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Biomedical subjects

M Christ

Publications and source records attributed to M Christ.

At least 19 recordsLinked to original sources
PubMed2006

Tumour necrosis factor-related apoptosis-inducing ligand and osteoprotegerin serum levels in psoriatic arthritis.

OBJECTIVES: The degree of bone loss in patients with psoriatic arthritis (PsA) has not been well-defined. We tested the hypothesis, whether serum levels of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), a pro-apoptotic cytokine and osteoprotegerin (OPG), an anti-osteoclastic cytokine, are associated with changes in biochemical markers of bone turnover or bone mineral density (BMD) in patients with PsA. METHODS: In a cross-sectional study, we evaluated biochemical markers of bone turnover, BMD and serum levels of TRAIL and OPG in 116 patients with PsA (mean age: 52+/-13 yrs). RESULTS: In patients with PsA, osteopenia was present in one-third of women and men, while osteoporosis was more frequent in men (10.2%) than in women (1.75%). Serum levels of TRAIL were significantly higher in patients with PsA (66.1+/-45.3 pmol/l) compared with controls (50.0+/-20.1 pmol/l, P<0.01), whereas OPG serum levels were not different. There were no associations between TRAIL or OPG serum levels with BMD and biochemical markers of bone turnover. However, TRAIL serum levels were associated with C-reactive protein (CRP) levels (R = 0.201, P<0.05), whereas OPG serum levels were associated with the erythrocyte sedimentation rate (R=0.215, P<0.05). CONCLUSION: In summary, BMD is decreased in one-third of patients with PsA, and predominantly men with PsA suffer from osteoporosis. While TRAIL serum levels are increased in PsA and correlated with CRP levels, neither TRAIL nor OPG serum levels are correlated with BMD or markers of bone metabolism.

Absorptiometry, Photon↗
PubMed2006

Right bundle branch block and long-term mortality in patients with acute congestive heart failure.

OBJECTIVES: Risk stratification in acute congestive heart failure (ACHF) is poorly defined. The aim of the present study was to assess the impact of right bundle brunch block (RBBB) on long-term mortality in patients presenting with ACHF. METHODS AND RESULTS: The initial 12-lead electrocardiogram was analysed for RBBB in 192 consecutive patients presenting with ACHF to the emergency department. The primary endpoint was all-cause mortality during 720-day follow-up. This study included an elderly cohort (mean age 74 years) of ACHF patients. RBBB was present in 27 patients (14%). Age, sex, B-type natriuretic peptide levels and initial management were similar in patients with RBBB when compared with patients without RBBB. However, patients with RBBB more often had pulmonary comorbidity. A total of 84 patients died during follow-up. Kaplan-Meier analysis revealed that mortality at 720 days was significantly higher in patients with RBBB when compared with patients without RBBB (63% vs. 39%, P = 0.004). In Cox proportional hazard analysis, RBBB was associated with a two-fold increase in mortality (hazard ratio 2.18, 95% CI 1.26-3.66; P = 0.003). This association persisted after adjustment for age and comorbidity. CONCLUSIONS: RBBB is a powerful predictor of mortality in patients with ACHF. Early identification of this high-risk group may help to offer tailored treatment in order to improve outcome.

Aged↗
PubMed2004

Autoimmunity, environmental exposure and vaccination: is there a link?

Although the wide clinical experience shows that vaccines are generally safe, concern has been expressed for a causal link between vaccines and autoimmune diseases. Even though the mechanisms of autoimmunity are ill-elucidated, the role of pre-existing risk factors including genetic predisposition and environmental factors is largely accepted. The present study was undertaken to test the hypothesis that vaccines can promote autoimmunity in genetically-prone individuals when simultaneously exposed to a chemical known to induce autoimmune reactions. Female lupus-prone (NZB x NZW) F(1) mice were given 1 microg or 10 microg of a hepatitis B vaccine at 2-week intervals in conjunction with 40 microg of mercuric chloride three times per week for 6 weeks. A marked increase in serum IgG levels and a slight increase in anti-nuclear autoantibody (ANA) levels were seen in the mice given 10 microg of the vaccine plus mercuric chloride. No straightforward conclusion can be drawn from these results because of the extreme experimental conditions of this study. Nevertheless, the results tend to support the hypothesis that vaccination could enhance the risk of autoimmunity in genetically susceptible individuals when exposed to certain environmental chemicals.

Animals↗
PubMed2004

[Premedication visits. Economizing at the cost of the patient?].

The older the patient, the higher the risk of perioperative cardiac complications. Therefore, patients at risk have to be identified and the appropriate diagnostic or therapeutic measures initiated. The most important factor in this context is whether a planned surgery can be postponed. Several strategies have been developed (e.g. Goldman index, Eagle criteria) and the American Heart Association (AHA/ACC) has produced guidelines concerning perioperative diagnosis and therapy of cardiac risk patients. The common goal of these strategies is always the risk classification of the patient by combining the operative risk and the risk factors of the patient. The further procedure (diagnostic or therapeutic measures) is based on the risk classification. If further invasive therapy proves to be necessary, the determining factor is the period of time for which the operation can be delayed. This appears to be about 3 months but if this is not possible the outcome could be improved with a beta-blocker therapy in advance. A working group from the university hospital in Marburg has developed a strategy for risk classification and further diagnostic and therapeutic measures as outlined in this article.

Adrenergic beta-Antagonists↗
PubMed2004

[Marburg model for optimization of stratification of the anaesthesiological risk].

The perioperative risk is mostly determined by the patient's cardiological condition and the type of surgical intervention. Therefore it is very important during the premedication visit to identify patients with cardiac risk factors. We suggest that patients be classified into three risk classes according to the ACC/AHA recommendations in advance of the preanaesthetic visit. The majority of patients with a low or medium anaesthesiological risk profile could be identified by simple asking, e.g. whether they are able to exercise physically for 20 min or to climb two staircases without resting. For the lowest risk no further evaluation is necessary. For the medium risk class an additional preoperative diagnosis or for the higher risk class a cardiological consultation or even postoperative intensive care monitoring could be necessary. The aim of such a system is to always minimise the rate of perioperative complications and delays in scheduled surgery.

Anesthesia↗
PubMed2004

[Significance of aldosterone antagonist therapy].

Since the introduction of ACE-inhibitors into clinical practice, the diuretic treatment with the classical aldosterone antagonist spironolactone has disappeared. It was generally believed that chronic treatment with ACE-inhibitors significantly reduces aldosterone secretion via reduction of angiotensin II-dependent aldosterone formation. However, aldosterone "escape" occurs: Even during chronic treatment with ACE-inhibitors, plasma levels of aldosterone rise again, which is associated with increased cardiovascular risk. Furthermore, extrarenal actions of aldosterone have been demonstrated, which detrimentally affect coagulation, autonomic activity, inflammatory signalling, hemodynamics, and fibrosis, subsequently leading to cardiovascular damage. Recently published studies (RALES, EPHESUS) convincingly support the concept of detrimental cardiovascular aldosterone actions even during chronic ACE-inhibition. In addition to those cardiovascular effects, aldosterone antagonism has beneficial impacts on ascites, chronic renal disease, renal volume regulation, and hypokalemia induced by diuretics. Of note, aldosterone dependent mechanisms are believed to be even involved in essential hypertension, and the value of aldosterone antagonism is currently tested in those patients. In conclusion, an old-fashioned, previously abandoned treatment strategy is currently celebrating its revival.

Aldosterone↗
PubMed2004

[Extracardiac causes of right ventricular insufficiency].

Evidence for manifest right ventricular dysfunction is considered a critical threshold in the development of a fatal event after acute pulmonary embolism. While the acute event impressively reflects the clinical significance of right ventricular function, various disorders such as idiopathic pulmonary arterial hypertension, secondary pulmonary hypertension in lung diseases, carcinoid heart disease, and portopulmonary hypertension can lead to chronic right ventricular failure. Adapted treatment makes it possible to alleviate the patients' distress and presumably also improve the prognosis. The clinical picture of right ventricular insufficiency can also be imitated in constrictive or adhesive pericarditis and pericardial tamponade. Pericardiocentesis of the tamponade provides initial hemodynamic improvement. Causal treatment is based on cytological findings and/or results of epicardial or pericardial biopsy to classify malignant and nonmalignant effusions. Cardiac surgery with pericardiolysis and (partial) pericardial resection remains the method of choice for symptomatic constrictive pericarditis.

Acute Disease↗
PubMed2003

Nongenomic effects of aldosterone on human renal cells.

The development of chronic renal insufficiency may be partially mediated by the nongenomic action of aldosterone. Here we investigate whether aldosterone could evoke a nongenomic action in primary cultures of human renal cells. Intracellular Ca(2+) ([Ca(2+)](i)) and cAMP were measured in human mesangial cells (MC), glomerular visceral epithelial cells (GVEC), and proximal and distal tubular epithelial cells (Ptec and Dtec) in the presence of aldosterone (10-100 nmol/liter) by fura-2 fluorescence and RIA, respectively. In MC, Ptec, and Dtec, aldosterone increased [Ca(2+)](i) within 1 min, whereas in GVEC, only a minor effect was found. Preincubation of cells with spironolactone did not blunt this effect. Hydrocortisone, used at a concentration 100-fold higher than that of aldosterone, did not affect [Ca(2+)](i.) In MC, Ptec, and Dtec, a dose-dependent increase ( approximately 1.3- to 1.5-fold) in intracellular cAMP levels was found. These data demonstrate a nongenomic action of aldosterone in human MC, Ptec, and Dtec. As these effects occur at concentrations close to free plasma aldosterone levels in man, they may be of physiological relevance and may contribute to renal injury.

Aldosterone↗
PubMed2002

Cytochrome P450 2C expression and EDHF-mediated relaxation in porcine coronary arteries is increased by cortisol.

OBJECTIVES/METHODS: In addition to nitric oxide (NO) and prostacyclin, endothelium-dependent dilation is mediated by the endothelium-derived hyperpolarizing factor (EDHF) which, in the coronary circulation, has been characterised as a metabolite of arachidonic acid synthesised by an cytochrome P450 (CYP) epoxygenase homologous to CYP 2C8/9. As the promotor regions of CYP 2C8 and 2C9 contain consensus sequences for glucocorticoid response elements, we determined the effect of cortisol on EDHF-mediated relaxations as well as on the expression of CYP 2C in isolated segments of porcine coronary artery. RESULTS: Bradykinin-induced NO-mediated relaxation of KCl-constricted arterial rings was slightly attenuated following exposure to cortisol. However, EDHF-mediated relaxations of U46619-constricted arterial rings assessed in the presence of the cyclo-oxygenase inhibitor diclofenac and the NO synthase inhibitor N(omega)nitro-L-arginine (0.3 mM), were significantly enhanced (maximum relaxation: 66+/-7%, P<0.05 vs. control rings: 36+/-8%). Cortisol treatment (0.1 microM, 24 h) did not affect the endothelium-independent relaxation elicited by sodium nitroprusside and acute incubation with cortisol (0.1 microM, 30 min) did not alter either NO- or EDHF-mediated responses. The expression of CYP 2C (quantified by RT-PCR, Western blot analysis and confocal microscopy) was enhanced in porcine coronary endothelial cells following incubation with cortisol for 18-24 h. CONCLUSIONS: These results demonstrate the concomitant upregulation of EDHF-mediated relaxations and CYP 2C expression by long-term treatment with cortisol. These observations support the concept that an epoxygenase homologous to CYP 2C8/9 plays a crucial role in the generation of EDHF-mediated responses in the coronary endothelium.

Animals↗
PubMed2002

Effect of murine recombinant IL-2 on the course of lupus-like disease in (NZBxNZW) F1 female mice.

The exacerbation of pre-existing autoimmune diseases is a potential toxic effect of immunoactive drugs. An increase in the incidence of autoimmune thyroiditis has been noted in patients treated with human recombinant interleukin-2 (rIL-2). In contrast, human rIL-2 tends to protect mice from autoimmunity. As the effects of murine rIL-2 on autoimmunity have not been reported in mice, lupus-prone female (NZBxNZW) F1 mice were treated with 20,000 IU murine rIL-2 intraperitoneally, twice weekly for 13 weeks, beginning at 15 weeks of age. No evidence of an exacerbating effect of murine IL-2 on the lupus disease of (NZBxNZW) F1 mice was observed as no change in the following parameters were seen, namely mean survival time, mean body weight, anti-DNA and antinuclear antibody production. These results show that: 1) like human rIL-2, murine rIL-2 does not exacerbate autoimmunity in mice; 2) the biological effects of human as well as murine rIL-2 in mice differ from those seen with human rIL-2 in man. These latter findings suggest that the selection of the relevant animal species for immunotoxicity studies with recombinant cytokines and derivatives may be less straightforward than previously thought.

Animals↗
PubMed2002

Bioequivalence of subcutaneous and intravenous body-weight-independent high-dose low-molecular-weight heparin Certoparin on anti-Xa, Heptest, and tissue factor pathway inhibitor activity in volunteers.

The objective of the study was to demonstrate the bioequivalence of subcutaneously (s.c.) and intravenously (i.v.) administered fixed, high-dose low-molecular-weight heparin (LMWH) on anti-activated factor X activity (anti-FXa). Secondary objectives were the analysis of the pharmacodynamic effects on Heptest, thrombin inhibition, tissue factor pathway inhibitor (TFPI), and the urinary excretion of LMWH in the randomized cross-over study following i.v. and s.c. application of 8000 anti-FXa units LMWH Certoparin in 18 healthy subjects. The bioequivalence following s.c. administration was demonstrated from the antilog of the point estimator for the application differences (s.c. minus i.v.) by an area under the activity-time curve (0-24 h) of 101% (range, 93-110%). LMWH was bioequivalent also on Heptest and TFPI, and was 50% on thrombin inhibition. The urinary excretion of biologically active material was 4.1 and 3.6% following i.v. and s.c. administration, respectively. Differences in the pharmacodynamic parameters of the assays indicate specific biological actions of high and low molecular sacharide chains of the LMWH.

Adult↗
PubMed2002

Alterations in platelet function during the ovarian cycle.

Steroid hormones may profoundly influence hemostasis; for example, as discussed for hormone replacement therapy, pregnancy and, being less obvious, for the ovarian cycle. We investigated primary hemostasis parameters using a platelet function analyzer (PFA-100) during the follicular and luteal phases in 18 healthy young women without oral contraceptives. During the follicular phase, the mean closure time (CT) was 164.7 +/- 56.7 s, and it decreased to 130.2 +/- 30.6 s in collagen/epinephrine cartridges in the luteal phase (P = 0.0095). No significant difference could be found for CT values in collagen/adenosine diphosphate cartridges during the follicular phase as compared with the luteal phase (97.2 +/- 24.2 s versus 89.6 +/- 18.4 s, P = 0.174). Negative correlations between the CT values in collagen/epinephrine cartridges and von Willebrand factor from both phases of the cycle were found (follicular phase: r = -0.53; luteal phase: r = -0.54). Fibrinogen and fibrinogen degradation products were significantly increased in the luteal phase (2.49 +/- 0.62 g/l versus 2.05 +/- 0.59 g/l and 0.12 +/- 014 versus 0.04 +/- 0.04, P = 0.02 for both parameters) as compared with the follicular phase. No significant differences could be detected for plasminogen, plasmin-antiplasmin complex, prothrombin fragment 1 + 2 and D-dimer between the groups. This study indicates that platelet function is periodically altered during the ovarian cycle due to the influence of progesterone and estrogen on von Willebrand factor concentrations.

Adult↗
PubMed2001

Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme a reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction.

BACKGROUND: Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) attenuate angiotensin II-induced cellular signaling. Because angiotensin II is involved in left ventricular (LV) remodeling after myocardial infarction (MI), we examined the effects of statin treatment in an experimental model of chronic heart failure after MI. METHODS AND RESULTS: Rats with extensive MI were treated with placebo or cerivastatin (0.3 mg/kg per day) as a dietary supplement or via gavage for 11 weeks starting on the 7th postoperative day. Infarct size and cholesterol levels were similar among all groups. LV cavity area, an index of LV dilatation, was reduced in MI rats on cerivastatin compared with placebo. LV end-diastolic pressure was increased in MI rats on placebo (24.1+/-4.1 mm Hg versus sham: 5.1+/-0.3 mm Hg; P<0.01), and it was significantly reduced by cerivastatin treatment (13.7+/-2.7 mm Hg; P<0.05 versus placebo). Cerivastatin partially normalized LV dP/dt(max) and dP/dt(min), indices of LV systolic and diastolic function, which were significantly reduced in MI rats on placebo. Improvement of LV function by cerivastatin was accompanied by a reduced expression of collagen type I and beta-myosin heavy chain. LV endothelial nitric oxide synthase was increased, whereas the nitrotyrosine protein level was decreased in MI rats by cerivastatin treatment. CONCLUSIONS: Cerivastatin improved LV remodeling and function in rats with heart failure. This effect was associated with an attenuated LV expression of fetal myosin heavy chain isoenzymes and collagen I. Statin treatment may retard the progression of chronic heart failure.

Animals↗
PubMed2001

Hypoxia modulates rapid effects of aldosterone on oxidative metabolism in human calf muscle.

Non-genomic effects of aldosterone on oxidative metabolism of skeletal muscle have been shown, recently. To further characterize these rapid effects on the increase of phosphocreatine (PCr) in the recovery period after isometric exercise, a randomized cross-over placebo-controlled study was conducted on 9 healthy volunteers. Hypoxia was chosen to test the dependence of the effect on oxygen supply and thus its relation to oxidative vs non-oxidative metabolism. Parameters related to the energy metabolism of calf muscles were measured by 31P magnetic resonance spectroscopy during four repetitive contractions in four different tests (hypoxia [FiO2=0.13] vs normoxia [FiO2=0.21], +/- 0.5 mg aldosterone). The area-under-curves of post-exercise PCr levels after the 4th contraction were significantly increased by aldosterone vs placebo during normoxia (875.5 +/- 5.1 vs 857.2 +/- 8.3%-min; p=0.02). In addition, aldosterone induced an undershoot of inorganic phosphate (Pi) in the recovery after isometric exercise (77.5 +/- 5.4 vs 88.9 +/- 5.1 mmol/l x min; p=0.05). Hypoxia blocked effects of aldosterone on PCr overshoot and Pi undershoot. Concentrations of ATP, ADP, phosphomonoesters, and intracellular pH were not affected by those interventions. In conclusion, these data demonstrate rapid actions of aldosterone on post-excercise PCr and Pi levels in human calf muscle, which are blocked by hypoxia. We hypothesize that aldosterone rapidly interferes with oxidative metabolism probably by direct modulation of ATP-turnover, which is induced by an oxygen-dependent imbalance of the ATP-synthesis and utilization rate.

Adult↗
PubMed2001

Influence of aldosterone vs. endothelin receptor antagonism on renovascular function in liquorice-induced hypertension.

BACKGROUND: The enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) provides mineralocorticoid receptor specificity for aldosterone by metabolizing glucocorticoids to their receptor inactive 11-dehydro derivatives. Inhibition of 11beta-HSD2 by liquorice-derived glycyrrhizic acid (GA) therefore results in sodium retention and hypertension. The present study investigated the effect of the aldosterone receptor antagonist spironolactone in comparison with the endothelin ET(A) receptor antagonist darusentan on renovascular endothelial function in liquorice-induced hypertension. METHODS: GA, a recognized inhibitor of 11beta-HSD2 was supplemented to the drinking water (3 g/l) of Wistar Kyoto rats over a period of 21 days. From day 8 to 21, spironolactone (5.8+/-0.6 mg/kg/day), darusentan (45.2+/-6.5 mg/kg/day), or placebo was added to chow (n=7 per group). After the animals were killed, vascular function of isolated renal artery segments was assessed by isometric tension recording. RESULTS: Relaxation of pre-constricted renal artery segments in response to acetylcholine (10(-10) to 10(-5) mol/l) was impaired by GA as compared with controls (12+/-4% vs 98+/-5% of norepinephrine 3x10(-7) mol/l), whereas endothelium independent relaxations were unaffected. Endothelin receptor antagonism improved renovascular endothelium-dependent relaxation (32+/-4%, P<0.05 vs placebo) whereas endothelium-dependent relaxation was completely normalized by aldosterone receptor antagonism (85+/-4%, P<0.01 vs placebo). CONCLUSIONS: In GA-induced hypertension, both aldosterone receptor antagonism and endothelin receptor antagonism normalize blood pressure and improve renovascular function and, thus, may represent a new therapeutic approach in cardiovascular disease associated with impaired 11beta-HSD2 activity.

Animals↗
PubMed2001

Interaction of rapid nongenomic cardiovascular aldosterone effects with the adrenergic system.

Interactions between the renin-angiotensin-aldosterone system and the adrenergic system are complex and have mainly been attributed to angiotensin II, with knowledge about aldosterone action much less advanced. Only recently has evidence been forthcoming that aldosterone blunts the baroreceptor reflex and lowers heart rate variability in humans. Both effects point to an adrenergic-like action of aldosterone. It has been proposed that this blunting of baroreceptor sensitivity is mediated nongenomically and that nongenomic aldosterone action itself is modulated by the adrenergic system. The aim of the present study was to prove the hypothesis of an interaction between the autonomic nervous system and rapid, nongenomic aldosterone effects. We conducted a randomized, double blind, 8-fold cross-over trial on 18 healthy male volunteers. After pretreatment with the beta-blocking agent esmolol, the beta-agonist dobutamine, the alpha(1)-agonist phenylephrine, or placebo, placebo (0.9% NaCl) or aldosterone (0.5 mg) was injected. After aldosterone injection the peak plasma levels were supraphysiological, reaching nanomolar concentrations. Primary target variables were differences in changes in mean arterial blood pressure, systemic vascular resistance, and cardiac output depending on the pretreatment. Cardiovascular parameters were measured by impedance cardiography during the maintained infusion of the adrenergic modulators for 45 min. Comparing pretreatments, diverse acute, and thus nongenomic, effects of aldosterone on mean arterial blood pressure were observed. After esmolol pretreatment, aldosterone caused an increase in mean arterial blood pressure by 4.1%, whereas after dobutamine pretreatment mean arterial blood pressure decreased by 1.6%, and the difference was statistically significant (P < 0.01). These effects were significant (P < 0.005) for the first 12 min, underlining their nongenomic nature. Our data support the hypothesis that aldosterone, via nongenomic mechanisms, has diverse effects on the cardiovascular system that depend on the preexisting adrenergic state. Furthermore, aldosterone blunts the blood pressure-lowering effect of the beta-blocking agent esmolol by a nongenomic mechanism.

Adrenergic alpha-Agonists↗