bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of potassium supplementation on insulin binding and insulin action in human obesity: protein‐modified fast and refeeding
Authors: NORBIATO GUIDO , BEVILACQUA MAURIZIO , MERONI RACHELE , RAGGI UMBERTO , DAGANI REGINA , SCORZA DANIELE , FRIGENI GIULIO , VAGO TARCISIO
Published: March 2008

Abstract. To investigate the role of potassium deficiency in the development of glucose intolerance during caloric deprivation, potassium balance was maintained within normality with oral potassium supplementation in a group of obese subjects who underwent protein‐modified fast and the results of the study of carbohydrate metabolism (oral glucose test, insulin receptors on monocytes and peripheral glucose utilization as assessed by euglycaemic clamp) were compared with those obtained in a group of obese subjects admitted to protein‐modified fast without potassium supplementation.

Caloric deprivation without oral potassium supplementation was followed by a negative potassium balance and a decrease of serum potassium levels; a decrease of the peripheral levels of insulin along with an increase in insulin receptors and a striking reduction of peripheral glucose utilization were also observed. The maintenance of normal potassium balance and normal serum potassium levels with oral potassium‐chloride supplementation was associated with higher peripheral levels of insulin (P < 0·01) and improvement of peripheral glucose utilization (P < 0·01) whereas the binding of insulin to monocytes was unchanged. The data suggest that potassium depletion during protein‐modified fast causes a decrease of the peripheral levels of insulin and a resistance to insulin action at the postreceptors sites which is reversed by potassium supply.
Effect of ovulation on haem metabolism in rabbits
Authors: LINDAHL JÜRGEN , WERNER BJÖRN , LERNER RICHARD
Published: March 2008

Abstract. To investigate the origin of the cyclic changes in the rate of endogenous carbon‐monoxide production (n̊CO) during the menstrual cycle, haem turnover was determined before and after chorion gonadotropic hormone‐induced ovulation in six female rabbits.

14C‐labelled delta‐aminolevulinic acid and glycine were administered and the excretion rate of 14CO (Å14CO) was measured for determination of hepatic and bone‐marrow haem turnover, respectively. Carbonmonoxide production (n̊CO) was measured to estimate total haem turnover.

After ovulation Å14CO was increased significantly the first 2 h of the early labelled peak after 14C‐ALA administration and was increased also at the first determination during the early peak after 14C‐glycine but statistically not significantly. The total excretion of labelled CO during the period of the early labelled peak was not increased with any of these precursors for haem synthesis. On the other hand n̊CO was increased 34% (P < 0·05) during the post‐ovulation period.

As the increase in ‘unassigned’ haem turnover was small and may be unaccompanied by a contemporary increase in bilirubin/CO production, it was concluded that the increase in n̊CO during the post‐ovulation period essentially depends on increased destruction of circulating red cells in the rabbit.
Effect of dipyrone, acetylsalicylic acid and acetaminophen on human neutrophil chemotaxis
Authors: MATZNER YAACOV , DREXLER RUTH , LEVY MICHA
Published: March 2008

Abstract. Dipyrone metabolites 4‐methylaminoantipyrine (MAA) and 4‐formylaminoantipyrine (FAA) as well as acetylsalicylic acid inhibited neutrophil migration toward zymosan‐activated serum. Inhibition was maximal (76·8 pL 19·0; 79·2 pL 12·5 and 80·0 pL 4·4%, respectively, P < 0·003) when suboptimal concentrations (0·3%) of the chemoattractant were used and could be demonstrated with drug concentrations comparable with plasma concentrations obtained in clinical use. Acetaminophen and other dipyrone metabolites 4‐aminoantipyrine (AA) and 4‐acetylaminoantipyrine (AAA) lacked chemotactic inhibitory potential. Only MAA and FAA inhibited mildly neutrophil random migration (18·1 pL 7·8 and 11·2 pL 3·4%, respectively). We suggest that blocking neutrophil movement plays a role in the anti‐inflammatory activity of dipyrone and acetylsalicylic acid, but their mechanism of inhibition remains obscure.
Vasoactive intestinal polypeptide stimulation of prolactin release and renin activity in normal man and patients with hyperprolactinaemia: effects of pretreatment with bromocriptine and dexamethazone
Authors: LIGHTMAN STAFFORD L. , UNWIN ROBERT J. , GRAHAM KENNETH , DIMALINE RODNEY , MCGARRICK GAIL
Published: March 2008

Abstract. Vasoactive intestinal polypeptide (VIP) was infused into normal volunteers and patients with hyperprolactinaemia. Heart rate increased from 62 pL 3 to 75 pL 3 beats min‐1 (P= 0·001) in controls and from 70 pL 2 to 78 pL 3 beats min‐1 (P= 0·001) in hyperprolactinaemics. Similarly, haematocrit increased from 38 pL 2 to 44 pL 1% (P= 0·001) and from 40 pL 1 to 43 pL 2% (P= 0·002) and plasma renin activity from 910 pL 59 to a peak of 3344 pL 282 pg ml‐1 h‐1 (P= 0·001) and from 1577 pL 671 to a peak of 4954 pL 1364 pg ml‐1 h‐1 (P= 0·001) in the two groups, respectively. Prolactin concentrations rose in the control group only, from 134 pL 11 to a peak of 377 pL 35 mU l‐1 (P= 0·001), whilst in the hyperprolactinaemics little change occurred from the pre‐infusion concentration of 3873 pL 2179 reaching a peak of 3998 pL 2347 mU l‐1 (P > 0·07).

In separate studies, the normal subjects were pretreated with either bromocriptine or dexamethazone. Dexamethazone did not alter any parameter of the response to VIP. Bromocriptine did not affect the heart rate, haematocrit or renin response to VIP but clearly inhibited the rise in prolactin which remained at unmeasurable concentrations throughout the infusion.
Three serum markers of collagen biosynthesis in Nigerians with cirrhosis and various infectious diseases
Authors: BOLARIN DEBAYO M. , SAVOLAINEN EEVA‐RIITTA , KIVIRIKKO KARI I.
Published: March 2008

Abstract. Serum immunoreactive prolyl hydroxylase protein, galactosylhydroxylysyl glucosyltransferase activity, and the aminoterminal propeptide of type III procollagen (S‐Pro(III)‐N‐P) were measured in twenty patients with cirrhosis and ninety with various infectious diseases, and the values were compared with those in sixty apparently healthy Nigerians. The means for all three markers were elevated significantly in the patients with cirrhosis (P < 0·001), acute viral hepatitis (P < 0·001), amoebic liver abscess (P < 0·001) and the early stages of Schistosoma mansoni infection (P < 0·001 for S‐Pro(III)‐N‐P, P < 0·005 for the two other markers). The mean S‐Pro(III)‐N‐P was also distinctly elevated during the early stages of Schistosoma haematobium infection (P < 0·01) and filariasis (P < 0·001), whereas none of the three markers was elevated during an acute attack of malaria. Significant correlations were found between the values for the three markers within the groups of patients with cirrhosis, amoebic liver abscess and schistosomiasis, the correlations for the pooled group of all patients being highly significant (P < 0·001). The data suggest that elevated hepatic collagen formation is found not only in cirrhosis but also in several infectious diseases. The three serum markers may be useful for showing the stages of active collagen formation in various liver diseases and for predicting the development of fibrosis in acute cases if the values remain elevated.
Effects on renal tubular protein reabsorption of the infusion of free haemoglobin
Authors: WHICHER J. T. , PARRY E. S.
Published: March 2008

Abstract. Hydroxy‐ethyl‐starch cryopreserved blood with a mean free haemoglobin content of 260 μmol/l (SD 57 μmol/l) was infused into five normal volunteers. The renal clearance of six proteins of differing molecular weight was measured together with an analysis of the qualitative changes in protein excretion during the infusion and over the following 48 h. Other aspects of renal tubular function were assessed by the measurement of urinary N‐acetyl‐β‐D‐glucosaminidase, phosphate and amino acids. Increased clearance of low molecular weight proteins and N‐acetyl‐β‐D‐glucosaminidase occurred during the 12 h following infusion. β2 microglobulin clearance × 103 creatinine clearance rose from a mean of 0·4 (SD 0·1) to a mean of 74·5 (SD 32·3) and N‐acetyl‐β‐D‐glucosaminidase from 54·2 units/mmol creatinine (SD 18·0) to 1525 units/mmol creatinine (SD 2318). Increased amounts of low molecular weight proteins were detected in the urine by crossed immunoelectrophoresis. Creatinine clearance remained unaltered. It is argued that these changes may be caused by the competitive inhibition of low molecular weight protein reabsorption in the renal tubule by filtered haemoglobin.
Renal glucose transport after kidney transplantation
Authors: SECCHI A. , HADJ‐AISSA A. , POZET N. , TOURAINE J. L. , POZZA G. , DUBERNARD J. M. , TRAEGER J.
Published: March 2008

Abstract. Tubular maximal transport of glucose (TmG), plasma glucose threshold (PGT) and fractional maximal tubular reabsorption (TmG/GFR) were measured in fourteen kidney‐grafted patients. Seven patients showed decreased PGT and normal or decreased TmG/GFR (type A or B renal glycosuria (RG)), whereas seven other patients showed normal values. No difference was found between the two groups with respect to parameters of renal function and to clinical parameters characterizing kidney transplantation. The only difference observed between the two groups was the rate of decrease of plasma creatinine levels during the 1st week after transplantation: it was faster in the group without renal glycosuria. No difference was seen between the two groups of patients with respect to the number of rejection episodes occurred over the first 12 months.
Differences in basal and stimulated cyclic AMP content in calvaria bones from normal mice and mice with an impaired lysosomal function (beige mice)
Authors: RANSJÖ M. , FREDHOLM B. B. , LERNER U. , GUSTAFSON G. T.
Published: March 2008

Abstract. Earlier we have shown that bone resorption is impaired in cultured calvaria from beige mice (an animal equivalent of the Chediak–Higashi syndrome in man). In the present study we have compared the concentrations of cyclic AMP and cyclic GMP in calvarial bones from beige mice with the nucleotide concentrations in bones from corresponding normal mice. In six independent experiments the basal concentrations of cyclic AMP was significantly (P < 0·01) higher in bones from beige mice (on an average 50% augmented). The ratio of cyclic AMP/cyclic GMP was 2·43 times higher (P < 0·01) in bones from beige mice. After stimulation with the phosphodiesterase inhibitor isobutylmethylxanthine and prostaglandin E2 no significant differences of cyclic AMP concentrations between beige and control mice could be registered. The response to adenosine was significantly higher (P < 0·005) in bones from beige mice (4·3 ± 0·4‐fold of basal cyclic AMP concentrations, mean ± SE) compared to control mice (1·9 ± 0·4‐fold of basal, mean ± SE). The increased basal concentration of cyclic AMP in calvaria from beige mice may be due to increased sensitivity to some agonists, such as adenosine, rather than simply being a function of cell mass.
Abnormality of adenylate cyclase regulation in human platelet membranes in renal insufficiency
Authors: JACOBSSON B. , RANSNÄS L. , NYBERG G. , BERGH C.‐H. , MAGNUSSON Y. , HJALMARSON Å.
Published: March 2008

Abstract. Adenylate cyclase in human platelets is under dual control of prostaglandins (PGI2 and PGE1) and catecholamines. The adenylate cyclase complex in membranes of platelets from ten patients with uraemia was investigated. The activation of the platelet cyclase by PGEi is increased in the uraemic state, Vmax 4436 ± 607 pmol cAMP mg‐1 15 min‐1. In the normal state Vmax is 2098 ± 309 pmol cAMP mg‐1 15 min‐1. The alpha2‐adrenergic receptor was assayed with 3H‐yohimbine binding. The density of receptors was equal in the uraemic (175 fmol mg‐1 membrane protein) and the normal (170 fmol mg‐1 membrane protein) states. Norepinephrine/3H‐yohimbine competition binding revealed that catecholamines were bound with normal affinity in platelets in uraemia. Yet the inhibition of adenylate cyclase through the alpha2–adrenergic receptor was diminished since Vmax values of adenylate cyclase with PGE1 and PGE2+ norepineprine did not significantly differ. In the normal state, norepinephrine significantly (P < 0·05) inhibited the PGE1 stimulated cyclase.

It is concluded that platelet adenylate cyclase in the uraemia has an increased capacity for activation which is the result of both a sensitized stimulatory mechanism (prostaglandin mediated) and a deficient inhibitory mechanism (catecholamine mediated). It is suggested that a defect exists in the inhibitory nucleotide binding protein (N1) which is the coupling unit between the adenylate cyclase catalytic subunit (C).
Abnormalities of in vitro responses to polyclonal activation of peripheral blood lymphocytes in patients with active sarcoïdosis
Authors: PASQUALI JEAN‐LOUIS , GODIN DOMINIQUE , URLACHER ARLETTE , PELLETIER ANTOINE , PAULI GABRIELLE , STORCK DANIEL
Published: March 2008

Abstract. A variety of immunological abnormalities have been described in patients with sarcoïdosis. At the blood level, both hypo and hyper immune responsiveness seem to coexist and were related to abnormal T cell and macrophage functions by using allogenic cocultures and/or lymphocyte fractionation. We tested several components of cell mediated responses with two in vitro models: (a) the pokeweed mitogen activation of B cells which is T cells and macrophage dependent; (b) the Epstein‐Barr virus (EBV) activation of B cells which is T cell‐ and macrophage‐indepen‐dent. We confirm previous data showing that PWM induced Ig Production of peripheral blood lymphocytes (PBL) of patients with sarcoïdosis is significantly reduced compared with normal PBL. However, this is associated with an increase of IgG, IgM synthesis of EBV‐infected PBL in these sixteen patients. Thus, there is no evidence for a complete B cell defect in sarcoïd PBL. Furthermore, by using limiting dilution analysis of antibody secreting cells, there is an increase of precursor B cells EBV infectable in PBL of sarcoïd patients but T cells are effective in reducing EBV‐induced B cell proliferation. Finally, these abnormalities are concomitant to the disease, disappear with it, and are apparently not correlated with the stage or the activity of sarcoïdosis.
Type IV collagen and laminin‐related antigens in human serum in alcoholic liver disease
Authors: NIEMELÄ ONNI , RISTELI LEILA , SOTANIEMI EERO A. , RISTELI JUHA
Published: March 2008

Abstract. The two major constituents of basement membranes are type IV collagen and laminin. Specific radioimmunoassays are described here for two structural domains of these proteins (7‐S collagen and the fragment PI, respectively) that allow the related antigens to be quantified in human serum. The serum 7‐S collagen antigen was uniform in size, whereas the laminin PI antigenicity was heterogeneous. These proteins were measured in sera from sixty‐three alcoholics, divided on the basis of liver histology into four groups: normal light microscopy, fatty liver, alcoholic cirrhosis with hepatitids and inactive cirrhosis. The group with cirrhosis and hepatitis had clearly elevated values in both assays, differing significantly from the others. A few pathological results were also seen in the other groups. The increases noted in 7‐S collagen concentration were larger than those in laminin PI. During follow‐up of a patient with cirrhosis and hepatitis the 7‐S collagen level in particular seemed to reflect the course of the disease. The elevated basement membrane protein concentrations in serum may be associated with the formation of real basement membranes in the perisinusoidal space, a process known as capillarization of the sinusoids which is found during the development of liver cirrhosis.
Active and acid‐activable inactive rennin during inhibition by indomethacin of prostaglandin synthesis in sodium‐replete man
Authors: LIJNEN P. , STAESSEN J. , FAGARD R. , GROESENEKEN D. , M'BUYAMBA‐KABANGU J. R. , GRAUWELS R. , AMERY A.
Published: March 2008

Abstract. The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid‐activable inactive renin was studied in nine healthy, sodium‐replete men, both at rest and exercise. These volunteers were investigated after pretreatment with placebo or indomethacin, 150 mg daily for 3 days.

Indomethacin induced a decrease in active (P= 0·004), total (P < 0·001) and inactive (P= 0·02) renin at rest recumbent and at rest, sitting. Inhibition of prostaglandins with indomethacin reduced (P < 0·001) active and total renin at each level of work load but not (P= 0·32) inactive renin. However the exercise‐induced stimulation (P < 0·05) of active and of total renin still occur during indomethacin.

Indomethacin reduced (P < 0·001) at rest, sitting and at maximal exercise the plasma concentrations of immunoreactive prostaglandins E2, prostaglandin F2α, and 13,14‐dihydro‐15‐keto‐prostaglandin Fα; the urinary excretion of immunoreactive prostaglandin E2 and F2α were also reduced.
Drug influences on rat hepatic macrophage enzyme production and release in vitro
Authors: TANNER A. R. , KEYHANI A. H. , WRIGHT R.
Published: March 2008

Abstract. Drug influences on hepatic macrophage enzyme release have been investigated using a rat model of macrophage recruitment and activation. N‐acetyl‐glucosaminidase (NAG), a lysosomal enzyme, and plasminogen activator (PA), a cytosolic enzyme, have been measured in both cell lysates and supernatants after 24 h in culture. 6‐mercaptopurine (6‐MP) and azathioprine significantly decreased (P < 0·03) the enhanced production of NAG by recruited macrophages following stimulation in vitro (total NAG activity, nmol substrate hydrolysed/μg cell protein; recruited macrophages exposed to endotoxin, no drug exposure 0·63 ± 0·08, azathioprine 0·44 ± 0·08, 6MP 0·36 ± 0·06). Prednisolone, azathioprine and 6MP significantly reduced (P < 0·05) the supernatant release of PA in response to endotoxin exposure in vitro by both cell types (supernatant PA values after 24 h in culture, recruited macrophages exposed to endotoxin, no drug 26·0 ± 2·9 units, prednisolone 18·5 ± 1·7 units, levamisole 27·3 ± 4·7 units, azathioprine 18·1 ± 2·3 units, 6MP 17·3 ± 1·5 units). The results from this study indicate that certain drugs used in human liver disease are able to modify the secretory activity of rat hepatic macrophages.
Regional and systemic effects of short‐term intense muscular work on plasma concentration and content of total and ionized calcium
Authors: LJUNGHALL S. , JOBORN H. , LUNDIN L. , RASTAD J. , WIDE L. , ÄKERSTRÖM G.
Published: March 2008

Abstract. Isokinetic work with one leg was carried out with maximal force for 2 min by five healthy subjects. The concentrations of plasma total calcium and of ionized calcium in the effluent from the leg increased by a mean of 13middot;6 ± 1middot;8% (SD) and 16middot;2 ± 2middot;0%, respectively. The corresponding rises in the resting arm were 7middot;7 ± 4middot;3% and 8middot;1 ± 3middot;0%. There was a close correlation (r= 0–86; P<0middot;001) between the degree of exercise‐induced acidosis and the rise in plasma ionized calcium. However, the calcium values normalized both in the leg and in the arm within 5 min after the exercise and were similar at the two measuring sites despite a lower pH in the leg sample.

During work there was a reduction of the plasma volume of 11middot;2 ± 6middot;0% in the regional (femoral) and 12middot;4 ± 4middot;2% in the systemic (antecubital) sample (P<0middot;001 compared to baseline values for both measurements). When adjustments were made for the reduction in plasma volume as well as for acidosis it was evident that, despite the apparent increases in the calcium concentrations, there was a net reduction of the plasma ionized calcium content (the total amount of plasma ionized calcium). This decrease was significantly (P<0middot;05) more pronounced in the exercising leg than in the systemic circulation but the difference could largely be explained by higher calcium‐lactate complex formation in the leg.
Relationship between turnover rate and oxidation rate of alanine in the post‐absorptive state and during parenteral nutrition before and after surgery
Authors: SAUERWEIN H. P. , MICHELS R. P. J. , CEJKA V.
Published: March 2008

Abstract. The influence of total parenteral nutrition and stomach resection on alanine turnover rate and alanine oxidation rate was measured in ten patients after single injection of U‐14 C‐alanine. Sequential studies were done in three patients. During parenteral nutrition alanine turnover was significantly higher than in the post‐abortive state (14·75 ± 2·56 μmol kg‐1 min‐1 and 8·48 ± 1·88 μmol kg‐1 min‐1, respectively; P<0·01, mean ± s.d.)‐ Surgery had no additional significant influence on alanine turnover. In the post‐absorptive state 4·71 ± 0·71 /μmol kg‐1 min‐1 was oxidized, during parenteral feeding before surgery 7·93 ± 1·93 μmol kg‐1 min‐1 (P<0·01 v. post‐absorptive state), and during parenteral feeding after surgery 7·67 ± 1·67 μmol kg‐1 min‐1. The percentages of alanine turnover used for oxidation in the post‐absorptive state and during parenteral feeding before and after surgery were 57 ± 11%, 54 ± 7% and 45 ±11%, respectively (no significant differences).

It is concluded that the degree of alanine oxidation seems to be directed by the degree of alanine turnover. A discussion about differences in alanine oxidation under different circumstances must therefore include a discussion about changes in alanine turnover.
Glucocorticoid hormone binding to human adipose tissue
Authors: LUNDHOLM K. , REBUFFE‐SCRIVE M. , BJC‐RNTORP P.
Published: March 2008

Abstract. Binding of triamcinolone was examined in cytosolic preparations of human adipose tissue obtained during surgery. A saturable specific binding was found. Non‐specific binding comprised on an average 28% of total binding. The affinity and concentration of binding sites were in the same order as previously described for glucocorticoid hormone binding in other tissues and in rat adipose tissue. There was a large difference in these variables between different individuals. The binding was inhibited competitively by non‐labelled triamcinolone, promegestone, dexa‐methasone and 17‐/?‐estradiol, in that order of potency. The promegestone inhibition was effective requiring only about 25% higher concentration than triamcinolone to obtain inhibition of half the triamcinolone binding. There was more binding of triamcinolone in omental than in subcutaneous abdominal adipose tissue when expressed per unit of protein and per unit cell surface area but not when expressed per adipocyte.
Fibrinolytic shut‐down after surgery: impairment of the balance between tissue‐type plasminogen activator and its specific inhibitor
Authors: D'ANGELO A. , KLUFT C. , VERHEIJEN J. H. , RIJKEN D. C. , MOZZI E. , MANNUCCI P. M.
Published: March 2008

Abstract. In nine patients with non‐malignant diseases undergoing major upper abdominal surgery, the mechanism of the postoperative fibrinolytic shutdown was investigated because of its potential significance for postoperative deep vein thrombosis by employing new and specific methods for assessing and stimulating the fibrinolytic system. The shut‐down was found to result from an impairment of the balance between tissue‐type plasminogen activator, t‐PA, and its recently discovered fast‐acting inhibitor. In this balance, the t‐PA antigen concentrations both in resting conditions and after stimulation evoked by desamino‐d‐arginine vasopressin (DDAVP) were found to be unchanged by surgery. However, there was a significant postoperative increase in t‐PA inhibitor levels. The release of t‐PA under the stimulus of DDAVP infusion overcame the postoperative shutdown of t‐PA activity. However, DDAVP infusion was associated with potentially unfavourable increases in the Factor VHI/von Willebrand factor complex. The discovery of increased t‐PA inhibitor in the postoperative period opens new possibilities for a rational approach to reduce or abolish the postoperative fibrinolytic shut‐down.
Heparin‐induced platelet aggregation in anorexia nervosa and in severe peripheral vascular disease
Authors: MIKHAILIDIS D. P. , BARRADAS M. A. , JEREMY J. Y. , GRACEY L. , WAKELING A. , DANDONA P.
Published: March 2008

Abstract. We have previously demonstrated that platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease are hyperaggregable. Since conventional heparins are known to activate platelets in vitro and occasionally induce thrombosis and consumptive thrombocytopenia in vivo, we have investigated the direct effect of a conventional heparin on platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease. Heparin at therapeutic concentrations was found to induce platelet aggregation of such platelets in vitro. In contrast, a recently developed low molecular weight heparinoid (Org 10172), at therapeutic concentrations, had no effect on these hyperaggregable platelets. We conclude that: (i) heparin may be potentially harmful to patients with hyperaggregable platelets; (ii) thrombocytopenia and thrombosis associated with heparin therapy may be mediated through a direct effect of heparin on platelets; (iii) it is unlikely that heparin induced thrombocytopenia is always mediated by classical immunological mechanisms, especially in patients with hyperaggregable platelets; and (iv) low molecular weight heparinoids may be safer anticoagulants in patients with platelet hyperaggregability.
Stimulatory cholinergic effect on the release of antiaggregatory activity into the circulation of cat and man and its modification by β‐adrenergic antagonists
Authors: SWIES J. , RADOMSKI M. , DEMBIŃSKA‐KIEĆ A. , KORBUT R. , GRYGLEWSKI R. J. , BRANDT R. , NOWAK J.
Published: March 2008

Abstract. The release of PGI2‐like activity into the circulation in response to cholinergic agonists and modification of this response by β‐adrenergic antagonists was investigated in anaesthetized cats and healthy humans. Antiaggregatory activity in the arterial blood was continuously assayed by measuring platelet aggregation on blood superfused collagen strip. In some of the human experiments, after the administration of the drugs, the conversion of [14C]‐arachidonate to [14C]‐prostaglandins in the pulmonary vascular bed was studied.

Cholinergic agonists stimulated the release of PGI2‐like activity into the circulation, which effect was potentiated in cats by β‐adrenergic antagonists. In humans the latter agents did not stimulate the conversion of [14C]‐arachidonate to prostaglandins in the pulmonary circulation and, moreover, inhibited the stimulatory cholinergic effect. The results suggest that an interplay between cholinergic and β‐adrenergic mediators may be involved, although in a different way in cats and in humans, in the release of PGI2‐like activity into the systemic circulation.
Production of leukotrienes and prostaglandins by human ascites cells
Authors: OUWENDIJK R. J. TH. , ZIJLSTRA F. J. , WILSON J. H. P. , VINCENT J. E. , BONTA I. L.
Published: March 2008

Abstract. Ascites was collected from six patients with liver cirrhosis and the cells isolated. These cells, mainly macrophages, were labelled with 14C‐arachidonic acid and stimulated with the calcium ionophore A23187. The metabolites formed were separated by HPLC. The main substances formed by the ascites cells were leukotriene B4, 5‐hydroxy‐6,8,11,14 eicosatetraenoic acid and leukotriene C4. Smaller amounts of thromboxane B2, 12‐hydroxy‐5,8,10 heptodecatrienoic acid and 6‐keto‐prostaglandin F1α were isolated. Human peritoneal macrophages are therefore capable of producing leukotrienes and prostaglandins. Production of these substances might play a role in some of the complications of patients with liver cirrhosis and ascites.
Rheological and transport properties of airway secretions in cystic fibrosis‐relationships with the degree of infection and severity of the disease
Authors: PUCHELLE E. , JACQUOT J. , BECK G. , ZAHM J. M. , GALABERT C.
Published: March 2008

Abstract. It has recently been suggested that in cystic fibrosis (CF), there is no rheological abnormality of airway secretions other than that associated with purulence, and that the apparent inhibition in the mucociliary transport rate might be partly due to a ciliary inhibitor present in these secretions. In order to ascertain this assumption, expectorated airway secretions were collected without salivary contamination in twenty‐four CF patients and the rheological properties were measured. Using a photometric method, the effects of CF sputum samples were analysed on the ciliary beat frequency (Fm) of the frog palate, and we measured their mucociliary transport rate (TR). In all but one CF sputum, TR and Fm were lower than that of the control frog mucus (median TR: 18±7 and 11±6 mm min‐1; median Fm: 12±3 and 11±3 Hz, respectively). In the eighteen patients in whom the rheological properties were outside the range for optimal mucociliary transport, the clinical Shwachman score was significantly (P<0±05) lower (median score: 66±2 points) than in the six patients with optimal rheologic properties (median score: 73 points). In the eleven CF patients with superinfection, the apparent viscosity (±0) was significantly higher (P<0±01; median ±0: 24±4 Pa. s) and TR, expressed as a percentage of the reference value, was significantly lower (P<0±05; median Tr: 54±5%) in comparison with the values obtained for the thirteen non‐superinfected CF patients (median ±0, 15 Pa. s and median TR: 66% respectively). The CF patients with markedly hypervis‐cous sputum (±0 higher than 30 Pa. s) exhibited a low Shwachman score.
Reduced strength of skin in osteogenesis imperfecta
Authors: OXLUND HANS , PEDERSEN ULRIK , DANIELSEN CARL CHRISTIAN , OXLUND INGER , ELBRØOND OLE
Published: March 2008

Abstract. The biochemical properties and ratio collagen type I/type III of skin biopsies from nine patients with osteogenesis imperfecta and nine age‐ and sex‐matched controls were studied. Four of six patients with osteogenesis imperfecta Sillence type I had pronounced reductions in skin tensile strength, decreased ratios of collagen type I/type III, primarily accomplished by reduced amounts of collagen type I, moderate or no disability. The three patients with osteogenesis imperfecta Sillence type III had severe skeletal deformities, but normal skin tensile strength, and ratios of collagen type I/type III within the normal range. These observations may be explained as resulting from various structural defects in the type I collagen of patients with osteogenesis imperfecta.
Effect of incremental doses of aspirin on bleeding time, platelet aggregation and thromboxane production in patients with cerebrovascular disease
Authors: BOSS A. HASAGER , BOYSEN G. , OLSEEN J. STEEN
Published: March 2008

Abstract. Bleeding time, thromboxane production and inhibition of platelet aggregation were studied before and during administration of acetylsalicylic acid in doses of 50, 100, 325 an 1000 mg daily in eighteen patients with cerebrovascular disease. Inhibition of thromboxane production and platelet aggregation was almost complete at 50 mg acetylsalicylic acid daily, and median bleeding time had increased significantly from 5±5 to 6±5 min at this dose and reached a maximum of 7±5 min at 100 mg daily. Further increase of the dose resulted in a slight decrease in bleeding time. It appears that a strong effect on platelet function can be achieved by small doses of acetylsalicylic acid, and that higher doses might be less effective.
Levels of ventricular myosin fragments in human sera after myocardial infarction, determined with monoclonal antibodies to myosin heavy chains
Authors: LEGER J. O. C. , BOUVAGNET P. , PAU B. , RONCUCCI R. , LEGER J. J.
Published: March 2008

Abstract. Serum levels of ventricular myosin heavy chains were quantitated in patients with acute myocardial infarction using a competitive radioimmunoassay involving monoclonal antibodies to the b‐type myosin heavy chains of a human ventricle. Among the seven antibodies selected for their higher affinity for ventricular myosin heavy chains, only four antibodies detected significant and variable myosin amounts in the serum samples of nineteen patients with acute myocardial infarction; the same antibodies occasionally detected, if at all, low myosin amounts in the sera of patients with no clinical sign of myocardial infarction, and no myosin in the serum of the healthy control subjects. The peak levels of myosin release were observed 4±6 ± 0±5 days (n= 13, P<0±01) after myocardial infarction and correlated rather well with the measured creatine kinase peak levels (the correlation coefficients were between 0±75 and 0±81, P<0±01, depending on the monoclonal antibody used for myosin determination). The time courses of myosin release varied according to the complexity of the heart attack observed. It was concluded that the titration of serum myosin was probably of little clinical value for therapeutic intervention during the acute phase of myocardial infarction; it could, however be an effective tool for retroactive detection of an infarct and for late estimation of infarct size.
Lymphocyte response to Klebsiella in ankylosing spondylitis
Authors: GROSS W. L. , LÜDEMANN G. , SCHMIDT K. , ULLMANN U.
Published: March 2008

Abstract The lymphocyte response of mononuclear cells (MNC) to Klebsiella (Klebs) was studied in ankylosing spondylitis (ASP) and, for comparison, in patients convalescing from Klebs infection and in HLA‐B27+ and B27‐ healthy blood donors. When large doses of various Klebs cell envelope structures were used, MNC from all healthy blood donors were stimulated to produce LIF but not to synthesize significant amounts of DNA. In contrast, MNC from convalescent patients showed LIF synthesis (but no significant proliferation) even when small doses of the Klebs biostructures were used. This heightened LIF response to Klebs was long‐standing and could be demonstrated even after serum antibodies had vanished. Very similarly, MNC from ASP patients did not proliferate significantly, but could be activated to produce LIF even with small doses of Klebs. The heightened LIF response to Klebs in ASP appeared to be correlated with the clinical activity and/or duration of the disease. In contrast, there was no correlation between the presence of HLA‐B27 in ASP patients or healthy controls and the LIF or proliferative response to Klebs.
Etidronate disodium for treating hypercalcaemia of malignancy: a double blind, placebo‐controlled study
Authors: HASLING C. , CHARLES P. , MOSEKILDE L.
Published: March 2008

Abstract The efficacy of intravenous etidronate disodium in controlling hypercalcaemia of malignancy was evaluated in a double blind, placebo‐controlled study. Twenty patients with known malignant disease and hypercalcaemia were randomly assigned on a 2:1 basis to etidronate 7·5 mg kg‐1body weight or placebo for 3–5 days. All patients received 3000 ml saline and 40 mg furosemide per day. Eighteen patients completed the study. Eleven of twelve in the etidronate group reached normocalcaemia compared to two of six in the placebo group (P=0·05). The etidronate group showed a greater decrease in serum calcium than the placebo group (P<0·02). The renal calcium excretion decreased significantly in the etidronate group, but not in the placebo group. A slight increase in serum creatinine was observed in the etidronate group compared to placebo on the first day of treatment. The difference however disappeared the following days. Intravenous etidronate treatment in combination with rehydration and furosemide constitutes a safe and efficient alternative in the treatment of hypercalcaemia of malignancy, although a first approach always should be rehydration.
Influence of peroral antibiotics upon the biotransformatory activity of the intestinal microflora in healthy subjects
Authors: MIDTVEDT T. , CARLSTEDT‐DUKE BODIL , HØVERSTAD T. , LINGAAS E. , NORIN ELISABETH , SAXERHOLT H. , STEINBAKK M.
Published: March 2008

Abstract. The effects of ampicillin, clindamycin or metronidazole, given perorally for 6 days to eighteen healthy volunteers, upon the following intestinal microflora‐associated characteristics (MACs) were evaluated: breakdown of mucin, formation of coprostanol, hydrolysis of bilirubin conjugates, formation of urobilinogen, and of some short chain fatty acids (SCFAs), presence of β‐aspartylglycine and inactivation of trypsin. Clindamycin markedly influenced the expression of all characteristics, but trypsin and β‐aspartylglycine, resulting in a pattern very much alike what has been found in germ‐free animals. Ampicillin caused a significant reduction in total amount of SCFAs (P<0·05) and urobilinogen (P<0·05) present in the faecal samples. Metronidazole caused a significant reduction in the formation of coprostanol and the deconjugation of bilirubin (P<0·05). We conclude that orally given antibiotics may cause major alterations in several parameters reflecting the normal biotransformatory activity of the intestinal microflora, probably caused by severe disturbances in the intestinal ecosystem.
High content of dietary linoleic acid does not reduce platelet reactivity in patients with hyperlipoproteinaemia
Authors: BOBERG M. , GUSTAFSSON I.‐B. , VESSBY B.
Published: March 2008

Abstract. Seventeen patients with hypertriglyceridaemia were given a lipid‐lowering diet with a high P/S‐ratio 2·1 during a 3‐week period. The very low density lipoprotein triglycerides decreased by 43%, low density lipoprotein cholesterol by 19% and high density lipoprotein cholesterol by 12%. There was a marked increase of linoleic acid (18:2 n‐6) in all plasma lipid esters with a concomitant decrease of the saturated and monounsaturated fatty acids. There was a slight increase of the linoleic acid metabolites 18:3 n‐6, 20:3 n‐6 and 20:4 n‐6 in serum triglycerides whereas the fatty acids of the n‐3 series decreased in all plasma lipid esters. In the platelets a similar pattern was found with an increase of linoleic acid and its metabolite 22:4 n‐6 and a decrease of 18:1 n‐9 as well as of the n‐3 fatty acids. No significant differences in platelet reactivity was found. However, in a few patients there was an increased platelet aggregation after the diet period. Our results suggest that this diet based on a very high content of linoleic acid may not affect platelet reactivity in a beneficial way. The reason may be an increased turnover of arachidonic acid in the platelets or an imbalance between the n‐6 and n‐3 series of fatty acids.
Angiotensin II, aldosterone and arginine vasopressin in plasma in congestive heart failure
Authors: PEDERSEN E. B. , DANIELSEN H. , JENSEN T. , MADSEN M. , SØRENSEN S. S. , THOMSEN O. Ø.
Published: March 2008

Abstract. Angiotensin II(AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined during basal conditions in seventeen patients with congestive heart failure and in seventeen control subjects. The same parameters were measured before and 1, 2 and 3 h after an oral water load of 20 ml (kg body weight)‐1 together with urine volume (V) and free water clearance (CH2O) in seven patients with congestive heart failure and in seven control subjects. AII, Aldo and AVP were significantly higher in heart failure than in control subjects (AII: 81 and 12 pmol l‐1 (medians), P < 0·01; Aldo: 411 and 103 pmol l‐1, P < 0·01; AVP: 5·3 and 2·0 pmol l‐1, P < 0·01). AVP was positively correlated to Aldo in both heart failure (ρ= 0·593, n= 17, P < 0·02) and control subjects (ρ= 0·511, n= 17, P < 0·05), but in neither of the groups to AII. V and CH2O were significantly lower in heart failure when compared to control subjects (maximum increase in CH2O 3·55 and 5·86 ml min‐1, P < 0·02), but did not correlate directly with either A II, Aldo or AVP. Creatinine clearance was reduced in heart failure. It is concluded that the activity of both the renin‐angiotensin‐aldosterone system and the osmoregulatory system is enhanced in congestive heart failure, presumably as a compensatory phenomenon in order to maintain arterial blood pressure. It is suggested that the decrease in free water clearance may be attributed to both an elevated level of vasopressin and a reduced glomerular filtration rate.
Immunoglobulin deposits in labial mucosal epithelium of patients suspected of Sjögren's syndrome
Authors: OXHOLM PETER , MANTHORPE ROLF , OXHOLM ANNEMETTE , SCHIØDT MORTEN
Published: March 2008

Abstract. Lower lip biopsies from twenty‐three consecutive patients under evaluation for Sjögren's syndrome, and from six normal controls, were investigated for deposits of immunoglobulins, fibrinogen and C3, using a direct immunofluorescence technique. Deposits of both IgG and IgA were demonstrated in the mucosal epithelium in three of six patients with primary Sjögren's syndrome. Similar IgG deposits were found in two of three patients with xerostomia and in one of three patients with Sjögren's syndrome secondary to rheumatoid arthritis. Immunoglobulins were located in close relation to cell surfaces in the basal and suprabasal layers of the epithelium. Double labelling experiments indicated a partial topographic concordance between the immunoglobulin deposits and OKT6 positive Langerhans cells in the epithelium. No deposits of immunoglobulins, fibrinogen or C3 were found in the remaining eleven patients and six normal controls. We conclude that deposits of IgG and IgA in the labial mucosal epithelium seem to be a characteristic finding in patients with primary Sjögren's syndrome as well as in patients with xerostomia. The diagnostic value of this new observation needs to be clarified in future studies.
Effect of short lasting hypoxia on the metabolic function of the perfused pig liver. Comparison of ischaemic and hypoxaemic hypoxia
Authors: WINKLER K. , KEIDING S. , TØNNESEN K. , TYGSTRUP N.
Published: March 2008

Abstract. The effects of hypoxaemia and ischaemia were compared in the perfused pig liver. Decreased hepatic oxygen uptake, galactose elimination, ATP phosphorylation and increased lactate output occurred when the oxygen supply was diminished below 55% of the mean of controls. Below the control limits for oxygen uptake and oxydative phosphorylation, the change in the above variables were correlated to the degree of hypoxia, with no quantitative differences regarding ischaemic or hypoxaemic hypoxia. Galactose elimination was correlated to the ATP concentration (r= 0·81). After 80 min of hypoxia almost complete recovery was seen. It can be inferred from the data that other factors than oxygen diffusion into the liver cells may limit oxydative metabolism. Long and severe hypoxia may be required before irreversible cellular damage occurs in the liver.
Effect of captopril on the cerebral circulation in chronic heart failure
Authors: PAULSON O. B. , JARDEN J. O. , VORSTRUP S. , HOLM S. , GODTFREDSEN J.
Published: March 2008

Abstract. Cerebral blood flow (CBF) was investigated in 8 patients with chronic heart failure (CHF) (functional class III) and in twelve controls before and after administration of 6·25 mg and 25 mg captopril, respectively. In four controls, CBF was measured by the intracarotid xenon‐133 (133Xe) injection technique using stationary external detectors, while inhalation of 133Xe and single photon emission computer tomography was used in the remaining cases. In the control group, the cerebral metabolic rate for oxygen was calculated from measurements of the arterio‐venous oxygen difference as well. Mean CBF was significantly (P < 0·01) lower in the patients with CHF as compared to our controls. Following captopril administration the mean arterial blood pressure decreased in the CHF patients, ranging from 5 to 40%. Three patients showed decreases of blood pressure to values of 56, 65, and 76 mm Hg, but no symptoms of cerebral hypoperfusion were elicited. CBF was unchanged after captopril administration, even in the patients showing a marked reduction in blood pressure. In the control group, the blood pressure, CBF and the cerebral metabolic rate for oxygen remained essentially constant following captopril administration.

It is concluded that the cerebral circulation is well preserved during captopril treatment of chronic heart failure. This might be explained by a shift of the lower limit of CBF autoregulation towards lower blood pressure levels.
Effect of obesity and weight reduction on biliary cholesterol saturation and the response to chenodeoxycholic acid*
Authors: REUBEN A. , QURESHI Y. , MURPHY G. M. , DOWLING R. H.
Published: March 2008

Abstract. Biliary cholesterol saturation indices (SI's) were measured in fasting duodenal bile from (i) obese and non‐obese individuals with and without cholesterol gallstones, (ii) obese individuals undergoing weight reduction and (iii) obese gallstone patients receiving chenodeoxycholic acid (CDCA) therapy. Biliary lipid secretion rates were also measured in three obese subjects before and during 11 days starvation. The mean SI in fifteen non‐obese controls (0·89 ± SEM 0·06) was significantly lower than that in the twenty‐four obese without (1·14 ± 0·07; P < 0·01), and in the twenty‐nine non‐obese with gallstones (1·30 ± 0·05; P < 0·001) while in sixteen obese gallstone patients, the mean SI of 1·55 ± 0·06 was significantly higher than that seen in the other three groups (P < 0·01–0·001). Although fifteen obese subjects lost 15% of their initial body weight during dieting, this did not change their SI's consistently. However in three obese individuals, total starvation did reduce the SI's and significantly lowered the biliary cholesterol secretion rate. Ten obese gallstone patients responded to 15·8 ± 0·3 mg CDCA kg‐1 day‐1 by developing unsaturated fasting duodenal bile (SI 0·89 ± 0·04). A further increase in CDCA dose to 19·0 ± 0·7 mg kg‐1 day‐1, as a result of reducing body weight, was more effective in lowering SI's (0·75 ± 0·06, range 0·51–1·0) than that achieved by increasing the dose to 18·9 ± 0·46 mg kg‐1 day‐1 through more capsules per day (SI o·89 ± 0·03, range 0·67 ‐ 1·25). These studies show that (i) biliary cholesterol SI's are greater when obesity and gallstones occur together than in either obesity or gallstones alone, and (ii) although weight loss in obese individuals does not consistently alter biliary cholesterol SI's, it may be beneficial in obese patients receiving CDCA therapy for gallstone dissolution.
Lipoprotein modifications during dietary treatment in patients with primary type V hyperlipoproteinaemia
Authors: MANZATO E. , MARIN R. , GASPAROTTO A. , BAGGIO G. , MARTINI S. , GABELLI C. , CREPALDI G.
Published: March 2008

Abstract. Type V hyperlipoproteinaemia is a disorder of lipid transport characterized by the accumulation in serum of chylomicrons and very low density lipoproteins. The purpose of the study was the analysis of serum lipids and lipoproteins by ultracentrifugation in nine patients with primary type V hyperlipoproteinaemia before and during dietary treatment. After 30 days of balanced isocaloric diet mean serum triglycerides fell from 25·4 ± 15·0 (mean ± SD) to 2·8 ± 1·7 mmol l‐1. At the same time the chylomicrons and the very low density lipoproteins of flotation rate higher than 100 disappeared from the serum while the remaining very low density lipoproteins maintained unaltered their normal protein–lipid composition. After 30 days the low density lipoproteins increased significantly in concentration (from 1·6 ± 0·8 to 4·1 ± 1·1 mmol l‐1 cholesterol) and their percentage content of cholesterol and triglyceride was increased and reduced, respectively. The highest concentration of intermediate density lipoprotein cholesterol was observed after 15 days of treatment (1·2 ± 0·6 mmol l‐1). The abnormally low concentrations and the physico‐chemical properties of the high density lipoproteins remained unchanged throughout the study (from 0·6 ± 0·2 to 0·8 ± 0·2 mmol l‐1 cholesterol concentration) and no high density lipoproteins two (HDL2) were observed at any time. The effects of this treatment were an increase in low density and marginal change in high density lipoproteins which are considered, respectively, a positive and a negative risk factor for atherosclerosis.