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Biomedical subjects

T Kurz

Publications and source records attributed to T Kurz.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of carvedilol and metoprolol in patients with acute myocardial infarction undergoing primary coronary intervention--the PASSAT Study.

BACKGROUND: The value of early therapy with beta-blocking agents in acute myocardial infarction (AMI) undergoing reperfusion is not yet well established. Newer beta-blocking agents such as carvedilol offer potential advantages in the setting of ischemia and reperfusion injury. METHODS: We randomized 100 patients with acute ST-elevation myocardial infarction (STEMI) to receive either 12.5 mg carvedilol or 50 mg metoprolol tartrate orally already before percutaneous coronary intervention (PCI) of the infarct-related artery, uptitrating to a daily target dose of 50 mg carvedilol or 150 mg metoprolol during the first week. Pts. were subjected to left ventricular (LV) angiography just before reperfusion and after 14 days to compare ejection fraction (EF) and regional wall motion abnormalities by quantitative LV analysis. Furthermore, kinetics of cardiac troponin T (cTnT), NT-proANP, NT-proBNP, endothelin, argenine vasopressin, epinephrine and norepinephrine were assessed during the first 12 hours and again at 2 weeks. In addition, reperfusion-induced rhythm abnormalities like VT, triplets, couplets, and bradycardic events were assessed continuously during the first 12 hours starting at reperfusion by Holter analysis. RESULTS: Both groups did not differ with respect to onset of pain, target vessel, extent of coronary heart disease, age, gender, rate of stenting or use of a GP IIb/IIIa inhibitor, pre- and postinterventional TIMI flow grade, time course of heart rate or blood pressure. There were neither significant differences in the cardiac and neurohumoral markers nor in the occurrence of arrhythmias between both treatment groups. Within 14 days, EF improved by 5.8+/-2.0% (mean+/-SEM) in the metoprolol group and by 5.2+/-2.1% in the carvedilol group (n.s.). Area of infarction was reduced by 6.1+/-2.9% in the metoprolol group and by 12.8+/-3.6% of total LV outline in the carvedilol group (n.s.). Maximum hypokinesia in the central infarcted region was diminished by 0.40+/-0.11 standard deviation (SD) in the metoprolol group and by 0.34+/-0.13 SD in the carvedilol group (n.s.). CONCLUSION: In the setting of direct PCI in acute STEMI, administration of carvedilol before reperfusion appears not to be superior to metoprolol with respect to myocardial injury and improvement of global and regional LV function. The study documents equivalent improvement of LV function and similar kinetics of cardiac and neurohumoral markers in pts. with acute STEMI undergoing direct PCI if the pts. were immediately treated with either carvedilol or metoprolol. Thus, superiority of carvedilol in experimental studies did not translate into a clinical benefit.

Administration, Oral↗
PubMed2006

Lysosomal labilization.

The lysosomal compartment is the place for cellular degradation of endocytosed and autophagocytosed material and a center for normal turnover of organelles as well as most long-lived proteins. Lysosomes were long considered stable structures that broke and released their many hydrolytic enzymes only following necrotic cell death. It is now realized that lysosomes instead are quite vulnerable, although in a heterogeneous way. Their exposure to a number of events, such as oxidative stress, lysosomotropic detergents and aldhydes, as well as overexpression of the p53 protein, causes time-and-dose-dependent lysosomal rupture that is followed by apoptosis or necrosis. Partial lysosomal rupture has often been found to be an early upstream event in apoptosis, while necrosis results from fulminant lysosomal rupture. Consequently, factors influencing the stability of lysosomes, for instance their content of labile and redox-active iron, seem to be essential for the survival of cells.

Animals↗
PubMed2005

A genome-wide screen on the genetics of atopy in a multiethnic European population reveals a major atopy locus on chromosome 3q21.3.

BACKGROUND: Dissecting complex diseases in underlying distinct traits and studying these for their genetic basis might enhance the power as well as the specificity, of detection of disease genes. These phenotypes are known as intermediate phenotypes. OBJECTIVE: We were interested in the atopic basis of asthma, and used the sensitization to mite (Dermatophagoides pteronyssinus) allergens as a pathophysiologically important intermediate phenotype. METHODS: This time we performed a genome-wide scan based on the same already used multiethnic European population consisting of 82 nuclear families with at least two affected siblings. We carried out nonparametric as well as parametric MOD-score analyses based on the genotypes of 603 microsatellite markers. RESULTS: In comparison with our first genome-wide candidate region search three novel regions additionally appeared to be significant. We obtained significant results for the region 2p12 with a MOD score of 3.35 and for the region 16q21 with a MOD score of 4.18. The most significant result was found for the region 3q21.3 with the same microsatellite marker, which showed significant linkage to atopic dermatitis (AD) in another study with a MOD score of 4.51 and an nonparametric linkage analysis (NPL) of 4.00. CONCLUSION: Our findings indicate that atopy, allergic asthma, allergic rhinitis and AD on the one hand are distinct traits on both the clinical and genetic basis, but on the other hand, our results also underline that these traits are closely related diseases concerning the atopic basis of the traits.

Antigens, Dermatophagoides↗
PubMed2004

Association study of polymorphisms within interleukin-18 in juvenile idiopathic arthritis and bronchial asthma.

BACKGROUND: Interleukin-18 (IL-18) plays an important role in the regulation of TH1 as well as TH2 immunologic responses and thus in the development of chronic inflammatory diseases. Positive association studies of polymorphisms in IL-18 with different diseases have underlined the involvement of IL-18 in the pathogenetics processes. Our interest was to test polymorphisms of IL-18 for association with a typical TH1-mediated disease--juvenile idiopathic arthritis--and the TH2-mediated disease bronchial asthma in Caucasian children. METHODS: We genotyped five polymorphisms that were in association with chronic inflammatory diseases (-607C, -137C, 113G, 127T, and -133G). This was performed by restriction fragment length polymorphism in populations of asthmatic children, control individuals, and children with antinuclear antibodies (ANA)-positive juvenile idiopathic arthritis. Statistical analysis was performed by the Armitage trend test; haplotypes were calculated by the Arlequine program. RESULTS: No significant association was found between any single nucleotide polymorphism or any haplotype and bronchial asthma or ANA-positive juvenile idiopathic arthritis. CONCLUSION: We conclude that the effect of IL-18 in the immunologic context of diseases like bronchial asthma or juvenile arthritis might be too complex to be reflected in a simple one-way association study. Furthermore, the polymorphisms under investigation might be nonfunctional.

Adolescent↗
PubMed2003

Norepinephrine release is reduced in cardiac tissue of Type 2 diabetic patients.

AIMS/HYPOTHESIS: The aim of this study was to assess whether cardiac catecholamine release is affected in patients with Type 2 diabetes mellitus. METHODS: A trial tissue was obtained from 19 diabetic (Type 2) and 43 non-diabetic patients undergoing coronary surgery. Endogenous norepinephrine release was examined under baseline conditions as well as during electrical field stimulation (effective voltage 5 V, stimulation frequency 4 Hz, pulse width 2 msec) by high performance liquid chromatography and electrochemical detection. Cardiac function and arterial blood pressure was assessed from coronary angiography. RESULTS: In atrial tissue from diabetic patients, stimulation-induced norepinephrine release was reduced by 25% compared with non-diabetic patients, while baseline norepinephrine release did not differ between both groups. Preoperative plasma glucose and haemoglobin A(1C) concentrations were increased in patients with diabetes, however, no relation was found to catecholamine release. Diabetic and non-diabetic patients did not differ regarding left ventricular ejection fraction and arterial blood pressure. CONCLUSION/INTERPRETATION: Cardiac norepinephrine release is suppressed in patients with Type 2 diabetes which could contribute to sympathetic neuropathy. The difference of norepinephrine release in diabetic and non-diabetic patients was independent of cardiac function and arterial blood pressure.

Aged↗
PubMed2003

Plasma catecholamines and N-terminal proBNP in patients with acute myocardial infarction undergoing primary angioplasty. Relation to left ventricular function and clinical outcome.

BACKGROUND: Neither profiles nor prognostic values of neurohormonal markers have been prospectively evaluated in patients with acute myocardial infarction (AMI) undergoing primary angioplasty. METHODS AND RESULTS: In 118 consecutive patients with AMI undergoing successful reperfusion (TIMI 2 and 3) by primary angioplasty, plasma concentrations of norepinephrine, epinephrine and N-terminal proBNP (NT-proBNP) were measured before, 60 min and 10 days after angioplasty. Catecholamine concentrations (mean+/-SEM) rose to a maximum in the first hour after angioplasty (norepinephrine: 602+/-44 ng/L, epinephrine: 213+/-24 ng/L) and returned to normal at day 10. Conversely, NT-proBNP levels maintained a further increase from 799+/-44 pmol/L at baseline to 924+/-54 pmol/L at day 10. A NT-proBNP concentration above median at 60 min post-angioplasty predicted major adverse cardiac events (n=27) during the 18-36 month follow-up with an odds ratio of 5.9 (1.7-20.3) and was superior to catecholamines, to left ventricular ejection fraction and to other established postinfarction risk markers. CONCLUSIONS: In a low-risk cohort of patients with AMI undergoing successful reperfusion therapy, plasma NT-proBNP concentrations are elevated for at least ten days. The prognostic value of early plasma NT-proBNP should be further evaluated concerning its ability to facilitate risk stratification of infarct patients.

Aged↗
PubMed2003

Promoter polymorphisms of the CD14 gene are not associated with bronchial asthma in Caucasian children.

Several studies have investigated the association of a promoter polymorphism in CD14 with atopic phenotypes. We screened this and another polymorphism in 182 asthmatic children and found no association with asthma. Furthermore, there was substantial linkage disequilibrium of the polymorphisms. Thus CD14 does not play a major role in the development of asthma in our population of Caucasian children.

Adolescent↗
PubMed2002

Partial loss of dopaminergic neurons in the substantia nigra, ventrotegmental area and the retrorubral area -- model of the early beginning of Parkinson's symptomatology?

To test substances which might have protective effects on the dopaminergic system it is necessary to use models with a pathological symptomatology of the early beginning, i.e. models in which the chance exists to arrest the otherwise progressive pathological processes (see Heim et al., 2001). 6-hydroxydopamine (6-OHDA) injected unilaterally into the ventrolateral striatum of rats (6 microg dissolved in 2 microl 0.2% ascorbic acid) leads to specific stereotyped movements after subcutaneous injection of apomorphine both 3 and 13 weeks after surgery. Ten weeks after surgery decreased spontaneous motor activity could be observed. Twelve weeks after 6-hydroxydopamine injection, the animals had difficulties in performing a spatial navigation task when the submerged escape platform was moved to another position. The switching of motor programs was less pronounced. The application of tyrosine-hydroxylase-staining showed a loss of ipsilateral neurones of the substantia nigra compacta as well as of dendrites in the pars reticulata, neurones in the ventral tegmental area and in the retrorubral area ipsilaterally as well as a loss of dopaminergic fibres both ipsilaterally and contralaterally in the striatum which should belong to the contralateral acting substantia nigra afferents. The loss of the neurones and the afferents was induced by the retrograde denervation following the 6-OHDA injection within the ventrolateral striatum. The question arises whether the model used here with the partially loss of dopaminergic neurons and fibres reflects some of pathological symptoms of Parkinson's disease in the early states.

Animals↗
PubMed2001

Effects of intracoronary low-dose enalaprilat as an adjunct to primary percutaneous transluminal coronary angiography in acute myocardial infarction.

Bradykinin accumulation is a potent cardioprotective mechanism underlying angiotensin-converting enzyme (ACE) inhibition in ischemia and/or reperfusion injury. There is, however, concern about treatment with ACE inhibitors in the very early phase of acute myocardial infarction (AMI) due to adverse systemic hemodynamic effects. We tested the hypothesis that cardiac bradykinin metabolism can be influenced by very low doses of intracoronary ACE inhibitors without harmful systemic effects in patients with AMI. Twenty-two patients with AMI in Killip classes II to III who underwent primary percutaneous transluminal coronary angiography (PTCA) were randomized to intracoronary enalaprilat (50 microg) or saline, given immediately after reopening of the infarct-related artery. Hemodynamics and electrocardiograms were monitored continuously and samples for determination of ACE activity, angiotensin II, bradykinin, kininogen, and cardiac marker proteins were collected from pulmonary arterial and central venous blood. Enalaprilat had no adverse effects on systemic hemodynamics, but rather stabilized arterial pressure and cardiac rhythm during reperfusion. Enalaprilat induced a 70% reduction of ACE activity and a significant increase of bradykinin in pulmonary arterial blood. Angiotensin II was not significantly affected by enalaprilat either in pulmonary arterial or in central venous blood. Myoglobin release was lower and the duration of reperfusion arrhythmias was significantly reduced in the enalaprilat group (p <0.05). Thus, in this pilot study, intracoronary enalaprilat infusion in the infarct-related artery is feasible in the setting of primary angioplasty and is safe and well tolerated. Effective cardiac ACE inhibition can be achieved by low-dose intracoronary enalaprilat, which primarily causes a potentiation of bradykinin.

Angioplasty, Balloon, Coronary↗
PubMed2001

Luminescence of transient bubbles at elevated ambient pressures.

The light emission of transient laser-produced cavitation bubbles in water is investigated in a range of ambient pressures up to 5 bar and laser energies up to 30 mJ. At elevated pressures bubble luminescence can be increased more than two fold for bubbles created with the same laser energy, and up to almost an order of magnitude comparing bubbles of the same maximum radius. Both the conversion of large laser energies into mechanical energy of the bubble, and the conversion of mechanical energy into light are improved at higher pressure.

Journal Article↗
PubMed2001

Regiospecific synthesis of 4-(2-oxoalkyl)pyridines.

[reaction: see text]. A new and operationally simple method has been developed for the regiospecific syntheses of 4-(2-oxoalkyl)pyridines from ketones and pyridine in good yields, using triflic anhydride to activate the pyridine ring.

Journal Article↗
PubMed2001

[Endoprosthetic surface replacement of the head of the humerus].

The concept of an endoprosthetic surface replacement of the humeral head differs from that of stemmed endoprostheses. It is the replacement of the destroyed joint surface with reconstruction of the normal anatomy and minimal bone resection. The aim of this prospective study was to evaluate the short-term results of a newly developed cup arthroplasty (Durom-Cup) for the humeral head. In a prospective study, 39 patients with 46 Durom-Cups were evaluated preoperatively and every 3 months postoperatively. The average follow-up was 15 +/- 9 months. The group included 28 shoulders with rheumatoid arthritis, 15 joints with osteoarthritis, and 3 humeral head necroses. The Constant-score and SAS-function score were used. The Constant-score increased from 20.25 +/- 9.06 points preoperatively to 46.62 +/- 14.05 at 3 months, to 48.11 +/- 14.49 at 6 months, and to 55.25 +/- 11.6 at 9 months postoperatively. The Constant-score stayed at this level during further follow-up and was 55.81 +/- 16.31 at 12 months postoperatively. The best results were seen in the group of humeral head necroses with a Constant-score of 71.0 +/- 12.2 compared to 54.66 +/- 13.89 in the group of osteoarthritis and 56.78 +/- 13.33 in patients with rheumatoid arthritis at 12 months postoperatively. The results with the Durom-Cup are encouraging so that cup arthroplasty seems to be a good alternative to stemmed prostheses. The main advantages of the humeral head resurfacing are the bone-preserving fixation and the relatively simple surgical technique.

Aged↗
PubMed2001

Ischemia-induced ventricular fibrillation in isolated perfused rat heart: role of alpha1A-adrenoceptor mediated activation of protein kinase C.

It previously has been reported in ischemic rat hearts that local release of noradrenaline triggers ventricular fibrillation via alpha1A-adrenoceptor stimulation. In order to elucidate the intracellular pathway mediating ventricular fibrillation in this setting, we used inhibitors or activators of protein kinase C in the absence or presence of the alpha1A-adrenoceptor antagonist WB 4101. Regional ischemia was induced in isolated perfused rat heart byligature of the left coronary artery. Pharmacological interventions were tested by addition of drugs to the perfusate 10 min prior to ligature and throughout 30 min of ischemia while the epicardial electrocardiogram was continuously monitored. Blockade of protein kinase C by polymyxin B (1 micromol/l) significantly reduced ventricular fibrillation to 40% (from 87% in controls). Similar effects were seen with the protein kinase C inhibitors staurosporine 10 nmol/l (46% vs. 91%) and cremophor RH 40 100 micromol/l (33% vs. 77%). Activation of protein kinase C by 1,2-dioctanoyl-sn-glycerol (DOG, 10 micromol/l) or phorbol 12-myristate 13-acetate (PMA, 10 nmol/l) did not affect ventricular fibrillation. In the presence of the alpha1A-adrenoceptor antagonist WB 4101 (0.1 micromol/l), which per se suppressed ventricular fibrillation to 17%, both DOG and PMA increased the occurrence of ventricular fibrillation to 73% and 75%, respectively, whereas the inactive phorbol ester 4alpha-phorbol 12,13-didecanoate (4alpha-PDD, 10 nmol/l) revealed no proarrhythmic effect. In summary, during regional ischemia in the isolated perfused rat heart, alpha1A-adrenoceptor stimulation induces ventricular fibrillation mainly by activating protein kinase C.

Adrenergic alpha-Antagonists↗
PubMed2001

Adenosine inhibits norepinephrine release in the postischemic rat heart: the mechanism of neuronal stunning.

OBJECTIVE: Numerous studies support the concept of impaired postischemic sympathetic neurotransmission in the heart. We hypothesized that postischemic neuronal dysfunction (neuronal stunning) is caused by a transient suppression of exocytotic norepinephrine (NE) release from sympathetic nerve terminals. Furthermore, we assessed the role of presynaptic adenosine-receptors and alpha2-adrenoceptors in neuronal stunning. METHODS AND RESULTS: Exocytotic NE release was induced by two electrical field stimulations (S(1) and S(2)) in isolated perfused rat hearts. S(1) was performed under baseline conditions and S(2) either during or following intervention. Results are expressed as mean S(2)/S(1) ratios+/-S.E.M. Stepwise increase of global ischemic periods (10, 20, and 30 min) induced a progressive suppression of NE release in the postischemic hearts, which was reversible during reperfusion. Both the degree and duration of NE suppression was dependent on the extent of the preceding ischemic period. Following 10-min ischemia complete recovery of NE release was achieved after 5-min reperfusion (1.07+/-0.12), whereas 5-min reperfusion did not restore NE release after 30 min (0.36+/-0.07) of ischemia. The adenosine-receptor antagonists 8-phenyltheophylline (8-PT; non-selective) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; adenosine A1-receptor subtype selective) significantly increased NE release after 30-min ischemia and 5-min reperfusion (0.78+/-0.06 and 0.64+/-0.07), while in the same experimental protocol blockade of alpha2-adrenoceptors by yohimbine failed to restore the postischemic release (0.24+/-0.06). In non-ischemic hearts the adenosine analogue R(-)N(6)-(2-phenylisopropyl)adenosine (R-PIA) resulted in a marked suppression of NE release (0.61+/-0.07). The inhibitory effect of R-PIA and 2-chloro-N(6)-cyclopentyladenosine (CCPA; adenosine A1-receptor subtype selective agonist) persisted 5 min after cessation of R-PIA (0.62+/-0.05) and CCPA (0.58+/-0.04). Activation of alpha2-adrenoceptors by 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304) also caused a reduction of NE release (0.50+/-0.02), but the release increased to control levels 5 min after cessation of UK 14,304 (0.90+/-0.06). CONCLUSIONS: The results establish the phenomenon of neuronal stunning in terms of a postischemic suppression of exocytotic NE release and provide evidence that neuronal stunning is mediated by endogenous adenosine through activation of presynaptic adenosine A1-receptors.

Adenosine↗
PubMed2001

Expression patterns and subcellular localization of a 52 kDa sucrose-binding protein homologue of Vicia faba (VfSBPL) suggest different functions during development.

A cDNA coding for a 54 kDa signal sequence containing protein has been isolated from a faba bean cotyledonary library and characterized. The deduced protein is designated Vicia faba SBP-like protein (VfSBPL) since it shares 58% homology to a 62 kDa soybean (Glycine max) protein (GmSBP) which has been described as a sucrose-binding and sucrose-transporting protein (SBP). VfSBPL as well as GmSBP are outgroup members of the large vicilin storage protein family. We were unable to measure any sucrose transport activity in mutant yeast cells expressing VfSBPL. During seed maturation in late (stage VII) cotyledons mRNA was localized by in situ hybridization in the storage parenchyma cells. At the subcellular level, immunolocalization studies proved VfSBPL accumulation in storage protein vacuoles. However, mRNA localization in stage VI cotyledons during the prestorage/storage transition phase was untypical for a storage protein in that, in addition to storage parenchyma cell labelling, strong labelling was found over seed coat vascular strands and the embryo epidermal transfer cell layer reminiscent of sucrose transporter localization. The VfSBPL gene is composed of 6 exons and 5 introns with introns located at the same sites as in a Vicia faba 50 kDa vicilin storage protein gene. The time pattern of expression as revealed by northern blotting and the GUS accumulation pattern caused by a VfSBPL-promoter/GUS construct in transgenic tobacco seeds was similar to a seed protein gene with increasing expression during seed maturation. Our data suggest different functions of VfSBPL during seed development.

Amino Acid Sequence↗
PubMed2001

Presynaptic regulation of cardiac norepinephrine release in ischemia.

In myocardial ischemia presynaptic regulation of norepinephrine release may be altered either by ischemic effects on presynaptic receptor signaling or by ischemia-evoked accumulation of endogenous agonists. Because presynaptic receptors are targets of several drugs. such alterations may have pharmacotherapeutic implications. We investigated the effect of brief ischemic periods on presynaptic regulation of norepinephrine release by alpha2-adrenoceptors, beta2-adrenoceptors, adenosine A1-, angiotensin AT1-, and bradykinin B2-receptors in isolated perfused rat hearts. Exocytotic norepinephrine release was evoked by electrical field stimulation. Paired stimulations were performed to compare the pharmacologic intervention (S2) with the release under baseline conditions (S1), and the effects of receptor agonists and antagonists were compared under nonischemic and stop-flow conditions. In summary. during brief myocardial ischemia, presynaptic modulation of norepinephrine release is differentially regulated. Autoinhibitory alpha2-adrenoceptors lose their activity, whereas stimulatory beta2-adrenoceptors are sensitized. Inhibitory adenosine A1-receptors gain importance during ischemia owing to endogenous adenosine formation. Bradykinin- and angiotensin-mediated stimulation of norepinephrine release is not affected under ischemic conditions.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2001

A unique complication during coronary angiography: peripheral embolism by selective right coronary engagement--a case report.

"Micro" and "macro" peripheral embolisms during coronary angiography have been described. In all these cases, the aorta or the left heart chambers have been the source of embolus. A patient who during coronary angiography for acute inferior myocardial infarction experienced acute embolism of the left common femoral artery. The source of the embolus was a thrombus-filled right coronary artery, and the precipitating cause was its selective engagement with a diagnostic Judkins right catheter. A brief review of literature is also presented.

Adult↗