bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensorineural hearing loss owing to deficient G proteins in patients with pseudohypoparathyroidism: results of a multicentre study
Authors: KOCH T. , LEHNHARDT E. , BOTTINGER H. , PFEUFFER T. , PALM D. , FISCHER B. , RADEKE H. , HESCH R. D.
Published: March 2008

Abstract. Pseudohypoparathyroidism (PHP) is a rare disorder that might be caused by an hereditary defect in the G protein system. These membrane‐bound proteins are responsible for the transduction of biological signals through the outer cell membrane. The investigation of 22 patients with PHP showed a symmetric sensorineural hearing loss in 63.6% of the subjects. In erythrocyte membrane preparations from blood samples of 15 of these patients, we measured the concentration of the stimulatory Gs protein and the inhibitory Gi protein by means of the Western blot analysis using selective antibodies against α‐subunits of G proteins. In nine of the 15 cases (60%), we found a distinct decrease in the amount of the Gs protein with a partial preponderance of the Gi protein. These patients had a considerable symmetric sensorineural hearing loss. Pathophysiological mechanisms and the possible role of G proteins in the inner ear are discussed.,
In vitro remodelling of plasma lipoproteins in whole plasma by lipoprotein lipase in primary and secondary hypertriglyceridaemia
Authors: LEVY E. , DECKELBAUM R. J. , THIBAULT R. L. , SEIDMAN E. , OLIVECRONA T. , ROY C. C.
Published: March 2008

Abstract. In patients with familial lipoprotein lipase deficiency (FLPL‐d) and glycogen storage disease type I (GSD‐I), hypertriglyceridaemia (1445 pM 247 and 1082 pM 312 mg dl‐1, n= 5 per group) was associated primarily with reduced extrahepatic lipoprotein lipase (LPL) activity (0.33 pM 0.33 and 1.69 + 0.38 μmol FFA ml‐1 h‐1) when compared with controls (4.83 pM 0.90). Hypercholesterolaemia was characterized by elevated LDL cholesterol (191 pM 30 and 344 pM 34 vs. 115 pM 5 mg dl‐1 in controls P <0.01) and low HDL cholesterol (12 pM 2 and 22 pM 2 vs. 56 pM 3 in controls, P < 0.001). In order to ascertain the role of LPL in the interconver‐sion and remodelling of lipoproteins in these disorders, we analysed lipid and lipoprotein profiles before and following in vitro incubation of patient plasma with purified milk LPL (EC 3.1.1.34) for 6 h at 37d̀C. The efficiency of exogenous LPL in vitro was demonstrated by the extent of hydrolysis of chylomicrons and of VLDL‐TG in both groups. Concomitant with the disappearance of TG‐rich lipoprotein particles, a consistent per cent increment of IDL (99.2 pM 30.8 and 43.9pM70.5), LDL (152.8 pM 36.2 and 137.0 pM 36.1) and of HDL2 (144.8 pM 29.4 and 99.8 pM 18.7) was observed in both groups of patients. The enhancement of the latter fractions contrasted with the decline of HDL3 mass concentration (25.4 pM 7.7 and 51.4pM5.8%), suggesting that a major shift of HDL3→HDL2 occurs following in vitro lipolysis by LDL. Simultaneous compositional and morphological changes of individual lipoprotein particles were noted, confirming the dynamic movement and exchange of neutral lipids and proteins. Specificity of LPL results was demonstrated by experiments in which incubation of the whole plasma at 37d̀C without exogenous lipolytic enzyme did not cause any substantial changes. The present study, therefore, demonstrates a correction of the major lipoprotein abnormalities associated with FLPL‐d and GSD‐I by exogenous LPL. No substantial difference was noted between primary (FLPL‐d) and secondary (GSD‐I) hyperlipidaemias. These studies allow us to conclude that a simple in vitro system, utilizing an exogenous source of LPL and plasma from patients, may serve as a suitable model for the study of the metabolic relationships of lipoproteins. However, in view of the fact that the extent of lipolysis achieved in vitro did not differ between FLPL‐d and GSD‐I, it may not be able to separate primary from secondary hyperlipaemias.,
Refeeding after starvation in the rat: comparative effects of lipids, proteins and carbohydrates on jejunal and ileal mucosal adaptation
Authors: BUTS J.‐P. , VIJVERMAN V. , BARUDI C. , KEYSER N. DE , MALDAGUE P. , DIVE C.
Published: March 2008

Abstract. To compare the tropic effect of different dietary nutrients on mucosal adaptation in the jejunum and ileum, adult rats were submitted to a 96‐h period of starvation and refed isocaloric liquid diets (1.5 kcal ml‐1) containing either protein (casein), carbohydrate (starch) or lipids. In the jejunum, 4 days of starvation caused mucosal hypoplasia, villus and crypt shortening and a decrease in the total activity of disaccharidases with the exception of lactase which was markedly enhanced. In contrast, mucosal hypoplasia was incomplete in the ileum which exhibited an increase in crypt depth and in the specific and total activities of disaccharidases and of aminopeptidase.

Compared with protein and carbohydrates, lipids exerted the strongest stimulatory effect for mucosal regeneration. In the jejunum as well as in the ileum, mucosal mass parameters, villus length, crypt depth and lactase activity did reverse towards their initial value within 1–3 days of refeeding lipids, even though the animals received only one‐third of their normal daily caloric intake. Our results indicate that the pattern of response to fasting differs between the proximal and distal small intestine, and that the intestinal changes induced by starvation are rapidly reversed by refeeding small amounts of a diet rich in fat.,
Endotoxin‐stimulated peritoneal macrophages obtained from continuous ambulatory peritoneal dialysis patients show an increased capacity to release interleukin‐1βin vitro during infectious peritonitis
Authors: FIEREN M. W. J. A. , BEMD G. J. C. M. VAN DEN , BONTA I. L.
Published: March 2008

Abstract. Interleukin‐1 (IL‐1) release by peritoneal macrophages obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) was studied in nine patients during an infection‐free period and eight patients during an infectious peritonitis, using an ELISA for IL‐ 1β. Without exogenous stimulation with LPS, peritoneal macrophages from infected and unin‐fected patients released the same amounts of IL‐lβ, 183pM40 pg ml‐1 24 h‐1) per 106 cells (means + SEM) and 251 pM 6 pg ml‐1, respectively. However, in response to a dose of 5 μg ml‐1 of LPS, peritoneal macrophages released significantly more (P < 0.005) IL‐1β during peritonitis (6579 β 2793 pg ml‐1 24 h‐1 per 106 cells) compared with the infection‐free period (1040 pM 182 pg ml‐1). These findings show that after microbial invasion of the peritoneal cavity, peritoneal macrophages are primed in vivo to release an increased amount of IL‐lβin vitro after subsequent exogenous stimulation with LPS, indicating that peritoneal mac‐rophage activation for IL‐1β secretion occurs in steps.,
Erythrocyte aggregation: the roles of cell deformability and geometry
Authors: REINHART W. H. , SINGH A.
Published: March 2008

Abstract. The sedimentation rate of erythrocyte under controlled conditions was used to study the influence of cell deformability and geometry on erythrocyte aggregation. The cell deformability, which is determined by the viscoelastic properties of the membrane, the cell geometry, and the cellular viscosity, was systematically altered. The viscoelasticity of the membrane was gradually decreased with increasing concentrations of glutaraldehyde (0.01–1.0%) or heat treatment at 47.5d̀C for increasing time intervals (0.80 min), which led to an increase at low concentrations and short incubation and then to a progressive decrease of erythrocyte aggregation. Changes of the osmolality were used to simultaneously alter the cell geometry and cellular viscosity in opposing directions. When the haematocrit level was held constant, the sedimentation rate decreased with increasing osmolality. With a constant erythrocyte number per volume, but changing haematocrit level, the highest sedimentation rate was observed at isotonicity. These results indicate that cell deformability and geometry play an important role in erythrocyte aggregation and sedimentation and may have implications on other cell‐cell interactions as well.,
Analysis of radiolucent gallstones by computed tomography for in vivo estimation of stone components
Authors: RAMBOW A. , STARITZ M. , WOSIEWITZ U. , MILDENBURGER P. , THELEN M. , BUSCHENFELDE K.‐H. MEYER ZUM
Published: March 2008

Abstract. Successful oral litholytic and other non‐operative therapies of gallstones require exact determination of the stone components. Since computed tomography (CT) provides highly sensitive measurement of density, we performed a study to evaluate whether CT measurement of stone density allows a prediction of the composition of radiolucent gallstones.

Twenty‐eight patients presenting with 29 radiolucent gallbladder (n= 17) or common bile duct stones (n=12) were included. Prior to operative or endo‐scopic therapy the attenuation values (Hounsfield Units, HU) were assessed in vivo by CT under standardized conditions (Somatom II, 125 KV, 130 mAs). After surgical or endoscopic stone removal the concrements were dehydrated, homogenized and then analysed by infra‐red spectroscopy. The previously measured Hounsfield units were not known to the investigator.

Eighteen cholesterol and 11 pigment stones could be identified. The attenuation values (Hounsfield units) of cholesterol stones amounting to 28–98 HU (48.7 pM 4.4 HU) differed significantly (P < 0.001) from pigment stones (90–120 HU/105.5 pM 2.8 HU). We conclude that computed tomography provides exact discrimination between cholesterol and non‐cholesterol stones in vivo. Since only cholesterol stones can be dissolved by cheno‐ and ursodeoxycholic acid we recommend measurement of the radiodensity of gallstones by CT prior to any litholytic therapy.

Furthermore the prediction of the stone composition facilitates the decision on extracorporeal shock wave lithotripsy and the selection of specific solvents for contact lysis via a nasobiliary probe.,
Follow‐up of the serum levels of extracellular matrix components in acute and chronic pancreatitis
Authors: ADLER G. , KROPF J. , GROBE E. , GRESSNER A. M.
Published: March 2008

Abstract. Time‐dependent serum concentrations of extracellular matrix proteins were studied in 32 patients with pancreatitis in order to find potential markers of the reparative response during the disease. Patients were subdivided by clinical and biochemical criteria: severe acute pancreatitis (n=10), moderate acute pancreatitis (n= 17), and acute attack of chronic pancreatitis (n= 5). Serum and plasma samples were collected on days 1–7, 10,14, and 21 for measurements of the aminoterminal propeptide of type III procolla‐gen (PIIINP), hyaluronic acid, laminin, fibronectin, and routine clinical‐chemical parameters. During an acute attack of chronic pancreatitis all parameters were within the reference range. In moderate acute pancreatitis concentrations of PIIINP, laminin, and hyaluronic acid fluctuated around the upper reference limit, but declined to mid‐normal levels at day 21. In severe acute pancreatitis all three parameters increased. In patients who died as a consequence of sepsis and multi‐organ failure the increase in PIIINP, laminin and hyaluronic acid was much more pronounced and paralleled by a decrease in plasma concentrations of fibronectin. In conclusion, this study revealed a relation between the severity of acute pancreatitis and the increase in serum concentrations of extracellular matrix components, especially PIIINP.
Adrenergic supersensitivity in Parkinsonians with orthostatic hypotension
Authors: SENARD J. M. , VALET P. , DURRIEU G. , BERLAN M. , TRAN M. A. , MONTASTRUC J. L. , RASCOL A. , MONTASTRUC P.
Published: March 2008

Abstract. The adrenergic status was studied through evaluation of platelet α2‐adrenoceptor number ([3H]‐yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with orthostatic hypotension; (2) Parkinsonians without orthostatic hypotension; and (3) control subjects. In Parkinsonians with orthostatic hypotension, systolic and diastolic blood pressures significantly (P < 0.05) decreased from 144 pM 9 and 76 pM 6 mmHg in the lying position to 95 pM 12 and 60 pM 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 pM 11 pg ml‐1, (P < 0.05) when compared with controls (219 pM 13 pg ml‐1) whereas no difference was noticed in Parkinsonians without orthostatic hypotension (195 pM 14 pg ml‐1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P < 0.01) lower in Parkinsonians with orthostatic hypotension (019 pM 0.03 μg kg‐1) when compared with Parkinsonians without orthostatic hypotension (0.86 pM 0.11 μg kg‐1) or with controls (0.68 pM 0.l μg kg‐1). Platelet x2‐adrenoceptor number was higher in Parkinsonians with orthostatic hypotension (313 pM 52 fmol mg‐1 protein) than in Parkinsonians without orthostatic hypotension (168 pM 9 fmol mg‐1 protein) or in controls (175 pM 4 fmol mg‐1 protein) with no change in Kd. This study demonstrates that in patients with Parkinson's disease, orthostatic hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet α2‐adrenoceptor number. These observations suggest the existence of an α‐adrenergic supersensitivity in response to the low levels of plasma noradrenaline.
Antibodies to cytoskeletal proteins in patients with Crohn's disease
Authors: MAYET W. J. , PRESS A. G. , HERMANN E. , MOLL R. , MANNS M. , EWE K. , BÜSCHENFELDE K. H. MEYER ZUM
Published: March 2008

Abstract. The immunologic basis of inflammatory bowel disease has been the focus of interest of a series of studies on Crohn's disease and the process of immune sensitization at the gastrointestinal mucosal level is functionally poorly understood. To date only few contradictory reports concerning the incidence of autoantibodies in patients with this disease exist. The aim of this study was to investigate the sera drawn from 60 patients suffering from biopsy‐proven Crohn's disease to evaluate the prevalence of autoantibodies against nuclear antigens and cytoskeletal proteins. Using standard methods, no anti‐nuclear antibodies or antibodies to extractable nuclear antigens could be detected. All sera were also negative for antibodies to double‐stranded DNA, anti‐mitochondrial antibodies, and antibodies to gastric parietal cells. Using sensitive enzyme‐linked immunosorbent assays with purified antigens and Western blotting with cytoskeletal proteins of human intestinal cells, the following antibodies could be demonstrated: cytokeratin 18 autoantibodies (IgG 20.0%; IgM 6.7%; IgA 13.3%), actin antibodies (IgG 36.7%; IgM 48.3%, IgA 26.7%), desmin antibodies (IgG 6.7%; IgM 15.08%; IgA 50%), vimentin antibodies (IgG 3.3%; IgM 16.7%; IgA 10.0%) and tropomyosin antibodies (IgG 3.3%; IgM 3.3%, IgA 5.0%). Statistically significant correlations could be found for levels of cytokeratin 18 antibodies (IgM‐type) and the BEST index of activity, and for levels of desmin antibodies (IgM‐type) and the van HEES index of activity. Highest levels could be measured for actin antibodies (IgG‐type) in patients with isolated disease manifestation in the colon. The mechanism of induction of autoantibodies against cytoskeletal components in Crohn's disease still remains obscure. Unmasking of hidden antigens after cell injury during the inflammatory process of disease might lead to sensitization and antibody production. The pattern of antibodies in patients with Crohn's disease seems to be different compared with that of connective tissue diseases.
Hepatitis B vaccination of haemodialysis patients: randomized controlled trial comparing plasma‐derived vaccine with and without pre‐S2 antigen
Authors: SMIT‐LEIJS M. B. L. , KRAMER P. , HEIJTINK R. A. , HOP W. C. J. , SCHALM S. W.
Published: March 2008

Abstract. The pre‐S2 protein of the hepatitis B virus envelope evokes anti‐pre‐S2 antibodies and enhances the anti‐HBs response after vaccination in mice. In order to evaluate the immunogenicity of the pre‐S2 Ag in man, 102 HBsAg, anti‐HBs, anti‐HBc‐negative haemodialysis patients were vaccinated at random according to one of four vaccination schedules: 5 μg plasma vaccine Pasteur (containing 1 % pre‐S2) or 20 μg plasma vaccine MSD (no pre‐S2) at 0, 1, 2, 4, 6 and 12 months; or 10 μg Pasteur or 40 μg MSD at 0, 1,2 and 6 months. Anti‐HBs levels were measured by RIA and expressed in IU 1‐1; anti‐pre‐S2 response was evaluated by both EIA and Western blot analysis.

Eighty‐four per cent (95% confidence interval: 75–93) of the patients exhibited an anti‐HBs response of 2 IU l‐1 or more and 71% (95% confidence interval: 61–81) reached an anti‐HBs level of at least 10 IU l‐1 within 13 months of the start of vaccination. Anti‐HBs response correlated with age (the response rate decreased with increasing age) but not with either the type of vaccine or dosage. An anti‐pre‐S2 response was observed in 16% (EIA) and 46% (Western blot) of the patients immunized with the Pasteur vaccine and none (EIA, Western blot) of the MSD group. The level of anti‐pre‐S2 antibodies correlated with high anti‐HBs titres; an anti‐pre‐S2 response occurred in only one anti‐HBs‐negative patient.

The addition of 1% pre‐S2 to the HBsAg plasma hepatitis B vaccine had no significant effect on the anti‐HBs response in haemodialysis patients and did not markedly broaden protective immunity. Further studies of recombinant vaccines with a higher pre‐S2 content are needed to document the possibility of enhanced immunogenicity of pre‐S2Ag‐containing hepatitis B vaccines in man.
Plasma volume changes during hypoglycaemia: the effect of autonomic blockade
Authors: HILSTED J. , FRANDSEN H. , CHRISTENSEN N.J. , NIELSEN S.L.
Published: March 2008

Abstract. To investigate the role of the autonomic nervous system in changes in blood volume and composition induced by acute hypoglycaemia in man, seven healthy subjects participated in three experiments on separate days: insulin‐induced hypoglycaemia with concomitant α‐adrenoceptor blockade; insulin‐induced hypoglycaemia with total autonomic blockade (α‐adrenoceptor blockade combined with β‐adrenoceptor blockade and atropine); and insulin‐induced hypoglycaemia without any autonomic blockade. In the experiments without autonomic blockade the peripheral venous hematocrit increased, plasma volume decreased, intravascular albumin content decreased and the transcapillary escape rate of albumin increased. In both experiments with autonomic blockade the increase in venous haematocrit was abolished, yet plasma volume decreased, intravascular albumin content decreased and the transcapillary escape rate of albumin increased in these experiments. Thus, the changes in plasma volume and composition in response to hypoglycaemia are due to the combined actions of adrenaline and of insulin.
Renal tubular sodium handling and plasma atrial natriuretic peptide, renin activity and aldosterone in untreated men under normal living conditions
Authors: CAPPUCCIO F.P. , STRAZZULLO P. , GIORGIONE N. , IACONE R. , FARINARO E. , BUCKLEY M.G. , MILLER M.A. , SAGNELLA G.A. , MacGREGOR G.A. , MANCINI M.
Published: March 2008

Abstract. The associations between renal tubular sodium handling and plasma levels of atrial natriuretic peptide, renin activity and aldosterone were studied in 295 untreated men under normal living conditions. The renal clearance of ingested lithium was used as a marker of proximal tubular sodium handling.

Plasma atrial natriuretic peptide was inversely related to creatinine clearance (r=– 0.148, P < 0.01) and directly and significantly related to the overall fractional excretion of sodium (r= 0.213, P < 0.001) and to distal (r= 0.151, P < 0.01) fractional sodium excretion. Plasma renin activity was inversely related to sodium excretion at both proximal (r=– 0.145, P < 0.05) and distal (r=–0.236, P < 0.001) tubular site, whereas plasma aldosterone was significantly and inversely related to distal sodium excretion only (r=–0.305, P < 0.001).

The association between plasma atrial natriuretic peptide and distal sodium excretion in a large sample of men under normal living conditions supports the view of a possible tubular effect of the hormone for the overall control of sodium excretion in man.
Suppression of proliferation of human epidermal keratinocytes by 1,25‐dihydroxyvitamin D3 Analysis of its effect on psoriatic lesion and of its mechanism using human keratinocytes in culture
Authors: KITANO Y. , IKEDA N. , OKANO M.
Published: March 2008

Abstract. Psoriasis is a genetically determined chronic disease of the skin, and an accelerated proliferation of epidermal keratinocytes is one of the pathophysiological characteristics of psoriatic lesion. Recently, it was reported that topical administration of 1,25‐dihydroxyvitamin D3 was effective for psoriasis. Our study was done to investigate the effect of 1,25‐(OH)2‐D3 on cell kinetics on human epidermal keratinocytes as a possible mechanism of its effect on psoriasis.

After 24‐h application of 1 μg g–1 1,25‐(OH)2‐D3 ointment to psoriatic lesion, the number of mitotic keratinocytes decreased. When the cultured human keratinocytes were exposed to 10–8 mol l–1 1,25‐(OH)2‐D3 for more than 9 days, inhibition of cell proliferation was noted. DNA distribution analysis by flow cytometry showed a decrease in cells in the S phase, and increase in 2c cells. This indicates blockade of the cell cycle in the G1 phase. The cell cycle time was not extended as a result of 1,25‐(OH)2‐D3‐treatment.
Regulation of myocardial isomyosin V1 in uraemic rats
Authors: RAMBAUSEK M. , KOLLMAR S. , KLUG D. , MEHLS O. , RITZ E.
Published: March 2008

Abstract. Cardiac hypertrophy of various aetiologies is consistently associated with increased expression of V3 isomyosin. Uraemia is associated with cardiac hypertrophy. In the present study, we examined regulation of isomyosin in uraemic rats, using gel electrophoresis. Cardiac hypertrophy in uraemic animals was associated with a relative increase in VI isomyosin. An increased proportion of VI isomyosin was demonstrable 3 days after subtotal nephrectomy (NX 63.0 ± 8.8%; control 43.6 ± 7.2%; P < 0.01) and persisted during uraemia of 80 days duration. Elevation of VI isomyosin, relative to pair‐fed controls, was observed in uraemic animals of various age. The proportion of VI isomyosin changed in the same direction as controls when several manouevers were used which changed the isomyosin pattern, but the difference between uraemic animals and controls persisted. We studied the effect of carbohydrate loading or deprivation, starvation or administration of energetically inadequate diets, castration or administration of androgens and sodium depletion. With each of the above interventions, a difference between subtotally nephrectomized animals and sham‐operated pair‐fed control animals was statistically significant (P < 0.05). Elevation of VI isomyosin persisted during combined alpha and beta blockade and was still found when blood pressure was normalized by ACE inhibition using Ramipril. It is concluded that cardiac hypertrophy of uraemia differs from all other forms of cardiac hypertrophy by the occurrence of increased proportion of VI isomyosin. The proportion of VI isomyosin responds adequately to regulatory signals but is set at an abnormally high level.
Complement activation and depletion during LDL‐apheresis by heparin‐induced extracorporeal LDL‐precipitation (HELP)
Authors: WÜRZNER R. , SCHUFF‐WERNER P. , FRANZKE A. , NITZE R. , OPPERMANN M. , ARMSTRONG V.W. , EISENHAUER T. , SEIDEL D. , GÖTZE O.
Published: March 2008

Abstract. The heparin‐induced extracorporeal elimination of low density lipoproteins (LDL) is a well‐established clinical procedure to markedly reduce cholesterol levels. The biocompatibility of this artificial filter system (HELP) was investigated by quantitation of representative complement proteins within the extracorporeal circuit using established ELISA procedures, based on monoclonal antibodies recognizing exclusively either native (C6, C7) or activated proteins (act.C3, C5a, TCC). HELP was found to be a self‐limiting extracorporeal system with respect to complement activation, since act.C3 and TCC, generated mainly at the plasma filter, were partially adsorbed to the following HELP specific filters to concentrations which were lower than those obtained before the plasma filter.C5a, which increased 14.5‐fold at the plasma filter was not eliminated by the following filters; however, elevated levels were not found in the patients at the end of apheresis and no leucocytopenia was observed.
The effect of virus infection on the adherence of leukocytes or platelets to endothelial cells
Authors: SPAN A.H.M. , VAN DAM‐MIERAS M.C.E. , MULLERS W. , ENDERT J. , MULLER A.D. , BRUGGEMAN C.A.
Published: March 2008

Abstract. It has been reported that atherosclerotic lesions contain genomic material belonging to members of the herpes family. This suggests that latent viral infection may be one of the atherogenic triggers. In this study we show that early infection of endothelial cell monolayers with Herpes Simplex virus type 1 (HSV‐1) or Cytomegalovirus (CMV) results in an increased monocyte (MC) and polymorphonuclear leukocyte (PMN) adherence, but not in an increased platelet adhesion. Further, is demonstrated that MC and PMN respond differently to virus infected endothelial cell monolayers: PMN adhesion to CMV infected cells is approximately 430% of the control adherence, while the MC adherence is increased to 160%. Also, a difference in virus acting is observed: the adherence of MC or PMN to HSV‐1 infected endothelial cells is caused by a secreted adherence promoting factor, while the adherence of MC or PMN to CMV infected endothelial cells seems to be a cell‐bound phenomenon. In addition, it was demonstrated that the augmentation of MC or PMN adherence to virus infected endothelial cells is sensitive to tunicamycin, suggesting that both virus infections induce the expression of glycoproteins on the endothelial cell membrane, which is responsible for the MC and PMN adhesion.

Thus, HSV‐1 and CMV infection of endothelium results in an increased adherence of leukocytes which is suggested, irrespective of the precise nature of the mechanism of virus induced atherosclerosis, to be the earliest event associated with endothelium cell damage.
Gemfibrozil in familial combined hyperlipidaemia: effect of added low‐dose cholestyramine on plasma and biliary lipids
Authors: ÖDMAN B. , ERICSSON S. , LINDMARK M. , BERGLUND L. , ANGELIN B.
Published: March 2008

Abstract. Gemfibrozil is frequently used for lipid‐lowering in familial combined hyperlipidaemia (FCHL) and in other forms of combined hyperlipidaemia. This therapy increases biliary cholesterol saturation, enhancing the risk for gallstone formation. Furthermore, in hypertriglyceridaemia, LDL cholesterol levels often tend to rise. We have explored the possibility that addition of a low dose of cholestyramine to gemfibrozil therapy obliterates these phenomena. Eighteen gallstone‐free patients with definite (n= 5) or probable (n= 10) FCHL, or combined hyperlipoproteinaemia (n= 3) were randomized to a 6 week treatment with gemfibrozil, 600 mg b.i.d., or gemfibrozil 600 mg b.i.d.plus 4 g cholestyramine o.d. After 6 weeks the patients were crossed over to the alternative treatment. Plasma lipoproteins and biliary lipids were determined at baseline and at the end of each period.

Institution of gemfibrozil treatment resulted in a decrease in plasma cholesterol by 15% (P < 0.05) and in plasma triglycerides by 47% (P < 0.05); HDL cholesterol increased by 18% (P < 0.05). Addition of cholestyramine further decreased plasma and LDL total cholesterol by 9% (P < 0.05). Total triglycerides and HDL cholesterol did not change.

Gemfibrozil treatment was associated with a rise in the relative biliary concentration of cholesterol from 5.6 ± 0.4 to 6.9 ± 0.5 molar percent (P < 001), and a parallel decrease in the relative concentration of bile acids, resulting in an increased cholesterol saturation of the bile, from 77.5 to 90.6% (P < 0.05). This change was not observed during the combined therapy (mean cholesterol saturation, 82.4%).

It is concluded that the addition of a low dose of cholestyramine neutralizes the negative effects on biliary lipid composition induced by gemfibrozil and strengthens some of the positive effects on plasma lipoprotein levels.
Dynamics of creatine kinase shuttle enzymes in the human heart
Authors: SYLVÉN C. , LIN L. , KALLNER A. , SOTONYI P. , SOMOGYI E. , JANSSON E.
Published: March 2008

Abstract. Myocardial cytoplasmic creatine kinase subunits M and B, mitochondrial CK (CKMIT), and citrate synthase (CS) were determined in 10 locations of the normal human heart (n= 8) and in papillary muscles of patients operated on for mitral regurgitation (n= 6). Compared to atrial biopsies, septal and left ventricular biopsies showed higher activities for CS(P < 0.0001), total CK (P < 0.05) and CKMIT (P < 0.0001). CKM was evenly distributed. CKB activity in the right septum and left ventricular locations were 0.5‐1% of total CK and 4–5 times lower than those of the atria and the right ventricular free wall. Activities of CS, CKB and CKMIT in right septal biopsies did not differ from those in left ventricular locations. The activities of CS, total CK, and CKM in papillary muscle from patients operated on for mitral regurgitation did not differ from that of healthy papillary muscle. CKMIT was about 40% lower (P < 0.02), whereas CKB was 15–20 times higher (P < 0.0001) than in the healthy heart. In conclusion, adaptations within the creatine kinase system occur in the human heart in health and disease. Small amounts of CKB in the normal left ventricle, as opposed to the right ventricular free wall, might be related to differences in myocardial perfusion during the cardiac cycle. In disease, a decreased CKMIT and dramatically increased CKB may indicate a stressed intracellular energy transfer. CK enzyme activities in right septal biopsy specimens may be used as an indication of metabolic stress on the myocardium of the left ventricle. Acute myocardial infarction in patients with a healthy heart might not give rise to increased serum CKMB levels.
The HELP‐LDL‐apheresis multicentre study, an angiographically assessed trial on the role of LDL‐apheresis in the secondary prevention of coronary heart disease
Authors: SEIDEL D. , ARMSTRONG V. W. , SCHUFF‐WERNER P.
Published: March 2008

Abstract. Fifty‐one patients with coronary heart disease (CHD) and LDL‐cholesterol levels 200 mg dl‐1 despite diet and drug therapy have been recruited into an angiographically controlled, multicentre, two‐year study to evaluate HELP‐LDL‐apheresis in the secondary prevention of CHD. There were five drop‐outs in the first year and 46 patients completed one year of therapy. An average of 2·791 of plasma was treated per patient every 7·7 days. Treatment was well tolerated and the incidence of side effects was small (2·9% of treatments). Mean pre‐/post‐apheresis LDL‐cholesterol levels decreased from 283/120 mg dl‐1 at baseline to 207/78 mg dl‐1 and 203/76 mg dl‐1 after 6 and 12 months, respectively. Mean pre‐/post‐apheresis HDL‐cholesterol levels rose significantly over the course of therapy from 40·5/36·6 mg dl‐1 to 44·8/39·7 mg dl‐1 and 48·2/41·3 mg dl‐1 after 0, 6 and 12 months, respectively. No major derangement of pre‐apheresis haemostasis nor of haematological or clinical chemical parameters had occurred after 12 months of treatment. The data from this study support the feasibility of HELP‐LDL‐apheresis as an adjunctive therapy for lowering cholesterol levels in CHD patients refractory to cholesterol‐lowering drugs while substantially improving the HDL/LDL ratio.
The effect on body composition and exercise performance of home parenteral nutrition when given as adjunct to chemotherapy of testicular carcinoma
Authors: HYLTANDER A. , DROTT C. , UNSGAARD B. , TÖLLI J. , KÖRNER U. , ARFVIDSSON B. , LUNDHOLM K.
Published: March 2008

Abstract. This study has evaluated whether long‐term and permanent total parenteral nutrition (TPN) can protect body composition and exercise capacity during iterated courses of chemotherapy (PVB) in men with testicular carcinoma. Thirty‐three men were randomly allocated by means of a computer based algorithm to receive either TPN (at hospital and home) during the entire chemotherapy period or to rely on spontaneous oral intake only. Nutrition status was assessed by measurements of whole body nitrogen (neutron activation), total body potassium, body water, urine creatinine excretion, loco‐regional body nutrition indexes (AMC, TSF) and biochemical plasma concentrations (albumin, thyroid hormones). Whole body respiratory gas exchanges were measured during resting, submaximal and maximal exercise. TPN was prescribed on an individual basis in all study patients to cover 150% of their measured caloric need; nitrogen was given as 0·2 g N kg‐1 day. All individuals were allowed to eat freely throughout the study.

TPN patients were in overall positive energy balance (+850 Kcal day‐1), while the control group was in negative balance (‐532 Kcal day‐1). This led to weight gain in the TPN group (+2·2 ± 1·0 kg) while the control group lost significant weight (‐4·2±1·1 kg). The average spontaneous oral caloric intake was 1014±153 Kcal day‐1 in the TPN group and 1484 ± 200 Kcal day‐1 in the control group; total protein intake corresponded to 1·5 g protein kg day‐1 in the TPN group and 0·7 kg day‐1 in the control group. Weight gain in TPN‐treated patients consisted only of fat accumulation without significant water retention, and they lost body nitrogen to the same extent as the control patients. The adaptation to undernutrition was better preserved in the control patients determined by indirect calorimetry. Maximal exercise capacity decreased during chemotherapy in both groups to the same extent from around 180 watts to 137 watts (p<0·001), but the relationship between oxygen uptake and submaximal work was not significantly influenced by chemotherapy or TPN in either of the two groups.

This study demonstrates that TPN was insufficient to protect body composition or even improve significantly the whole body nitrogen sparing and working capacity when given daily for more than eight weeks as adjunct to chemotherapy in patients with oral food intake reduced by 25–30%. Fat accumulation was the only measurable benefit. It is proposed that this is another example of the inefficiency of artificial nutrition to protect lean body mass in patients with light to pronounced negative caloric balance.
Copper metallothionein in patients with hepatic copper overload
Authors: HUNZIKER P. E. , STERNLIEB I.
Published: March 2008

Abstract. We studied the Cu‐MT present in the hepatic cytosol obtained from 7 patients suffering from conditions associated with hepatic Cu overload (Wilson's disease, biliary atresia, familial cholestatic cirrhosis). Since chromatographic methods appropriate for the isolation of Zn‐ and Cd‐MT were unsuitable for Cu‐MT, we developed an indirect procedure for the estimation and resolution of the latter. This procedure involved the preparation of apo‐MT and its reconstitution to holo‐MT with Zn or Cd. Three predominant isoforms of MT were present in all specimens. Our results indicate that at most 36 ± 5% of the Cu present in the 10 kDa fraction of cytosol is bound to MT in the liver of patients with hepatic copper overload.
Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro‐entero‐pancreatic hormones in man Feedback control of cholecystokinin and gastrin secretion
Authors: SCHMIDT W. E. , CREUTZFELDT W. , HÖCKER M. , NUSTEDE R. , CHOUDHURY A. ROY , SCHLESER A. , ROVATI L. C. , FÖLSCH U. R.
Published: March 2008

Abstract. The effect of the potent specific cholecystokinin (CCK) receptor antagonist loxiglumide on meal‐stimulated plasma concentrations of CCK, gastrin, pancreatic polypeptide (PP), neurotensin, glucosedependent insulinotropic polypeptide (GIP), insulin and C peptide was investigated in a placebo‐controlled study in 10 healthy male volunteers. Intravenous infusion of loxiglumide (10 mg kg‐1 h‐1) significantly augmented integrated incremental IR‐CCK levels 7·3‐fold after stimulation by a standard breakfast (504·54 vs 3·665±365 pmol‐1 135 min‐1, P<0·001), as measured by a specific CCK radioimmunoassay. Basal IR‐CCK concentrations were not affected by administration of loxiglumide. Oral treatment with bile acids (2 g ursodeoxycholic acid plus 2 g chenodeoxycholic acid) together with the meal abolished this augmentation, whereas high‐dose substitution with pancreatic enzymes (4·2 g pancreatin) reduced elevated IR‐CCK levels by only 38%. CCK‐like bioactivity, determined by a bioassay using rat pancreatic acini, was not detectable in all samples that contained loxiglumide at plasma concentrations of 100–250 μg ml‐1. Plasma gastrin concentrations in response to the breakfast were elevated 3·2‐fold during loxiglumide infusion and not influenced by substitution with bile acids or pancreatic enzymes. Meal‐stimulated integrated incremental plasma PP concentrations were significantly suppressed (55–65% inhibition, P<0·01) by loxiglumide. Infusion of the CCK receptor antagonist only slightly increased postprandial peak plasma glucose, insulin and C‐peptide levels, whereas GIP and neurotensin levels were not significantly influenced. These findings suggest: (i) CCK secretion is under feedback control by intraduodenal bile acids and to a lesser extent by pancreatic enzymes; (ii) simultaneous extraction of CCK and loxiglumide results in circulating plasma CCK‐like bioactivity of zero; (iii) gastrin secretion is feedback controlled via an indirect mechanism probably involving CCK‐induced somatostatin secretion; (iv) release of PP is under inhibitory control of CCK; (v) CCK does not play a major role as insulinotropic hormone in the entero‐insular axis in humans.
No decrease of 1,25(OH)2D3 receptors and duodenal calbindin‐D9k in uraemic rats
Authors: SZABO A. , MERKE J. , THOMASSET M. , RITZ E.
Published: March 2008

Abstract. In parathyroids of uraemic patients or animals, decreased specific binding of 1,25(OH)2D3 has been observed and implicated in the genesis of secondary hyperparathyroidism of renal failure. We re‐examined binding of 1,25(OH)2D3 using chromatin preparations for receptor characterization which differed from previous studies (a) by inclusion of protease inhibitors (PMSF, aprotinin) and molybdate in the extraction buffer and (b) by omitting the K‐extraction step. With this method, the Nmax in the intestinal mucosa and parathyroids of uraemic animals was significantly higher, while the receptor sedimentation constant (S), DNA affinity and KD were all unchanged. The ratio of occupied to total receptors was not significantly altered. The regulation of 1,25(OH)2D3 receptors in response to acute injection of 1,25(OH)2D3 was abnormal. Calbindin‐D9k concentration in the intestines of uraemic and control rats was comparable both before and after administration of 1,25(OH)2D3.

The present data demonstrate (a) increased 1,25(OH)2D3 receptors and (b) unchanged 1,25(OH)2D3‐dependent synthesis of calcium binding protein (CaBP) in experimental uraemia.
The effect of angiotensin‐l converting enzyme inhibition on insulin action in healthy volunteers
Authors: GANS R. O. B. , BILO H. J. G. , NAUTA J. J. P. , POPP‐SNIJDERS C. , HEINE R. J. , DONKER A. J. M.
Published: March 2008

Abstract. Acute hyperinsulinaemia, achieving insulin levels within the physiological range, induces sodium retention. At the same time an activation of the reninangiotensin system occurs, with a rise in plasma renin activity (PRA) and angiotensin‐II level but no change in plasma aldosterone. After administration of higher, pharmacological doses of insulin an increase in systolic blood pressure and heart rate can also be observed, while further increases in PRA and angiotensin‐II are noted. To determine whether angiotensin‐II is involved in observed insulin actions, we studied the renal and cardiovascular effects of three dosages of insulin (50 (Ins I), 300 (Ins II) and 500 (Ins III) mU kg‐1 h‐1) in healthy subjects after one week of treatment with the angiotensin‐I converting enzyme inhibitor enalapril (10 mg twice a day), using the euglycaemic clamp technique. Control data were obtained from two previously conducted experiments in the same subjects, one with infusion of insulin and one with the insulin solvent only. The effect of insulin on fractional sodium excretion, blood pressure and heart rate was unaffected by enalapril, which precludes any involvement of the renin‐angiotensin system with regard to these aspects of insulin action. Insulin sensitivity increased significantly during treatment with enalapril (with enalapril: Ins I: 11·3 ± 3·0, Ins II: 20·0±3·4 and Ins III: 20·6±3·9 mg kg‐1 min‐1 glucose (mean±SD); without enalapril: Ins I: 8·7±2·3, Ins II: 13·7±3·0 and Ins III: 15·5±3·1 mg kg‐1 min‐1 glucose; P<0·05). When this latter finding can be confirmed in a randominized study, enhancement of tissue sensitivity to the glucose‐lowering actions of insulin by enalapril must be considered a property common to all members of this class of drugs.
In vitro inhibition of Helicobacter pylori urease: biochemical and ultrastructural analysis
Authors: NILIUS M. , BODE G. , LEHNHARDT G. , MALFERTHEINER P.
Published: March 2008

Abstract. Inhibition of H. pylori urease was studied by means of electron‐microscopy and electrophoretic methods using different urease inhibitors, such as acetohydroxamic‐acid (AHA), L‐ascorbic acid (AsA), copper ions, a combination of L‐ascorbic acid with copper ions and UV light. AHA in two different concentrations and AsA at a concentration of 0·1 mg ml‐1 showed incomplete inhibition of H. pylori urease activity in our electrophoretic experiments. Only membrane‐bound activity was inhibited with AHA but not the activity localized within the cytoplasma as demonstrated by electron‐microscopy. AsA at a concentration of 0·5 mg ml‐1 and the combination of copper ions (1 μg ml‐1) with AsA completely inhibited the urease activity as demonstrated by electron‐microscopy and electrophoretic experiments. Cu2+ ions in high concentrations (100 μg ml‐1) and UV light exposure for more than 4 h induced a complete disintegration of H. pylori. Electrophoresis showed no active protein after UV light exposure of 2 h. Different urease inhibitors tested in this study showed dose‐dependent inhibitory effects on H. pylori urease in vitro.
The influence of fractions of abnormal erythrocytes on aggregation
Authors: SINGH A. , REINHART W. H.
Published: March 2008

Abstract. Erythrocytes with abnormal shapes and deformability reduce cell aggregation and hence sedimentation. It is not known what influence small fractions of these abnormal cells have on the sedimentation behaviour of normal cells. We have used three different methods to alter erythrocyte properties (glutaraldehyde, heat treatment, and metabolic depletion). The admixture of such cells in increasing fractions to normal cells affected the sedimentation behaviour in three different ways. Heat‐treated erythrocytes decreased the sedimentation proportionally. Small fractions of glutaraldehyde‐treated cells increased the sedimentation, which was explained by a pro‐aggregatory change of surface properties by glutaraldehyde. With 50% or more glutaraldehyde‐treated cells sedimentation was inhibited, which was due to excessive formation of aggregates occupying the entire tube. The presence of small fractions of echino‐cytes produced by metabolic depletion decreased cell sedimentation disproportionally, which was explained by an inability of spiculated cells to form aggregates with normal erythrocytes. These results indicate that erythrocyte sedimentation is affected by fraction of abnormal cells in a complex way. Many diseases are characterized by fractions of abnormal erythrocytes. Our results may, therefore, contribute to a better understanding of these conditions.
Accelerated cholesteryl ester transfer in patients with insulin‐dependent diabetes mellitus
Authors: BAGDADE J. D. , RITTER M. C. , SUBBAIAH P. V.
Published: March 2008

Abstract. Abnormalities in cholesteryl ester transfer (CET) may play a role in the development of diabetic arterial vascular complications. To assess this important step systematically in reverse cholesterol transport, we have studied 20 treated, clinically stable, normolipidaemic patients. Contrary to the impairment in CET described previously in NIDDM, the mass of CE transferred from HDL to VLDL+LDL was significantly greater in IDDM patients than in controls at 1,2, and 4 h (P<0.001). When the d<1.063 plasma fractions from IDDM subjects were combined with controls d<1.063 fractions, an accelerated CET response was observed which was identical to that found in intact IDDM plasma. This finding, which indicates that this disturbance in CET was associated with the acceptor lipoproteins, was confirmed when we found that it was reproduced by the addition of IDDM VLDL and not LDL to control d>1.063 fractions.

Changes observed in lipoprotein core lipid composition were consistent with accelerated CET occurring in IDDM in vivo: the TG/CE core lipid ratio was decreased in VLDL from six subjects (diabetic 9.5±0.8 vs control 12.9±3.4; P<0.1) and increased in their HDL (diabetic 0.55±0.11 vs control 0.42±0.04; P<0.025). No correlation was demonstrable between estimates of diabetic control (glycoalbumin, fasting glucose) and CET. These data indicate that CET may be abnormally increased in normolipidaemic IDDM patients. A defect of this type may be atherogenic because it increases the number of lipoprotein particles in plasma which resemble cholesteryl ester‐enriched chylomicron and VLDL remnants but whose normal receptor‐mediated catabolism may be altered.
Effect of low protein diet on the renal response to meat ingestion in diabetic nephropathy
Authors: PINTO J. R. , BENDING J. J. , DODDS R. A. , VIBERTI G.‐C.
Published: March 2008

Abstract. We measured the renal haemodynamic and proteinuric response to a meat meal (MM) in ten persistently proteinuric insulin‐dependent diabetic patients in a randomized cross‐over study of 3 weeks on low protein diet (LPD) or normal protein intake (NPD). On LPD, protein intake (0.64±0.05 vs 1.15±0.09 g kg‐1 body weight (BW) per day, P<0.001), plasma urea (6.6±1.3 vs 11.0±2.0 mmol 1‐1, P<0.01) and urea appearance (0.06±0.01 vs 0.16±0.03 gN kg‐1 body weight per day, P<0.001) were lower. Baseline glomerular filtration rate (GFR), renal plasma flow (RPF) and renal vascular resistance (RVR) were similar on the two diets and there were no significant average changes in these variables after the meat meal on either diet (NPD, before vs after MM: GFR: 67±11 vs 71±13 ml min‐1 1±73 m‐2; RPF: 479±70 vs 512±81 ml min‐1 1±73 m‐2; RVR: 181±45 vs 179±52 mmHg min‐1 1‐1); (LPD, before vs after MM: GFR: 64±10 vs 67±11 ml min‐1 1±73 m‐2; RPF: 506±60 vs 533±52 ml min‐1 1±73 m‐2; RVR: 151±28 vs 146±32 mmHg min‐1 1‐1). However, all patients with baseline GFR above 60 ml min‐1 1.73 m‐2 showed a GFR rise in response to the meat meal on both diets, while patients with lower baseline values tended to reduce their GRF. Baseline fractional albumin clearance was lower on LPD (geometric mean [range]: 1.15 [0.10–50.53].10‐4) than on NPD (l.74[0.17–56.99]×10‐4). MM produced a significant increase in the fractional clearance of albumin of ±69% on NPD to 2±94(0±37–113±42)×10‐4 (P<0.02), and of ±62% on LPD to 1.86(0.13–82.90)×10‐4(P<0.01). The magnitude of these changes was not statistically different. In proteinuric insulin‐dependent diabetic patients on NPD the renal vasodilatory response to a meat meal is blunted particularly when basal GFR is depressed. LPD does not restore physiological renal response and, while reducing baseline proteinura, fails to prevent proteinuric effect of meat ingestion.