bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Studies on the Pathogenesis of Hangover
Authors: Ylikahri R. H. , Huttunen M. O. , Eriksson C. J. P. , Nikkilä E. A.
Published: March 2011

Abstract. A variety of metabolic parameters were evaluated in 23 healthy male volunteers, after ethanol administration (1.5 g/kg) and correlated to the symptoms of hangover. The degree of intoxication and hangover were estimated using a simple test program according to which 11 subjects had severe and 12 mild hangover. Sequential determinations of blood ethanol, acetaldehyde, glucose, lactate, free fatty acids (FFA), triglycerides (TG) and ketone bodies were made during the 21 hours after administration. Each subject served as his own control by taking part in an identical experimental session but receiving no ethanol.

The maximal hangover occurred 12 to 14 hours after the initiation of drinking. At this time almost all of the ethanol and acetaldehyde had been eliminated from the blood. The intensity of the hangover did not correlate with the peak concentrations of ethanol or acetaldehyde in the blood. Marked hypoglycaemia regularly followed the administration of ethanol, but the nadir blood glucose values had no correlation with the intensity of hangover. Ethanol induced a significant rise in blood lactate concentration, the extent of which was similar in subjects with mild or severe hangover.

During the most intensive hangover plasma FFA level increased when compared to the values observed during the control period. These concentrations were significantly higher in subjects with severe hangover than in those whose hangover was mild. An increase in plasma TG concentration regularly followed ethanol administration but the extent of the rise did not correlate with the degree of intoxication or hangover. Ethanol had a marked antiketogenic effect during the first 8 hours of the experiment after which the concentration of ketone bodies rose rapidly above the control level. Again the changes showed no correlation with the intensity of hangover.

The results indicate that the intensity of hangover bears little relation to the changes in the metabolite concentrations measured. This suggests that the symptoms of hangover can not be accounted for by the ethanol‐induced alterations of the major blood metabolite concentrations.
Comparison between Fractional Turnover Rate of Endogenous Plasma Triglycerides and of Intralipid® (Intravenous Fat Tolerance Test) in Man*
Authors: Rössner S. , Boberg J. , Carlson L. A. , Freyschuss Ulla , Lassers B. W. , Rössner S.
Published: March 2011

Abstract.The validity of the intravenous fat tolerance test (IVFTT) as a tracer for the fractional turnover rate of endogenous plasma triglycerides (TG) has been studied in 32 fasting men with either normal or elevated plasma TG concentrations. The endogenous plasma TG turnover was determined by sampling arterial and hepatic vein blood, determination of splanchnic net secretion of plasma TG and calculation of fractional TG turnover rate. Later the fractional elimination rate of exogenous TG was determined following a single IV injection of Intralipid® (IVFTT). The TG fractional removal rate constants derived from these two tests were significantly correlated (r= 0.6‐0.7) but IVFTT gave higher absolute values. A statistical evaluation showed that the error for the determination of the fractional turnover rate of endogenous TG and the IVFTT were about 30–50% and 10% respectively. It is probable that the correlation would have been still better if the error for the estimation of endogenous plasma TG turnover had been lower. A significant negative correlation was found between very low density lipoprotein‐TG concentration and fractional removal rate of both endogenous and exogenous plasma TG (r= −0.7–0.8).
Classification of Hypothyroidism in Evaluating Patients after Radioiodine Therapy by Serum Cholesterol, T3‐Uptake. Total T4, FT4‐Index, Total T3, Basal TSH and TRH‐Test*
Authors: Wenzel K. W. , Meinhold H. , Raffenberg M. , Adlkofer F. , Schleusener H.
Published: March 2011

Abstract. During a follow‐up examination of patients after radioiodine therapy for thyrotoxicosis, 128 patients without recurrent hyperthyroidism were investigated for the clarification of different degrees of hypothyroidism. The clinical diagnosis and the conventional tests for circulating thyroid hormones were compared to the estimation of serum thyroid stimulating hormone (TSH), and to the thyrotropin‐releasing hormone (TRH) test, which was performed with 500 μg synthetic TRH I.V., and referred to age and sex specific normal ranges. Moreover, serum triiodothyronine (T3) was estimated by radioimmunoassay. Results: 1. A gradual classification of biochemical group‐differences gave more significant discrimination than a division into groups based on clinical impression. Different grades of severity of hypothyroidism could be demonstrated by highly significant differences of free thyroxine index (FT4‐Index) between the 1st group of patients with low FT4‐Index and a 2nd group with raised basal TSH (and normal FT4‐Index), between the 2nd group and a 3rd group with an elevated value of Δ TSHmax (and normal FT4‐Index and basal TSH), and between the 3rd group and a 4th group of biochemically normal reacting patients and controls. There was a less significant difference with very considerable overlap between clinically established groups. 2. T3‐uptake, total T4 and FT4‐Index are not sufficient for detecting hypothyroidism in individual patients, although their group‐differences are significant in biochemical classification. 3. Neither between clinical nor between biochemical groups was there any significant correlation with serum cholesterol. 4. Triiodothyronine can be normal or elevated in a situation with low T4 and raised TSH concentrations. Conclusions: Evidence could be given that hypothyroidism is a graded phenomenon. Its classification by biochemical data is more reasonable than a clinical division. Advancing severity of hypothyroidism after radiation therapy is compensated during a certain period by supplementary production of triiodothyronine. As thyroid hormone concentration in patients with pathological serum TSH or TRH‐test is significantly lower than in euthyroid patients or in controls, replacement therapy in early stages of hypothyroidism also seems reasonable.
The Kinetics of Plasma Free Fatty Acid and Triglyceride Transport in Patients with Idiopathic Hypertriglyceridaemia and Their Relation to Carbohydrate Metabolism
Authors: Adams P. W. , Kissebah A. H. , Harrigan P. , Stokes T. , Wynn V.
Published: March 2011

Abstract. Plasma free fatty acid and triglyceride transport kinetics were assessed in 20 patients with idiopathic hypertriglyceridaemia. None of these patients had abnormal glucose tolerance. They included 10 patients in whom the serum triglyceride elevation was due to an increase in the circulating VLDL (Fredrickson Type IV) and 10 in whom the increase in plasma VLDL was associated with hyperchylomicronaemia (Fredrickson Type V). These were compared with a control group of 27 normal subjects.—Increased plasma triglyceride turnover with normal clearance was observed in the Type IV patients suggesting that the hypertriglyceridaemia in these patients was predominantly due to enhancement of plasma triglyceride production. The plasma triglyceride concentration correlated closely with the changes in triglyceride turnover rate.—Studies performed in the Type V patients showed an increase in the plasma triglyceride turnover rate in only 3 subjects, while in the remaining patients the turnover values were similar to those of the control subjects. The increase in serum triglyceride concentration found in some of the patients was due to an increase in plasma triglyceride production. However, in the majority of patients in this group impairment of plasma triglyceride clearance was the predominant abnormality.—In both hypertriglyceridaemic groups the plasma FFA flux was markedly increased and correlated significantly with the degree of hypertriglyceridaemia. The increase in triglyceride turnover observed in Type IV patients and some of the Type V patients correlated closely with the enhancement of plasma FFA flux suggesting that the increase in triglyceride production in these patients was secondary to enhanced lipolysis.—The plasma insulin response to an oral glucose load was markedly increased in both groups of hypertriglyceridaemic patients and correlated significantly with the elevation in serum triglyceride concentration. The plasma insulin response also correlated with the plasma free fatty acid turnover.—The results suggest that the initial lesion in these patients was related to insulin unresponsiveness in adipose tissue resulting in enhanced lipolysis with secondary changes in insulin secretion and plasma triglyceride transport kinetics.
Dibromsulphalein (DBSP) Estimation of Hepatic Transport Function in Man*
Authors: Dhumeaux D. , Berthelot P. , Javitt N. B.
Published: March 2011

Abstract. Bromsulphalein (BSP) and dibromsulphalein (DBSP) were given separately in equimolar amounts by intravenous injection or infusion to 15 apparently healthy individuals and 33 individuals with hepatobiliary disease. The slope (K) of the plasma disappearance rate, the relative storage capacity (S) and the maximum biliary excretion rate (Tm) for both BSP and DBSP were calculated and the mean values for each group determined.—In the normal group, K for DBSP, 0.234 ± 0.023 (1 SD), was found to be significantly greater than K for BSP, 0.151 ± 0.042, indicating a more rapid plasma disappearance rate for DBSP. Similarly, S was significantly higher for DBSP, 124.6 ± 56.6 μmol/μmol/100 ml, than for BSP, 67.7 ± 34.1. The Tm for DBSP however, 10.9 ± 1.6 μmol/min., was not significantly different from that for BSP, 9.5 ± 1.7.—In the patients with cirrhosis, there was reduction in K, S, and Tm, which was of the same order of magnitude for both dyes, indicating that DBSP is as sensitive as BSP in the detection of liver disease. Since DBSP is not conjugated in vivo, this suggests that the modifications of BSP disposition in cirrhosis are attributable primarily to a defect in the transport function of the liver cell. Defective conjugation of BSP therefore probably does not contribute importantly to the BSP abnormalities observed in cirrhotic patients.
Intrarenal Haemodynamics in Rats during Haemorrhagic Hypotension*
Authors: Sandoz P. , Grandchamp A. , Truniger B.
Published: March 2011

Abstract. Previous studies of intrarenal haemodynamics by wash‐out with inert gas suggested that haemorrhagic hypotension (HH) in the dog causes a redistribution of intrarenal blood flow with a patchy cortical hypoperfusion, mainly due to an increased concentration of circulating catecholamines. In the present experiments intrarenal haemodynamics were studied by the same methods in the rat during prolonged HH with a mean arterial BP of 51 mm Hg. Under these conditions inert gas wash‐out studies showed a decrease in compartment I (CP I) flow fraction (“cortical flow fraction”) from 81.5% to 43.2% of total renal blood flow (RBF). CP I blood flow dropped from 3.13 ml/min. to 0.63 ml/min. per g kidney weight. Total renal vascular resistance increased by a factor of 1.2 as compared with control conditions. These changes in intrarenal haemodynamics were considerably smaller than those observed in the dog under comparable conditions. In contrast to observations in the canine kidney no patchy areas of cortical hypoperfusion occurred in the rat, and there was no evidence of stratification of cortical blood flow during HH. Instead, there was an even reduction in cortical blood flow from the subcapsular area to the cortico‐medullary border as indicated by inert gas wash‐out studies and 85krypton autoradiographs. The meaning and pathogenesis of the observed differences between both species remains to be defined. It is suggested that in the rat the reaction of the renal vasculature to sympathoadrenal stimuli and/or to angiotensin might be different from that in the dog.
Origin and Nature of the Proteins of Bile
Authors: Dive Ch. , Nadalini R. A. , Vaerman J.‐P. , Heremans J. P.
Published: March 2011

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.
Incorporation Rate of Leucine into Proteins in Human Liver Slices
Authors: Stakeberg H. , Gustafson A. , Schersén T.
Published: March 2011

Abstract.The rate of incorporation of leucine into hepatic proteins in liver slices from 42 patients was studied. Zero order kinetics for the incorporation of leucine in relation to the incubation time and to the amount of incubated proteins were obtained, provided that the medium contained a complete amino acid mixture with a concentration 4 times that of normal human serum. — Inulin space and water content of the preparation were of the same magnitude as reported for rat liver. The presence of fructose (5.5 mM) in the medium caused an inhibition of the rate of incorporation of leucine into proteins. Insulin in the medium, however, stimulated the incorporation rate. — Assuming that the rate of incorporation of leucine into hepatic proteins is representative of protein synthesis, the half‐life of liver proteins can be calculated to be 35 days for subjects below 60 years of age. For those who were older than 60 years, the protein turnover rate was approximately 30% higher.
The Effect of Cholestyramine on the Elimination of Cholesterol as Bile Acids in Patients with Hyperlipoproteinaemia Type II and IV
Authors: Einarsson Kurt , Hellström Kjell , Kallner Mora
Published: March 2011

Abstract. The turnover of 14 C‐cholic acid and 3 H‐chenodeoxycholic acid was studied in hyperlipaemic patients before and during treatment with cholestyramine. — In five female patients with hyperlipoproteinaemia type IIa the pool size and turnover of cholic acid as well as the total formation of bile acids were significantly lower than in female normolipaemic controls. During treatment with cholestyramine, cholic acid synthesis rose 4–18 fold and the turnover of chenodeoxycholic acid increased about twice. In three of the patients these changes were associated with a normalization of the serum cholesterol levels. Mainly due to the high turnover of cholic acid, total bile acid synthesis was above the normal range in the five male patients with hyperlipoproteinaemia type IV. During treatment with cholestyramine, the serum lipids and cholic acid formation remained unchanged but the turnover of chenodeoxycholic acid increased by a factor of about two. This resulted in a decrease of the abnormally high initial ratio between the formation of cholic acid and chenodeoxycholic acid. The unequal response to cholestramine treatment is taken to be a further indication that hyperlipoproteinaemia type II and type IV are different entities of disease affecting cholesterol and bile acid metabolism.
Hypertriglyceridaemia Secondary to Liver Disease
Authors: Müller P. , Fellin R. , Lambrecht J. , Agostini B. , Wieland H. , Rost W. , Seidel D.
Published: March 2011

Abstract. Some patients with liver dysfunction show a marked hypertriglyceridaemia, a phenomenon most frequently accompanied by cholestasis.

In this report we have identified, isolated and characterized an abnormally large (300–700 Å), triglyceride rich, low density lipoprotein, (d 1.019‐1.063 g/ml) designated β‐lipoprotein (β2‐LP), from the plasma of patients with hypertriglyceridaemia secondary to liver disease. The βa‐LP differs significantly in its percent composition and protein moiety from the unique lipoprotein‐X (LP‐X) specific for cholestasis and also from normal β‐lipoproteins, both of which are also present in the patients LDL fraction. Furthermore, some evidence is provided suggesting that the β2‐LP is likely to represent an intermediate particle of chylomicron metabolism, which accumulates in this disease due to a markedly diminished hepatic lipase activity.
The Effect of Acute Uraemia on Gluconeogenesis in Isolated Perfused Rat Livers
Authors: Fröhlich Jürgen , Schölmerich J. , Hoppe‐Seyler G. , Maier K. P. , Talke H. , Schollmeyer P. , Gerok W.
Published: March 2011

Abstract. The effect of acute uraemia on glucose and urea formation by isolated perfused livers of fasting rats was investigated.

The basal gluconeogenesis following nephrectomy was significantly increased as compared to normal and sham operated controls. Enhanced glucose formation was associated with an increase in both urea synthesis and output of the poorly metabolizable amino acids valine, leucine, and isoleucine. In the presence of a mixture of amino acids (serine, threonine, lysine, glutamic acid, ornithine, and citrulline) all added at near physiological concentrations, the stimulating effect of uraemia on gluconeogenesis was further enhanced. This was paralleled by an increased formation of urea and an increased uptake of the amino acids. It is concluded that acute uraemia may stimulate glucose synthesis by increased substrate supply. This seems to be achieved by at least two different mechanisms, namely increased protein degradation and accelerated amino acid utilization.
The Effect of Pregnancy on the Control of Lipolysis in Fat Cells Isolated from Human Adipose Tissue
Authors: Elliott Jennifer A.
Published: March 2011

Abstract. 1. Lipolysis has been estimated by measuring the release of glycerol in isolated adipose tissue cells obtained from women in early prognancy, late pregnancy and 1–3 days post partum and from non‐pregnant women. 2. Adipocytes of women at the end of pregnancy exhibited higher rates of lipolysis in response to adrenaline (1.5–15 μM) plus phentolamine (13 μM) than those of non‐pregnant women or those in early pregnancy. 3. Lipolysis in response to adrenaline plus phentolamine in fat cells from women 1–3 days post partum was reduced compared to that at the end of gestation but was enhanced relative to that in the non‐pregnant or early pregnant state. 4. Basal lipolysis also tended to be greatest at term. 5. Under conditions where the production of cyclic AMP was not rate limiting for the stimulation of lipolysis, that is in the presence of dibutyryl cyclic AMP (1 mM) or adrenaline (15 μM) plus phentolamine (13 μM) plus caffeine (1 mM), the release of glycerol in cells from women at term and in the puerperium was greater than that in women in the non‐pregnant or early pregnant state. 6. Cell levels of cyclic AMP rose after incubation with adrenaline (6 μM) plus phentolamine or adrenaline (15 μM) plus phentolamine plus caffeine (1 mM) but were similar in all four groups of women. 7. It is concluded that the observed enhancement of lipolysis demonstrated in fat cells from women at the end of pregnancy reflects an increase in hormone‐sensitive lipase activity rather than a modification of hormone receptor site sensitivity or of the rates of synthesis or breakdown of cyclic AMP. 8. This increase in adipose tissue lipolysis at the end of gestation could contribute to the reported rise in plasma nonesterified fatty acids in the final weeks of pregnancy.
Regional and Systemic Haemodynamic Effects of Some Vasopressins: Structural Features of the Hormone which Prolong Activity
Authors: Cort J. H. , Albrecht I. , Nováková J. , Mulder J. L. , Jošt K.
Published: March 2011

Abstract. Cardiac output and regional blood flows to myocardium, gut, uterus and kidney were determined in anaesthetised female rats by a single injection of 86RbC1. 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”) Nα‐glycyl‐glycyl‐glycyl‐lysine‐vasopressin, Nαglycyl‐glycyl‐glycyl‐arginine‐vasopressin and Nα‐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 Nα‐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.
Discrepancy between the Measurement of Thyroxine‐Binding Prealbumin Plasma Level and Binding Capacity in Protein‐Calorie Malnutrition
Authors: Ingenbleek Y. , De Nayer Ph. , De Visscher M.
Published: March 2011

Abstract. The measurement of thyroxine‐bindung prealbumin (TBPA) in protein‐calorie malnutrition by two different techniques leads to the recognition of an unexpected discrepancy. Whereas TBPA plasma levels as measured by immunodiffusion are markedly decreased to 29.3 % of the normal, those recorded by maximal binding capacity (TBPAcap) are characterized by a wide dispersion. In the control group, the ratio between TBPA and TBPA plasma level is 9.1. In the malnourished group on admission, the same ratio is 30.0. The possibility of a qualitative effect in the tetrameric TBPA structure, with the binding of additional thyroxine (T4) molecules on the secondary binding sites, has been investigated. This hypothesis has been discarded by Scatchard plot studies. The normal 1:1 molar ratio between TBPA and T4 is unaffected in protein‐deficient patients. Discrepant results obtained for TBPAcap and TBPA levels appear to be the consequence of low plasma protein levels, leading to an artifact in the electrophoretic method.
Granulocyte Collagenase, Elastase and Plasma Protease Inhibitors in Purulent Sputum
Authors: Ohlsson Kjell , Tegner Hans
Published: March 2011

Sputum was collected from patients with purulent chronic bronchitis. Immuno‐chemical techniques using rabbit antiserum against human granulocyte collagenase and elastase showed the presence of both enzymes. Also the serum protease inhibitors ***α1‐antitrypsin and α2−macroglobulin were demonstrated. Their Protease inhibiting capacity was saturated. Granulocyte elastase and collagenase occurred not only in complexes with the inhibitors, but also as free enzymes. All sputa showed free proteolytic, elastolytic and collagenolytic activity. The concentration of collagenase was equal in the sol phase and in the gel phase of the sputa, but most of the elastase was bound to the gel phase.
Force Velocity Characteristics of Oesophageal Muscle: Interaction of Isoproterenol and Calcium
Authors: Cohen Sidney
Published: March 2011

The purpose of this study was to evaluate the interaction of isoproterenol and calcium upon the force velocity characteristics of opossum oesophageal circular muscle, in vitro. Isotonic and isometric recordings were used to determine the velocity of shortening and force, respectively. All muscle was studied at its length of optimal tension development (Lo). To determine the effect of isoproterenol upon muscle contractility, studies were performed at 2.5 mM and 5.0 mM calcium Kreb's solution. The maximal velocity of shortening (V max) and the peak force (Po) of oesophageal muscle were 6.2 ± 0.3 mm/s and 16.8 ± 1.0 gm, respectively, at 2.5 mM calcium. Isoproterenol (10−5 M) decreased the V max to 4.9 ± 0.6 mm/s and the Po to 9.8 ± 1.3 gm (P < .01). Increased calcium (5.0 mM), alone, did not alter either V max or Po. However, at 5.0 mM calcium, 10−5 isoproterenol reduced the V max to 6.0 ± 0.6 mm/s (P > .05) and the Po to 13.9 ± 0.8 gm (P < .05). These studies indicate that isoproterenol significantly reduces the V max and Po of oesophageal smooth muscle during the neural mediated “off response”. This effect of isoproterenol is reversed, in part, by an increase in calcium concentration.
Contrasting Effects on Plasma Lipoproteins of Intravenous Versus Oral Administration of a Triglyceride‐Phospholipid Emulsion
Authors: Thompson G.R. , Segura R. , Hoff H. , Gotto A.M.
Published: March 2011

Abstract. The effect of fat on plasma lipoproteins was compared when administered by the oral and intravenous routes to healthy control subjects on a low fat diet for 5–6 weeks. During this time each subject underwent two 5 day periods of fat supplementation with a soya bean triglyceride‐egg yolk phospholipid Emulsion (Intralipid), once via intragastric tube, once intravenously. Changes in plasma lipoproteins Were assessed by measurement of their lipid and protein content. Intragastric fat administration significantly decreased the level of very low density lipoprotein (VLDL), whereas intravenous fat administration Caused a significant rise in low density lipoprotein (LDL). Morphological evidence of persistence of exogenous phospholipid in plasma following intravenous fat administration was confirmed by alterations in the fatty acid composition of lecithin in the d 1.006‐1.063 fraction of plasma. In vitro studies showed that exchange readily occurred between Intralipid and LDL lecithin, causing the latter to assume a more saturated Pattern. It is concluded that the occurrence of similar changes in vivo could explain the rise in low density lipoprotein following intravenous fat, possibly by influencing the catabolic rate of the apoprotein. Hydrolysis of ingested phospholipids during absorption presumably explains why none of these changes occurred after oral fat supplementation, and would seem to be an important regulatory function of the small intestine in relation to plasma lipoprotein metabolism.
Observations on the Effect of CO2 and Temperature the Sickling Phenomenon
Authors: Rampling M. W.
Published: March 2011

Abstract. The explanation of the effect of CO2 on the sickling phenomenon has, in the past, been based solely on the alteration of the oxygen affinity of haemoglobin induced by the CO2, and hence solely on the oxygen saturation of the haemoglobin. A re‐investigation of this phenomenon, reported here, shows that this explanation is inadequate; rather, a full explanation requires the use of Perutz's hypothesis that the haemoglobin molecule can exist in various conformationally distinct states, the relative concentrations of which are dependent not only on the oxygen saturation of the molecules but also on other factors such as pH and 2,3‐diphosphoglycerate (DPG) concentration. The effect of temperature on the sickling phenomenon is explained in a similar fashion. Low temperature is found to have no effect on the morphology of irreversibly sickled cells.
The Effect of Propranolol and Phentolamine on Serum Gastrin Concentration in Response to Respiratory Acidosis in Normal Man
Authors: Kaess H. , Utz G. , Teckentrup U. , Hauck A.M. , Dörner M.
Published: March 2011

Abstract. Serum gastrin concentration and basal acid secretion were studied in normal subjects under the influence of respiratory acidosis induced by CO2 rebreathing. During the intragastric instillation of 100 ml/h 0·5 M bicarbonate a significant increase of gastrinaemia from 130 to 158 pg/ml (p < 0·01) occurred in ten subjects during respiratory acidosis (pCO2 62 torr, pH 7·25). Under the intragastric instillation of 100 ml/h 0·1 N HCl the rise of gastrin concentration in response to CO2 rebreathing (pCO2 68 torr, pH 7·20) was not significant. The relationship between the decrease of pH and the increase of the gastrin concentration was shifted in the direction of a greater systemic acidosis compared to the results performed in the presence of a neutral intragastric pH. 50 μg/kg propranolol intravenously produced a decrease of gastrin concentrations from 145 to 127 pg/ml (p < 0·01) and a total suppression of hyper‐gastrinaemia in response to CO2 rebreathing, suggesting activation of beta‐cell receptors in respiratory acidosis. The infusion of phentolamine in a dose of 0·6 to 1·8 mg/min. resulted in a rise of gastrin concentration from 140 to 165 pg/ml (p < 0·01) which was not further elevated during respiratory acidosis. The basal acid secretion showed a significant rise in response to CO2 rebreathing, which was abolished by the administration of propranolol.
Mechanisms of Albumin Loss during Peritoneal Dialysis in Man
Authors: Bianchi R. , Mariani G. , Pilo A. , Carmassi F.
Published: March 2011

Abstract. Albumin loss in the dialysate was evaluated during a total of 5 peritoneal dialyses carried out on 3 uraemic patients. The measurements were made by two different methods, the first based on the evaluation in the dialysate of intravenously injected radioiodinated albumin, the second one based on a radioimmunoassay of the protein in the dialysate. The results obtained showed three main mechanisms of protein loss during peritoneal dialysis: 1) albumin shift from extravascular sites adjacent to the peritoneum, 2) direct passage of albumin from blood stream to peritoneal cavity, and 3) tendency of the inter‐dialysis peritoneal fluid to equilibrate with plasma proteins. Furthermore, the observations made on a patient with evident peritonitis proved the importance of the intrinsic biological properties of the peritoneum in determining the amplitude of protein wasting by the dialysate.
Plasma Catecholamines and Blood Substrate Concentrations: Studies in Insulin Induced Hypoglycemia and after Adrenaline Infusions
Authors: Christensen N.J. , Alberti K.G.M.M. , Brandsborg O.
Published: March 2011

Abstract. Plasma adrenaline‐blood glucose interrelationships in insulin‐induced hypoglycaemia in man have been studied using a sensitive double‐isotope derivative method for adrenaline estimation. Plasma adrenaline reached a peak of 1.24 ng/ml at 45 minutes after insulin while blood glucose reached a nadir of 22 mg/100 ml at 30 minutes. There was a strong correlation both between the rise in adrenaline and the degree of hypoglycaemia and between the rise in adrenaline and the post‐hypoglycaemic rise in glucose. Plasma noradrenaline rose from 0.29 to 0.59 ng/ml, the rise correlating with the rise in adrenaline. Changes in pulse rate preceded and were unrelated to changes in plasma catecholamines. Fuel mobilisation in response to adrenaline infusion (6 μg/min. for 20 min.) in normoglycaemic man was also studied. Plasma adrenaline concentration rose from a mean of 0.02 ng/ml to 0.71 ng/ml while plasma noradrenaline concentration was unchanged. Blood glucose rose from 71 to 98 mg/100 ml while plasma insulin decreased from 11 to 8 μ/ml. Blood lactate rose by 0.85 mM while pyruvate concentration remained unchanged. Blood glycerol concentration rose twofold and ketone body concentration threefold but there was little change in the concentrations of the glucogenic amino acids, alanine, glutamate and glutamine. Both the 3‐hydroxybutyrate/acetoacetate ratio and the lactate/pyruvate ratio rose implying a more reduced intracellular state due presumably to increased hepatic fatty acid oxidation. It is concluded that adrenaline enhances the recycling of lactate and spares glucose through the mobilitsation of lipids but that amino acids are little affected.
Effect of Fasting on Two Postheparin Plasma Triglyceride Lipases and Triglyceride Removal in Obese Subjects
Authors: Huttunen J.K. , Ehnholm C. , Nikkilä E.A. , Ohta M.
Published: March 2011

Abstract. A new method was used for selective measurement of lipoprotein lipase and hepatic lipase in human postheparin plasma. Hepatic lipase was assayed in 1.0 M NaCl without addition of serum, and the activity of lipoprotein lipase was determined in 0.1 M NaCl after immunoprecipitation of hepatic lipase with specific antiserum. The activity of both these enzymes and the total lipolytic activity were measured in plasma samples taken during a 4‐h infusion of heparin. Each of the activities was related to basal serum triglyceride concentration and to the fractional removal constant (K) of Intralipid in 13 obese subjects before and after prolonged fasting. During a normal isocaloric diet the lipolytic activities showed a biphasic response to heparin infusion in all subjects. A peak activity was reached within 30 minutes (“early response”) and thereafter the lipase activities decreased to a constant level maintained during the rest of the heparin infusion (“late response”). The early response of lipoprotein lipase showed a significant inverse correlation with the basal serum triglyceride level (r = −0·85) and a significant positive correlation with the fractional removal rate of Intralipid (r = +0·84). The late response of lipoprotein lipase was not related to either of these parameters. The early response of hepatic lipase was not correlated with basal triglyceride concentration or Intralipid removal, whereas the late response of this enzyme showed a significant negative correlation with the removal rate of Intralipid (r = −0·82). After fasting for several days the acute response of all lipolytic activities to heparin was markedly decreased or totally abolished, but the magnitude of the late response was similar to that seen in the fed state. The fractional removal rate of Intralipid was slightly increased by starvation. All correlations between postheparin plasma lipases and serum triglyceride concentration and removal disappeared in fasting subjects. It is concluded that the rapidly releasable lipoprotein lipase probably reflects the activity of the tissue enzyme(s) which is responsible for the primary removal of very low density lipoprotein (VLDL) triglycerides and chylomicrons. It is probable that this component of the postheparin plasma lipolytic activity is derived from the endothelial lipoprotein lipase pool. This enzyme plays a key role in the efflux of plasma triglycerides under normal conditions, and it is thus one determinant of plasma triglyceride level. Prolonged fasting obviously changes the triglyceride removal sites and mechanism but does not impair the removal efficiency.
Interaction of Secretin and Insulin on Human Forearm Metabolism
Authors: Chisholm D.J. , Klassen G.A. , Dupre J. , Pozefsky T.
Published: March 2011

Abstract. The effect of secretin on forearm metabolism (muscle compartment) was examined in the presence of low and high concentrations of insulin. Continuous infusions (30 min. duration) of secretin 12 ng/min. (SEC), insulin 160 ng/min. (INS) or these doses of insulin and secretin together (INS + SEC) were delivered into the brachial arteries of normal volunteers. SEC alone was without significant effect on forearm metabolism. INS as previously reported, stimulated glucose and potassium uptake and inhibited the output of some amino acids from the deep venous bed. The two hormones together (INS + SEC) increased maximum lactate (p <*** 0·025) and alanine output (p < 0·005) beyond that observed with INS alone. A marked calcium output occurred (p <*** 0·001) with the combined infusion which was not observed with either hormone alone. Potassium metabolism with INS + SEC was similar to that observed with INS alone. These results suggest that these two hormones, acting in concert, stimulate glycolysis and net calcium efflux. This joint action of insulin and secretin may have a physiological role in the immediate postprandial period.
Radioimmunoassay of Prostaglandins Fα, E1 and E2 in Human Plasma
Authors: Dray F. , Charbonnel B. , Maclouf J.
Published: March 2011

Abstract. Antibodies against prostaglandins (PG)F2α, E1 and E2 were obtained in rabbits immunized with respectively PG F2α, PG E1 and PG E2 conjugated to bovine serum albumin by carbodiimide. A radioimmunoassay capable of measuring 7 pg of PG Fα, 2 pg of PG E2 and 14 pg of PG E1 in human peripheral plasma is described. Plasma samples (pH 3, citric acid) are extracted with cyclohexane: ethyl acetate, 1:1 and then chromatographed on silicic acid columns to separate the prostaglandins into three fractions: fraction I, PG A, PG B and some unknown immunoreactive compounds; fraction II, PG E and fraction III, PG Fα. The recovery is 80 % ± 6.2. Mean plasma levels in adults of PG Fα and PG E, expressed in pg/ml: ‐PG Fα 12 ± 2.8 (n = 25 men), 8 ± 2.3 (n = 18 women, follicular phase), 7 ± 1.4 (n= 18 women, luteal phase). ‐PG El 40.5 ± 7.6 (n = 13 men), 38 ± 17.1 (n = 10 women). ‐PG E2 4.5 ± 1 (n = 12 adult subjects).

The major characteristics of the method described herein are the following: ‐ a large volume of plasma has to be processed (10 ml or more for PG Fa and PG E1, 5 ml or more for PG E2). ‐ a chromatographic step is necessary to separate the different prostaglandins which makes it possible to circumvent problems of immunological cross reactivity and interference with unknown immunoreactive compounds. ‐ great care has been taken in collection of blood samples, especially to insure complete removal of blood cells namely platelets.
Effects of Burn Injury on Insulin Secretion and on Sensitivity to Insulin in the Rat in vivo
Authors: Frayn K.N.
Published: March 2011

Abstract. Both insulin resistance and impairment of insulin secretion are know to occur in man after injury. The relative importance of these effects was studied in rats 2 h after a non‐lethal 20 % dorsal scald. No impairment of insulin secretion was found after this injury. Concentrations of both blood glucose and plasma insulin were elevated in scalded rats. Scalded rats responded to intravenous glucose injection (1.0 g/kg) with a further rise in plasma insulin concentration, which remained normal for the prevailing blood glucose concentration. However, marked impairment of glucose tolerance was observed, indicating the presence of insulin resistance. After intravenous insulin injection (1.0 U/kg) the initial rate coefficient for fall of blood glucose concentration was significantly lower (p < 0.02) in scalded (mean 3.9% min.−1) than in control rats (mean 6.3% min.−1). The minimum in blood glucose concentration after insulin injection was reached at 10 min. in control rats, but not until 60 min. after injection in scalded rats. This difference was due to a delay in compensation for the hypoglycaemia in the scalded rats, since the rate of disappearance of insulin measured by injection of a tracer of 125I‐laelled bovine insulin was not decreased after this injury. It was concluded that the impairment of glucose utilization in scalded rats (Heath and Corney, 1973) is due to decreased sensitivity to insulin rather than to suppression of insulin release.
Synthesis of Immunoglobulins and 15 Other Proteins by Diseased Human Kidneys*
Authors: Poortmans J. , Bienenstock J.
Published: March 2011

Summary. In an effort to determine the synthetic capacity of human kidneys for serum proteins, pieces of both kidneys removed at operation prior to transplantation were placed in organ culture. Incubation with 14C labelled amino acids and subsequent radioimmunoelectrophoresis with antisera to all five classes of immunoglobulins showed synthesis of IgG by all 5 pairs of kidneys of IgA and IgE by 4, and of IgM by 2. None synthesized IgD. Radioimmunoelectrophoresis with specific antisera to 15 non‐immunoglobulin proteins revealed synthesis of lactoferrin and uromucoid while several other serum proteins, such as α1 antitrypsin and α2 macroglobulin, known for their binding properties, showed apparent synthesis. No evidence for secretory component synthesis was seen despite positive immunofluorescent localization in the tubular cells. Further, Zn α2 and b̊2GP also showed positive immunofluorescence but negative synthesis. It seems possible that these latter proteins may not be synthesized by the tubular cells but rather may be actively excreted or reabsorbed by them.
Inheritable abnormal lipoprotein metabolism in Werner's syndrome similar to familial hypercholesterolaemia
Authors: MORI S. , YOKOTE K. , MORISAKI N. , SAITO Y. , YOSHIDA S.
Published: March 2011

Studies were made on the abnormality of lipoprotein metabolism and its cause in 10 patients with Werner's syndrome. Seven of the 10 patients had hypercholesterolaemia (above 250 mg dl−1). Six of the seven patients with hypercholesterolaemia had thickened Achilles' tendons (> 9 mm). A significant positive correlation (P < 0·01) was found between the serum total cholesterol levels and the thickness of Achilles' tendons in these 10 patients, suggesting that the substance precipitated in the thickened tendons is derived from serum cholesterol. Some first‐degree relatives of three patients with both hypercholesterolaemia and xanthoma‐like thickening of Achilles' tendons also suffered from hypercholesterolaemia. Moreover, the low density lipoprotein (LDL) receptor activities in peripheral lymphocytes of five patients with both hypercholesterolaemia and xanthoma‐like tendons were significantly (P < 0·001) lower than those of controls, whereas the LDL receptor activities of two patients without hypercholesterolaemia were almost the same as those of controls. These findings suggest that, at least these five patients with lower lymphocyte LDL receptor activities, and probably another patient with both hypercholesterolaemia and xanthoma‐like thickening of Achilles' tendons suffered from familial hypercholesterolaemia (FH). If this is the case, this high frequency of association of Werner's syndrome with FH (in six of 10 patients) suggests some relationship between these two diseases.
Evidence for abnormal platelet glycoprotein expression in diabetes mellitus
Authors: TSCHOEPE D. , ROESEN P. , KAUFMANN L. , SCHAUSEIL S. , KEHREL B. , OSTERMANN H. , GRIES F. A.
Published: March 2011

In 41 diabetics (27 type I, 14 type II) and in 23 healthy controls the number of glycoprotein (GP) GPIB and GPIIB/IIIA molecules were determined on resting, peripheral platelets by means of flowcytometry after immunostaining with monoclonal antibodies which bind independently from the state of activation. The average number of both glycoproteins per platelet was significantly elevated (GPIB: 54100 times 1·27±1 vs. 39100 times 1·3±1 GPIIB/IIIA: 77500 times 1·3±1 vs. 62700 times 1·3±1, in diabetic patients. Platelet volume was significantly correlated with the number of GPIB molecules on normal and diabetic platelets (r (normal) = 0·52 ± 0·07; r (diabetic) = 0·46 ± 0·1). Additionally, von Willebrand factor‐related antigen (vWF: AG) was increased to 129% × 1·3 ± 1 in diabetics vs. 111% × 1·4 in controls. The increase of vWF: AG was significantly correlated with HbA1 (r = 0·38*) and seemed to depend on chronic hyperglycaemia. Since platelet glycoprotein receptor status is regulated by the bone‐marrow megakaryocyto‐ thrombopoiesis, our observations support the hypothesis that platelet hyperactivity in the diabetic state may be due to primarily altered production of platelets with an increased number of functional glycoproteins. This may be paralleled by increased plasma levels of cytoadhesive proteins like vWF: AG, which interact with the studied glycoproteins and thereby potentiate the risk of disturbed microhaemorrheology.
Physical conditions and challenging behaviour in people with intellectual disability: a systematic review
Authors: de Winter C. F. , Jansen A. A. C. , Evenhuis H. M.
Published: March 2011

Background  Challenging behaviour is a major problem among people with intellectual disabilities. Physical factors may be an important cause. The aim of the present systematic review was to determine the physical conditions associated with challenging behaviour.

Methods  A literature search was conducted in PubMed and the Cochrane systematic review database for empirical studies published between 1990 and 2008. The quality of all the studies that met the inclusion criteria was assessed using the SIGN‐50 methodology checklists.

Results  The search identified 45 studies, which looked at general medical conditions, motor impairment, epilepsy, sensory impairment, gastrointestinal disease, sleep disorders, dementia and others. There were four high‐quality observational studies, seven well‐conducted observational studies, 21 observational studies of low methodological quality and 13 non‐analytical studies. There were significant and independent associations between challenging behaviours and urinary incontinence, pain related to cerebral palsy and chronic sleep problems, and between self‐injurious behaviour and visual impairment. No association was found with hearing impairment, bowel incontinence, mobility impairment or epilepsy. Many other physical conditions were not addressed at all.

Conclusion  Medical conditions can play a role in challenging behaviour, and this should be evaluated in the clinical setting. So far, the level of evidence is generally low, and longitudinal studies are completely lacking. We recommend a systematic approach to research examining the role of physical conditions in challenging behaviour, the ultimate aim being to establish a basis for the development of clinical guidelines.