bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oestrogen receptor gene variation is a determinant of coronary reactivity in healthy young men
Authors: Lehtimäki T. , Laaksonen R. , Mattila K. M. , Janatuinen T. , Vesalainen R. , Nuutila P. , Laakso J. , Jaakkola O. , Koivula T. , Knuuti J. 
Published: March 2003

AbstractBackground Oxidised low‐density lipoprotein (ox‐LDL) is a determinant of impaired coronary function and oestrogens inhibit its formation probably throughout genetically‐variable oestrogen receptor 1 (ESR1) in artery wall. We hypothesized that the ESR1 polymorphism might influence coronary function and reactivity as measured by positron emission tomography (PET), which allows the detection of coronary dysfunction before appearance of angiographic lesions.Materials and methods Fifty‐one healthy young men (aged 35 ± 4 years), with normal or slightly‐elevated serum cholesterol, underwent PET with intravenous adenosine. ESR1 PvuII genotypes P/P, P/p, and p/p in addition to the plasma autoantibody titre against ox‐LDL, a marker of in vivo oxidation, were determined.Results The ESR1 genotype persisted as the only significant predictor of adenosine stimulated coronary flow (P = 0·035) after adjustment for other coronary risk factors. Subjects with P/P genotype had 33·4 and 41·8% lower adenosine‐stimulated flow values than subjects with P/p and p/p genotypes (P = 0·030). Furthermore, plasma levels of ox‐LDL titre were on average 59 and 77% higher in subjects with P/P genotype than in subjects with P/p or p/p genotypes (P = 0·049).Conclusions These tentative findings from our pilot study provide evidence that genetic variation in ESR1 may modify coronary reactivity and LDL oxidation and reflect differences in the early pathogenesis of coronary dysfunction in these healthy young men.
Amadori‐albumin correlates with microvascular complications and precedes nephropathy in type 1 diabetic patients
Authors: Schalkwijk C. G. , Chaturvedi N. , Twaafhoven H. , Van Hinsbergh V. W. M. , Stehouwer C. D. A. ,   the EUCLID Study Group
Published: March 2003

AbstractBackground Amadori‐albumin, a major glycated protein, is involved in experimental hyperglycaemia‐induced microvascular complications, and is associated with advanced nephropathy in Type I diabetic patients in humans. Our aim was to assess the association of Amadori‐albumin with early nephropathy and with retinopathy in Type I diabetic patients and the involvement of chronic low‐degree inflammation therein.Design and Methods Amadori‐albumin, the Amadori product of haemoglobin (HbA1c), C‐reactive protein, and fibrinogen levels were measured in the EUCLID study, a 2‐year randomised, double‐blind, placebo‐controlled trial of lisinopril in 447 Type I diabetic patients. Retinal photographs were taken in 341 patients at baseline and 294 at follow up.Results Amadori‐albumin was positively associated with albumin the excretion rate and retinopathy status (P = 0·0001 and P = 0·02 for trend, respectively) and with the progression from normoalbuminuria to (micro)albuminuria (38·6 U mL−1 in nonprogressors, 44·3 U mL−1 in progressors; P = 0·02), but not with the development or progression of retinopathy during a 2‐year follow up. Amadori‐albumin levels at baseline were associated with C‐reactive protein and fibrinogen (P = 0·0007 and P = 0·0001, respectively). C‐reactive protein and fibrinogen were also associated with albumin excretion rates (P = 0·03 and P = 0·01, respectively) and retinopathy status (P = 0·02 and P = 0·0006, respectively). Adjustment for these inflammatory markers did not markedly attenuate the association between Amadori‐albumin and the albumin excretion rate, while adjustment for fibrinogen, but not C‐reactive protein, abolished the association between Amadori‐albumin and retinopathy. Lisinopril had no impact on the association between the levels of Amadori‐albumin and albumin excretion rates or retinopathy.Conclusions Amadori‐albumin was associated with early nephropathy and with retinopathy in Type I diabetic patients and preceded an increase in albumin excretion rate, but not retinopathy. A chronic low‐degree inflammation does not appear to be involved in Amadori‐albumin‐associated microvascular complications in Type I diabetes.
Effects of combined treatment with pravastatin and ursodeoxycholic acid on hepatic cholesterol metabolism
Authors: Hillebrant C.‐G. , Nyberg B. , Gustafsson U. , Sahlin S. , Björkhem I. , Rudling M. , Einarsson C. 
Published: March 2003

AbstractBackground Treatment with ursodeoxycholic acid and also, to some degree, statins reduces cholesterol saturation of bile. The present study aimed [1] to study the effects of combined treatment with ursodeoxycholic acid and pravastatin on hepatic cholesterol metabolism and [2] to evaluate if the addition of pravastatin to ursodeoxycholic acid treatment has beneficial effects on the lipid composition of gallbladder bile in gallstone patients.Materials and methods Nineteen patients with cholesterol gallstones were subjected to combined treatment with ursodeoxycholic acid (500 mg bid) and pravastatin (20 mg bid) for three weeks before cholecystectomy. Eleven patients received ursodeoxycholic acid only and 20 untreated gallstone patients served as controls. Gallbladder bile was collected, and for both the patients receiving combined treatment and the controls a liver biopsy was also obtained peroperatively.Results The cholesterol saturation of bile averaged 59% in the patients on combined treatment, 60% in the ursodeoxycholic acid‐treated patients, and 130% in the untreated controls. In the patients receiving ursodeoxycholic acid, this bile salt constituted approximately 60% of all bile salts. The patients receiving combined treatment had reduced cholesterol synthesis, as reflected by a 45% reduction in serum lathosterol. The activity and the mRNA levels of cholesterol 7α‐hydroxylase and the mRNA levels for the low density lipoprotein‐receptor were not significantly affected.Conclusions Pravastatin does not further reduce the cholesterol saturation of bile in gallstone patients treated with ursodeoxycholic acid, although hepatic cholesterol synthesis is inhibited. The study supports the important concept that de novo synthesized cholesterol is not particularly important for biliary cholesterol secretion in humans.
Ca2+ mobilization in saphenous vein smooth muscle cells derived from patients with primary varicosity
Authors: Schuller‐Petrovic S. , Stessel H. , Brunner F. 
Published: March 2003

AbstractBackground  Human primary varicosity is associated with ‘weakness’ of the vein wall. We investigated whether the reduced responsiveness of varicose veins to physiological vasoconstrictors might result from impaired Ca2+ mobilization in venous smooth muscle.Materials and methods  The hypothesis was tested in cells derived from phenotypically different vein segments that were obtained from the inguinal saphenous vein (tissue with incompetent valves), the distal portion of the long saphenous vein just above the medial ankle (clinically healthy tissue), and from a tributary to the long saphenous vein just below the knee (incompetent and overtly varicose tissue). Saphenous vein from patients undergoing cardiac surgery served as control. Cytosolic free Ca2+ levels ([Ca2+]i) were determined with the fura‐2 method in cultured medial smooth muscle cells of third to sixth passage (21–23 measurements per tissue derived from five controls and seven patients).Results  Angiotensin II (10 nmol L−1 to 10 µmol L−1) induced a significantly (P < 0·05) smaller rise in [Ca2+li response in cells derived from incompetent or varicose segments (∼70 nmol L−1) than in cells derived from clinically healthy vein (∼130 nmol L−1) or controls (∼170 nmol L−1). Likewise, the effect of endothelin‐1 (100 nmol L−1) on [Ca2+]i was considerably less in cells derived from segments with incompetent valves or from varicose vessel segments than in cells derived from control patients (P < 0·05). In organ baths, endothelium‐denuded strips of varicose vessels contracted significantly less in response to these agonists than clinically healthy segments from the same patient.Conclusions  The reduced contractility of diseased human varicose veins in response to angiotensin II and endothelin‐1 involves impaired Ca2+ mobilization.
Variability of Nt‐proANP and C‐ANP
Authors: McDowell G. , Patterson C. , Maguire S. , Shaw C. , Nicholls D. P. , Hall C. 
Published: March 2003

AbstractBackground Natriuretic peptides are frequently measured in patients with chronic cardiac failure (CCF). We set out to compare the variability of atrial natriuretic peptide (C‐ANP) and its precursor N‐terminal pro‐ANP (Nt‐proANP) to decide which would be more suitable for routine use.Methods Ten males with compensated CCF (age range 62–76 years) were studied, with matched controls. Blood was withdrawn every 2 min for 90 min from a forearm vein, and plasma C‐ANP and Nt‐proANP were measured by radioimmunoassay.Results Levels were elevated in the patient group [C‐ANP: median 268 (range 171–423) vs. 40 (28–56) ng L−1, P < 0·0002 Mann–Whitney U‐test; Nt‐proANP: 1955 (562–4451) vs. 621 (409–961) pmol L−1, P < 0·003]. A similar number of ‘peaks’ was observed in both groups with both peptides, about one every 10 min, and their relative height was similar in both groups. Variability was greater for C‐ANP than for Nt‐proANP in both patients [coefficient of variation of means 51 (range 36–70) vs. 3·6 (2·1–6·2)%, P < 0·01; sign test] and controls [65 (49–83) vs. 8·9 (4·7–13·5)%, P < 0·01].Conclusion Nt‐proANP is less variable than C‐ANP and hence more suited for diagnostic or prognostic use.
Differential regulation of atrial and brain natriuretic peptides and its implications for the management of left ventricular volume overload
Authors: Dzimiri N. , Moorji A. , Afrane B. , Al‐Halees Z. 
Published: March 2003

AbstractBackground In this study, we investigated the possibility that the atrial and brain natriuretic peptide expression in left ventricular volume overload (VOL) is transcriptionally regulated. We further evaluated the diagnostic and/or prognostic potential of this expression for the management of patients with this disorder.Design We compared the myocardial mRNA expression and plasma levels of the two peptides in VOL patients using donor hearts and in healthy blood donors as controls.Results The atrial natriuretic peptide (ANP) mRNA was elevated by 38% (P < 0·03) in the right atrium and by 53% (P < 0·003) in the left atrium, but was unchanged in the ventricular chambers of the patient group (n = 19) compared with controls (n = 8). Plasma ANP concentration was elevated by 62% (P < 0·001) compared with blood donor controls (n = 79). It increased slightly (by 36%) 2 h following surgery, and remained at 64% higher (P < 0·03 vs. presurgery) for the 5 days following surgery. The brain natriuretic peptide (BNP) mRNA was elevated by approximately one‐fold in both the left ventricle (P < 0·02) and right atrium (P < 0·05), by 94% (P < 0·02) in the right ventricle and by 89% (P < 0·05) in the left atrium. Its plasma level in the patients was 3·4‐fold (P < 0·00003) higher than in control subjects. It increased significantly by 1·2‐fold (P < 0·01) 2 h following surgery, but dropped significantly (P < 0·05 vs. 2 h post surgery) to presurgical levels 5 days following surgery.Conclusion The results show chamber‐specific elevation in both atrial and brain natriuretic peptide expression and differences in their circulating levels in VOL, suggesting that BNP is a potential prognostic indicator in the postsurgical management of these patients.
Prediction of body weight changes caused by changes in energy balance
Authors: Christiansen E. , Garby L. 
Published: March 2003

AbstractBackground Experimental difficulties have so far restricted knowledge of the effects of energy imbalance on change in body weight. Direct measurement requires that the subjects are kept under dietary supervision for several months while the activity is being measured.Materials and methods The effects of energy balance can be calculated using a combination of fundamental principles and directly measurable data: the law of energy conservation (increase in combustible energy equals the difference between energy intake and energy expenditure); data on energy expenditure of fat and lean tissues; and data on the composition of added/removed tissue during weight change.Results and Conclusions We obtained an explicit differential equation describing the development of body weight over time, with energy intake and energy expenditure as control variables. Using this model it is possible to isolate and analyse the measured effects of parameters not included in the model, such as age or ‘adaptivity’ of the body.
Inhaled nitric oxide: more than a selective pulmonary vasodilator
Authors: Gianetti J. , Bevilacqua S. , De Caterina R. 
Published: March 2003

AbstractBecause of its high diffusing capacity through the alveolar–blood barrier and its high selectivity for the pulmonary vasculature, inhaled nitric oxide (NO) has been recently shown to be a viable and efficient approach to restore pulmonary NO deficiency.The most relevant applications of inhaled NO are in infants with primary pulmonary hypertension or hypoxia. In these patients, inhaled NO improves gas exchange and ventilation‐perfusion matching, reduces the length of hospitalization and is without severe detrimental effects. The use of inhaled NO has also been extended to adults with pulmonary hypertension and the acute respiratory distress syndrome. In addition, recent clinical evidence supported by data from animal models, shows beneficial extra‐pulmonary effects of inhaled NO, including protection against myocardial ischaemia‐reperfusion injury.
High oxidized LDL and elevated plasma homocysteine contribute to the early reduction of myocardial flow reserve in healthy adults
Authors: Laaksonen R. , Janatuinen T. , Vesalainen R. , Lehtimäki T. , Elovaara I. , Jaakkola O. , Jokela H. , Laakso J. , Nuutila P. , Punnonen K. , Raitakari O. , Saikku P. , Salminen K. , Knuuti J. 
Published: March 2003

AbstractBackground Impairment of coronary blood flow reserve has been shown to be an early manifestation of atherosclerosis and coronary artery disease (CAD). We studied more closely the contribution of various risk factors on early deterioration of coronary function.Materials and methods Fifty‐one young, apparently healthy adults, with normal or mildly elevated serum cholesterol levels but without other major risk factors for CAD, such as diabetes or hypertension, underwent positron emission tomography (PET) studies. Coronary flow reserve (CFR) was measured using O15‐water. In addition to the classical risk factors, the role of several new risk indicators, such as low‐density lipoprotein (LDL) oxidation, infection (Chlamydia pneumoniae antibodies), and inflammation parameters (adhesion molecules, ICAM, VCAM, selectin, and C‐reactive protein), homocysteine and body iron stores were investigated.Results Elevated lipid and lipoprotein levels were not associated with reduced coronary reactivity. However, high autoantibody titers against oxidized LDL (oxLDL) were associated with 21% lower CFR than low oxLDL (P < 0·05). Furthermore, high homocysteine levels predicted low CFR (P < 0·05). The other measured parameters, Chlamydia pneumoniae antibody levels, C‐reactive protein and adhesion molecule concentrations did not associate with myocardial blood flow. In a stepwise regression model, oxLDL (P = 0·03), homocysteine (P = 0·04) and triglycerides (P = 0·018) were significant predictors of CFR.Conclusions The present study suggests an important role for oxidized LDL and plasma homocysteine on early impairment of coronary reactivity in young adults.
Pneumococcal immune adherence to human erythrocytes
Authors: Hament J.‐M. , Van Dijk H. , Fleer A. , Aerts P. C. , Schoenmakers M. , De Snoo M. W. , Th. Dekker B. H. A. , Kimpen J. L. L. , Wolfs T. F. W. 
Published: March 2003

AbstractBackground Human red blood cells bind various C3b‐coated microorganisms via their C3b/CR1 receptor, a phenomenon referred to as immune adherence. The aim of the present study was to measure pneumococcal adherence to human red blood cells by flow cytometry and to study kinetic aspects of this binding.Material and methods We quantified pneumococcal adherence to human erythrocytes by FACS analysis and tested the involvement of antibodies and complement activation in this process.Results Pneumococci are able to bind to human red blood cells in the presence of human serum. Coating with C3b/C4b appeared obligatory for pneumococcal adherence to red blood cells. The ligand on erythrocytes was confirmed to be complement receptor 1. Kinetic studies showed that innate (mannose‐binding lectin) and specific immune factors (IgG antibodies) contributed to the binding of C3b‐coated pneumococci to human erythrocytes. After initial binding, serum‐derived factor I was found to induce bacterial detachment from the erythrocyte.Conclusions Pneumococci are able to adhere to red blood cells. Both the classical and lectin complement pathways are important for optimal C3b‐coating of pneumococci for immune adherence. Bound pneumococci are detached from red blood cells by factor I. These findings are in line with the hypothesis of immune adherence in which human erythrocytes are able to bind pneumococci and target the bacteria to the reticulo‐endothelial system in the spleen.
Iron, hepatic stellate cells and fibrosis in chronic hepatitis C
Authors: Rigamonti C. , Andorno S. , Maduli E. , Morelli S. , Pittau S. , Nicosia G. , Boldorini R. , Sartori M. 
Published: March 2003

AbstractBackground/aims  In patients with chronic hepatitis C, hepatic iron concentration correlates with liver fibrosis. However, it is not clear whether this correlation merely reflects the presence of more active disease, or iron exacerbates chronic hepatitis C virus (HCV)‐induced damage through activation of hepatic stellate cells and regeneration of hepatocytes.Materials and methods  We studied 72 HCV‐positive patients, staged according to the Ishak’s score system. We measured hepatic iron concentration with spectrophotometry and evaluated the number of hepatic stellate cells (using monoclonal antibody against alpha smooth muscle actin) and proliferating hepatocytes (using monoclonal antibody against Ki67). Iron and ferritin serum levels were also determined.Results  Hepatic iron concentration correlated statistically with ferritin serum level (r = 0·59, P < 0·001), with grading (r = 0·47, P < 0·001) and staging (r = 0·51, P < 0·001) scores for chronic hepatitis in the whole group of patients. Hepatic iron concentration correlated positively with stellate cell number (r = 0·55, P = 0·004) and Ki67‐positive hepatocyte number (r = 0·36, P = 0·08) in patients with chronic hepatitis C and low grading score (< 3).Conclusions In patients with chronic hepatitis C and low grading score, hepatic iron could play a role in the activation of hepatic stellate cells and in the progression of fibrosis.
Iron and immunity: a double‐edged sword
Authors: Weiss G. 
Published: March 2003

AbstractIron is a crucial element for many central metabolic pathways of the body. Lack of iron leads to growth arrest and anaemia while increased accumulation of this metal, as it occurs in highly frequent inherited diseases such as hereditary haemochromatosis and thalassaemia, is associated with toxic radical formation and progressive tissue damage. As shown by several groups, iron also modulates immune effector mechanisms, such as cytokine activities (IFN‐γ effector pathways towards macrophages), nitric oxide (NO) formation or immune cell proliferation, and thus host immune surveillance. Therefore, gaining control over iron homeostasis is one of the central battlefields in deciding the fate of an infection with intracellular pathogens or a malignant disease. Thus, the reticulo‐endothelial system has evoked sophisticated strategies to control iron metabolism in general and especially the handling of the metal within immune cells.
Impact of genetic defects on coronary atherosclerosis in patients suspected of having familial hypercholesterolaemia
Authors: Descamps O. S. , Gilbeau J.‐P. , Luwaert R. , Heller F. R. 
Published: March 2003

AbstractBackground In the present study we assessed whether the presence of genetic mutations typical of familial hypercholesterolaemia (FH) was associated with greater atherosclerosis in the coronary vessels in patients with severe hypercholesterolaemia and a family history of early cardiovascular disease.Materials and methods Two hundred and thirty‐five patients selected for having severe hypercholesterolaemia and a family history of cardiovascular disease were classified as FH (57 men and 38 women) or non‐FH (84 men and 56 women) according to a genetic analysis of the LDL‐R or ApoB genes. Coronary atherosclerosis was evaluated by performing a thoracic CT scan and exercise stress testing.Results Familial hypercholesterolaemia individuals had a significantly higher prevalence of coronary calcification than the non‐FH patients from among both the men (OR = 3·90; 95% CI 1·86–8·19; P < 0·001) and the women (OR = 2·34; 95% CI 1·01–5·48; P = 0·05). In exercise stress testing, ECG abnormalities suggestive of cardiac ischaemia were found with a higher prevalence in the FH patients than the non‐FH patients from among both the men (OR 6·15; 95% CI 2·16–17·5; P < 0·001) and the women (OR 4·76; 95% CI 0·91–24·6; P = 0·06). All differences were statistically significant after adjusting for age and cholesterol and for most classical risk factors that differed between the FH and non‐FH groups.Conclusion Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher prevalence of coronary artery calcifications and a positive exercise stress test. These results suggest that despite a similar phenotype, patients carrying mutations suggestive of FH may have a greater cardiovascular risk than patients without these mutations.
Dose‐effect relations of loop‐ and thiazide‐diuretics on calcium homeostasis: a randomized, double‐blinded Latin‐square multiple cross‐over study in postmenopausal osteopenic women
Authors: Rejnmark L. , Vestergaard P. , Pedersen A. R. , Heickendorff L. , Andreasen F. , Mosekilde L. 
Published: March 2003

AbstractBackground Thiazide diuretics (TDs) reduce whereas loop diuretics (LDs) increase urinary calcium. We studied the effects of different doses of a TD and LD on electrolytes, calcitropic hormones and biochemical bone markers.Subjects and methods In a five‐period crossover study, comparing four active doses with placebo, 40 postmenopausal women with osteopenia were treated with different doses of LD bumetanide (n = 20, 0·5–2·0 mg per day) or TD bendroflumethiazide (n = 20, 2·5–10 mg per day). Each treatment period lasted 1 week.Results Urinary calcium decreased dose‐dependently in response to the bendroflumethiazide. The best hypocalciuric effect was achieved by 5 mg day−1 of bendroflumethiazide. Total plasma calcium levels increased, whereas ionised calcium at ambient pH‐values decreased because of increased pH‐values in response to the bendroflumethiazide. Plasma PTH levels did not change, whereas a slight dose‐dependent increase occurred in plasma 1,25(OH)2D levels. As a marker of bone formation, plasma osteocalcin levels increased. Conversely, bumetanide dose‐dependently increased renal calcium losses with a concomitant increase in plasma PTH and 1,25(OH)2D levels. Plasma osteocalcin levels increased and bone‐specific alkaline phosphatase levels decreased dose‐dependently.Conclusion Whether a LD or TD is chosen as diuretic therapy affects calcium homeostasis. The effects of LDs are potentially harmful to bone. Further studies are needed to evaluate whether long‐term treatment with LDs causes osteoporosis. Until then, we suggest using, if possible, a TD rather than a LD as diuretic therapy in order not to risk deleterious effects on bone metabolism.