bluuebunny/crossref_metadata_2025 huggingface dataset:
Affinity of LDL to a human arterial proteoglycan among male survivors of myocardial infarction
Authors: LINDÉN T. , BONDJERS G. , CAMEJO G. , BERGSTRAND R. , WILHELMSEN L. , WIKLUND O.
Published: March 2008

Abstract. In the present study, the hypothesis that the affinity of LDL to arterial proteoglycans might discriminate myocardial infarction patients from controls were tested. The patients were 52 men who had sustained a myocardial infarction at an age of 50 years or less and the controls, selected from a random population sample, were matched to the patients for age and sex. Serum cholesterol, triglycerides, LDL‐cholesterol, HDL‐cholesterol and apoB discriminated patients from controls. In addition, LDL reactivity with arterial proteoglycans was significantly higher in patients than in controls. In a multiple regression analysis, with patient or control as the dependent variable, apoB levels, LDL proteoglycan reactivity and serum triglycerides appeared as independent contributors to the regression. These observations indicate that LDL reactivity with arterial proteoglycans is a new, highly significant factor which discriminates between young myocardial infarction patients and controls.
Effect of a soluble bacterial carbohydrate fraction on the viscosity of intestinal contents in healthy subjects and patients with Crohn's disease
Authors: HAZENBERG M. P. , PENNOCK‐SCHRÖDER A. M. , WENSINCK F. , MERWE J. P. VAN DE
Published: March 2008

Abstract. Supernatants of faecal suspensions from patients with Crohn's disease (CD) showed much lower viscosity than those from healthy subjects. Material responsible for the viscosity could be precipitated with ethanol. Gel filtration indicated that the viscosity was not due to the glycoprotein fraction but to a fraction with higher molecular weight and relatively high contents of muramic acid suggesting a bacterial origin. The concentration and viscosity of this fraction are less in faeces from patients with CD than in that of healthy subjects.
Oral E2 prostaglandins affect endocrine cell populations in the gastric antrum of the rat
Authors: URIBE A. , GRIMELIUS L. , THEODORSSON L. E. , RIIS‐ANGELO L. , JOHANSSON C.
Published: March 2008

Abstract. The aim of the present study was to investigate antral endocrine cell populations and tissue and circulating hormone levels following a 4‐week oral regimen with prostaglandin E2 (25, 250 and 5000 μg kg‐1 b.i.d.) or a stable methyl analogue (5 and 50 μg kg‐1 b.i.d.). Epithelial hyperplasia of the gastric antrum was observed with the highest dose of prostaglandin E2 and both doses of the analogue, as evaluated by stereological methods and conventional cell count. The treatments significantly affected the endocrine cell population. Somatostatin‐immunoreactive cells were increased in proportion to the increased epithelial cellularity and plasma levels of somatostatin were increased in parallel. The tissue content of somatostatin‐like immunoreactivity differed according to the extraction procedure used, and was significantly higher than controls in specimens extracted in neutral water. In the neutral extracts an immunoreactive somatostatin of unidentified molecular structure dominated quantitatively over somatostatin 14 and 28, which were the major components in acetic acid extracts.

The serotonin‐immunoreactive cell population was also significantly increased by natural prostaglandin E2 and the analogue but the gastrin cell population was not significantly affected by treatments. Accordingly, no significant changes were observed in tissue or plasma gastrin levels.

It is concluded that the epithelial hyperplasia of the antral epithelia produced by E2 prostaglandins is associated with selective changes of endocrine cell populations. The changes were proportional to the increases of epithelial cellularity and required quantitative determination of the total antral volume to be detected. It may seem surprising that the most consistent finding in the hyperplastic antral mucosa was an increase of somatostatin‐immunoreactive cell population, and elevated tissue and plasma concentrations of this peptide, which has anti‐trophic actions on gastrointestinal epithelia. It is possible that somatostatin increments contribute to restrict the hyperplasia and are responsible for the reduced new cell production observed in prostaglandin‐induced hyperplasia of gastric and intestinal epithelia.
Statistical analysis of fever interval data
Authors: STOK C. J. , MEER J. W. M. VAN DER , KRUSEMAN A. C. NIEUWENHUIJZEN
Published: March 2008

Abstract. Periodic fever syndromes usually do not show a clear fixed periodicity, and hence cannot be described by the mean and the standard deviation of the interval length. In those cases statistical tools must be used. Fever interval data can be described as a random point process; the renewal density function and its Fourier transform can be used to uncover hidden periodicities. In this report the estimation and evaluation of the renewal density function are described. The data of three patients with periodic fever were investigated. In one of these patients, suffering from periodic fever originating at the level of the hypothalamus, a 30‐day periodicity was observed. In a female patient with hyperimmunoglobulinaemia D and periodic fever, menstruation often coincided with or was preceded by a fever episode. In the third patient with a Familial Hibernian Fever‐like syndrome, an irregular fever pattern and no periodicity were found. The computerized analysis of the fever intervals may be useful in assessing various periodic fever syndromes.
Osteogenesis imperfecta: insufficient collagen synthesis in early childhood as evidenced by analysis of compact bone and fibroblast cultures
Authors: BRENNER R. E. , VETTER U. , NERLICH A. , WÖRSDORFER O. , TELLER W. M. , MÜLLER P. K.
Published: March 2008

Abstract. We analysed the composition of compact bone from 30 patients suffering from various forms of osteogenesis imperfecta (OI). Collagen and total protein content per cell of controls increased with the age of the donors, but were generally low in OI. In fibroblast cultures controls had a maximum of collagen synthesis between 2 and 9 years of age, an observation which was not seen in OI cells. In bone collagen both OI type II patients showed overhydroxylation of lysyl residues as did some patients with OI type III (25%) and OI type IV (33%). The collagen of OI type I patients was never found to be overmodified. In controls, collagen III was found exclusively during fetal time while it was present in significant amounts in bone tissue of all types of OI. The proportion of collagen V was somewhat higher in OI bones (about twice) than in controls. Our data suggest that the normal increase of collagen synthesis is defective in patients with OI. Perhaps some of these changes are due to specific molecular defects in collagen while others may be due to defective regulation of the maturation process.
Effects of 3‘‐azido‐3’‐deoxythymidine (AZT) on short‐term cultured human peripheral blood lymphocytes
Authors: TAURIS P. , MØLLER B. , PETERSEN C. MUNCK , BLACK F. T.
Published: March 2008

Abstract. Although an optimal dose‐regimen has still not been established, the antiviral drug 3‘‐azido‐3‘‐deoxythymidine is known to improve the clinical condition of patients suffering from acquired immunodeficiency syndrome and acquired immunodeficiency syndrome‐related complex.

The drug effect has mainly been assessed in terms of survival time and/or immunological parameters.

One of the most prominent immunological features associated with immunodeficiency virus infection is a persistant hypergammaglobulinaemia due to in vivo polyclonal B‐lymphocyte activation. In vitro this is reflected by a hyporesponsiveness of peripheral blood B‐lymphocytes to mitogen and antigen induced activation.

The present paper deals with the in vitro impact of 3′‐azido‐3′‐deoxythymidine on the immunoglobulin secretion in short‐term cultures of peripheral blood lymphocytes. Twenty‐four human immunodeficiency virus antibody positive (seropositive) and 24 antibody negative (seronegative) individuals were studied. In addition, T‐ and B‐cell proliferation and the distribution of cell surface markers were determined in 3′‐azido‐3′‐deoxythymidine‐supplemented cultures of peripheral blood lymphocytes from eight seronegative subjects.

At concentrations similar to those reported in clinical trials, 3′‐azido‐3′‐deoxythymidine was found to suppress the mitogen and antigen induced proliferation of T‐cells from seronegative subjects. In contrast, B‐cell proliferation and the distribution of membrane markers appeared to be unaffected by the drug. Furthermore, 3′‐azido‐3′‐deoxythymidine did not alter the i vivo immunoglobulin secretion capacity in autologous or allogeneic cultures of lymphocytes from seropositive subjects.

In human immunodeficiency virus‐infected individuals the number of unactivated, circulating B‐cells is significantly reduced. The present results indicate that the functional capacity of these ‘remaining’ cells may be seriously impaired during antiviral therapy with 3′‐azido‐3′‐deoxythymidine.
Intravenous and subcutaneous administration of a long‐acting somatostatin analogue: effects on glucose metabolism and splanchnic haemodynamics in healthy subjects
Authors: ERIKSSON L. S. , WAHREN J.
Published: March 2008

Abstract. The effect of SMS 201–995, a long‐acting somatostatin analogue, on splanchnic blood flow and glucose metabolism, was investigated in five groups of healthy subjects. Groups A (n= 4), B (n= 5), C (n= 5) and D (n= 5) were studied before, during and after a 60‐min intravenous infusion of SMS (1.7, 0.8,0.2 and 0.1 μg min‐1, respectively). Group E (n=6) was investigated before and for 6 h after a subcutaneous injection of 25 μg of SMS. The splanchnic blood flow decreased by 20–25% in all groups in response to SMS and remained low during the entire observation periods. Arterial concentrations of glucose showed a 15–20% decline during SMS infusion in Groups A and B (P<0.05–0.01) and a less pronounced decrease in the other groups. Fifteen minutes after the end of infusion the glucose levels started to rise and in group A, the levels were significantly higher than basal (+25%, P<0.05–0.01) at 90–180 min after the end of infusion. The net splanchnic glucose production, determined in groups A and B, decreased by 65–75% in response to SMS infusion. Towards the end and immediately after the infusions, however, the net glucose output increased, but decreased again at 30–60 min after the end of infusion. Arterial, insulin and glucagon concentrations decreased significantly during infusion in all groups. This decline was more pronounced for insulin (50%) than for glucagon (20–25%) and insulin concentrations remained low for a longer period after the end of infusions. After subcutaneous injection both insulin and glucagon levels were low for up to 6 h. Arterial ammonia concentrations decreased and the concentrations of threonine, serine, glutamine, glycine, valine, leucine, phenylalanine, lysine and histidine all rose after i.v. infusion of SMS.

It is concluded that SMS exerts a similar, but more prolonged, influence on splanchnic blood flow and the secretion of insulin and glucagon as compared to somatostatin. In addition, the high circulating levels of glucose after the end of infusion, in the face of low splanchnic glucose output, suggests that SMS has a direct effect on peripheral glucose uptake.
Ligand‐specific and non‐specific in vivo modulation of human epidermal cellular retinoic acid binding protein (CRABP)
Authors: HIRSCHEL‐SCHOLZ SUSANNE , SIEGENTHALER G. , SAURAT J.‐H.
Published: March 2008

Abstract. Retinoic acid (RA) is bound intracellularly by a specific, low molecular weight protein (CRABP), that is unrelated to its nuclear receptor and whose function and regulation are still unknown. In the present study we were able to obtain an in vivo modulation of CRABP by different stimuli in one of the major target organs of RA: the human skin. We found increased CRABP after daily application during 4 days of natural or synthetic retinoids (RA, acitretin, isotretinoin, Ro137410, retinol), that have either a high affinity to CRABP or can be transformed into RA. Only Ro150778 with no affinity and no reported transformation had no effect. No macro‐ or microscopical changes could be observed with any of the tested compounds. Induction of inflammatory and hyperproliferative changes in the skin by topical dithranol treatment, UVB irradiation or scotch tape stripping also induced a significant increase of CRABP 3 days after exposure. Topical diflucortolone showed not only a tendancy to decrease intrinsic CRABP levels, but significantly reduced the retinoid stimulated rise of CRABP.

Thus we conclude that the increase of CRABP in a fully differentiated adult tissue seems to be a biological phenomenon following processes of inflammation and proliferation with a lag of several days, while retinoids seem to be able to induce such a rise independently of, or before, the appearance of such processes. Corticosteroids seem to be inhibitors of this reaction. We discuss the hypothesis that CRABP might function as an intracellular ‘buffer’ in the case of RA overload.
Effect of HELP‐LDL‐apheresis on serum concentrations of human lipoprotein(a): kinetic analysis of the post‐treatment return to baseline levels
Authors: ARMSTRONG V. W. , SCHLEEF J. , THIERY J. , MUCHE R. , SCHUFF‐WERNER P. , EISENHAUER T. , SEIDEL D.
Published: March 2008

Abstract. In addition to LDL, Lp(a) can be quantitavely eliminated from plasma in an extracorporeal LDL‐apheresis procedure based on precipitation with heparin at pH 5.12. The rates of return of postapheresis Lp(a) and LDL‐cholesterol concentrations to baseline levels were investigated in six individuals with familial hypercholesterolaemia (one homozygote, five heterozygote) and one normolipaemic individual. The first‐order disappearance constants (k) were derived for LDL and Lp(a) according to Apstein et al. [1]. The k values for LDL in the homozygous FH and the normolipaemic individual were 0.082 and 0.43 respectively while the heterozygous FH patients had k values intermediate between the two (median 0.231; range 0.116–0.261). The first‐order disappearance constants of Lp(a) did not correlate with those of LDL. The homozygous FH and normolipaemic individuals had Lp(a) k values of 0.158 and 0.199 respectively; the corresponding values in the heterozygous FH patients were: median 0.142; range 0.045–0.179.
The glomerular sieving of pepsinogen A and C in man
Authors: KATE R. W. TEN , PALS G. , RES J. C. J. , KAMP G. J. VAN , VERHEUGT F. W. A. , PRONK J. C. , DONKER A. J. M. , ERIKSSON A. W. , MEUWISSEN S. G. M.
Published: March 2008

Abstract. Pepsinogen A (PGA) and pepsinogen C (PGC) are negatively charged, low molecular weight (LMW) proteins with a striking difference in renal handling: PGA (molecular weight 43 500 daltons) shows a high fractional excretion while the fractional excretion of PGC (molecular weight 40 500 daltons) is low, presumably due to tubular reabsorption. As these data suggest a high glomerular sieving of pepsinogens, we assessed the glomerular sieving coefficient (GSC) of PGA, PGC and several other proteins from their renal extractions'. For this purpose blood samples were obtained simultaneously from the aorta (A) and right renal vein (V) in nine patients undergoing an elective heart catheterization.

After correction of the A‐V differences for diuresis with the A‐V difference of transferrin, GSCs (± SEM) for PGA and PGC were 0.90±0.14 and 0.85 ± 0.17, respectively, GSC of β2‐microglobulin being 0.90 ± 0.12. For albumin and IgG, known to have a low GSC, low values were found.

It is concluded that the GSC of a LMW protein in man can be calculated from both its A‐V difference over the kidney and the A‐V difference of an inert marker with a GSC of 1, provided they are corrected by the A‐V difference of an inert marker with a GSC of 0. Our results demonstrate that PGA and PGC are almost freely filtered through the glomerular basement membrane despite their size and negative net molecular charge.
Murine tissue macrophages synthesize and secrete amyloid proteins different to amyloid A (AA)
Authors: RAMADORI G. , RIEDER H. , SIPE J. , SHIRAHAMA T. , BÜSCHENFELDE K.‐H. MEYER ZUM
Published: March 2008

Abstract. We recently demonstrated that serum amyloid A (SAA) gene expression can be induced in extrahepatic sites with exception of the brain. Furthermore we demonstrated that tissue macrophages express SAA‐gene constitutively and that SAA‐gene expression can be increased by endotoxin. Until now the protein corresponding to the SAA‐specific mRNA contained in macrophages has not been identified. We compared proteins precipitated from endogenously labelled samples by three antisera against amyloid A (AA) raised in different laboratories. Radiolabeled samples were derived from murine hepatocyte cultures, from cell‐free translation of acute phase liver RNA or hepatocytes RNA and from peritoneal macrophages as well as Kupffer cells. All three antisera recognize a protein of 12.5 kDa Mr produced by hepatocytes (SAA), and a major protein of 14.3 kDa Mr contained in the cell‐free translation products; this is the precursor of the mature SAA as demonstrated by cleavage experiments with canine pancreas microsomal enzymes. The antisera also recognize two proteins—a major one of 14.5 kDa Mr and a second of 12.5 kDa Mr contained in the supernatants and cell lysates of liver and peritoneal macrophages. New antisera raised against the two proteins do not recognize any protein, either of hepatocyte or of cell‐free translation samples; they specifically precipitate two proteins from macrophage samples with the same molecular mass as that of the proteins precipitated by the anti SAA antisera. Murine acute phase sera do not react with the new antisera. However, amyloid deposits of amyloidotic mice specifically react with the new antisera. We describe two new components of murine amyloid produced by tissue macrophages.
Human leucocyte rheology and tissue ischaemia
Authors: CIUFFETTI G. , MERCURI M. , RIZZO MARIA TERESA , LOMBARDINI RITA , MANNARINO E.
Published: March 2008

Abstract. Reports suggest that white blood cells are involved in the development of tissue ischaemia. No studies on leucocyte rheology in the earliest stages of ischaemia exist. In 10 peripheral vascular disease (PVD) patients, 10 stable angina pectoris (SAP) patients and two groups of 10 matched controls leucocytes were separated by density and adherence into their granulocyte, lymphocyte and monocyte subpopulations. Blood samples were taken from the PVD group and respective controls before and after treadmill exercise (5 min 2 km‐1 h‐1, 12% slope) and from the SAP patients and controls before and after cycle ergometer test (25 W every 3 min). All the subpopulations were filtered through five micron diameter pore filters. Compared to controls, calf pain in the PVD patients was associated with an increase in monocyte filterability (P<0.01). ST depression in the SAP patients was linked to impaired granulocyte filterability (P<0.04). Therefore leucocyte rheology appears impaired in the earliest stages of ischaemia.
Extra‐pancreatic action of glibenclamide in man: reduction in vitro of the inhibitory effect of glucagon and epinephrine on the hepatic key glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK)
Authors: BELFIORE F. , RABUAZZO AGATA M. , IANNELLO SILVIA , CAMPIONE ROSA , CASTORINA S. , URZI F.
Published: March 2008

Abstract. Human liver slices (surgery biopsies) were preincubated with glucagon or epinephrine for 10 min at 37°C in Krebs‐Henseleit solution at pH 7.4, in the absence or presence of glibenclamide, and then homogenized and assayed for phosphofructokinase (PFK) and pyruvate kinase (PK) activity at subsaturating, near physiological, substrate concentrations (suitable for detecting regulatory effects). Preincubation with 10 μM glucagon (n= 7) or 10 μM epinephrine (n= 7) resulted in a reduction of PFK activity of 25% (P < 0.02) and 29% (p < 0.05), respectively. Addition of 2 μM glibenclamide in the preincubation mixture reduced the inhibitory effect of glucagon by 99% (P < 0.05) and that of epinephrine by 70% (p < 0.01). Likewise, 10 μM glucagon (n= 6) or 10 μM epinephrine (n= 4) reduced PK activity by 40% (P < 0.01) and 46% (P < 0.01), respectively. Addition of 2 μM glibenclamide significantly reduced the inhibitory effect of glucagon by 77% (P < 0.05) and that of epinephrine by 33% (P < 0.05). In the absence of the hormones, glibenclamide was without effect. Thus, glibenclamide opposes the inhibitory effect of glucagon and epinephrine on two key hepatic glycolytic enzymes. Since the inhibition of key glycolytic enzymes favours gluconeogenesis, the observed action of glibenclamide, if it occurs also in vivo, might reduce the glucagon‐ and epinephrine‐stimulated gluconeogenesis, and could be regarded as an insulin‐like action.
Polymorphism of apolipoprotein E influences levels of serum apolipoproteins E and B in the human neonate
Authors: STEINMETZ A. , THIEMANN ELISABETH , CZEKELIUS P. , KAFFARNIK H.
Published: March 2008

Abstract.To gain more insight into the genetic vs. environmental influence of the apoE phenotypes on plasma lipoprotein variation we studied human umbilical cord sera at birth. Apolipoprotein E genetic phenotypes were determined in 110 individuals by immunoblottrag and shown to be identical to the adult human isoforms with six phenotypes present and occurring at a similar frequency as reported previously for the adult population in the same area. Total serum cholesterol and triglyceride levels were low in the neonates and did not differ significantly between apoE phenotypes. On the other hand as in the aduit, levels of apoE and B differed significantly between the phenotypes. ApoE was highest in individuals with the 62 allele and lowest in individuals expressing apoE4, and vice versa for apoB.

We conclude that apoE phenotypes in human umbilical cord blood serum are already associated with pronounced differences in apoE and B levels in the newborn. The study demonstrates that the association of apoE and apoB levels with the apoE polymorphism occurs independently of significant enteral nutrition in the relatively constantin uteroenvironment.
Molecular analysis of acute intermittent porphyria in a Finnish family with normal erythrocyte porphobilinogen deaminase
Authors: GRANDCHAMP B. , PICAT C. , KAUPPINEN R. , MIGNOTTE V. , PELTONEN L. , MUSTAJOKI P. , ROMÉO P. H. , GOOSSENS M. , NORDMANN Y.
Published: March 2008

Abstract. Porphobilinogen deaminase, the third enzyme of the haem biosynthetic pathway, is encoded by two distinct mRNA species expressed in a tissue‐specific manner from a single gene. These two mRNAs are transcribed from two promoters and only differ in their first exon. An inherited deficiency or porphobilinogen deaminase in man is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease.

In the present report, we describe the molecular abnormality responsible for a variant form of acute intermittent porphyria where the enzyme defect is restricted to non‐erythroid cells. Upon cloning and sequencing the mutant allele of a patient from a large Finnish kindred, a single‐base substitution within the 5′‐splice donor sequence of intron 1 was found at the last position of exon 1 (CGCT).

The identification of this mutation allowed us to detect asymptomatic gene carriers among family members using in vitro amplification of DNA and hybridization of the target sequence to allele‐specific oligonucleotides.
The effect of testosterone replacement on plasma lipids and apolipoproteins
Authors: JONES D.B. , BILLET J.S. , PRICE W.H. , EDWARDS C.R. W. , BEASTALL G.H. , HIGGINS B. , SHEPHERD J. , HORN D. B. , WENHAM P. R. , SWEETING V. M.
Published: March 2008

Abstract. Ten men with Klinefelter's syndrome were studied to assess the effect of testosterone replacement on plasma lipids and apolipoproteins. Measurements taken before the insertion of a testosterone ester implant were compared with those obtained 1 week and 4 weeks later.

Mean plasma testosterone, androstenedione, total cholesterol and calculated LDL‐cholesterol increased significantly after 1 and 4 weeks. No significant changes were seen in total plasma concentrations of HDL‐cholesterol, HDL‐cholesterol subfractions 2 and 3 or in apoplipoproteins A‐I, A‐II or B.

A significant correlation was seen between total cholesterol and plasma oestradiol concentrations (Rs=0.61; P < 0.001). A significant negative correlation was seen between the concentrations of total testosterone and total triglyceride (Rs= ‐0.56; P < 0.005) but not with the other lipid parameters.

Testosterone replacement is associated with slight but potentially adverse changes in plasma cholesterol levels.
Natural occurrence of IgE antibodies to peptide hormones in man
Authors: KHALAF A. ‐N. , KERP L. , SCHLIEBS B. , JÄGLE M. , PETERSEN K.‐G.
Published: March 2008

Abstract. IgE antibodies to peptide hormones or their fragments were investigated using specific radioaller‐gosorbent tests. Ninety‐six sera were obtained from otherwise healthy individuals with a positive RAST to at least one common allergen and without previous contact to exogenous hormones. Total serum IgE was normal (< 300 ng ml‐1) in 41 and elevated in 55 sera. Only one serum with normal total IgE had reagins to proinsulin. In sera with elevated total IgE positive tests (> 8 times background) were observed frequently: hGH 9.1%, GHRH1–44 5.5%, GHRH1–29 12.7%, erythropoietin 10.9%, human calcitonin 14.6%, salmon calcitonin 1.8%, ACTH 5.5%, insulin 14.6%, proinsulin 7.3%, insulin A chain 1.8%, insulin B chain 18.2%, C‐peptide 9.1%, and IGF 9.1%.

The data show natural occurrence of reagins to peptide hormones in atopic persons. A risk at exposure to these peptides may exist in about 1% of the general population.
Relationship between the metabolism of antipyrine, hexobarbital and theophylline in patients with liver disease as assessed by a ‘cocktail’ approach
Authors: SCHELLENS J. H. M. , JANSSENS A. R. , WART J. H. F. VAN DER , VELDE E. A. VAN DER , BREIMER D. D.
Published: March 2008

Abstract. Antipyrine (AP), hexobarbital (HB) and theophylline (TH) were administered simultaneously (‘cocktail’ design) to 24 patients with various types of liver disease. Clearance (CI) of AP, HB and TH and formation clearance of the AP‐metabolites 3‐hydroxy‐methylantipyrine (HMA), norantipyrine (NORA) and 4‐hydroxyantipyrine (OHA) were determined and correlation coefficients and orthogonal least‐squares regression lines calculated between the clearance and formation clearance parameters. The results were compared with those obtained in a study in which the same ‘cocktail’ was administered to 26 healthy control subjects.

In the patients ClAP, ClHB and CITH were 23.0±14.3 ml min‐1, 206±128 ml min‐1 and 39.9 ± 26.1 ml min‐1 respectively. All values were considerably lower than those found in the control subjects. With regard to AP metabolism preferential impairment of NORA formation was observed. Relatively high correlation coefficients were found between ClAP, ClHB and C1TH, which suggests, like the results of orthogonal regression analysis, a strong correlation between total metabolism of these probe drugs. Therefore it is likely that impairment in oxidation in patients with liver disease not only leads to reduction in clearance but also to reduced substrate selectivity of cytochrome P‐450 isozymes.
Plasma dihydroxyphenylalanine (DOPA) is independent of sympathetic activity in humans
Authors: ELDRUP E. , CHRISTENSEN N. J. , ANDREASEN J. , HILSTED J.
Published: March 2008

Abstract. To clarify the origin of plasma DOPA (3,4‐Dihydroxyphenylalanine), the relationship between plasma DOPA and acute or chronic changes in sympathetic activity has been studied. Plasma DOPA and noradrenaline (NA) concentrations were measured by reverse‐phase high‐performance liquid chromatography with electrochemical detection. Administration of clonidine to healthy men decreased plasma NE markedly compared to no drug. Plasma DOPA decreased slightly but significantly with time, but values were identical after clonidine compared to no drug. Baseline plasma NE concentrations were significantly reduced in diabetic patients with autonomic neuropathy compared to diabetics without neuropathy, whereas baseline plasma DOPA concentrations were similar in the three groups investigated: 6–55 (5.03 7.26, median [interquartile range], n= 8) nmol 1‐1 in diabetics with neuropathy, 7.41 (5.79–7.97, n= 8) nmol 1‐1 in diabetics without neuropathy, and 6.85 (5.58–7.36, n=8) nmol 1–1 in controls. No relationship was obtained between baseline values of plasma NE and plasma DOPA. Plasma DOPA did not change in the upright position, whereas plasma NE increased significantly. Our results indicate that plasma DOPA is not related to sympathetic activity and may be of non‐neuronal origin.
Adenosine receptor mediated stimulation of ventilation in man
Authors: JONZON B. , SYLVÉN C. , BEERMANN B. , BRANDT R.
Published: March 2008

Abstract. We wanted to examine how adenosine stimulates ventilation in man. Bolus doses of adenosine were given i.v. in an antebrachial vein in multiples of 2.65 mg. The minute ventilation was increased by adenosine 5.3 to 15.9 mg (median values) from control 12.6 ± 1.9 1 min‐1 to 42.5 ± 4.7 1 min‐1 in a dose‐dependent manner. The adenosine receptor antagonist theophylline, 58.3 ± 3.3 (mean±SEM) µniol 1‐1 plasma, inhibited the response by approximately 25%. Dipyridamole 10 mg, an adenosine uptake blocker, enhanced the effect of adenosine by approximately 60%. The ventilation was not affected by metoprolol, atropine, naloxone or cromolyn sodium but was attenuated by hyperventilation.

The respiratory stimulation started before chest pain and cardiovascular effects such as AV‐block were encountered. It is concluded that this respiratory stimulation shows characteristics of adenosine receptor mediated responses but the location of such adenosine receptors is uncertain. The findings are compatible with a stimulatory or facilitating effect of adenosine on afferent pathways.
Erythrocyte sodium‐lithium countertransport in primary and renal hypertension:relation to family history
Authors: CARR S. J. , THOMAS T. H. , WILKINSON R.
Published: March 2008

Abstract. Sodium‐lithium countertransport (Na‐Li CT) has been reported to be increased in essential hypertension (EHT) but the nature and degree of distinction from normal controls is unclear. Of 44 unselected patients with EHT in the hospital hypertension clinic 36% had Na‐Li CT greater than the normal control range and 70% of these had a family history of hypertension. Almost all the patients with normal Na‐Li CT had no family history of hypertension. Analysis of variance showed that raised Na‐Li CT was related to both a family history of hypertension and a family history of a cardiovascular event. Of 23 patients with hypertension secondary to renal disease, 43% had Na‐Li CT greater than the normal control range and raised Na‐Li CT was related to both a family history of hypertension and a family history of cardiovascular event in the same way as EHT. Raised Na‐Li CT was not characteristic of EHT but identified a subgroup of patients with EHT and a family history of hypertension, some of whom also had renal disease.
The cytoplasmic Ca2+ response to glucose as an indicator of impairment of the pancreatic β‐cell function
Authors: HELLMAN B. , BERNE C. , GRAPENGIESSER E. , GRILL V. , GYLFE E. , LUND P.‐E.
Published: March 2008

Abstract. The effects of glucose on the cytoplasmic Ca2+ concentration (Ca2+i) regulating insulin release were investigated using pancreatic β‐cells representative for the normal and diabetic situations. Increase of the glucose concentration resulted in a slight lowering of Ca2+i followed by a rise, often manifested as high amplitude oscillations. The Ca2+i‐lowering component in the glucose action associated with suppression of insulin release became particularly prominent when the β‐cells were already depolarized by tolbutamide. Glucose‐induced inhibition of insulin release was observed also in experiments with rats made diabetic with streptozotocin or alloxan. Other studies indicated lowering of plasma insulin after intravenous glucose administration in patients with insulin‐ and noninsu‐lin‐dependent diabetes mellitus. Brief exposure of β‐cells to 2–2 mmol 1‐1 streptozotocin resulted in impairment of the response to glucose, manifested as disappearance of the cyclic variation of Ca2+i. The results indicate that glucose‐induced depolarisation is a vulnerable process, the disturbance of which may contribute to insulin secretory defects in diabetes mellitus.
Neuro‐humoral control of insulin secretion
Authors: BOBBIONI‐HARSCH E. , JEANRENAUD B.
Published: March 2008

Abstract. Hypothalamic extract from normal rats was shown to contain a principle able to stimulate insulin secretion both in vivo and in vitro.

This substance, whose peptidic nature was demonstrated by enzymatic digestion, has a molecular weight of about 1000 Daltons. An active release of this peptide was obtained when incubating hypothalamic fragments under appropriate stimulatory conditions (i.e. KC1 50 mmol 1‐1 in the incubation medium) (i.e. molecular weight and insulin secretion stimulating activity) similar to the hypothalamic peptide was evidentiated in the plasma of normal rats. Since manipulations of hte hypothalamus (i.e. electrical lesions or stimulations) could respectively decrease or enhance the plasma concentration of this substance, the hypothalamic origin of the insulin secretion stimulating principle present in the plasma was strongly suggested. The possible participation of this hypothalamic peptide to the neural control of insulin secretion is suggested.
Hormones as regulators of pancreatic secretion in man
Authors: ADLER G. , BEGLINGER C.
Published: March 2008

At the beginning of the century, Pavlov Suggested that the pancreas was exclusively controlled by the nervous reflex mechanisms. In 1902, Bayliss & Starling published their experiments on secretin and claimed that the nervous regulation is ‘superfluous and improbable’. In the following decades, especially after the discovery of CCK, it was generally held that exocrine pancreatic secretion is regulated mainly by hormones. The present summary clearly demonstrates the importance of the cholinergic system in regulating exocrine pancreatic secretion and the complexity of neurohormonal interactions. The question is no longer hormones or nerves, but rather a very complicated coordination of neural. hormonal and possible paracrine effects, resulting in the control of exocrine pancreatic activity. In this complex regulatory system, the cholinergic control is central with hormones such as CCK or secretin modulating the response.
Measurement of tissue cholecystokinin (CCK) concentrations by bioassay and specific radioimmunoassay: characterization of the bioactivity of CCK‐58 before and after tryptic cleavage
Authors: HÖCKER M. , SCHMIDT W. E. , WILMS H. M. , LEHNHOFF F. , NUSTEDE R. , SCHAFMAYER A. , FÖLSCH U. R.
Published: March 2008

Abstract. Cholecystokinin (CCK) was measured in an extract of porcine brain by a bioassay system based on the enzyme release from isolated pancreatic acini and a specific radioimmunoassay. The tissue extract represented a crude peptide preparation of porcine brain that contained several molecular forms of CCK, most of them of high molecular weight including CCK‐58. The different molecular forms of CCK in the porcine brain extract were isolated by high performance liquid chromatography (HPLC). Determination of CCK‐like bioactivity and immunoreactivity after HPLC was performed in parallel by bioassay and radioimmunoassay, respectively CCK‐58 was the most abundant molecular form in the porcine brain extract, followed by CCK‐33, and CCK‐8. Both assay systems measured similar relative concentrations of all different molecular forms of CCK. To elucidate the biological potency of CCK‐58 before and after tryptic cleavage, a CCK‐58‐enriched fraction was prepared by HPLC. Part of this material was quantitatively cleaved by trypsin resulting in the formation of small molecular forms of CCK. Bioactivity and immunoreactivity of equal amounts of cleaved and uncleaved material (= CCK‐58) were determined by bioassay and radioimmunoassay in parallel. Cleavage of CCK‐58 increased CCK‐like bioactivity by 260% and CCK‐like immunoreactivity by 310%. These results indicate that in a rat pancreatic acini system, porcine CCK‐58 exerts 25–30% bioactivity compared to smaller CCK forms. The specific CCK antiserum G‐160 seems to possess 25–30% affinity to CCK‐58 in comparison to trypsin‐cleaved CCK‐58. It can be concluded that this antiserum exhibits an affinity to different molecular forms of CCK which parallels their relative bioactivity. This indirectly confirms that antiserum G‐160 detects the sulphated tyrosine residue within the central region of CCK‐8, which is crucial for CCK‐like bioactivity, and shows binding characteristics probably similar to a pancreatic acinar CCK receptor.
Interruption of the entero‐pancreatic axis: effects of induced malabsorption
Authors: CASPARY W. F.
Published: March 2008

Abstract. The rate of intestinal absorption depends not only on the mode of ingestion and the chemical nature of nutrients ingested, but largely on the regulatory gastrointestinal motility processes and the digestive‐absorptive capacity of the gastrointestinal tract.

This review is mainly concerned with modes of nutrient absorption and their regulatory mechanisms.

Modulation of intestinal absorptive processes possibly seems to be a valuable therapeutic strategy in various metabolic (diabetes mellitus) and gastrointestinal diseases.
The effect of α‐adrenergic blockade on responses of peripheral blood cells to acute insulin‐induced hypoglycaemia in humans
Authors: FISHER B. M. , HEPBURN D. A. , SMITH J. G. , FRIER B. M.
Published: March 2008

Abstract. Acute hypoglycaemia provokes rapid changes in peripheral blood cell counts. To examine possible adrenergic mechanisms modulating these changes, counts of peripheral blood cells including lymphocytes, granulocytes and erythrocytes were measured in response to acute hypoglycaemia in a group of six normal subjects in control conditions (study 1), and during α‐adrenergic blockade with phentolamine (study 2). In study 1 hypoglycaemia provoked a biphasic leucocyte response, with an early rise in lymphocyte count and a later rise in granulocyte count. The erythrocyte count increased modestly following hypoglycaemia. During α‐adrenergic blockage, the rise in total leucocyte count was diminished, with the rise in the lymphocyte count being greatly obtunded. These findings suggest that the increments of peripheral lymphocyte and erythrocyte counts in response to acute insulin‐induced hypoglycaemia are mediated via α‐adrenoreceptors.
Autoradiographic localization of Na+‐dependent L‐valine uptake by the jejunum of streptozotocin‐diabetic rats
Authors: DEBNAM E. S. , EBRAHIM H. Y.
Published: March 2008

Abstract. The mechanisms involved in the increased Na+‐dependent nutrient uptake across intestine of diabetic animals are poorly understood. Here we have studied the effect of acute (7d) and chronic (30–40d) diabetes on the autoradiographic localization of 3H‐L‐valine accumulation by rat jejunal villi and on entero‐cyte migration rate. In control rats, Na+‐dependent valine uptake was confined to enterocytes on the upper 20–23% of the villus. In intestine from diabetic rats, however, this area was extended to occupy the upper 42–45% of an enlarged villus surface. Hyperphagia was not responsible for the expanded functional surface and systemic factors are therefore implicated in the adaptive response. Enterocyte migration rate was found to be unaffected by diabetes but an increased villus height in this condition resulted in an additional 13.5 h in enterocyte lifespan. These data are compatible with the hypothesis that during diabetes the earlier maturation of enterocyte absorptive function produces an epithelial surface containing a higher proportion of mature enterocytes.
Are the serum levels of endotoxin‐binding proteins reliable predictors of complications in the course of peritonitis?
Authors: BERER D. , KITTERER W. R. , BERGER H. G.
Published: March 2008

Abstract. In the present study, the serum levels of the endotoxin‐binding proteins transferrin, α2‐macroglo‐bulin and Gc‐globulin were nephelometrically determined in the morning of the first day after surgical treatment of peritonitis. The aim was to determine whether the occurrence of organ failure can be predicted by the serum levels of the described proteins. A serum level of transferrin below 1.15 g 1−1 allows the prediction of organ failure with a sensitivity of 78.6% and a specificity of 81.8%. As in the case of α2‐macroglobulin, sensitivity and specificity reached 67.8% and 72.7% respectively at a border level of 1.05 g 1−1. The predictive value of Gc‐globulin, limit 0.2 g 1−1, was in the same range. So the serum levels of these proteins allow an early prediction of forthcoming organ failure in the course of peritonitis. Furthermore, these results support the significance of the endotoxin interaction with these proteins.
Normal homeostasis of fibrinolysis in nephrogenic diabetes insipidus in spite of defective V2‐ receptor‐mediated responses of tissue plasminogen activator release
Authors: BROMMER E. J. P. , BRINK H. , DERKX F. H. M. , SCHALEKAMP M. A. H. , STIBBE J.
Published: March 2008

Abstract. Three patients with congenital, nephrogenic diabetes insipidus (NDI) from two unrelated families were tested for haemostatic and fibrinolytic responses to DDAVP infusion and venous occlusion. None of the three patients showed a response of factor VIII:C, vWF:Ag or t‐PA to DDAVP, a V2‐agonist. However, the baseline levels of these factors in the patients' plasma were normal and during venous occlusion a rise in t‐PA antigen and t‐PA activity was observed in all patients. One patient showed a definite response of the t‐PA antigen level to exercise. It is concluded that (extrarenal) V2‐receptor‐mediated responses are absent in these patients, but that baseline homeostasis and the response to venous occlusion and physical exertion are intact. Presumably, these depend on other mechanisms. This observation denies a central role for vasopressin receptors in the on‐demand regulation of clotting and clot dissolving properties of the blood.
Experimental atherosclerosis: effects of oestrogen and atherosclerosis on thromboxane and prostacyclin formation
Authors: FOGELBERG MONICA , VESTERQVIST O. , DICZFALUSY U. , HENRIKSSON P.
Published: March 2008

Abstract. We evaluated the effect of oestrogen and experimental atherosclerosis on the in vivo formation of thromboxane and prostacyclin in rabbits. Twenty‐four New Zealand White rabbits were divided into four groups. One group received control diet, one group received control diet and oestrogen, one group received control diet supplemented with 1% cholesterol and one group received cholesterol supplemented diet and oestrogen during 3 months. The in vivo formation of thromboxane and prostacyclin were measured as 2,3‐dinor‐TxB2 and 2,3‐dinor‐6‐keto‐PGFlx in urine by gas chromatography/mass spectro‐metry.

All rabbits on cholesterol diet became hypercholes‐terolaemic and developed atherosclerosis. As in previous experiments cholesterol and oestrogen‐treated rabbits had only minor atherosclerosis compared to purely cholesterol‐fed rabbits. The in vivo production of thromboxane in oestrogen‐treated rabbits decreased from 1641 ± 162 pg mg−1 creatinine pretreat‐ment to 808±92 pg mg−1 creatine at 12 weeks (P = 0.0001). In contrast, the in vivo production of prostacyclin increased during oestrogen treatment (P = 0.0027). The in vivo production of prostacyclin decreased during pure cholesterol feeding without oestrogen 1384 ± 219 pg mg−1 creatinine to 702 ±142 pg mg−1 creatinine (P = 0.0091). The ratio of in vivo prostacyclin to thromboxane formation increased 2–3‐fold during oestrogen therapy (P = 0.0007).

In summary the study shows a pronounced reduction in the in vivo thromboxane formation and an increase in the ratio of prostacyclin/thromboxane production during oestrogen therapy. In parallel with this we found in this experiment, as well as in other experiments, a drastic reduction in atherosclerotic involvement during oestrogen therapy. These putative favourable changes in prostanoid formation during oestrogen treatment could add further positive actions of oestrogen on atherosclerosis in addition to previously described reductions in atherogenic lipopro‐teins and increases in high density lipoprotein cholesterol.
Biliary lipids in familial combined hyperlipidaemia: effects of acipimox therapy
Authors: ERICSSON S. , ERIKSSON M. , ANGELIN B.
Published: March 2008

Abstract. Biliary lipid composition and plasma lipo‐protein levels were determined in nine gallstone‐free male patients with familial combined hyperlipidaemia (FCHL). In the basal situation, stimulated fasting duodenal bile from the patients contained a higher relative concentration of cholesterol than bile obtained from age‐ and sex‐matched normal controls (n= 22), 6.5 ± 0.3 (SEM) vs. 4.7 ± 0.2 mol % (P<0.01). This resulted in a higher cholesterol saturation of bile from FCHL patients, 85±6 vs. 70±2% (P<0.05).

After 6 weeks of treatment with acipimox, 750 mg day‐1, total plasma triglycerides were lowered from 7.5± 1.5 to 4.6 ± 0.7 mmol l‐1 (P<0.05) and plasma cholesterol decreased from 8.0 ±0.1 to 7.1 ±0.3 mmol l‐1 (P<0.05) in the FCHL patients. These changes were mainly due to a decrease in very low density lipoprotein concentrations while low density lipopro‐tein levels remained unaltered.

The relative proportion of cholesterol in stimulated fasting duodenal bile was reduced from 6.5±0.3 to 4.3 ± 0.5 mol % (P<0.01), resulting in ‘normalization’ of biliary cholesterol saturation, from 85 ± 6 to 58±6% (P< 0.005). No correlations between the changes in biliary lipid composition and those in plasma lipoprotein levels were observed.

The results indicate that treatment with acipimox in patients with FCHL, a disorder commonly associated with supersaturated bile, does not increase biliary cholesterol, and presumably not the risk for gallstone formation.
Abnormal 3,4‐dihydroxyphenylalanine (dopa) concentrations in plasma and urine of patients with cystic fibrosis
Authors: SCHÖNI M. H. , TÜRLER K. , KÄSER H. , KRAEMER R.
Published: March 2008

Abstract. Plasma and urine concentrations of the free amino acid 3,4‐dihydroxyphenylalanine (dopa) were determined in a blind study in 16 children and adolescents with cystic fibrosis (CF), eight heterozy‐gote parents of these children and in 11 healthy subjects who served as controls. To exclude any drug interference with catecholamine metabolism and to evaluate a tentative basic metabolic alteration in cystic fibrosis, the same determinations were done in 11 newly diagnosed infants (age 1–84 months). Free plasma dopa was significantly (P<0.01) elevated in CF (27.0 ± 6.1 nmol l‐1 vs. 19.1 ±5.0 nmol l‐1 in the controls); heterozygotes had the lowest concentration: 11.5 ± 5.8 nmol 1 (P<0.01 compared with normals). Increased plasma dopa concentrations were measured in the newly diagnosed infants (35.4± 16.9 nmol l‐1). Renal dopa clearance was the same in cystic fibrosis (9.26 ± 5.71 ml min‐1 1.73 m‐2) and controls (10.87 ± 2.46 ml min‐1 1.73 m‐2). A concommitant elevation of metabolic products as dopamine and noradrenaline in plasma and urine was noticed. These data are consistent with a dopa abnormality in this genetic disease.