bluuebunny/crossref_metadata_2025 huggingface dataset:
Impairment of Growth Hormone and Insulin Secretion in Hyperthyroidism
Authors: Cavagnini F. , Peracchi M. , Raggi U. , Bana R. , Pontiroli A. E. , Malinvemi A. , Pinto M.
Published: March 2008

Abstract. The pattern of growth hormone (GH) and im‐munoreactive insulin (IRI) secretion in response to insulin hypoglycaemia, arginine infusion and oral glucose load has been investigated in a group of hyperthyroid subjects. In twenty patients, compared with twenty normal controls, GH secretion was significantly reduced in response to both insulin hypoglycaemia and arginine infusion. Arginine‐induced IRI secretion was also clearly decreased. In ten patients who had undergone a 100 g oral glucose load, hyperglycaemia failed to suppress GH levels, which increased paradoxically. Slightly impoverished IRI secretion and impaired glucose tolerance were observed in these subjects. In five patients, re‐examined soon after restoration of euthyroidiszn, no significant changes in glucose tolerance and IRI secretion were noted; instead, a slightly improved GH response to the provocative stimuli and the restoration of a normal GH suppression by glucose were observed. – The possibility is emphasized that in hyperthyroidism an enhancement of the catecholamine effect induced by thyroid hormones is involved in the diminished GH and IRI secretion.
Galactose Metabolism in a Patient with Hereditary Galactokinase Deficiency
Authors: Gitzelmann Richard , Wells Henry J. , Segal Stanton
Published: March 2008

Abstract. The ability of a galactokinase deficient patient to metabolize galactose, galactitol and galactonate was quantitated. In galactokinase deficiency, conversion of galactose to CO2 is minimal. Apparently the defect is extensive, involving all tissues. Galactitol and galactonate, injected intravenously, were not metabolized. The administration of C‐1 and C‐2 labelled galactose resulted in 14CO2 excretory patterns similar to that observed in uridyltransferase deficient mutants. The different fates of C‐1 and C‐2 observed in this galactokinase deficient patient give support to the existence of a direct oxidative pathway for galactose. Galactonate, although present in urine during the period of observation following injection of radioactive galactose failed to become labelled.
Metabolic Studies on the Pathogenesis of Hangover
Authors: Ylikahri R. H. , Huttunen M. O. , Eriksson C. J. P. , Nikklä E. A.
Published: March 2008

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 hypoglycemia 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.
Leukocyte Glucocerebrosidase Deficiency Diagnostic in Adult Gaucher's Disease with Negative Bone Marrow Biopsy. Some Properties of the Enzyme in Leukocytes and Spleen
Authors: Klibansky Ch. , Hoffmann J. , Pinkhas J. , Algom D. , Dintzman M. , Ben‐Bassat M. , de Vries A.
Published: March 2008

Abstract. A sixty‐one year‐old man with Gaucher's disease is described. The disease was manifested by splenomegaly, hypersplenism and elevations of serum acid phosphatase and immunoglobulin but no bone lesions were roentgenologically demonstrable and bone marrow biopsy failed to reveal Gaucher cells. The diagnosis was established prior to splenectomy by the finding of decreased β‐D‐gIucoside glucohydrolase (β‐D‐GGH) activity in his peripheral leukocytes. Examination of the surgically removed spleen revealed Gaucher cells, a large excess of glucocerebroside and decreased β‐D‐GGH activity. Splenectomy was followed by normalization of haemoglobin, white cell and platelet counts and of the serum acid phosphatase and immunoglobulin levels. The patient's leukocyte β‐D‐GGH activity showed an optimum pH similar to that of normal leukocyte enzyme, about 5.4, using both glucocerebroside (Glc‐Cer) and 4‐methylumbelliferyl‐β‐D‐glu‐copyranoside (MU‐Glc) as substrate. The patient's spleen β‐D‐GGH activity showed a pH optimum of about 4.5, which differed slightly from that of normal spleen enzyme. The Km values of β‐D‐GGH in the patient's leukocytes for Glc‐Cer and MU‐Glc were 1.35 × 10‐4 M and 3.6 × 10‐3 M, respectively, i.e. in the normal range. The patient's splenic tissue Km values were for Glc‐Cer and MU‐Glc 0.52×10‐4M and 5.8×10‐3 M, respectively, as compared to 0.30×10‐4 M and 5.0 × 10‐3 M in a normal control.
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.
Published: March 2008

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. & ‐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).
Plasma Cyclic AMP and Total Catecholamines during Acute Myocardial Infarction in Man
Authors: Strange Richard C. , Vetter Norman , Rowe Michael J. , Oliver Michael F.
Published: March 2008

Abstract. There is marked alteration in endocrine activity during acute myocardial infarction (AMI). Many of the hormones involved act by changing target cell concentrations of adenosine 3′: 5′ monophosphate (cyclic AMP). Since cyclic AMP can escape from cells, changes in intracellular concentrations of the nucleotide may be reflected in changes in plasma levels. The purpose of this study was to determine whether plasma cyclic AMP concentrations alter during the development of AMI.–Elevation of plasma cyclic AMP concentrations was noted during the first few hours following the onset of symptoms of AMI. The highest concentrations, recorded in a group of four patients with shock, showed a range of 54–193 pmol/ml which was significantly elevated compared to the normal range of 9–22 pmol/ml. This increase in plasma cyclic AMP correlated significantly and positively with plasma concentrations of total catecholamines. Patients with the worst prognosis had the highest plasma concentrations of cyclic AMP and total catecholamines.
Clearance of Antipyrine‐Dependence of Quantitative Liver Function
Authors: Andreasen Per Buch , Ranek Leo , Statland Bernard E. , Tygstrup Niels
Published: March 2008

Abstract. The purpose of the present study was to assess tile influence of liver disease on the hepatic drug‐metabolizing enzyme systems. The clearance of antipyrine was found to be significantly decreased in 13 patients with liver disease compared with 9 control patients (18.5 and 58.6 ml/min. respectively). Among the patients with liver disease, those with a severely reduced capacity for work had significantly lower clearance of antipyrine than non incapacitated patients (12.5 and 25.4 ml/min. respectively). The clearance of anti pyrine was significantly correlated with the galactose elimination capacity, the serum albumin and the prothrombin values. The results indicate that the drug‐metabolizing capacity of the liver changes in parallel with the other metabolic functions, and the use of the clearance of antipyrine as a quantitative test of liver function is suggested.
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 2008

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.
The Mechanism of Action of Clofibrate and Tetranicotinoylfructose (Bradilan) on the Kinetics of Plasma Free Fatty Acid and Triglyceride Transport in Type IV und Type V Hypertriglyceridaemia
Authors: Kissebah A. H. , Adams P. W. , Harrigan P. , Wynn V.
Published: March 2008

Abstract. The kinetics of plasma free fatty acid and triglyceride transport were assessed in 20 patients with idiopathic hypertriglyceridaemia. These patients were subdivided according to lipoprotein pattern into Type IV and Type V patients. The effects of clofibrate therapy on plasma free fatty acid and triglyceride kinetics were assessed in these patients. Clofibrate produced a marked reduction in serum triglyceride associated with a significant reduction in triglyceride turnover as well as enhancement of triglyceride clearance. The reduction in triglyceride concentration produced by clofibrate was found to correlate with the reduction in free fatty acid turnover indicating that this drug decreased the availability of free fatty acid turnover indicating that this drug decreased the availability of free fatty acids for hepatic esterification. Clearance of endogenous plasma triglyceride was markedly enhanced in those patients in whom it was markedly impaired before treatment. – Having discontinued clofibrate for six weeks the same patients received bradilan (tetranicotinoylfructose) and kinetic measurements were repeated. It was evident that bradilan had a greater hypotriglyceridaemic effect than clofibrate in both groups of patients. The effect of bradilan was the result of inhibition of free fatty acid turnover and consequently a marked reduction in triglyceride turnover. Bradilan, unlike clofibrate, did not affect the mechanisms responsible for the clearance of plasma triglycerides.
Urea‐Cycle Enzymes in Normal Liver and in Patients with Alcoholic Hepatitis
Authors: Maier K.‐P. , Volk B. , Hoppe‐Seyler G. , Gerok W.
Published: March 2008

Abstract Urea‐cycle enzymes and omithine‐ketoacid‐transaminase have been measured in biopsy specimens of liver from healthy subjects and from patients suffering from alcoholic hepatitis. Both groups of subjects received a hospital diet of about 100 g of protein daily. Extraction of enzymes from biopsy specimens was performed by a standardized technique.–The DNA content of liver did not vary significantly between the groups, whereas protein content was significantly lower in patients with alcoholic hepatitis than in controls (p < 0.05). Of the enzymes tested, the activities of carbamyl‐phosphate synthetase and arginase were significantly decreased (p < 0.05 and p < 0.005 respectively) in patients with alcoholic hepatitis. Activities of arginosnccinate lyase, ornithine‐ ketoacid‐transaminase and ornithine‐carbamylphosphate transaminase remained unchanged in both groups.–These results demonstrate that alterations in arginase and carbamylphoa‐phate synthetase‐activities in the liver of patients with alcoholic hepatitis precede the histological manifestation of liver cirrhosis, which is associated with a significant decrease in some urea cycle enzymes [3, 15, 16]. Therefore the determination of arginase and carbamylphosphate synthetase in needle‐biopsies of human liver represent sensitive parameters of liver cell necrosis during the course of alcoholic hepatitis.
Measurement of and Correction for Incubation Damage in Radioimmunoassay
Authors: Orskov H. , Seyer‐Hansen K.
Published: March 2008

Abstract. The role of incubation damage in the radioimmunoassay of human plasma insulin, human plasma growth hormone and rat plasma growth hormone was studied. Damage was measured as the fraction of labelled material which migrated from the origin in wick paper chromatography of samples without antibody. The experiments demonstrated, that recovery of added hormone differed increasingly from 100% as incubation damage increased. Recoveries were found to be too high using the double antibody technique, and too low using chromatographic technique. However, satisfactory recoveries could be obtained in chromatographic assay after correction for the experimentally determined incubation damage using the general formula: % Bound=100×(B‐KD)/ (100‐KD) where B is the apparent antibody‐bound fraction, D the damage fraction, both expressed as percent of the total radioactivity. K is determined experimentally.
Nature and Origin of the Proteins of Bile
Authors: Dive Ch. , Heremans J. F.
Published: March 2008

Abstract. The specific radioactivities in serum and bile were compared in patients recovering from biliary surgery after intravenous injection of 131I‐labelled albumin, oroso‐mucoid, transferrin and immunoglobulins IgA and IgG. It was found that the major plasma proteins occurring in hepatic bile are entirely derived from the circulating plasma, except for part of the IgA which is of local origin.–A comparative analysis of the concentrations of the different proteins in the two media further indicates that transfer from plasma to bile proceeds along two parallel pathways. One of these consists of bulk transport without distinction being made between the proteins; the other one involves a selection of the proteins as a function of their molecular size, revealing the existence of a semi‐permeable barrier interposed between the plasma and the biliary compartments. To account for the observed sieve effect, the pores of this membrane ought to have a mean radius of about 127 Å.
Operation of the “Glucose‐Fatty Acid Cycle” during Experimental Elevations of Plasma Free Fatty Acid Levels in Man
Authors: Balasse E. O. , Neef M. A.
Published: March 2008

Abstract. In order to determine whether increased plasma free fatty acid (FFA) levels inhibit glucose utilization in man, glucose metabolism was studied in 8 normal subjects both under basal conditions and during experimental elevations of plasma FFA concentrations induced by the administration of high fat meals and heparin. A primed constant infusion of 1‐14C‐glucose was used to measure the rate of turnover, the fractional removal rate and the rate of oxidation of plasma glucose under both experimental conditions. Elevations of FFA levels (+117%) were accompanied by a 9% reduction in both the fractional removal rate of glucose and the hepatic glucose production so that glycaemia remained unchanged. The % glucose converted to CO2 and the % CO2 derived from plasma glucose decreased respectively by 13.5% and 21.7%, while unlabelled CO2 production remained unchanged. This reduction in glucose utilization occurred despite a significant rise in insulin concentration indicating that high FFA levels reduce sensitivity to insulin. The tissue implicated in the inhibitory effect of FFA on overall glucose utilization cannot be determined from these experiments but it is suggested that muscle participated in these metabolic changes. These data provide further arguments supporting the view that plasma FFA participate in the regulation of glucose metabolism in man.
A Mathematical Model for the Glucose Induced Insulin Release in Man
Authors: Cerasi E. , Fick G. , Rudemo M.
Published: March 2008

Abstract. The dynamics of the insulin response to intravenously administered glucose were studied in man. It was shown that (a) insulin response to prolonged stimulation is biphasic; (b) if the glucose stimulus is repeated with short intervals, inhibition of the second response occurs; (c) if longer time‐intervals are used, enhancement of the response is noted at the second stimulation. These findings suggest that when the pancreatic islets are exposed to hyperglycaemia, three, kinetically distinct phenomena are initiated. Glucose induces almost instantaneous initiation of insulin release. Shortly thereafter, the pancreas enters a refractory phase. Thirdly, and at a later stage, a state of potentiation is built up in the islets. The effect of glucose on insulin synthesis is not considered here.–Against this background, and based on an earlier model, a mathematical model for the analysis of the glucose‐insulin interplay during glucose infusions was constructed. The model describes the eventual occurrence of glucosuria, changes in the concentration of glucose in its pool, and mimics the effects of regulatory hormones when hypoglycemia appears. Insulin secretion is assumed to be con trolled, in a multiplicative manner, by an immediate glucose function, a hypothetical potentiator that is slowly generated by glucose, and a negative factor with a shorter time‐course which corresponds to the refractory phase of the pancreas. A three compartment model is used in the simulation of the metabolism and distribution of insulin after its release. Finally, glucose utilization is described as a multiplicative function, related to the prevailing concentrations of glucose in blood and insulin in the extracellular space.–This model is able to simulate all the experimental situations described in this report, both in normal man and in the diabetic syndrome, in which insulin secretion shows varying degrees of impairment. The results of the simulation of individual experiments are given either as a set of theoretical parameter values, or described as the insulin response of the model to a standard, hypothetical glucose stimulus. The latter alternative is an attractive method for objectively evaluating the insulin response to a standard glucose load in clinical materials.
Rate of Synthesis of Albumin in Relation to Serum Levels of Essential Amino Acids in Patients with Bacterial Overgrowth in the Small Bowel
Authors: Yap S. H. , Hafkenscheid J. C. M. , van Tongeren J. H. M. , Trijbels J. M. F.
Published: March 2008

Summary. Bacterial overgrowth in the small bowel has been recognised in 11 patients with the aid of the breath‐test with [glyco‐l‐“C] cholic acid and by the determination of the amount of bacteria in the jejunal juice. In all but one patient hypoalbuminaemia, from 21.9 to 42.9 g/1, was observed. This low level of serum albumin can be due to an excessive intestinal protein‐loss or to a decreased rate of synthesis of albumin as the result of an insufficient delivery of amino acids to the liver. In 11 patients with bacterial overgrowth the rate of synthesis of albumin has been determined by the 14C‐carbonate method. Compared to a control group the rate of albumin synthesis and the serum level of valine, leucine, lysine and tryptophan were significantly decreased in the patients with bacterial overgrowth. A positive correlation was found between the rate of albumin synthesis and the serum levels of valine, isoleucine, leucine and tryptophan. When the serum levels of these 4 essential amino acids were low, the rate of albumin synthesis was depressed.
Interaction of Vasopressins and Linear N‐Terminal ACTH Fragments in the Induction of Natriuresis
Authors: Cort J. H. , Cort J. , Nováková J. , Škopková J.
Published: March 2008

Abstract. Because a) a mixture of alpha‐melanotropin (MSH) and corticotropin (l‐13)‐tridecapeptide (1–13 ACTH) has apparently been isolated from natriuretic fractions of posterior pituitary which also contained arginine‐vasopressin, and b) the natriuretic activity of the isolated fraction was greater than that of any of the above three peptides (synthetic) given separately, possible interaction was studied with model substances in the chloralosed cat preparation. It was found that with both alpha‐MSH and lysine‐vasopressin, extracted samples were more natriuretic than synthetic samples despite an equivalence of pressor activities. When combined with arginine‐vasopressin in one injectate, synthetic alpha‐MSH, 1–4 ACTH, 1–13 ACTH‐amide and 1–18 ACTH all showed potentiation of natriuretic activities with no effect on pressor activity. This effect was not shown by synthetic 4–10 ACTH and 5–18 ACTH, or by extracted alpha‐MSH. It was concluded that the 1–4 sequence Ser‐Tyr‐Ser‐Met, regardless of whether the N‐terminal is free or blocked, can potentiate the natriuretic action of vasopressin.
Dynamics of Insulin Release and Microtubular‐Microfilamentous System
Authors: Obberghen E. Van , Devis G. , Somers G. , Ravazzola M. , Malaisse‐Lagae F. , Malaisse W. J.
Published: March 2008

Abstract. Colchicine failed to inhibit and actually enhanced insulin release evoked by gliclazide at a low glucose concentration (0.3 mg/ml). The facilitating action of colchicine was invariably present, whatever the concentration of (2.10‐5 to 10‐3 M) and length of exposure to (25 to 120 min.) the mitotic spindle‐inhibitor. Colchicine, and similarly cyto‐chalasin B, also minimized the reduction in insulin output otherwise observed during the second of two successive stimulations with sulphonylurea. These data suggest that the short‐lived secretory response evoked by sulphonylurea corresponds to a modality of insulin release which does not require the oriented intracellular transport of secretory granules.
Dynamics of Insulin Release and Microtubular‐Microfilamentous System
Authors: Malaisse W. J. , Obberghen E. Van , Devis G. , Somers G. , Ravazzola M.
Published: March 2008

Abstract. A model is proposed to account for the phasic nature of insulin release. It is suggested that one modality of secretion results from the mobilization of secretory granules already located in the close vicinity of the microfilamentous cell web. This corresponds to a fraction of the initial secretory response to a high glucose concentration, the residual release of insulin provoked by glucose in the presence of diazoxide, and the total release of insulin evoked by sulphonylurea at a low glucose concentration. A second modality of release, which i3 characteristic of the late phase of glucose‐induced insulin secretion, is thought to correspond to the mobilization of secretory granules transported to the periphery of the β‐cell along oriented microtubular pathways. Whether only one or both modalities of release are initiated by a given insulino‐tropic stimulus may depend on the magnitude and duration of the changes induced by secretagogues in the insular handling of calcium.
The Effect of Cholestyramine on the Elimination of Cholesterol as Bile Acids in Patients with Hyperlipoproteinaemia Type II and IV
Authors: Einarsson Kurt , Hellstrom Kjell , Kallner Mora
Published: March 2008

Abstract. The turnover of 14C‐oholic acid and 3H‐chenodeoxycholic acid was studied in hyperlipaemic patients before and during treatment with cholestyramine. – In five female patients with hyperlipoproteinaemia type Ila the pool size and turnover of cholic acid as well as the total formation of bile acids were significantly lower than in female normolipae‐mic controls. During treatment with cholestyramine, cholic acid synthesis rose 4–18 fold and the turnover of chenodeoxy‐cholic 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 cholest‐ramine 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.
Increased Excretion of a Glucose‐Containing Tetrasaccharide in the Urine of a Patient with Glycogen Storage Disease Type II (Pompe's Disease)
Authors: Hallgren P. , Hansson G. , Henriksson K. G. , Hager A. , Lundblad A. , Svensson S.
Published: March 2008

Abstract. A glucose‐containing tetrasaccharide (13 mg/24 h) was isolated from the urine of a ten year old boy with the childhood form of glycogen storage disease type II (Pompe's disease). The structure, established by Bugar analysis, methylation analysis, optical rotation and enzymatic degradation was found to be α‐D‐Glc p (1→6)‐α‐D‐Glcp (1→4)‐α‐D‐Glc p (1→4)‐D‐Glc. The same compound was also isolated in small amounts (1 mg/24 h) from normal urine. Larger glucose‐containing oligosaccharides, not detected in normal urine were also present in the urine of the Pompe case.
The Effect of Acute Uraemia on Gluconeogenesis in Isolated Perfused Rat Livers
Authors: Fröhlich J. , Schölmerich J. , Hoppe‐Seyler G. , Maier K. P. , Talke H. , Schollmeyer P. , Gerok W.
Published: March 2008

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 iso‐leucine. In the presence of a mixture of amino acid3 (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.
Enzyme‐Induced Modifications of Beta Cell Function
Authors: Lambert A. E. , Henquin J.‐C. , Orci L. , Renold A. E.
Published: March 2008

Abstract. The effects upon immunoreaetive insulin (IRI) release of beta cell membrane modifications induced by pronase, a mixture of proteolytic enzymes extracted from Streptomyces griseus, have been studied in isolated islets of Langerbans. Pretreatment of the islets for 90 min with 4 μg/ml pronase did not modify their IRI content; it slightly increased the basal rate of IRI release and potentiated the secretory response to glucose, leucine and tolbutamide during incubation. In perifused islets, the rapid phase of IRI secretion in response to glucose was more markedly enhanced than the late phase. After preincubation with 4 μg/ml pronase, glucose‐induced IRI release was reversible and abolished in the absence of calcium. Pretreatment for 90 min with 500 μg/ml pronase decreased IRI content of the islets by approximately 25% and provoked a pronounced but transient rise of basal IRI release. This was considered to be a leakage of IRI from damaged beta cells since it persisted in a medium deprived of calcium. The rapid secretory phase in response to glucose was preserved in perifused islets whereas the late phase was markedly reduced. The secretory responses to leucine and tolbutamide were almost completely obliterated. When pretreatment with pronase was carried out in a calcium‐depleted medium, basal IRI release from islets preincubated with 500 μg/ml pronase was only slightly increased whereas IRI secretion induced by glucose was inhibited by 40 and 65%, respectively in islets pre treated with 4 and 500 μg/ml pronase. These results indicate that pronase‐induced modifications of the beta cell membrane influence IRI secretion in a way which depends on the concentration of the enzyme and the presence of extracellular calcium. They are considered to support the hypothesis that membrane systems are involved in IRI releasing mechanisms.
Canalicular Bile Production in Man*
Authors: Prandi D. , Erlinger S. , Glasinović J. ‐C. , Dumont M.
Published: March 2008

Abstract. Bile flow, erythritol clearance (measured after administration of 14C‐erythritol) and bile acid excretion were studied in 8 non‐icteric patients operated upon for gallstone disease without biliary obstruction in whom a T‐tube had been inserted. Bile flow increased from the 2nd (0. 27 ± SEM 0. 01 ml/min) to the 7th (0. 50 ± SEM 0. 05 ml/min) postoperative days and remained stable thereafter. Because the values obtained between the 7th and the 15th postoperative days (average: 0. 46 ± SEM 0. 02 ml/min) were not lower and were of the same order of magnitude as those previously reported in the literature for quantitative bile collections, it was assumed that bile collection had been complete. Bile‐to‐plasma concentration ratio of erythritol was 0. 77 ± SEM 0. 04. The regression line between erythritol clearance and bile flow had a slope of 0. 99 (indicating that increments in clearance were followed by equivalent increments of flow) and an intercept for a zero‐clearance of 0. 11, suggesting a ductular/ductal secretion of 0. 11 ml/min. The relationship between erythritol clearance and bile acid excretion suggested that canalicular bile was formed both of a bile acid‐dependent flow (11 μl of water being excreted per umol of bile acid secreted) and a bile acid‐independent flow of 0. 16 ml/min (or 35 % of the average bile flow). These findings indicate that erythritol clearance provides a valid estimate of canalicular bile flow in man and that the three bile fractions previously postulated in animals (canalicular bile acid‐dependent, canalicular bile acid‐independent and ductular/ductal) may also be present in man.
Insignificance of Gluconeogenesis in Human Blood Platelets
Authors: Schrijver J. , Koster J. F. , Hülsmann W. C.
Published: March 2008

Abstract. Human blood platelets contain no detectable activity of the enzymes fructose diphosphatase (EC 3. 1. 3. 11), phospho‐enolpyruvate carboxykinase (EC 4. 1. 1. 32) and pyruvate carboxylase (EC 6. 4. 1. 1.). Glucose‐6‐phosphatase (EC 3. 1. 3. 9) activity is very low.

Phosphofructokinase present in human blood platelets, catalyzes a reaction which can be stimulated by AMP in a platelet homogenate, due to the presence of endogenous ADP and myokinase. These enzymes are responsible for the formation of fructose‐6‐phosphate from fructose‐1, 6‐diphosphate.

Pyruvate kinase (EC 2. 7. 1. 40) in human blood platelets belongs to the M‐type, which is not inhibited by ATP, at least not under the conditions applied.

The results obtained indicate that gluconeogenesis in human blood platelets is not present in the way which has been established for liver and kidney.
Studies on Urea Cycle Enzymes in Rat Liver during Acute Uraemia
Authors: Hoppe‐Seyler G. , Maier K. P. , Schollmeyer P. , Frohlich J. , Talke H. , Gerok W.
Published: March 2008

Abstract. Activities of urea cycle enzymes were measured in the liver of starved rats 12 and 48 h after bilateral nephrectomy. Control experiments (sham‐operated, starved rats) revealed that the activities of only two enzymes of the cycle are altered in the uraemic state: argininosuccinic acid synthetase (EC 6. 3. 4. 5.), which is considered to be rate limiting for urea production and carbamyl phosphate synthetase (EC 2. 7. 2. 5.). Alterations in ornithine concentration of the liver, a possible cause of an increased urea production rate, could not be detected previously (21). Our present results do not support the concept that a decrease of the activity of ornithine‐6‐amino transferase (EC 2. 6. 1. 13), leading to an increase in the ornithine content of the liver is responsible for the accelerated urea production rate in the liver of acute uraemic rats.
Liver Inclusions in Erythropoietic Protoporphyria
Authors: Wolff K. , Wolff‐Schreiner E. , Gschnait F.
Published: March 2008

Abstract. Needle‐like inclusions have been found, by electron microscopy, in the livers of two unrelated patients with erythropoietic protoporphyria. Since they have not been noted in other hepatic conditions but do occur in the livers of protoporphyric mice it is suggested that they represent markers for proto‐porphyric liver disease.

Paracrystalline inclusions that have been previously described in Wilson's disease and porphyria cutanea tarda were also present in the hepatocytes of one of these patients.
Therapeutic Use of Transfer Factor*
Authors: Grob P. J. , Franke Ch. , Reymond J. ‐F. , Frei‐Wettstein M.
Published: March 2008

Abstract. Transfer Factor (TF) was produced by ultrafiltration of repeatedly frozen and thawed, pooled buffy coats of healthy blood donors. One unit of TF Zurich was defined as the cell extract originating from 1–2 × 109 leucocytes. In collaboration with physicians and immunologists, 409 units TF have been given to 45 patients. Besides local pain and occasional fever no side effects were observed. Immune conversions and beneficial clinical effects were seen in 11 and 10 patients, respectively, out of 12 patients with chronic candidiasis. Immune conversion was also observed in patients with multiple sclerosis, while the clinical effects cannot yet be judged. The series also included patients with subacute sclerosing panencephalitis, HBAg‐positive disorders, various immunodeficiency diseases, malignant melanoma and miscellaneous tumours. Immune conversion occurred only occasionally and the clinical effect was either nonexistent or not judgeable. In the discussion the results of other investigators using TF therapy are included.
Lipoprotein of the Density 1. 006–1. 020 in the Plasma of Patients with Type III Hyperlipoproteinaemia in the Postabsorptive State
Authors: Patsch J. R. , Sailer S. , Braunsteiner H.
Published: March 2008

Abstract. Using a rate zonal ultracentrifugal technique in 10 patients with type III hyperlipoproteinaemia, very low density lipoproteins (VLDL) (d < 1. 006, Sf > 20), an intermediate lipoprotein density class with a Sf range of 15–20 (Lp III), and low density lipoproteins (LDL) (Sf 6–8) could be isolated from the plasma. The Lp III was found as a symmetrical peak between VLDL and LDL; its plasma concentration was 248 mg/100 ml plasma (mean), 92–469 mg/100 ml plasma (range); the Lp III/LDL ratio was 0. 65 (mean), 0. 25–2. 3 (range); the chemical composition w/w was 35. 8 % total cholesterol, 19. 3 % triglycerides, 24. 3 X phospholipids, and 20. 4 % protein (mean). In agarose gel electrophoresis, the Lp III migrated faster than LDL, but slower than VLDL. By means of a double immunodiffusion technique and immunoelectrophoresis, apo‐Lp B and apo‐Lp C were detectable. In an angle head rotor at 1. 4 times 108 g. min. Lp III can be separated from VLDL at a solvent density of 1. 006, and from LDL at a density of 1. 025. In the postabsorptive state in one patient with type I hyperlipoproteinaemia, five with type II and 20 with type IV, and in 50 healthy persons of both sexes, this Lp III peak was not found. The finding of a high concentration of Lp III and a rather low concentration of LDL in the plasma of patients with type III hyperlipoproteinaemia can be regarded as further evidence for an impaired catabolism of VLDL to LDL at Lp III (“intermediate” lipoprotein).
Changes in Insulin Immunoreactivity across the Coronary Circulation in Man during Infusions of Glucose and a Fat Emulsion
Authors: Carlson L. A. , Kaijser L. , Rossner S. , Wahlqvist M. W. , Wide L.
Published: March 2008

Abstract. The extraction of immunoreactive insulin by the human heart has been examined using the technique of coronary sinus catheterisation. The subjects were 12 male volunteers. During the study infusions of a fat emulsion and glucose were given in an effort to create a “steady fed state”. The higher arterial insulin immunoreactivities which were observed during the infusions were associated with greater arterial coronary sinus differences in insulin immunoreactivity. The possibility of insulin degradation by the heart is discussed. During prolonged exercise the process of insulin removal by the heart appeared more active.
Effects of Insulin and of NSILA‐S on the Perfused Rat Heart: Glucose Uptake, Lactate Production and Efflux of 3–0‐Methyl Glucose
Authors: Meuli C. , Froesch E. R.
Published: March 2008

Abstract. 200 μU of insulin per ml perfusion medium stimulated glucose uptake and lactate production by the isolated perfused rat heart about 5 and 10 fold, respectively. Nonsuppressible insulin‐like activity (NSILA‐S) extracted from human serum had almost the same maximal effects. Mol per mol the two substances were equally effective and, correspondingly, the dose‐response curves were very similar. NSILA‐S accelerated the efflux of 3–0‐methyl glucose from the heart cells to the same extent as insulin. It can be concluded that NSILA‐S acts on heart muscle in a very similar way to that of insulin.
Hepatic Balances of Glucose and Insulin in Response to Physiological Increments of Endogenous Insulin during Glucose Infusions in Dogs.
Authors: Camu F.
Published: March 2008

Abstract. Hepatic glucose uptake was measured in dogs in relation to physiological increments of plasma insulin levels under steady state conditions. Endogenous insulin secretion was stimulated by the infusion of small glucose loads, achieving normoglycaemia or mild hyperglycaemia. The measurement of hepatic arterial and portal venous blood flows allowed calculation of the relationships between net hepatic balances of insulin and glucose, the magnitude of insulin extraction by the liver and the hepatic sensitivity to physiological levels of insulin. During normoglycaemia, small glucose loads (2 and 4. 5 mg/min. kg) reduced hepatic glucose output without a concomitant increase of the estimated total glucose utilization. No changes in arterial or hepatic venous plasma insulin levels occurred. Portal venous plasma insulin alone rose under the influence of the glucose stimulus. In the presence of hyper‐glycaemia, the liver further reduced its glucose output. Infusions of 11. 3 mg/min. kg glucose resulted in reversal of hepatic glucose output to a net uptake of glucose. However, due to the large amounts of insulin emerging from the liver, peripheral tissue glucose utilization was significantly increased. A strong inverse correlation existed between arterial glucose concentration and hepatic glucose output as well as between portal venous plasma insulin level and hepatic glucose output. The net hepatic balance of insulin was promptly raised in response to the glucose perfusions, even when normoglycaemia was maintained. A highly significant, inverse correlation was demonstrated between net hepatic balance of insulin (i. e. net uptake of insulin by the liver) and hepatic glucose output. Hepatic insulin extraction ratio and hepatic plasma insulin clearance increased during glucose administration but no evident relationship to portal venous plasma insulin levels was found. These data suggest that insulin rather than glucose is the primary agent responsible for the reversal of the hepatic gradient of glucose in vivo.
Double Isotope Measurement of Peritoneal Clearance of Iodide and Albumin Loss during Peritoneal Dialysis in Man
Authors: Mariani G. , Bianchi R. , Pilo A. , Palla R. , Toni M. G. , Cazzuola F.
Published: March 2008

Summary. 131I‐labelled Human Serum Albumin and 125I‐sodium iodide were used to measure protein loss from the peritoneum and peritoneal clearance of iodide in a group of 8 uraemic patients, each one being studied after a different number of dialyses.

Both albumin loss and iodide clearance reached a maximum at about the 10th dialytic treatment and then tended towards the initial levels.

Protein loss as determined isotopically was markedly lower than indicated by direct radioimmunoassay measurements performed in three cases. Fitting experimental points by a model which assumes direct passage of protein from plasma to peritoneal cavity suggests the presence of a “delay” pool between plasma and the peritoneal cavity itself (extravascular sites adjacent to peritoneum?).

The shorter retention time of the dialysis solution in the abdomen (4–8 minutes) seemed to us to cause lower protein losses than reported by authors using longer retention times.
Effects of Oral Contraceptive Therapy on the Orcadian Patterns of Cortisol and Thyrotropin (TSH)
Authors: Cauter E. Van , Golstein J. , Vanhaelst L. , Leclercq R.
Published: March 2008

Abstract. The daily variation of serum Cortisol and thyrotropin (TSH) has been simultaneously recorded every 30‐min. in 4 women taking the same oral contraceptive containing oestrogens and progestogens and in 4 control women. The circadian rhythm of Cortisol persisted under contraceptive therapy with about a 2. 5 fold elevat ion of the mean level and amplitude of the basal rhythm. Theoretical equilibrium calculations of the circadian variations of the free, transcortin‐bound and albumin‐bound Cortisol fractions showed that these elevations are explained qualitatively and quantitatively by an oestrogen‐induced increase of the same order of the transcortin cortisol‐binding sites. As a consequence of the already high saturation of transcortin in normal conditions, the magnitude of the variation of free Cortisol level resulting from a burst in Cortisol secretion varies with the time of day. The role of albumin as a buffer is thereby emphasized. The early morning maximum, characterizing the normal TSH daily pattern, appeared to be considerably enhanced in women under contraceptive therapy. If the circadian variations of TSH are driven by thyrotropin releasing hormone (TRH), these higher morning peaks probably reflect a higher burst of TRH secretion rather than an increased responsiveness of the pituitary to TRH secretion induced by contraceptive therapy. Finally these results do not support the hypothesis of a regulation of TSH circadian variations by an inhibiotry action of Cortisol. Contraceptive therapy does not appear to play a role at the level of the central clock or on the resetting mechanism.
Glucuronidation in Cultures of Human Skin Epithelial Cells
Authors: Rugstad H. E. , Dybing E.
Published: March 2008

Abstract. Glucuronidation of p‐aminophenol, p‐nitrophenol and bilirubin has been investigated in cultures of human skin epithelial cells (HE cells) and human skin fibroblasts (FB) and in homogenates from the same cells. HE cells in culture glucoronidated p‐aminophenol and p‐nitrophenol at rates of about 5 and 10 nmol/mg cell protein per h respectively. Bilirubin was not conjugated by HE cells. In homogenates from HE cells supplemented with UDP glucuronic acid (UDPGA) both p‐aminophenol and p‐nitrophenol were glucuronidated at about the same rate as by living cells in culture. Assuming that the transferase activity is the same in the whole cells compared to the homogenates, transferase activity and not UDPGA production may be the limiting factor in glucuronidation of p‐aminophenol and p‐nitrophenol in these cells. The glucuronidation rate of HE cells was not increased by benzpyrene or benzanthrazene. FB did not glu‐curonidate p‐aminophenol, p‐nitrophenol or bilirubin.
Excretion of Trypsin‐Like Activity, Electrolytes and Protein in Mixed and Parotid Saliva of Patients with Cystic Fibrosis of the Pancreas†
Authors: Schoni M. , Kaiser D. , Drack E. , Axmacher U.
Published: March 2008

Abstract. The esterolytic activity of mixed and parotid saliva in cystic fibrosis (CF) patients and normal subjects was determined using BAEE (α‐Benzoyl‐1‐arginine‐ethylester) as the substrate. Using soybean‐trypsin‐inhibitor the trypsin‐like activity (TLA) was measured and plotted as a function of parotid flow rate. In addition calcium, protein and pH were determined. Trypsin‐like activity in mixed and parotid saliva showed large individual variations in CF and normal children. In parotid saliva we could not find any significant difference, whereas a reduction of TLA in mixed saliva of CF patients was observed. The fact that our normal values fell within the range of heterozygotes reported by Rao et al. (19), makes their hypothesis of a close relationship between reduced TLA and the genetic defect very doubtful. Protein, calcium and pH increased with augmented salivation and no difference between CF patients and normal age matched children could be found except for the pH at a flow rate above 0.75 ml/min per m2 body surface where significantly lower pH values resulted. The relevance of reduced TLA to the pathogenesis of cystic fibrosis is discussed.