bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of acute bile acid pool depletion on total and ionized calcium concentrations in human bile*
Authors: GLEESON D. , MURPHY G. M. , DOWLING R. H.
Published: March 2008

Abstract. Although calcium salts are important components of gallstones, there are few data on the total and ionized calcium content of human bile. Therefore, in 14 fasting T‐tube patients studied 7–11 days after cholecystectomy, we measured bile flow, bile acid [BA], total [CaTOt] and free ionized [Ca++] calcium concentrations, in 20–30 min bile collections during acute BA pool depletion induced by 6–8 h of continuous bile drainage. During washout of the BA pool there were parallel falls in bile flow, BA output and total calcium output (correlation coefficients ranging from 0.59 to 0.99; P< 0.02–0.001). In 12 of the 14 patients, [CaTOT] also fell (from 1.84 ± 0.29 to l.32 ± 0.34 mmol L‐1) in parallel with [BA] (from 34.0 ± 14.0 to 8.2 ± 8.0 mmol L‐1; r= 0.75–0.98; P<0.005). In contrast, biliary [Ca++] remained virtually unchanged. These data suggest that the BAs are linked to the bound, rather than to the free, ionized, fraction of biliary calcium, which is consistent with in vivo calcium binding by BAs. A model is proposed in which BA‐induced biliary calcium secretion results from (i) bile acid‐induced water flow via solvent drag; and (ii) calcium binding in the bile canaliculus by bile acids, which induces paracellular diffusion of Ca++, thereby maintaining [Ca++] independent of [BA].
Renal clearance of atrial natriuretic peptide during acute unilateral complete ureteral obstruction in the pig
Authors: FRØKLER J. , DJURHUUS J. C. , PEDERSEN E. B.
Published: March 2008

Abstract. Renal extraction and renal plasma clearance of atrial natriuretic peptide from pigs with complete unilateral ureteral obstruction (UUO) and from intact anaesthetized pigs were determined from arterio‐venous differences in plasma atrial natriuretic peptide and measured renal plasma flow. The effect of administration of either a cyclooxygenase inhibitor or an angiotensin converting enzyme inhibitor was examined during UUO. Renal extraction ratio and renal clearance rate of plasma atrial natriuretic peptide (ANP) in the intact pig was stable during the 15 h observation period. UUO resulted in a significant (P<0.05) temporary increase in renal extraction ratio and a significant (P<0.05) reduction in the renal clearance rate of atrial natriuretic peptide. During cyclooxygenase inhibition there was a significant increase in the renal extraction ratio of ANP. During angiotensin II converting enzyme inhibition, renal handling of atrial natriuretic peptide did not differ from that observed in control animals. The present data demonstrate that atrial natriuretic peptide is extracted by the obstructed kidney. Despite the significant reduction in renal blood flow during indo‐methacin administration, renal clearance of ANP was unaltered. The increase in ipsilateral renal extraction of atrial natriuretic peptide immediately after ureteral obstruction and indomethacin administration could be explained either by a direct influence of PGE2 on the renal haemodynamics altering renal extraction of ANP, or by a compensatory mechanism attempting to preserve renal function.
Fast transmission of alterations in plasma phosphatidylcholine/sphingomyelin ratio and lyso phosphatidylcholine levels into changes of red blood cell membrane phospholipid composition after low density lipoprotein apheresis
Authors: KULSCHAR R. , ENGELMANN B. , BRÄUTIGAM C. , DUHM J. , THIERY J. , RICHTER W. O.
Published: March 2008

Abstract. In order to evaluate whether changes in plasma phospholipid composition are rapidly transmitted to the red blood cell membrane (RBCM) under in vivo conditions, the levels of major phospholipids in plasma, low density and high density lipoproteins (LDL and HDL) as well as in RBCM were determined before (pre), directly after (post) and 2 days after (48 h post) LDL apheresis in six patients with severe hypercholesterolaemia. LDL apheresis induced a 30–70% decrease in plasma and LDL cholesterol and total phospholipid levels within 2–3 h. Concomitantly, the percentages of plasma phosphatidylcholine (PC) and the PC/sphingomyelin (SM) ratio were increased compared to initial values. The percentage of plasma lyso PC (LPC) determined before apheresis in the patients was 30% lower with respect to the mean level of LPC in a normolipidaemic control. For LPC of LDL no differences were observed between normolipidaemia and hypercholesterolaemia. LDL apheresis induced a rise by about one third in the percentage of plasma LPC. At 48 h post, plasma LPC levels reapproached pre‐apher‐esis levels, while the percentages of PC and the PC/SM ratio remained elevated. The pattern of changes induced by apheresis in plasma PC, SM and LPC levels was mimicked by changes in RBCM phospholipids. Strong positive relationships were noted for PC, SM and PC/SM as determined at pre, post and 48 h post between plasma and RBCM. In summary, changes in plasma PC, LPC, and PC/SM ratios as induced by LDL apheresis are rapidly transmitted to the RBCM under in vivo conditions, most probably as a result of phospholipid transfer between both compartments. In addition, the percentages of LPC in plasma and LDL particles of patients with severe hypercholesterolaemia are certainly below the levels of LPC reported to mediate biological effects of in vitro oxidized LDL.
Plasma homocysteine and menopausal status**
Authors: WOUTERS M. G. A. J. , MOORREES M. Th. E. C. , MOOREN M. J. VAN DER , BLOM H. J. , BOERS G. H. J. , SCHELLEKENS L. A. , THOMAS C. M. G. , ESKES T. K. A. B.
Published: March 2008

Abstract. The aim of the study was to measure the concentrations of plasma homocysteine in premeno‐pausal and postmenopausal women, and to examine a possible relationship between plasma homocysteine and oestrogen status. Homocysteine metabolism was studied by a standardized oral methionine loading test, and oestrogen status was assessed by the measurement of serum 17β‐oestradiol. Forty‐six pre‐menopausal and 26 postmenopausal healthy women without a history of vascular disease or adverse pregnancy outcome were recruited by public advertisement. The main outcome measures were the concentrations of fasting and postmethionine plasma homocysteine, and serum 17β‐oestradiol. Fasting plasma homocysteine concentrations (mean ± SD) were significantly higher in postmenopausal women as compared to premenopausal women (12 ± 4 μmol L‐1 and 10 ± 3 μmol L‐1, respectively) as well as postmethionine plasma homocysteine concentrations (46 ± 16 μimol L‐1 and 32 ± 9 μmol L‐1, respectively). In premenopausal women, postmethionine plasma homocysteine was negatively and significantly correlated to serum 17β‐oestradiol (r=‐0.34). It is concluded that plasma homocysteine concentrations, both fasting and after methionine loading, are significantly higher in postmenopausal women than in premenopausal women. In premenopausal women, the higher concentrations of serum 17 β‐oestradiol may account in part for the lower concentrations of postmethionine plasma homocysteine.
Assessment of cardiac autonomic control by heart period variability in patients with early‐onset familial obesity
Authors: PETRETTA M. , BONADUCE D. , FILIPPO E. DE , MUREDDU G. F. , SCALFI L. , MARCIANO F. , BIANCHI V. , SALEMME L. , SIMONE G. DE , CONTALDO F.
Published: March 2008

Abstract. For quantitative assessment of cardiac autonomic control, time and frequency domain measures of heart period variability were calculated by 24 h Holter recording in 10 young obese women with early‐onset familial obesity and in 10 control subjects. Ultra low frequency and very low frequency power were lower in obese subjects than in controls (P < 0.05). High frequency power, a pure measure of vagal tone, was comparable between the two groups. However, low frequency power, which analysed over a 24 h Holter recording reflects parasympathetic more than sympathetic activity, was slightly lower in obese subjects than in controls (P= 0.06). Body mass index showed an inverse correlation with total power (r= ‐0.62; P < 0.05) and separately with ultra low (r=‐0.59; P < 0.01), very low (r= ‐0.64; P < 0.005), low (r= ‐0.61; P < 0.005) and high frequency power (r=—0.53; P < 0.05). These results demonstrate a parasympathetic withdrawal increasing body weight. The reduction of ultra low frequency and very low frequency power, which are associated with sudden death, may help to explain the higher cardiovascular risk in obesity.
Monoclonal lymphocyte proliferation and bcl‐2 rearrangement in essential mixed cryoglobulinaemia
Authors: ELLIS M. , RATHAUS M. , AMIEL A. , MANOR Y. , KLEIN A. , LISHNER M.
Published: March 2008

Abstract. A patient with essential mixed cryoglobulinaemia (EMC) type II and hepatitis C virus (HCV) infection, in whom immunophenotypic and genotypic studies demonstrated a clonal proliferation of B lymphocytes, is described. Fluorescent in situ hybridization with probes to Ig heavy chain gene and to the oncogene bcl‐2 demonstrated a translocation of bcl‐2 to the immunoglobulin heavy chain locus on chromosome 14. A sharp rise in the level of the monoclonal IgM was associated with a second genetic aberration [t(8:22) (q24:q11)]. No other clinical evidence of disease progression could be demonstrated. Low grade lymphoproliferative disorder with typical cyto‐genetic abnormalities developed on the background of EMC and HCV. Clinical progression was associated with a second genetic abnormality involving the myc oncogene. It is possible that HCV chronic infection may indirectly influence oncogenes associated with lymphoma.
Lack of plasma lipid peroxidation during LDL‐apheresis by heparin‐induced extracorporeal LDL‐precipitation
Authors: WIELAND E. , SCHETTLER V. , CREUTZFELDT C. , KICKBUSCH H. , SCHUFF‐WERNER P.
Published: March 2008

Abstract. The heparin‐induced extracorporeal precipitation of low density lipoproteins (HELP) is a well established clinical apheresis procedure to markedly reduce cholesterol levels. The biocompatibility of this filter system was investigated by the determination of lipid peroxidation products. Both lipid hydro‐peroxides and thiobarbituric acid reactive substances (TBARS) were determined before, during and after 38 aphereses in 21 patients undergoing regular HELP treatment. Although HELP patients had significantly elevated TBARS compared to 93 healthy controls (3.13 ±0.64 vs. l.66±0.50 μmol L‐1; P<0.01), no significant differences were observed compared to either 104 patients suffering from angiographically confirmed coronary heart disease (3.42 ±0.81 μmol L‐1; P> 0.05 vs. HELP patients) or 38 aged‐matched hyperlipidaemic patients (3.30 ±0.75 μmol L‐1; P>0.05 vs. HELP patients), neither of which were included in the HELP programme. No lipid hydroperoxides were detected in the plasma of HELP patients either before or after the extracorporeal treatment. After the LDL‐apheresis TBARS were significantly decreased (2.60 ± 0.52 μmol L‐1) compared to the values before the treatment (P<0.01). There was no evidence for the formation of lipid hydroperoxides within the HELP circuit. It is suggested, therefore, that plasma lipids are not oxidized by the HELP procedure.
Measurement of human chorionic gonadotropin‐related immunoreactivity in serum, ascites and tumour cysts of patients with gynaecologic malignancies
Authors: GROSSMANN M. , HOERMANN R. , GOCZE P. M. , OTT M. , BERGER P. , MANN K.
Published: March 2008

Abstract. Human chorionic gonadotropin (hCG)‐like molecules have been reported to be elevated in a substantial fraction of serum samples from patients with various gynaecologic tumours and have been discussed as possible markers in these malignancies. Employing highly sensitive and specific immunoradio‐metric assays, we determined total hCG‐related immunoreactivity (hCG/hCGβ), as well as free α‐subunit (α‐SU), common to all glycoprotein hormones, in serum (n= 106) and malignant effusions (n= 26) of women with gynaecologic malignancies. For comparison, we also measured hCG/hCGβ in nonmalignant ascitic fluids (n= 21). HCG/hCGd̃ serum levels were elevated (>5 IU L‐1) in 39 of 106 patients (37%) with gynaecologic malignancies, whereas free α‐SU was above normal range only in seven (6.6%). Frequencies of hCG/hCGβ elevations were similar in women with endometrial (n= 39), cervical (n= 40) and ovarian (n= 27) cancer, being 30%, 35% and 41%, respectively. In malignant ascites (n= 15) and tumour cyst fluids (n= 11) of patients with ovarian cancer, hCG/ hCGβ concentrations were significantly higher than in the corresponding serum samples and benign ascitic samples. Free α‐SU, on the other hand, was increased in only one of 26 malignant effusions. In conclusion, hCG/hCGβ is frequently elevated in serum of patients with endometrial, cervical and ovarian cancer and may serve as a tumour marker in these malignancies, particularly in patients where other markers are negative. In this respect, analysis of ascitic or tumour cyst fluids may be of higher diagnostic value as serum measurements.
Serum concentration of endogenous G‐CSF in women during the menstrual cycle and pregnancy
Authors: MAKINODA S. , MIKUNI M. , FURUTA I. , OKUYAMA K. , SAGAWA T. , FUJIMOTO S.
Published: March 2008

Abstract. Although granulocyte‐colony stimulating factor (G‐CSF) is commonly used in the field of supportive therapy for cancer treatment, the serum concentration of endogenous G‐CSF in healthy women is still obscure due to the low sensitivity (30 pg mL‐1) of the usual enzyme immunoassay. With the development of a highly sensitive (l.0 pg mL‐1) chemiluminescent immunoassay by Kiriyama et al., we have clarified the changes of serum G‐CSF levels in healthy women during the menstrual cycle and pregnancy. The G‐CSF concentration showed a peak value of 27.3± 2.5 pg mL‐1 (mean±SEM) at the ovulatory phase during the menstrual cycle, which is significantly higher than in all other phases (P < 0.0001, unpaired t‐test). A significantly higher value compared to the menstrual cycle, except during the ovulatory phase, was also revealed throughout pregnancy (P < 0.0001, unpaired t‐test). These results suggest that G‐CSF plays an important role in ovulation and the maintenance of pregnancy.
Apolipoprotein E and lipoprotein lipase co‐ordinately enhance binding and uptake of chylomicrons by human hepatocytes
Authors: MANN W. A. , MEYER N. , WEBER W. , RINNINGER F. , GRETEN H. , BEISIEGEL U.
Published: March 2008

Abstract. ApoE and LpL are important in the metabolism of triglyceride rich lipoproteins, and defects in either or both may result in hyperlipidaemia. It has previously been shown that ApoE and LPL specifically enhance cellular catabolism of lipoproteins by various cell lines. The authors determine in this paper the effect of ApoE and LpL on chylomicron and LDL binding and uptake by human hepatocytes in primary culture. Separate addition of ApoE and LpL greatly enhanced binding and uptake of chylomicrons. Simultaneous addition of ApoE and LPL further increased chylomicron uptake in an additive way. For LDL a different situation was observed: neither ApoE nor LPL mediated a significant increase of lipoprotein uptake. The authors conclude that ApoE and LpL co‐ordinately enhance binding and uptake of chylomicrons by primary human hepatocytes. The effect appears to be independent of LDL receptors and the co‐ordinate effect of ApoE and LPL may be important for normal chylomicron catabolism.
Post‐operative erythropoiesis is limited by the inflammatory effect of surgery on iron metabolism
Authors: BIESMA D. H. , WIEL A. VAN DE , BEGUIN Y. , KRAAIJENHAGEN R. J. , MARX J. J. M.
Published: March 2008

Abstract. The decrease in haemoglobin concentration commonly observed after major surgery is usually corrected by red cell transfusions or oral iron medication. The increased awareness of blood‐transmissible diseases has led to the restrictive use of homologous blood and to interest in alternatives for correcting anaemia. We investigated the pathophysiology of postoperative anaemia by studying variables of erythropoiesis, iron metabolism, and inflammation in 48 consecutive patients who underwent total hip replacement. Haemoglobin concentration remained low during 14 days after surgery with only a mild increase in erythropoietin concentration and reticulocyte count. No increase in serum transferrin receptor concentration was observed during the first 2 weeks after surgery. Postoperative serum ferritin increased, whereas serum iron, transferrin and transferrin saturation decreased significantly. There was a marked increase in interleukin‐6 and C‐reactive protein with maximal values on the 1st and 4th postoperative day, respectively. At 6 weeks after surgery, haemoglobin concentration and variables of iron metabolism were almost at the preoperative level and serum transferrin receptor concentration was significantly increased, indicating increased erythropoietic activity. These changes were preceded by the normalization of interleukin‐6 and C‐reactive protein levels. Haemoglobin, iron, transferrin, and ferritin concentrations were not influenced by iron therapy during the postoperative period and no differences of erythropoietic and iron variables were observed between transfused and non‐transfused patients. In conclusion, post‐operative erythropoiesis is associated with an inflammatory effect of surgery on iron metabolism, which can explain, despite a slightly increased production of erythropoietin, the persistence of anaemia and the lack of effect of iron supplementation after surgery.
Serotonin acts as a radical scavenger and is oxidized to a dimer during the respiratory burst of human mononuclear and polymorphonuclear phagocytes*
Authors: SCHUFF‐WERNER P. , SPLETTSTÖSSER W. , SCHMIDT F. , HUETHER G.
Published: March 2008

Abstract. Isolated human mononuclear and polymorphonuclear phagocytes were stimulated in the presence and absence of serotonin (5‐HT), the major secretory product of activated platelets, and the release of reactive oxygen metabolites during the respiratory burst was assessed by luminol‐enhanced chemilumi‐nescence. In the presence of 5‐HT, a dose‐dependent suppression of the chemiluminescence signal occurred, irrespective of the stimulus used to elicit the respiratory burst. A similar suppression of luminol‐enhanced chemiluminescence was also seen in a radical generating cell free system. 5‐HT was found to be oxidized by the reactive oxygen species released by stimulated phagocytes. This oxidation is prevented in the presence of other antioxidants. The major 5‐HT oxidation product was isolated by gel chromatography and identified by mass‐spectrometry as a 5‐HT dimer, probably 5,5′‐dihydroxy‐4,4′‐bitryptamine. It is concluded that the 5‐HT released from activated thrombocytes at sites of inflammation and endothelial cell damage acts as a true scavenger of reactive oxygen species generated during the respiratory burst of stimulated phagocytes and may thus modulate various aspects of cell‐mediated defence reactions.
Intracoronary magnesium is not protective against acute reperfusion injury in the regional ischaemic‐reperfused dog heart
Authors: SCHLACK W. , BIER F. , SCHÄFER M. , UEBING A. , SCHÄFER S. , BORCHARD U. , THÄMER V.
Published: March 2008

Abstract. Intravenous magnesium lowers mortality in patients with suspected myocardial infarction. We tested the hypothesis that the protective effect may be due to a direct, local influence of magnesium on myocardial reperfusion injury in a dog model of ischaemia/reperfusion. Ten anaesthetized open chest dogs underwent 1 h of left anterior descending artery (LAD) occlusion and 6 h of reperfusion. The animals received intracoronary (i.c.) magnesium aspartate (Mg, n= 5) or vehicle infusion (n= 5) for the first hour of reperfusion. Mg infusion was adapted to actual LAD flow (ultrasonic flow probe) to increase regional plasma concentration by 4 mmol L‐1. Regional myocardial function was measured as percent systolic wall thickening (sWTh, sonomicrometry). Intracoronary Mg increased LAD flow during application (at 15min reperfusion; Mg, 194±44 (mean±SD); control, 116±41 mLmin‐1 100g‐1, P< 0.01). sWTh decreased during coronary occlusion from 14.3 ± 7.1 % to ‐ 4.7 ± 2.7% in the control group and from 14.8±2.5% to ‐4.1 ±3.1% in the Mg group. Throughout the reperfusion period wall function remained depressed in both groups to a similar degree (control, ‐ 3.5 ± 1.8%; Mg, ‐ 3.0 ± 1.9% at 6 h reperfusion). Global haemodynamics were not different. Infarct size after 6h reperfusion (TTC staining) was similar in both groups (Mg, 20.6±5.0; control, 24.4±8.7% of area at risk). Regional magnesium application (i.e.) to post‐ischaemic reperfused myocardium had no influence on infarct size or post‐ischaemic regional wall function in this model. The beneficial action of systemic Mg in patients with myocardial infarction is probably not due to an early direct protective effect on ischaemic‐reperfused myocardium.
Liposoluble vitamins and naturally occurring carotenoids in porphyria cutanea tarda
Authors: ROCCHI E. , STELLA A. M. , CASSANELLI M. , BORGHI A. , NARDELLA N. , SEIUM Y. , CASALGRANDI G.
Published: March 2008

Abstract. The authors consider two groups of patients with overt sporadic porphyria cutanea tarda (PCT) from different continents, with the aim of evaluating the possible impairment of the liposoluble antioxida‐tive system, given the possible synergic effect of porphyrins and iron in promoting oxidative cellular damage. Twenty‐three Italian outpatients with overt sporadic PCT and 11 outpatients with PCT from Buenos Aires (Argentina) were matched with 60 patients with liver cirrhosis and 52 healthy Italian controls. Serum levels of alpha‐ and beta‐carotene, cryptoxanthin, zeaxanthin, lutein, lycopene, retinol and alpha‐tocopherol were detected by a high‐performance liquid chromatographic technique devised in our laboratory, which afforded an accurate and simultaneous resolution of all these compounds. The results point to a significant reduction in plasma levels of alpha‐ and beta‐carotene in both the PCT populations with respect not only to controls, but also to the cirrhotic population, which had more severe liver damage. Moreover, other carotenoids with proven antioxidative properties, like cryptoxanthin and lycopene, are greatly reduced in our PCT populations. This confirms the suggested synergic effect of iron and porphyrins in the oxidative intracellular damage with consequent depletion of antioxidative liposoluble molecules.
Effect of colectomy with ileo‐anal anastomosis on the biliary lipids
Authors: GALATOLA G. , FRACCHIA M. , JAZRAWI R. P.
Published: March 2008

Abstract. Total colectomy with ileo‐anal anastomosis is an effective treatment for ulcerative colitis and familial adenomatous polyposis. The absence of the colon and the coexistence of bile acid malabsorption may increase bile lithogenicity, but data on biliary lipid composition in patients with this operation is lacking. Our aim was to assess bile lithogenicity, bile composition and mass of biliary lipids within the gallbladder. We studied 11 patients with total colectomy and ileo‐anal anastomosis and 16 healthy controls. We measured the percentage composition of conjugated bile acids and the masses within the gallbladder of the three main biliary lipids. This method, in contrast with measurement of cholesterol saturation index, can determine the cause of bile lithogenicity in terms of absolute modifications of the biliary lipids. There was no difference in the cholesterol saturation index between patients and controls. Colectomy patients had reduced masses of all three biliary lipids (medians and ranges, mmol): cholesterol (Ml (0.03–0.24) vs. 0.36 (0.02–0.96), P<0.02; bile acid 1.62 (0.75–5.21) vs. 3.95 (1.27–8.70), P<;0.01; phospholipids 0.35 (0.07–0.69) vs. 1.14 (0.14–3.00), P>0.002. They also had reduced per cent deoxycholic acid: 3.8 (0.0–27.6) vs. 17.4 (6.4–44.7), P< 0.005, and increased percent cholic acid: 44.9 (23.3–71.4) vs. 34.3 (19.2–57.9), P<0.05. We conclude that, despite having bile acid malabsorption, patients with colectomy and ileo‐anal anastomosis have a normal cholesterol saturation index, caused by a concomitant reduction in the masses of all three biliary lipids. The reduced per cent biliary deoxycholic acid may help explain the reduced cholesterol and phospholipid masses in these patients. Total colectomy with ileo‐anal anastomosis does not seem to predispose to the formation of cholesterol gallstones.
Simvastatin decreases the hepatic secretion of very‐low‐density lipoprotein apolipoprotein B‐100 in heterozygous familial hypercholesterolaemia: pathophysiological and therapeutic implications
Authors: WATTS G. F. , CUMMINGS M. H. , UMPLEBY M. , QUINEY J. R. , NAOUMOVA R. , THOMPSON G. R. , SÖNKSEN P. H.
Published: March 2008

Abstract. We studied six patients with heterozygous familial hypercholesterolaemia (FH) before and after 8 weeks of treatment with simvastatin (40 mg day‐1), an inhibitor of 3‐hydroxy‐3‐methyl‐glutaryl‐Coenzyme A. Simvastatin decreased plasma low‐density lipoprotein (LDL) cholesterol by 43% (P= 0.002), triglycerides by 27% (P= 0.05) and mevalonic acid (a measure of in vivo cholesterol synthesis) by 20% (P= 0.002); high‐density lipoprotein cholesterol increased by 17% (P= 0.02). The hepatic secretion rate of very‐low‐density lipoprotein apolipoprotein B‐100 (VLDL apoB) was measured directly using a primed, constant intravenous infusion of l‐[13C]‐leucine with monitoring of the isotopic enrichment of apoB by gas chromatography‐mass spectrometry; fractional secretion rate (FSR) was derived using a mono‐exponential function. Simvastatin decreased the FSR, ASR and pool size of VLDL apoB by 17% (14.3 (SEM 3.6)) vs. (11.9 (SEM 3.5) pools day‐1, P= 0.10), 83% (51.4 (SEM 17.9) vs. (8.6 (SEM 1.4), P= 0.007mgkg‐1day‐1) and 65% (234.2 (SEM 30.4) vs. 82.6 (SEM 24.0)mg, P= 0.02), respectively. The change in the ASR of VLDL apoB was significantly correlated with the change in plasma LDL cholesterol concentration (P= 0.04), but not with the change of triglyceride or mevalonic acid. We conclude that the hepatic secretion of VLDL apoB in FH is decreased by simvastatin, which may partly explain the fall in plasma cholesterol. This effect does not appear to be directly related to the inhibition of cholesterol synthesis and may be due to decreased hepatic delivery of cholesterol esters via the LDL receptor‐independent pathway, but these mechanisms require further investigation.
Influence of residual C‐peptide secretion on the arginine vasopressin response to hypoglycaemia and metoclopramide in insulin‐dependent diabetes
Authors: CHIODERA P. , VOLPI R. , CAPRETTI L. , SPERONI G. , CAFFARRI G. , COLLA R. , CAIAZZA A. , COIRO V.
Published: March 2008

Abstract. Arginine vasopressin (AVP) hypersecretion in response to metoclopramide or to insulin‐induced hypoglycaemia has been described in type I diabetes mellitus. In the present study, we examined whether residual endogenous insulin secretion may play a role in the control of this abnormal AVP secretory pattern. For this purpose, 21 insulin‐dependent diabetic men and 10 age‐ and weight‐matched normal men were tested with MCP (20 mg in an i.v. bolus). On a different occasion, subjects were tested with insulin (0.15IU kg‐1). The diabetic patients were subdivided into C‐peptide negative patients (CpN, 11 patients without detectable endogenous pancreatic β cell activity) (group I) and C‐peptide positive patients (CpP, 10 patients with residual endogenous insulin secretion) (group II). Experiments started after optimization of the metabolic status of the diabetic men by 3 days of treatment with continuous subcutaneous insulin infusion. The basal concentrations of AVP were similar in all groups. The administration of MCP induced a striking elevation in plasma AVP levels in the normal controls and in the diabetic subjects of groups I and II. However, the AVP rise was significantly higher in group I and group II than in normal controls. Furthermore, group I diabetics showed higher AVP increments than group II. Insulin induced a similar hypoglycaemic nadir in all subjects at 30 min, even though the diabetic subjects of groups I and II had a delayed recovery in blood glucose levels. The hypoglycaemic pattern was similar in group I and II. Hypoglycaemia induced a striking AVP increase in the normal controls. However, significantly higher AVP responses to hypoglycaemia were observed in the diabetic men of group I and group II than in the normal controls. Furthermore, group I diabetics showed higher AVP increments than group II. These data indicate that the hypothalamic‐pituitary disorder affecting the AVP response to MCP and insulin‐induced hypoglycaemia in well controlled type I diabetic men is inversely related to residual β‐cell activity.
Hyperlipidaemia in renal transplantation—risk factor for long‐term graft outcome
Authors: DIMÉNY E. , WAHLBERG J. , LITHELL H. , FELLSTRÖM B.
Published: March 2008

Abstract. The role of hyperlipidaemia for the outcome of renal transplantation was evaluated in a prospective study involving 151 patients. Graft losses were associated with more pronounced pre‐transplant lipid abnormalities. An increased risk of graft loss during the first two post‐transplant years was found in patients with marked pre‐transplant hypercholestero‐laemia (≥6.9 mmol L‐1, P= 0.014; relative risk 2.2). Hypercholesterolaemia ≥6.9mmol L‐1 at 6 months after transplantation, present in 41/115 patients, was associated with a lower GFR (P= 0.007) and more pronounced albuminuria (P= 0.009) at 2 years. In patients with graft dysfunction (serum creatinine >160μmol L‐1) at 2 years, more pronounced lipid abnormalities before and at 6 months after transplantation were found. Between 6 months and 2 years, total and LDL cholesterol did not change significantly, but HDL cholesterol decreased (P= 0.03). In conclusion, hyperlipidaemia is also a risk factor for the long‐term outcome in renal transplantation. Further investigations are needed to determine whether graft losses and late graft failure can be prevented or ameliorated by treating hyperlipidaemia in renal transplantation.
Four week administration of an ACE inhibitor and a cardioselective β‐blocker in healthy volunteers: no influence on insulin sensitivity
Authors: HEINEMANN L. , HEISE T. , AMPUDIA J. , SAWICKI P. , SINDELKA G. , BRUNNER G. , STARKE A. A. R.
Published: March 2008

Abstract. In most, but not all, studies antihypertensive treatment with angiotensin converting enzyme inhibitors (ACE inhibitors) improves insulin sensitivity, whereas β‐blockers decrease insulin sensitivity. However, there was a significant increase in body weight with β‐blockers and changes in the body potassium homeostasis with ACE inhibitors. In order to compare the drug specific metabolic effects of an ACE inhibitor and a cardioselective β‐blocker controlling these factors, we measured insulin sensitivity in a randomized, double‐blind cross‐over study in 22 healthy volunteers (age 27 ± 3 years; BMI 22.0± 1.5kg m‐2 (mean ± SD)) during euglycaemic glucose clamps before and after 4 weeks' administration of 5mg Lisinopril or 5mg Bisoprolol. Both drug phases were separated by 4 weeks of no drug administration. During the insulin sensitivity measurements potassium concentrations were clamped at basal levels by means of a variable i.v. potassium infusion. Body weight was monitored at weekly intervals and kept constant within ± 1 kg of the subjects' baseline weight throughout the entire study period. Insulin sensitivity did not change significantly during either drug administration period. The insulin sensitivity index of the 22 volunteers after administration of the ACE inhibitor was 7.9±2.4 mL min‐1 m2μU‐1 mL‐1 (basal index 8.3 ± l.9mL min‐1 m2μ‐1 mL‐1, and 7.5 ± 2.1 mL min‐1 m2μU‐1 mL‐1 after administration of the β‐blocker (basal index 8.2 ± l.9mL min‐1 m2μ=‐1 mL‐1; NS). In order to maintain blood potassium concentrations during the glucose c lamps at basal levels of 3.9 ± 0.3 mmol l‐1 a mean of 7.9±4.2 mval of potassium had to be infused during the low insulin step and a mean of 24.1 ±9.7mval during the high insulin step. Systolic and diastolic blood pressure were lowered significantly by Lisinopril (5±8 mmHg and 7 ± 9 mmHg) and Bisoprolol (7 ± 7 mmHg and 4 ± 8 mmHg; NS between both drugs), respectively. In healthy normo‐tensive subjects administration of Lisinopril or Bisoprolol for 4 weeks does not influence insulin sensitivity, when appropriate experimental conditions are maintained.
Reduced glomerular size‐ and charge‐selectivity in clinically healthy individuals with microalbuminuria
Authors: JENSEN J. S. , BORCH‐JOHNSEN K. , DECKERT T. , DECKERT M. , JENSEN G. , FELDT‐RASMUSSEN B.
Published: March 2008

Abstract. The pathophysiologic mechanism behind microalbuminuria, a potential atherosclerotic risk factor, was explored by measuring fractional clearances of four endogenous plasma proteins of different size and electric charge (albumin, β2‐microglobulin, immunoglobulin G, and immunoglobulin G4). Twenty‐eight clinically healthy individuals with microalbuminuria, defined as a urinary albumin excretion of 6.6–150μg min‐1, and 60 matched control subjects were studied. Fractional immunoglobulin G clearance was higher (geometric means (95% confidence intervals)) 3.0 (2.3–3.9) × 10‐6, n= 28, vs. 2.1 (1.8–2.4) × 10‐6, n= 60; P= 0.02), whereas the ratio immunoglobulin G clearance/immunoglobulin G4 clearance was lower (geometric means (95% confidence intervals)) 1.8 (1.4–2.2), n= 28, vs. 2.3 (2.0–2.5), n= 60; P= 0.03) in microalbuminuric than in normoalbuminuric individuals. Fractional β2‐micro‐globulin clearance was similar in the two groups. Since total IgG and the IgG4 subclass are of similar size and configuration but electrically neutral and negative, respectively; these findings indicate that microalbuminuria is associated with decreased size‐ and charge‐selectivity of the glomerular vessel wall. Hypotheti‐cally, such alterations may reflect generalized vascular abnormalities linking microalbuminuria to athero‐genesis.
Letters to the Editor
Authors: PhD A. SALA , PhD G. FOLCO
Published: March 2008

LTC4 in normal urine
Mast cell differentiation antigens: expression in normal and malignant cells and use for diagnostic purposes
Authors: VALENT P.
Published: March 2008

Abstract. Antibodies against haemopoietic differentiation antigens are widely used for the identification and classification of leukaemic cells. Mast cells are distinct haemopoietic cells and express a unique composition of antigens. They can be differentiated from basophils and all other lymphohaemopoietic cells by using antibodies to cell surface receptors and granular mediator molecules. This paper provides evidence that antibodies against mast cell antigens can be used to identify and classify malignant cell populations in patients with mastocytosis.
Urodilatin (Ularitide, INN): a potent bronchodilator in asthmatic subjects
Authors: FLÜGE T. , FABEL H. , WAGNER T.O.F. , SCHNEIDER B. , FORSSMANN W. G.
Published: March 2008

Abstract. Atrial natriuretic peptide (CDD/ANP‐99–126) has been identified as a bronchodilator in various species including humans. We investigated the effect of urodilatin (CDD/ANP‐95–126) in 18 clinically stable asthmatics showing an increase of the FEV1 by ≥15% after salbutamol inhalation. Prior to the study inhaled β2‐agonists were withheld for 8 h. After baseline measurements of lung function parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25), blood pressure, and heart rate in intravenous infusion of 20, 40 or 60 ng kg‐1 min‐1 urodilatin was administered for 40min in the morning. All measurements were repeated every 10 min during the infusion, for 30 min thereafter, and after the inhalation of l.25 mg salbutamol. Forty and 60 ng kg‐1min‐1 urodilatin showed a significant effect on the central (FEVl, PEF, MEF75) and peripheral airways (MEF50, MEF25) after 10 min infusion (P<0.05). A broncho‐dilation not significantly different from l.25 mg salbutamol was induced by 40 ng kg‐1 min‐1 in the central airways only, while 60 ng kg‐1 min‐1 led to a similar effect at all levels of the bronchial tree. Lung function parameters returned to baseline within 30 min after cessation of the urodilatin infusion. Heart rate showed a tendency to increase after 40min infusion (P<0.05), but blood pressure did not change significantly. In conclusion, the maximal bronchodilating effect of intravenous urodilatin in clinically stable asthmatics was comparable to l.25 mg salbutamol.
Neurohumoral antecedents of vasodepressor reactions
Authors: JACOBS M. C. , GOLDSTEIN D. S. , WILLEMSEN J. J. , SMITS P. , THIEN TH. , DIONNE R. A. , LENDERS J. W. M.
Published: March 2008

Abstract. Vasodepressor (vasovagal) syncope, the most common cause of acute loss of consciousness, can occur in otherwise vigorously healthy people during exposure to stimuli decreasing cardiac filling. Antecedent physiological or neuroendocrine conditions for this dramatic syndrome are poorly understood. This study compared neurocirculatory responses to non‐hypotensive lower body negative pressure (LBNP) in subjects who subsequently developed vasodepressor reactions during hypotensive LBNP with responses in subjects who did not. In 26 healthy subjects, LBNP at ‐15 and ‐40mmHg was applied to inhibit cardiopulmonary and arterial baroreceptors. All the subjects tolerated 30min of LBNP at ‐15 mmHg, but during subsequent LBNP at ‐40 mmHg 11 subjects had vasodepressor reactions, with sudden hypotension, nausea, and dizziness. In these subjects, arterial plasma adrenaline responses to LBNP both at ‐15 and at ‐40 mmHg exceeded those in subjects who did not experience these reactions. In 16 of the 26 subjects, forearm noradrenaline spillover was measured; in the eight subjects with a vasodepressor reaction, mean forearm noradrenaline spillover failed to increase during LBNP at ‐15mmHg (Δ= ‐0.06±(SEM) 0.04pmol min‐1 100mL‐1), whereas in the eight subjects without a vasodepressor reaction, mean forearm noradrenaline spillover increased significantly (Δ=0.31±0.13pmolmin‐1100mL‐1). Plasma levels of β‐endorphin during LBNP at ‐15 mmHg increased in some subjects who subsequently had a vasodepressor reaction during LBNP at ‐40 mmHg. The findings suggest that a neuroendocrine pattern including adre‐nomedullary stimulation, skeletal sympathoinhibition, and release of endogenous opioids can precede vasodepressor syncope.
The reproducibility and comparability of tests of the peripheral chemoreflex: comparing the transient hypoxic ventilatory drive test and the single‐breath carbon dioxide response test in healthy subjects
Authors: CHUA T. P. , COATS A. J. S.
Published: March 2008

Abstract. Both the transient hypoxic ventilatory drive test and the single‐breath carbon dioxide (CO2) response test have been used to assess peripheral chemoreflex sensitivity. We tested their comparability in 14 healthy adults (10 men, aged 31–73 years, mean 55.4 years). The within‐subject reproducibility of both tests was also assessed (n= 7 for each). The mean transient hyoxic ventilatory response was 0.287 ± 0.0591min‐1 (%Sao2)‐1 (mean ± SEM, range 0.018–0.718) and single‐breath CO2 response was 0.276 ± 0.0411 min‐1T‐1 (range 0.081–0.501). Both tests were reproducible with a mean coefficient of variation of 20.1% and 17.7%, respectively. There was, however, no significant correlation between the results of the transient hypoxic and single‐breath CO2 tests when data were compared by linear regression analysis (r= 0.23, P= 0.43), suggesting that separate pathways of the peripheral chemoreflex existed for hypoxia and hypercapnia, respectively, and that these tests were specific for each. The authors conclude that these tests are reproducible but need to be used in combination for an adequate assessment of the peripheral chemoreflex.
Relation of endothelins to volume regulating neurohumoral systems in patients with cirrhosis of the liver
Authors: GÜLBERG V. , GERBES A. L.
Published: March 2008

Abstract. The aim of the present study was to investigate the relationship between ET plasma concentrations and other hormonal systems in acute volume regulation of patients with cirrhosis. Ten healthy controls and 10 cirrhotic patients, five without and five with ascites were studied after 1 h in a sitting posture and subsequently subjected to 1 h head‐out water immersion. Blood was collected for determinations of ET‐1, ET‐3, ANF, aldosterone, renin activity and noradrenaline. In addition, in 10 patients with compensated cirrhosis the effect of loop diuretics on ET‐3, aldosterone and renin was studied. ETs in cirrhosis were significantly (P<0.01) higher than in controls both before (ET‐1, 19.6 ± 1.3pgmL‐1 vs. 11.8 ± 0.4pgmL‐1; ET‐3, 18.5±1.4pgmL‐1 vs. 9.5 ± 0.5 pgmL‐1) and after water immersion (ET‐1, 18.6± 1.2 pgmL‐1 vs. 12.4±0.3 pgmL‐1; ET‐3,18.7 ± 1.7pgmL‐1 vs. 10.0±0.5pg mL‐1). In cirrhotic patients, basal and immersion concentrations of ET‐1 were significantly correlated to noradrenaline plasma concentrations (r= 0.79, P<0.05). ET‐3 plasma concentrations in cirrhosis were correlated to renin activity (r= 0.65, P<0.05). Furthermore, ET‐3 in cirrhosis was inversely correlated to systolic and mean arterial blood pressure (r= ‐0.55, P<0.01 and r= ‐0.50, P<0.05, respectively). To investigate the effect of hypovolaemia in compensated cirrhosis, 10 patients without ascites were studied before and after treatment with loop diuretics. In compensated cirrhosis ET‐3 was significantly increased 6h after oral diuretic treatment (17.9 ± 1.0 pgmL‐1 vs. 15.5±0.4pg mL‐1, P< 0.001). The presented data demonstrate relations of endothelins, particularly of ET‐3 to neurohumoral systems in patients with cirrhosis of the liver.
Circulating and tissue guanylin immunoreactivity in intestinal secretory diarrhoea*
Authors: KUHN M. , KULAKSIZ H. , CETIN Y. , FRANK M. , NOLD R. , ARNOLD R. , BÖKER K. , BISCHOFF S.C. , MANNS M.P. , FORSSMANN W.G.
Published: March 2008

Abstract. Guanylin is a recently discovered peptide hormone that activates intestinal guanylate cyclase (GC‐C) and thereby stimulates intestinal chloride secretion. Immunohistochemistry showed its presence in enterochromaffin (EC) cells of the gut. In vitro studies suggested that guanylin plays an important role in the endogenous modulation of intestinal salt and water secretion. In the present study the concentration of circulating immunoreactive (1R)— guanylin in plasma of patients with intestinal diarrhoea due to chronic bowel inflammation and patients with carcinoid tumours were measured with a specific radioimmunoassay. In 22 patients with Crohn's disease and eight patients with ulcerative colitis, plasma concentrations of IR‐guanylin were 44 ± 3 and 42± 4 fmol mL‐1, respectively. Levels were not different from that in 44 healthy volunteers suggesting that the circulating hormone is not involved in diarrhoea of these patients. In 17 patients with symptomatic carcinoid tumors the median concentration of circulating IR‐guanylin was significantly enhanced (94±16 fmol mL‐1, range 37–312 fmol mL‐1). Immunohistochemistry revealed the presence of immunoreactive guanylin in carcinoid tissues, suggesting that these tumours co‐release guanylin along with their usual resident hormone, serotonin. Enhanced local secretion of guanylin may play a causal role in diarrhoea of these patients and its elevation in plasma may be of diagnostic value in this type of endocrine tumours.
Lichen planus and hepatitis C virus in the Northern Kyushu region of Japan
Authors: NAGAO Y. , SATA M. , TANIJSAWA K. , ITOH K. , KAMEYAMA T.
Published: March 2008

Abstract. Oral lichen planus (OLP) is a common oral disorder that manifests a mucosal reaction to a variety of aetiological factors, including liver disorder. This study investigated the relationship between OLP and hepatitis C virus (HCV) infection by studying the prevalence of hepatitis B and C virus infection or liver disease in 45 patients with OLP in the Northern Kyushu region of Japan where the prevalence of HCV infection is the highest in the country. Serum hepatitis B virus surface antigen (HBsAg) was positive in only four patients. Serum anti‐HCV or serum HCV RNA was positive in 28 (62%) and 27 (60%) of 45 OLP patients, respectively. The majority (35 of 45, 78%) of OLP patients suffered from liver disease, including chronic hepatitis C (22/45, 49%), HCV‐related liver cirrhosis (two), and HCV‐related hepatocellular carcinoma (two). These results suggest that HCV is a major cause of OLP.
Pre‐operative evaluation of risk factors for complications in patients with primary hyperparathyroidism
Authors: LIND L. , LJUNGHALL S.
Published: March 2008

Abstract. Impairments in cardiovascular, respiratory and kidney function are considered as risk factors for complications following surgery. As the indication for surgery in asymptomatic primary hyperparathyroidism (HPT) is controversial, 123 patients undergoing surgery for HPT and 104 control subjects scheduled for common surgical procedures were evaluated pre‐operatively. Compared with the age‐ and sex‐matched control group, serum calcium (P<0.001), creatinine (P<0.001) and glucose (P<0.002) were all increased in the HPT group, while peak expiratory flow (PEF) was decreased (P<0.004). Furthermore, the patients with HPT, compared with controls, were more often receiving antihypertensive medication (P<0.005) and were more likely to have a history of congestive heart disease (P<0.001), thromboembolic diseases (P<0.005), stroke (P<0.006) or diabetes mellitus (P<0.002). Increased frequencies of ST‐segment depression (P<0.001) and T‐wave abnormalities (P<0.005) at electrocardiography together with an increased prevalence of heart enlargement visible at chest radiography (P<0.001) were also seen in the HPT group when compared with the controls. All HPT patients and controls survived, but one HPT patient suffered a myocardial infarction in the post‐operative period. In conclusion, the present study showed the pre‐operative risk factor profile to be altered in HPT subjects with impairments in both cardiovascular and respiratory functions as well as in kidney function and glucose control. These findings should be kept in mind when the indications for surgery in asymptomatic patients with HPT are discussed.
Vascular reactivity to noradrenaline and neuropeptide Y in the streptozotocin‐induced diabetic rat
Authors: SAVAGE M. W. , BODMER C. W. , WALKER A. B. , BUCHAN I. E. , MASSON E. A. , WILLIAMS G.
Published: March 2008

Abstract. The study aimed to assess vascular reactivity to noradrenaline with and without neuropeptide Y in diabetic rats, and to determine whether any abnormality could be attributed to insulin deficiency or to hyperglycaemia per se. The authors compared non‐diabetic rats (n= 9) and rats with streptozotocin‐induced diabetes that were either untreated (n= 10), or treated with insulin (n= 9) or food restriction (n= 8) to restore near‐normoglycaemia. After 4 weeks of diabetes, contractile responses to noradrenaline (0.24–48 μmolL‐1), without and with neuropeptide Y (0.1 μmolL‐1), were assessed using an isometric myograph in two mesenteric arteries from each rat. Vessels from untreated diabetic rats were significantly more reactive to noradrenaline than the control vessels when tested without (P<0.0001) but not with (P= NS) neuropeptide Y. Diabetic rats rendered nearly normoglycaemic through food restriction showed dose‐response curves that were very similar to the untreated diabetic group (P= NS). By contrast, insulin‐treated diabetic vessels showed reduced sensitivity to noradrenaline, with and without neuropeptide Y, compared with both the diet‐restricted and untreated vessels (both Pμ0.0001). The authors conclude that vascular sensitivity to noradrenaline, without or with neuropeptide Y, is reduced over a wide dose range in vessels taken from rats treated in vivo with insulin; furthermore, vessels taken from diabetic rats not treated with insulin (hypoinsulinaemic) tended to be more reactive than either control vessels or those taken from the insulin‐treated rats. The latter group of rats were probably hyperinsulinaemic for much of the time; the results may therefore support the hypothesis that insulin acts as a vasodilator.