bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory effects of pertussis toxin on the cAMP generating system in human mononuclear leucocytes
Authors: GRIESE M. , GRIESE S. , REINHARDT D. 
Published: March 2008

Abstract. In a previous investigation of children infected with pertussis during the first week of paroxysmal stage, we found a 50–75% reduction of the isoprenaline (IPN)‐induced cAMP response in peripheral MN leucocytes. In order to characterize these findings further, intact human MN leucocytes from healthy adults were treated with PT in vitro. Basal, as well as prostaglandin E1‐stimulated cAMP levels were decreased by PT in a dose‐dependent fashion over a range of 0.01 to 1000 ng ml‐1 to about 65% of control levels. Stimulation of PT‐pretreated cells (100 ng ml‐1, 90 min, 37 C) showed significantly reduced IPN and PGE1induced cAMP accumulation, indicated by a depression and shift of the dose response curves to the right. In contrast, cAMP generation was unchanged by forskolin, a diterpene that is believed to directly stimulate adenylyl cyclase. The anti‐allergic drug ketotifen had no direct effects on basal, IPN or PGE1‐ induced cAMP responses; however the inhibitory actions of PT pretreatment on cAMP levels were diminished (basal and isoprenaline‐stimulated) or reversed (PGE1‐stimulated).To further locate the site of impaired cAMP responses, β‐adrenoceptor binding, as well as displacement characteristics of the receptor, were estimated by 1251‐cyanopindolol binding to a plasma membrane fraction pretreated with or without PT. No differences in β‐adrenoceptor number or in the affinities of the binding sites could be detected. These data are in close agreement with the findings on MN leucocytes from pertussis‐infected children and support the notion of PT‐induced impaired signal transduction in the cAMP generating system in human MN leucocytes.
Cholesterol synthesis in patients with glutathione deficiency
Authors: GUSTAFSSON J. , CARLSSON B. , LARSSON A. 
Published: March 2008

Abstract. 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase catalyses the rate‐limiting step in cholesterol synthesis. Glutathione (GSH) has been postulated to be an important activator of HMG‐CoA reductase in vivo.HMG‐CoA reductase activity was assayed in cultured fibroblasts from healthy children. Solubilized enzyme preparations were prepared by ultracentrifu‐gation after freezing and thawing of fibroblasts. Such treatment increased the relative enzyme activity markedly. Enzymological assay conditions were established. Addition of GSH stimulated the reaction, whereas there was inhibition after addition of glutathione disulphide (GSSG). The inhibitory effect of GSSG could be reversed by the addition of excess GSH.Fibroblast preparations, deficient in GSH, were obtained from children with glutathione synthetase deficiency or from normal subjects after the growth of fibroblasts in the presence of buthionine sulphoximine. Solubilized enzyme preparations from GSH‐deficient fibroblasts had HMG‐CoA reductase activities lower than or comparable with those of control preparations.The results indicate only some reduction in the capacity for cholesterol synthesis in subjects with glutathione deficiency.The existence of additional activation mechanisms in vivo, alternative to GSH, for thiol‐dependent modulation of HMG‐CoA reductase activity seems likely.,
Increased high‐density lipoprotein cholesterol concentration in alcoholics is related to low cholesteryl ester transfer protein activity
Authors: SAVOLAINEN M. J. , HANNUKSELA M. , SEPPÄNEN S. , KERVINEN K. , KESÄNIEMI Y. A. 
Published: March 2008

Abstract. Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl esters from HDL to apo B‐containing lipoproteins. Since alcoholics have high HDL cholesterol and low LDL cholesterol levels, a defect in cholesteryl ester transfer could be responsible for the alcohol‐induced alteration in cholesterol distribution between lipoproteins. To test this hypothesis, we compared CETP activity in plasma from 30 alcoholics without severe liver damage and 16 control subjects.Plasma CETP activity was 28% lower in the alcoholics compared with the controls (P < 0.001), while the teetotallers among the latter had slightly higher CETP activity than those who consumed alcohol in moderation. CETP activity increased slowly after ethanol withdrawal, but did not reach the control level within the 7‐day observation period. A positive correlation was observed between plasma CETP activity and the LDL cholesterol/HDL cholesterol ratio (r= 0.480, P < 0.002), whereas CETP activity showed a negative correlation with HDL cholesterol level (r= ‐0.467, P < 0.001).The results indicate that defective transfer of cholesteryl esters from HDL to LDL contributes to the high HDL cholesterol levels in alcoholics.
Spinal and forearm bone mass in relation to ageing and menopause in healthy Italian women
Authors: ORTOLANI S. , TREVISAN C. , BIANCHI M.L. , CARACENI M.P. , ULIVIERI F.M. , GANDOLINI G. , MONTESANO A. , POLLI E.E. 
Published: March 2008

Abstract. Most studies concerning bone status have been performed in Nordic and Anglo‐Saxon countries and few data are available on southern European populations.We performed a cross‐sectional study on spine and forearm bone mass in 234 healthy Italian women and related the results to age and time since menopause.Forearm bone mass does not decline in premenopausal age, whereas, as far as the spine is concerned, a significant reduction appears 3 years before the mean age of menopause; in both cases, the occurrence of menopause accounted for an accelerated phase of bone loss. In postmenopausal women both spine and forearm bone mass show a stronger correlation with years since menopause than with age. According to a linear exponential model, the rate of spinal bone loss per year since menopause is around 4% in the first 3 years which slows down to around 2% in the 5th year; the corresponding rates of forearm bone loss are 2% and 1.3%, respectively.
High blood pressure and insulin resistance: influence of ethnic background
Authors: FERRANNINI E. , HAFFNER S.M. , STERN M.P. , MITCHELL B.D. , NATALI A. , HAZUDA H.P. , PATTERSON J.K. 
Published: March 2008

Abstract. Hyperinsulinaemia links non‐insulin dependent diabetes (NIDDM), obesity, and hypertension, each an insulin‐resistant state in its own right. Insulin resistance predicts the occurrence of NIDDM, and plays a major role in its pathogenesis. We tested the hypothesis that hyperinsulinaemia may also predict hypertension in a sample (n= 2905) of the mixed population of San Antonio, in which hyperinsulinaemia and NIDDM are more prevalent among Mexican‐Americans than non‐Hispanic whites. Whilst in the whole sample the hypertensives had significantly (P < 0.001) higher plasma insulin concentrations than the normotensives, high blood pressure was significantly (P < 0.01) more frequent among non‐Hispanic whites than Mexican‐Americans regardless of diabetes status. After adjusting for factors (age, sex, body mass, and body fat distribution) known to affect insulin levels, a direct relationship between post‐glucose plasma insulin concentrations and prevalence of hypertension was still present in both ethnic groups. In Mexican‐Americans, however, the standardized prevalence of hypertension was significantly (P < 0.001) lower at any given insulin concentration. Post‐glucose plasma glucose levels also were directly related to hypertension prevalence in both groups; again, the regression line was shifted downward and, furthermore, less steep (P < 0.02) in Mexican‐Americans, suggesting relative protection against the negative effect of hyperglycaemia on blood pressure. Dyslipidaemia (higher total cholesterol and triglyceride, and lower HDL‐cholesterol concentrations) was strongly associated with hyperinsulinaemia and blood pressure in both ethnic groups. After adjusting for plasma insulin, only hypertriglyceridaemia was associated with high blood pressure, with no inter‐ethnic difference.We conclude that in this population hyperinsulinaemia is characteristic of hypertension but does not explain its prevalence against a divergent ethnic background. Other factors that determine high blood pressure must interact with insulin resistance to determine the prevalence rate of hypertension in the population.
The recovery of renal function in rats after release of unilateral ureteral obstruction: the effects of moderate isotonic saline loading
Authors: HARRIS K.P.G. , PURKERSON M.L. , KLAHR S. 
Published: March 2008

Abstract. Following 24 h of ureteral obstruction in the rat, renal blood flow and glomerular filtration rate are markedly depressed. The effect of saline loading on post‐obstructive glomerular filtration (GFR) was studied in 15 female Sprague‐Dawley rats in the awake state, 4 h following the release of 24 h of unilateral ureteral obstruction.Group I (n= 8) received 39 μl min ‐1of 0.9% saline only for 1 h prior to study and Group II (n= 7) received 78 μl min‐1of 0.9% saline for the whole 4 h prior to study. The Cin and CPAH of the post‐obstructed kidney were significantly reduced over control values in both groups. Saline loading (Group II) resulted in an improvement in Cin in the post‐obstructed kidney compared with group I (3.22 ± 0.14 vs.219 ± 0.14 ml/min/kg BW, P < 0.001). This was independent of any change in CPAH.In two further groups of rats the saline loading protocol was shown to cause a rise in the excretion of urinary cGMP in the post‐obstructed kidney, but not the contralateral control kidney. In addition, administration of exogenous atriopeptin (1–24) to non‐saline loaded animals resulted in a qualitatively similar alteration in renal function to saline loading, namely a rise in Cin and an increase in excretion of cGMP by the post‐obstructed kidney, and no change in CPAH.The results show that the decrease in GFR following release of unilateral ureteral obstruction may be improved by moderate saline loading possibly by enhancing the release of endogenous atrial peptide, and that the decline in GFR after release of ureteral obstruction is at least in part independent of renal plasma flow.
Different β‐adrenoceptor‐effector coupling in human ventricular and atrial myocardium
Authors: SCHWINGER R. H. G. , BÖHM M. , PIESKE B. , ERDMANN E. 
Published: March 2008

Abstract. To examine whether the downregulation of β‐adrenoceptors is accompanied by reduced β‐adrenoceptor‐mediated effects in atrial as well as in ventricular myocardium, we investigated the β‐adrenoceptor‐effector coupling in atrial and papillary muscle strips from patients with terminal heart failure (heart transplantation because of dilated cardiomyopathy; New York Heart Association Class IV, NYHA IV) and moderate heart failure (mitral valve replacement, NYHA II‐III) and in tissue from non‐failing hearts. The isometric force of contraction induced by isoprenaline (0·001‐1 μmoll‐1) or Ca2+ 1·8–15 mmoll‐1) in atrial muscle strips and papillary muscle strips has been measured. We also examined the number of β‐adrenoceptors in both tissues by radioligand binding.The degree of heart failure affected neither the potency (EC50: control: 0·01 (0·001‐0·082) μmoll‐1; NYHA II‐III: 0·01 (0·001‐0·125) μmoll‐1; NYHA IV: 0·01 (0·001‐0·160) μmoll‐1) nor the efficacy (NYHA IV: 7·8 ± 1·0 mN; NYHA II‐III: 6·1 ± 0·7 mN; control: 7·7 ± 0·9 mN) of the isoprenaline‐mediated increase in force of contraction in atrial muscle strips. This is in spite of a reduced number of β‐adrenoceptors in moderately (NYHA II‐III) and terminally (NYHA IV) failing atrial myocardium compared to non‐failing atrial myocardium (P<0·05). In contrast, in papillary muscle strips increasing degrees of heart failure were accompanied by a progressive reduction of the isoprenaline‐mediated increase in force of contraction (P<0·05) as well as by a progressive decrease of β‐adrenoceptors (P<0·05). In papillary muscle strips, there was a significant (P<0·05) rightward shift of the isoprenaline concentration‐response curve in failing myocardium as compared to controls. In addition, the potency of isoprenaline to increase force of contraction was lower in left ventricular myocardium compared to right atrial tissue. The Ca2+ ‐mediated maximal increase in force of contraction in atrial and papillary muscle strips was similar in non‐failing and failing myocardial tissue.In conclusion, a surplus of β‐adrenoceptors for mediating positive inotropic effects seems to exist only in atrial but not in left ventricular human myocardium. Therefore, the efficacy of the β‐adrenoceptor‐effector coupling, at least in terms of positive inotropic effects, cannot be inferred for any tissue in the human myocardium.
Hyperparathyroidism and abnormal 1,25(OH)2vitamin D3 metabolism in experimental lead intoxication
Authors: SZABO A. , MERKE J. , HÜGEL U. , MALL G. , STOEPPLER M. , RITZ E. 
Published: March 2008

Abstract. Clinical evidence points to disturbed calcium metabolism in lead (Pb) intoxication. To further clarify the mechanisms involved, serum levels of 1,25(OH)2D3, receptors for 1,25(OH)2D3 as well as size and ultrastructure of parathyroid glands were examined in Wistar Kyoto rats exposed to 1% lead (Pb) acetate in drinking water for 10 weeks (short‐term study) or 0·001 – 1 % Pb acetate for 24 weeks (long‐term study). After administration of Pb for 10 weeks, bone Pb was significantly increased (641±66·9 (SD) vs. 0·648±0·39 mg kg‐1 ash in controls). Total serum calcium and ionized Ca2+ (1·15±0·031 vs. 1·25±0·03 mmol 1‐1) were significantly decreased. Renal function (Ccr) was unchanged, but urinary cAMP excretion and circulating 1,25(OH)2D3 (177±10·9 vs. 232±18·9 pmol 1‐1) were diminished. Specific binding of 1,25(OH)2D3 was increased in parathyroids (Bmax 128±4·7 vs. 108±0·6 fmol mg‐1 protein) and intestinal mucosa; Bmax failed to adequately rise in response to pretreatment with 1,25(OH)2D3 (2·10 ng day‐1 for 4 d) in Pb‐exposed animals. Receptor characteristics (sedimentation constant, KD, DNA affinity) were unchanged. Parathyroid weight was significantly increased (178·25 vs. 96·34 μg) with no change of estimated nuclear volume, cell volume or cell ultrastructure. After 24 weeks of Pb exposure, a dose‐dependent but non‐linear increase of parathyroid weight was noted between 0·001% and 1% Pb in drinking fluid.The present study documents secondary hyperparathyroidism associated with, and presumably caused by, hypocalcaemia and low 1,25(OH)2D3 levels, in experimental Pb intoxication.
HCV infection, hepatic HLA display and composition of the mononuclear cell inflammatory infiltrate in chronic alcoholic liver disease
Authors: FRENI M. A. , AJELLO A. , RESTA M. L. , GAETA G. B. , SPADARO A. , FAVA A. , CALAPRISTI I. , ALESSI N. , FERRAÙ O. 
Published: March 2008

Abstract. Viral infection may play a role in alcoholic liver disease with histological features of chronic active hepatitis (CAH). Human leucocyte antigen (HLA) hepatocellular display is supposed to allow HLA‐restricted T‐lymphocyte cytotoxicity in chronic viral hepatitis.We studied the presence of serum anti‐hepatitis C virus (HCV) antibodies, the hepatic HLA display and the composition of the mononuclear cell infiltrate in 16 patients with alcoholic liver disease and histological features of CAH and in 11 patients with alcohol‐related degenerative changes. All patients were negative for hepatitis B virus (HBV) markers.Anti‐HCV were tested by microplate ELISA. Class I HLA A, B, class II HLA DR, lymphocytes pan T, T helper/inducer, T suppressor/cytotoxic, B, and K NK cells were stained on liver cryostat sections by monoclonal antibodies and double indirect immunoperoxi‐dase.Anti‐HCV were present in all the patients with features of CAH and absent in those with only degenerative changes. In livers with features of CAH the mononuclear cell infiltrate consisted largely of T lymphocytes with marked prevalence of suppressor/cytotoxic cells in periportal and lobular areas. K NK cells were rare. Class I HLA, diffusely displayed on bile duct epithelium and on sinusoidal cells, also appeared on liver cells in the areas of periportal and lobular necrosis, namely on the hepatocytes in close contact with suppressor/cytotoxic T cells. In livers with only degenerative changes class I HLA were diffusely displayed on bile duct epithelium and on sinusoidal cells but absent on the hepatocytes. In all the specimens HLA DR antigens were expressed on sinusoidal and inflammatory cells.In alcoholic liver disease with features of CAH the presence of anti‐HCV and the close contact of T‐cytotoxic cells to hepatocytes expressing class I HLA suggest a pathogenetic role of HCV and an HLA‐restricted T‐cytotoxic mechanism of hepatocellular necrosis.
Incomplete suppression of hepatic glucose production in non‐insulin dependent diabetes mellitus measured with [6,6‐2H2]glucose enriched glucose infusion during hyperinsulinaemic euglycaemic clamps
Authors: POWRIE J. K. , SMITH G. D. , HENNESSY T. R. , SHOJAEE‐MORADIE F. , KELLY J. M. , SÖNKSEN P. H. , JONES R. H. 
Published: March 2008

Abstract.We have minimized methodological errors in the isotope dilution technique by using stable isotope, [6,6‐2H2]glucose, thus avoiding the problem of contamination of tritiated glucose tracers and, by maintaining a constant plasma tracer enrichment have reduced error due to mixing transients. Using these modifications we have calculated hepatic glucose production in 20 patients with non‐insulin‐dependent diabetes mellitus during low (1 mU kg‐1 min‐1) and high (8 mU kg‐1 min‐1) dose insulin infusions. Mean fasting hepatic glucose production was 14.2 ±0.8 μnol kg‐1 min‐1. This suppressed by only 68% to 4.6&±0.8 μmol kg‐1 min‐1 during the low‐dose insulin infusion (plasma insulin 0.85 ±0.05 nmol 1‐1) and did not suppress further during the high‐dose insulin infusion (plasma insulin 14.55±0.83 nmol 1‐1). Hepatic glucose production was significantly higher than zero throughout the study.Thus, we have found that minimization of known errors in the isotope dilution technique results in physiologically plausible and significantly positive values for hepatic glucose production indicating that the liver is resistant to insulin in patients with non‐insulin‐dependent diabetes mellitus.
Accumulation of iron in erythroblasts of patients with erythropoietic protoporphyria
Authors: RADEMAKERS L. H. P. M. , KONINGSBERGER J. C. , SORBER C. W. J. , FAILLE H. BAART DE LA , HATTUM J. VAN , MARX J. J. M. 
Published: March 2008

Abstract. We have studied the iron metabolism in nine patients with erythropoietic protoporphyria (EPP) and three patients with sideroblastic anaemia (SA). All, except one EPP patient were iron deficient. The SA patients had a secondary haemochromatosis.The bone marrow aspirates of patients with SA and also three patients with EPP had a high incidence of ring sideroblasts. Ultrastructural examination of the bone marrow consistently showed finely dispersed electron‐dense deposits localized in mitochondria of erythroblasts in all patients with EPP and SA. Mito‐chondrial electron energy‐loss spectroscopy (EELS) indicated identical iron compounds in erythroblasts of all EPP and SA patients.These findings indicate that the mitochondrial iron utilization is disturbed in EPP and SA. The observation of mitochondrial iron deposition in erythroblasts in EPP and SA suggests that this feature is not of pathognomonic value for diagnosis of SA, but is apparently the result of an inefficient haem synthesis, in EPP due to a defective ferrochelatase. The mitochondrial iron deposition does not depend on the iron status (iron overload or iron deficiency) of the EPP patient.
Coxsackie B3 myocarditis induces a decrease in energy charge and accumulation of hyaluronan in the mouse heart
Authors: WALDENSTRÖM A. , FOHLMAN J. , ILBÄCKY N. G. , RONQUIST G. , HÄLLGREN R. , GERDIN B. 
Published: March 2008

Abstract. Interstitial oedema in chronic inflammation and ischaemia is related to an accumulation of hyaluronan (hyaluronic acid; HA) in the interstitium. As interstitial oedema will affect the oxygen transport in the interstitium we have evaluated whether accumulation of HA is related to signs of myocardial energy depletion in virus induced myocarditis. Myocarditis was induced in Balb/c mice by inoculation of Coxsackie B3 virus. The extractable HA content of the myocardium increased progressively from a baseline value of 153 ± 26 μg g‐1 dry weight to a maximum of 286 ± 78 μg g‐1 dry weight at day 7, whereafter there was a slight decline. Affinity histochemistry visualized HA in the endo‐perimysium in healthy myocardium. At day 5 after Coxsackie B3 inoculation there was a general widening of the endomysium, which exhibited a positive staining for HA. In conjunction with focal inflammatory infiltrates the staining for HA was even more pronounced.The energy rich adenylates were reversibly affected by the Coxsackie B3 infection. There was a slight, but significant decline in EC from 0.74 ± 0.05 in the control group to a minimum value of 0.64 ± 0.10 at day 5, whereafter a restitution was observed at days 7 and 10. The total adenine nucleotide pool was similarly decreased from 27.8 ± 2.9 μmol g‐1 dry weight in controls to 24.6 ± 2.1 μg g‐′ dry weight at day 5, and normalized at days 7 and 10.The data suggest that virus induced myocarditis is associated with a local accumulation of HA in the myocardium. Accumulation of HA is reasonably not a major pathophysiological component in the disturbed energy metabolism seen, but may be of interest for genesis of arrhythmias and possibly sudden death.
Plasma aluminium in a reference population: the effects of antacid consumption and its influence on biochemical indices of bone formation
Authors: SHARP C. A. , PERKS J. , WORSFOLD M. , DAY J. P. , DAVIE M. W. J. 
Published: March 2008

Abstract. Aluminium is involved in the etiology of several complications of chronic renal failure and has been firmly established as having toxic effects on bone tissue. We have measured plasma aluminium together with serum osteocalcin, procollagen I C‐terminal peptide and total alkaline phosphatase activity in healthy subjects and in a group of subjects who consumed aluminium‐containing and non‐aluminium containing antacid preparations, with normal renal function. Age‐related healthy reference ranges for plasma aluminium are presented and the effects of chronic antacid consumption on plasma aluminium and biochemical markers of bone formation investi gated.In 172 healthy subjects the mean plasma aluminium concentration was 4.4 ± 2.9 μg L‐1, men having a significantly greater circulating aluminium load than women (5–4 ± 2.8 μg L‐1 vs. 4.0 ± 2.8 μg L‐1 respect ively (P = 0.0039)). Older men were found to have significantly higher plasma aluminium levels than younger men. Increased plasma aluminium was seen in subjects taking antacids although this was not asso ciated with significant changes in most indices of bone formation.