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Biomedical subjects

G Kojda

Publications and source records attributed to G Kojda.

At least 19 recordsLinked to original sources
PubMed2006

[Angioedema due to ACE inhibitors and AT(1) receptor antagonists].

Acute drug-induced angioedema is a non-pruritic swelling of subcutaneous and submucosal tissue. It most occur occurs the mouth and larynx as well as lips and eyelids; less often other skin regions or even the gut can be involved. ACE inhibitor (ACEi)- induced angioedema typical occurs after several years on medication. A 72-year-old woman developed recurrent ACEi-induced angioedema. The drug was stopped and she received an AT(1)-receptor antagonist as an alternative antihypertensive. This medication also led to angioedema, which was not immediately recognized as medication-associated. AT(1)-receptor antagonists are not suitable alternatives for ACEi because they also carry an increased risk for inducing angioedema.

Aged↗
PubMed2006

[Mona Lisa syndrome: idiopathic facial paralysis during pregnancy].

Mona Lisa has been pregnant shortly before the famous painting of Leonardo da Vinci was created (1503-1506). Recently, it has been speculated that Mona Lisa's famous smile is caused by facial muscle contracture and/or synkinesis after Bell's palsy with incomplete nerval regeneration. During pregnancy the incidence of Bell's palsy is increased up to 3.3 times compared to nonpregnant women. The etiology, associated factors as well as various treatment options aiming at the prevention of associated complications and improving recovery of facial nerve function have intensively been evaluated over the past three decades. However, the preferred mode of therapy management, particularly in pregnant women, remains undecided. Corticosteroids may be beneficial if they are applied after the first trimester.

Bell Palsy↗
PubMed2006

Increased cardiac endothelial nitric oxide synthase expression in patients taking angiotensin-converting enzyme inhibitor therapy.

BACKGROUND: The efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in large clinical trials, but knowledge of the underlying mechanisms remains incomplete. Therefore, this study investigated the impact of ACE inhibitor therapy on cardiac nitric oxide (NO) synthases in patients with coronary artery disease (CAD) or heart failure. PATIENTS AND METHODS: The mRNA expression was quantified by standard calibrated competitive RT-PCR, protein expression by Western blotting and NOS activity by monitoring the conversion of [3H]arginine to [3H]citrulline during enzymatic formation of NO in tissue homogenates of myocardium of patients with, or without, ACE inhibitor treatment before elective coronary artery bypass grafting or heart transplantation. RESULTS: The mRNA expression (amol microg(-1) RNA) of endothelial NO synthase (eNOS) was higher (22.5 +/- 4.8, n = 23) in the atrial myocardium of patients taking ACE inhibitor treatment, before elective coronary artery bypass grafting, compared with patients not taking this therapy (8.9 +/- 0.7, n = 33, P < 0.0001). The ACE inhibitor therapy increased eNOS protein expression from [(9 +/- 0.7) relative units (RUs) to (12 +/- 0.9) RUs, P < 0.05, respectively] and cardiac NOS activity from 17.6 +/- 1.3 to 23.7 +/- 1.1 pmol mg protein(-1) min(-1) (P < 0.001, respectively). Inducible and neuronal NO synthase expression was not changed by the ACE inhibition. A similar up-regulation of eNOS by ACE inhibition was found in the left ventricles of patients with heart failure. The augmented endothelial NOS expression and activity was not the result of differences in clinical characteristics and concomitant therapy between the patient groups. CONCLUSION: Increased eNOS expression and activity might contribute to the beneficial effects of ACE inhibitor therapy in the treatment of CAD and heart failure.

Aged↗
PubMed2005

Organic nitrates in cardiovascular disease.

Therapeutic activation of the vascular NO/cGMP pathway is induced by a variety of stimuli/mediators including physical activity, supplementation with the precursor L-arginine and organic nitrates which generate NO in the vasculature. The necessity of an enzymatic reduction for NO generation from these drugs as well as differences in the activity of the NO/cGMP pathway within the vascular tree determine the unique hemodynamic changes elicited by organic nitrates. These changes include preferential venodilation, vessel-size specific arterial dilation and improvement of the aortic distensibility and Windkessel-function. Some animal experiments and clinical investigations suggest that nitrates may also be endowed with cardioprotective and/or vasoprotective effects. "Early entry" therapy with nitrates do not significantly improve survival in myocardial infarction but increases the beneficial effects of the ACE-inhibitor enalapril by 50%. Furthermore, nitrates have been shown to improve survival in heart failure, but prognostic effects in stable angina pectoris are unknown. Short-term experimental and clinical investigations suggest that nitrate tolerance induced by nitroglycerin is associated with toxic effects in the vasculature, but this is not true for pentaerythrityl tetranitrate and isosorbide mononitrate. The observed endothelial dysfunction induced by a continuous treatment with nitroglycerin may be an additional risk for patients who receive continuous nitroglycerin to treat conditions such as unstable angina and acute heart failure. In general, nitrates are remarkably safe drugs and are well tolerated. Appropriate clinical trials are needed to answer the question whether nitrates can do more than symptomatic relief in cardiovascular disease.

Angina, Unstable↗
PubMed2005

Increased C-reactive protein in ACE-inhibitor-induced angioedema.

AIMS: This study was designed to identify new factors which may contribute to angiotensin-converting-enzyme-inhibitor (ACEI)-induced angioedema. METHODS: In a retrospective cohort study we examined 25 patients who used an ACEI and presented at our emergency room with acute angioedema as well as 18 patients with unknown cause of angioedema and a total of 21 patients on ACEI-therapy without previous angioedema. We measured markers of inflammation such as acute-phase proteins (C-reactive protein, fibrinogen), leukocyte count and body temperature. RESULTS: The mean interval between initiation of ACEI treatment and first manifestation of angioedema was 35.8 +/- 5.3 months. During symptomatic angioedema, mean plasma levels of C-reactive protein and fibrinogen were significantly increased by 7.3-fold and 1.5-fold, respectively, while leukocyte count and body temperature were normal. These changes disappeared after successful treatment of angioedema and were not found in patients with angioedema of unknown cause and those receiving ACEI without having experienced angioedema. CONCLUSION: Our findings demonstrate for the first time that ACEI-induced angioedema is associated with strongly increased plasma levels of CRP. We suggest that CRP is involved in the pathophysiology of ACEI-induced angioedema.

Aged↗
PubMed2004

[ACE inhibitor-induced angioedema in the head and neck region. A matter of time?].

BACKGROUND: Angioedema in the head and neck region is potentially life-threatening and may occur as a side effect of inhibitors of the angiotensin-converting-enzyme (ACEI). So far, little is known about the time between the first application of ACEI and the occurrence of angioedema, or of possible cofactors and laboratory changes. MATERIAL AND METHODS: A total of 21 patients with angioedema during the course of ACEI treatment were compared to 11 patients with angioedema of unknown cause. These were retrospectively analysed for the following criteria: (1) duration of ACEI medication, (2) leading and concomitant diseases, (3) history of allergies, (4) co-medication, (5) laboratory changes, (6) treatment success, and (7) manifestation of recurrent episodes. RESULTS: The mean interval between the initiation of ACEI therapy and the first occurrence of angioedema exceeded 2 years. Values for the acute phase proteins C-reactive protein (CRP) and fibrinogen were significantly increased in the ACEI group compared to the control group. CONCLUSIONS: In any case of angioedema in the head and neck region, a side effect of ACEI must be taken into consideration even if the medication has been taken for months or years.

Adult↗
PubMed2004

[Symptoms and therapy for pregnancy rhinitis].

Pregnancy rhinitis is a common condition with long-lasting nasal congestion without signs of infection, allergy or tumor, starting at any time during pregnancy and disappearing completely within 2 weeks of delivery. Risk factors are smoking, sensitisation to house dust mites and chronic sinusitis. Hormonal influences are most likely; however, a definitive pathophysiological concept does not exist. Various treatment options are presented and a stepwise therapeutic strategy for pregnancy rhinitis is developed.

Administration, Intranasal↗
PubMed2003

The negative inotropic effect of sevoflurane is not mediated through nitric oxide synthase in rat papillary muscle.

Sevoflurane has dose-dependent negative inotropic effects on myocardial contractility. The current study investigated whether the nitric oxide pathway is involved in these effects. A laboratory, ex-vivo experiment was performed on 66 isolated papillary muscles. Effects of increasing concentrations of sevoflurane (1, 2 and 3 MAC) were assessed in control conditions, in the presence of Nw-nitro-L-arginine (L-NOARG) and in beta-adrenergic stimulated rat papillary muscles. Contractility was assessed by total developed tension. In baseline conditions, the administration of increasing concentrations of sevoflurane caused a dose-dependent reduction in contractility of respectively 8.6 +/- 1.7%, 14.4 +/- 4.8% and 23.6 +/- 3.9%. This negative inotropic effect was not significantly altered by the administration of the NO-synthase inhibitor L-NOARG (p = 0.09). Under continuous administration of 3 MAC sevoflurane, 4 consecutive concentrations of isoproterenol induced a mean increase of contractility of respectively 43.0 +/- 13.7%, 65.9 +/- 22.6%, 131.2 +/- 25.6% and 122.3 +/- 31.2%. After administration of L-NOARG, the 4 consecutive concentrations of isoproterenol induced a mean increase in contractility of respectively 36.0 +/- 8.5%, 75.0 +/- 17.8%, 143.0 +/- 42.8% and 120.0 +/- 51.4% (p = 0.85). These data indicated that the negative inotropic effects of sevoflurane in rat papillary muscles, both in basic as in beta-adrenergic stimulated conditions, were not altered by blocking the NO-cGMP-system.

Adrenergic beta-Agonists↗
PubMed2001

The effect of peroxynitrite on the catalytic activity of soluble guanylyl cyclase.

Soluble guanylyl cyclase (sGC) is a key enzyme of the *NO/cGMP pathway. Many cardiovascular disorders are associated with reduced *NO-mediated effects, while vascular superoxide (O(2)*(-)) production is increased. Both radicals rapidly react to peroxynitrite. We investigated whether peroxynitrite affects the activity and protein expression of sGC in intact vascular preparations. Catalytic sGC activity and expression of the sGC-beta(1) subunit was measured by conversion of radiolabeled GTP and western blot, respectively, using cytosolic extracts from rat aorta that had been incubated for 4 h with *NO/O(2)*(-) systems (devoid of free *NO) generating either 0.13 microM or 7.5 microM peroxynitrite/min. Incubation of rat aorta with 0.13 microM peroxynitrite/min had no effect. In striking contrast, incubation with 7.5 microM peroxynitrite/min resulted in a shift of the concentration-response curve obtained with a *NO donor (p =.0004) and a reduction of maximal specific activity from 3579 +/- 495 to 2422 +/- 265 pmol cGMP/mg/min (p =.036). The expression of the sGC-beta(1) subunit was unchanged. Exposure of aorta to the O(2)*(-) component had no effect, while exposure to the *NO-component reduced sGC expression to 58.8 +/- 7% (p <.001) and maximal sGC activity from 4041 +/- 992 to 1429 +/- 491 pmol cGMP/mg/min (p =.031). These data suggest that continuous generation of extracellular peroxynitrite might interfere with the *NO/cGMP signaling in vascular cells.

Animals↗
PubMed2001

Upregulation of vascular NAD(P)H oxidase subunit gp91phox and impairment of the nitric oxide signal transduction pathway in hypertension.

In this study we analyzed the role of vascular NAD(P)H oxidase in the generation of O(2)(-) and the endothelial impairment of NO signal transduction pathway in hypertension. In aortic rings of 15-month-old stroke-prone spontaneously hypertensive rats (SHR15) we found a 10-fold increased expression of NAD(P)H oxidase subunit gp91phox mRNA associated with a 3-fold increased production of O(2)(-) compared to age-matched Wistar rats (WIS15). Vasorelaxation studies in aortas of SHR15 showed a strongly diminished response to acetylcholine, NO-donor S-nitroso-N-acetyl-d,l-penicillamine, and organic nitrate glyceryl trinitrate compared to WIS15. Soluble guanylate cyclase (sGC) activity and sGC beta(1)-subunit protein expression was downregulated in aortas and lungs of SHR15. These data suggest an upregulation of vascular NAD(P)H oxidase and an impairment of the NO signal transduction pathway in hypertension.

Animals↗
PubMed2001

Dysfunctional regulation of endothelial nitric oxide synthase (eNOS) expression in response to exercise in mice lacking one eNOS gene.

BACKGROUND: Previous data suggest that 1 endothelial NO synthase (eNOS) gene is sufficient to allow normal expression and function of eNOS under basal conditions. We hypothesized that this might not hold true for conditions known to increase eNOS gene expression, such as exercise. METHODS AND RESULTS: Male mice heterozygous for a disruption of the eNOS gene (eNOS(+/)(-)) and normal C56Bl/6J mice (eNOS(+/+)), 3 to 4 months of age, underwent exercise training for 3 weeks. Nontrained mice were exposed to the exercise environment (noise and vibration of the treadmill) without exercise for an identical period. In eNOS(+/+) mice (n=7), exercise increased aortic eNOS protein expression by 3.4+/-0.4-fold (P<0.002). This was associated with a greater vascular cGMP accumulation on stimulation with acetylcholine (P<0.05). Furthermore, exercise training increased eNOS mRNA (1.78+/-0.4-fold) and protein (1.76+/-0.17-fold) in left ventricular tissue, as determined by competitive reverse transcription-polymerase chain reaction and Western analysis (P<0.05 for both). In striking contrast, exercise had no effect on aortic eNOS expression and cGMP accumulation in eNOS(+/)(-) mice (P>0.05). Thus, although eNOS expression appears to be normal in eNOS(+/)(-) mice under basal conditions, these mice are unable to increase eNOS expression during exercise. CONCLUSIONS: These findings show that regulation of eNOS expression during exercise requires the presence of both alleles of the gene and may have implications for conditions in which polymorphisms of eNOS are present in only 1 allele in humans. These individuals may have a normal vascular reactivity under basal conditions but may be unable to adapt their vascular reactivity in response to exercise training.

Animals↗
PubMed2001

TGF-beta(1) downregulates PTHrP in coronary endothelial cells.

Parathyroid hormone-related peptide (PTHrP) is expressed throughout the cardiovascular system including coronary endothelial cells. Factors involved in the regulation of cardiac PTHrP expression have not been examined before. This study investigates the influence of transforming growth factor (TGF)-beta(1)on ventricular PTHrP expression. Coronary endothelial cells were isolated from ventricles of adult rats and PTHrP protein expression in these cultures was analysed by immunoblotting. TGF-beta(1)caused a concentration-dependent reduction in PTHrP protein within 24 h. In transgenic mice over-expressing TGF-beta(1)ventricular PTHrP protein expression and release was reduced compared to non-transgenic littermates. Similar concerns hold for PTHrP mRNA content (RT-PCR). Since ventricular TGF-beta(1)expression increases under pathophysiological conditions like arterial hypertension, ventricular PTHrP expression was further determined in aging spontaneously hypertensive (SHR-SP) and normotensive rats. TGF- beta(1)expression was increased in SHR-SP and ventricular PTHrP mRNA expression was downregulated at the age of 10 months. PTHrP expression did not recover in elder SHR-SP in which TGF-beta(1)expression was normalized again. Finally, we investigated ventricular PTHrP expression in rats after banding of the ascending aorta which generates a pressure induced hypertrophy without an induction of TGF-beta(1)expression. In ventricles from these animals, PTHrP expression was transiently increased and normalized at day 3. In conclusion, PTHrP expression was reduced under all conditions in which coronary endothelial cells were exposed to TGF-beta(1). PTHrP expression does not correlate with cardiac hypertrophy. Since coronary endothelial cells represent the majority of PTHrP producing cells in the ventricle its downregulation by TGF- beta(1)seems to be relevant for the paracrine effects of PTHrP.

Aging↗
PubMed2001

The effect of high-dose pentaerythritol tetranitrate on the development of nitrate tolerance in rabbits.

Experimental studies with therapeutic doses of pentaerythritol tetranitrate (PETN) have shown unexpected actions such as a lack of nitrate tolerance and vasoprotective effects in atherosclerosis. We investigated the effect of a 3-week treatment with low- (6 mg kg(-1) day(-1), n=10) and high-dose (100 mg kg(-1) day(-1), n=10) oral PETN given twice daily on the development of nitrate tolerance in rabbits. We measured aortic relaxation in response to acetylcholine, S-nitroso-N-acetyl-D,L-penicillamine and PETN, constriction in response to phenylephrine and production of reactive oxygen species (ROS). Mean aortic pressure (AOPmean) and heart rate were measured after a single oral dose of PETN (50 mg kg(-1), n=6) and after increasing doses of pentaerythritol dinitrate (PEDN, n=5) and pentaerythritol mononitrate (PEMN, n=5) in anaesthetized rabbits. Oral PETN, even at high dosage, was not associated with nitrate tolerance. None of the aortic ring studies showed a difference in the responses to the vasodilators, while the vasoconstriction to phenylephrine was slightly reduced in both PETN groups. The production of vascular ROS was also not different. Oral PETN reduced AOPmean transiently (-19.3+/-4.4%, P<0.01 vs. controls) and i.v. administration of both PEMN and PEDN reduced AOPmean dose dependently (P<0.05, ANOVA). These results suggest that oral PETN elicits minor nitrate tolerance. This unique feature might be due to the slow onset of vasodilator activity of the predominantly active metabolites PEDN and PEMN and might contribute to the vasoprotective activity of PETN in atherosclerosis.

Animals↗
PubMed2001

Impaired vasodilator response to organic nitrates in isolated basilar arteries.

1. The differential responsiveness of various sections and regions in the vascular system to the vasodilator activity of organic nitrates is important for the beneficial antiischaemic effects of these drugs. In this study we examined the vasodilator activity of organic nitrates in cerebral arteries, where vasodilation causes substantial nitrate induced headache. 2. Isolated porcine basilar and coronary arteries were subjected to increasing concentrations of glyceryl trinitrate (GTN), isosorbide-5-nitrate (ISMN) and pentaerythritol tetranitrate (PETN). S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and endothelium-dependent vasodilation was investigated for comparison purpose. 3. The vasodilator potency (halfmaximal effective concentration in -logM) of GTN (4.33+/-0.1, n=8), ISMN (1.61+/-0.07, n=7) and PETN (>10 microM, n=7) in basilar arteries was more than 100 fold lower than that of GTN (6.52+/-0.06, n=12), ISMN (3.66+/-0.08, n=10) and PETN (6.3+/-0.13, n=8) observed in coronary arteries. 4. In striking contrast, the vasodilator potency of SNAP (halfmaximal effective concentration in -logM) was almost similar in basilar (7.76+/-0.05, n=7) and coronary arteries (7.59+/-0.05, n=9). Likewise, no difference in endothelium dependent relaxation was observed. 5. Denudation of the endothelium resulted in a small increase of the vasodilator potency (halfmaximal effective concentration in -logM) of GTN (4.84+/-0.09, n=7, P<0.03) in basilar arteries and similar results were obtained in the presence of the NO-synthase inhibitor N(omega)-nitro-L-arginine (4.59+/-0.05, n=9, P<0.03). 6. These results suggest that cerebral conductance blood vessels such as porcine basilar arteries seems to have a reduced expression and/or activity of certain cellular enzymatic electron transport systems such as cytochrome P450 enzymes, which are necessary to bioconvert organic nitrates to NO.

Animals↗
PubMed2001

The nitric oxide donor pentaerythritol tetranitrate can preserve endothelial function in established atherosclerosis.

Recent results suggested that long-term treatment with a low dose of the organic nitrate pentaerythritol tetranitrate (PETN, 6 mg kg(-1) per day) for 16 weeks slightly decreases aortic superoxide production in normal rabbits. We sought to determine if PETN can preserve endothelium dependent relaxation (EDR) in atherosclerotic rabbits. Three groups of 9 - 10 New Zealand White rabbits received a cholesterol chow (0.75%) for 16 weeks. One group (CHOL16) served as control and two groups were fed for another 16 weeks a cholesterol-chow without (CHOL32) or with 6 mg PETN kg(-1) per day (PETN32). Isolated aortic rings of CHOL16 showed a typical impairment of EDR with a maximal relaxation at 1 microM acetylcholine of 28+/-16%. In CHOL32-rings EDR was completely impaired. In striking contrast, EDR in PETN32 (24+/-15%) was similar to that of CHOL16 indicating a protective effect of PETN on endothelial function. Vascular superoxide production measured with the lucigenin method was not different between the groups. Aortic lesion formation in PETN32 was smaller than in CHOL32 (P<0.008). The onset of copper-induced LDL-oxidation (lag-time) after 16 weeks of cholesterol feeding (214+/-9 min) was reduced in CHOL32 (168+/-24 min, P=0.035) but not in PETN32 (220+/-21 min). This indicates prevention of increased LDL oxidation by PETN. The halfmaximal effective vasodilator concentrations of PETN (in -logM) were identical in CHOL16 (7.9+/-0.1), CHOL32 (7.6+/-0.2) and PETN32 (7.7+/-0.2). Similar results were obtained with S-nitroso-N-acetyl-D,L-penicillamine. These data suggest that PETN can reduce the progression of lesion formation, endothelial dysfunction and of LDL-oxidation in established atherosclerosis.

Animals↗
PubMed2001

Comparison of neuronal and endothelial isoforms of nitric oxide synthase in stably transfected HEK 293 cells.

The neuronal and endothelial isoforms of nitric oxide (NO) synthase (nNOS and eNOS, respectively) both catalyze the production of NO but are regulated differently. Stably transfected HEK 293 cell lines containing nNOS, eNOS, and a soluble mutant of eNOS were therefore established to compare their activity in a common cellular environment. NOS activity was determined by measuring L-[3H]citrulline production in homogenates and intact cells, the conversion of oxyhemoglobin to methemoglobin, and the production of cGMP. The results indicate that nNOS is more active than eNOS, both in unstimulated as well as calcium-stimulated cells. Under basal conditions, the soluble mutant of eNOS appeared to be slightly more active than wild-type eNOS in terms of NO and cGMP formation, suggesting that membrane association may be crucial for inhibition of basal NO release but is not required for stimulation by Ca2+-mobilizing agents. The maximal activity of soluble guanylate cyclase was significantly reduced by transfection with wild-type eNOS due to downregulation of mRNA expression. These results demonstrate that nNOS and eNOS behave differently even in an identical cellular environment.

Calcium Chloride↗