bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired responsiveness to the effect of glucagon on plasma adenosine 3‘:5’‐cyclic monophosphate in normal man
Authors: HENDY G. N. , TOMLINSON S. , O'RIORDAN J. L. H.
Published: March 2008

Abstract. Small doses (10–150 μg; 3–45 nmol) of glucagon caused a dose‐dependent increase in plasma adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) concentration when injected into man. Infusion of glucagon (75 ng min‐1 kg‐1) for 2 h into normal subjects resulted in an initial increase in plasma cyclic AMP concentration, then a decline despite continuation of the hormone infusion and maintenance of high concentrations of circulating immunoreactive glucagon. When an injection of glucagon was given at the termination of such an infusion, the subsequent increase in plasma cyclic AMP concentration was markedly reduced when compared to that observed after a control injection which had not been preceded by a glucagon infusion. When the glucagon was injected at the end of an infusion of 1000 MRC units of bovine parathyroid hormone (BPTH) over 2 h, the plasma cyclic AMP response was normal. Conversely, after infusion of glucagon the response to injected BPTH was normal. This impairment of response was therefore specific to the hormone that had been administered and was not due to altered metabolism of circulating cyclic AMP. This phenomenon may be important in the regulation of the hormonal response by the target tissue.
Plasma secretin concentration in man: effect of intraduodenal glucose, fat, amino acids, ethanol, HCI, or ingestion of a meal
Authors: FAHRENKRUG J. , MUCKADELL O. B. SCHAFFALITZKY DE
Published: March 2008

Abstract. The effect of infusing isotonic saline, isotonic and hypertonic glucose, fat emulsion, amino acids, ethanol, and hydrochloric acid into the duodenum on the plasma concentration of immunoreactive secretin was studied in seven normal subjects. Only hydrochloric acid showed any effect. After acidification of the duodenum with hydrochloric acid a significant rise in plasma secretin concentration was observed from 1.3 ± 0.4 pmol X 1‐1 (mean ± SEM) to a peak value of 13.0 ± 1.2 pmol X 1‐1 after 5 min. The concentration returned to the basal level within 15 min. In eight other normal subjects the plasma secretin concentration was measured after the ingestion of a protein‐rich meal. No significant changes were observed during the 2 h postprandial period.
Possible sites of interaction of acute renal failure with amino acid utilization for gluconeogenesis in isolated perfused rat liver
Authors: FRÖHLICH J. , HOPPE‐SEYLER G. , SCHOLLMEYER P. , MAIER K. P. , GEROK W.
Published: March 2008

Abstract. Experiments were performed to elucidate the mechanisms involved in the enhanced conversion of amino acids to glucose in acute uraemic rats. Increased gluconeogenesis from a mixture of serine, threonine, lysine, glutamate, ornithine and citrulline was confirmed using a non‐recirculating perfusion system. Stimulation was concentration dependent, being most pronounced at physiological amino acid concentrations. Stimulation of glucose and urea formation could be mimicked by using serine alone whereas with lactate and pyruvate inhibition of gluconeogenesis was observed. Serine dehydratase activity was significantly elevated following nephrectomy. Further, the uptake of the non‐metabolizable amino acid α‐aminoisobutyrate was considerably increased. It is concluded that serine may play a special role as substrate for the additional glucose formation in acute uraemic rats, probably mediated by an activation of serine dehydratase. Acceleration of amino acid transport seems to represent an additional component of stimulation of amino acid utilization in acute uraemia.
Effect of physical exercise on erythrocyte lipids, biliary cholesterol and bile lithogenicity in rats
Authors: SIMKO VLADO , KELLEY ROBERT
Published: March 2008

Abstract. Male Wistar rats were exercised (E) by daily 1 h swimming for 24 days. Sedentary controls (S) were caged individually. Bile analysis at the end of the experiment (24 h after the last exercise) showed a decrease in bile cholesterol (CH) (P<0.02) and phospholipids (PL) (P<0.01) in the exercising animals, but no significant change in the bile acids (BA). These changes in the exercising rats resulted in a decreased CH saturation of bile: in an improvement in the (BA + PL)/CH ratio (P= 0.05) and a trend to a decrease in the per cent saturation of bile CH. Exercise did not affect the bile flow or bile acid flux rate. Exercise decreased erythrocyte phospholipids (P<0.01). The effect of exercise on bile was associated with a trend to lower CH in the erythrocytes and in the adipose tissue and thus most likely does not represent a shift of cholesterol from the liver to the peripheral tissues. Physical exercise may be a preventing factor in cholesterol gallstone formation.
Determination of splenic blood flow by inhalation of radioactive rare gases
Authors: HUCHZERMEYER H. , SCHMITZ‐FEUERHAKE I. , REBLIN T.
Published: March 2008

Abstract. We have evaluated the 133Xenon inhalation method for the determination of splenic blood flow. In twenty‐two healthy persons the blood flow was on average 109 ± 4 ml/100 g X min, which is equivalent to a total blood flow of about 170 ml/min. In patients with chronic fatty liver hepatitis specific blood flow was reduced (81 ± 10 ml/100 g X min) as it was in patients with cirrhotic liver without splenomegaly (75 ± 2 ml/100 g X min). With increasing weight of the spleen, the total blood flow rises, although specific blood flow is low. Our results obtained by the 133Xenon inhalation method are similar to results obtained by others using intraarterial injection of tracer gas. The advantages of the inhalation method as a non‐traumatic method are: (1) the stress for the patient is very small; (2) blood flow measurements can be repeated within short periods of time.

We consider for the present the 133Xenon inhalation method to be the method of choice for the determination of the splenic blood flow.
The influence of hydrazine, phenelzine and nialamide on gluconeogenesis and cell respiration in the perfused guinea‐pig liver
Authors: HAECKEL R. , OELLERICH M.
Published: March 2008

Abstract. Hydrazine (2 mmol/l) and phenelzine (0.5 mmol/l), which are known to produce hypoglycaemia, inhibit glucose formation from lactate in the perfused guinea‐pig liver. The hydrazone formed from pyruvate and phenelzine exerted the same effect at concentrations of only 0.05 mmol/l. It is suggested that the hydrazones are the substances which are effective.

All these compounds inhibited pyruvate consumption and decreased CO2 production by the perfused liver which, together with the pattern of hepatic metabolite concentrations, indicate that they diminish pyruvate metabolism. None of them influenced the activities in vitro of pyruvate carboxylase, phosphoenolpyruvate carboxykinase and pyruvate dehydrogenase. The hydrazone compound caused an increase of the ATP/ADP ratio at lower concentrations and an opposite effect above 0.5 mmol/l.

Nialamide, another hydrazine derivative, also reduced hepatic gluconeogenesis but led to a marked decrease in the hepatic ATP/ADP ratio and liver cell respiration accompanied by a rise in the 3‐hydroxybutyrate/acetoacetate ratio.
Hereditary deficiency of phosphoglycerate kinase: a new variant in erythrocytes and leucocytes, not associated with haemolytic anaemia
Authors: KRIETSCH WOLFGANG K. G. , KRIETSCH HELGARD , KAISER WOLFRAM , DUNNWALD MANFRED , KUNTZ GÜNTER W. K. , DUHM† JOCHEN , BÜCHER THEODOR
Published: March 2008

Abstract. An X‐chromosome linked phosphoglycerate kinase deficiency in erythrocytes and leucocytes was discovered in a large German kindred. Seven males of two generations were found to have only 21% of the normal enzyme activity in their erythrocytes, and twelve females of three generations showed various degrees of this defect. The differences in the expression of the deficiency in heterozygote females are explained by the Lyon hypothesis.

The deficiency is caused by a variant enzyme, named phosphoglycerate kinase Munchen. Although it differs from the normal enzyme electrophoretically, the two enzymes resemble one another closely in many respects. They have essentially the same Km for the substrates of the backward reaction, identical pH optima and similar rates of thermal inactivation. In contrast to the nine previously described phosphoglycerate kinase deficiencies, all of which are associated with haemolytic anaemia, the carriers of phosphoglycerate kinase München show no overt clinical symptoms. The erythrocyte concentrations of adenine nucleotides and 2,3‐diphosphoglycerate are normal.
Isoenzyme pattern of alkaline phosphatase in the serum of children with leukaemia after long‐term chemotherapy
Authors: SCHWENK H. U. , VÖLKER H. H. , OHLEN J.
Published: March 2008

Abstract. Chemotherapy was discontinued in thirteen children with acute lymphoblastic leukaemia after 2–3 years without relapse. In the following months, a continuous increase was observed in the serum alkaline phosphatase. A maximum was reached at different times but all patients had normal values again after 19 months. The rise in the total activity is due to an isolated increase of the bone isoenzyme. Increased enzyme activity in this post‐therapy phase of the disease does not signify liver damage from the preceding chemotherapy, but rather is due to an increased osteoblast activity associated with a temporary increase in growth rate.
Protein synthesis in human skeletal muscle tissue: influence of insulin and amino acids
Authors: LUNDHOLM KENT , SCHERSTÉN TORE
Published: March 2008

Abstract. The effects of a mild stimulation of endogenous insulin secretion on the rate of incorporation in vitro of amino acids into human skeletal muscle protein were compared with the effects on this rate of adding insulin and amino acids in vitro. An intravenous infusion of 0.83 mmol glucose per kg body weight increased both plasma glucose and insulin levels significantly. The rate of incorporation of leucine into protein in isolated muscle fibres was significantly higher if the subjects had received the glucose infusion. Both insulin and a high concentration of amino acids in the incubation medium stimulated this rate. Amino acids stimulated the rate more than insulin and insulin did not further stimulate the amino acid‐stimulated rate. On the other hand, the stimulation of the rate of incorporation by amino acids was the same whether the subjects had received saline and were thus in a basal state or whether they had been infused with glucose (which itself stimulated the rate). The rate of incorporation of leucine was correlated with the tissue concentration of RNA but the correlation was weaker when the rate was stimulated by amino acids than under other experimental conditions. Leucine stimulated the rate of incorporation of phenylalanine but phenylalanine did not stimulate the rate of incorporation of leucine.

It is concluded that the rate of incorporation rate of amino acids into protein in isolated human skeletal muscle fibres is subjected to hormonal and amino acid control.
The effect of gastrin on basal and aminoacid‐stimulated insulin and glucagon secretion in man
Authors: REHFELD JENS F. , HOLST JENS J. , KÜHL CLAUS
Published: March 2008

Abstract. The effect of gastrin on basal and aminoacid‐stimulated glucagon and insulin secretion was studied in eleven normal young subjects. The concentrations of glucagon, insulin and gastrin in plasma or serum were measured radioimmunochemically. The results of amino‐acid‐stimulation were compared to those obtained during a protein‐rich meal.

Intravenous injection of synthetic human gastrin‐17 in doses from 15.6 ng to 1 μg/kg increased the concentration of glucagon and insulin in peripheral venous blood to a maximum within 5 min. In spite of the enhanced concentrations of insulin induced by gastrin, corresponding concentrations of glucose were either unchanged or increased. Infusion of a mixture of fifteen aminoacids increased the concentrations of glucose, glucagon and insulin. While the increases in glucose and insulin concentrations were similar to those obtained after a protein‐rich meal, the glucagon response was much larger after the infusion. Injection of gastrin‐17 after 30 min of infusion of aminoacids did not potentiate either the glucagon or the insulin response.

The results indicate that gastrin, besides stimulating insulin secretion, can also stimulate glucagon secretion in a dose‐dependent manner. The concentrations of gastrin necessary to stimulate glucagon secretion significantly correspond to the concentrations found in diseases with endogenous hypergastrinaemia (achlorhydria and Zollinger‐Ellison syndrome). While gastrin potentiates the glucose‐induced insulin secretion, it does not potentiate neither the aminoacid‐induced insulin nor glucagon secretion.
Increased plasma noradrenaline and serum gastrin in patients with duodenal ulcer
Authors: BRANDSBORG O. , BRANDSBORG M. , LØVGREEN N. A. , CHRISTENSEN N. J.
Published: March 2008

Abstract. Serum gastrin, serum insulin, plasma noradrenaline, plasma adrenaline, pulse rate and blood pressure were measured repeatedly during 24 h in six patients with duodenal ulcer and in six control subjects.

Mean serum gastrin concentration was 3–4 times higher in duodenal ulcer patients than in controls during both the day and at night. Serum insulin was the same in both groups of subjects.

Overnight fasting and mean supine plasma noradrenaline as well as mean supine pulse rate were significantly higher in duodenal ulcer patients than in controls. Plasma adrenaline and arterial blood pressure were the same in patients and controls.

These results suggest that sympathetic nervous activity is increased in patients with duodenal ulcer. The increased sympathetic nervous activity may mean that duodenal ulcer patients are subject to more stress than normal subjects or may be compensatory to increased vagal nervous activity presumed by some authors to be present in such patients.
The influence of meal frequency on diurnal lipid, glucose and cortisol levels in normal subjects
Authors: TERPSTRA J. , HESSEL L. W. , SEEPERS J. , GENT C. M. VAN
Published: March 2008

Abstract. Diurnal levels of serum triglyceride, cholesterol, free fatty acids, glucose, and cortisol were measured in four normal persons on a fixed solid 65% carbohydrate diet under steady state conditions in a metabolic unit.

Triglyceride levels in all subjects showed similar patterns, which unexpectedly did not bear a simple relation to meal frequency or distribution. With three equivalent meals per day at 09.00, 12.00 and 17.00 hours, ‘fasting’ triglyceride levels increased by about 0.3 g/1 from a minimum value between 03.00 and 05.00 hours in the morning till before breakfast. After breakfast there was a continued rise till about 15.00 hours and then an overall fall in spite of the meal at 17.00 hours. Isocaloric change to eight equivalent meals, consumed between 09.00 and 23.00 hours, resulted in a similar although slightly more even triglyceride, pattern. On eight equivalent meals, spaced evenly over the entire 24 h period, a different pattern was found with lower triglyceride values at daytime than at night.

Increase in meal frequency did not result in a lowering of mean diurnal triglyceride levels. The cholesterol pattern followed the triglyceride pattern most clearly in subjects with high triglyceride levels. Glucose showed the expected postprandial increments.

Cortisol rhythm did not change on varying meal frequency.
Increase of the lipoprotein‐lipase activity in human skeletal muscle during clof ibrate administration
Authors: LITHELL HANS , BOBERG JONAS , HELLSING KRISTOFFER , LUNDQVIST GUDMAR , VESSBY BENGT
Published: March 2008

Abstract. Lipoprotein‐lipase activity was determined in tissue from the skeletal muscle of the leg and the subcutaneous adipose tissue of the abdomen in fourteen patients before and after 1 month of clofibrate administration. The concentrations of serum triglycerides decreased by, on the average, 37% in a group of thirteen patients which mainly consisted of subjects with type‐IV hyperlipoproteinaemia. Clofibrate administration was associated with an average increase of the skeletal muscle‐tissue lipoprotein‐lipase activity of 50% (P< 0.005). There was a significant correlation between the percentage changes in skeletal muscle‐tissue lipoprotein‐lipase activity and those of the triglycerides concentrations and the K2‐values in an intravenous fat tolerance test during clofibrate treatment. Adipose‐tissue lipoprotein‐lipase activity did not change significantly. One patient with type‐I hyperlipoproteinaemia had very low values of skeletal muscle‐tissue lipoprotein‐lipase activity and moderately low adipose‐tissue lipoprotein‐lipase activity. In this patient, neither the tissue lipoprotein‐lipase activity nor the triglycerides concentration changed during clofibrate therapy. Fasting serum insulin concentrations decreased significantly during clofibrate administration and the percentage decrease was significantly correlated to the percentage increase of skeletal‐muscle lipoprotein‐lipase activity. It is suggested that the lowering of insulin levels is a possible mechanism through which glucagon activity is enhanced and this may increase skeletal muscle‐tissue lipoprotein‐lipase activity.
On the relationship between ketonuria and natriuresis during fasting and upon refeeding in obese patients*
Authors: KOLANOWSKI J. , BODSON A. , DESMECHT P. , BEMELMANS S. , STEIN F. , CRABBE J.
Published: March 2008

Abstract. This study was conducted to assess whether the natriuresis occurring early in a fast, and the renal sodium retention setting in upon carbohydrate or protein refeeding, can be entirely accounted for on the basis of concomitant changes in renal ketone body and ammonia excretion. To this end, the renal excretion of sodium, 3‐hydroxybutyrate (3‐OHB) and ammonium was determined in non‐diabetic obese subjects submitted to total fast according to the following protocols: (1) 6 day fast: considered as control group (n= 11); (2) 8 day fast save for an isolated 100 g oral glucose load on day 4 (n= 12); (3) 8 day fast with, on day 4, the same glucose load followed by a 6 h infusion of glucagon, 1 mg in 500 ml 5% glucose (n= 7); (4) 5 day total fast followed by 3 days of protein refeeding (53 g protein daily; n = 8). All subjects were refed with a mixed 4.2 MJ diet at the end of the studies.

During the initial 3 days of fast, natriuresis was proportional to urinary 3‐OHB excretion while urinary ammonium had not yet increased. Glucose administration on day 4 led abruptly to sodium retention, lasting for 2 days, and correlated with the decline in 3‐OHB excretion. The fall in ketonuria resulted from a drop both of plasma 3‐OHB level and of the renal clearance of 3‐OHB. Glucagon prevented this glucose‐induced reduction in urinary Na as well as in 3‐OHB excretion and clearance, through a direct action on the kidney.

These results are in keeping with an important role of ketonuria in changes in sodium excretion during fasting and after carbohydrate refeeding. On the other hand, protein refeeding was followed by a decrease in sodium excretion despite persisting elevated ketonuria. Since, in these conditions, blood glucose levels rose, glucose availability to the kidney tissue may represent an alternative factor influencing renal sodium handling in fasting subjects.
The galactose elimination capacity as a quantitative measure of liver function in acute carbon tetrachloride intoxication of rats
Authors: VILSTRUP HENDRIK
Published: March 2008

Abstract. In rats given rising single doses of carbon tetrachloride (CCl4) intragastrically the relation between dose and mortality, between time after injection and the quantitative liver function measured by the galactose elimination capacity (GEC), and between the dose and the GEC, was examined. The change in hepatic contents of galactose metabolites after CC14 was measured. There was a linear relation between the dose and mortality. No rat died later than 36 h after injection. Following injection of a dose lethal to 15% of rats the GEC fell to 40% of control after 36 h and was normalized after 72 h. There was a dose dependent decrease in the GEC with rising doses given 36 h earlier up to a dose lethal to 15%. Galactose metabolites other than UDP‐galactose, which was decreased, were not affected by CCl4, suggesting a general enzyme depression. The results are compatible with the concept of proportionality between the GEC and ‘the functioning liver mass’ and indicate that the GEC presents prognostically valuable information during acute hepatic insufficiency.
Initial cholesterol esterif ication rate in hyperlipoproteinaemia: effects of triglyceride‐rich Iipoproteins
Authors: PATSCH W. , LISCH H.‐J. , SAILER S. , BRAUNSTEINER H.
Published: March 2008

Abstract. The initial cholesterol esterification rate (LCAT activity) was determined in ninety‐four hyper‐lipidaemic subjects. LCAT activity was elevated in hypertriglyceridaemia, whereas patients with hyper‐cholesterolaemia had normal activities. In hypertri‐glyceridaemic subjects LCAT activity correlated with the concentrations of d 1.006 lipoproteins, plasma triglycerides, cholesterol and cholesterol esters and phospholipid levels. Addition of d < 1.006 lipoproteinto normal plasma resulted in a dose dependent stimulation of enzyme activity with a sigmoidal response curve. When the d < 1.006 lipoproteins were removed from hypertriglyceridaemic plasma by ultracentrifugation, the enzyme activity in the residual d > 1.006 fraction dropped, but still was higher than in normal plasma and correlated with the amount of d 1.006 lipoproteins originally present. Thus, high LCAT activity in hypertriglyceridaemia cannot be explained solely by the presence of an increased d < 1.006 lipoprotein concentration. An increase of enzyme concentration or changes in concentration or composition of other lipoproteins (high density lipoproteins) may contribute to the high LCAT activity in hypertriglyceridaemia.
Plasma renin substrate sensitivity to oestrogens and oestrogen metabolism in cirrhosis
Authors: DEGOS F. , BENHAMOU J. P. , MENARD J. , SALMON J. , RAYNAUD J. P.
Published: March 2008

Abstract. Oestrogen stimulation of plasma renin substrate (PRS) was studied in men with alcoholic cirrhosis. PRS values, before and I,2,4 and 6 days after a single oral administration of 100 pg of an oestrogen derivative, 11β‐methoxy‐17–ethynyl‐1,3,5(10)‐estratriene‐3,17β‐diol (Moxestrol), were measured by radioimmunoassay of generated angiotensin I in five men with normal liver function and five men with alcoholic cirrhosis. Basal PRS was 0.93 ± 0.22 nmol/ml (mean ± 1 SD) in the normal men and significantly lower (P<0.01) in the men with cirrhosis (0.33±0.14 nmol/ml). Two days after administration of Moxestrol, PRS rose significantly but transiently (P<0.05) to 1.41 ±0.42 nmol/ml in the normal men and to 0.47 ± 0.15 in the cirrhotic men, the relative increase (˜50%) being similar in both groups. A study of the plasma kinetics and urinary excretion of Moxestrol was also performed to evaluate its metabolic clearance rate and absorption. Since the intestinal absorption of [14C] Moxestrol was not depressed in cirrhotic men, the low PRS values recorded are probably the consequence of hepatocyte dysfunction.
Biochemical, genetic and ultrastructural study of a family with the sea‐blue histiocyte syndrome/chronic non‐neuronopathic Niemann‐ Pick disease
Authors: FRIED K. , BEER S. , KRESPIN H. I. , LEIBA H. , DJALDETTI M. , ZITMAN D. , KLIBANSKY C.
Published: March 2008

Abstract. Deficient leucocyte sphingomyelinase activity has been demonstrated in a patient with the sea‐blue histiocyte syndrome. Family studies revealed that two other cases previously diagnosed on clinical and histo‐chemical criteria also had a pronounced diminution of sphingomyelinase activity. Both parents of the affected individuals were carriers of the disease as indicated by sphingomyelinase activity intermediate between normal and diseased subjects. Additional heterozygous carriers were found among the siblings and other relatives of the patients. This family study supports further the hypothesis that the sea‐blue histiocyte syndrome and chronic Niemann‐Pick (Type B) disease are the same.
Alpha‐adrenergic antilipolytic effect of adrenaline in human fat cells of the thigh: comparison with adrenaline responsiveness of different fat deposits
Authors: LAFONTAN M. , DANG‐TRAN L. , BERLAN M.
Published: March 2008

Abstract. The present results show that isolated fat cells from the subcutaneous adipose tissue of the lateral part of the thigh exhibit resistance to adrenaline. However, inability of adrenaline to induce lipolysis is not linked to a β‐receptor defect since a β‐adrenoceptor‐stimulating agent (isoproterenol) exerts a clear lipid mobilizing effect. The blocking of α‐adrenoceptors by phentolamine (an α‐adrenoblocking drug) unmasks the strong lipolytic effect of adrenaline. Moreover, our investigation demonstrates the occurrence of an inhibiting effect of adrenaline on theophylline‐induced lipolysis. This inhibitory effect is suppressed by phentolamine and strengthened by propranolol (β‐adrenoblocking drug). Thus it seems that one of the important facts able to explain adrenaline resistance of the adipocytes from the subcutaneous adipose tissue of the thigh could be increased alpha‐adrenergic responsiveness initiated by mixed agonists such as adrenaline or noradrenaline.

Moreover, our data demonstrate that the differences in the lipolytic responses to adrenaline between isolated fat cells taken from different sites could be linked to a variable α‐adrenergic‐inhibiting effect rather than a modified β‐adrenergic effect. In conclusion, the balance between the two receptor site activities could be different according to the anatomical localization of the fat deposits, thus explaining the differences in adrenaline responsiveness reported in this paper.
Sulphur containing amino acids in chronic renal failure with particular reference to homocystine and cysteine‐homocysteine mixed disulphide
Authors: WILCKEN D. E. L. , GUPTA VATSALA J.
Published: March 2008

Abstract. We measured plasma sulphur amino acids in twenty‐two patients with chronic renal failure and compared the findings with those obtained in twenty‐two normal subjects. In fasting blood (08.00 hours) cysteine‐homocysteine mixed disulphide was significantly increased in the renal patients, mean values (± SD) being 8.2 ± 3.4 and 3.1 ± 1.0 μmol/l respectively (P < 0.001). The increase was positively correlated with reduced renal function, as assessed by serum creatinine (r= 0.62; P < 0.01). Homocystine was detected in nineteen patients, the mean concentration (± SD) being 1.7 ± 0.6 μmol/l; it was not found in any normal subject. Methionine levels were not different but there were significant increases in cystine (P < 0.001) and taurine (P < 0.05) in the patients. Similar values for these amino acids were found in a second blood sample drawn at 16.00 hours. Changes in the other neutral and acidic amino acids measured were in agreement with those reported in chronic azotaemia. We concluded that plasma levels of all the principal sulphur amino acids except methionine are elevated in chronic renal failure emphasizing the importance of the kidney in sulphur excretion. Prolonged accumulation of homocysteine and cysteine‐homocysteine mixed disulphide may be relevant to the development of accelerated vascular disease in patients with chronic renal failure by producing endothelial damage.
Acute dietary effects on plasma lipids, lipoproteins and lipolytic enzymes in healthy normal males
Authors: SCHLIERF G. , JESSEL S. , OHM J. , HEUCK C. C. , KLOSE G. , OSTER P. , SCHELLENBERG B. , WEIZEL A.
Published: March 2008

Abstract. Diurnal plasma lipids and lipoproteins were studied in twelve healthy young males on corn oil and palm oil diets, respectively. The major triglyceride fatty acids were determined serially in the lipoprotein classes during the day. Lecithin‐cholesterol acyl transferase, lipoprotein lipase and hepatic triglyceride lipase were also measured.

Diurnal changes of triglycerides and cholesterol were confined to lipoproteins of d< 1·006 kg/l. There was a diurnal rise of lecithin‐cholesterol acyl transferase activity with corn oil but not with palm oil. Fasting and postprandial postheparin lipoprotein lipase and hepatic triglyceride lipase were similar but there was a significant correlation of postprandial hepatic lipase with postprandial plasma triglycerides on palm oil.

Marked diurnal changes of triglyceride fatty acids were observed not only in ‘very low density lipoprotein’ but also in high‐density lipoprotein amounting to approximately one third of total high density lipoprotein triglyceride fatty acids.
Inhibition of fracture healing by indomethacin in rats
Authors: SUDMANN EINAR , DREGELID EINAR , BESSESEN ATLE , MØRLAND JØRG
Published: March 2008

Abstract. The effect of indomethacin (2 mg/kg/day) on the healing of closed unimmobilized femoral fractures was examined in rats. A standard femoral fracture was produced in 205 male adolescent rats, and three different experiments were done. In a long‐term experiment, the rats were treated with either indomethacin or placebo for 29 days and fracture healing followed for a maximum of 91 days. In two short‐term experiments, the rats were treated with either indomethacin or placebo for a week and followed for a maximum of 122 days. The effect of age was studied in one experiment. Indomethacin plasma levels were about 1 μg/ml in the indomethacin‐treated animals. In the long‐term experiment, indomethacin inhibited fracture healing (P< 0·006) and increased the angulation between the femur fragments. In the short‐term experiments indo‐methacin inhibited fracture healing (P< 0·033) and increased the interfragmentary angle as well as fracture instability. All untreated fractures healed within 10 weeks in younger rats (210 g), whereas only 44% healed in older rats (295 g).
The subcellular localization of peptidase activity in the human jejunum
Authors: NICHOLSON J. A. , PETERS T. J.
Published: March 2008

Abstract. The subcellular localization of peptidase activity in the normal human jejunum has been investigated. Subcellular organelles were fractionated by density gradient centrifugation. The localization of peptidases was determined by comparing the distributions of peptidase activities with those of organelle ‘marker’ enzymes. The organelles and their markers were: cytosol—lactate dehydrogenase; brush border—neutral α‐glucosidase, γ‐glutamyl transferase and leucyl‐2‐naphthylamidase; plasma membrane—5′‐nucleotidase; lysosomes—N‐acetyl‐β‐glucosaminidase; mitochrondria—malate dehydrogenase; endoplasmic reticulum—alkaline α‐glucosidase; peroxisomes—catalase.

Thirteen dipeptides, seven tripeptides, two tetrapeptides, two pentapeptides and a hexapeptide were used as substrates. The distribution of dipeptidyl peptidase IV was also determined.

Irrespective of whether the NH2‐terminal or COOH‐terminal amino acid was neutral, basic or acidic, the major or exclusive locus of dipeptidase activity was cytosolic. All of the activity against a dipeptide with the amino acid proline at the NH2‐terminus was in the cytosol.

The distribution of tripeptidase activity was quite different. Although the cytosol hydrolysed all tripeptides, as much as 50% of tripeptidase activity was particulate. For both tetrapeptides, one of the pentapeptides and the hexapeptide, the major or exclusive locus of activity was the brush border membrane. Pentaphenylalanine, however, was hydrolysed by both the cytosol and the brush border. Dipeptidyl peptidase IV was localized in the brush border.
Synthesis of fatty acids and cholesterol by liver, adipose tissue and intestinal mucosa from obese and control patients
Authors: ANGEL A. , BRAY G. A.
Published: March 2008

Abstract.Biopsies of adipose tissue, liver and small bowel mucosa obtained from grossly obese and control subjects were used to study absolute rates of fatty acid, cholesterol, and other nonsaponifiable lipid synthesis using glucose as substrate and3H2O as the isotopic marker. Fatty acid synthesis in subcutaneous adipose tissue expressed on a cell basis was greater in obese than control subjects and was stimulated by a high concentration of insulin (1000 μU/ml), but not by a lower amount (100 μU/ml), Fatty acid synthesis in omental adipose tissue exceeded by 3‐fold that of subcutaneous fat. Fatty acid synthesis in obese liver was twice that of control liver and 20 times greater than obese adipose tissue. In terms of total organ activity fatty acid synthesis in fat tissue equalled or exceeded that of liver in both obese and control subjects. The cholesterol content of obese adipose tissue 1·86 ±0·11 mg/g exceeded that of controls 1·47±0·07 mg/g. All tissues examined synthesized cholesterol and nonsaponifiable lipids, liver >> adipose tissue > small bowel mucosa. Nonsaponifiable lipid synthesis per gram of adipose tissue or liver was similar in obese and control tissues. The synthesis of total nonsaponifiable lipids including sterols, hydrocarbons and squalene was appreciable in adipose tissue and was approximately 15% of that of liver. However, cholesterol synthesis in the liver expressed in terms of total organ activity was 50 times that in adipose tissue. The study demonstrates by direct comparison that liver is the dominant cholesterogenic organ in man and also shows that adipose tissue is a significant site of formation of fatty acids and nonsaponifiable lipids.
Capillary permeability in healthy males with different insulin response to glucose
Authors: BERGLUND BO , EFENDIĆ SUAD , STRANDELL TORE , LUFT ROLF
Published: March 2008

Abstract. The capillary permeability in human skeletal muscle, expressed as capillary diffusion capacity (CDC) for 51Cr‐EDTA, was determined during exercise with a local clearance method in two groups of healthy male subjects: a younger group with a mean age of 30 years and an older one with a mean age of 58 years. The main finding was that, in both age groups, CDC was significantly negatively correlated to the early phase of insulin response to an intravenous glucose load. No correlation was found between CDC and peripheral insulin sensitivity. CDC was significantly higher in the older age group (P < 0·01) independent of insulin response, blood flow and body weight. These data indicate that subjects with low insulin response to glucose have a higher capillary permeability than high responders, and that muscle capillary permeability increases with age.
Glucose tolerance, plasma insulin and α‐lipoproteins in young male myocardial infarction survivors compared with controls matched on serum cholesterol concentration
Authors: BERGSTRAND R. , WIKLUND O. , HOLM G. , WEDEL H.
Published: March 2008

Abstract. In order to identify metabolic risk factors other than hypercholesterolaemia, all cases of acute myocardial infarction, diagnosed in males aged under 40 years, were studied over a period of 6 years in Göteborg, Sweden. Twenty out of twenty‐four patients who were alive at the time of the study were compared with forty controls matched for serum cholesterol concentration. A previous report has noted lower apolipoprotein A (apoA) and a higher α‐lipoprotein triglyceride concentration in these young myocardial infarction patients compared with the matched controls.

Basal blood glucose, oral glucose tolerance and plasma insulin levels did not differ between the patients and controls, i.e. decreased glucose tolerance and elevated plasma insulin levels were not found to be additional risk factors for myocardial infarction in young males if serum cholesterol concentration was taken into consideration. This finding could be explained by the fact that patients and controls were all high cholesterol individuals and a difference between the patients and the general population is still possible.

Low apoA was a risk factor independent of serum cholesterol as well as glucose intolerance and elevated plasma insulin levels.
Extrapancreatic action of sulphonylureas: effect of gliquidone on insulin and glucagon binding to rat liver plasma membranes
Authors: BACHMANN W. , BÖTTGER I. , HASLBECK M. , MEHNERT H.
Published: March 2008

Abstract. Gliquidone (a second generation sulphonylurea) was administered orally to normal rats 1 h before killing. Gliquidone treatment led to a decrease in plasma glucose, an increase in insulin and a diminution in glucagon concentration. Insulin binding to liver plasma membranes was enhanced by 40% in comparison with controls, whereas glucagon binding was slightly diminished. These findings indicate a greater sensitivity of liver cells to insulin during sulphonylurea treatment and support the view that sulphonylureas potentiate insulin action on the liver.
Regulation of sterol synthesis in leukaemic blast cells: a defect resembling familial hypercholesterolaemia
Authors: BETTERIDGE D. J. , KRONE W. , FORD J. M. , GALTON D. J.
Published: March 2008

Abstract. Leucocytes from normal subjects and from patients with acute myeloblastic leukaemia incubated for 9 h in the absence of lipoproteins increased their rate of sterol biosynthesis from [2‐14C]acetate three‐fold. Subsequent addition of complete serum, low density lipoprotein or cholesterol in a non‐lipoprotein form suppressed sterol synthesis in leucocytes from normal subjects. In contrast, complete serum or low density lipoprotein totally failed to suppress sterol synthesis in leukaemic blast cells. However, when these cells were incubated with cholesterol in a non‐lipoprotein form suppression of sterol synthesis occurred as in normal leucocytes. These results suggest that leukaemic blast cells behave like cells from patients with familial hypercholesterolaemia in showing failure of regulation of sterol synthesis by low density lipoprotein.
Plasma equilin concentrations in an oophorectomized woman following ingestion of conjugated equine oestrogens (Premarin)
Authors: MORGAN M. R. A. , WHITTAKER P. G. , DEAN P. D. G. , LENTON E. A. , SEXTON L. , COOKE I. D.
Published: March 2008

Abstract. The plasma equilin concentration was 25·2 nmol/l (6·7 ng/ml) 4 h after an oral dose of Premarin (1·25 mg), and a maximum concentration of 20·5 nmol/l (5·5 ng/ml) was recorded 3 h after a smaller dose (0·625 mg) was given. 24 h later, the plasma equilin was still considerable, being 6·1 nmol/l (1·6 ng/ml) and 3·7 nmol/l (1·0 ng/ml) for the larger and smaller dosages recpectively. The findings for equilin are considerably higher than physiological oestrogen concentrations and in addition show that daily therapy with Premarin could lead to cumulation of the steroid.
Metabolic activity of human polymorphonuclear leucocytes: relation to ingestion rate
Authors: TORRES MARTINE , PROST DOMINIQUE DE , HAKIM JACQUES , GOUGEROT MARIE‐ANNE
Published: March 2008

Abstract. The ingestion rate and oxygen‐dependent metabolic activities of normal human polymorphonuclear leucocytes were measured with heat‐killed Klebsiella as the particle. Since the experimental conditions were similar for each measurement, it was possible to make direct correlations between each oxygen‐dependent reaction and (1) ingestion rate and (2) the other oxygen‐dependent reactions.

In the controls, oxygen‐uptake was more reliably correlated (r= 0.960) with ingestion rates than with (in order of reliability) hydrogen peroxide produced (r= 0.860) and iodination (r= 0.858 and 0.813 for 100 and 20 μmol/l iodide respectively). Hydrogen peroxide production (r= 0.988), nitroblue tetrazolium reduction (r= 0.969) and cytochrome c reduction (r= 0.862) were more reliably correlated to oxygen‐uptake than to ingestion rate, and iodination was better related to hydrogen peroxide production (r= 0.90 and 0.819 for 100 and 20 μmol/l iodide respectively) than to ingestion rate.

From these findings it was possible to locate primary defects in abnormal polymorphonuclear leucocytes from individual patients with pyogenic infections, idiopathic refractory anaemia or idiopathic oesteomyelofibrosis with splenomegaly, even when several deficiencies existed.
Stimulation by intragastrically administered E2 prostaglandins of human gastric mucus output
Authors: JOHANSSON C. , KOLLBERG B.
Published: March 2008

Abstract. Prostaglandin E2 and 15(R)15 methyl prostaglandin E2 were instilled intragastrically to study gastric mucus output in healthy male subjects during an infusion of pentagastrin. Mucus was measured by determining total, free, and bound N‐acetyl neuraminic acid (NANA) in gastric recoveries. NANA is a sialic acid located at the end terminals on the carbohydrate chains of mucus glycoprotein. It contributes to viscosity and prevents enzymatic degradation of mucus.

The methyl analogue of prostaglandin E2 increased the gastric output of NANA and inhibited gastric acid secretion in a dose‐dependent fashion. NANA produced in response to the analogue was bound to mucus glycoprotein. Prostaglandin E2 increased the output of NANA without affecting the gastric acid secretion. Both prostaglandin E2 and its methyl analogue increased volumes, pH, and NANA content of gastric aspirates withdrawn prior to start of the pentagastrin infusion, indicating a stimulation of the alkaline gastric secretion.

The results show that oral E2 prostaglandins have dual effects on gastric secretion, and that their ability to stimulate mucus production is not secondary to gastric acid inhibition. Further studies are needed to examine whether their effect is mainly to increase the incorporation of NANA into mucus glycoproteins, or to stimulate the release and/or production of gastric mucus, and also to quantitate the gastric nonparietal secretion.

The stimulatory properties of E2 prostaglandins on gastric mucus and alkaline secretion may be one mechanism by which they protect the gastric mucosa against experimentally induced damage.
The effects of albumin bound fatty acids on the platelet inhibitory function of human endothelial cells
Authors: NORDØY ARNE , SVENSSON BIRGIT , HOAK JOHN C.
Published: March 2008

Abstract. This study was carried out to evaluate the effects of albumin‐bound fatty acids on the anti‐platelet effects of endothelial cells. Primary cultures of human endothelial cells (ECM), grown in confluent monolayers, were incubated with plasma or growth medium enriched with albumin‐bound fatty acids (FA) for 2–20 h. The effects of ECM on ADP‐induced platelet aggregation (PA) and collagen‐induced PA and prostaglandin synthesis in platelet‐rich plasma were tested.

ECM released an inhibitor of platelet reactions which resembled the activity of PGI2 (prostacyclin). The inhibitory activity was increased by preincubation of ECM with arachidonic acid (AA). A moderate decrease of the activity was obtained by incubation with longchain saturated, monoenoic and dienoic unsaturated fatty acids. A pronounced decrease of the inhibitor was obtained by incubation with di‐homo‐γ‐linolenic acid (DHLA).

Paired combinations of AA with the other fatty acids in the incubation medium partially restored the inhibitor activity obtained by the separate FA.

The stimulation of the inhibitor by AA was dose dependent and high concentrations of AA reduced this activity.

The present study indicates that the quantity and quality of the plasma free fatty acids can affect the endothelial cells' ability to act as a non‐thrombogenic surface.
Biochemistry and histology of the connective tissue of Dupuytren's disease lesions
Authors: BAZIN S. , LOUS M. LE , DUANCE V. C. , SIMS T. J. , BAILEY A. J. , GABBIANI G. , 'ANDIRAN G. , PIZZOLATO G. , BROWSKI A. , NICOLETIS C. , DELAUNAY A.
Published: March 2008

Abstract. When compared to age‐matched control aponeurosis, lesions of Dupuytren's disease contain higher contents of water, collagen and chondroitin‐sulphate, as well as increased proportions of soluble collagen and of reducible cross‐links; these indicate synthesis of new collagen. The lesions show also increased amounts of type III collagen and an increased hydroxylation and glycosylation of the reducible cross‐links. All these parameters are characteristic of granulation and scar tissues. Type III collagen was located by means of immunofluorescence on thin argyrophilic fibres and also within the large fibre bundles which appeared to be disrupted into microbun‐dles. The increase of type III collagen and the presence of myofibroblasts in the apparently unaffected aponeurosis show that the disease is widespread and suggest that it is initiated within the aponeurosis and propagated by the cells migrating along the collagen bundles.
Effect of lipoprotein concentration and lecithin: cholesterol acyltransferase activity on cholesterol esterification in human plasma after plasma exchange
Authors: THANABALASINGHAM S. , THOMPSON G. R. , TRAYNER I. , MYANT N. B. , SOUTAR A. K.
Published: March 2008

Abstract. The rate of cholesterol esterification in plasma, plasma lecithin cholesterol acyltransferase (LCAT) activity and plasma lipoprotein levels have been measured in five subjects who underwent therapeutic plasma exchange to reduce their plasma cholesterol concentration. In the week following the exchange the cholesterol esterification rate and the plasma triglyceride concentration returned rapidly in parallel to pre‐exchange levels, while high density lipoprotein (HDL) cholesterol and LCAT activity returned to normal more slowly but also in parallel. The data suggest that the rate‐limiting factor for cholesterol esterification in plasma is unlikely to be solely the enzyme levels, but is probably a combination of factors, including the enzyme level and either substrate availability or product removal. Plasma very low density lipoprotein (VLDL) may either provide substrates for the reaction or provide a means of removing one of the products from the site of reaction.
Arterial blood gas tensions in acute severe asthma
Authors: RUDOLF MICHAEL , RIORDAN J. F. , GRANT B. J. B. , MABERLY D. J. , SAUNDERS KENNETH B.
Published: March 2008

Abstract. We have studied the serial changes in arterial blood gases in fourteen patients with acute severe asthma, all of whom a standard therapeutic regime and had similar measurements made at identical time intervals under standard conditions.

Hypoxaemia on admission was a constant finding, and the arterial oxygen tension often took a week or longer to return to a normal level. Treatment with 60% inspired oxygen provided a safe means of relieving hypoxaemia, provided that blood gases were measured before and during oxygen therapy.

Most patients had a normal arterial carbon dioxide tension, which indicated the severity of their illness. Acid‐base disturbances, when present, were mild and needed no specific treatment.

Age, duration of the acute attack, and severity of airways obstruction were all unrelated to the changes in blood gas tensions, and pulse rate was found to be a poor predictor of hypoxaemia in elderly asthmatics.

Serial measurements of the arterial blood gases should be made in all patients with acute severe asthma.
The role of polymorphonuclear leucocytes and T lymphocytes in experimental murine amyloidosis
Authors: KEDAR I. , RAVID M.
Published: March 2008

Abstract. Washed cells, from ascitic fluid, which contained predominantly polymorphonuclear leucocytes from casein treated donor mice, induced accelerated amyloid formation in untreated syngeneic recipient animals. A similar transfer model, with lymph node cell suspension, was ineffective. Amyloidogenesis was completely blocked by colchicine treatment of the donors while treatment of the recipients had no effect. A casein induced amyloidogenic stimulus was transferred from nude C3H mice to their normal litter‐mates. When the order was reversed, no amyloidosis occurred in the nude recipients. These experiments indicate the possible involvement of two cells in the biphasic process of casein induced murine amyloid formation: the polymorphonuclear leucocyte in the first phase and the T lymphocyte in the second.