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A Slivka

Publications and source records attributed to A Slivka.

At least 73 records · Page 4Linked to original sources
PubMed1989

In vivo formation of hydroxyl radicals following intragastric administration of ferrous salt in rats.

Accidental poisoning by oral iron preparations is a serious problem in young children. We investigated the formation of hydroxyl radicals (.OH) in rats after intragastric instillation of ferrous sulfate. .OH was detected via its reaction with intragastrically administered 2-keto-4-methylthiobutyrate to generate ethylene gas. Ascorbic acid is typically present in oral iron preparations in order to facilitate absorption by maintaining iron in the reduced state. However, ascorbate possesses two properties that can affect .OH, recycling of oxidized iron to the ferrous state augments .OH production, while ascorbate in high concentration scavenges .OH. In experiments conducted in vitro, both actions were evident, depending upon the concentration of ascorbate. In parallel experiments conducted in vivo, the scavenging action of ascorbate was more prominent. Experiments in vitro with .OH-scavengers (dimethylsulfoxide, ethanol) and with the enzyme, catalase, confirmed both the presence of .OH and its dependence upon generated hydrogen peroxide during the oxidation of ferrous salt by molecular oxygen. Hydroxyl radicals (and/or reactive higher oxidation states of iron) may play a role in tissue damage after accidental overdose of oral iron.

Administration, Oral↗
PubMed1989

Risk associated with heparin withdrawal in ischaemic cerebrovascular disease.

Intravenous heparin is frequently used to treat thromboembolic disease, but the consequences of stopping heparin have not been studied systematically. To determine whether discontinuing heparin poses a clinical risk, we examined the charts of 378 patients treated with heparin for transient ischaemic attack (TIA), reversible ischaemic neurological deficit, or ischaemic stroke from October 1979 to June 1985. Clinical deterioration, or a new TIA or stroke was more likely (p = 0.01) during the 24 hours after heparin was stopped in patients not already on aspirin or warfarin (10/143, 7%) than in patients receiving aspirin or warfarin before heparin withdrawal (3/215, 1%). Stopping heparin in patients not receiving aspirin or warfarin appears to expose them to an increased risk for TIA, stroke, or clinical deterioration.

Adult↗
PubMed1988

Studies on the autoxidation of dopamine: interaction with ascorbate.

An oxygen electrode was used to monitor the reaction between dopamine (DA, 1-20 mM) and oxygen at pH 7.4 and 37 degrees C, in both the presence and absence of ascorbate (10 mM). The selected concentrations approximate levels within DA neurons. Diethylenetriaminepentaacetic acid (DTPA, 0.1 mM) was used to suppress catalysis by trace metals in the reagents. Separate experiments with catalase showed that oxygen consumption could be equated with the formation of hydrogen peroxide. Depending upon the experimental conditions, ascorbate acted either as an antioxidant, suppressing oxygen consumption (H2O2 production) to 6-8% of the expected rate, or as a prooxidant, amplifying oxygen consumption by 640%. The antioxidant action is consistent with the scavenging of superoxide radicals by ascorbate. The prooxidant action is probably the result of redox cycling of a pre-melanin oxidation product derived from DA. Analyses conducted by high-performance liquid chromatography with electrochemical detection revealed formation of a product with a very low oxidation potential; the product was not 6-hydroxydopamine. These observations may be relevant to concepts of toxicity mediated by DA within neuronal systems.

Ascorbic Acid↗
PubMed1988

Increase in extracellular dopamine in the striatum during cerebral ischemia: a study utilizing cerebral microdialysis.

Unilateral ligation of the left common carotid artery in anesthetized Mongolian gerbils resulted in a steep rise in extracellular dopamine in the ipsilateral striatum in 9 out of 19 animals. Extracellular dopamine was measured by cerebral dialysis in vivo and reached a peak of 0.19 mM at 40 min. At the same time, the level of homovanillic acid fell, whereas the levels of ascorbate and 3,4-dihydroxyphenylacetic acid remained relatively constant. In a separate group of animals studied with a combined dialysis/electrochemistry probe, a rise in the in vivo chronoamperometric signal in three out of six animals correlated with a rise in extracellular dopamine. The number of animals responding in these experiments (roughly 50%) corresponds to the frequency of incompetent Circle of Willis, as well as literature reports of the frequency of signs of stroke in unanesthetized gerbils. These results show a remarkable accumulation of dopamine in extracellular fluid in response to cerebral ischemia. Released dopamine appears to be responsible for the elevated in vivo electrochemical signal previously reported.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Depletion of brain glutathione in preweanling mice by L-buthionine sulfoximine.

Previous studies indicated that DL-buthionine sulfoximine (DL-BSO), an agent that inhibits the biosynthesis of GSH in liver and other peripheral organs, fails to suppress levels of GSH in the CNS. In the current study, preweanling mice responded to repeated injections of L-BSO with marked declines (79.6-86.5%) of GSH content in brain and spinal cord. In adult mice, the same treatment schedule produced only modest declines (17.8-29.2%) of GSH content in brain and a 55.9% decline in spinal cord. Pretreatment of preweanling mice with L-BSO represents a tool for studying the role of GSH in the CNS.

Aging↗
PubMed1987

Histochemical evaluation of glutathione in brain.

Glutathione (GSH) is a ubiquitous cellular sulfhydryl compound with a variety of essential functions. A histochemical method that was developed by others for the localization of GSH in tissue sections was used to study the localization of GSH in rodent and primate brain. Sections of freshly frozen tissue were stained for 4 min with Mercury orange dissolved in toluene, and viewed by fluorescence microscopy for the product of the reaction with soluble sulfhydryl compounds. Soluble sulfhydryl compounds are comprised almost exclusively of GSH. Although the brain exhibits strong staining characteristics, reflecting the millimolar levels of GSH that are detected by chemical assay, very little stain is seen in neuronal somata. Pretreatment of animals with diethyl maleate resulted in depletion of GSH from brain (measured by high performance liquid chromatography), as well as decreased Mercury orange staining. The staining pattern observed in the brain may indicate that GSH is primarily localized to non-neuronal elements, such as glia, and/or in axons and nerve terminals.

Animals↗
PubMed1987

Reduced and oxidized glutathione in human and monkey brain.

Prior animal studies have indicated that levels of oxidized glutathione (GSSG) in brain and other organs are low, comprising several percent, or less, of the total glutathione. An exception is seen in reports for autopsy and biopsy specimens of human brain, where very high levels of GSSG have been indicated. The latter observations imply an unusual redox state for human brain. In the current study, GSSG and reduced glutathione (GSH) were measured in monkey brain and autopsy specimens of human brain. Levels of GSSG were 1.2% or less, of the total glutathione. These results are similar to those for rodent brain, but disagree with earlier reports concerning human brain.

Aged↗
PubMed1985

Hydroxyl radical attack on dopamine.

Hydroxyl radicals were generated in the presence of 1 mM dopamine (3,4-dihydroxyphenylethylamine) at pH 7.2 (50 mM phosphate buffer) by the following two mechanisms: 1) a classic Fenton-type reaction between hydrogen peroxide and a ferrous chelate (ferrous diethylenetriaminepentaacetate) and 2) the cyclical redox reactions of iron-EDTA/ascorbate. Three ring-monohydroxylated products of dopamine were detected by high performance liquid chromatography with electrochemical detection: 2-hydroxydopamine, 5-hydroxydopamine, and 6-hydroxydopamine in an approximate ratio of 3:2:1. Scavengers of hydroxyl radicals (dimethyl sulfoxide, mannitol, ethanol) suppressed the yields of products in a concentration-dependent manner. The formation of nonphysiologic hydroxylated forms of dopamine can provide a probe for the formation of hydroxyl radicals in dopamine neurons.

Ascorbic Acid↗
PubMed1982

Monocyte and granulocyte-mediated tumor cell destruction. A role for the hydrogen peroxide-myeloperoxidase-chloride system.

Human monocytes stimulated with phorbol myristate acetate were able to destroy a T lymphoblast cell target (CEM). Stimulated human granulocytes were also capable of mediating CEM cytotoxicity to a comparable degree as the monocyte. CEM destruction was dependent on the pH and the effector cell number. Both monocyte or granulocyte mediated cytotoxicity were inhibited by the addition of catalase, whereas superoxide dismutase had no inhibitory effect. In addition, CEM were protected from cytolysis by the effector cells by the myeloperoxidase inhibitors, azide and cyanide, or by performing the experiment under halide-free conditions. Glucose oxidase, an enzyme system capable of generating hydrogen peroxide, did not mediate CEM cytotoxicity, while the addition of purified myeloperoxidase dramatically enhanced cytolysis. Hypochlorous acid scavengers prevented CEM destruction by the glucose oxidase-myeloperoxidase-chloride system but neither hydroxyl radical nor singlet oxygen scavengers had any protective effect. These hypochlorous acid scavengers were also successful in inhibiting monocyte or granulocyte-mediated CEM cytotoxicity. Based on these observations we propose that human monocytes or granulocytes can utilize the hydrogen peroxide-myeloperoxidase-chloride system to generate hypochlorous acid or species of similar reactivity as a potential mediator of CEM destruction.

Chlorides↗
PubMed1982

Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation.

The model hydrogen peroxide-myeloperoxidase-chloride system is capable of generating the powerful oxidant hypochlorous acid, which can be quantitated by trapping the generated species with the beta-amino acid, taurine. The resultant stable product, taurine chloramine, can be quantitated by its ability to oxidize the sulfhydryl compound, 5-thio-2-nitro-benzoic acid to the disulfide, 5,5'-dithiobis(2-nitroben-zoic acid) or to oxidize iodide to iodine. Using this system, purified myeloperoxidase in the presence of chloride and taurine converted stoichiometric quantities of hydrogen peroxide to taurine chloramine. Chloramine generation was absolutely dependent on hydrogen peroxide, myeloperoxidase, and chloride and could be inhibited by catalase, myeloperoxidase inhibitors, or chloride-free conditions. In the presence of taurine, intact human neutrophils stimulated with either phorbol myristate acetate or opsonized zymosan particles generated a stable species capable of oxidizing 5-thio-2-nitrobenzoic acid or iodide. Resting cells did not form this species. The oxidant formed by the stimulated neutrophils was identified as taurine chloramine by both ultraviolet spectrophotometry and electrophoresis. Taurine chloramine formation by the neutrophil was dependent on the taurine concentration, time, and cell number. Neutrophil-dependent chloramine generation was inhibited by catalase, the myeloperoxidase inhibitors, azide, cyanide, or aminotriazole and by chloride-free conditions, but not by superoxide dismutase or hydroxyl radical scavengers. Thus, it appears that stimulated human neutrophils can utilize the hydrogen peroxide-myeloperoxidase-chloride system to generate taurine chloramine. Based on the demonstrated ability of the myeloperoxidase system to generate free hypochlorous acid we conclude that neutrophils chlorinate taurine by producing this powerful oxidant. The biologic reactivity and cytotoxic potential of hypochlorous acid and its chloramine derivatives suggest that these oxidants play an important role in the inflammatory response and host defense.

Cells, Cultured↗
PubMed1981

Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells.

Human neutrophils stimulated with phorbol myristate acetate were able to destroy suspensions or monolayers of cultured human endothelial cells. Neutrophil-mediated cytotoxicity was related to phorbol myristate acetate concentration, time of incubation and neutrophil number. Cytolysis was prevented by the addition of catalase, while superoxide dismutase had no effect on cytotoxicity. The addition of the heme-enzyme inhibitors, azide or cyanide, markedly stimulated neutrophil-mediated damage while exogenous myeloperoxidase failed to stimulate cytolysis. Neutrophils isolated from patients with chronic granulomatous disease did not destroy the endothelial cell targets while myeloperoxidase-deficient neutrophils successfully mediated cytotoxicity. Endothelial cell damage mediated by the myeloperoxidase deficient cells was also inhibited by catalase but not superoxide dismutase. The addition of purified myeloperoxidase to the deficient cells did not stimulate cytotoxicity. Glucose-glucose oxidase, an enzyme system capable of generating hydrogen peroxide, could replace the neutrophil as the cytotoxic mediator. The addition of myeloperoxidase at low concentrations of glucose oxidase did not increase cytolysis, but at the higher concentrations of glucose oxidase it stimulated cytotoxicity. The destruction of endothelial cells by the glucose oxidase-myeloperoxidase system was inhibited by the addition of hypochlorous acid scavengers. In contrast, neutrophil-mediated cytolysis was not effectively inhibited by the hypochlorous acid scavengers. Based on these observations, we propose that human neutrophils can destroy cultured human endothelial cells by generating cytotoxic quantities of hydrogen peroxide.

Cell Survival↗
PubMedDate not supplied

Santorinicele in pancreas divisum: diagnosis with secretin-stimulated magnetic resonance pancreatography.

A Santorinicele, or cystic dilatation of the dorsal pancreatic duct at the minor papilla, is seen in a small number of patients with pancreas divisum and may indicate obstruction at the minor papilla, a risk factor for pancreatitis. We present a case of a Santorinicele that was diagnosed with secretin-stimulated magnetic resonance pancreatography and treated with minor papillotomy.

Aged↗
PubMedDate not supplied

Brush cytology during ERCP for the diagnosis of biliary and pancreatic malignancies.

Endoscopic retrograde cholangiopancreatography is a valuable tool in the diagnosis and management of pancreaticobiliary diseases. The diagnostic sensitivity of brush cytology is reported as between 18% and 70% for malignant bile duct or pancreatic duct strictures. We report our findings in 74 patients with pancreaticobiliary strictures who underwent ERCP. Brush cytology was performed on 55 bile duct specimens and 19 pancreatic duct specimens. No complications related to the procedure occurred; 4 specimens (5.4%) were unsatisfactory for interpretation. Strictures were benign in 22 patients (12 pancreatitis, 5 sclerosing cholangitis, 3 Mirizzi syndrome, and 2 papillitis) and malignant in 52 patients (29 pancreatic carcinoma, 10 cholangiocarcinoma, 6 metastatic disease, 4 pancreatic mucinous ductal ectasia, 1 ampullary carcinoma, and 2 non-functioning islet cell tumors). The nature of the stricture was confirmed by surgery, surgical biopsy, necropsy, or follow-up. The overall results for brush cytology were sensitivity 56.2%, specificity 100%, positive predictive value 100%, negative predictive value 51.2%, and accuracy 70%. Our results confirm the value, safety, and utility of obtaining cytologic specimens at the time of ERCP; confirmation was obtained in 65.5% of pancreatic carcinoma cases. Although a negative result does not exclude pancreaticobiliary malignancy, a positive result confirms this diagnosis.

Bile Duct Neoplasms↗
PubMedDate not supplied

Ultra high field MRI at 8 Tesla of subacute hemorrhagic stroke.

PURPOSE: Optimal treatment strategies and neurologic outcome after stroke depend on an accurate characterization of the lesion. There is a need for high resolution noninvasive imaging for assessment of the infarct size, perfusion, and vascular territory. MRI at the ultra high field (UHF) of 8 T offers unprecedented resolution, but its utility for stroke evaluation has not been determined yet. METHOD: A 55-year-old man with hypertension experienced sudden onset of speech arrest and right-sided hemiparesis that resolved in < 24 h with minimal neurologic deficit. MRI at 1.5 T showed initially a left posterior frontal lesion with subacute infarct (hyperintense on T2-weighted spin echo images) and right-sided frontal and periventricular lesions consistent with chronic infarct. There were many smaller white matter lesions. Delayed studies showed high signal changes involving the gray matter only on T1-weighted images. RESULTS: Gradient echo and rapid acquisition with relaxation enhancement (RARE) multislice images revealed a serpentine area of low signal in the left posterior frontal lobe gray matter suggestive of a hemorrhagic infarct, right-sided frontal lesion also showing iron deposits, multiple periventricular and cortical areas with abnormal high signal regions that were consistent with old infarcts, and numerous small vessels readily visible, more prominent on the right. CONCLUSION: MRI at 8 T displays lesions with a high resolution and striking anatomic details. Susceptibility to iron and sensitivity to detect blood products are increased at 8 T. The imaging characteristics at high field are different from those at low field, but both represent findings of iron products.

Humans↗