bluuebunny/crossref_metadata_2025 huggingface dataset:
Origin and Nature of the Proteins of Bile
Authors: Dive Ch. , Nadalini R. A. , Vaerman J.‐P. , Heremans J. F.
Published: March 2008

Abstract. In the dog, as shown before in the human, the major plasma proteins in hepatic bile (albumin, orosomucoid, transferrin and immunoglobulin IgG), with the exception of immunoglobulin IgA, were found to be derived entirely from the plasma. Biliary IgA was shown to have two sources, the plasma and local biosynthesis. These conclusions were based on comparisons on specific radioactivities of different proteins in plasma and bile, after intravenous injection of canine plasma whose proteins had been labelled biosynthetically with tritium. – The transfer of plasma proteins from blood to bile was found to proceed along two parallel pathways, one involving bulk transfer of unmodified plasma, and one based on molecular sieving favouring the transfer of plasma proteins of low molecular weight. – From a comparative study of hepatic lymph and plasma, it was concluded that the molecular sieve process was completed by the time the plasma proteins reached the interstitial fluid. The sieving membrane was therefore assigned anatomically to the vascular walls, which were found to have the properties of an isoporous membrane with a pore radius of 102 Å. No further molecular sieving was found to take place during the crossing of the second barrier between blood and bile, viz. the epithelial sheet separating interstitial fluid from the bile.
Albumin Catabolism Measurement by a Double Tracer Technique in Uraemic Patients During a Single Dialytic Treatment*
Authors: Mariani G. , Bianchi R. , Pilo A. , Palla R. , Toni M. G. , Fusani L.
Published: March 2008

Abstract. In order to explain the pathogenesis of protein depletion in chronic uraemia, 13 measurements of albumin catabolism were performed in uraemic patients undergoing haemo‐ or peritoneal dialysis treatment; during either the early phase or steady uraemic state.

Catabolism was determined during a single haemo‐ or peritoneal dialysis by a double tracer technique (Human Serum Albumin and sodium iodide labelled with two different isotopes of iodine). The output from both albumin and iodine systems was measured in the dialysis solution flowing out from the peritoneum or artificial kidney. The radioactive iodide arising in dialysate from albumin breakdown was concentrated by the use of an anion exchange resin.

Catabolic rate was three times the normal in 3 patients showing clinical features of hypercatabolism (true rapid loss of body weight) in the early phase of uraemia, or during relapse of it; albumin turnover rate returned to normal in 2 of these patients, when measured during clinical steady state conditions. This behaviour suggests highly increased catabolism, not counterbalanced by a correspondingly increased synthesis, as the cause of albumin depletion in chronic uraemia.
Recovery of Function and Structure of Dog Ileum and Colon Following Two Hours' Acute Ischaemia*
Authors: Robinson J. W. L. , Haroud M. , Winistorfer B. , Mirkovitch V.
Published: March 2008

Abstract. Loops of dog small intestine and colon have been subjected to two hours' acute ischaemia and their recovery has been studied by functional and histological examinations. – Immediately after the ischaemia, both organs show serious necrotic lesions of the mucosal surface, their active transport capacities are abolished, mucosal Na+‐K+‐ATPase activities are reduced, and a significant liberation of acid phosphatase into the efferent blood is observed. The lesions of the ileal loops are more severe than those of the colonic loops. – The ileal loops have a finite, albeit greatly reduced function 24 hours after the trauma. After 3 days, amino‐acid transport has normalised but sugar transport is still reduced. Histological examination confirms that epithelial cells cover the villi of most samples after 24 hours, and normalisation is almost complete after three days. All parameters are normal after one week. – In five cases out of eight, the colonic mu cosa is replaced by a compact polymorphonuclear infiltration bathing in a haemorrhagic exudate 24 hours after the ischaemic period; it is evidently quite functionless. In three loops the mucosa is preserved, but only one had functional activity. Three days after the trauma, functional activity is finite, but lower than that of the control loops; histological study reveals a disorganised mucosa, often with ulcers surrounded by relatively healthy tissue. At seven days, mean transport capacity is normal but there are still pathological signs at the microscopic level. – The results show that the ileum is more sensitive to ischaemic damage, but has a greater regenerative potential than the colon. There is a good relationship between the functional and structural state of the tissues.
Effect of Cholesterol Feeding on Cholesterol Biosynthesis in Maternal and Foetal Rat Liver
Authors: Calandra S. , Quartaroli G. C. , Montaguti M.
Published: March 2008

Summary. Hepatic cholesterol biosynthesis has been studied in rat foetuses whose mothers had been fed on a cholesterol rich diet during the last week of gestation. Foetal liver was found to be capable of synthesizing cholesterol from acetate in vitro. The rate of incorporation of labelled acetate into digi‐tonin precipitable sterols, fatty acids and CO2 in foetal liver was much higher than that found in maternal liver.

Cholesterol feeding reduced the rate of sterol synthesis in maternal liver but it did not have any appreciable effect on foetal liver. In order to investigate whether this lack of feed‐back control in foetal liver could be attributable to an obstacle to the placental transfer of dietary cholesterol. C‐cholesterol was administered to the pregnant rats and its distribution in maternal and foetal liver and plasma was studied.

Our results indicate that placental transfer of cholesterol from mother to foetus occurs very slowly so that only a small proportion of labelled cholesterol is found in foetal plasma over a 48 hour period following the administration of radioactive cholesterol. Cholesterol transferred from the mother into the foetal plasma is efficiently taken up by the foetal liver. These findings would suggest that the low amount of dietary cholesterol transferred from the mother into the foetal plasma is not sufficient to activate the control mechanism of the cholesterol biosynthetic pathway in the foetal liver.
Collagen Biosynthesis in Normal Human Skin, Normal and Hypertrophic Scar and Keloid
Authors: Craig R. D. P. , Schofield J. D. , Jackson S. S.
Published: March 2008

Summary. A comparison of the rates of synthesis of collagen in normal skin, normal and hypertrophic scars, and keloids has been made by measuring the rate of incorporation of [14C]‐proline into peptide‐bound [14C]‐hydroxyproline by tissue minces in vitro. The rate of synthesis of collagen, as measured by this technique, was significantly higher in skin than in normal scars whether the incorporation of radioactivity into hydroxyproline were expressed in terms of wet weight of tissue, weight of tissue DNA or weight of tissue hydroxyproline. The abnormal scar types exhibited similar rates of collagen synthesis, which were significantly higher than the rate in normal scars. Although the rates in both abnormal scar types appeared to be similar to that in normal skin when expressed in terms of wet weight of tissue, and weight of tissue hydroxyproline, they were seen to be lower than in skin in terms of weight of tissue DNA. The rate of synthesis of proteins generally, as measured by total radioactivity in non‐diffusible peptides, was highest in normal skin and hypertrophic scar and lowest in keloid. The ratio of radioactivity in non‐diffusible hydroxyproline to total non‐diffusible radioactivity was almost twice as high in keloid as in normal scar, with intermediate values being observed in hypertrophic scar and normal skin. This indicated that collagen accounted for a higher proportion of the proteins being synthesised in keloid than in normal scar. The results confirm previous conclusions, from determination of the activity of the enzyme collagen proline hydroxylase, that the excessive accumulation of collagen in hypertrophic scars and keloids may, at least in part, be due to abnormally high rates of collagen synthesis in comparison to normal scars.
Histamine Receptors in the Synovial Microcirculation
Authors: Grennan D. M. , Rooney P. J. , Onge R. A. St. , Brooks P. M. , Zeitlin I. J. , Dick W. C.
Published: March 2008

Abstract. This study was designed to investigate the respective roles of H1 and H2 receptors in the control of the microcirculation by examining the effectiveness of the H2 receptor antagonist metiamide (Met.) and Hj receptor antagonist mepyramine is blocking the action of histamine on synovial perfusion. Synovial perfusion was monitored indirectly by calculating the half‐life (T1/2‐ min.) of the clearance rate of 133Xe from canine diarthrodial joints. The 133Xe clearance rate, unaffected by metiamide alone, was consistently increased by histamine alone. Metiamide produced a dose related effect on the histamine response with consistent abolition of response at high dose ratios of metiamide to histamine variable response at intermediate and a pronounced histamine response at low dose ratios. Mepyramine produced no such antagonism of the histamine response and in certain doses, by itself caused an increase in 133Xe clearance rate. This effect of mepyramine was thought to be related to its histamine releasing properties a view supported by the reduction in this vasodilator response following certain doses of metiamide. The response of the 133Xe clearance rate to histamine returned approximately one hour after treatment with metiamide (500 yg) and metiamide did not antagonise the effects of a and 8 adrenergic agents on the 133Xe clearance rate. Thus, this study has provided evidence for the presence of H2 but not Hj receptors in the synovial microcirculation
The Sources of Plasma Cyclic AMP: Studies in the Rat using Isoprenaline, Nicotinic Acid and Glucagon
Authors: Strange R. C. , Mjøs O. D.
Published: March 2008

Abstract. The effects of intravenous administration of isoprenaline, glucagon and nicotinic acid on plasma concentrations of cyclic AMP in rats are described. In order to determine the relative importance of the liver as a source of extracellular cyclic AMP, the effects of the hormones were investigated in intact and functionally hepatectomised rats. The results showed that hepatectomy did not prevent an isoprenaline‐stimulated increase in plasma cyclic AMP concentrations, although glucagon was without effect on plasma nucleotide concentrations in this group of animals. It is suggested that the liver is essential for the action of glucagon but that isoprenaline can increase plasma cyclic AMP concentrations in hepatectomised animals by increasing extrahepatic release of the nucleotide. Since inhibition of adipose tissue lipolysis with nicotinic acid did not prevent an isoprenaline or glucagon‐stimulated increase in plasma cyclic AMP concentrations, adipose tissue is discounted as a major source of plasma cyclic AMP.
Regional and Systemic Haemodynamic Effects of Some Vasopressins: Structural Features of the Hormone which Prolong Activity
Authors: Cort J. H. , Albrecht I. , Noväkovä J. , Mulder J. L. , Jošt K.
Published: March 2008

Abstract. Cardiac output and regional blood flows to myocardium, gut, uterus and kidney were determined in anaesthetised female rats by a single injection of 86RbCl. The haemodynamic responses were measured at various time intervals up to 2 h after single I. V. injections of lysine‐vasopressin and the following of its analogues: a) with extended peptide chains at the N‐terminal (including “hormonogens”) Na‐glycyl‐glycyl‐glycyl‐lysine‐vasopressin, Na‐glycyl‐glycyl‐glycyl‐arginine‐vasopressin and Na‐D‐valyl‐lysine‐vasopressin, b) “carba” modifications desamino‐carba6‐arginine‐vasopressin, desamino‐carba6‐D‐arginine8‐vasopressin, desamino‐carba6‐ornithine8‐vasopressin, desamino‐dicarba‐arginine‐vasopressin and c) other steric alterations ‐ desamino‐D‐arginine8‐vasopressin and desamino‐N‐methylarginine8‐vasopressin. Sub‐pressor doses of lysine‐vasopressin were followed by marked reductions in gut and uterus blood flows which reached a peak at 10 min. and had completely receded by 60 min. The presence of steric alterations in the C‐terminal tripeptide of the molecule‐ D‐arginine or N‐methylarginine in sequence position 8‐ practically completely eliminated vascular activity. The same was true for Na‐D‐valyl‐lysine‐vasopressin. None of the latter three analogues showed any inhibitor properties to the action of lysine‐vasopressin. The two hormonogens (triglycyl N‐terminal extensions) had to be given in doses 10 times greater to obtain a vasoconstrictor effect in gut and uterus equivalent in amplitude to that of lysine‐vasopressin, but this effect was still present to the same degree 2 h later with the hormonogen of lysine‐vasopressin, and was only starting to return to baseline values at the same time with the arginine‐vasopressin hormonogen. The vascular potency of both mono‐carba L‐analogues was higher than that of lysine‐vasopressin, and the effect was as prolonged as with the hormonogens. The dicarba analogue also showed a prolonged action, but with much reduced potency. No significant changes in renal or myocardial blood flows were observed at all. Molecular features of vasopressin smooth muscle activity were discussed, and a receptor model was proposed. It was suggested that the ‐S‐S‐, ‐SCH2 and ‐CH2CH2‐bridges in the above analogues are not directly bound in the peptide‐receptor complex and constitute the limiting factor determining complex duration, or persistence of the active peptide in the “receptor compartment”. These results provide an experimental basis for possible clinical application of triglycyl‐vasopressin and carba‐vasopressin in bleeding from both gut and uterus and for induction of menstruation.
Quantitative Iodination of Human Blood Polymorphonuclear Leukocytes
Authors: Hakim J. , Cramer E. , Boivin P. , Troube H. , Boucherot J.
Published: March 2008

Abstract. It was shown by Pincus and Klebanoff that a correlation existed between leukocytic iodination measured in vivo and microbicidal leukocytic activity. We have analysed the results of this test in relation to time and in the presence of variable quantities of polymorphonuclear leukocytes (PMN). The values observed per time and PMN unit proved to be equivalent in the presence of 2. 5 × 105 PMN or 5. 0 × 105 PMN per 0.5 ml of incubation medium, measured after 10, 20 and 30 minutes or in the presence of 1. 0 × 106 PMN, measured after 10 minutes. That is to say iodination is proportional to leukocyte concentration and incubation time. Increase of either the quantity of cells or the incubation time, beyond the area we defined, reduce iodination per cell and per unit of time. Concerning the patients with an insufficient iodination, we have studied 2 parameters in the presence of 5. 0 × 105 PMN:1) initial iodination measured after 10 and 20 minutes and 2) stability of iodination measured after 60 minutes. These two parameters were equally affected in two cases with myelofibrosis, 3 patients with acquired refractory anaemia, one with chronic lymphoid leukaemia, one with erythroleukaemia, one with hairy cell leukaemia, one with systemic mastocytosis and almost complete myeloperoxidase deficiency, one with sickle cell disease, two with liver diseases and two with chronic myeloid leukaemia. The iodination at the 60th minute was more affected than at the 10th minute with a patient with myelofibrosis and 4 other patients with acquired refractory anaemias. The significance of these differences is not well understood; however the meaning of the decrease in the iodination of whatever type is that a PMN anomaly exists directly related to the myeloperoxidase H2O2 halogenation system, or to one of the stages of engulfment and/or metabolic events preceeding it and leading to the production of H2O2. This test, with the alterations we introduced, is suggested as a test for detection of functional PMN abnormalities.
Human Milk Lipases
Authors: Hemell O.
Published: March 2008

Abstract. Human milk contains a bile salt‐stimulated lipase in amounts that, at pH 6. 5 and in the presence of bile salts, might account for a total hydrolysis of the milk triacylglycerols in less than 30 min. In the absence of bile salts the enzyme has no activity against milk fat or against emulsified trioleylglycerol. The primary bile salts sodium cholate and sodium chenodeoxycholate and their taurine and glycine conjugates, but not the secondary bile salt sodium deoxycholate or its taurine and glycine conjugates, caused a pronounced activation of the enzyme against emulsified trioleylglycerol. The lipase was stable at pH 3. 5 and 37°C for 1 hour. It was inactivated when incubated with trypsin or chymotrypsin at pH 6. 5 but these inactivations were almost abolished in the presence of bile salts. High concentrations of pepsin slowly inactivated the enzyme at pH 4. 0. The bile salt‐stimulated lipase in human milk is thus stable enough to be active in the intestine, and it is present in high enough activity to contribute significantly to the hydrolysis of the milk triaclyglycerols in the intestine.
The Role of Calcium in Insulin Action
Authors: Clarke P. V. , Kissebah A. H. , Hope‐Gill H. , Vydelingum N. , Tulloch B. , Fraser T. R.
Published: March 2008

Abstract. The in‐vitro antilipolytic response to insulin and procaine hydrochloride by adipose tissue from young rats (150–180 g) and lean mice has been compared with that from aged Wistar rats (600 g) and obese (ob/ob) hyperglycaemic mice. 1. The adipose tissue from the obese mice showed diminished responsiveness to insulin and to procaine hydrochloride. Response to these agents, however, was restored by prewashing the tissue, suggesting that the apparent resistance in this tissue reflected saturation of the insulin receptors to endogenous insulin. 2. In adipose tissue of old Wistar rats the antilipolytic effect of insulin was also impaired, but this was not restored after extensive washing. Unlike adipose tissue ghosts prepared from young rats, insulin did not decrease the binding of calcium to ghost membrane preparations from old rats. Neither did insulin inhibit the adrenaline stimulated calcium efflux from perifused isolated fat cells prepared from old rats. These results suggest that the insulin response of fat cells from old rats is impaired because of a defect either in their insulin receptors or in their post‐receptor responses. 3. Procaine‐hydrochloride, however, when added to the medium perifusing fat cells of these old rats inhibited the adrenaline stimulated lipolysis, reduced the Ca efflux and decreased the binding of Ca to fat cell ghosts; as it did with similar preparations of young rats. Thus the cells from old rats still show full post‐receptor responsiveness to an insulin‐like stimulus, provided the stimulus for such a response is given at a point beyond the insulin receptor itself. The results suggest that the insulin resistance observed in old rat fat cells may be related to some by deficiency in the insulin receptors, possibly due to their lower replacement with age.
Endothelial Injury Induced by Bacterial Endotoxin: Effect of Complement Depletion
Authors: Evensen S. A. , Pickering R. J. , Batbouta J. , Shepro D.
Published: March 2008

Abstract. The role of complement activation in the pathogenesis of endothelial injury caused by bacterial endotoxin was investigated in the rat. DNA synthesis in aortic endothelium was compared 48 hours after an intravenous injection of endotoxin (50–500 μg) in normal rats and in rats depleted of haemo‐lytic complement by purified cobra venom factor. At the time of endotoxin administration the rats treated with cobra venom factor had less than 3% of the normal haemolytic complement level, their fibrinogen level was increased and clot retraction was impaired. Endotoxin stimulated endothelial DNA synthesis to the same degree in normal and in complement‐depleted rats. Cobra venom factor alone did not stimulate endothelial DNA synthesis. The complement‐depleted rats given 500 μg endotoxin were less thrombocytopenic than normal rats at the time of sacrifice, but the difference was not statistically significant. We conclude that the injurious effect endotoxin has on endothelium is not mediated by activation of late components of complement.
Effects of Myocardial Revascularization Following Acute Coronary Occlusion in Pigs
Authors: Althaus U. , Janett J. , Scholl E. , Riedwyl H.
Published: March 2008

In a comparative study in pigs the extent of myocardial infarction has been estimated following a temporary three hour coronary occlusion and following a permanent coronary ligation. For evaluation of the cellular injury the infarct size has been determined by a histochemical staining procedure and correlated with serum enzyme studies (creatine phosphokinase, a‐hydroxybutyric dehydrogenase) in the surviving animal. No significant difference could be detected between the two experimental groups and the extent of cellular damage was similar. A strict linear correlation was found between the serum enzyme activity plotted logarithmically and the morphological infarct size. Likewise the incidence of ventricular fibrillation depended on the extent of cellular injury. Myocardial revascularization does not appear to benefit a pig heart subjected to an acute coronary occlusion lasting three hours or more. Revascularization may even be harmful by creating a haemorrhagic infarct, as found in all the animals submitted to a transient coronary occlusion.
Effects of Fructose and Glucose on Ethanol‐Induced Metabolic Changes and on the Intensity of Alcohol Intoxication and Hangover
Authors: Ylikahri R.H. , Leino T. , Huttunen M. O. , Pösoö A. R. , Eriksson C.J.P. , Nikkilä E.A.
Published: March 2008

Abstract.The effects of fructose and glucose on the metabolic changes induced by ethanol and on the intensity of alcohol intoxication and hangover were studied in 109 healthy male volunteers. After 10 hours of fasting, the subjects were given 1.75 g of ethanol per kg body wt during 3 hours under controlled laboratory conditions. Fructose or glucose were administered either simultaneously with ethanol or 12 hours later during the hangover period. The intensity of alcohol intoxication and hangover were estimated 10 times during the experimental period of 20 hours using subjective and objective rating scales. Sequential determinations of blood ethanol, acetaldehyde, glucose, lactate, free fatty acids, triglycerides, ketone bodies and capillary blood acid‐base balance were also made during the experiment. Under these experimental conditions neither fructose nor glucose had any significant effect on the intensity of alcohol intoxication and hangover. The sugars also had no significant effect on the rate of ethanol elimination or on the blood acetaldehyde concentration during the course of the experiment. Blood glucose concentration was decreased and blood lactate, free fatty acid and ketone body concentrations were increased during the hangover period in the subjects who had been given only ethanol. These subjects also had a marked metabolic acidosis during hangover. Glucose and fructose significantly inhibited the metabolic alterations induced by ethanol. In this respect fructose was more effective than glucose. The results indicate that both fructose and glucose effectively inhibit the metabolic disturbances induced by ethanol but they do not affect the symptoms or signs of alcohol intoxication and hangover. The results support the view that hangover is not directly related to the metabolic effects of ethanol or to its metabolic products.
Distribution of Serum Zinc Between Albumin and α2‐Macroglobulin in Patients with Decompensated Hepatic Cirrhosis
Authors: Schechter P.J. , Giroux E.L. , Schlienger J.L. , Hoenig V. , Sjoerdsma A.
Published: March 2008

Lower concentrations of total serum zinc (540 ± 111 μg/1, mean ± SEM)., and of albumin‐bound serum zinc (295 ± 113 μg/1) and a higher concentration of a2‐macroglobulin‐bound zinc (245 ± 69 μg/1) were found in 25 patients with decompensated hepatic cirrhosis, compared to 28 healthy subjects (835 ± 91; 679 ± 83; 156 ± 27 μg/1 respectively). Levels of total and albumin‐bound zinc were significantly and positively correlated with serum albumin levels. Higher levels of α2‐macroglobulin‐bound zinc were associated with higher levels of α2‐macroglobulin in these patients (2.8 ± 0.8 g/1) compared to normals (2.3 ± 0.6). Hence, not only do decompensated cirrhotics exhibit a lower serum zinc level but a greater proportion of this zinc is associated with the tightly bound, and presumably metabolically more inert, serum fraction. This situation exaggerates the zinc deficiency state of the severe cirrhotic.
Lipids and Lipoproteins in Chronic Uraemia. A Study of the Influence of Regular Haemodialysis**
Authors: Daubresse J.C. , Lerson G. , Plcmteux G. , Rorive G. , Luyckx A.S. , Lefebvre P.J.
Published: March 2008

Plasma lipids and lipoproteins were studied in a group of chronic uraemic patients seme of whan were maintained by regular haemodialysis. Compared with healthy individuals, there was a significant increase in plasma triglycerides and in the prebeta‐1‐ and prebeta‐2‐lipoprotein plasma concentrations. There was no difference between dialyzed and undialyzed patients. Carbohydrate intake was normal, basal plasma insulin and free fatty acid levels were within the normal range. There was no correlation between plasma triglyceride levels and the degree of hypoalbuminaemia, the latter being marked in 30% of the patients. Basal plasma glucagon levels were very high in nearly all dialyzed patients and post‐heparin lipoprotein‐lipase activity was very low in dialyzed patients. In our experience, regular haemodialysis for 32 weeks did not improve hypertriglyceridaemia.
Influence of Bile Acids upon Biliary Cholesterol and Phospholipid Secretion in the Dog
Authors: Poupon R. , Grosdemouge M. L. , Dumont M. , Erlinger S.
Published: March 2008

The relationship between taurocholate or taurochenodeoxycholate secretion and cholesterol and phospholipid secretion in bile was studied in anaesthetized dogs infused with graded doses of these bile acids. Cholesterol output was linearly related to bile acid output during both taurocholate and taurochenodeoxycholate infusions. On the average 1.45 nmol and 4.70 nmol of cholesterol were secreted per umol of taurocholate or taurochenodeoxycholate respectively (P < 0.001). A linear relationship was also observed between phospholipid secretion rate and taurocholate or taurochenodeoxycholate secretion rates. However, the amounts of phospholipid secreted per ymol of taurocholate or taurochenodeoxycholate (respectively 0.10 and 0.15 μmol) were not significantly different. Thus, bile was less saturated with cholesterol during taurocholate infusions than during taurochenodeoxycholate infusions. These results are consistent with the hypothesis that micelle formation by bile acids is a major determinant of cholesterol and phospholipid secretion in the dog.
Removal of Exogenous Plasma Triglycerides in Forearm Muscle and Subcutaneous Tissue of Hyper‐and Normotriglyceridaemic Men
Authors: Rössner S. , Eklund B. , Kaijser L. , Olsson A.G. , Walldius G.
Published: March 2008

Absolute arterio‐venous removal and fractional removal of blood‐borne exogenous triglyceride particles by skeletal and subcutaneous tissues were determined in eight normotriglyceridaemic and six hypertriglyceridaemic men. Estimations were made by simultaneously sampling blood from catheters inserted into a brachial artery, and in the distal direction, into a superficial and deep vein, draining subcutaneous tissue and skeletal muscle respectively. During the infusion of the fat emulsion IntralipidR for 3 hours steady arterial concentrations of exogenous TG particles were found, indicating first order kinetics.

In all subjects absolute arterio‐venous and fractional removal of triglycerides were about twice as high in skeletal muscle as in subcutaneous tissue. In skeletal muscle the fractional removal and absolute removal were significantly higher in normotriglyceridaemic than in hypertriglyceridaemic subjects (p < 0.001). No decrease in removal with time was observed, which would have suggested saturation of removal sites. Mean fractional removal in skeletal muscle was significantly correlated with the k2 value determined by an intravenous fat tolerance test before the infusion study (r = 0.61, p < 0.05). In subcutaneous tissue fractional removal was also significantly higher in normotriglyceridaemic subjects (p < 0.05).

The results suggest that in both skeletal muscle and subcutaneous tissue the removal system is impaired in hypertriglyceridaemic subjects. This finding supports the concept that a decreased elimination capacity in these tissues may partly account for triglyceride elevation in hypertriglyceridaemic subjects.
Screening for medullary carcinoma of the thyroid in families with Sipple's syndrome: evaluation of new stimulation tests
Authors: TELENIUS‐BERG MARGARETA , ALMQVIST SVEN , BERG BERTEL , HEDNER PAVO , INGEMANSSON STIG , TIBBLIN STEN , WÄSTHED BIRGITTA
Published: March 2008

Abstract. In search of new practical diagnostic methods for the early diagnosis of hereditary medullary carcinoma of the thyroid (MCT) calcitonin release has been studied following induction by pentagastrin, cholecystokinin‐pancreozymin (the C‐terminal octapeptide, C8‐CCK, and the native swine extract), and ethanol in eighteen cases of MCT (all but one clinically occult), three ‘borderline cases’, seven first degree relatives of patients with hereditary MCT and thirty‐five healthy controls.

Pentagastrin, subcutaneous (s.c.) or intravenous (i.v.), induced a pronounced and rapid increase of serum calcitonin within 2–5 min. The elevation was roughly proportional to the tumour mass as estimated at operation. Seventeen out of eighteen MCT patients responded to s.c. pentagastrin with a significant increase in serum calcitonin and the response correlated well with that induced by calcium infusion test. Only two blood samples, at times 0 and 5 min, were necessary for diagnosis. In the MCT patients, i.v. pentagastrin produced more pronounced elevations of serum calcitonin than did s.c. pentagastrin, whereas no increase was seen in the control group. The subjective discomfort caused by i.v. pentagastrin was somewhat more intense but lasted shorter than that induced by s.c. administration. No serious complications were seen.

All of nine MCT patients responded to C8‐CCK with increments in serum calcitonin exceeding those of the control group and both of two responded similarly to the native cholecystokinin‐pancreozymin extract. Generally the serum calcitonin response was lower and more variable after C8‐CCK than after s.c. or i.v. pentagastrin, and the subjective discomfort was also more pronounced with abdominal cramps during the injection. Ethanol in the dose used was the least effective stimulator for serum calcitonin release.

Clinically suspected MCT carriers with palpable tumours can be diagnosed by determination of the basal, i.e. non‐stimulated serum calcitonin levels. Other possible Sipple genome carriers, who are at the time clinically healthy with normal basal serum calcitonin, should be subjected to a s.c. or i.v. pentagastrin stimulation test at each examination. These tests are much simpler to perform than a calcium infusion test, but seem to have about the same sensitivity.
Characteristics and behaviour of arylesterase in human serum and liver
Authors: BURLINA A. , MICHIELIN E. , GALZIGNA L.
Published: March 2008

Abstract. Human arylesterase is localized in liver microsomes where the presence of different electrophoretic bands corresponding to the serum bands can be recognized.

Serum arylesterase is mainly a result of liver activity and its high level might be explained by a low rate of elimination in urine. The behaviour of arylesterase towards inhibitors shows certain similarities to that of some of the proteases, such as trypsin.

The clinical value of serum arylesterase determination in assessing liver function is confirmed by its isoenzyme behaviour in cirrhossis and porto‐caval shunt.
Biochemical measurements in Paget's disease of bone
Authors: WALTON R. J. , PRESTON C. J. , BARTLETT M. , SMITH R. , RUSSELL R. G. G.
Published: March 2008

Abstract. In a group of eighty‐three patients with untreated Paget's disease of bone, plasma alkaline phosphatase activity (AP), plasma non‐protein‐bound hydroxyproline concentration (PHP) and urinary excretion rate of total hydroxyproline (THP) were closely correlated with each other but not with fasting plasma concentrations of calcium or inorganic phosphate. Probit plots of AP and THP showed log‐normal distributions overlapping the normal ranges.
Reduced binding of added zinc in serum of patients with decompensated hepatic cirrhosis
Authors: GIROUX EUGENE , SCHECHTER PAUL J. , SCHOUN JOSIANE , SJOERDSMA ALBERT
Published: March 2008

Abstract. Binding of zinc to macromolecules when added to serum was measured by ultrafiltration. At a final ratio of 0.6 mol zinc per mol albumin, zinc dissociable by glycine was significantly greater in diluted serum from patients with decompensated alcoholic cirrhosis than in normal serum samples similarly prepared. Low serum zinc concentrations, often observed in patients with alcoholic cirrhosis, may be related in part to a reduced affinity of plasma albumin for exchangeable zinc.
The permeability of the blood—brain barrier during electrically induced seizures in man
Authors: BOLWIG TOM G. , HERTZ MARIANNE M. , PAULSON OLAF B. , SPOTOFT HANS , RAFAELSEN OLE J.
Published: March 2008

Abstract. The blood‐brain barrier (BBB) in man was studied during various conditions using the indicator dilution method of Crone [8]. Using 113mIn‐DTPA as reference substance the extraction, E, of the small test substances 24Na+, 36Cl‐, 14C‐urea and 14C‐thiourea was estimated from the areas under the venous outflow curves following intracarotid slug injection of tracers. Interlaminar diffusion and red cell carriage were taken into consideration when calculating E. Cerebral blood flow (CBF) was measured using the intra‐arterial 133Xe‐injection method. Twenty‐two patients receiving electro‐convulsive therapy (ECT) were studied before and during seizures and during hypercapnia. Before seizures the extraction values in % were as follows: ENa+ 1.6, ECl‐ 1.9, Eurea 3.9 and Ethiourea 7.8; the corresponding values for the permeability‐surface area products (PS) in ml/100 gX min were 0.5, 0.3, 0.7, 4.1, respectively. During seizure a decrease of Ethiourea and an increase of PSurea were significant. During hypercapnia PSNa and PSthiourea rose significantly.

Due to the similarity of the findings in those two high flow situations it is suggested that the changes of CBF and not the epileptic activity are responsible for the changes in permeability. The mechanism of action may be a stretching of endothelial cells in the cerebral vessels or an opening up of new capillaries, or a combination of both.
Influence of sex, testicular development and liver function on the bioavailability of oral testosterone
Authors: NIESCHLGA E. , CÜPPERS H. J. , WICKINGS E. J.
Published: March 2008

Abstract. The bioavailability of orally administered testosterone was investigated in normal and hypogonadal men, prepubertal boys, normal women, and in patients with fatty liver, liver cirrhosis and surgical portocaval shunts. Peripheral testosterone concentrations remained unchanged in normal men and men with fatty liver, whereas a steep increase was observed in all other groups. The greatest increase was seen in patients with compensated liver cirrhosis and with portocaval shunts. The steep increase of peripheral testosterone in boys, women and hypogonadal men is attributed to their having a lower activity of androgen‐metabolizing liver enzymes than normal men. The increase in patients with cirrhosis is most likely caused by intra‐ and extra‐hepatic portocaval shunts.
Treatment of experimental murine amyloidosis with dimethyl sulfoxide
Authors: KEIZMAN I. KEDAR , GREENWALD M. , RAVID M.
Published: March 2008

Abstract. Dimethyl sulfoxide was administered intravenously for 60 days to twenty mice with casein‐induced amyloidosis. Partial or total disappearance of amyloid deposits occurred in all treated animals. The urine of these animals contained a substance from which amyloid fibrils could be synthesized. A control group of mice with casein‐induced amyloidosis given saline injections showed massive amyloid deposition in the liver and in the spleen at the end of the experiment. Neither the urine of these mice nor the urine of normal control mice treated with dimethyl sulfoxide contained substances from which amyloid fibrils could be synthesized. It is our assumption that dimethyl sulfoxide treatment of mice with amyloidosis resulted in a break up of amyloid fibres into small subunits which were excreted in the urine.
Influence of glucagon on natriuresis and glucose‐induced sodium retention in the fasting obese subject*
Authors: KOLANOWSKI J. , SALVADOR G. , DESMECHT P. , HENQUIN J. C. , CRABBÉ J.
Published: March 2008

Abstract. The role which glucagon could play in the mechanism of fasting natriuresis and renal sodium retention associated with carbohydrate refeeding was studied in thirty‐seven non‐diabetic obese subjects.

In nine obese subjects undergoing a 7 day fast without any additional treatment (control group), the renal sodium excretion exceeded intake through the whole experimental period, with maximal natriuresis on day 2 of the fast. Blood glucose and plasma insulin (IRI) levels fell rapidly from the first day of fast on, while pancreatic glucagon (IRG) titres rose from day 1 to day 4, declining slightly thereafter.

When additional subjects received intravenous glucose on day 4 (n= 6), there was a rise in blood glucose concentration and in IRI associated with a rapid drop in IRG restricted to the period of glucose infusion. The resulting antinatriuresis occurred essentially during the following 36 h, while IRG and IRI levels had returned to fasting levels. A comparable glucose load on day 4 associated with 0.1 mg glucagon (n= 5) still led to the glucose‐induced antinatriuresis while 1 mg glucagon added to a similar glucose infusion completely abolished its antinatriuretic effect (n= 6). Glucagon infused alone on day 4 of fast aggravated fasting natriuresis (n= 5) but was devoid of this effect when administered 24 h after the glucose load (n= 6).

These data indicate that fasting hyperglucagonaemia or its reduction upon glucose refeeding, cannot be considered as directly involved in renal mechanism(s) responsible for fasting natriuresis of antinatriuretic effects of carbohydrate. It is suggested that the role of glucagon is indirect, possibly through its influence on ketogenesis which in turn may alter renal sodium handling.
Effects of bile and bile acids on cultured human fibroblasts
Authors: TRIAS XAVIER , STREBEL HANS MAX , PAUMGARTNER GUSTAV , WIESMANN ULRICH N.
Published: March 2008

Abstract. Impaired healing induced by leakage of bile has been postulated as one factor responsible for complications after reconstructive bile duct surgery. The cytotoxicity of human bile and its major bile acids on cultured human fibroblasts was therefore studied by evaluation of their effects on cell morphology and growth, on synthesis and secretion of 35SO4‐mucopoly‐saccharides and on release of a lysosomal enzyme. Normal human fibroblasts derived from a standard culture strain (MRC‐5) were grown to confluence and exposed to: (1) sterile human T‐tube bile, (2) a mixture of bile acids resembling that of human bile, or (3) various concentrations of the glycine‐ and taurine conjugates of cholic, chenodeoxycholic or deoxycholic acid. Medium containing whole bile (total bile acid concentration 0.25, 0.75 or 1.6 mmol/l) exerted time and dose dependent cytotoxic effects on morphology and growth and release of lysosomal enzyme. Synthesis and secretion of 35SO4‐mucopolysaccharides were markedly inhibited. The bile acid mixture exhibited the same time and dose dependent effects. The conjugates of deoxycholic acid were found to be the most toxic of the individual bile acids studied.
Differences in heparin‐released lipolytic activity in the superficial and deep veins of the human forearm
Authors: HEAF D. J. , KAIJSER L. , EKLUND B. , CARLSON L. A.
Published: March 2008

Abstract. Various doses of heparin were given as a single injection into the brachial artery of each of twelve fasting healthy males. Plasma lipolytic activity was measured in samples obtained before and at frequent time intervals after heparin injection, in the artery and the deep and superficial veins of the same forearm.

As little as 0.15 U heparin produced a rapid and detectable relase of lipolytic activity in both deep and superficial veins. A series of tenfold increases in the dose produced correspondingly greater releases in the veins but the increments in the release were smaller than the increments in the dose. Three repeated 15 U doses of heparin, separated by 30 min, in the same subject gave a high degree of reproducibility of the release of lipolytic activity in both deep and superficial veins. 90% of the lipase activity in the vein was inhibited by 1 M NaCl.

In all subjects the release of lipolytic activity was higher in the deep vein, which predominantly drains muscle, than in the superficial vein, which drains mostly subcutaneous tissues such as skin and adipose tissue. This indicates that muscle is a tissue of considerable importance as a source of post heparin plasma lipolytic activity.
Studies on the catecholamine resistance in fat cells from patients with phaeochromocytoma
Authors: SMITH U. , SJÖSTRÖM L. , STENSTRÖM G. , ISAKSSON O. , JACOBSSON B.
Published: March 2008

Abstract. In order to elucidate the mechanism for cate‐cholamine‐resistance, known to occur after prolonged administration, adipose tissue specimens were obtained from ten patients with phaeochromocytoma. The specimens were preincubated for different periods of time, and then incubated with noradrenaline in vitro.

After excision the fat cells were resistant to noradrenaline and a concentration that would have been supramaximal in normal fat cells was required to elicit a significant lipolytic response. In contrast to fat cells from control patients, the cellular levels of cAMP did not increase in response to noradrenaline. The phosphodiesterase (PDE) activity was 4–5 times higher in the specimens from the patients with phaeochromocytoma than in the control tissues. The presence of high PDE activity in these fat cells was also suggested by the fact that exceedingly high theophylline concentrations were required to elicit a lipolytic effect.

After extending the preincubation period in fresh medium, the tissue sensitivity to catecholamines was largely restored. Simultaneously, the PDE activity declined about 50% (but was still higher than in the control tissues) and the levels of cAMP tended to increase in response to noradrenaline. Thus, the data suggest that one important mechanism for the catecholamine‐resistance in this state is the presence of high PDE activity.

Prolonged stimulation of fat cells with noradrenaline in vitro leads to catecholamine‐resistance which, at least partly, may be due to the formation of a hormone antagonist which also leaks out into the surrounding medium. Taken together with the present data it seems that at least two mechanisms may influence the cellular sensitivity to catecholamines: (a) the formation of a hormone antagonist; and (b) an adaptive increase in PDE activity.
Influence of cholic and chenodeoxycholic acid on biliary cholesterol secretion in man
Authors: LINDBLAD L. , LUNDHOLM K. , SCHERSTÉN T.
Published: March 2008

Abstract. The interrelationships between biliary bile acid, lecithin and cholesterol secretion rates were studied during depletion of the bile acid pool and during duodenal administration of cholic or chenodeoxycholic acid in thirteen patients 7–12 days after operation for uncomplicated gallstone disease. The mean lecithin secretion rate was significantly higher during cholic acid than during chenodeoxycholic acid infusion. The relationship between bile acid and cholesterol secretion rates was curvilinear, y=x/(a+bx) during bile acid pool depletion and during duodenal cholic acid infusion. At low bile acid secretion rates, during bile acid pool depletion and during cholic acid infusion, the lecithin secretion rate was significantly correlated to the cholesterol secretion rate. The bile acid and cholesterol secretion rates were not significantly correlated during chenodeoxycholic acid infusion. However, under this experimental condition a significant curvilinear relationship between lecithin and cholesterol secretion rates was found. The hepatic bile became unsaturated in cholesterol at significantly lower bile acid secretion rate during chenodeoxycholic acid infusion (10.7 ± 0.3 μmol min‐1) than during cholic acid infusion (15.6 ± 0.5 μmol min‐1).
Quantitation of thrombin‐antithrombin III complexes in human blood
Authors: COLLEN D. , COCK F. DE , VERSTRAETE M.
Published: March 2008

Abstract. Human thrombin‐antithrombin III complex was generated in defibrinated plasma by activation of the intrinsic coagulation system and isolated using affinity chromatography on insolubilized heparin and gel filtration. The resulting material probably contained factor Xa‐antithrombin III and factor IXa‐antithrombin III as well, although no specific identification of these complexes was made. An antiserum was raised, in rabbits, against this complex and rendered specific for neoantigens by absorption with fresh human plasma in the presence of inhibitors (heparin and p‐nitrophenyl‐p'‐guanidinoben‐zoate). Further purification of the ‘specific’ antibodies was achieved by immunoabsorption on the insolubilized complex. Polystyrene particles were coated with the resultant antisera and used in an agglutination test for the determination of thrombin‐antithrombin III complexes in the plasma of healthy subjects and various patients.

Purified thrombin‐antithrombin III complex at a concentration of 0.3‐0.6 μ/ml caused a distinct agglutination of the particles, whereas purified prothrombin and antithrombin III at concentrations of 250 μg/ml did not. Coagulation of human blood resulted in a progressive generation of agglutinating activity in the serum, reaching a maximum titre of 1/320 to 1/640. Sera from patients with rheumatoid arthritis also agglutinated the particles but this activity would be removed by absorbing the rheumatoid factor on insolubilized human IgG.

The thrombin‐antithrombin III titre in 95% of plasma samples from fifty‐six male and thirty‐two female healthy subjects was less than or equal to 1/8. In nine patients with overt signs of intravascular coagulation of various origin, the thrombin‐antithrombin III titres varied from 1/30 to 1/120. It is concluded that in vivo activation of the coagulation system is associated with the appearance of circulating thrombin‐antithrombin III complexes which can be directly assayed in plasma on the basis of their neoantigenic expression.