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Biomedical subjects

H Caner

Publications and source records attributed to H Caner.

At least 37 records · Page 2Linked to original sources

Antioxidant action of the antiarrhythmic drug mexiletine in brain membranes.

Mexiletine is a class Ib antiarrhythmic drug used in the treatment of ventricular arrhythmias. The Na+ channel blocker mexiletine inhibits calcium influx in cells via decreasing reverse operation of the Na+-Ca2+ exchanger. Thus this drug is shown to protect the CNS white matter against anoxic/ischemic injury. The aim of our study was to investigate if this drug could act as an antioxidant drug as well. The antioxidant action of this drug was studied under different oxidant conditions in vitro, and thiobarbituric acid-reactive substances were measured to follow lipid peroxidation. Mexiletine inhibited iron-ascorbate-H2O2-induced lipid peroxidation in brain membranes, liver microsomes and phospholipid liposomes, being most effective in brain membranes. The inhibition was dose- and time-dependent. Mexiletine also inhibited copper-ascorbate-H2O2-induced lipid peroxidation but to a lesser extent. It is concluded that mexiletine has a dual effect toward oxidative injury in brain, both by inhibiting Na+-Ca2+ exchanger-dependent Ca2+ influx and by acting as an inhibitor of lipid peroxidation. However, as this drug is effective at millimolar concentrations, it should be considered less active than natural antioxidants that are effective at micromolar concentrations.

Animals↗

Intracranial meningiomas. Analysis of 344 surgically treated cases.

The authors present 344 (230 females, 114 males) surgical cases of intracranial meningioma. A total of 370 interventions (344 primary procedures, 10 reexplorations for neurologic deterioration, 16 operations for recurrence) were made. Mean follow-up was 38 months. The overall evaluation revealed that 306 (88.95%) patients were completely normal or in a better condition than before operation. 18 (5.23%) were in a worse condition after operation and 20 (5.81%) died. Results suggested that complications and mortality were mostly related to localization and large volume; we also still have problems with aggressive and malignant meningiomas.

Adult↗

Interesting radiologic findings in suprasellar mass lesions. Report of three cases.

The authors report three quite rare lesions of the sellar/parasellar region. They are namely; pituitary abscess, cystic macroadenoma and osteochondroma. In none of the cases, the preoperative diagnostic priority was not same as the final histopathologic diagnosis. The radiologic findings of these pathologies are discussed with emphasis on differential diagnosis.

Abscess↗

A genetic animal model of human neocortical heterotopia associated with seizures.

Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner. The bilateral heterotopia is prominent below the frontal and parietal neocortices but is rarely observed in temporal neocortex. Neurons in the heterotopia exhibit neocortical-like morphologies and send typical projections to subcortical sites; however, characteristic lamination and radial orientation are disturbed in the heterotopia. The period of neurogenesis during which cells in the heterotopia are generated is the same as in the normotopic neocortex; however, the cells in the heterotopia exhibit a "rim-to-core" neurogenetic pattern rather than the characteristic "inside-out" pattern observed in normotopic neocortex. Similar to the human syndrome of double cortex, some of the animals with the tish phenotype exhibit spontaneous recurrent electrographic and behavioral seizures. The tish rat is a unique neurological mutant that shares several features with a human cortical malformation associated with epilepsy. On the basis of its regional connectivity, histological composition, and period of neurogenesis, the heterotopic region in the tish rat is neocortical in nature. This neurological mutant represents a novel model system for investigating mechanisms of aberrant neocortical development and is likely to provide insights into the cellular and molecular events contributing to seizure development in dysplastic neocortex.

Animals↗

An unusual dumbbell form of cavernous hemangioma of the cervical spine.

Cavernous hemangiomas are vascular malformations of the central nervous system that may rarely affect the epidural space of the spine. We report a case of an epidural cavernous hemangioma which was originating from the left C8 nerve root and extending anteriorly to the apex of the left lung.

Adult↗

An alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective.

Overactivation of calcium-activated neutral protease (calpain) has been implicated in the pathophysiology of several degenerative conditions, including stroke, myocardial ischemia, neuromuscular degeneration, and cataract formation. Alpha-mercaptoacrylate derivatives (exemplified by PD150606), with potent and selective inhibitory actions against calpain, have been identified. PD150606 exhibits the following characteristics: (i) Ki values for mu- and m-calpains of 0.21 microM and 0.37 microM, respectively, (ii) high specificity for calpains relative to other proteases, (iii) uncompetitive inhibition with respect to substrate, and (iv) it does not shield calpain against inactivation by the active-site inhibitor trans-(epoxysuccinyl)-L-leucyl-amido-3-methylbutane, suggesting a nonactive site action for PD150606. The recombinant calcium-binding domain from each of the large or small subunits of mu-calpain was found to interact with PD150606. In low micromolar range, PD15O6O6 inhibited calpain activity in two intact cell systems. The neuroprotective effects of this class of compound were also demonstrated by the ability of PD150606 to attenuate hypoxic/hypoglycemic injury to cerebrocortical neurons in culture and excitotoxic injury to Purkinje cells in cerebellar slices.

Acrylates↗

Attenuation of AMPA-induced neurotoxicity by a calpain inhibitor.

The effects of a membrane-permeable inhibitor of calpain, Cbz-Val-Phe-H, were examined in an in vitro model of neurotoxicity. Cerebellar slices from young rats were treated with the glutamate receptor agonist, amino-3-hydroxy-5-methyl-4-isoazole propionic acid (AMPA), and cytotoxicity was quantified using conventional histological techniques. Slices treated with AMPA exhibited damage to 83.0% of cerebellar Purkinje cells. In contrast, only 23.6% of Purkinje cells were damaged in slices treated with Cbz-Val-Phe-H and AMPA. These findings indicate that calcium-activated proteolysis is a critical event in AMPA-induced toxicity, and provide evidence that calpain inhibitors are capable of attenuating this form of excitotoxic damage in the central nervous system.

Amino Acid Sequence↗

Lipid peroxide level increase in experimental hydrocephalus.

The aetiology of incomplete adrenergic denervation and reduction in the number and caliber of the cerebral vessels in hydrocephalus is still obscure. Stretching of the blood vessels alone is far from explaining these major vascular changes. Previous studies have shown that increased lipid peroxidation produces toxic effects on vessels. This experimental study was designed to investigate the possible aetiology of vascular changes in hydrocephalic rats with special reference to lipid peroxidation. Hydrocephalus was induced by injecting 50 mg/Kg sterilized kaolin suspension into the cisterna magna in 10 rats (Group A). A sham operation was performed for Group B. After three weeks the rats were anaesthetized and perfused transcardially. The brains were dissected, and cut to visualize the degree of hydrocephalus. The arteries of the circle of Willis were removed for light microscopic examination and the brains were kept for the measurement of lipid peroxidation levels. Light microscopic studies of cerebral arteries in hydrocephalic rats revealed spastic vessels with folding and corrugation of the lamina elastica. The level of lipid peroxidation in group A (260 +/- 9.129 nmol TBAR/gr wet tissue) was significantly higher than that of group B (106 +/- 3.59 nmol TBAR/gr wet tissue). It is suggested that vascular changes observed in hydrocephalic rats may be due to the high level of lipid peroxidation, which in turn may be the consequence of ischaemia caused by the hydrocephalus related stretching of cerebral vessels.

Animals↗

Effect of systemic hypotension on cerebral energy metabolism during chronic cerebral vasospasm in primates.

The influence of systemic hypotension on cerebral blood flow (CBF) and energy metabolism during chronic cerebral vasospasm after subarachnoid hemorrhage was studied in 15 monkeys. Changes in the phosphorus spectrum, as demonstrated by in vivo phosphorus-31 (31P) magnetic resonance (MR) spectroscopy, or in regional CBF were measured in the parietal cortex during graded hypotension. Sequential changes in the phosphorus spectrum were observed during moderate hypotension in the animals 7 days after the introduction of an autologous blood clot around the right middle cerebral artery (MCA). Angiograms revealed a reduction in vessel caliber by approximately 50% in the right MCA. The mean CBF in the spasm side decreased in parallel with a decrease in the mean arterial blood pressure (MABP) from 120 to 40 mm Hg, indicating the abolition of autoregulation. There were no significant differences in the mean percentage totals of inorganic phosphate (Pi), phosphocreatine (PCr), adenosine triphosphate (ATP), and pH between the hemispheres at baseline MABP before hypotension. The values of PCr, ATP, and pH decreased significantly (p < 0.05) and Pi increased significantly (p < 0.05) at an MABP of less than 60 mm Hg in the involved hemisphere. The ratio of PCr:Pi decreased in parallel with a decrease in MABP. The ATP showed a stepwise decrease during moderate hypotension (MABP 60 mm Hg) and was reduced significantly 20 minutes after the beginning of hypotension (p < 0.05). The results indicate that, during chronic vasospasm, changes in cerebral energy metabolism are coupled with changes in CBF in the state of impaired autoregulation. There exists a critical level for ischemia below which high-energy phosphorus metabolites become markedly depleted. It is suggested that 31P MR spectroscopy may be useful to evaluate the ischemic vulnerability of brain tissue in order to prevent delayed neurological deficit during cerebral vasospasm.

Animals↗

Meningiomas of the lateral ventricle. Report on six cases.

In this study 6 patients who had meningioma of the lateral ventricle are reviewed. The incidence is 1.8% of cases of meningiomas in our series. Microsurgical techniques were employed in all patients. There was no death and the follow-up period was between 5 months and 10 years. No recurrence was seen. Although the origin of these tumors is still not known, DUNN and KERNOHAN note that the choroid plexus has the potential for the production of meningothelial, fibrous, or mixed patterns. Our pathological results confirmed this suggestion.

Adult↗

Effects of hydrocephalus on the sympathetic nerves of cerebral arteries, investigated with WGA-HRP anterograde tracing in the rat.

The effects of hydrocephalus on the plexus of sympathetic nerves of the intracranial vessels were investigated using wheat germ agglutinin combined with horseradish peroxidase (WGA-HRP). Hydrocephalus was induced by injection of kaolin into the cisterna magna of rats. Three weeks later the superior cervical ganglion (SCG) of one side received WGA-HRP. Three days later the circle of Willis and the contralateral superior cervical ganglion were dissected out. The intensity of labelling and density on the cerebral vessels and the number of labelled neurons on the contralateral superior cervical ganglion were calculated. The intensity of labelled nerves and thick bundles were significantly decreased, although tracing the nerve fibers throughout the length of the vessels was possible. The number of labelled neurons in the contralateral superior cervical ganglion indicated that the injection technique of WGA-HRP into the ganglion was correct in all rats. These results are in favour of the assumption, that the hydrocephalus related incomplete adrenergic denervation of the sympathetic perivascular nerve plexus was mainly due to neuropraxia of the nerve fibers rather than anatomical interruption of the axons.

Animals↗

Low density in the posterior aspect of the intervertebral disk in the patient with herniated nucleus pulposus. A prospective study of 50 cases.

It was previously reported that a low density are in the posterior aspect of the intervertebral disk is an additional computed tomography (CT) finding suggesting a herniated nucleuos pulposus. In this report the incidence of this finding, its correlation with the duration of symptoms and severity of herniation, were studied on 59 herniated intervertebral disks of 50 cases.

Adult↗