bluuebunny/crossref_metadata_2025 huggingface dataset:
Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease
Authors: KUUTTI‐SAVOLAINEN EEVA‐RIITTA , ANTTINEN HENRIK , MIETTINEN TATU A. , KIVIRIKKO KARI I.
Published: March 2008

Abstract. Serum galactosylhydroxylysyl glucosyltransferase activity exceeded the 95% confidence limit of the controls in eleven out of thirteen patients with primary biliary cirrhosis, four out of seven with portal cirrhosis, all four with acute hepatitis and all seven with cancer having liver metastases, whereas it was below this limit in most patients with fatty liver, extrahepatic cholestasis and cholangitis, and in seven out of fourteen cases with cancer without liver metastases or with other malignant diseases. Liver galactosylhydroxylysyl glucosyltransferase activity was elevated in the same diseases, and there was a high correlation between these two measures (P < 0.005). Serum galactosylhydroxylysyl glucosyltransferase activity also correlated with serum immunoreactive prolyl hydroxylase protein (P < 0.001), and liver galactosylhydroxylysyl glucosyltransferase activity with liver prolyl hydroxylase activity (P < 0.001), but not with liver immunoreactive prolyl hydroxylase protein. Serum galactosylhydroxylysyl glucosyltransferase activity did not correlate with liver hydroxyproline, and liver galactosylhydroxylysyl glucosyltransferase activity only weakly. Serum galactosylhydroxylysyl glucosyltransferase activity correlated with serum alkaline phosphatase in primary biliary cirrhosis (P < 0.001) but not in any other disease, and with serumaspartate aminotransferase (P < 0.05) and total bilirubin (P < 0.05) in the pooled group of all patients with non‐malignant liver disease. The results suggest that assays of serum galactosylhydroxylysyl glucosyltransferase activity and liver galactosylhydroxylysyl glucosyltransferase activity in liver disease may give useful information on the actual hepatic collagen synthesis.
Polymyalgia arteritica: a clinical review
Authors: DOUGLAS J. G. , FORD M. J. , INNES J. A. , MUNRO J. F.
Published: March 2008

Abstract. In a series of thirty‐seven consecutive patients with polymyalgia arteritica, twenty‐five had polymyalgia rheumatica and twelve had cranial arteritis. Some failed to respond promptly to low doses of prednisolone and it is recommended that the initial dose should be in the order of 40 mg daily. An ESR above 40 mm in the first hour was present in four patients 3 months after admission; three were found to have rheumatoid disease and one pulmonary tuberculosis.

Symptomatic relapses occurred in fourteen patients on twenty‐one occasions and all responded to an increase in the daily dose of maintenance prednisolone. Most occurred in the first year and were attributable to an excessively rapid reduction in steroid therapy. Relapses occurring in patients on a stable dose of prednisolone were commonly associated with the development of rheumatoid disease. In elderly patients who have relapsed, or who have had arteritic complications, life‐long prednisolone therapy appears justifiable.
Substituting polyunsaturated for saturated fat as a single change in a Swedish diet: effects on serum lipoprotein metabolism and glucose tolerance in patients with hyperlipoproteinaemia
Authors: VESSBY B. , GUSTAFSSON I.‐B. , BOBERG J. , KARLSTRÖM B. , LITHELL H. , WERNER I.
Published: March 2008

Abstract. A diet with a high content of polyunsaturated fatty acids (PUFA) with a ratio between polyunsaturated and saturated fatty acids (P/S) of 20 and a fat content of 44% was worked out. After an initial 2 weeks' period on a control diet (P/S ratio 0–2) the PUFA diet was fed under isoenergetic conditions at a metabolic ward for 2 weeks to thirty patients with hyperlipoproteinaemia type IIa (n= 7), type IIb (n= 5) and type IV (n=18). The two diets were based on ordinary foodstuff and differed only in regard of the quality of the fat, while the amount of fat as well as the content of other nutrients were kept constant. Compared with the control diet the serum cholesterol concentration decreased by 10%, 13% and 12% on the PUFA diet in patients with hyperlipoproteinaemia type IIa, IIb and IV respectively. In hyperlipoproteinaemia Ila the low density lipoprotein cholesterol decreased by 9% (n.s.) and the high density lipoprotein cholesterol by 16% (P < 005). In hyperlipoproteinaemia type lib the very low density lipoprotein cholesterol decreased by 18% (P < 005), the low density lipoprotein cholesterol by 13% (P < 005) and the high density lipoprotein cholesterol by 5% (n.s.). In type IV the very low density lipoprotein cholesterol decreased by 18% (P < 0–01), the low density lipoprotein cholesterol by 7% (P < 0–05)) while the high density lipoprotein cholesterol remained unchanged. The serum triglyceride concentration decreased by 10% (type IIa), 14% (type lib) and 13% (type IV) on the PUFA diet. The serum concentrations of apolipoprotein A‐I and B were reduced by 6% (P < 0–05) and 11% (P < 005) respectively in patients with hyperlipoproteinaemia type IV while the serum apolipoprotein concentration did not change in the patients with hypercholesterolae‐mia. Inverse relationships between very low density lipoprotein triglycerides and high density lipoprotein cholesterol were found before treatment (r= 0–49, P < 0–01) which was altered by the treatment (r= 0–28, P > 005). The very low density lipoprotein triglycerides were also found to be inversely related to low density lipoprotein cholesterol both on the control diet (r= ‐0–65, P < 0001) and the PUFA diet (r= ‐0–56, P < 001). The regression lines of the latter equations were parallel. The intravenous glucose tolerance was improved (P < 0 05) in patients with hyperlipoproteinaemia type IV on the PUFA diet. The fatty acid composition of the serum lipid esters was significantly changed during the treatment. The relative concentrations of oleic acid and saturated fatty acids decreased while the linoleic acid content increased. The effects of the PUFA diet were less pronounced than the effects of conventional lipid lowering diets where also the fat content has been reduced and where complex carbohydrates have been substituted for simple carbohydrates.
Molecular forms of gastrin in peptic ulcer: comparison of serum and tissue concentrations of G17 and G34 in gastric and duodenal ulcer subjects
Authors: CALAM J. , DOCKRAY G. J. , WALKER R. , TRACY H. J. , OWENS D.
Published: March 2008

Abstract. We have studied the relationships between the main molecular forms of gastrin (G17 and G34) in the serum, antral and duodenal mucosa of duodenal (DU) and gastric (GU) ulcer patients. Fasting serum G17 was similar in both DU and GU (about 6 pmol/1) and in both groups increased about three‐fold with feeding. In contrast, basal serum G34 was significantly higher in GU (29 pmol/1) than in DU (12 pmol/1) and the peak post prandial increase over basal of G34 was also higher in GU (57 pmol/1) compared with DU (10 pmol/1). In sharp contrast, in the same groups of DU and GU patients mean total antral gastrin concentrations were similar (about 12 nmol/g), and in both groups 95% of antral gastrin was G17, most of the remainder being G34. In both groups total duodenal gastrin concentrations were about 20% those in antral mucosa and about 70% of duodenal gastrin was attributable to G34. The higher serum G34 in GU could therefore be explained by increased secretion of duodenal gastrin, but further work is needed to examine whether there might also be preferential secretion of antral G34 in GU, or a difference in the metabolism (or volume of distribution) of gastrin variants in GU and DU.
Intestinal solubilization, absorption, pharmacokinetics and bioavailability of chenodeoxycholic acid*
Authors: LEON MAURIZIO PONZ DE , LORIA P. , CARULLI N. , MURPHY G. M. , DOWLING R. HERMON
Published: March 2008

Abstract. Little is known about the physical state, intestinal solubilization, absorption and bioavailability of chenodeoxycholic acid used in the medical treatment of gallstones. Therefore the concentrations of unconjugated chenodeoxycholic acid were measured in the supernatant and precipitate phases of intestinal contents aspirated from stomach, duodenum and jejunum of nine control subjects who took 500 mg chenodeoxycholic acid (4 times 125 mg gelatin‐coated capsules) either fasting or together with a standard liquid meal. Chenodeoxycholic acid solubility was markedly influenced by luminal pH but was little affected by endogenous conjugated bile acids when their concentrations were > 1–2 mmol/1.

Systemic bioavailability of 250, 500 and 750 doses of chenodeoxycholic acid was measured in five subjects by comparing areas under 4 h serum concentration‐time curves after giving the bile acid first as a bolus intraduodenal aqueous infusion of 3H‐labelled chenodeoxycholic acid containing either 14C‐polyethylene glycol or bromsulphthalein as non‐absorbable markers, and then as gelatin‐coated capsules by mouth.

Absorption was assessed by measuring the ratio of marker: bile acid in intestinal contents aspirated for 2 h from sites 60 and 120 cm distal to the duodenal infusion port and in three subjects quantitative recovery of marker was measured proximal to an occluding intestinal balloon. Absorption of duodenally‐infused chenodeoxycholic acid was 96–99% complete and bioavailability was complete with the 250 and 500 mg doses but fell to 81% with the 750 mg dose.
The effect of cigarette smoke condensate on a,‐antitrypsin, antileukoprotease and granulocyte elastase
Authors: OHLSSON KJELL , FRYKSMARK ULLA , TEGNER HANS
Published: March 2008

Abstract. Unfractionated cigarette smoke condensate was found to affect α1‐antitrypsin and antileukoprotease, which are the dominating enzyme inhibitors in the respiratory tract. The electrophoretic and crossed immunoelectrophoretic precipitate patterns of these inhibitors were grossly altered and their inhibiting capacity reduced in both a dose and time dependent way. Other plasma proteins were also affected by cigarette smoke condensate, which in high concentrations caused precipitation of most serum proteins.

Human granulocyte elastase was reduced in functional activity by similar concentrations of the smoke condensate as the inhibitors. Although the elastolytic activity was markedly reduced, the esterolytic activity was reduced to a lesser degree.
Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man
Authors: FITZGERALD G. A. , BARNES P. , HAMILTON C. A. , DOLLERY C. T.
Published: March 2008

Abstract. Six normotensive volunteers were infused with L‐adrenaline at 001, 003, 005, 0075 and 010 μg/kg‐1 min‐1, each increment lasted 10 min. Plasma adrenaline rose from 0–27 to 4–61 nmol/1, and there were dose‐related increases in plasma renin activity, blood glucose, plasma cyclic AMP and plasma free fatty acids, but not in plasma noradrenaline and cyclic GMP. Levels of circulating adrenaline previously noted in essential hypertensives had minimal cardiovascular effects. The secretion rate of adrenaline and its rate of clearance from the circulation were calculated from plasma samples taken during an hour‐long infusion (0–083 ± 0006 μg kg‐1 min‐1) of L‐adrenaline in the same individuals. The secretion rate ranged from 1 40 to 601 nmol/min with a mean (±SEM, 6) of 2–82 ±0–76 nmol/min. Mean clearance (±SEM, 6) was 9–41 ± 1 ‐37 1/min and ranged from 4–86 to 14.611/min. The decline of plasma adrenaline following the infusion was biexponential.

Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation.
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. , D'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.
Quantitative studies of ver low densit lipoprotein: conversion to low densit lipoprotein in normal controls and primar hperlipidaemic states and the role of direct secretion of low densit lipoprotein in heterozgous familial hpercholesterolaemia
Authors: JANUS E. D. , NICOLL A. , WOOTTON R. , TURNER P. R. , MAGILL P. J. , LEWIS B.
Published: March 2008

Abstract. Autologous 131I‐labelled ver low densit lipoprotein (VLDL) and 125I‐labelled low densit lipoprotein (LDL) were injected into seven normal subjects and twent‐eight geneticall classified hperlipidaemic patients to quantitate lipoprotein interconver‐sion. The apoprotein B specific activit‐time curves for VLDL and intermediate densit lipoprotein (IDL, densit = 1 006–1019 g/ml) intersected at or before the IDL‐B maximum in thirt‐one studies (five normal controls and twent‐six hperlipidaemic subjects) impling that all IDL‐B ma be derived from VLDL‐B. The fractional conversion of VLDL‐B to LDL‐B (densit 1 019‐1 063 g/ml) following a simultaneous spike injection of 131I‐VLDL and 125‐LDL was obtained b deconvolution of the 125I and 131I‐LDL‐B activit curves. 21–65% (mean = 44%) of VLDL‐B was converted to LDL‐B in twent‐three subjects studied. The mean conversion time ranged from 10 to 24 h in ten normotriglceridaemic subjects and from 19 to 42 h (mean = 33 h) in twelve hpertriglceridaemic subjects. In one patient with broad‐β disease the mean conversion time was 55 h. LDL‐B production from VLDL‐B and total LDL‐B snthetic rate were essentiall equal in normal controls and normocholesterolaemic subjects and in the patient with broad‐β disease. But in all six patients with familial hpercholesterolaemia LDL‐B snthetic rate significantl exceeded LDL‐B production from VLDL‐B, indicating direct secretion of 20–72% of LDL‐B at a rate which correlates positivel with plasma LDL concentration. Three of five patients with familial combined hperlipidaemia showed a lesser but nevertheless significant direct secretion of LDL‐B.
Enhanced pulmonary and intestinal activation of procarcinogens and mutagens after chronic ethanol consumption in the rat
Authors: SEITZ HELMUT K. , GARRO ANTHONY J. , LIEBER CHARLES S.
Published: March 2008

Abstract. Recent epidemiological surveys have indicated that alcoholics exhibit increased incidences of a variety of cancers. We have investigated, as a possible contributing factor to carcinogenesis in this population, the effect of chronic ethanol consumption on metabolic activation of procarcinogens by microsomes isolated from lungs and small intestine. These tissues are major sites through which procarcinogens enter the body and are also potential sites of procarcinogen metabolism.

Rat litter‐mates were pair‐fed nutritionally adequate liquid diets which contained either ethanol as 36% of total energy or an equivalent energy content of carbohydrates in place of ethanol. Chronic ethanol consumption produced significant increases in pulmonary microsomal cytochrome P‐450 and microsomal ethanol oxidation. The ethanol diet also enhanced the capacity of pulmonary microsomes to activate compounds present in tobacco pyrolyzates to mutagens detectable in the Ames Salmonella auxotroph reversion assay. The ethanol diet did not alter the capacity of pulmonary microsomes to hydroxylate benzo(a)pyrene (BaP) or to activate BaP to a mutagen. In contrast, microsomes from the upper small intestine of ethanol‐fed rats did exhibit both higher levels of BaP hydroxylase activity and enhanced activation of BaP to a mutagen. The ethanol feeding also enhanced the capacity of the intestinal microsomes to activate to mutagens both tryptophan pyrolyzate and 2‐aminofluorene but did not influence the metabolic activation of these promutagens by pulmonary microsomes. Chronic ethanol consumption thus influences carcinogen metabolism in the intestine and lung in a manner which varies with respect to both carcinogen and tissue.
Disorder of collagen metabolism in a patient with osteogenesis imperfecta (lethal type): increased degree of hydroxylation of lysine in collagen types I and III
Authors: KIRSCH EMILIE , KRIEG THOMAS , REMBERGER KLAUS , FENDEL HELMUT , BRUCKNER PETER , MÜLLER PETER K.
Published: March 2008

Abstract. Types I, II and III collagen were isolated from calvarium, skin and cartilage from a patient with recessive lethal osteogenesis imperfecta. The distribution of the various collagen types was normal in all three tissues. The α‐chains were purified by molecular sieve and ion‐exchange chromatography and were found to differ from the corresponding α‐chains of age‐matched controls only in that the α1(I), α2 and α1 (III) chains contained higher amounts of hydroxylysine with proportionally less lysine. α1(II) was normal. The excess hydroxylysine residues were all glycosylated in the case of α1(I) chains, but only partly so for the α2 chains. Similar observations were made with collagen from fetuses at various stages of development. In these fetuses, however, the increase in the degree of hydroxylation of lysine in αl(I), α2 and αl(III) varied with age, being highest in the youngest fetus. Seen in the context of embryonic development, the collagen of the patient would correspond to that of a fetus younger than 18 weeks, and one could speculate that the defect seen in this patient is the result of a disturbed process of maturation of connective tissue.
Erythrocyte membrane adenosine triphosphatase activities in patients with endogenous depression and healthy subjects
Authors: RYBAKOWSKI JANUSZ , POTOK ELŻBIETA , STRZYÆWSKI WŁODZIMIERZ
Published: March 2008

Abstract. Specific activities of erythrocyte membrane Na‐K ATP‐ase, Mg ATP‐ase and Ca‐Mg ATP‐ase were measured in twenty‐five patients with endogenous depression both during acute phase of the illness and in remission as well as in sixteen healthy subjects. The three ATP‐ase activities were significantly lower during depressive phase than in remission period. The ATP‐ase values of depressive patients in remission did not differ from those of healthy controls. No difference was found in respect to parameters studied between the group of patients with depression in the course of bipolar manic‐depressive psychosis and patients with unipolar depression both in depression and remission. These data may suggest that the reduced activity of ATP‐ases in depressed patients is not due to a primary genetic defect but is an episodic change associated with depression. In view of consistency of this phenomenon its diagnostic and research potential is worthy of further study.
Familial apolipoprotein CII deficiency: plasma lipoproteins and apolipoproteins in heterozygous and homozygous subjects and the effects of plasma infusion
Authors: MILLER N. E. , RAO S. N. , ALAUPOVIC P. , NOBLE N. , SLACK J. , BRUNZELL J. D. , LEWIS B.
Published: March 2008

Abstract. Plasma lipoproteins and apolipoproteins have been studied in a kindred with familial apolipoprotein CII (apo CII) deficiency. As in two other recently documented pedigrees, apo CII deficiency appeared to be transmitted as an autosomal recessive trait. The homozygous state was characterized by gross fasting hypertriglyceridaemia, complete absence of apo CII from plasma and failure of plasma to activate lipoprotein lipase. Post‐heparin plasma hepatic triglyceride lipase activity was normal. Hypertriglyceridaemia reflected chylomicronaemia and elevated Sf 100–400 and Sf 20–100 lipoprotein concentrations; lipoproteins of Sf 12–20 (LDL1), Sf 0–12 (LDL2), F1.23.5–9 (HDL2) and F1.20–3.5 (HDL3) were greatly reduced in concentration. Low density lipoproteins (1.006–1.063 g/ml), isolated by preparative ultracentrifugation, and high density lipoproteins, isolated by heparin/Mn++, were triglyceride‐enriched. Electroimmunoassays revealed additionally low plasma concentrations of apolipoproteins AI, AII and B and very high concentrations of apolipoproteins CIII and E in the homozygote. The parents of the proband (heterozygotes) were normotriglyceridaemic, and had normal lipoprotein lipid concentrations and normal apolipoprotein AI, AII, B, CIII and E concentrations, in spite of having low apo CII concentrations.

Activation of lipoprotein lipase in the homozygote by intravenous infusion of 200 ml fresh‐frozen plasma rapidly reduced the plasma concentrations of chylomicrons and very low density lipoproteins (VLDL). Within VLDL, the decrease in concentration occurred sequentially in the Sf 100–400 and Sf 20–100 subclasses. These changes were associated during a 4‐day study period with reciprocal increases in LDL1, LDL2, HDL2 and HDL3. The plasma concentrations of apo AI and apo B also increased, associated with a less marked fall in that of apo CIII; the apo AII and apo E concentrations were unchanged.

These observations support other evidence that apo CII is a cofactor for the catabolism of chylomicrons and both major subfractions of VLDL by lipoprotein lipase in man, and that human LDL1 and LDL2 are derived, at least in part, from triglyceride‐rich lipoprotein catabolism. They also suggest that both major subfractions of HDL acquire additional components during triglyceride‐rich lipoprotein catabolism. In normal subjects the plasma apo CII concentration appears to be greatly in excess of that required for adequate activation of lipoprotein lipase.
Gamma‐glutamyltransferase, aspartate aminotransferase and alkaline phosphatase as markers of alcohol consumption in out‐patient alcoholics
Authors: GLUUD C. , ANDERSEN I. , DIETRICHSON O. , GLUUD B. , JACOBSEN A. , JUHL E.
Published: March 2008

Abstract. Serum activity of gamma‐glutamyltransferase, aspartate aminotransferase and alkaline phosphatase were determined in 316 patients attending an out‐patients clinic for treatment of alcoholism. The activity of gamma‐glutamyltransferase was raised in 34% and that of aspartate aminotransferase and alkaline phosphatase in 18% and 7%. Neither the activity of gamma‐glutamyltransferase, aspartate aminotransferase nor alkaline phosphatase showed any significant (P>0.05) correlation with the history of alcohol consumption. The activities of gamma‐glutamyltransferase and aspartate aminotransferase were raised significantly more often in patients with recent alcohol consumption than in patients who had abstained for more than 9 days. The concentration of alkaline phosphatase was not significantly (P>0.05) different in these groups. The predictive value of raised and normal activities of gamma‐glutamyltransferase, in deciding whether a patient had had recent alcohol consumption or not, was not superior to the predictive value of raised and normal activities of aspartate aminotransferase.
IIeal dysfunction and bacterial overgrowth in patients with Crohn's disease
Authors: RUTGEERTS P. , GHOOS Y. , VANTRAPPEN G. , EYSSEN H.
Published: March 2008

Abstract. The intestinal bile acid metabolism was studied in sixty‐one patients with non‐operated Crohn's disease (twenty‐seven ileitis and thirty‐four ileocolitis patients) by means of the 14C‐glycocholate breath test with marker‐corrected faecal analysis before and after a short course of antibiotics. The results of the combined breath and faecal analysis were compared with the data of other tests detecting bacterial overgrowth and ileal dysfunction. Fifteen of the sixty‐one patients (25%) presented with a 14C excretion pattern consistent with bacterial overgrowth of the small bowel. Repetition of the combined breath and faecal analysis after antibiotic treatment revealed that concurrent ileal dysfunction was present in at least six of these fifteen patients. In twenty other patients elevated marker‐corrected 14C faecal excretion indicated ileal dysfunction. Thus, the overall incidence of ileal dysfunction amounted to 26/61 (44%). The sensitivity of the bile acid breath test with marker‐corrected stool analysis was comparable to that of aerobic and anaerobic jejunal cultures in twenty non‐selected patients for the detection of bacterial overgrowth, and to that of chemical bile acid measurement in stools for the detection of ileal dysfunction. The bile acid breath test with faecal analysis was more sensitive than measurement of glycine‐taurine ratio in bile (twenty patients) and the Schilling test.
Effect of angiotensin‐ll blockade on systemic and hepatic haemodynamics and on the renin‐angiotensin‐aldosterone system in cirrhosis with ascites
Authors: ARROYO V. , BOSCH J. , MAURI M. , RIBERA F. , NAVARRO‐LÓPEZ F. , RODÉS J.
Published: March 2008

Abstract. We have studied the effect of angiotensin‐II blockade with saralasin on the cardiovascular and hepatic haemodynamics and on the renin‐angioten‐sin‐aldosterone system in fourteen patients with cirrhosis and ascites. Control measurements showed that most of the patients had a low mean arterial pressure, high plasma volume, normal or high cardiac index, low peripheral resistance and high plasma renin activity and aldosterone concentration. The wedged hepatic venous pressure was increased in each patient and the estimated hepatic blood flow was normal in most of them.

Overall, saralasin induced a significant reduction of the mean arterial pressure, cardiac index and peripheral resistance. The decrease of the peripheral resistance was greater than that of the cardiac index. Six of the patients developped a marked reduction of the mean arterial pressure with low doses of saralasin (1–2.5 μg/kg/min), and they had significantly higher plasma renin activity and lower mean arterial pressure than the remaining eight patients who showed a slight or no hypotensive response in spite of infusing saralasin up to a dose of 10 μg/kg/min. Overall, the decrease of the mean arterial pressure correlated directly with the baseline values of plasma renin activity.

Angiotensin‐II blockade induced a significant reduction of the wedged hepatic venous pressure. The hepatic blood flow did not show any significant change. The decrease of the wedged hepatic venous pressure was directly related to the reduction of the mean arterial pressure and also to the control plasma renin activity.

Our study indicates that in most patients with cirrhosis, ascites and high plasma renin activity, arterial pressure is maintained by the effect of endogenous angiotensin II on the peripheral vasculature, and we suggest that a pre‐existing arterial hypotension secondary to an arteriolar vasodilatation is the cause of renin release in these patients. Our results also show that angiotensin‐II blockade is accompanied by a reduction of the post‐sinusoidal hepatic vascular resistance.
Evaluation of renal tubular damage in liver cirrhosis by urinary enzymes and beta‐2‐microglobulin excretions
Authors: GATTA A. , AMODIO P. , FRIGO A. , MERKEL C. , MILANI L. , ZUIN R. , RUOL A.
Published: March 2008

Abstract. To assess the renal tubular damage in liver cirrhosis the fractional clearances of beta‐2‐micro‐globulin (B2m‐fr. cl) and malate‐dehydrogenase (MDH‐fr. cl) were measured respectively in sixty‐four and in forty‐six out of seventy‐nine patients with liver cirrhosis of different aetiology; furthermore the fractional excretions of gammaglutamyl‐transpeptidase (fr‐GGT) and of alpha‐glucosidase (fr‐AGL) were determined in fifty‐three and in forty of them respectively. In all patients glomerular filtration rate (GFR) and renal plasma flow (RPF) were also measured. Twenty‐five subjects were studied as a control group for the enzyme excretions, sixteen for B2m‐fr. cl.

B2m‐fr. cl and MDH‐fr. cl—indexes of tubular functions—on the average were normal and only slightly increased respectively in cirrhotics compared to controls. Nevertheless fr‐GGT and fr‐AGL—indexes of cytolysis of tubular cells—on the average were massively increased in cirrhotics compared to controls, particularly in those with reduced RPF and/or GFR.

No clear relationship between the indexes of tubular damage studied and the indexes of liver function was found.

Our results show that: (1) A renal tubular anatomical damage was found by means of an increase in the release of enzyme from tubular cells in patients with liver cirrhosis, particularly in those with a significant reduction of RPF and/or GFR; even so renal reab‐sorbtion of low molecular weight proteins is generally maintained. (2) The tubular damage does not seem to be related to the degree of liver impairment.
Immediate effects of captopril in acute left ventricular failure secondary to myocardial infarction
Authors: BRIVET FRANÇOIS , DELFRAISSY JEAN‐FRANCOIS , GIUDICELLI JEAN‐FRANÇOIS , RICHER CHRISTINE , LEGRAND ALAIN , DORMONT JEAN
Published: March 2008

Abstract. In eight patients with acute left ventricular failure secondary to myocardial infarction the haemo‐dynamic effects of captopril (25 mg), an orally active converting enzyme inhibitor, were measured. Haemo‐dynamic modifications were maximal at 60 min and lasted for 2–3 h. Pulmonary wedge pressure fell from 23–5± 4.9(mean ± SD)to 16–8 ± 4.7 mmHg(P<0–01), cardiac output rose from 3–24 ± 1 to 4–05 ± 0–91 1/min (P<001). Systemic vascular resistance decreased from 27–34 ± 3–81 to 17.52 ± 1–65 mmHg min 1‐1 (P<001). Mean arterial pressure fell from 89.6 ± 13.9 to 75.7±0 16.3 mmHg (P<0001) while heart rate was not significantly modified. Six patients who had high pretreatment plasma renin activity values responded by a decrease in ventricular filling pressure and/or an increase in cardiac output. One patient with normal initial plasma renin activity value showed similar haemodynamic effects. These data suggest that in the short term captopril is a vasodilator with both arterial and venous effects and improves cardiac function in acute left ventricular failure secondary to myocardial infarction.
The effect of antipyrine, phenobarbitol and rifampicin on thyroid hormone metabolism in man
Authors: OHNHAUS E. E. , BÜRGI H. , BURGER A. , STUDER H.
Published: March 2008

Abstract. The effect of three different liver microsomal enzyme inducing drugs on thyroid hormone metabolism was investigated. Seven volunteers were randomly allocated in a crossover design to either antipyrine (1200 mg), phenobarbital (100 mg) or rifampicin (1200 mg) daily for 14 days. Before and after each treatment the following parameters of enzyme induction were measured: antipyrine clearance, y‐glutamyltranspepti‐dase, d‐glucaric acid and 6‐β‐hydroxycortisol urinary excretion. In addition, thyroxine‐binding globulin (TBG), T3‐resin uptake (RT3U), thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3), reverse T3 (rT3), and thyroid stimulating hormone (TSH) were estimated. Following antipyrine and phenobarbital antipyrine clearance increased by about 45%, while with rifampicin an increase of 125% was observed. The indices of thyroid function did not change following phenobarbital and antipyrine, but after rifampicin T4, FT4 and rT3 decreased by about 14%, and T3 increased by 25%.

In addition, the impact of rifampicin on the clearance of injected 125I‐T4 was investigated in six additional volunteers by blocking thyroid iodine uptake. The 125I‐T4 halflife decreased from 155 to 106 h and its clearance increased from 35 to 50 ml/h, while a fall in T4, FT4 and rT3 by about 40% and no rise but a decrease in T3by 25% occurred. Therefore an increased clearance of T4 and rT3 but not of T3 seems likely following rifampicin, which might be due to enhanced hepatic metabolism and biliary excretion.
Age dependent differences in human bile acid metabolism and 7α‐dehydroxylation
Authors: van der WERF S. D. J. , HUIJBREGTS A. W. M. , LAMERS H. L. M. , HENEGOUWEN G. P. van BERGE , van TONGEREN J. H. M.
Published: March 2008

Abstract. It has been suggested that transformation of secondary bile acids into (co)carcinogenic compounds may have a role in the development of cancer of the large bowel. Because of age dependent differences of this disease we undertook a study of cholic and deoxycholic acid metabolism of eleven young adults (group A, 20–30 years old) and eleven elderly persons (group B, 55–75 years old) with a double isotope dilution method. Daily food intake was standardized individually and gut transit time measured with radio‐opaque pellets and labelled chromium chloride.

The 7α‐dehydroxylation fractions (the ratio of deoxycholic acid input rate from the large bowel to cholic acid synthesis rate) were higher in group B (P < 0.01) due to higher deoxycholic acid input rates (P < 0.005), especially when individuals from both groups with rapid gut transit were compared. As contributory factor was recognized the higher fractional turnover rate of cholic acid in group B. Pool sizes and synthesis rates of cholic acid and gut transit times were similar. In group A, but not in B, gut transit times correlated with deoxycholic acid input rates (P <0.01).

The differences in bile acid metabolism may be related to a more effective colonic absorption of deoxycholic acid in the elderly persons with a concomitant decrease of active ileal absorption of cholic acid in the elderly persons. Differences in diet or gut transit time between both groups do not seem to be the underlying mechanism.
Kidney function and size in normal subjects before and during growth hormone administration for one week
Authors: CHRISTIANSEN J. SANDAHL , GAMMELGAARD J. , ØRSKOV H. , ANDERSEN A. R. , TELMER S. , PARVING H.‐H.
Published: March 2008

Abstract. Kidney function and size were studied in seven normal male subjects before and after administration of highly purified human growth hormone for 1 week. Glomerular filtration rate, renal plasma flow (steady‐state infusion technique with urinary collections using 125I‐iothalamate and 131I‐hippuran) kidney size (ultrasonic scanning) and urinary excretion rates of albumin and β2‐microglobulin (radioimmunoas‐says) were measured. Highly purified growth hormone was injected subcutaneously, 2 IU in the morning and 4 IU in the evening. Glomerular filtration rate increased from (mean ± SEM) 114 ± 5 to 125±4ml/min x 1.73 m2 (P <0.01) and renal plasma flow increased from 554 ±30 to 601 ±36 ml/min ×1.73 m2(P < 0.01). Kidney size and urinary excretion rates of albumin and β2‐microglobulin did not change significantly.

Our results show that raising plasma growth hormone into a range similar to that found in insulin‐dependent diabetics enhances glomerular filtration rate and renal plasma flow, while kidney size remains unchanged. Increased renal plasma flow is the major determinant of growth hormone induced elevation in glomerular filtration rate. Growth hormone may thus contribute to the enhancement of glomerular filtration rate and renal plasma flow typically found in insulin‐dependent diabetics.
Activation of the glycogenolytic cascade in human polymorphonuclear leucocytes by different phagocytic stimuli
Authors: BORREGAARD NIELS , JUHL HENNING
Published: March 2008

Abstract. Human polymorphonuclear leucocytes were found to respond to activation by immunoglobulin opsonized latex particles and to complement opsonized zymosan particles with a rapid transient increase in cAMP concentration, dissociation of the cAMP dependent protein kinase, activation of gly‐cogen phosphorylase and glycogen break down. However, since phosphorylase kinase was not activated, the activation of phosphorylase is believed to be secondary to non‐covalent activation of phosphorylase kinase by Ca2+.

Activation by the soluble stimulator phorbol myri‐state acetate resulted in activation of phosphorylase and glycogen break down, whereas no changes in cAMP concentration, protein kinase activity, or phosphorylase kinase activity were observed. The activation of phosphorylase is ascribed to an increase in cytosolic Ca2+ concentration.

The response to stimulation by zymosan was strongly inhibited by ethylene glycol‐bis‐(b‐aminoethyl ether)‐N,N'‐tetraacetic acid, which did not affect stimulation by either latex particles or phorbol myristate acetate. The same differential effect of ethylene glycol‐bis‐(8‐aminoethyl ether)‐N,N'‐tetra‐acetic acid was observed when the response of the cells was measured as increase in oxygen consumption and activation of the hexose monophosphate shunt.
Inefficacy of bicarbonate infusions on the cource of postischaemic acute renal failure in the rat
Authors: SPORER H. , LANG F. , OBERLEITHNER H. , GREGER R. , DEETJEN P.
Published: March 2008

Abstract. Since bicarbonate has been reported to elicit fast recovery from acute renal failure in man, clearance studies were performed to compare the effects of sodium bicarbonate and saline infusion on renal function in postischaemic renal failure in the rat. In a first set of experiments the left kidney and in a second both kidneys were clamped for a period of 45 min and renal function monitored up to 2 10 min after release of the clamp. Glomerular filtration rate (ml/min) decreased following clamping from (mean values ± SEM) 1.33±0.09 to0.12+0.02(saline)or 1.43±O.l to 0.08 ± 0.01 (bicarbonate) in the unilaterally clamped kidney and from 2.94 k 0.20 to 0.41 ± 0.10 (saline) or 2.81 k0.17 to 0.22±0.03 (bicarbonate) when both kidneys were clamped. Fractional excretion of water and sodium increased to a similar extent in saline and bicarbonate treated animals. Plasma potassium decreased (from 3.37 ± 0.10 to 2.95 ± 0.07 [unilaterally clamped kidneys] or from 5.2 & 0.4 to 4.4 ± 0.2 [bilaterally clamped kidneys]) in bicarbonate treated but remained constant in saline treated animals, an effect not related to altered renal potassium excretion. In conclusion, no evidence was found that bicarbonate improves renal function in postischaemic renal failure.
Lack of clinical and physiological relationship between gastrin and calcitonin in man
Authors: HEYNEN G. , BRASSINE A. , DAUBRESSE J.C. , LIGNY G. , KANIS J. , GASPAR S. , FRANCHIMONT P.
Published: March 2008

Abstract. The clinical and physiological relevance of the relationship between gastrin and calcitonin has been investigated in normal subjects and in patients suffering from gastritis or duodenal ulcer. Basal plasma levels of calcitonin are increased in these patients but there is no significant relationship between calcitonin and gastrin levels. Acute pentagastrin injection in normal male subjects increased significantly (P < 0.05) plasma calcitonin levels whereas lower doses of pentagastrin which are known to stimulate gastric secretion are without effect on calcitonin levels. Moreover, stimulation of gastrin secretion by a protein test meal and by intragastric administration of a calcium chloride solution is not followed by any significant increase of plasma calcitonin levels. These results suggest that the stimulation of calcitonin secretion by gastrin and its synthetic analogue pentagastrin is a pharmacological rather than a physiological phenomenon.
Clinical and biological effects of low doses of (3 amino‐1 hydroxypropylidene)‐1,1‐bisphosphonate (APD) in Paget's disease of bone
Authors: HEYNEN G. , DELWAIDE P. , BIJVOET O. L. M. , FRANCHIMONT P.
Published: March 2008

Abstract. At doses varying between 500 and 1500 mg/day, the disodium salt of (3 amino‐1 hydroxypro‐pylidene)‐1,1‐bisphosphonate (APD) has been shown to induce rapid and complete biochemical responses in Paget's disease of bone, but a short‐lived and self‐limited fever has been observed in 30–40% of patients. The present study is an open and unrandomized trial, performed to explore the use of lower doses of APD (250 and 50 mg/day) given for 6 months to fourteen patients suffering from Paget's disease of bone. Subjective clinical improvement and complete biochemical remission (as assessed by normalization of urinary hydroxyproline excretion and plasma alkaline phosphatase concentration) was observed in ten out of eleven patients given 250 mg/day, but fever did not occur. Thus, a significant decrease in urinary hydroxyproline excretion was noted as early as 15 days after the beginning of the treatment (from 4.5 to 1.3 μmol/l GF; P > 0.05) whereas plasma alkaline phosphatase concentration fell significantly only 1 month later (from 330 to 195 IU/ml; P > 0.05). Both mean (± SEM) urinary hydroxyproline excretion (0.98 ± 0.08 μmol/l GF) and plasma alkaline phosphatase concentration (70 ± 8 IU/ml) were in the normal range after 6 months of treatment. Plasma calcium and phosphorus concentration, urinary calcium excretion and TmP/GFR decreased whereas plasma immunoreactive parathyroid hormone concentration increased. These changes were statistically significant (P < 0.05) only transiently and disappeared at the time when bone formation (assessed by plasma alkaline phosphatase) returned to normal. An increase in total body retention of 47Ca during the second month of treatment was documented in five patients (P < 0.05), compatible with a positive calcium balance. Plasma immunoreactive calcitonin did not change (P > 0.05). After 6 months of treatment at 50 mg/day, APD also induced significant decreases in urinary hydroxyproline excretion (from 4.23 to 1.73 μmol/l GF; P < 0.05) and plasma alkaline phosphatase concentration (from 360 to 162 IU/ml; P < 0.05) but biochemical remissions were not complete and these two variables were significantly higher than the corresponding values in the group of patients receiving 250 mg APD/day. Less marked changes were also noted in all the other variables measured. Biological and clinical tolerance was good in all the patients. It is concluded that 250 mg/day of APD is an effective dose schedule, capable of reducing to normal levels the indirect indices of bone turn‐over, but in contrast with higher doses, without inducing fever.
Renal hypomagnesaemia in human diabetes mellitus: its relation to glucose homeostasis
Authors: McNAIR PETER , CHRISTENSEN MERETE SANVIG , CHRISTIANSEN CLAUS , MADSBAD STEN , TRANSBØL IB
Published: March 2008

Abstract. Interrelations between magnesium and glucose metabolism were studied in 215 insulin‐treated diabetic out‐patients aged 7–70 years. All had normal serum creatinine concentrations (below 115 μmol/l) and none had other diseases or received drugs known to interfere with mineral metabolism. A definite hypomagnesaemia (< normal mean —2 SD) and hypermagnesiuria (> normal mean + 2 SD) occurred in 38.6% and 55% of the patients. In the presence of hypermagnesiuria the serum magnesium concentration was inversely correlated to the urinary magnesium excretion rate (R=–0.23, P<0.02). Serum magnesium correlated inversely with both fasting blood glucose (R=—0.32, P<0.001) and the urinary glucose excretion rate (R=–0.22, P<0.005). The urinary magnesium excretion rate correlated directly with the same variables (R= 0.27, P<0.001 and R= 0.58, P<0.001, respectively). These data indicate that the net tubular reabsorption of magnesium is decreased in diabetic patients in presence of hyperglycaemia, leading to hypermagnesiuria and hypomagnesaemia.
Relationships between the metabolism of high‐density and very‐low‐density lipoproteins in man: studies of apolipoprotein kinetics and adipose tissue lipoprotein lipase activity
Authors: MAGILL P. , RAO S. N. , MILLER N. E. , NICOLL A. , BRUNZELL J. , HILAIRE J. ST. , LEWIS B.
Published: March 2008

Abstract. In order to gain further insight into the relationship between high‐density lipoprotein (HDL) metabolism and plasma triglyceride transport, measurements were made of HDL cholesterol concentration, apoprotein (apo) AI and AII metabolism, very‐low‐density lipoprotein (VLDL) apo B metabolism, and heparin‐elutable adipose tissue lipoprotein lipase (LPL) activity in seventeen subjects with a wide range of plasma triglyceride concentrations (0.8–25 mmol/l).

The fractional catabolic rate (FCR) of VLDL apo B was directly related to LPL activity (r=+ 0.80), providing evidence that the activity of the enzyme in adipose tissue is a determinant of the rate of lipolysis of VLDL in man. HDL cholesterol concentration was a positive function of both VLDL apo B FCR (r=+ 0.74) and LPL activity, a finding consistent with previous evidence for the origin of a proportion of HDL cholesterol from ‘surface remnants’ liberated during VLDL catabolism. The FCRs of both apo AI and apo AII were inversely related to VLDL apo B FCR (AI, r= ‐ 0.52; AII, r= ‐ 0.69) and to LPL activity. The synthetic rate of apo AII, but not that of apo AI, was positively correlated with VLDL apo B synthesis (r=+ 0.71). Thus, the metabolism of the major proteins of HDL in man appears to be closely associated with VLDL metabolism.
Kinetics of primary bile acids in patients with non‐operated Crohn's disease
Authors: RUTGEERTS P. , GHOOS Y. , VANTRAPPEN G.
Published: March 2008

Abstract. The metabolism of cholic acid and cheno‐deoxycholic acid was studied in seventeen patients with non‐operated Crohn's disease, eleven ileitis and six ileocolitis patients. The turnover of cholic acid was significantly increased in patients with ileitis (k= 2.0±1.13 days‐1; P<0.001) and ileocolitis (k= 0.91±0.47 days‐1; P<0.005) as compared to normals (k= 0.35±0.19 day‐1). Although chenodeoxycholic acid was better preserved in the enterohepatic circulation than cholic acid its turnover was also significantly faster in ileitis (k= 0.81±0.56 days‐1; P<0.005) and ileocolitis patients (k= 0.62±0.18 days‐1; P<0.01) than in normals (k= 0.20±0.09 days‐1). The fractional turnover of cholic acid was related to the length of ileal involvement (r= 0.761; P<0.001; n= 17). Patients with Crohn's ileitis tended to preserve normal fasting total bile acid pools by increased synthesis of primary bile acids and efficient absorption of deoxycholic acid and ursodeoxycholic acid by the normal colon. Patients with active ileocolitis had decreased total fasting pool sizes (2.62±1.83 mmol; P<0.001) as compared to normals (7.69±1.61 mmol). In these patients there was no increase in bile acid synthesis as compared to normals and secondary bile acids were absent from bile. It is concluded that the colon has an important role in maintaining the fasting pool size to a normal level in the presence of an interrupted enterohepatic circulation of bile acids due to ileal disease.
Erythrocyte deformability in dialysed and non‐dialysed uraemic patients
Authors: INAUEN W. , STÄUBLI M. , DESCOEUDRES C. , GALEAZZI R. L. , STRAUB P. W.
Published: March 2008

Abstract. In thirty‐one uraemic patients, fourteen on conservative treatment and seventeen on long‐term haemodialysis, erythrocyte deformability, measured as filtration half‐time in a paper filtration experiment, was studied. The two groups were comparable concerning age, sex and kidney disease.

Although the mean filtration half‐time for erythrocyte suspensions was normal in non‐dialysed patients there was a positive linear correlation (P<0.01) between serum creatinine and filtration half‐time in this group. Filtration half‐time was increased in dialysed patients, indicating impaired deformability in the latter (P<0.001). Filtration half‐time showed a good inverse correlation with the packed red cell volume in the non‐dialysed (P<0.001) and in the dialysed group (P<0.01).

As pre‐ and post‐dialysis filtration half‐times were the same, it appeared that the more severe uraemic state of dialysed patients was responsible for the impairment of erythrocyte deformability and not the dialysis procedure itself.