Search PubMed⌕ Search

Biomedical subjects

C Haug

Publications and source records attributed to C Haug.

At least 19 recordsLinked to original sources
PubMed1999

Depending on their concentration oxidized low density lipoproteins stimulate extracellular matrix synthesis or induce apoptosis in human coronary artery smooth muscle cells.

Various lines of evidence indicate that oxidative stress resulting in lipid peroxidation and protein modification is involved in the pathogenesis of atherosclerosis and coronary heart disease. We have investigated the effect of modified (oxidized) low-density lipoproteins (oxLDL) on collagen and fibronectin synthesis in cultured human coronary artery smooth muscle cells (HCA-SMC). As shown by immunofluorescence microscopy and time-resolved fluorescence immunoassay, oxLDL dose-dependently stimulated collagen type I and fibronectin synthesis in cultured HCA-SMC. The effect on matrix synthesis was biphasic, with a maximum effect at concentrations between 1 and 10 microg/ml oxLDL. Higher oxLDL concentrations (>25 microg/ml) were cytotoxic. Beside oxLDL, malondialdehyde-modified LDL also stimulated extracellular matrix synthesis. In the presence of 100 microg/ml ascorbic acid, 25, 50 and 100 microg/ml oxLDL induced apoptosis within 6-8 hours (demonstrated by TUNEL-reaction, annexin-V binding and APO-2.7-expression). Apoptosis was not induced by normal (unmodified) LDL and malondialdehyde-modified LDL. The radical scavengers and antioxidants TROLOX and probucol and the hydrogen peroxide eliminator catalase significantly reduced oxLDL-induced apoptosis. Our results demonstrate that low concentrations of oxLDL are profibrogenic by stimulating extracellular matrix synthesis, whereas higher oxLDL concentrations induce oxidative stress and apoptosis in coronary artery smooth muscle cells. The profibrogenic effect might be relevant in the formation of atherosclerotic plaques, and the proapoptotic effect might contribute to an increased plaque vulnerability.

Apoptosis↗
PubMed1998

Gallstone prevalence in Germany: the Ulm Gallbladder Stone Study.

The Ulm Gallbladder Stone Study is the first ultrasound-based epidemiologic survey of cholecystolithiasis in the former West Germany. A study population of 1116 blood donors (656 men, age 38.0 +/- 12.0 years; 460 women, age 34.1 +/- 11.2 years) at the Central Blood Bank of the German Red Cross in Ulm was examined between April 1994 and February 1995. Based on age, subjects were assigned to one of four groups (18-30, 31-40, 41-50, and 51-65 years). Following a structured interview of each study subject, an ultrasound examination was carried out and a blood sample obtained for laboratory study. Overall, 6.0% (95% (95% CI: 4.8%-7.6%) of all study subjects (5.8% of the men and 6.3% of the women) exhibited evidence of current or past gallbladder disease (cholelithiasis or history of cholecystectomy). The prevalence of gallbladder disease correlated positively with age, reaching a maximum of 13.7% (9.5-20.0) in the 51- to 65-year-old age group, and also correlated as with body mass index (BMI). Female subjects with previous full-term pregnancies showed a higher prevalence of cholelithiasis, but this difference was not statistically significant for age-adjusted analysis. Subjects with a family history of cholelithiasis were found to suffer from gallstones in 11.5% (8.0-16.7) of cases compared with 4.6% (3.4%-6.3%) of subjects without such family history. Autopsy studies conducted in Germany have shown the prevalence of gallstones to be about 13.1% in men and 33.8% in women. Our sonographic data are relatively low in comparison. This may be due, in part, to the specific selection characteristics inherent in retrospective autopsy studies, such as age distribution and the presence of other pathologic factors associated with increased risk for cholelithiasis. The Ulm data rank in the lower third of the prevalence range reported for European sonographic studies to date. Age, positive family history, and increased BMI all correlated positively with the prevalence of gallbladder disease (P < 0.05). For the study population as a whole, there was no gender-specific increased risk for the development of gallstones.

Adult↗
PubMed1998

Endothelin release by rabbit proximal tubule cells: modulatory effects of cyclosporine A, tacrolimus, HGF and EGF.

BACKGROUND: Previous studies have suggested that endothelins, a family of 21 amino acid peptides with potent vasoconstrictive and mitogenic properties, are involved in the pathogenesis of acute and chronic renal failure. In addition, endothelin seems to play an important role in mediating the nephrotoxic side effects of cyclosporine A (CsA) and tacrolimus. The present study investigated the production of endothelin-1 (ET-1) and endothelin-3 (ET-3) by bipolar differentiated rabbit proximal tubule cells (PT-1 cells), and the modulatory effect of CsA, tacrolimus, hepatocyte growth factor (HGF) and epidermal growth factor (EGF) on ET-1 and ET-3 release. METHODS: ET-1 and ET-3 mRNA was detected by RT-PCR, immunoreactive endothelin was localized to PT-1 cells by immunofluorescence staining with antibodies against ET-1 and ET-3. ET-1 and ET-3 release into the culture medium was determined by specific radioimmunoassays after solid phase extraction. RESULTS: PT-1 cells exhibited a time-dependent increase of ET-1 release up to an incubation period of 36 hours, whereas ET-3 release already reached a steady state level after four hours. PT-1 cells, cultured on filter membranes, released a significantly higher amount of immunoreactive ET-1 into the basolateral compartment than into the apical compartment. ET-3 release did not differ significantly between the basolateral and the apical compartment. Supplementation of the cell culture medium with 10% fetal calf serum induced a marked increase of the basolateral and apical ET-1 release, whereas ET-3 release was only slightly increased. CsA and tacrolimus (0.5 to 5000 microgram/liter) induced a significant, dose-dependent increase of ET-1 and ET-3 release by PT-1 cells with a maximum stimulation at a CsA concentration of 500 microgram/liter (P < 0.001) and a tacrolimus concentration of 50 microgram/liter (P < 0.001). HGF and EGF (10-10 to 10-8 mol/liter) exerted a significant (P < 0.001) dose-dependent inhibitory effect on ET-1 release, whereas ET-3 release was not significantly reduced. Coincubation of PT-1 cells with CsA or tacrolimus and HGF or EGF also resulted in a marked reduction of ET-1 release. CONCLUSIONS: The present data suggest that ET-1 and ET-3 release by cultured rabbit proximal tubule cells are regulated differently, and that the stimulatory effect of CsA and tacrolimus on ET-1 release is antagonized by HGF and EGF.

Animals↗
PubMed1998

Effect of diltiazem and verapamil on endothelin release by cultured human coronary smooth-muscle cells and endothelial cells.

Recent data suggest that endothelin (ET) production is enhanced in coronary atherosclerotic lesions. In several studies, an anti-atherosclerotic effect has been attributed to calcium-channel antagonists. This study aimed to investigate whether ET release from cultured human coronary artery smooth muscle and endothelial cells is influenced by the calcium-channel antagonists diltiazem and verapamil. Coronary plaque smooth-muscle cells (SMCs) were isolated from primary stenosis plaque material. Normal coronary smooth muscle and endothelial cells were obtained from organ donors. Addition of diltiazem (5, 15, 25, 50, or 100 micrograms/ml) and verapamil (0.25, 2.5, 25, 50, or 75 micrograms/ml) to the culture medium induced in all three cell types a dose-dependent reduction in ET secretion (coronary plaque SMCs: diltiazem 98.1 +/- 1.5, 94.9 +/- 5.0, 82.0 +/- 6.4**, 63.3 +/- 3.7***, 38.9 +/- 2.4***; control 108.4 +/- 2.8; verapamil 97.0 +/- 7.7, 91.9 +/- 5.5, 67.3 +/- 4.5**, 30.6 +/- 3.0***, 27.6 +/- 2.2***; control 103.4 +/- 6.1 pg/10(4) cells, n = 6; normal coronary SMCs: diltiazem 9.6 +/- 0.7, 8.7 +/- 0.6, 5.4 +/- 0.5***; 3.7 +/- 0.5***, 3.2 +/- 0.4***; control 10.7 +/- 0.5; verapamil 10.3 +/- 0.9, 10.0 +/- 0.7, 6.6 +/- 0.5***, 4.0 +/- 0.3***, 3.0 +/- 0.3***; control 11.1 +/- 0.6 pg/10(4) cells, n = 6; means +/- SEM, **p < 0.01, ***p < 0.001 vs. control). These data suggest that ET release from cultured coronary smooth muscle and endothelial cells is decreased by diltiazem and verapamil. In further studies, it remains to be elucidated whether the local application of diltiazem or verapamil might have a beneficial effect on the progression of coronary atherosclerosis.

Aged↗
PubMed1998

Direct enzyme immunometric measurement of plasma big endothelin-I concentrations and correlation with indicators of left ventricular function.

Recent studies have suggested that the plasma concentrations of endothelin-1, a potent vasoconstrictive peptide, are increased in patients with congestive heart failure. This study aimed to evaluate a new direct ELISA for big endothelin-1 (the precursor of endothelin-1), in comparison with a big endothelin-1 ELISA using plasma sample extraction, and to investigate whether plasma big endothelin-1 concentrations correlate with indicators of left ventricular function. The direct ELISA yielded significantly (P < 0.001) lower results than the assay with extracted samples (0.9 +/- 0.5 pmol/L vs 2.7 +/- 1.9 pmol/L; n = 90); however, the results of the two assays were closely correlated (r = 0.86, P < 0.001). Plasma big endothelin-1 concentrations exhibited a significant (P < 0.001) negative correlation (r = -0.46, r = -0.40) with the left ventricular ejection fraction and a significant positive correlation (r = 0.40, P < 0.001; r = 0.36, P < 0.01) with the left ventricular end-diastolic pressure and the left ventricular end-diastolic (r = 0.42, r = 0.38, P < 0.001) and end-systolic (r = 0.52, r = 0.47, P < 0.001) volume indices. Plasma big endothelin-1 concentrations were notably greater in patients with New York Heart Association (NYHA) class II-IV symptoms than in patients without cardiac disease or in patients categorized to NYHA class I. These data suggest that plasma big endothelin-1 concentrations, measured by a direct ELISA, correlate with hemodynamic indicators and symptoms of left ventricular dysfunction.

Adult↗
PubMed1996

Increased endothelin release by cultured human smooth muscle cells from atherosclerotic coronary arteries.

OBJECTIVES: Endothelin, a 21-amino acid peptide initially purified from the medium of cultured endothelial cells, is a potent vasoconstrictor exerting its effects predominantly in a paracrine or autocrine manner. Recent data indicate that endothelin is also synthesized by cultured vascular smooth muscle cells and that endothelin is an effective stimulator of smooth muscle cell proliferation. This study aimed to investigate the endothelin release of cultured human smooth muscle cells, isolated from coronary plaques and from normal coronary tunica media, and to determine circulating endothelin concentrations in patients with coronary artery disease compared to control subjects. METHODS: Coronary plaque material was extracted by thrombendarterectomy during aorto-coronary bypass grafting (n = 19). Segments of normal coronary arteries were obtained at autopsy (n = 33). Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells with antibodies against smooth muscle alpha-actin. Venous blood samples were drawn from patients with coronary artery disease undergoing cardiac catheterization (n = 32) and from control subjects (n = 38). Endothelin concentrations in culture medium and in plasma samples were measured by radioimmunoassay after Sep Pak C18 extraction. RESULTS: Cultured smooth muscle cells, isolated from coronary plaques, released a significantly (P < 0.001) higher amount of immunoreactive endothelin into the culture medium (39.2 +/- 3.9 pg/10(4) cells, mean +/- s.e.m., 31 supernatant samples) than smooth muscle cells from normal coronary tunica media (3.9 +/- 0.8 pg/10(4) cells, 28 samples). Circulating endothelin concentrations were slightly elevated (P < 0.01) in patients with coronary artery disease (3.8 +/- 0.2 pg/ml) compared to control subjects (3.0 +/- 0.2 pg/ml). CONCLUSIONS: These data suggest that the endothelin production is markedly increased in smooth muscle cells of coronary atherosclerotic plaques. The enhanced endothelin release may stimulate smooth muscle cell proliferation in a paracrine or autocrine manner and thus may contribute to the development or progression of coronary artery disease.

Cells, Cultured↗
PubMed1996

Insulin-like growth factors and their binding proteins before and after weight loss and their associations with hormonal and metabolic parameters in obese adolescent girls.

OBJECTIVE: To investigate serum concentrations of insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) in obese adolescent girls before and after weight reduction and to examine their associations with hormonal and metabolic parameters. PATIENTS AND METHODS: 73 girls (age: 15.0 +/- 1.1 y, BMI: 31.1 +/- 3.8 kg/m2) participated in this 6 w intervention study. RESULTS: (1) Compared to 100 normal-weight girls of same age the obese subjects had increased levels of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 and normal levels of IGF-II. (2) After weight loss (8.1 +/- 2.0 kg) IGF-II and IGFBP-2 increased and IGF-I, IGFBP-1, IGFBP-3 and the ratio IGF-I/IGFBP-3 decreased significantly. (3) Correlation analysis revealed that fasting insulin levels of the patients were positively correlated with IGF-I but inversely with IGFBP-1 and IGFBP-2. IGFBP-2 was associated with several metabolic parameters: it showed an inverse correlation with uric acid and triglyceride levels. The ratio IGFBP-2 to IGFBP-1 was inversely correlated with total cholesterol and LDL-cholesterol. In addition, IGFBP-2 was inversely correlated with the waist-to-hip ratio of the girls. CONCLUSIONS: These studies of a homogeneous group of patients give further insight into possible physiological regulations and roles of IGFs and IGFBPs. The main conclusion is that obesity has to be considered for interpretation of serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3. Furthermore, out results suggest that (i) the decrease in IGF-I/IGFBP-3 after weight loss could be partly responsible for the impaired growth velocity seen in obese children during hypocaloric feeding and (ii) low IGFBP-2 and high IGFBP-1 levels are associated with an unfavorable atherogenic risk factor profile.

Adolescent↗
PubMed1995

Elevated plasma endothelin concentrations in cyclosporine-treated patients after bone marrow transplantation.

Administration of cyclosporine is often associated with the development of renal dysfunction and hypertension. Since recent data from animal experiments provide evidence that endothelin, a potent vasoconstrictive peptide, might play a role in mediating cyclosporine-related renal and cardiovascular side-effects, the present study was designed to investigate whether plasma endothelin concentrations are elevated in cyclosporine-treated patients. Plasma endothelin concentrations, determined by radioimmunoassay after Sep Pak C18 extraction, were significantly elevated in cyclosporine-treated patients after bone marrow transplantation (8.3 +/- 1.4 ng/l, n = 28) compared to patients not treated with cyclosporine after bone marrow transplantation (3.9 +/- 0.2* ng/l, n - 11), patients with haematological disorders (3.9 +/- 0.3** ng/l, n = 11) not treated with bone marrow transplantation and to normal control subjects (3.1 +/- 0.2*** ng/l, n = 33) (*P < 0.05, **P < 0.01, ***P < 0.001). Furthermore, plasma endothelin levels exhibited a significant correlation with cyclosporine concentrations (r = 0.57, P < 0.01). The present data, demonstrating elevated plasma endothelin concentrations in cyclosporine-treated patients, suggest that the cyclosporine-associated renal and cardiovascular side-effects might in part be mediated by cyclosporine-induced stimulation of endothelin release.

Adult↗
PubMed1995

Cyclosporine A stimulates endothelin release.

Administration of cyclosporine A is often associated with the development of renal dysfunction and hypertension. Because recent data provide evidence that endothelin (ET) might be involved in mediating cyclosporine-associated cardiovascular and renal side effects, the present study aimed to investigate the influence of cyclosporine A on ET release from cultured smooth-muscle cells and whether ET plasma concentrations are elevated in cyclosporine-treated patients. Addition of cyclosporine A to the medium of cultured human smooth-muscle cells, isolated from atherosclerotic iliac arteries, induced a dose-dependent increase in ET release. ET plasma levels were significantly elevated in cyclosporine-treated patients after bone marrow transplantation, compared to control groups. These data suggest that enhanced ET release might be involved in mediating the cyclosporine-associated side effects.

Cells, Cultured↗
PubMed1994

Release of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist after intravenous immunoglobulin administration in vivo.

We investigated the in vivo effects of one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) on a number of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist (IL-1Ra) in plasma in 12 patients with primary hypogammaglobulinemia. A significant and rapid increase in plasma levels of IL-6, IL-8, and tumor necrosis factor alpha (TNF alpha) was seen within 1 hour after IVIG infusion. This increase was accompanied by a more prolonged elevation in levels of both types of soluble TNF receptors (sTNFRs), which remained elevated throughout the study period (44 hours) although they reached peak levels within 1 hour. After an initial increase in the ratio between TNF alpha and sTNFRs, this ratio decreased to values significantly lower than baseline values 20 and 44 hours postinfusion with approximately 600-fold molar excess of sTNFRs to TNF alpha (trimer). Although only a modest but statistically significant increase in plasma levels of IL-1 beta was seen, IVIG infusion was followed by a marked increase in plasma levels of IL-1Ra with 1,000-fold molar excess of IL-1Ra to IL-1 beta in some patients. The demonstrated effects of IVIG infusion on the cytokine network, particularly the induction of IL-1Ra and sTNFRs release, might be important for the therapeutic effects of IVIG in several immune-mediated disorders.

Adult↗
PubMed1994

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure.

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8 pg/ml; ANP: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 +/- 1.8%, ANP 40.2 +/- 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 +/- 1.0 and 60.3 +/- 4.0 pg/ml in patients with normal LVEDP and 31.7 +/- 3.6 and 118.3 +/- 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001) or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Changes in brain natriuretic peptide and atrial natriuretic peptide plasma concentrations during hemodialysis in patients with chronic renal failure.

The present study aimed to investigate whether brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), cortisol and thyroid hormone concentrations change during hemodialysis in patients with chronic renal failure. Blood samples were withdrawn in 30 patients with chronic renal failure before hemodialysis, 2 hours after the beginning and at the end of hemodialysis. ANP and BNP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. Cortisol, T3, T4, FT4 and TSH serum concentrations were measured by enzyme immunoassay. BNP and ANP plasma levels were strongly elevated in patients with renal failure (BNP 22.4 fold, ANP 4.7 fold versus controls [n = 20]) and decreased significantly (p < 0.001) during hemodialysis (BNP [pg/ml]: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8; ANP [pg/ml]: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5). BNP plasma concentrations showed a stronger elevation than ANP plasma levels and a less pronounced decrease during hemodialysis (BNP: 13.5 +/- 1.8%, ANP: 40.2 +/- 3.5%, p < 0.001) which might in part be due to the longer half-life of BNP. Cortisol and TSH levels did not change significantly whereas T3, T4 and FT4 levels increased significantly (p < 0.001) during hemodialysis. Since corticosteroids and thyroid hormones stimulate natriuretic peptide release, these data suggest that the dialysis-induced decrease of ANP and BNP plasma concentrations is not augmented by a loss of cortisol or thyroid hormones during hemodialysis. The present data provide support that BNP and ANP plasma concentrations are sensitive indicators of the extracellular fluid volume status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗