28 results on '"Ulucan C"'
Search Results
2. Stress cardiomyopathy (Tako-Tsubo) following radiofrequency ablation in the right ventricular outflow tract
- Author
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Hasdemir, C., primary, Yavuzgil, O., additional, Simsek, E., additional, Ulucan, C., additional, and Cinar, C. S., additional
- Published
- 2008
- Full Text
- View/download PDF
3. Increased Aldosterone Levels in a Model of Type 2 Diabetes Mellitus
- Author
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Fredersdorf, S., primary, Endemann, D., additional, Luchner, A., additional, Heitzmann, D., additional, Ulucan, C., additional, Birner, C., additional, Schmid, P., additional, Stoelcker, B., additional, Resch, M., additional, Muders, F., additional, AJ Riegger, G., additional, and Weil, J., additional
- Published
- 2008
- Full Text
- View/download PDF
4. ß1 and ß2-Adrenergic Receptor Polymorphisms and Idiopathic Ventricular Arrhythmias.
- Author
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Ulucan C, Cetintas V, Tetik A, Eroglu Z, Kayikcioglu M, Can LH, Payzin S, Aydin M, and Hasdemir C
- Abstract
Genetics and Idiopathic Ventricular Arrhythmias. Introduction: Idiopathic ventricular arrhythmias commonly refer to ventricular tachycardia (VT) and/or frequent/monomorphic premature ventricular contractions (PVC) in patients with structurally normal heart. Activation of sympathetic tone has been shown to play an important role in the provocation and maintenance of these arrhythmias.We investigated whether common single nucleotide polymorphisms in the beta1 and beta2-adrenergic receptors are associatedwith idiopathic ventricular arrhythmias.Methods: A total of 143 unrelated patients presenting with idiopathic ventricular arrhythmias were prospectively included in a case-control association study. Patient population was matched by age and gender to the unrelated, healthy control subjects (N = 307). All study subjects were of Turkish (Anatolian Caucasian) descent. Allele and genotype frequencies of the Gly389Arg and Ser49Gly polymorphisms of the beta1-adrenergic receptor and Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms of the beta2-adrenergicreceptor were compared between patient population and control subjects. The genotype frequencies were in Hardy-Weinberg equilibrium.Results: Patients with idiopathic ventricular arrhythmias had higher frequency of Arg389Arg genotype (22.4% vs 1.6%, P < 0.001), Arg389Gly49 (5.24% vs 0.73%, P = 0.005), and Arg389Ser49 (36.7% vs 13.6%, P < 0.001) haplotypes of the beta1-adrenergic receptor, and higher frequency of Gly16Gly (31.5% vs 13.4%, P < 0.001), Glu27Glu genotypes (18.2% vs 10.1%, P = 0.006) and Gly16Gln27Thr164 (15.3% vs 7.4%, P = 0.002), Gly16Glu27Thr164 (13.1% vs 7%, P = 0.004), and Gly16Glu27Ile164 (13.2% vs 6%, P = 0.002) haplotypes of the beta2-adrenergic receptor compared to control subjects.Conclusion: Our data suggest that common single nucleotide polymorphisms in the beta1 and beta2-adrenergic receptors are significantly associated with idiopathic ventricular arrhythmias in Turkish population. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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5. Disruption of type 5 adenylyl cyclase enhances desensitization of cyclic adenosine monophosphate signal and increases Akt signal with chronic catecholamine stress.
- Author
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Okumura S, Vatner DE, Kurotani R, Bai Y, Gao S, Yuan Z, Iwatsubo K, Ulucan C, Kawabe J, Ghosh K, Vatner SF, Ishikawa Y, Okumura, Satoshi, Vatner, Dorothy E, Kurotani, Reiko, Bai, Yunzhe, Gao, Shumin, Yuan, Zengrong, Iwatsubo, Kousaku, and Ulucan, Coskun
- Published
- 2007
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- View/download PDF
6. Are `neutral cells` in the rostral ventro-medial medulla subtypes of on- and off-cells?
- Author
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Ellrich, J., Ulucan, C., and Schnell, C.
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- 2000
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7. Pseudonormalization: clinical, electrocardiographic, echocardiographic, and angiographic characteristics.
- Author
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Ulucan C, Yavuzgil O, Kayikcioglu M, Can L, Payzin S, Kultursay H, Soydan I, Hasdemir C, Ulucan, Cem, Yavuzgil, Oğuz, Kayikçioğlu, Meral, Can, Levent, Payzin, Serdar, Kültürsay, Hakan, Soydan, Inan, and Hasdemir, Can
- Abstract
Objective: Spontaneous pseudonormalization (PN) is a unique 12-lead electrocardiography (ECG) finding which has been reported to be associated with severe, transmural myocardial ischemia. To date, a paucity of data exists about the incidence and clinical characteristics of patients with PN. Therefore the aim of this study was to investigate the incidence and the electrocardiographic, echocardiographic, and angiographic characteristics of patients with PN.Methods: Clinical, laboratory, electrocardiographic, echocardiographic, and angiographic characteristics of 12 consecutive patients with PN on 12-lead ECG (Group 1) were compared with patients (Group 2, n=28) presenting with acute coronary syndrome (ACS) associated with ST-T wave changes without PN.Results: All patients presented with chest pain. The incidence of PN among patients presenting with ACS was 1%. Pseudonormalization was present in precordial leads in 11 and in inferior leads in 1 patient. Nine out of 12 (75%) patients in Group 1, 16 out of 28 (57%) patients in Group 2 had elevation of cardiac enzymes compatible with acute myocardial infarction. Severely narrowed or totally occluded ischemia and/or infarction-related coronary arteries were present in all patients in Group 1, in 20 (71%) patients in Group 2. Three patients in Group I and one patient in Group 2 had coronary artery thrombus formation. Group 1 patients had worse coronary collateral grading in comparison to Group 2 patients.Conclusion: Pseudonormalization is a rare entity and it is typically associated with severely narrowed or totally occluded coronary arteries along with thrombus formation, and poor coronary collateral development. [ABSTRACT FROM AUTHOR]- Published
- 2007
8. Genetics and idiopathic ventricular arrhythmias: the role of ethnic diversity and gender difference.
- Author
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Ulucan C, Can LH, and Hasdemir C
- Published
- 2008
9. Premature Atrial Contraction-Induced Cardiomyopathy: Recognition of a Distinct Phenotype of Arrhythmia-Induced Cardiomyopathy in Humans.
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Hasdemir C, Kocabas U, Kilic S, Kose S, Kilic S, Gunduz R, Ulucan C, Yagmur B, Sahin H, Celen C, Orman MN, Yuksel A, Aydin M, Payzin S, Juang JJ, and Antzelevitch C
- Subjects
- Humans, Phenotype, Atrial Premature Complexes complications, Atrial Premature Complexes diagnosis, Cardiomyopathies diagnosis, Cardiomyopathies etiology, Ventricular Premature Complexes complications, Ventricular Premature Complexes diagnosis
- Published
- 2023
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- View/download PDF
10. Antihypertrophic effects of combined inhibition of the renin-angiotensin system (RAS) and neutral endopeptidase (NEP) in progressive, tachycardia-induced experimental heart failure.
- Author
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Birner C, Ulucan C, Bratfisch M, Götz T, Dietl A, Schweda F, Riegger GA, and Luchner A
- Subjects
- Aldosterone blood, Angiotensin-Converting Enzyme Inhibitors pharmacology, Animals, Disease Models, Animal, Gene Expression Regulation drug effects, Heart Failure physiopathology, Male, Natriuretic Peptide, Brain genetics, Neprilysin antagonists & inhibitors, RNA, Messenger metabolism, Rabbits, Renin blood, Renin-Angiotensin System drug effects, Tachycardia physiopathology, Ventricular Dysfunction, Left physiopathology, Ventricular Remodeling drug effects, Cardiomegaly prevention & control, Cardiovascular Agents pharmacology, Heart Failure drug therapy, Pyridines pharmacology, Thiazepines pharmacology
- Abstract
Vasopeptidase inhibition (VPI), a therapeutic strategy by dual inhibition of both ACE and neutral endopeptidase 24.11, has not shown a prognostic benefit over ACE inhibition in chronic severe heart failure (CHF). Nevertheless, the effects of early treatment by VPI on cardiac remodelling have not been well assessed. We analysed the effects of early chronic VPI (50 mg/kg/day Omapatrilat) on cardiac remodelling and neurohumoral function during the progression of rapid ventricular pacing-induced heart failure in rabbits (early left ventricular dysfunction [ELVD]: 10 days at 330 bpm, CHF: further 10 days at 360 bpm). VPI-treated animals (ELVD-VPI n = 6; CHF-VPI n = 8) and placebo treated animals (ELVD n = 6; CHF n = 7) were compared with control rabbits (CTRL n = 5). LV fractional shortening (FS) and enddiastolic diameter (LVEDD) were assessed by echocardiography (12 MHz probe). LV BNP- and LV IL-6 gene expression was analysed quantitatively by real time PCR. Neurohumoral function was assessed by ANP, cGMP, plasma renin activity (PRA) and Aldosterone. In ELVD, LVEDD and atrial mass were significantly increased (both p < 0.05). This increase was markedly attenuated by VPI (both p < 0.05 vs. placebo). CHF was associated with a further increase in atrial mass and an increase in LV mass (both p < 0.05), which was again attenuated by VPI (atrial mass, p < 0.05 vs. untreated). LV BNP mRNA was significantly increased in CHF (p < 0.05 vs. control), and chronic VPI completely abolished this increase in ELVD and significantly attenuated it in CHF (p < 0.05 vs. CHF-placebo). Beyond that, the increase of cGMP was augmented by chronic VPI (p < 0.05 vs. placebo in CHF) in heart failure and that of Aldosterone was attenuated (p < 0.05 vs. placebo in ELVD), whereas PRA was temporarily increased (p < 0.05 vs. placebo in ELVD). Combined inhibition of ACE and NEP by VPI significantly inhibits early cardiac remodelling and LV BNP gene expression. If initiated early enough, it may slow down cardiac remodelling and represents a promising therapeutic strategy in progressive heart failure.
- Published
- 2012
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11. Tachycardia-induced cardiomyopathy in patients with idiopathic ventricular arrhythmias: the incidence, clinical and electrophysiologic characteristics, and the predictors.
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Hasdemir C, Ulucan C, Yavuzgil O, Yuksel A, Kartal Y, Simsek E, Musayev O, Kayikcioglu M, Payzin S, Kultursay H, Aydin M, and Can LH
- Subjects
- Comorbidity, Electrocardiography statistics & numerical data, Female, Germany epidemiology, Humans, Incidence, Male, Middle Aged, Risk Assessment, Risk Factors, Cardiomyopathies diagnosis, Cardiomyopathies epidemiology, Tachycardia, Ventricular diagnosis, Tachycardia, Ventricular epidemiology, Ventricular Premature Complexes diagnosis, Ventricular Premature Complexes epidemiology
- Abstract
Introduction: Idiopathic ventricular arrhythmias in the form of monomorphic premature ventricular contractions (PVC) and/or ventricular tachycardia (VT) can cause tachycardia-induced cardiomyopathy (TICMP). The aim of this study was to determine the incidence, clinical and electrophysiologic characteristics, and the predictors of TICMP in patients with idiopathic ventricular arrhythmias., Methods: Study population consisted of 249 consecutive patients (148 F/101 M, 45 ± 20 y/o) with frequent PVCs and/or VT. All patients underwent transthoracic echocardiography and 24-hour Holter monitoring. TICMP was defined as left ventricular ejection fraction (LVEF) of ≤50% in the absence of any detectable underlying heart disease and improvement of LVEF ≥15% following effective treatment of index ventricular arrhythmia., Results: Seventeen (6.8%) patients had TICMP. Patients with TICMP compared to patients with preserved LVEF were more likely to be male (65% vs 39%, P = 0.043) and asymptomatic (29% vs 9%, P = 0.018), and were more likely to have higher PVC burden (29.4 ± 9.2 vs 8.1 ± 7.4, P < 0.001), persistence of PVCs throughout the day (65% vs 22%, P = 0.001), and repetitive monomorphic VT (24% vs 0.9%, P < 0.001). PVC burden of 16% by ROC curve analysis best separated the patients with TICMP compared to patients with preserved LVEF (sensitivity 100%, specificity 87%, area under curve 0.96)., Conclusions: TICMP was relatively common (∼1 in every 15 patients) in our study population. The predictors of TICMP were male gender, absence of symptoms, PVC burden of ≥16%, persistence of PVCs throughout the day, and the presence of repetitive monomorphic VT., (© 2011 Wiley Periodicals, Inc.)
- Published
- 2011
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12. Epac increases melanoma cell migration by a heparan sulfate-related mechanism.
- Author
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Baljinnyam E, Iwatsubo K, Kurotani R, Wang X, Ulucan C, Iwatsubo M, Lagunoff D, and Ishikawa Y
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- Animals, Cell Line, Tumor, Guanine Nucleotide Exchange Factors genetics, Humans, Melanoma pathology, Melanoma, Experimental metabolism, Melanoma, Experimental pathology, Mice, Mice, Nude, Neoplasm Invasiveness, Neoplasm Transplantation, Phosphatidylinositol 3-Kinases physiology, Protein Transport, Signal Transduction, Tubulin metabolism, Cell Movement physiology, Guanine Nucleotide Exchange Factors physiology, Heparitin Sulfate biosynthesis, Melanoma metabolism, Sulfotransferases metabolism, Syndecan-2 metabolism
- Abstract
Melanoma, the most malignant form of human skin cancer, has a poor prognosis due to its strong metastatic ability. It was recently demonstrated that Epac, an effector molecule of cAMP, is involved in regulating cell migration; however, the role of Epac in melanoma cell migration remains unclear. We thus examined whether Epac regulates cell migration and metastasis of melanoma. Epac activation, by either specific agonist or overexpression of Epac, increased melanoma cell migration. Deletion of endogenous Epac with small interfering RNA decreased basal melanoma cell migration. These data suggested a major role of Epac in melanoma cell migration. Epac-induced cell migration was mediated by translocation of syndecan-2, a cell-surface heparan sulfate proteoglycan, to lipid rafts. This syndecan-2 translocation was regulated by tubulin polymerization via the Epac/phosphoinositol-3 kinase pathway. Epac-induced cell migration was also regulated by the production of heparan sulfate, a major extracellular matrix. Epac-induced heparan sulfate production was attributable to the increased expression of N-deacetylase/N-sulfotransferase-1 (NDST-1) accompanied by an increased NDST-1 translation rate. Finally, Epac overexpression enhanced lung colonization of melanoma cells in mice. Taken together, these data indicate that Epac regulates melanoma cell migration/metastasis mostly via syndecan-2 translocation and heparan sulfate production.
- Published
- 2009
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13. Increased aldosterone levels in a model of type 2 diabetes mellitus.
- Author
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Fredersdorf S, Endemann DH, Luchner A, Heitzmann D, Ulucan C, Birner C, Schmid P, Stoelcker B, Resch M, Muders F, Riegger GA, and Weil J
- Subjects
- Actins genetics, Albuminuria, Aldosterone analogs & derivatives, Aldosterone urine, Animals, Blood Pressure, Cytochrome P-450 CYP11B2 genetics, Diabetes Mellitus, Experimental blood, Diabetes Mellitus, Experimental genetics, Diabetes Mellitus, Experimental physiopathology, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 physiopathology, Diabetic Nephropathies genetics, Diabetic Nephropathies physiopathology, Diabetic Nephropathies urine, Disease Models, Animal, Heart Rate, Male, RNA, Messenger genetics, Rats, Rats, Zucker, Reverse Transcriptase Polymerase Chain Reaction, Aldosterone blood, Diabetes Mellitus, Type 2 blood
- Abstract
Background: Aldosterone is an important mediator of cardiovascular and renal remodeling. Type II diabetes mellitus leads to renal and cardiac end organ damage. We investigated the renin-angiotensin-aldosterone system in a model of type 2 diabetes mellitus with known diabetic nephropathy and cardiac remodeling, the Zucker Diabetic Fatty rat with and without ACE-inhibition (ZDF and ZDF+ACE-I) and its control, the Zucker Lean (ZDL) rat., Methods: Male animals were studied from an age of 7-24 weeks. At ages 7, 14, 17, 20, and 23 weeks, urinary excretion of aldosterone-glucuronide and potassium was assessed. ACE-inhibition with ramipril was started orally at week 13 (1 mg/kg/d). At the end of the study rats were sacrificed and plasma aldosterone concentration and plasma renin activity were measured. Aldosterone synthase (CYP11B2) mRNA expression in the adrenals, kidney, heart and adipose tissue was assessed by real-time PCR. Urinary albumin excretion as marker for diabetic nephropathy was measured in metabolic cages and correlated to aldosterone., Results: Plasma aldosterone concentration and aldosterone-glucuronide was significantly elevated in ZDF rats, and significantly reduced by ACE-inhibiton. In contrast, plasma renin activity was significantly reduced in ZDF rats and normalized by ACE-inhibition. The urinary aldosterone correlated significantly to albuminuria. Adrenal CYP11B2 expression was not significantly higher in ZDF rats. CYP11B2 mRNA was not detected in the kidney, heart and adipose tissue., Conclusion: In ZDF rats, urinary and plasma aldosterone levels were elevated despite reduced plasma renin activity. The reversible effect of ACE-inhibition shows that the up-regulation of aldosterone must be dependent of the renin-angiotensin-system in this type II diabetes model. The correlation between aldosterone and diabetic nephropathy suggests a clinical relevance of this observation.
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- 2009
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14. Epac1 is upregulated during neointima formation and promotes vascular smooth muscle cell migration.
- Author
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Yokoyama U, Minamisawa S, Quan H, Akaike T, Jin M, Otsu K, Ulucan C, Wang X, Baljinnyam E, Takaoka M, Sata M, and Ishikawa Y
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- Animals, Aorta embryology, Aorta growth & development, Aorta metabolism, Cell Shape, Cells, Cultured, Cyclic AMP analogs & derivatives, Cyclic AMP pharmacology, Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors, Cyclic AMP-Dependent Protein Kinases metabolism, Disease Models, Animal, Female, Femoral Artery injuries, Femoral Artery metabolism, Femoral Artery pathology, Gestational Age, Guanine Nucleotide Exchange Factors antagonists & inhibitors, Guanine Nucleotide Exchange Factors genetics, Male, Mice, Mice, Inbred ICR, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular embryology, Muscle, Smooth, Vascular growth & development, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle enzymology, Pregnancy, Protein Kinase Inhibitors pharmacology, Rats, Rats, Wistar, Thionucleotides pharmacology, Time Factors, Transduction, Genetic, Tunica Intima drug effects, Tunica Intima embryology, Tunica Intima growth & development, Up-Regulation, Cell Movement drug effects, Guanine Nucleotide Exchange Factors metabolism, Muscle, Smooth, Vascular metabolism, Myocytes, Smooth Muscle metabolism, Signal Transduction drug effects, Tunica Intima metabolism
- Abstract
Vascular remodeling after mechanoinjury largely depends on the migration of smooth muscle cells, an initial key step to wound healing. However, the role of the second messenger system, in particular, the cAMP signal, in regulating such remodeling remains controversial. Exchange protein activated by cAMP (Epac) has been identified as a new target molecule of the cAMP signal, which is independent from PKA. We thus examined whether Epac plays a distinct role from PKA in vascular remodeling. To examine the role of Epac and PKA in migration, we used primary culture smooth muscle cells from both the fetal and adult rat aorta. A cAMP analog selective to PKA, 8-(4-parachlorophenylthio)-cAMP (pCPT-cAMP), decreased cell migration, whereas an Epac-selective analog, 8-pCPT-2'-O-Me-cAMP, enhanced migration. Adenovirus-mediated gene transfer of PKA decreased cell migration, whereas that of Epac1 significantly enhanced cell migration. Striking morphological differences were observed between pCPT-cAMP- and 8-pCPT-2'-O-Me-cAMP-treated aortic smooth muscle cells. Furthermore, overexpression of Epac1 enhanced the development of neointimal formation in fetal rat aortic tissues in organ culture. When the mouse femoral artery was injured mechanically in vivo, we found that the expression of Epac1 was upregulated in vascular smooth muscle cells, whereas that of PKA was downregulated with the progress of neointimal thickening. Our findings suggest that Epac1, in opposition to PKA, increases vascular smooth muscle cell migration. Epac may thus play an important role in advancing vascular remodeling and restenosis upon vascular injury.
- Published
- 2008
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15. Beta1 and beta2-adrenergic receptor polymorphisms and idiopathic ventricular arrhythmias.
- Author
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Ulucan C, Cetintas V, Tetik A, Eroglu Z, Kayikcioglu M, Can LH, Payzin S, Aydin M, and Hasdemir C
- Subjects
- Adolescent, Aged, Aged, 80 and over, Female, Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, Humans, Incidence, Male, Middle Aged, Risk Factors, Turkey epidemiology, Young Adult, Polymorphism, Single Nucleotide genetics, Receptors, Adrenergic, beta-1 genetics, Receptors, Adrenergic, beta-2 genetics, Risk Assessment methods, Tachycardia, Ventricular epidemiology, Tachycardia, Ventricular genetics
- Abstract
Introduction: Idiopathic ventricular arrhythmias commonly refer to ventricular tachycardia (VT) and/or frequent/monomorphic premature ventricular contractions (PVC) in patients with structurally normal heart. Activation of sympathetic tone has been shown to play an important role in the provocation and maintenance of these arrhythmias. We investigated whether common single nucleotide polymorphisms in the beta(1) and beta(2)-adrenergic receptors are associated with idiopathic ventricular arrhythmias., Methods: A total of 143 unrelated patients presenting with idiopathic ventricular arrhythmias were prospectively included in a case-control association study. Patient population was matched by age and gender to the unrelated, healthy control subjects (N = 307). All study subjects were of Turkish (Anatolian Caucasian) descent. Allele and genotype frequencies of the Gly389Arg and Ser49Gly polymorphisms of the beta(1)-adrenergic receptor and Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms of the beta(2)-adrenergic receptor were compared between patient population and control subjects. The genotype frequencies were in Hardy-Weinberg equilibrium., Results: Patients with idiopathic ventricular arrhythmias had higher frequency of Arg389Arg genotype (22.4% vs 1.6%, P < 0.001), Arg389Gly49 (5.24% vs 0.73%, P = 0.005), and Arg389Ser49 (36.7% vs 13.6%, P < 0.001) haplotypes of the beta(1)-adrenergic receptor, and higher frequency of Gly16Gly (31.5% vs 13.4%, P < 0.001), Glu27Glu genotypes (18.2% vs 10.1%, P = 0.006) and Gly16Gln27Thr164 (15.3% vs 7.4%, P = 0.002), Gly16Glu27Thr164 (13.1% vs 7%, P = 0.004), and Gly16Glu27Ile164 (13.2% vs 6%, P = 0.002) haplotypes of the beta(2)-adrenergic receptor compared to control subjects., Conclusion: Our data suggest that common single nucleotide polymorphisms in the beta(1) and beta(2)-adrenergic receptors are significantly associated with idiopathic ventricular arrhythmias in Turkish population.
- Published
- 2008
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16. Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP.
- Author
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Birner CM, Ulucan C, Fredersdorf S, Rihm M, Löwel H, Stritzke J, Schunkert H, Hengstenberg C, Holmer S, Riegger G, and Luchner A
- Subjects
- Animals, Biomarkers blood, Chronic Disease, Disease Models, Animal, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myocardial Infarction blood, RNA, Messenger blood, Rabbits, Species Specificity, Ventricular Dysfunction, Left blood, Heart Failure blood, Interleukin-6 blood, Natriuretic Peptide, Brain blood, Nerve Tissue Proteins blood, Protein Precursors blood
- Abstract
Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.
- Published
- 2007
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17. Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy.
- Author
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Ulucan C, Wang X, Baljinnyam E, Bai Y, Okumura S, Sato M, Minamisawa S, Hirotani S, and Ishikawa Y
- Subjects
- Adenylyl Cyclases genetics, Adenylyl Cyclases metabolism, Animals, COS Cells, Cardiotonic Agents, Carrier Proteins metabolism, Cell Line, Cell Line, Tumor, Chlorocebus aethiops, Cyclic AMP-Dependent Protein Kinase Catalytic Subunits, Cyclic AMP-Dependent Protein Kinases genetics, Cyclic AMP-Dependent Protein Kinases metabolism, GTP-Binding Protein alpha Subunits, Gs genetics, GTP-Binding Protein alpha Subunits, Gs metabolism, Gene Expression Regulation, Developmental, Guanine Nucleotide Exchange Factors genetics, Heart growth & development, Humans, Hypertrophy, Isoenzymes genetics, Isoenzymes metabolism, Isoproterenol, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Signal Transduction physiology, rap1 GTP-Binding Proteins genetics, rap1 GTP-Binding Proteins metabolism, Guanine Nucleotide Exchange Factors metabolism, Heart embryology, Myocardium metabolism, Myocardium pathology
- Abstract
Although it has been shown that Epac1 mRNA is expressed ubiquitously and Epac2 mRNA predominantly in the brain and endocrine tissues, developmental and pathophysiological changes of these molecules have not been characterized. Developmental changes were analyzed in murine heart, brain, kidneys, and lungs by RT-PCR analysis, which revealed more drastic developmental changes of Epac2 mRNA than Epac1. Only the Epac2 mRNA in kidney showed a transient expression pattern with dramatic decline into adulthood. In addition to developmental changes, we found that Epac gene expression was upregulated in myocardial hypertrophy induced by chronic isoproterenol infusion or pressure overload by transverse aortic banding. Both Epac1 and Epac2 mRNA were upregulated in isoproterenol-induced left ventricular hypertrophy, whereas only Epac1 was increased in pressure overload-induced hypertrophy. Stimulation of H9c2, cardiac myoblast cells, with fetal calf serum, which can induce myocyte hypertrophy, upregulated Epac1 protein expression. We also demonstrated that Epac was the limiting moiety, relative to Rap, in the Epac-Rap signaling pathway in terms of stoichiometry and that Epac stimulation led to the activation of ERK1/2. Our data suggest the functional involvement of Epac in organogenesis and also in physiological as well as pathophysiological processes, such as cardiac hypertrophy. Furthermore, our results suggest the importance of the stoichiometry of Epac over that of Rap in cellular biological effects.
- Published
- 2007
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18. Angiographic analysis of the anatomic relation of coronary arteries to mitral and tricuspid annulus and implications for radiofrequency ablation.
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Hasdemir C, Yavuzgil O, Payzin S, Aydin M, Ulucan C, Kayikcioglu M, Can LH, Turkoglu C, and Kultursay H
- Subjects
- Adolescent, Adult, Aged, Arrhythmias, Cardiac diagnostic imaging, Catheter Ablation adverse effects, Coronary Stenosis diagnostic imaging, Coronary Stenosis etiology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Postoperative Complications, Predictive Value of Tests, Prognosis, Prospective Studies, Arrhythmias, Cardiac surgery, Catheter Ablation methods, Coronary Angiography, Coronary Vessels, Mitral Valve diagnostic imaging, Tricuspid Valve diagnostic imaging
- Abstract
Coronary artery (CA) narrowings and/or occlusions after radiofrequency ablation (RFA) have been reported. The aim of this study was to describe the in vivo topographic anatomy of CAs and their anatomic relation to the mitral and tricuspid annulus using selective coronary angiography. Fifty consecutive patients undergoing RFA for narrow QRS complex tachycardia were included in the study. Multipolar electrode catheters were inserted into the right atrial appendage, His bundle region, distal coronary sinus (CS), and right ventricle. A mapping catheter was placed across the subeustachian isthmus (SEI). Selective coronary angiography was performed. The maximum and minimum distances between the distal CAs and the mapping catheter located along the mitral and tricuspid annulus were measured during systole and diastole and in right and left anterior oblique projections. The large (> or =1.5 mm) distal right CA was < or =5 mm from the mapping catheter in the SEI in 4 patients (8%). The large posterolateral branch of the right CA was < or =2 mm from the CS Os-middle cardiac vein in 10 patients (20%). The large left circumflex CA was < or =2 mm from the floor or ceiling of the CS in 7 patients (14%) and < or =2 mm from the CS catheter at the lateral and anterolateral mitral annulus in 12 patients (24%). RFA was canceled in 2 patients because of the close proximity (< or =2 mm) of the distal CA to the ablation site. In conclusion, large CAs are frequently located in close proximity to the common ablation sites. Coronary angiography should be considered in children and adults who may develop any signs or symptoms suggestive of acute CA occlusion until larger controlled series are available.
- Published
- 2007
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19. cAMP-mediated regulation of CYP enzymes and its application in chemotherapy.
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Ishikawa Y, Suzuki S, Otsu K, Ulucan C, Iwatsubo K, and Eguchi H
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- Adenylyl Cyclases metabolism, Animals, Antineoplastic Agents therapeutic use, Cyclic AMP metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, Enzyme Activators pharmacology, Humans, Neoplasms drug therapy, Phosphorylation, Prodrugs therapeutic use, Antineoplastic Agents metabolism, Cytochrome P-450 Enzyme System metabolism, Prodrugs metabolism
- Abstract
Certain anti-cancer prodrugs are subject to cytochrome P450 (CYP)-mediated metabolism and become more active. Because CYP activity may be regulated by phosphorylation via adenylyl cyclase/protein kinase A, selective adenylyl cyclase subtype activators may be utilized in future chemotherapy to regulate CYP activity as a switch in a tumor tissue-specific manner.
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- 2007
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20. Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats.
- Author
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Fredersdorf S, Weil J, Ulucan C, Birner C, Büttner R, Schubert T, Böger CA, Debl K, Muders F, Riegger GA, and Luchner A
- Subjects
- Angiotensin-Converting Enzyme Inhibitors pharmacology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Animals, Antihypertensive Agents pharmacology, Antihypertensive Agents therapeutic use, Atrial Natriuretic Factor blood, Blood Glucose metabolism, Blood Pressure drug effects, Diabetes Mellitus, Experimental blood, Diabetes Mellitus, Experimental physiopathology, Heterocyclic Compounds, 3-Ring pharmacology, Heterocyclic Compounds, 3-Ring therapeutic use, Male, Microscopy, Polarization methods, Podocytes pathology, Protease Inhibitors therapeutic use, Proteinuria physiopathology, Ramipril therapeutic use, Rats, Rats, Zucker, Renin-Angiotensin System drug effects, Triglycerides blood, Weight Gain drug effects, Diabetes Mellitus, Experimental drug therapy, Neprilysin antagonists & inhibitors, Podocytes drug effects, Protease Inhibitors pharmacology, Proteinuria drug therapy
- Abstract
Inhibition of the renin angiotensin aldosterone system (RAAS) produces protective effects on cardio-renal injury in type 2 diabetes. Vasopeptidase inhibitors (VPI) represent a new pharmacological tool, acting by simultaneous inhibition of the RAAS and neutral endopeptidase. We examined the effects of chronic VPI on renal function and morphology in experimental type 2 diabetes as compared to angiotensin converting enzyme inhibition (ACE-I). Zucker diabetic fatty rats aged 13 weeks were treated with either VPI (AVE7688, ZDF-VPI, n = 8) or ACE-I (Ramipril, ZDF-ACE-I, n = 7) or placebo (ZDF, n = 8). Heterozygous rats served as non-diabetic controls (Ctr, n = 8). Both treatments led to a similar decrease in blood pressure. After 10 weeks of treatment, ZDF developed marked albuminuria. The latter was significantly attenuated in ZDF-VPI as compared to ZDF and ZDF-ACE-I. Renal histology revealed a significant expansion in the glomerular tuft area in all ZDF groups. However, expression of glomerular desmin, which has been recognized as a sensitive marker of early podocyte damage, was significantly increased in ZDF as compared to Ctr. Desmin was reduced in ZDF-VPI but not in animals treated with ACE-I. There was a correlation between albumin excretion and desmin-positive glomerular area. In experimental type 2 diabetes, albuminuria correlates to podocyte damage. These hallmarks of diabetic nephropathy are attenuated by VPI to a greater extent than by ACE-I alone. These findings suggest that podocyte damage is an early critical step in the progression of diabetic nephropathy, and that VPI is a promising pharmacological tool in the treatment of diabetic renal disease.
- Published
- 2007
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21. Demonstration of ventricular myocardial extensions into the pulmonary artery and aorta beyond the ventriculo-arterial junction.
- Author
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Hasdemir C, Aktas S, Govsa F, Aktas EO, Kocak A, Bozkaya YT, Demirbas MI, Ulucan C, Ozdogan O, Kayikcioglu M, Can LH, and Payzin S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cadaver, Chi-Square Distribution, Female, Humans, Male, Middle Aged, Tachycardia, Ventricular pathology, Aorta, Thoracic anatomy & histology, Heart Ventricles anatomy & histology, Pulmonary Artery anatomy & histology
- Abstract
Background: A subgroup of outflow tract (OT) ventricular tachycardias (VT) originate from the aortic sinuses or the main stem of the pulmonary artery. The anatomic substrate for these tachycardias is unknown. The aim of this study was to investigate the presence of ventricular myocardial extensions (VME) into the pulmonary artery (PA) and aorta (Ao) beyond the ventriculo-arterial junction (VAJ) and determine the anatomical and histological characteristics of these muscle extensions., Methods: Ninety-five consecutive human hearts obtained at autopsy were studied. Longitudinal strips of tissue containing each cusp, aortic, and pulmonary artery walls and left and right ventricular outflow tracts were excised and histologically analyzed. Anatomical measurements, including length and thickness of VMEs, obtained at autopsy, were made., Results: VMEs beyond the VAJ were found in 21 of 95 (22%) patients studied. VMEs were found in 16 of 95 PAs (17%) and 7 of 95 Aos (7%) were examined. VMEs were located within the adventitia in 23 (88%) and on the epicardial surface in three (12%). The majority of VMEs were in continuity with the underlying ventricular OT muscle tissue. Myocellular hypertrophy and fibrosis were present in 19 (73%) and fatty tissue between the layers of VME in 18 (69%). Clinical data were available in 14 of 21 patients with positive VME. None of the patients (clinical data available group) had history of cardiac disease or signs or symptoms (palpitations or syncope) of cardiac disease., Conclusions: VMEs into the PA and Ao beyond the VAJ are relatively common. It seems that their mere presence does not predispose to OT VTs. There are probably intrinsic arrhythmogenic properties in tissues specific to these regions in those patients who develop OT VTs.
- Published
- 2007
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- View/download PDF
22. Brugada-type ECG pattern and extreme QRS complex widening with propafenone overdose.
- Author
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Hasdemir C, Olukman M, Ulucan C, and Roden DM
- Subjects
- Adolescent, Drug Overdose, Female, Humans, Suicide, Attempted, Syndrome, Bundle-Branch Block chemically induced, Bundle-Branch Block diagnosis, Electrocardiography drug effects, Heart Conduction System drug effects, Propafenone poisoning, Ventricular Fibrillation chemically induced, Ventricular Fibrillation diagnosis
- Published
- 2006
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23. Isotretinoin (13-cis-retinoic acid) associated atrial tachycardia.
- Author
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Hasdemir C, Sagcan A, Sekuri C, Ildizli M, Ulucan C, and Ceylan C
- Subjects
- Acne Vulgaris drug therapy, Adolescent, Diagnosis, Differential, Electrocardiography, Humans, Male, Isotretinoin adverse effects, Tachycardia, Supraventricular chemically induced
- Abstract
We describe a 16-year-old boy who presented with palpitations for 1 week while being on isotretinoin treatment for nodulocystic facial acne for 3 months. Twenty four-hour Holter monitoring showed frequent premature atrial beats and episodes of nonsustained atrial tachycardia. He never had any episodes of palpitations previously. His complaints almost disappeared within a week after stopping the treatment. He remained asymptomatic since the discontinuation of the drug. The temporal relationship between isotretinoin treatment and patient's symptoms in the presence of documented arrhythmia suggests a drug-related cause. As a result, clinicians should be aware of the possible arrhythmogenic effect of isotretinoin.
- Published
- 2005
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24. Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats.
- Author
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Fredersdorf S, Thumann C, Ulucan C, Griese DP, Luchner A, Riegger GA, Kromer EP, and Weil J
- Subjects
- Animals, Atrial Natriuretic Factor metabolism, Blotting, Northern, Cardiomegaly drug therapy, Cardiomegaly pathology, Collagen Type I, Diabetes Mellitus, Experimental drug therapy, Diabetes Mellitus, Experimental physiopathology, Echocardiography, Fibronectins, Fibrosis pathology, Heart Ventricles drug effects, Heart Ventricles pathology, Image Processing, Computer-Assisted, Immunohistochemistry, Insulin therapeutic use, Laminin, Male, Myocardial Contraction drug effects, Myocardium pathology, RNA, Messenger analysis, Rats, Rats, Zucker, Cardiomegaly etiology, Diabetes Mellitus, Experimental pathology, Hyperinsulinism physiopathology, Myocardial Contraction physiology, Ventricular Function
- Abstract
Heart failure is known to be a complication of insulin-dependent (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) even in the absence of coronary heart disease or hypertension. The mechanisms leading to diabetic cardiomyopathy are unknown. The aim of the study was to characterize structural and functional alterations in hyperinsulinemic Zucker diabetic fatty (ZDF) rats treated with or without insulin. Diabetic animals showed a twofold increase in cardiomyocyte volume with increased left ventricular ANP but not BNP mRNA levels in spite of a reduced plasma renin activity (PRA) 2 months after onset of diabetes compared to nondiabetic littermates. These changes were associated with an increase in left ventricular performance as assessed by echocardiography. Insulin treatment led to a significant increase in body weight (BW), total heart weight, myocardial protein content, and left ventricular mass (LVM). Perivascular fibrosis and laminin thickness were significantly augmented in diabetic rat myocardium irrespective of insulin treatment, whereas interstitial collagen I and fibronectin were similarly found in diabetic and control myocardium. Initial stages of diabetic cardiomyopathy in hyperinsulinemic rats are characterized by cardiomyocyte hypertrophy and enhanced cardiac contractility. It is suggested that hyperinsulinemia may be involved in cardiac hypertrophy.
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- 2004
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25. Effects of acetylsalicylic acid and morphine on neurons of the rostral ventromedial medulla in rat.
- Author
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Ulucan C, Schnell C, Messlinger K, and Ellrich J
- Subjects
- Analgesics, Opioid administration & dosage, Animals, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Aspirin administration & dosage, Electromyography, Injections, Intravenous, Jaw innervation, Male, Medulla Oblongata drug effects, Medulla Oblongata physiology, Microelectrodes, Morphine administration & dosage, Muscle, Skeletal drug effects, Muscle, Skeletal physiology, Neurons physiology, Nociceptors drug effects, Nociceptors physiology, Rats, Rats, Wistar, Reflex drug effects, Analgesics, Opioid pharmacology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Aspirin pharmacology, Morphine pharmacology, Neurons drug effects
- Abstract
Morphine exerts its analgesic effect via the endogenous pain control system consisting of the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM). Acetylsalicylic acid (ASA) may also act via this system, but so far this has only been demonstrated for the inhibitory effect on the tail-flick reflex with extremely high doses (200-300 mg/kg). Both drugs show synergistic effects on PAG neurons in vitro. It is unclear whether this mechanism accounts for the well-known analgesic synergism of these drugs in vivo. Thus, the effects of ASA (30 mg/kg) and morphine on off- and on-cells in the RVM and the jaw-opening reflex (JOR) were investigated in anesthetized rats. Under morphine, off-cell activity increased (+34%), on-cell activity decreased (-98%) and the reflex was suppressed (-53%). ASA increased off-cell activity (+20%) and decreased the activity of on-cells (-52%). After preceding ASA administration, the effects of morphine on off- and on-cells and on the reflex did not alter statistically. The experiments document the modulatory effect of a clinically relevant dose of ASA on RVM cells. This effect resembles that of morphine. The results do not support the hypothesis of a mediation of the analgesic synergism of morphine and ASA by the PAG-RVM-network in vivo.
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- 2003
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26. Atypical on-, off- and neutral cells in the rostral ventromedial medulla oblongata in rat.
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Schnell C, Ulucan C, and Ellrich J
- Subjects
- Action Potentials drug effects, Afferent Pathways drug effects, Afferent Pathways physiology, Analgesics, Opioid pharmacology, Animals, Hot Temperature adverse effects, Male, Medulla Oblongata cytology, Medulla Oblongata drug effects, Morphine pharmacology, Neural Inhibition drug effects, Neurons cytology, Neurons drug effects, Nociceptors drug effects, Nociceptors physiology, Physical Stimulation adverse effects, Raphe Nuclei cytology, Raphe Nuclei drug effects, Rats, Rats, Wistar, Reticular Formation cytology, Reticular Formation drug effects, Action Potentials physiology, Medulla Oblongata physiology, Neural Inhibition physiology, Neurons physiology, Pain physiopathology, Raphe Nuclei physiology, Reticular Formation physiology
- Abstract
It is generally assumed that the response pattern of on-, off- and neutral cells in the rostral ventromedial medulla (RVM) to noxious stimulation is independent of stimulation site. But recent studies have shown that a remarkable number of RVM neurons do not have whole-body receptive fields. These so-called atypical neurons were extracellularly recorded in lightly anaesthetized rats. The receptive fields to noxious thermal and mechanical stimulation applied to the tail, the extremities and the craniofacial region were determined in 57 RVM neurons. In 24 atypical off-cells, 12 on-cells and 21 neutral cells, the response pattern evoked by noxious pinch to the nose, forehead and ear most frequently differed from the responses to noxious tail heat. The modulatory effects of intravenously administered morphine were examined in 21 cells. In contrast to the general assumption that morphine activates off-cells, inhibits on-cells and has no effect on neutral cells, in atypical RVM neurons 5 of 6 off-cells, 2 of 6 on-cells and 5 out 9 neutral cells showed a different response pattern to systemical administration of morphine. The results show that a RVM cell classification that is exclusively based on the behaviour to noxious tail heat can neither sufficiently predict the response pattern to different noxious stimuli, especially in the craniofacial region, nor reliably predict the modulatory effect of morphine in RVM neurons. The fact that the neutral cells responded in an off or on manner to noxious stimulation different from noxious tail heat and that morphine modulated activity in many neutral cells suggests that these cells are probably subtypes of on- and off-cells.
- Published
- 2002
- Full Text
- View/download PDF
27. Is the response pattern of on- and off-cells in the rostral ventromedial medulla to noxious stimulation independent of stimulation site?
- Author
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Ellrich J, Ulucan C, and Schnell C
- Subjects
- Animals, Electromyography, Forelimb, Hindlimb, Hot Temperature, Male, Pain physiopathology, Physical Stimulation, Rats, Rats, Wistar, Reticular Formation physiology, Tail, Medulla Oblongata physiology, Nociceptors physiology, Raphe Nuclei physiology, Trigeminal Nerve physiology
- Abstract
The classification of on- and off-cells in the rostral ventromedial medulla is based on the response pattern to noxious tail heat. It is generally assumed that on- and off-cells respond equally to noxious stimulation anywhere on the body surface, but so far this assumption has not been systematically examined. In the present study the effects of noxious thermal and mechanical stimuli applied to the tail, the extremities and the craniofacial region on the extracellularly recorded activity of 13 on- and 23 off-cells were investigated in lightly anesthetized rats. In 3 out of 13 on-cells and 11 out of 23 off-cells the response pattern evoked by noxious stimulation of the extremities or the craniofacial region differed from the response pattern elicited by noxious tail heat. In comparison with the response pattern to noxious tail heat, stimulation of the extremities or the craniofacial region reproducibly evoked opposite reactions in 2 on- and 9 off-cells and did not change neuronal activity in one on- and 2 off-cells. The results of the present study raise the question of whether the response pattern of on- and off-cells in the rostral ventromedial medulla can be sufficiently predicted by a classification that is exclusively based on the cellular behavior to noxious heat stimulation of the tail.
- Published
- 2001
- Full Text
- View/download PDF
28. Are 'neutral cells' in the rostral ventro-medial medulla subtypes of on- and off-cells?
- Author
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Ellrich J, Ulucan C, and Schnell C
- Subjects
- Action Potentials physiology, Animals, Hot Temperature adverse effects, Male, Medulla Oblongata cytology, Neurons cytology, Nociceptors cytology, Pain pathology, Physical Stimulation adverse effects, Raphe Nuclei cytology, Rats, Rats, Wistar, Reticular Formation cytology, Medulla Oblongata physiology, Neurons classification, Neurons physiology, Nociceptors physiology, Pain physiopathology, Raphe Nuclei physiology, Reticular Formation physiology
- Abstract
The classification of cells in the rostral ventromedial medulla (RVM) is based on the response pattern to noxious tail heat: on-cell activity increased, off-cell activity decreased, and activity of neutral cells is unaffected by noxious heat tail stimulation. It is generally assumed that on-, off- and neutral cells respond equally to noxious stimulation applied anywhere on the body surface, but so far this assumption has not been systematically examined. In the present study the effects of thermal and mechanical stimuli applied to the tail, the extremities and the orofacial region on the extracellularly recorded activity of 14 neutral cells were investigated in lightly anesthetized rats. Although the neutral cells did not respond to noxious tail heat, all of them responded to most of the other stimuli in an on- or off-manner. Especially cell responses to pinch stimuli applied to the skin of the ear, the forehead and the nose differed from the neutral behavior. The fact that the neutral cells in the present study responded in an off- or on-manner by applying noxious stimuli different from noxious tail heat suggests that these cells are possibly subtypes of on- and off-cells in the RVM.
- Published
- 2000
- Full Text
- View/download PDF
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