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Biomedical subjects

C Barlas

Publications and source records attributed to C Barlas.

At least 19 recordsLinked to original sources

Differential regulation of striatal G protein levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration in C57 BL/6 mice.

The dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to produce a severe Parkinsonian state in both humans and animals. Unlike idiopathic Parkinson's disease, however, most MPTP models show some degree of behavioral recovery with time. Here we report that stimulatory G proteins are differentially regulated in the striatum of C57 BL/6 mice following systemic MPTP administration. As measured by Western blotting, the striatal stimulatory G proteins Gs and Golf were reduced by 20% and 25% at 10 days following cessation of MPTP treatment, despite a significant impairment in striatal dopamine levels (<90% reduction). Conversely, Gs and Golf levels were upregulated by 15% and 30% at 10 months following MPTP withdrawal. No change was observed in striatal inhibitory G proteins or any cortical G protein at any time post-treatment. These results suggest that G protein upregulation may play a role in mediating behavioral recovery following MPTP administration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Modulation of dopamine receptor agonist-induced rotational behavior in 6-OHDA-lesioned rats by a peptidomimetic analogue of Pro-Leu-Gly-NH2 (PLG).

The present study was undertaken to determine if the previously reported in vitro interactions of the Pro-Leu-Gly-NH2 (PLG) peptidomimetic analogue 3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacet amide (PAOPA) with the dopaminergic system could be exhibited in an in vivo animal model using 6-hydroxydopamine (6-OHDA)-lesioned rats. In this model, PAOPA was found to potentiate the contralateral rotational behavior induced by either apomorphine or L-DOPA. PAOPA was 100-fold more potent than PLG, and produced a fourfold greater response than PLG when administered i.p. PAOPA also potentiated contralateral rotations induced by SKF-38393 and quinpirole. In summary, the results of this study indicate that PAOPA, a conformationally constrained peptidomimetic analogue of PLG, can modulate dopaminergic activity in vivo with higher potency and efficacy than PLG.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Modulation of brain catecholamine absorbing proteins by dopaminergic agents.

Catecholamine absorbing proteins (CATNAPs) are localized in the brain and thus far have no known biochemical and pharmacological characteristics consistent with other receptor proteins or metabolic enzymes in the central nervous system. The oxidative metabolism of catecholamines in the brain, especially the catabolism of dopamine and its conjugation with metabolic brain proteins, results in the production of highly toxic free radicals. Since such processes are implicated in the pathophysiology of various neurodegenerative diseases, including parkinsonism, and since CATNAPs bind catecholamines with high affinity, there is a need to further investigate if these novel proteins could play a protective role against these harmful catecholamine metabolites. In this study, we demonstrate the purification, pharmacological characterization and modulation of CATNAPs, as the first steps necessary to elucidate the function of these proteins in the brain. First, CATNAPs were identified from tissues using [3H]N-n-propylnorapomorphine (a specific dopamine receptor agonist) and [125I]6-hydroxy-5-iodo[N(N-2,4-dinitro-phenyl)- aminopropyl]1,2,3,4-tetrahydronaphthalene ([125I]DATN; a highly specific ligand synthesized in our laboratory). Three proteins, with molecular masses of 47, 40 and 26 kDa, were identified and purified, which allowed for the subsequent production of antibodies against each of these CATNAPs. The effects of in vivo chronic administration of several dopaminergic agents on CATNAPs were also examined by Western immunoblotting. L-3,4-Dihydroxyphenylalanine (L-DOPA) treatment in rats resulted in the increase of all of the three proteins, as compared to controls. Treatment in rats with the dopamine depleting agent, reserpine, produced a significant decrease in all of the three CATNAPs. In addition, the effects of direct administration of apomorphine, dopamine, epinephrine, isopropylnorepinephrine, norepinephrine, N-n-propylnorapomorphine and 6-hydroxydopamine on CATNAP levels in rats were examined. Interestingly, we observed an increase (as compared to control) of the 47, 40 and 26 kDa proteins in animals treated with dopamine, norepinephrine, N-n-propylnorapomorphine and apomorphine. In contrast, animals treated with 6-hydroxydopamine showed significant decreases in the levels of all three proteins. It is evident that as the concentration of catecholamines increases, there is a corresponding increase in the levels of CATNAPs in the brain. These results clearly demonstrate the pharmacological modulation of CATNAPs by dopaminergic agents and suggest their possible role in the cytoprotection against damage caused by free radicals generated by oxidative stress.

Adrenergic Uptake Inhibitors↗

A neurochemical basis for the antipsychotic activity of loxapine: interactions with dopamine D1, D2, D4 and serotonin 5-HT2 receptor subtypes.

Loxapine is a typical neuroleptic that shows great structural and functional homology to the atypical antipsychotic clozapine. Chronic loxapine treatment is usually associated with extrapyramidal symptoms (EPS), whereas clozapine treatment is not. Conversely, loxapine does not produce the agranulocytosis that often results from protracted clozapine treatment. Earlier studies of loxapine have usually implicated D2 receptor blockade as the cause of the tardive dyskinesia that occurs with chronic treatment. More recently, loxapine's ability to potentiate serotonergic neurotransmission has also been implicated. In this study, the pharmacological affinities of loxapine for the dopamine D1, D2, D4, as well as serotonin-2 (5-HT2) and NMDA receptor subtypes, were investigated through direct radioreceptor assays. The findings indicate that loxapine displays an extremely strong binding affinity for dopamine D4 and serotonin 5-HT2 receptors, which suggests that both serotonergic and dopaminergic mechanisms contribute to the antipsychotic drug action and EPS associated with loxapine in the treatment of schizophrenia.

Antipsychotic Agents↗

Giant congenital coronary artery fistula to left superior vena cava and right atrium with compression of left pulmonary vein simulating cor triatriatum--diagnostic value of magnetic resonance imaging.

A 3-year-old girl with a continuous murmur on auscultation was found to have left coronary artery to right atrial fistula simulating cor triatriatum sinister on echocardiography. Coronary angiography of the patient was also insufficient to clarify the exact pathologic anatomy. Magnetic resonance imaging showed that the main drainage of the aneurysmal coronary artery was to the left superior vena cava, resulting in a diffuse arteriovenous fistula in the lower lobe of the left lung by compressing its pulmonary vein.

Child, Preschool↗

Unusual complication of femoro-popliteal saphenous vein bypass--aneurysm formation.

An aneurysm as an unusual complication of saphenous vein bypass for femoro-popliteal occlusive disease is reported. The aneurysm developed 1 year following the bypass procedure. A diagnosis of Behçet's disease based on microscopic immunological examination and the clinical picture was suspected following successful aneurysmectomy.

Anastomosis, Surgical↗

Tuberculous otitis media in a four-month-old infant.

Tuberculosis of the middle ear is currently a rare disease but still occurs and may cause permanent hearing loss. A four-month-old infant with chronic left-ear drainage was diagnosed with tuberculous otitis media by biopsy examination and PPD positivity without BCG. He was treated successfully with antituberculous therapy. Tuberculosis should be considered in the differential diagnosis of chronic ear infection, especially in young infants.

Humans↗

Ruptured abdominal aortic aneurysm with fistula into the right iliac vein.

Arteriovenous fistula between major abdominal vessels is an unusual complication of ruptured abdominal aortic aneurysm. It most frequently occurs between the aorta and the inferior vena cava, however, it is rare when occurring between the aorta and iliac veins. A case of an arteriovenous fistula (AVF), secondary to erosion of an arteriosclerotic abdominal aortic aneurysm into both the retroperitoneum and the iliac vein is presented. The literature is reviewed and the symptoms and the treatment are discussed.

Aorta, Abdominal↗