TXA2/PGH2 receptors. Over the past few years, new synthetic antagonists with high specificity allowed the modulation of biological responses to endogenous eicosanoids. These compounds will, therefore, considerably promote our understanding of the biological function and significance of arachidonate metabolites. The present review summarizes current concepts that have arisen concerning platelet and vascular PGI2 and TXA2/PGH2 receptors, their transmembrane signal transduction, as well as their possible implications in the pathophysiology of cardiovascular disease.
Inhibition of secondary bile acid formation in the large intestine by lactulose in healthy subjects of two different age groups
Authors: NAGENGAST F. M. , HECTORS M. P. C. , BUYS W. A. M. , TONGEREN J. H. M. VAN
Published: March 2008

Abstract. Secondary bile acids have been implicated in colonic carcinogenesis. Transformation of primary into secondary bile acids (7α‐dehydroxylation) in the large bowel is a pH‐dependent process. Inhibition of this reaction could be achieved by lowering colonic pH. We, therefore, studied the effects of lactulose (a non‐absorbable disaccharide), which is capable of acidifying colonic contents, on secondary bile acid metabolism. Because this metabolism is age dependent, lactulose was given (0·3 g kg‐1 twice daily for 12 weeks) to nine middle‐aged (age 31–54 years; mean 45·7) and ten elderly subjects (age 56–81 years; mean 66·4). Twice before, and after 6 and 12 weeks' lactulose administration, biliary and faecal bile acids, whole gut transit time, faecal weight and dry weight, and faecal pH were recorded. The concentration of (iso)lithocholic and deoxycholic acid in faeces was higher in elderly subjects (P<0·05) but the excretion was comparable. After lactulose the concentration and excretion of the major secondary bile acids decreased. The primary bile acid fraction rose from 5% before, to more than 20% after, lactulose (P<0·05). Faecal weight increased and faecal dry weight decreased, resulting in a higher faecal water output during lactulose. Whole gut transit time did not change. The faecal pH dropped after 6 (P<0·05) and further after 12 weeks' lactulose (P<0·05). The percentage deoxycholic acid in bile was higher, and cholic acid lower, in elderly subjects (P<0·05). After lactulose the deoxycholic acid content decreased (P<0·05) and chenodeoxycholic acid content increased (P<0·01) in the whole group (n= 19). The cholic acid content did not change. The results show that lactulose can reduce secondary bile acid formation in the large bowel and that the effect is not mediated through acceleration of intestinal transit. Acidification of colonic contents seems to be the major factor in this reduction.
Skeletal muscle and whole body protein turnover in thyroid disease
Authors: MORRISON W. L. , GIBSON J. N. A. , JUNG R. T. , RENNIE M. J.
Published: March 2008

Abstract. The effects of disturbances of thyroid hormone secretion on leg and whole body amino acid and protein metabolism have been investigated in seven patients with untreated thyrotoxicosis and eight patients with untreated hypothyroidism; the results were compared to those obtained in 11 normal control subjects. After treatment, the patients were restudied. Arterio‐venous exchanges of tyrosine and 3‐methylhistidine across leg tissue in the post‐absorptive state were used as indices of net protein balance and myofibrillar protein breakdown, respectively. Whole body protein turnover was measured using stable isotope labelling techniques with 1‐[1‐13C] leucine. Efflux of tyrosine from leg tissues was six‐fold greater in patients with untreated thyrotoxicosis than in normal control subjects (– 19·39 ± 2·21 vs. – 4·20 ± 0·31 nmol 100 g‐1 leg tissue min‐1, P<0·005, mean ± SEM), but 3‐methylhistidine efflux was not significantly different (– 0·11 ± 0·03 nmol 100 g‐1 leg tissue min‐1 vs. 0·14 ± 0·02 nmol 100 g‐1 leg tissue min‐1). After treatment, when the thyrotoxic patients became euthyroid, tyrosine efflux was normalized (at – 4·94 ± 0·84 nmol 100 g‐1 leg tissue min‐1) and 3‐methylhistidine efflux was unchanged. In hypothyroid patients, neither tyrosine nor 3‐methylhistidine effluxes were significantly different from those in normal subjects. Whole body leucine flux (equivalent to appearance of leucine from protein breakdown) was significantly lower in both the thyrotoxic and hypothyroid patients compared with normal subjects (101 ± 7, 97 ± 7 and 133 ± 6 μmol leucine kg‐1 h‐1, respectively); however, even greater relative depressions were observed in removal of leucine from the free pool by non‐oxidative routes, i.e. by whole body protein synthesis (thyrotoxic, 56 ± 4, hypothyroid, 61 ± 4 and normal subjects, 89 ± 5 μmol leucine kg‐1 h‐1, respectively). After treatment of thyrotoxicosis and hypothyroidism whole body protein synthesis became normalized in both patient groups. The results suggest that derangement of thyroid function (with either an excess or a deficiency of thyroid hormone), leads to alterations of whole body leucine metabolism, probably reflecting alterations in tissue protein synthesis and breakdown, which are consistent with observed losses of body protein mass, and which reverse on treatment. The net loss of protein in thyrotoxic myopathy appears to be due more to a depression of muscle protein synthesis rather than to an increase in muscle protein breakdown.
Studies on calcium exchange in platelets in human diabetes
Authors: BERGH C.‐H. , HJALMARSON Å. , HOLM G. , ANGWALD EVA , JACOBSSON B.
Published: March 2008

Abstract. Calcium has a key role in platelet aggregation. In order to assess the role of calcium metabolism in the platelet in diabetes mellitus, calcium exchange into and out of the cytosol was investigated in platelets from eight patients with insulin‐treated diabetes with a mean duration of 10 years without any clinical complications. Their mean HbAIc (glycosylated haemoglobin) was 9% (normal range 3·4–5·4%). Influx rate of 45Ca2+ was significantly increased by 35% in diabetic platelets compared with controls. The efflux rate was significantly reduced during the first 15 min but total efflux measured over 2 h was equal in diabetic and control platelets. Access to sequestered non‐mitochondrial calcium in the dense tubular system was gained by permeabilization of the cells with saponin. Into cells loaded with 45Ca2+, Inositol 1, 4, 5 triphosphate (IP3) was introduced and release of the sequestered ion would be determined. In control platelets calcium release was prompt and amounted to 43%. In diabetic platelets the response to IP3 was blunted and was only 17%. The nutritional and hormonal status influenced the response to IP3 in diabetes and, to a lesser extent, in controls. In the fasting state and without insulin the release was reduced but in the fed state and after insulin the release of calcium from diabetic platelets was equal to those of controls. It is concluded that abnormalities exist in platelet calcium handling in diabetes that can be influenced by insulin and the nutritional status. These abnormalities may well contribute to the increased ability for platelet aggregation in the diabetic state, and the insulin and nutritional influence underlines the importance of the metabolic status when studying platelet function.
Stimulation of pancreatic secretion in man by a protease inhibitor (camostate)
Authors: ADLER G. , MÜLLENHOFF A. , KOOP I. , BOZKURT T. , GÖKE B. , BEGLINGER C. , ARNOLD R.
Published: March 2008

Abstract. Pancreatic secretion and plasma cholecystokinin (CCK) and secretin levels were measured in 10 healthy volunteers after application of a serine protease inhibitor (camostate) to study the mechanism of feedback regulation. Camostate produced a strong inhibition of trypsin and chymotrypsin activity in duodenal juice for 1 h. This was accompanied by an increase in duodenal aspirate volume and pancreatic enzyme secretion under both basal and secretin‐stimulated conditions. Due to inhibition of tryptic activity, survival of lipase activity in duodenal juice was prolonged. In control experiments we ruled out that the volume and the pH of the solution were responsible for stimulation of pancreatic secretion. The protease inhibitor did not alter pancreatic secretion, which was stimulated by a test meal. Plasma levels of CCK and secretin were not changed after duodenal perfusion of camostate. These observations suggest that trypsin and chymotrypsin are involved in feedback regulation of pancreatic secretion in man which is, however, not mediated by CCK or secretin.
Glycogen and lactate synthetic pathways in human skeletal muscle in relation to obesity, weight reduction and physical training
Authors: ALLENBERG K. , NILSSON MARIANNE , LANDIN KERSTIN , LINDGÄRDE FOLKE
Published: March 2008

Abstract. The effects of obesity, weight reduction, and physical condition on the concentrations of glucose‐6‐phosphate (G‐6‐P) and glycogen, and the activities of glycogen synthase (GS) and lactate dehydrogenase (LD) were determined in resting vastus or gastrocnemius muscles of 40 healthy subjects. In obese women the activity of GS was 50% (P<0·05) lower than in lean women with similar levels of glycogen and G‐6‐P, whereas no difference was found in the activity of LD. Calorie restriction induced a 4·5% (P<0·05) decrease in body weight from 82·5 kg corresponding to a 3·2% (P<0·05) decrease in body mass index from 30·9 kg m‐2. The total and fractional activities of glycogen synthase were increased by 50% (P<0·05), whereas muscle glycogen content was reduced by 40% (P<0·05). The G‐6‐P concentration and the activity of LD remained unchanged. In well‐trained young men the concentrations of G‐6‐P and glycogen were, respectively, 250% (P<0·05) and 50% (P<0·05) higher than in non‐trained. The fractional and total activities of GS were 90% (P<0·05) and 50% (P<0·05) higher, respectively, and the total activity of LD was only half (P<0·05) that of non‐trained subjects. In conclusion, physical training enhances the activity of GS, despite a concomitantly increased glycogen content, and thus seems to exert a more efficient stimulus on glycogen synthase than weight reduction. It is indicated that physical training may provide a clinically important contribution to blood glucose reduction in hyperglycaemic conditions.
Enhanced calcitonin secretion in the rat after parathyroidectomy and during chronic calcium deprivation
Authors: RAUE F. , WIELAND UTE , WEILER CHRISTINE , ZIEGLER R.
Published: March 2008

Abstract. The thyroidal content of calcitonin (CT) and the serum calcitonin responses to acute hypercalcaemia were studied in female rats during chronic hypocalcaemia induced by parathyroidectomy (PTX), a low calcium (Ca) diet, or both. The thyroidal CT content of the PTX animals 50 days after surgery was twice that of intact rats. An acute intraperitoneal (i.p.) calcium load on day 50 after PTX resulted in an increase in serum CT twice as large as that observed in control animals. Reversal of the chronic hypocalcaemia with 1,25(OH)2D3 resulted in a reduction in thyroidal CT as well as a depression of the calcium‐induced CT response. In each case the values were similar to those observed in normocalcaemic controls. A low calcium diet increased the thyroidal CT content in intact rats and induced a further increase in PTX rats. The CT response to an acute Ca load was exaggerated by a low calcium diet in intact as well as in PTX rats.

These results suggest that in the rat chronic hypocalcaemia enhances CT storage and secretion.