bluuebunny/crossref_metadata_2025 huggingface dataset:
Sulphur amino‐acid degradation in subjects with hereditary glutathione synthetase deficiency (5‐oxoprolinuria)
Authors: MÅRTENSSON JOHANNES , KÅGEDAL BERTIL , LARSSON AGNE
Published: March 2008

Abstract. The role of a low intracellular glutathione concentration in sulphur amino‐acid degradation was investigated in two sisters (10 and 13 years old) with glutathione‐synthetase deficiency, by determination of the urinary excretion of sulphur amino‐acids and their main degradation products.

The urinary excretion of total sulphur and inorganic sulphate was normal, indicating adequate dietary intake of sulphur amino‐acids and normal oxidation to inorganic sulfate. Decreased excretion of N‐acetylcysteine was found in the younger sister, which could be due to a reduced intracellular availability of cyst(e)ine. Increased excretion of mercaptolactate was found in the older sister, probably featuring a more catabolic condition in this subject. She also had an increased excretion of thiosulphate. Low excretion of thiocya‐nate was observed in both subjects, probably a consequence of a reduced dietary intake of thiocyanate or its precursors. Neither glutathione nor γ‐glutamylcysteine were detectable in urine. The excretion of cystei‐nylglycine was clearly reduced, reflecting that this dipeptide mainly is a degradation product of glutathione.
Discrepancies in the catabolic pathways of human and rat high‐density lipoprotein apolipoprotein A‐I in the rat
Authors: HOOFT FERDINAND M. VAN ‘T , TOL ARIE VAN
Published: March 2008

Abstract. The in vivo metabolism in the rat of radioiodinated human and rat high‐density lipoprotein was compared with a double‐label procedure using 125I and 131I. While rat high‐density lipoprotein showed a biphasic serum decay, human high‐density lipoprotein was characterized by a monoexponential serum decay. No differences were observed between the serum decay of human high‐density lipoprotein‐2 and ‐3 subfractions, isolated by rate zonal ultracentrifugation. The catabolic sites of human and rat high‐density lipoprotein were analysed using the lysosomal cathepsin inhibitor leupeptin. Radioiodinated rat high‐density lipoprotein was catabolized by the kidneys and by the liver. In contrast, radioiodinated human high‐density lipoprotein was catabolized almost exclusively in the liver. No difference in the catabolic sites of human high‐density lipoprotein‐2 and ‐3 subfractions was observed. The catabolic sites of human high‐density lipoprotien apolipoprotein A‐I in the rat were further analysed using the O‐(4‐diazo‐3‐[125I]iodobenzoyl)sucrose label. Compared with rat high‐density lipoprotein apolipoprotein A‐I, the kidneys played a minor role in the catabolism of human high‐density lipoprotein apolipoprotein A‐I. It is concluded that in the rat the catabolic pathways of the apolipoprotein A‐I moieties of rat and human high‐density lipoproteins are different, indicating that homologous high‐density lipoproteins should be used for the investigation of in vivo metabolism.
Experimental studies on the adult respiratory distress syndrome: effects of induced DIC; granulocytes and elastase in mini pigs
Authors: STOKKE T. , BURCHARDI H. , HENSEL I. , HÖRL W. H.
Published: March 2008

Abstract. The potential role of granulocyte proteinases on experimentally induced ARDS was evaluated. In order to investigate the acute effects on lung function, elastase (330 U kg‐1 h‐1) or thrombin (75–150 U kg‐1 h‐1) was continuously infused into anaesthetized and mechanically ventilated mini pigs. Both elastase as well as thrombin induced a progressive respiratory failure with prompt increase in pulmonary vascular resistance, and decrease of cardiac output, further a pulmonary leukostasis, and a disturbance of blood coagulation leading to hypocoagulability. High proteolytic activity selectively in the lung indicates a possible role of proteinases released from sequestered polymorphonuclear neutrophils. Similar results following elastase infusion were however obtained in leukopenic animals pretreated with a single dose of dimethylmyleran (5 mg kg‐1) which depleted the granulocytes totally. These results offer the possibility that elastase itself may cause respiratory failure and lung tissue damage. On the other hand the digestion pattern of phosphorylase kinase by lung tissue homo‐genates of thrombin‐ or elastase‐infused mini pigs clearly indicates that elastase is only one of several mediators which may cause experimentally induced ARDS even in the absence of granulocytes.
Fibronectin replacement in patients with fulminant hepatic failure
Authors: HUGHES R. D. , IMAWARI M. , BIHARI D. , ALMASIO P. L. , LANGLEY P. G. , WILLIAMS R.
Published: March 2008

Abstract Patients with fulminant hepatic failure have low levels of the plasma opsonizing protein fibronectin together with cardiovascular disturbances similar to those in septic shock where microembolization of capillary beds by particulate debris has been proposed to lead to multi‐organ failure. Six patients with fulminant hepatic failure received a bolus injection of a concentrated fibronectin‐rich preparation. The mean plasma immunoreactive fibronectin level increased from 53 ± SE 12 μg ml‐1 initially to 295 ± 30 μg ml‐1 (P < 0·001) at 1 h after fibronectin administration. The in vitro plasma opsonic activity was also increased from 5·6 ± 3·6% of control to 102 ± 13% (P < 0·005) at 1 h. No similar effect was observed with the clearance of microaggregated albumin, but as its clearance is probably not dependent on fibronectin it may reflect a different aspect of reticuloendothelial cell function. No significant changes were observed in cardiopulmonary function or oxygen utilization and it is possible this is because clearance of opsonized particles is limited by damage to Kupffer cells.
Osteoporosis with hip fracture: changes in calcium regulating hormones
Authors: STEVENSON J. C. , ALLEN P. R. , ABEYASEKERA G. , HILL PATRICIA A.
Published: March 2008

Abstract It has been suggested that there are two distinct types of involutional osteoporosis in women. Loss of ovarian function causes spine and wrist fractures in middle‐aged women whilst a decline in renal endocrine function and bone formation is responsible for fractures, especially of the hip, in elderly women. We have investigated calcium regulation in post‐menopausal women with hip fractures in their seventh decade together with non‐osteoporotic controls of similar age. The major findings were reduced secretion of calcitonin (P < 0·01) and 1,25 dihydroxyvitamin D (P < 0·025) in the osteoporotics as compared with controls. No differences in plasma levels of calcium, parathyroid hormone and 25 hydroxyvitamin D were observed. Our results show some similarities with those reported in both proposed types of osteoporosis, suggesting considerable overlap between them. Secondary hyperparathyroidism does not appear to be a usual feature of osteoporotic women with hip fracture up to age 75 years. Our hormonal findings are more in keeping with marked oestrogen deficiency, suggesting that loss of ovarian function is a major determinant of the osteoporosis in these women.
Human biliary β‐glucuronidase: correlation of its activity with deconjugation of bilirubin in the bile
Authors: HO K.‐J. , HSU S.‐C. , CHEN J.‐S. , HO L.‐H. C.
Published: March 2008

Abstract Total and conjugated bilirubin contents of gallbladder and hepatic biles before and after 24‐h incubation at 37°C and β‐glucuronidase activity of hepatic biles were determined in forty‐eight patients divided equally into four groups: no stones or control (C), cholesterol stones (CS), black pigment stones (black PS), and brown pigment stones (brown PS). The percent conjugation of bilirubin is lower in gallbladder biles and hepatic biles after incubation, particularly in black PS and brown PS, when compared with hepatic biles before incubation. Mean endogenous β‐glucuronidase activities at pH 5·2 were 12·0, 15·5, 44·5 and 147·7 nmol min‐1 ml‐1 for C, CS, black PS, and Brown PS, respectively, which correlated well with the degree of deconjugation of bilirubin in gallbladder and hepatic biles and with the rate of deconjugation of hepatic bile incubated at 37°C. Only four biles in brown PS exhibited bacterial enzyme activity. We concluded that though bacterial β‐glucuronidase might be responsible for deconjugation of bilirubin in some patients in brown PS, endogenous biliary β‐glucuronidase could play a key role in the pathogenesis of pigment cholelithiasis.
Effects of Legionella pneumophila sonicate on human neutrophil granulocyte and monocyte chemotaxis
Authors: RECHNITZER C. , KHARAZMI A. , NIELSEN H.
Published: March 2008

Abstract The interaction of L. pneumophila serogroup 1 sonic extract with human polymorphonuclear neutrophils and monocytes was studied in an in vitro chemotaxis assay. The sonicate showed heat‐stable chemotactic activity towards neutrophils and monocytes. It also exhibited cytotoxicity for neutrophils but not for monocytes. Incubation and pretreatment with the sonicate at apparently non‐toxic concentration resulted in inhibition of the chemotactic response of neutrophils to various chemoattractants while monocyte chemotaxis was unaffected. The inhibitory activity was reduced to one half by heat treatment of the sonicate. High endotoxic activity was demonstrated in both heated and non‐heated extract. Only two antigens (nos 1 and 61) were identified in the sonicate exposed to 121°C for 1 h. It is therefore suggested that the lipopolysaccharide (no. 61) of L. pneumophila could contribute to the chemotactic activity. The adverse effects exerted by L. pneumophila on neutrophils may be one of the mechanisms by which Legionella bacteria resist the normal phagocytic host defences.
Hepatic regeneration and metabolism after partial hepatectomy in diabetic rats: effects of insulin therapy
Authors: JOHNSTON D. G. , JOHNSON G. A. , ALBERTI K. G. M. M. , MILLWARD‐SADLER G. H. , MITCHELL J. , WRIGHT R.
Published: March 2008

Abstract The effect of insulin deficiency on liver regeneration has been assessed in untreated v. insulin‐treated streptozotocin (65 mg kg‐1) diabetic rats, 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased from 12 to 48 h after partial hepatectomy and insulin treatment caused a further minor increase at 24 h. [6‐3H]Thymidine uptake in untreated rats peaked at 24 h (12·5 ± 3·4% of total cells labelled). Insulin therapy produced a delayed 168% rise in uptake at 48 h. Insulin deficiency alone in sham‐operated animals caused a 33% decrease in hepatic [ATP], while [ADP] rose by 43% and [AMP] by 86% at 12 h. Partial hepatectomy produced only minor further abnormalities in untreated animals. Insulin therapy increased hepatic [ATP] and decreased [ADP] and [AMP] 12 h after partial hepatectomy, but [ATP] remained decreased (15%) and [ADP] and [AMP] increased (45% and 73% respectively) compared with insulin‐treated sham‐operated controls. Metabolite changes observed after partial hepatectomy in untreated animals, including a decrease in hepatic [glycogen] and increases in [triglyceride] and the ratios of [lactate]:[pyruvate] and [3‐hydroxybutyrate]:[acetoacetate], were partially reversed by insulin treatment. Insulin deficiency thus impairs regeneration after partial hepatectomy and magnifies the decline in hepatic intracellular energy state and the metabolite changes associated with liver regrowth.
Ciclosporin and prednisone v. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study
Authors: KAHALY G. , SCHREZENMEIR J. , KRAUSE U. , SCHWEIKERT B. , MEUER S. , MULLER W. , DENNERAUM R. , BEYER J.
Published: March 2008

Abstract Forty patients with Graves' ophthalmopathy stages III–V were divided into two groups in a random manner according to their year of birth. Group I received prednisone in decreasing dosage. Group II received prednisone at a comparable dosage and ciclosporin. Steroids were discontinued after 10 weeks in the two groups. In the patients of group II, ciclosporin was continued over 12 months. The therapeutic effect was assessed by an activity score based on subjective and objective symptoms (computerized tomography and sonography of the orbit, Hertel values, clinical findings). All signs of endocrine ophthalmopathy improved significantly in both groups (P less than 0·01 in group I; P less than 0·001 in group II). The improvement was significantly greater in group II (P less than 0·05) according to the predefined score. After corticosteroids were discontinued, inflammatory signs recurred in nine patients in group I and in one of group II. During the observation period of 12 months, relapses occurred in eight out of twenty patients in group I and in only one out of twenty in group II. Muscle thickness decreased in nine patients in group II, 6 months after beginning therapy. At this time, the results were not influenced in any of the twenty patients in group I. Microsomal antibodies decreased significantly (P less than 0·001) in the ciclosporin group, whereas no change was seen in the other group. Renal values rose within the normal range in group II. In this group, an infection with Klebsiella pneumoniae occurred in one patient after 4 months of therapy. A rebound phenomenon after stopping ciclosporin has not yet been observed. Thus the drug ciclosporin proved to be effective both in terms of improvement of the acute effect as well in relapse prophylaxis of Graves' ophthalmopathy.
Creatine kinase and creatine kinase B‐subunit in stable and unstable angina pectoris
Authors: THYGESEN K. , HØRDER M. , KRØLL L. , PETERSEN P. HYLTOFT , HAGHFELT T.
Published: March 2008

Abstract. Repetitive ischaemic episodes may have a cumulative effect leading to irreversible myocardial cell damage with enzyme release. Using plasma creatine kinase (CK) and creatine kinase B‐subunit (CK‐B) concentrations this theory has been tested in forty‐eight patients admitted with acute chest pain, but without ECG signs of acute myocardial infarction (AMI). The patients were classified into four groups: Fourteen patients with non‐ischaemic heart disease (non‐IHD), seventeen with stable angina pectoris (SAP), ten with unstable angina pectoris (UAP), and seven patients who developd AMI during the study period. The enzyme variation in non‐IHD delineates the background noise, and the increased variability in AMI indicates the full scale of the enzyme signals in cases of irreversible cell damage. Patients with SAP have the same enzyme signal as the background noise in respect of both CK and CK‐B. However, in UAP the signal of CK‐B equals the background noise, whereas the CK signal is separated from the latter. The reason may be that the signal to noise ratio of CK‐B is poor and the analytical sensitivity low. Therefore, the behaviour of CK‐B in this study does not support the above theory although our findings for CK indicate that the consequence of repeated ischaemic attacks is slight enzyme release.
Comparison of plasma 3,4‐dihydroxyphenylethylene glycol (DHPG) and norepinephrine levels as indices of sympathetic activity in man
Authors: HOWES L. G. , HAWKSBY CATHERINE C. , REID J. L.
Published: March 2008

Abstract. Plasma levels of norepinephrine (NE) and the NE metabolite 3,4‐dihydroxyphenylethylene glycol (DHPG) were measured simultaneously following sympathetic activation induced by standing, cold pressor testing and bicycle exercise at progressively increasing workloads in normal volunteers. Free DHPG and NE levels both increased with sympathetic activation, but free NE levels were a more sensitive index of change. In addition, plasma free NE levels more closely reflected the fall in heart rate following exercise than free DHPG. In contrast to free levels, conjugated DHPG and NE levels did not change significantly after exercise. Supine resting free DHPG/ NE ratios were always greater than 2·0, but fell progressively with increasing sympathetic activation because of a proportionately greater rise in NE than DHPG. The simultaneous measurement of plasma free DHPG and NE does not offer advantages over free NE levels as an index of sympathetic activity in man, but may be of use in the diagnosis of pheochromocytoma and in studies of NE metabolism.
Serum isoamylase activities during infusions of glucose and amino acids
Authors: ŜKRHA JAN , ŜRÁMKOVÁ JARMILA , REHÁK FRANTIŜEK , PACOVSKÝ VLADIMÍR
Published: March 2008

Abstract. This investigation was undertaken to examine the influence of intravenously administered glucose and amino acids on serum isoamylase activities. Significantly decreased serum pancreatic isoamylase was observed during administration of 20% glucose and 8% amino acid solutions intravenously for 2 h as compared with physiological saline solution (P< 0·005). A significant negative correlation was found between mean values of pancreatic isoamylase (P‐isoamylase) in serum and glucose in plasma (r= 0·91, P<0·01). We propose that glucose may block the flux of pancreatic amylase across the basola‐teral membrane of the acinar cell into the blood stream. The mechanisms by which amino acids may decrease P‐isoamylase activity in serum are not quite clear. Amino acid stimulated release of pancreatic glucagon which has an inhibitory effect on amylase secretion is highly probable.
Ex vivo perfusion of plasma over protein A columns in human mammary adenocarcinoma. Evidence for a protein A leaking by radioimmunoassay
Authors: KINET J. P. , HUNT J. , FOIDART J. B. , DESOROUX A. , MAHIEU Ph.
Published: March 2008

Abstract. A solid phase radioimmunoassay (RIA) has been developed for detection of protein A in human serum or plasma using plates coated with specific goat anti‐protein A IgG and affinity‐purified anti‐protein A F (ab')2 fragments labelled with 125Iodine as a tracer. This RIA detected 25 ng of protein A per ml of serum or plasma. The ‘intra‐plate’ coefficient of variation (CV) was 4·26%, whereas the ‘inter‐plate’ CV was 5·86%, even in the presence of aggregated IgG. The presence of protein A was searched for by this RIA in samples collected during ex vivo perfusion of the plasma of patients suffering from a metastatic mammary adenocarcinoma either over columns of ‘native’ protein A (seven patients; group A) or over columns of protein A in which the Fc‐binding capacity was destroyed (five patients; group B). A protein A leaking occurred with the same incidence (about 20% of the sessions) in both groups. However, major acute side effects (hypotension, chills, mild fever, etc.) and necrolytic responses were seen only in some patients from group A. In these cases, the incidence of side effects, but not of tumoricidal responses, increased with the protein A serum concentrations reached 1 h after the end of the sessions (25–150 ng ml‐1). The data suggest that the therapeutic efficacy of ex vivo protein A immunoadsorption in breast cancer is related to the Fc‐binding capacity of the columns rather than to a leakage of ‘native’ protein A into the blood stream.
Relationship of angiotensin II, aldosterone, arginine vasopressin, adrenaline and noradrenaline in plasma, blood and extracellular volumes to blood pressure in chronic glomerulonephritis
Authors: DANIELSEN H. , PEDERSEN E. B. , CHRISTENSEN N. J.
Published: March 2008

Abstract. Blood volume, extracellular volume, blood pressure and the plasma levels of angiotensin II, aldosterone, adrenaline, noradrenaline and arginine vasopressin were determined in sixteen normotensive (group 1) and thirteen hypertensive patients (group 2) with chronic glomerulonephritis and in eleven normotensive control subjects (group 3). Blood volume and extracellular volume did not differ between the groups and no significant differences were found in any of the hormones measured when comparing group 1 or group 2 with group 3. In the hypertensives but not in the normotensives or control subjects, a highly significant positive correlation was found between diastolic blood pressure and blood volume (rho = 0·75, P < 0·01) and between diastolic blood pressure and extracellular volume (rho = 0·74, P < 0·01). Blood volume and extracellular volume correlated (P < 0·05) in each of the groups. In conclusion, although no expansion of either blood or extracellular volume was found in chronic glomerulonephritis, a positive volume‐pressure relationship could be demonstrated in hypertensive patients suggesting a role of volume factors in the pathogenesis in early stage chronic glomerulonephritis. The study does not give support to a major role of either angiotensin II, arginine vasopressin or catecholamines in the maintenance of non‐malignant hypertension in early stage chronic glomerulonephritis.
Effect of immunoglobulin preparations on the aggregation of human erythrocytes
Authors: MAEDA NOBUJI , SEKIYA MISUZU , KAMEDA KENJI , SHIGA TAKESHI
Published: March 2008

Abstract. The aggregation of human erythrocytes induced by four kinds of immunoglobulin preparations was examined by a low shear rheoscope. After removing anti‐A+ and anti‐B+ activities contaminated in all preparations by incubating with erythrocytes of different blood groups, the facilitating effect on the rouleau formation of erythrocytes was compared: (i) The effect of polyethyleneglycol‐treated preparation was the same in A+‐, B+‐, AB+‐ and O+‐erythrocytes. (ii) Sulfonation did not affect the velocity of rouleau formation. (iii) Some of pepsin‐treated preparations showed the strongest facilitation for A+‐, B+‐ and AB+‐erythrocytes, but the facilitation was much weaker for O+‐erythrocytes. The others showed the weak facilitation for all types of erythrocytes (especially O+‐erythrocytes). (iv) Plasmin treatment markedly decreased the velocity of rouleau formation of AB+‐ and O+‐erythrocytes, but was not of A+‐ and B+‐erythrocytes.
Effect of prostacyclin on renal kallikrein release in man
Authors: PIERUCCI A. , SIMONETTI B. M. , CIABATTONI G. , TAGGI F. , MORABITO S. , VASTANO S. , PUGLIESE F.
Published: March 2008

Abstract. The aim of this research was to study exogenous prostacyclin effect on urinary kallikrein excretion (UKK) in man, to define whether prostacyclin‐induced renin release and/or endogenously released cyclooxygenase products were responsible for prostacyclin‐induced enhancement of UKK, to determine furosemide effect on UKK. Prostacyclin was infused in eight healthy men and repeated after propranolol and indomethacin treatment. Prostacyclin caused a dose‐dependent increase of UKK. Pretreatment with propranolol and indomethacin did not affect prostacyclin‐induced enhancement of UKK, although it reduced absolute values of plasma renin activity. Furosemide increased UKK and simultaneously urinary 6‐keto‐prostaglandin F1α. We conclude that prostacyclin induces an increase in UKK in a dose‐dependent manner; furosemide‐induced renal prostacyclin synthesis is temporally related to enhancement of UKK; partial dissociation of UKK from plasma renin activity under propranolol and indomethacin treatment and in response to furosemide might suggest a direct effect of prostacyclin on UKK.
Altered functions of peripheral blood monocytes in homosexual males and intravenous drug users with persistent generalized lymphadenopathy
Authors: ROUX‐LOMBARD PASCALE , ALADJEM D. , BALAVOINE J.‐F. , CHOFFLON M. , DESPONT J.‐P. , HIRSCHEL B. , JEANNET M. , KAPANCI Y. , LANG R. , TOCCANIER M.‐F. , VOINIER B. , WILHELM A. , DAYER J.‐M. , CRUCHAUD A.
Published: March 2008

Abstract. Persistent generalized lymphadenopathy (PGL) is observed predominantly in subjects at risk of developing AIDS. Twenty‐seven individuals belonging to such groups: twelve homosexual males and fifteen intravenous drug users, were investigated for immunological abnormalities with particular attention to monocyte functions. They were compared with five AIDS patients. Twenty out of twenty‐two individuals had anti‐LAV/HTLV‐III antibodies and most had abnormalities characteristic of AIDS: polyclonal hypergammaglobulinemia, decreased cell‐mediated immunity, inverted T‐cell helper/suppressor ratio and histological alterations of lymph nodes. As for peripheral blood monocyte functions, phagocytic capacity and production of O2‐ were normal and bactericidal capacity was decreased. Monocytes cultured in the presence of concanavalin A produced less PGE2 and more IL‐1/MCF than normal monocytes. Similar abnormalities were found using monocytes from AIDS patients. These data suggest that (i) monocytes from patients with PGL have functional alterations that may be either intrinsic or secondary to lymphocyte dysfunction(s); (ii) these alterations do not account for the decreased capacity of lymphocytes to respond to mitogens but (iii) may explain the uncontrolled activation of B cells.
Differentiation of bone marrow cells from myelodysplastic patients in the presence of 1,25 dihydroxyvitamin D3 or 13‐cis retinoic acid
Authors: NAGLER A. , RICKLIS I. , GAZIT E. , TATARSKY I. , FABIAN I.
Published: March 2008

Abstract. The separate effects of vitamin D3 (1,25(OH)2D3) and 13‐cis retinoic acid on the differentiation in liquid culture of marrow cells from seven patients with myelodysplastic syndrome (MDS) were studied. Following incubation with 1,25(OH)2D3), an increasing number of myeloid cells acquired the morphological appearance of mature monocyte‐macrophages and reacted positively to fluoride‐sensitive naphthyl acetate esterase and specifically bound My4 monoclonal antibody (McAb). Incubation of bone marrow cells with 13‐cis retinoic acid enhanced the number of cells with the morphological appearance of metamyelocytes and mature granulocytes as well as those that reacted positively with AS‐D naphthol chloroacetate esterase. The results suggest that the differentiation pattern of myeloid precursor cells from MDS patients can be modulated by 1,25(OH)2D3 and 13‐cis retinoic acid.
Interactions of stress hormones on lipid and carbohydrate metabolism in man with partial insulin deficiency
Authors: PERNET A. , JOHNSTON D.G. , HAMMOND V. , ØRSKOV H. , ALBERTI K.G.M.M.
Published: March 2008

Abstract. The metabolic responses to 4‐h infusions of adrenaline (3 μg kg‐1 h‐1) and cortisol (10 mg m‐2 h‐1 for 2 h followed by 5 mg m‐2 h‐1 for 2 h), separately and in combination, have been studied in six healthy subjects with concurrent somatostatin infusion (250 μg h‐1). A combined infusion of adrenaline, cortisol, glucagon (180 ng kg‐1 h‐1) and somatostatin has also been studied. Somatostatin plus adrenaline and somatostatin plus cortisol resulted in hyperglycaemia (at 240 min, somatostatin plus adrenaline 11·4 ± 0·4 mmol l‐1, P < 0·001; somatostatin plus cortisol 6·7 ± 0·3 mmol l‐1, P < 0·05; somatostatin alone 4·9 ± 0·4 mmol l‐1). No synergistic effect on blood glucose was seen with adrenaline and cortisol together. When glucagon was added, blood glucose rose more rapidly than without glucagon (9·3 ± 0·4 mmol l‐1v. 7·2 ± 0·5 mmol l‐1 at 45 min, P < 0·001), but plateau values were similar. Plasma NEFA levels were raised by somatostatin plus adrenaline (0·55 ± 0·04–1·82 ± 0·11 mmol l‐1 at 60 min). Somatostatin plus cortisol had no more effect on plasma NEFA than somatostatin alone. During the combined infusion of somatostatin plus adrenaline plus cortisol, a synergistic effect on plasma NEFA was observed (2·30 ± 0·11 mmol l‐1 at 60 min, P < 0·01 v. somatostatin plus adrenaline). This occurred despite a small escape of insulin secretion. The lipolytic actions of adrenaline are potentiated by elevated circulating cortisol levels in insulin‐deficient man. Glucagon does not modify this response, but accelerates the development of hyperglycaemia.
Antipyrine clearance and metabolite formation: the influence of liver volume and smoking
Authors: SPOELSTRA P. , TEUNISSEN M.W.E. , JANSSENS A.R. , WEEDA B. , DUIJN W. VAN , KOCH C.W. , BREIMER D.D.
Published: March 2008

Abstract. The influence of liver volume and cigarette smoking on antipyrine clearance and metabolite formation was studied in seventeen volunteers (eight smokers, nine non‐smokers). Inter‐test coefficient of variation of liver volume (as determined by ultrasound) was 6·3%. The mean antipyrine clearance was 49·3±18·3 ml min‐1 and when normalized for liver volume 36·1±10·1 ml min‐1 l‐1. The antipyrine clearance per unit volume of liver was significantly higher in smokers (43·0±10·5 ml min‐1 l‐1), than in non‐smokers (30·0α4·6 ml min‐1 l‐1) (P < 0·01). No significant difference was found between the two groups as to the excreted amounts of 4‐hydroxyantipyrine (OHA), norantipyrine (NORA), and 3‐hydroxymethylantipyrine (HMA). Normalized for liver volume the mean clearances for production (Clm) of these metabolites were significantly higher in the group of smokers than in the group of non‐smokers. The greatest change was observed for OHA formation. However, analysis of variance showed that the differences in the percentages of change of the mean Clm of these metabolites in the two groups are not significant.
Adrenaline infusion evokes increased thromboxane B2 production by platelets in healthy men: the effect of beta‐adrenoceptor blockade
Authors: LAUSTIOLA K. , KAUKINEN S. , SEPPÄLÄ E. , JOKELA T. , VAPAATALO H.
Published: March 2008

Abstract. The effects of direct adrenergic stimulation, achieved by 60‐min adrenaline infusion (0·1–0·2 μg kg‐1 min‐1), on thromboxane B2 (TxB2) production by platelets in whole blood ex vivo and on ADP‐induced platelet aggregation were studied in seven healthy male volunteers. The effects of two beta‐adrenergic blocking agents, pindolol and practolol, on the adrenaline‐induced changes were furthermore analyzed. Adrenaline administration resulted in an about ten‐fold elevation in plasma adrenaline, and an about threefold increase in TxB2 production by platelets at 30 min of infusion. The increased TxB2 production persisted throughout the entire adrenaline infusion, and up to 30 min of postinfusion period (recovery). Pindolol blunted markedly the effects of adrenaline on platelet TxB2 production, whereas practolol seemed to have only a weak effect. The sensitivity of platelets to ADP‐induced aggregation did not change during the 60 min of adrenaline infusion. However, at 60 min of recovery the platelets showed a significantly increased sensitivity to ADP. Correspondingly, pindolol treatment did not affect platelet sensitivity during the infusion period, but at 60 min of recovery it had caused a significantly decreased sensitivity of platelets to ADP‐stimulation. Plasma‐free fatty acids increased markedly during the adrenaline infusion. This increase was totally blocked by pindolol, but only partly by practolol. The present results demonstrate that adrenaline, at plasma levels seen for example, in complicated myocardial infarction, stimulates platelet TxB2 production and increases the sensitivity of platelets to ADP after the infusion. Pindolol, but not practolol, inhibits these adrenaline‐induced changes in platelet behaviour.
Angiogenic factor from human term placenta. Purification and partial characterization
Authors: BURGOS H.
Published: March 2008

Abstract. Angiogenic and growth promoting factors from human amniochorion and placenta at term were released mostly as high molecular weight components (factor‐carrier protein higher than 100 000 molecular weight) by extraction with 10% propan‐2‐ol, distilled water, and 50 mmol l‐1 Tris/HCl pH 7·2 containing 50–150 mmol l‐1 NaCl. They were isolated from the extracting media by adsorption on DEAE‐Sepharose CL6B, a chromatographic agar based anion exchanger, and fractionated by chromatographic permeation on dextran gel Sephacryl S‐300 yielding a low molecular weight component (between 400 and 1100 mol wt) with angiogenic and mitogenic capacities. Chromatographic behaviour and physico‐chemical characteristics suggest it may be a peptide.

Presence of an angiogenic and mitogenic factor in human amniochorion may explain the profuse neovascular formation and increased rate of healing obtained in the treatment of chronic ulcers by application of amniochorionic membranes as biological dressings. Preparation of purified angiogenic factor, on the other hand, opens the possibility of its wider application in the treatment of burns, open wounds and denuded areas in general.
Heparin half‐life and sensitivity in normal subjects and in patients affected by deep vein thrombosis
Authors: BENCHEKROUN S. , EYCHENNE B. , MERICQ O. , COLOMBANI A. , DOUSTE‐BLAZY Ph. , BARRET A. , SIE P. , BONEU B.
Published: March 2008

Abstract. In some patients affected with deep vein thrombosis (DVT) it is necessary to administer large doses of heparin to achieve proper anticoagulation. To investigate the clinical relevance of this phenomenon, we studied the heparin half‐life and the heparin sensitivity after a bolus IV injection of 60 i.u. kg‐1 in seven healthy volunteers and eight DVT patients investigated on day 1 or 2 and again between day 10 and 20 of the heparin therapy. The heparin half‐life, the in vitro and ex vivo heparin sensitivity, were comparable in the healthy volunteers and in the patients at both times of investigation. However, there were large interindividual variations in the controls and in the patients, not correlated to the levels of any coagulation factors. Thus, the heparin hyperconsumption phenomenon occasionally observed in a given patient reflected individual characteristics and was no value in the diagnosis of DVT.
Antagonist capacities of nifedipine, captopril, phenoxybenzamine, prostacyclin and indomethacin on cyclosporin A induced impairment of rat renal function
Authors: DIEPERINK H. , LEYSSAC P. P. , STARKLINT H. , JØRGENSEN K. A. , KEMP E.
Published: March 2008

Abstract.Experimental evidence indicates that cyclosporin A (CyA) nephrotoxicity is due to renal arteriolar constriction, reducing renal blood flow, glomerular filtration rate (GFR), and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle. The proximal tubular fractional reabsorption (PFR) is increased. Therefore, the impact on renal function of vasodilating agents was studied in rats given CyA. Conscious catheterized rats and clearance techniques were used. In acute experiments a preexisting CyA‐nephrotoxicity was resistant to infusion of phenoxybenzamine, prostacyclin, captopril, nifedipine and indomethacin. Concomitant treatment with captopril and CyA did not improve renal function, while concomitant treatment with CyA and nifedipine improved GFR to 1·13±0·34 ml min‐1g‐1kidney weight (gKW) (n=19,P<0·05), as compared to CyA and placebo treated controls (n=12, 0·83±0·32 ml min‐1g‐1KW). Nifedipine also reduced FPR (88·6±5·1% vs. 83·2±5·6%.P<0·01), and increased lithium clearance from 99±54 to 184±64 μl min‐1g‐1KW (P<0·001). The results are further evidence that CyA nephrotoxicity includes renal vasoconstriction, and indicates that calcium entry blockade is nephroprotective in the case of CyA toxicity.
Bile acids in peroxisomal disorders
Authors: ELDERE J. R. VAN , PARMENTIER G. G. , EYSSEN H. J. , WANDERS R. J. , SCHUTGENS R. B. , VAMECQ J. , HOOF F. VAN , POLL‐THE B.‐T. , SAUDUBRAY J. M.
Published: March 2008

Abstract. We examined serum bile acids in patients with different peroxisomal disorders. Patients with Zellweger syndrome (n= 23), infantile form of Refsum disease (n= 6) and neonatal adrenoleukodystrophy (n= 4) consistently had increased levels of bile acid precursors. Patients with X‐linked adrenoleukodystrophy, (n= 5) classical Refsum disease (n= 3), hyperpipecolic acidaemia (n= 4) and rhizomelic chondrodysplasia punctata (n= 9) did not have increased bile acid precursor levels. Total serum bile acids (41 μg ml‐1) and the percentage of bile acid precursors (80%) were highest in typical Zellweger patients who died young. Long‐living Zellweger patients, neonatal adrenoleukodystrophy patients and infantile Refsum disease patients had, on average, less cholestasis and a lower percentage of bile acid precursors. We also observed that total serum bile acids and the percentage of bile acid precursors decreased with age in longliving Zellweger patients. Screening for bile acid precursors, combined with very long chain fatty acids analysis is, in our experience, an easy and reliable firstline approach to the detection of peroxisomal disorders.
Bezafibrate therapy and biliary lipids: effects of short‐term and long‐term treatment in patients with various forms of hyperlipoproteinaemia
Authors: ERIKSSON M. , ANGELIN B.
Published: March 2008

Abstract. Several hypolipidaemic drugs increase biliary cholesterol saturation and induce the formation of cholesterol gallstones. In order to determine the influence of bezafibrate, a clofibrate analogue with hypolipidaemic properties, on bile lipid composition, we studied twelve patients with various forms of hyperlipoproteinaemia (six type IIA, three type IIB and three type IV hyperlipoproteinaemia; six had a genetic diagnosis of familial hypercholesterolaemia and five familial combined hyperlipidaemia). After 4 weeks of therapy, when serum lipids were significantly reduced, the relative proportion of cholesterol in stimulated fasting duodenal bile was increased by 28% (P < 0·001). Phospholipids were concomitantly increased and bile acids decreased, resulting in an increase in biliary cholesterol saturation from 89 ± 4% to 105 ± 8% (SEM, P < 0·02). The changes induced were similar in patients with familial hypercholesterolaemia and familial combined hyperlipidaemia. After 1 year of continued treatment, serum lipid responses were unaltered. The changes in biliary lipids were also persistent as the relative cholesterol concentration remained increased by 33% (P < 0·01) and cholesterol saturation averaged 106 ± 8% (P<0·02). Although the effect on bile cholesterol appeared to be transient in some patients, the results of the present study suggest that the risk of cholesterol gallstone formation may be increased during bezafibrate therapy.
Periodic courses of human 1–34 parathyroid peptide alternating with calcitriol paradoxically reduce bone remodelling in spinal osteoporosis
Authors: REEVE J. , ARLOT MONIQUE , PRICE T. R. , EDOUARD C. , HESP R. , HULME PATRICIA , ASHBY J. P. , ZANELLI JOAN M. , GREEN J. R. , TELLEZ M. , KATZ D. , SPINKS T. J. , MEUNIER P. J.
Published: March 2008

Abstract. In an attempt to achieve an anabolic response in both axial and peripheral bone, we treated twelve patients with osteoporosis using human 1–34 parathyroid peptide given discontinuously. The peptide was given as seven daily subcutaneous injections followed by 21 days' treatment with 0·25 mg calcitriol orally. This regime was repeated cyclically for at least sixteen cycles, of which the first four were at a lower dose of hPTH 1–34 than used subsequently. The results of treatment were monitored by kinetic, densitometric, histomorphometric and biochemical studies performed before and during treatment. Two patients developed hPTH 1–34 binding in their plasma during treatment: this was presumed to be due to the development of antibodies. The remainder, instead of increasing their indices of bone turnover as judged by iliac bone histomorphometry, were found to have consistent reductions in trabecular resorption surfaces. The other indices of bone formation and resorption measured showed no change or comparable reductions. The small increases seen in total body calcium were consistent with ‘in‐filling’ of deleted basic multicellular units (BMUs). Because there is no evidence that calcitriol alone causes comparable reductions in activation of bone remodelling in osteoporosis, interruption of treatment with hPTH 1–34 after 7 days may have led to a failure of the activation mechanism to proceed to the resorption stage, with a consequent overall reduction in remodelling activity. This type of treatment regime, with its calcitonin‐like effect, might be effective in reducing net bone loss due to imbalance between bone formation and resorption at the BMU level, particularly in patients with increased numbers of BMUs (‘high turnover’ osteoporosis). However, it proved a less promising regime than daily injections of PTH 1–34 or sodium fluoride plus calcium therapy for the substantial reversal of axial trabecular bone loss in patients able to respond to these therapies.
Neutrophils are hyperpolarized after exudation and show an increased depolarization response to formyl‐peptide but not to phorbol myristate acetate
Authors: ZIMMERLI W. , SELIGMANN B. E. , GALLIN J. I.
Published: March 2008

Abstract. The migration of polymorphonuclear leucocytes (PMN) to extravascular sites and the interaction with chemotactic substances at such locations is called exudation. Since stimulation of PMN in vitro modifies the characteristics of PMN, we asked the question whether similar modifications take place during in‐vivo exudation. We found that resting guinea‐pig peritoneal exudate PMN were hyperpolarized in comparison to blood PMN of the same species. Guinea‐pig and human exudate PMN responded to lower N‐formylmethionylleucylphenylalanine (fmet‐leu‐phe) concentrations than blood PMN and exhibited a larger membrane depolarization. Furthermore, experiments with the fluorescence‐activated cell sorter revealed increased forward light scatter from resting exudate PMN compared to blood PMN. Experiments with the fluorescence‐activated cell sorter using the fluoresceinated ligand fmet‐leu‐phe‐lysin‐fluorescein (fmet‐leu‐phe‐lys‐F) indicated that the priming of exudate PMN was associated with increased fmet‐leu‐phe‐lys‐F binding on the individual cells. In contrast, phorbol myristate acetate (PMA) did not induce an increased membrane depolarization response in human and guinea‐pig exudate PMN. With this stimulus, the only sign of priming was the shorter activation time in exudate PMN compared to blood PMN. Thus, in‐vivo exudation modifies the characteristics of resting and stimulated PMN. The priming is different for different stimuli. Increased responsiveness to fmet‐leu‐phe may be due to fmet‐leu‐phe receptor upregulation. The distinct characteristics of exudate PMN that we describe may allow definition of clinical situations in which PMN are primed in vivo.
Renal haemodynamics and sodium handling after hyperoncotic albumin infusion in sodium‐restricted normal man
Authors: BOER W. H. , KOOMANS H. A. , MEES E. J. DORHOUT
Published: March 2008

Abstract. The effect of plasma volume expansion with hyperoncotic albumin (HA) on renal haemodynamics and segmental tubular sodium (Na) handling was studied in eight water‐loaded normal men. Clearance studies were performed before, during and after a 60‐min infusion of 300 ml 20% HA. Sodium intake was restricted (20 mmol day‐1) to mimic clinical conditions of relative hypovolaemia in which HA is often applied. Plasma volume rose by 740±160 ml after infusion and colloid oncotic pressure (COP) by 3·6±1·3 mm Hg. No natriuresis was induced. In fact, Na output fell from 43±29 to 28±25 μmol min‐1 during infusion, returning to 41±36 μmol min‐1 afterwards. Corresponding clearances of inulin were 121±19, 110±19 and 117±21 ml min‐1 and of p‐aminohippurate (CPAH) 602±87, 637±100 and 751±148 ml min‐1. Fractional reabsorption of sodium in the proximal tubules (FPRNa), assessed from maximal free‐water and lithium clearance, rose consistently during infusion but diverging patterns (further rise, no change or fall) were seen afterwards. Fractional distal reabsorption remained unchanged both during and after HA infusion. Changes in plasma volume and CPAH in the post‐infusion period were correlated. These results indicate that, despite considerable plasma volume expansion, HA infusion does not enhance Na excretion in Na‐restricted subjects. This is mainly due to elevation of plasma COP, which reduces glomerular filtration and enhances proximal reabsorption. The biphasic response in FPRNa, an initial increase during infusion that abates afterwards, can be explained from a secondary rise in peritubular capillary hydrostatic pressure related to an increased renal perfusion.
Cysteinyl leukotrienes as mediators of staphylococcal enterotoxin B in the monkey
Authors: SCHEUBER P. H. , DENZLINGER C. , WILKER D. , BECK G. , KEPPLER D. , HAMMER D. K.
Published: March 2008

Abstract. The role of cysteinyl leukotrienes (LTs) in the action of staphylococcal enterotoxin B (SEB) was investigated in unsensitized monkeys using inhibitors of prostanoid synthesis and LT action and by measuring generation of LT in vivo. LY 171883, a selective LTD4/LTE4 receptor antagonist, proved highly efficient in inhibiting immediate‐type hypersensitivity reactions in the skin and protecting against the emetic response provoked by SEB in a concentration‐dependent manner. Inhibition of prostanoid formation by pretreatment of monkeys with indomethacin or aspirin did not influence SEB responses. Based on chromatographic and radioimmunologic analysis, the generation of endogenous cysteinyl LTs was demonstrated in vivo. The concentration of LTE4, the major biliary cysteinyl LT detected, increased ten‐fold and a novel cysteinyl LT metabolite in urine indicated strongly enhanced LT generation upon challenge with SEB. Cysteinyl LTs are important mediators in the patho‐physiology of SEB‐induced enteric intoxication. Therefore, cysteinyl LT antagonists may be of therapeutic value in the treatment of this intestinal disorder.
Serum amyloid A protein compared with C‐reactive protein, alpha 1‐antichymotrypsin and alpha 1‐acid glycoprotein as a monitor of inflammatory bowel disease
Authors: CHAMBERS R. E. , STROSS P. , BARRY R. E. , WHICHER J. T.
Published: March 2008

Abstract. The serum concentrations of serum amyloid A protein (SAA), C‐reactive protein (CRP), alpha 1‐antichymotrypsin (alpha 1‐ACT) and alpha 1‐acid glycoprotein (alpha 1‐AGP) have been measured in eighty‐six patients with Crohn's disease, twenty‐five patients with ulcerative colitis and twenty‐two patients with the irritable bowel syndrome. In the Crohn's and ulcerative colitis group significant increases in concentration were observed in all four proteins, which parallelled disease severity as defined by other conventional laboratory parameters formulated into a simple activity index. In the irritable bowel group no significant changes were seen. Serum amyloid A and CRP concentrations were significantly lower in ulcerative colitis than in Crohn's disease when mild, but did not differ significantly when severe. Serum amyloid A correlated well with CRP (r= 0·83) and alpha 1‐ACT (r= 0·80), but less well with alpha 1‐AGP (r= 0·65). Serum amyloid A was the most sensitive protein (77%) but had the lowest specificity (74%). C‐reactive protein was less sensitive (58%) than SAA but had greater specificity (100%). Alpha 1‐ACT had a sensitivity and specificity similar to CRP and, therefore, provided little or no additional information. Alpha 1‐AGP, although also 100% specific, had the lowest sensitivity (34%) and, therefore, is probably the least useful acute phase monitor of inflammatory bowel disease. The role, and associated problems, of SAA measurements are discussed.