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Biomedical subjects

H Caner

Publications and source records attributed to H Caner.

At least 19 recordsLinked to original sources
PubMed2000

Systemic administration of mexiletine for attenuation of cerebral vasospasm following experimental subarachnoid haemorrhage.

Mexiletine is a class Ib drug that is widely used to treat ventricular arrhythmias. This compound is mainly known as a sodium channel blocker, but studies have demonstrated that it can also activate ATP-sensitive K+ channels and block Ca2+ channels. Recent in vitro data from experiments on liposomes indicate that mexiletine is also a potent antioxidant. The unique activity profile of this drug raised the possibility that it might be of benefit in limiting cerebral vasospasm. Our first series of experiments assessed the effects of mexiletine on transclivally exposed rabbit basilar arteries. The arteries were treated with 50-mM KCl, 20-nM endothelin-1 (ET-1), or 100-microM lysophosphatidic acid (LPA) in the presence or absence of 400-mM mexiletine. Vasoconstriction caused by KCl, ET-1, and LPA was inhibited by mexiletine. In a second series of experiments, subarachnoid haemorrhage (SAH) was induced in rabbits by injecting 3-ml of autologous arterial blood into the cisterna magna. Forty-eight hours after SAH induction, transclivally exposed basilar arteries exhibited a spastic constriction that was partially reversed by topical application of 400-microM mexiletine. In a third set of experiments, mexiletine was administered orally at dosages of 80-, 20, and 5-mg/kg/day t.i.d., beginning 3 hours before SAH to study the prevention of vasospasm. In a separate group of animals, 80- and 20-mg/kg/day t.i.d. of mexiletine was administered 21 hours post-SAH induction, to study the reversal of vasoconstriction. Microscopic analysis of vessels from controls (no SAH), SAH-only, and SAH + mexiletine groups indicated there was 71.43% vascular constriction in the SAH-only group compared with controls. Considerable vasorelaxation was seen in the prevention study, in which average arterial cross-sectional areas were reduced by only 17.86% and 39.29% in the mexiletine 80- and 20-mg/kg/day groups, respectively, compared with controls (p < 0.001). Compared with controls, average arterial cross-sectional areas were reduced by 53.58% and 64.29% in the mexiletine 80- and 20-mg/kg/day reversal groups, respectively. Our findings indicate that mexiletine induces potent relaxation in cerebrovascular arteries contracted with various agents, and that it prevents and partially reverses SAH-induced vasoconstriction.

Administration, Topical↗
PubMed2000

Ogilvie's syndrome as a rare complication of lumbar disc surgery.

BACKGROUND: In this study we report a rare complication after lumbar surgery, Ogilvie's syndrome, that presents as acute colonic dilatation in the absence of mechanical obstruction. CASE: A 43-year-old obese woman underwent lumbar surgery for L4-L5 lumbar disc herniation. The patient complained of persistent abdominal distention and lack of bowel sounds. Plain radiography and ultrasonography revealed massive dilatation of the colon. Nasogastric aspiration was initiated and all analgesic drugs were withdrawn. Abdominal distention gradually disappeared within three days. CONCLUSIONS: Only three cases of Ogilvie's syndrome following lumbar spinal surgery have been reported in the literature. In our case obesity, chronic constipation, and narcotic drugs were the most likely precipitating causes. Ogilvie's syndrome may resolve with conservative treatment, but if the cecal diameter continues to increase, colonoscopy or laparotomy may be needed to prevent perforation of colon.

Adult↗
PubMed1999

Giant posterior fossa teratoma.

In this study we report a rare case of a giant midline posterior fossa teratoma; its clinical presentation, radiological appearance, treatment and outcome, with an extensive review of the literature.

Brain Neoplasms↗
PubMed1999

Akinetic mutism after fourth ventricle choroid plexus papilloma: treatment with a dopamine agonist.

BACKGROUND: Akinetic mutism is a behavioral state wherein a patient seems to be awake but does not move or speak. Several patients are reported to have developed mutism after posterior fossa surgery. We present a patient who developed akinetic mutism after total excision of a choroid plexus papilloma of the fourth ventricle, and who was treated with bromocriptine. CASE DESCRIPTION: An 18-year-old woman was admitted with akinetic mutism, which had developed 6 days after posterior fossa surgery. She had had no neurologic deficit in the first 5 days after surgery and could communicate with her family. Despite antioedematous therapy and daily lumbar punctures to drain cerebrospinal fluid, there was no clinical improvement after she entered the akinetic mute state. Brain magnetic resonance revealed ventriculomegaly; brain single photon emission computed tomography revealed bilateral reduction of perfusion in the frontal region. Because daily lumbar drainage did not result in clinical improvement, shunt placement was not considered. Bromocriptine therapy was begun at a dose of 2x2.5 mg; 24 hours later, the patient started to speak and move her upper extremities. Further improvement occurred over the following week when the dose was increased to 3x2.5 mg. Bromocriptine was replaced with a placebo to determine whether the neurologic improvement was caused by the medicine. The patient's neurologic status deteriorated progressively; therefore, bromocriptine was restarted and she was discharged from the hospital. During the 6 months of follow-up, the patient has remained in good health. CONCLUSIONS: The etiology of akinetic mutism is not clear. Monoaminergic pathways, particularly dopaminergic cell groups, are most probably involved in this syndrome, because bromocriptine has a dramatic effect on these patients, as demonstrated in our case.

Adolescent↗
PubMed1999

Intellectual property and chirality of drugs.

Chirality has emerged as a key issue in drug design, discovery and development. Chiral switches are drugs that are already approved and claimed as racemates but that have been redeveloped as single enantiomers. The legal state of the art of patentability of chiral switches, as derived from US and European precedents, is reviewed. The issues of intellectual property in the pending chiral switches of the blockbuster drugs ibuprofen, fluoxetine and omeprazole are analysed.

Journal Article↗
PubMed1999

Chronic subdural haematoma following caesarean section under spinal anaesthesia.

Intracranial subdural haematoma is a rare complication of spinal anaesthesia. This report describes the case of a 31-year-old woman who presented with post partum headache following spinal anaesthesia for caesarean section. Bilateral haematomata were evacuated via burr-holes performed under total intravenous anaesthesia and the patient made a complete and uneventful recovery. The recognized causes of subdural haematoma are discussed.

Adult↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1993

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↗
PubMed1993

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↗