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G Cohen

Publications and source records attributed to G Cohen.

At least 271 records · Page 15Linked to original sources

Exposure of striatal [corrected] synaptosomes to L-dopa increases levels of oxidized glutathione.

Incubation of striatal synaptosomes with L-dopa and glucose in either the presence or absence of 10 microM reserpine resulted in a rise in the level of oxidized glutathione (GSSG) within the isolated tissue pellet. The rise in GSSG was concentration dependent in the range of 0.04-1.0 mM L-dopa. With 1.0 mM L-dopa in the presence of reserpine, the GSSG level was elevated by 7.0 +/- 0.7 pmol/mg original striatal tissue, which corresponds to an increase of 38.0 +/- 4.5% compared with control. The rise in GSSG reflects an oxidative stress. The oxidation of dopamine by monoamine oxidase generates H2O2, which is normally detoxified by glutathione peroxidase to yield GSSG. In the presence of clorgyline or pargyline (two monoamine oxidase inhibitors), the rise in GSSG was suppressed by 88-92%, as was the formation of DOPAC. NSD-1055 and carbidopa (two inhibitors of dopa-decarboxylase) also significantly suppressed (50-60%) the rise in GSSG. These data show that the synthesis of dopamine from L-dopa, with subsequent catabolism of dopamine, can evoke a significant rise in the level of GSSG, which reflects the oxidant stress associated with monoamine oxidase activity.

3,4-Dihydroxyphenylacetic Acid↗

Decarboxylation of DL-2,4-dihydroxyphenylalanine (2,4-DOPA) to 2,4-dihydroxyphenylethylamine in mouse striatal slices.

Decarboxylation of an unnatural analogue of DOPA by brain aromatic amino acid decarboxylase was measured by HPLC with electrochemical detection. Incubation of striatal slices with DL-2,4-dihydroxyphenylalanine (2,4-DOPA) resulted in biosynthesis and accumulation of 2,4-dihydroxyphenylethylamine, which was completely blocked by carbidopa. 2,4-DOPA induced a significant decrease in endogenous dopamine, but the loss was not prevented by carbidopa. Since 2,4-DOPA is a potential pro-drug for melanoma chemotherapy, further evaluation of its neurobiologic properties is needed.

Animals↗

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↗

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↗

In vivo ethane production in vitamin E-deficient rats with DMH-induced colon cancer.

The effect of both a vitamin E-deficient and a high polyunsaturated fat (PUFA) diet was tested on rats injected with the colon carcinogen 1,2-dimethylhydrazine (DMH). In vivo lipid peroxidation was monitored by measuring exhaled ethane from the animals. Higher mean weights were found in animals fed high PUFA and vitamin E-sufficient diets. There was no difference in ethane exhalation between DMH-treated and control animals regardless of diet. Mean ethane exhalation was highest in animals fed either vitamin E-deficient or high PUFA diets. There was no difference in tumor formation between the vitamin E-deficient and the vitamin E-sufficient groups. The high PUFA groups had more tumors than the low PUFA groups. Diet was shown to be the major factor affecting ethane exhalation. There was no evidence that vitamin E-deficiency promoted DMH-induced tumors or that DMH caused increased lipid peroxidation.

1,2-Dimethylhydrazine↗

Variations in the monoamine oxidase-inhibitory activity ("tribulin?") in pig's urine.

Sandler and his colleagues (see Sandler, 1982) have demonstrated the presence of an endogenous inhibitor of the enzyme monoamine oxidase (MAO) and of benzodiazepine receptor binding in the urine and blood plasma of man and rat. The concentrations of this material increased under stress conditions and it has been named "tribulin". In the present experiments MAO-inhibitory activity was found in extracts of urine and plasma samples of domestic pigs. Evidence was obtained that the inhibitory activity was higher when pigs experienced slight discomfort. Thus it appears that pigs produce a substance similar to tribulin. It may become possible to use such MAO-inhibitory activity as an indicator in the assessment of interaction with the environment in pig husbandry.

Animals↗

Construction of an ordered overlapping library of bacteriophage P1 DNA in phage vector lambda D69.

A library of bacteriophage P1 DNA was constructed in the phage vector lambda D69. The DNA of some 150 randomly chosen lambda-P1 hybrid phages containing P1 DNA fragments 5-10 kb in size was analyzed by restriction endonuclease digestion using enzymes EcoRI, BglII, and BamHI that cleave P1 DNA at known positions on the physical map of P1. Approximately one third of the phages contained P1 DNA inserts having two or more restriction sites for any one of these enzymes, thus allowing the location of the insert to be determined with respect to the physical map. Genetic tests allowed detection of lambda-P1 hybrid phages possessing inserts with functional P1 ban and CmR genes. A subset of 18 phages was analyzed in more detail; their P1 DNA inserts comprise an ordered collection of overlapping P1 DNA fragments that cover almost 98% of the P1 genome.

Bacteriophage lambda↗

Pain characteristics and treatment in an outpatient cancer population.

Thirty of 100 consecutive outpatients at a comprehensive cancer center were assessed by their physicians as having pain due to cancer severe enough to require regular or narcotic medication. These 30 patients and their physicians then were approached with a semistructured questionnaire about pain characteristics and management. Pain severity correlated only with age older than 55 years. Patients tended to rate their pain as more severe than did their physicians, but believed that pain medications generally were effective. Side effects of pain medication and patient fears of dependence on medication appeared to be more important limiting factors in achieving complete pain relief from medication than undermedication by physicians. Both patients and physicians acknowledged a relationship between emotional state and pain, but there was a greater appreciation among patients than physicians of the usefulness of techniques such as relaxation and distraction in pain control.

Adult↗

Haemodynamic effects of verapamil administration after large doses of fentanyl in man.

Thirteen patients with good left ventricular function undergoing coronary artery revascularization were studied to determine the cardiovascular effects of verapamil, 75-150 micrograms X kg-1, after a large dose (100 micrograms X kg-1) of fentanyl, with pancuronium for muscle relaxation. The patients were continued on their usual cardiovascular medications until the time of surgery, which included nitrates, beta adrenergic blockers, and nifedipine. Anaesthesia with fentanyl was associated with decreases in mean arterial blood pressure, systemic vascular resistance, left ventricular stroke work index, and circulating catecholamine levels. Mean values were not further changed by verapamil, but individual patients had additional modest decreases in blood pressure and systemic vascular resistance. Cardiac index, however, was well maintained. Plasma catecholamines remained depressed after verapamil under the study condition. Thus, in patients with good left ventricular function, clinically relevant doses of verapamil were well tolerated even in the presence of an anaesthetic that included large doses of fentanyl, with suppression of circulating catecholamine levels.

Adult↗

Upper airway stability and apnea during nasal occlusion in newborn infants.

Brief end-expiratory airway occlusions were performed in 22 preterm babies, 17 with and 5 without clinical apnea, and 4 full-term babies, 1 with Pierre-Robin syndrome. Airway stability was evaluated by comparing pressures measured simultaneously in the chest and nasal passages during occluded inspiratory efforts. The airway remained patent throughout all 301 trials in 20 babies during rapid-eye-movement (REM) and quiet sleep. Airway closure occurred during 31/102 trials in 6 babies (5 preterm and 1 term with Pierre-Robin syndrome), more commonly in quiet than in REM sleep. Overall and within individuals, mean closing pressures were significantly lower than the mean maximum falls in airway pressure recorded during occlusions without closure. Mixed-obstructive and obstructive apnea was significantly more frequent in babies with airway closure than in those without (5.3 +/- 4.0 vs. 0.4 +/- 0.8 episodes/h). Pauses in breathing greater than or equal to 3 s occurred during 28% of occlusions in preterm infants and 2% of occlusions in full-term babies. There was no significant difference between the mean frequency of pauses during occlusion and during the preceding control period or in the incidence of pauses in occlusions with vs. those without closure. It is concluded that the airway of most preterm and full-term babies is remarkably stable under load. Intermittent closure occurs in certain infants and may be related to airway muscle dysfunction.

Airway Obstruction↗