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1.
Value Health ; 17(7): A555, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27201819
2.
Photochem Photobiol ; 83(3): 714-21, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17076544

RESUMEN

By using saturating flash, we investigated the change in the rapid fluorescence rise when Lemna minor leaf was exposed to different light conditions and treated with exogenous electron acceptors (methyl viologen and duroquinone) and electron donor (hydroxylamine). Investigation was carried out by using combined pulse amplitude modulated fluorometer and plant efficiency analyzer system, which were employed simultaneously to provide different light conditions and to induce rapid fluorescence rise respectively. We have shown that when leaf of L. minor was exposed to different conditions of illumination, rapid fluorescence rise was greatly influenced by the electron transport functions beyond quinone A-plastoquinone reduction. This was indicated by the change in both fluorescence yield and appearance time of the different transients. When exogenous electron donor (hydroxylamine) and acceptors (methyl viologen and duroquinone) were applied in in vivo condition, we showed that rapid fluorescence rise represented a reliable indicator of PSII-PSI electron transport state and energy dissipation process.


Asunto(s)
Clorofila/química , Transporte de Electrón , Fluorescencia , Luz , Complejo de Proteína del Fotosistema II/metabolismo , Clorofila A , Paraquat , Complejo de Proteína del Fotosistema II/efectos de la radiación , Hojas de la Planta , Plastoquinona
3.
Biosens Bioelectron ; 79: 568-73, 2016 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-26749098

RESUMEN

The present work was dedicated to the development of a lab-on-chip device for water toxicity analysis and more particularly herbicide detection in water. It consists in a portable system for on-site detection composed of three-electrode electrochemical microcells, integrated on a fluidic platform constructed on a glass substrate. The final goal is to yield a system that gives the possibility of conducting double, complementary detection: electrochemical and optical and therefore all materials used for the fabrication of the lab-on-chip platform were selected in order to obtain a device compatible with optical technology. The basic detection principle consisted in electrochemically monitoring disturbances in metabolic photosynthetic activities of algae induced by the presence of Diuron herbicide. Algal response, evaluated through oxygen (O2) monitoring through photosynthesis was different for each herbicide concentration in the examined sample. A concentration-dependent inhibition effect of the herbicide on photosynthesis was demonstrated. Herbicide detection was achieved through a range (blank - 1 µM Diuron herbicide solution) covering the limit of maximum acceptable concentration imposed by Canadian government (0.64 µM), using a halogen white light source for the stimulation of algal photosynthetic apparatus. Superior sensitivity results (limit of detection of around 0.1 µM) were obtained with an organic light emitting diode (OLED), having an emission spectrum adapted to algal absorption spectrum and assembled on the final system.


Asunto(s)
Técnicas Biosensibles/instrumentación , Diurona/análisis , Herbicidas/análisis , Dispositivos Laboratorio en un Chip , Microalgas/fisiología , Contaminantes Químicos del Agua/análisis , Diurona/metabolismo , Técnicas Electroquímicas/instrumentación , Herbicidas/metabolismo , Microalgas/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Contaminantes Químicos del Agua/metabolismo , Calidad del Agua
4.
Photochem Photobiol ; 81(3): 649-53, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15686444

RESUMEN

The photosynthetic activity of marine phytoplankton from five algal classes (Phaeodactylum tricornutum, Skeletonema costatum, Thalassiosira oceanica, Thalassiosira weissflogii, Dunaliella tertiolecta, Mantoniella squamata, Emiliania huxleyi, Pavlova lutheri and Heterosigma akashiwo) was investigated under identical growth conditions to determine interspecies differences. Primary photochemistry and electron transport capacity of individual species were examined by pulse amplitude-modulated (PAM) fluorescence. Although few differences were found in maximal photosystem II (PSII) photochemical efficiency between various species, large differences were noticed in their PSII-photosystem I (PSI) electron transport activity. We found that species such as T. oceanica and M. squamata have much lower photochemical activity than H. akashiwo. It appeared that processes involved in electron transport activity were more susceptible to change during algal evolution compared with the primary photochemical act close to PSII. Large variations in the nonphotochemical energy dissipation event among species were also observed. Light energy required to saturate photosynthesis was very different between species. We have shown that M. squamata and H. akashiwo required higher light energy (>1300 micromol m(-2) s(-1)) to saturate photosynthesis compared with S. costatum and E. huxleyi (ca 280 micromol m(-2) s(-1)). These differences were interpreted to be the result of variations in the size of light-harvesting complexes associated with PSII. These disparities in photosynthetic activity might modulate algal community structure in the natural environment where light energy is highly variable. Our results suggest that for an accurate evaluation of primary productivity from fluorescence measurements, it is essential to know the species composition of the algal community and the individual photosynthetic capacity related to the major phytoplankton species present in the natural phytoplankton assemblage.


Asunto(s)
Fluorometría/métodos , Fotosíntesis/fisiología , Complejo de Proteína del Fotosistema II/fisiología , Fitoplancton/fisiología , Transporte de Electrón/fisiología , Biología Marina , Fotosíntesis/efectos de la radiación , Complejo de Proteína del Fotosistema II/efectos de la radiación , Fitoplancton/clasificación , Fitoplancton/efectos de la radiación , Factores de Tiempo
5.
Neurobiol Aging ; 18(5): 555-7, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9390784

RESUMEN

Complement activation is present in the brain in Alzheimer's disease (AD), and C1q concentrations are decreased in AD cerebrospinal fluid (CSF). To determine whether concentrations of other complement proteins are also altered in AD CSF, we measured concentrations of C3a and SC5b-9 in CSF from patients with probable AD (n = 19), normal aged controls (n = 11), and normal younger controls (n = 15). C3a concentrations were similar between AD and aged controls, but threefold higher than in younger controls (p < 0.05 vs. both groups). A similar pattern was found with SC5b-9, though the increase was only twofold and statistically significant only for AD vs. younger controls. These results suggest that an increased generation of complement proteins in localized areas of the AD brain does not result in elevated concentrations of these proteins in CSF, compared with age-matched controls. Increased C3a (and, to a lesser extent, SC5b-9) in aged controls may be due to increased complement activation, increased central nervous system production, and/or blood-brain barrier leakage of these proteins.


Asunto(s)
Envejecimiento/líquido cefalorraquídeo , Enfermedad de Alzheimer/líquido cefalorraquídeo , Complemento C3a/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Complejo de Ataque a Membrana del Sistema Complemento , Proteínas del Sistema Complemento/líquido cefalorraquídeo , Proteínas del Sistema Complemento/metabolismo , Femenino , Glicoproteínas/líquido cefalorraquídeo , Glicoproteínas/metabolismo , Humanos , Masculino , Persona de Mediana Edad
6.
Arch Neurol ; 49(5): 555-8, 1992 May.
Artículo en Inglés | MEDLINE | ID: mdl-1580820

RESUMEN

Malignant tumors of the pituitary gland may mimic pituitary adenomas both in clinical presentation and in imaging, and often present with neurologic findings including visual field loss and extraocular movement palsies. We describe a 58-year-old woman without known malignancy who presented with extraocular movement weakness, loss of facial sensation, and a sellar plasmacytoma; a 49-year-old woman with oculomotor palsy, no known malignancy, and rapidly failing vision who had metastatic lung carcinoma; and a 70-year-old woman with metastatic breast carcinoma who presented with rapidly failing vision and a metastasis to the anterior lobe of the pituitary. These cases illustrate several important features of malignancy in the pituitary fossa: that it can mimic a "nonfunctioning" pituitary adenoma in clinical presentation and imaging; that rapidly progressive visual loss, extraocular movement palsies, or facial sensory loss may help to distinguish it from a benign adenoma; and that when the pathologist evaluates an alleged "nonsecretory" or "nonfunctional" adenoma, metastases should be included in the differential diagnosis.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Adenocarcinoma/secundario , Adenocarcinoma/terapia , Adenoma/terapia , Anciano , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neoplasias Hipofisarias/secundario , Neoplasias Hipofisarias/terapia
7.
Toxicol Sci ; 61(1): 128-34, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11294983

RESUMEN

Sperm analyses are often incorporated into reproductive toxicity studies in rats. Due to the relative ease of collecting multiple samples throughout a study, semen analysis in non-rodents such as dogs offers the opportunity to assess potential development of functional effects of compounds on male reproduction over time. In the present study, semen parameters were evaluated in beagle dogs during and at termination of a chronic toxicity study with the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin. Male dogs received 0, 10, 40, or 120 mg/kg orally in gelatin capsules for up to 104 weeks (n = 10/group). After 52 weeks of dosing, 3 dogs/group were euthanized, and 2/group were withdrawn from treatment for a 12-week reversal period and euthanized at Week 64. The remaining 5/group continued treatment until Week 104. Semen was collected from all animals for 3 consecutive weeks prior to termination of the 52-week animals (Weeks 50, 51, 52) for analysis of sperm parameters, using manual methods of evaluation. Semen was collected from the remaining animals at Weeks 64, 78, 91, and 104, and was analyzed. At necropsy, testes, epididymides, and prostates were weighed and evaluated histologically, and epididymal sperm counts were determined. Serum cholesterol was decreased 25--60% at all doses during the study. There were no drug-related differences in semen volume and color, total sperm count, and sperm concentration, morphology, progressiveness, and percent motility during treatment with atorvastatin. There were also no effects on reproductive organ weights or histopathology, and no effects on epididymal sperm count. Thus, incorporation of semen analyses into this study allowed the evaluation of potential male reproductive effects in dogs at multiple time points during the study. Statistical power calculations demonstrated acceptable statistical power (> 80%) for semen sperm count, concentration, morphology, and motility with group sizes of 8--10 animals, and for semen sperm count and concentration or epididymal sperm count with group sizes of 3--5 animals, using the methodology described in this paper.


Asunto(s)
Acilcoenzima A/antagonistas & inhibidores , Acilcoenzima A/efectos de los fármacos , Colesterol/análisis , Epidídimo/efectos de los fármacos , Ácidos Heptanoicos/análisis , Ácidos Heptanoicos/farmacología , Tamaño de los Órganos/efectos de los fármacos , Próstata/efectos de los fármacos , Pirroles/análisis , Pirroles/farmacología , Semen/citología , Semen/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , Espermatozoides/anomalías , Espermatozoides/citología , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Atorvastatina , Colesterol/sangre , Perros , Eyaculación , Epidídimo/crecimiento & desarrollo , Epidídimo/patología , Ácidos Heptanoicos/sangre , Masculino , Próstata/crecimiento & desarrollo , Próstata/patología , Pirroles/sangre , Recuento de Espermatozoides , Testículo/crecimiento & desarrollo , Testículo/patología , Factores de Tiempo
8.
J Neurosci Methods ; 75(1): 59-68, 1997 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-9262145

RESUMEN

An important experimental challenge in research with squirrel monkeys (Saimiri scureus) is the development of a reliable closed intravenous system for long term drug self-administration studies and the collection of multiple timed blood samples. A surgical procedure using a vascular access port (VAP) system was developed to provide easy access for venous samples or drug infusions. Daily experiments in chaired monkeys were simple and reliable for durations of up to 6 h. The quantitative performance of the VAP system was evaluated by the number of days until port failure for self-administration studies and the number of days during which blood samples could be collected beyond an initial time of 91 days. The mean best performance for VAP system functional time for self-administration studies was 437 +/- 73 and the mean worst performance was 281 +/- 79. The mean best performance for blood withdrawal functional time was 362 +/- 81 and the mean worst performance was 332 +/- 85. The qualitative performance of the VAP system is described including complications that developed during the procedure; corresponding suggestions for corrective actions are discussed. Enhancements to increase port performance are also recommended.


Asunto(s)
Recolección de Muestras de Sangre/métodos , Catéteres de Permanencia , Trastornos Relacionados con Sustancias , Animales , Masculino , Reproducibilidad de los Resultados , Saimiri , Autoadministración
9.
Brain Res ; 738(2): 265-74, 1996 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-8955522

RESUMEN

Ceruloplasmin (CP), the major plasma anti-oxidant and copper transport protein, is synthesized in several tissues, including the brain. We compared regional brain concentrations of CP and copper between subjects with Alzheimer's disease (AD, n = 12), Parkinson's disease (PD, n = 14), Huntington's disease (HD, n = 11), progressive supranuclear palsy (PSP, n = 11), young adult normal controls (YC, n = 6) and elderly normal controls (EC, n = 7). Mean CP concentrations were significantly increased vs. EC (P < 0.05) in AD hippocampus, entorhinal cortex, frontal cortex, and putamen. PD hippocampus, frontal, temporal, and parietal cortices, and HD hippocampus, parietal cortex, and substantia nigra. Immunocytochemical staining for CP in AD hippocampus revealed marked staining within neurons, astrocytes, and neuritic plaques. Increased CP concentrations in brain in these disorders may indicate a localized acute phase-type response and/or a compensatory increase to oxidative stress.


Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Encéfalo/fisiología , Ceruloplasmina/metabolismo , Cobre/metabolismo , Degeneración Nerviosa/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Encéfalo/metabolismo , Encéfalo/patología , Estudios de Casos y Controles , Recuento de Células , Hipocampo/patología , Humanos , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/patología , Enfermedad de Huntington/fisiopatología , Persona de Mediana Edad , Neuronas/patología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Parálisis Supranuclear Progresiva/metabolismo , Parálisis Supranuclear Progresiva/patología , Parálisis Supranuclear Progresiva/fisiopatología
10.
Eur J Pharmacol ; 432(2-3): 187-94, 2001 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-11740955

RESUMEN

Factor Xa is a serine protease positioned at the convergence point of the intrinsic and extrinsic coagulation pathways and is therefore an attractive target in the development of novel anticoagulant drugs. The objective of this study was to evaluate the efficacy of CI-1031 (N-[2-[5-amidino-2-hydroxyphenoxy]-6-[3-(1-methyl-1H-imidazolin-2-yl)-phenoxy]-3,5-difluoropyrid), a potent and selective inhibitor of Factor Xa, in a canine electrolytic injury model of arterial and venous thrombosis. Enoxaparin (enoxaparin sodium), a low molecular weight heparin currently approved for treatment and prevention of deep vein thrombosis and unstable angina, was also tested for efficacy in this model. CI-1031 was administered intravenously to anesthetized dogs at three doses: 1.25, 2.5 and 5 microg/kg/min (n=5 for each group) as a continuous infusion for 5.5 h. The control group (n=5) received a continuous infusion of vehicle (3.69 mmol citric acid and 0.9% sodium chloride solution) at a rate of 1 ml/kg/h. Ninety minutes after administration of CI-1031 prothrombin times increased 1.2-, 1.6- and 2.0-fold over baseline values in the 1.25, 2.5 and 5 microg/kg/min groups, respectively. The time to formation of an occlusive thrombus in the femoral arteries averaged 69+/-5 min in the control group compared to 127+/-19, 192+/-33 and 219+/-15 min in the low-, mid- and high-dose CI-1031 groups. In the femoral veins, occlusion time in the controls averaged 56+/-11 min compared to 153+/-22, 137+/-30 and 214+/-26 min in the three treatment groups. Thrombus weights in the control arteries averaged 51+/-4 mg compared to 45+/-5, 28+/-10 and 15+/-3 mg in the CI-1031 treated groups. On the venous side, control thrombus weights averaged 96+/-18 mg compared to 75+/-16, 51+/-16 and 25+/-4 mg in the low-, mid- and high-dose CI-1031 groups. A plasma CI-1031 concentration of approximately 400 ng/ml was associated with a 50% reduction in thrombus weight relative to control animals. Enoxaparin was administered intravenously at a loading dose of 50, 100 or 200 IU/kg for 1 h followed by a maintenance infusion of 25, 50 or 100 IU/kg/h for 4.5 h. The most dramatic changes in coagulation parameters were observed in thrombin time with virtually no changes in prothrombin time. Enoxaparin elicited a dose-dependent increase in time to thrombotic occlusion and a dose-dependent decrease in thrombus weight similar to that observed with CI-1031. Time to occlusion in the enoxaparin-treated groups averaged 117+/-33, 188+/-32 and 217+/-22 min in the low-, mid- and high-dose groups in the femoral arteries and 84+/-22, 171+/-31 and 133+/-33 min in the femoral veins. Thrombus weights averaged 33+/-10, 12+/-5 and 10+/-4 mg in the arteries and 32+/-9, 13+/-2 and 21+/-6 mg in the veins in the low-, mid- and high-dose groups. Blood loss with CI-1031 tended to be less than enoxaparin at doses that provided comparable efficacy. These results demonstrate that CI-1031, like enoxaparin, is an effective antithrombotic agent in an established canine model of arterial and venous thrombosis. CI-1031 provided dose-dependent efficacy with minimal changes in ex vivo coagulation parameters, suggesting it may be a safe and effective antithrombotic agent for both arterial and venous indications.


Asunto(s)
Amidinas/farmacología , Anticoagulantes/farmacología , Enoxaparina/farmacología , Piridinas/farmacología , Trombosis/prevención & control , Trombosis de la Vena/prevención & control , Amidinas/sangre , Animales , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Electrólisis/efectos adversos , Inhibidores del Factor Xa , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Piridinas/sangre , Tiempo de Trombina , Trombosis/etiología , Factores de Tiempo , Trombosis de la Vena/etiología
11.
Brain Res Bull ; 52(6): 553-8, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10974496

RESUMEN

Studies with cerebrospinal fluid from subjects with Parkinson's disease suggest that purine abnormalities may be present in this disorder. The effects of purines on dopamine metabolism have not been characterized, though adenosine is known to inhibit dopaminergic neurotransmission. In this study, dopamine, its precursor 3,4-dihydroxyphenylalanine (DOPA), and its degradation products 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured in rat pheochromocytoma PC12 cells following 24-h incubation with 5, 50, and 500 microM adenosine, adenine, guanosine, guanine, hypoxanthine, xanthine, and uric acid. Incubation with adenosine increased DOPA, DOPAC, and HVA, while adenine treatment decreased DOPA. Guanosine (500 microM) decreased DOPA, dopamine, and DOPAC, while lower concentrations increased DOPAC and HVA. Incubation with guanine decreased dopamine, and xanthine decreased dopamine and DOPAC. Hypoxanthine and uric acid exerted minimal effects. These results indicate that purines exert a variety of effects on dopamine metabolism. The influence of purine metabolism on the dopaminergic deficit in the Parkinsonian brain merits further investigation.


Asunto(s)
Dopamina/metabolismo , Células PC12/efectos de los fármacos , Células PC12/metabolismo , Purinas/metabolismo , Purinas/farmacología , Adenina/metabolismo , Adenina/farmacología , Adenosina/metabolismo , Adenosina/farmacología , Animales , Modelos Animales de Enfermedad , Guanina/metabolismo , Guanina/farmacología , Guanosina/metabolismo , Guanosina/farmacología , Hipoxantina/metabolismo , Hipoxantina/farmacología , Neostriado/metabolismo , Neostriado/patología , Neostriado/fisiopatología , Vías Nerviosas/metabolismo , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Neuronas/metabolismo , Neuronas/patología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Ratas , Sustancia Negra/metabolismo , Sustancia Negra/patología , Sustancia Negra/fisiopatología , Ácido Úrico/metabolismo , Ácido Úrico/farmacología , Xantina/metabolismo , Xantina/farmacología
12.
Brain Res Bull ; 45(3): 297-9, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9510422

RESUMEN

The significance of guanine nucleotides and nucleosides in neurodegenerative disorders is suggested by recent reports that these molecules enhance neurite branching and astrocyte proliferation. The objective of this study was to investigate the influence of increased dopamine metabolism, produced by 5-day treatment of rabbits with reserpine (2 mg/kg) or levodopa (LD) (50 mg/kg), on striatal concentrations of guanosine, guanine, and their metabolites. Reserpine treatment decreased striatal guanosine by 41% and increased guanine by 50%, while LD decreased guanosine by 48% (all p < 0.01 vs. vehicle-treated controls). LD also increased guanine by 22% (not statistically significant). Xanthine and uric acid concentrations were unchanged. Because of the neurotrophic properties of guanosine and guanine, changes in striatal concentrations of these purines secondary to increased dopamine (DA) turnover may have relevance for survival of remaining dopaminergic neurons in Parkinson's disease (PD).


Asunto(s)
Cuerpo Estriado/metabolismo , Dopaminérgicos/farmacología , Dopamina/metabolismo , Guanina/metabolismo , Guanosina/metabolismo , Reserpina/farmacología , Animales , Cuerpo Estriado/citología , Levodopa/farmacología , Masculino , Neuronas/efectos de los fármacos , Conejos
13.
Brain Res Bull ; 47(6): 663-7, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10078623

RESUMEN

Levodopa treatment in Parkinson's disease has been suggested to contribute to disease progression through free radical generation. We compared the time course of levodopa-induced dopamine metabolism, and the resulting oxidative stress, between rat brain regions with varying dopaminergic innervation. At 1, 4, 8, and 12 h after levodopa administration (100 mg/kg), dopamine, dihydroxyphenylacetic acid, and homovanillic acid were measured in striatum and ventral midbrain, regions containing marked dopaminergic innervation, and in prefrontal cortex and cerebellum, which possess little dopaminergic innervation. Malondialdehyde, a marker of oxidative stress, was measured in additional animals. The return of dopamine and its metabolites to control concentrations tended to be slower (by 3-8 h) in cerebellum and prefrontal cortex than in dopaminergic regions. Malondialdehyde concentrations were decreased (p < 0.05) in ventral midbrain 8 h posttreatment, but increased in cerebellum 12 h posttreatment. We concluded that levodopa increases dopamine metabolism in nondopaminergic as well as dopaminergic regions, with delayed clearance of dopamine and its metabolites in nondopaminergic regions. The slower return of dopamine to control levels in nondopaminergic regions may be relevant to some of the side effects of levodopa. No support was found for the hypothesis that levodopa treatment induces oxidative stress.


Asunto(s)
Encéfalo/metabolismo , Dopaminérgicos/farmacología , Dopamina/metabolismo , Levodopa/farmacología , Peroxidación de Lípido/efectos de los fármacos , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Encéfalo/efectos de los fármacos , Cerebelo/efectos de los fármacos , Cerebelo/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Ácido Homovanílico/metabolismo , Masculino , Mesencéfalo/efectos de los fármacos , Mesencéfalo/metabolismo , Estrés Oxidativo/fisiología , Enfermedad de Parkinson Secundaria/metabolismo , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
14.
J Neurosurg ; 69(3): 459-60, 1988 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-3042921

RESUMEN

One potential source of computerized tomography image artifact during stereotaxic data acquisition is scatter from standard steel-tipped fixation pins as supplied for use with the Brown-Roberts-Wells stereotaxic headframe. In some cases, this can hinder selection of periventricular targets. Replacement of the steel-tipped pins with aluminum-tipped pins, which produce less artifact, helps to facilitate stereotaxic intervention.


Asunto(s)
Ventriculografía Cerebral/métodos , Técnicas Estereotáxicas/instrumentación , Tomografía Computarizada por Rayos X/métodos , Aluminio , Humanos , Acero
15.
Clin Neuropharmacol ; 17(4): 370-9, 1994 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9316685

RESUMEN

In Parkinson's disease (PD), a compensatory increase in dopamine (DA) turnover occurs in the remaining nigrostriatal dopaminergic neurons, resulting in greater exposure of each neuron to hydrogen peroxide (H2O2) derived from oxidative deamination of DA. The formation of oxyradicals from H2O2 is regarded as a mechanism that could contribute to the progression of PD, and incubation of rat striatal synaptosomes with levodopa (LD) results in an increase in oxidized glutathione (GSSG), indicative of oxidant stress. The present study was undertaken to determine whether striatal GSSG levels increase in response to administration of LD in vivo. Acute and repeated (3-week) treatment of normal rats with LD at doses of up to 100 mg/kg did not increase striatal GSSG despite marked increase in DA turnover. These results suggest that intact striatum may possess increased defense capacity against oxidant stress generated by increased DA turnover as compared with isolated synaptosomes.


Asunto(s)
Antiparkinsonianos/farmacología , Dopamina/metabolismo , Glutatión/metabolismo , Levodopa/farmacología , Estrés Oxidativo/fisiología , Sustancia Negra/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Glutatión/análogos & derivados , Disulfuro de Glutatión , Masculino , Enfermedad de Parkinson/metabolismo , Ratas , Ratas Sprague-Dawley , Sustancia Negra/efectos de los fármacos
16.
Mutat Res ; 414(1-3): 63-75, 1998 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-9630520

RESUMEN

The micronucleus assay is a widely accepted method for evaluation of clastogens and aneugens. In the current study, acridine orange (AO) supravital staining was adapted for flow cytometric usage to assess micronucleated cells in rat bone marrow and spleen. Cyclophosphamide was used as a positive control test compound and results were compared to manual scoring in Wright-stained slides. In bone marrow, both manual and flow cytometric methods demonstrated positive dose response-trends for micronucleated polychromatic erythrocytes (MNPCE). Significant elevations in MNPCE were observed at all doses of cyclophosphamide, and comparisons between methods in bone marrow were not statistically different. The flow cytometric method was more sensitive in spleen samples, showing dose- and time-related increases in micronuclei compared with manual scoring. AO proved to be a sensitive discriminator of RNA and DNA, allowing distinct separation of polychromatic erythrocytes (PCE), normochromic erythrocytes (NCE), total nucleated cells (TNC), and micronucleated populations within both PCE and NCE regions. These results support the use of AO-based flow cytometry to provide a rapid and sensitive indicator of micronuclei inducers.


Asunto(s)
Naranja de Acridina , Citometría de Flujo/métodos , Pruebas de Micronúcleos/métodos , Animales , Células de la Médula Ósea/citología , Ciclofosfamida/farmacología , Estudios de Evaluación como Asunto , Ratas , Bazo/citología
17.
Mutat Res ; 414(1-3): 49-61, 1998 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-9630510

RESUMEN

Cytotoxic insult to bone marrow frequently impairs the proliferating and maturational abilities of erythroid cells. Typically, a ratio of enucleated, immature polychromatic erythrocytes (PCE) to mature normochromatic erythrocytes (NCE) is used to assess cytotoxicity in the micronucleus (MN) assay. The effects of cyclophosphamide (CP) on PCE/NCE ratio in rat bone marrow and spleen were assessed by a newly developed flow cytometric procedure using glutaraldehyde-fixed, acridine orange (AO)-stained cells, and compared to manual scoring of PCE/NCE in Wright stained slides. Comparison of methods showed that manual and flow cytometric determination of PCE were not statistically different. Several other parameters of cytotoxicity could be simultaneously assessed because the method allowed use of unfractionated whole bone marrow/spleen cell samples. Absolute numbers of total nucleated cells (TNC), a ratio of TNC to total erythrocytes (TE), and determination of RNA content within the PCE population demonstrated dose- and time-dependent effects with CP treatment. Shifts in RNA content were particularly sensitive, correctly identifying all CP-treated from control specimens, even in those samples where PCE/NCE ratio was similar. The AO methodology provided a more rapid, statistically-superior, and thorough approach in the assessment of bone marrow and spleen cytotoxicity than the conventional manual method of scoring PCE/NCE ratio alone.


Asunto(s)
Naranja de Acridina , Eritrocitos/fisiología , Células Precursoras Eritroides/fisiología , Citometría de Flujo/métodos , Pruebas de Micronúcleos/métodos , Alquilantes/farmacología , Animales , Células de la Médula Ósea/fisiología , Muerte Celular , Ciclofosfamida/farmacología , ARN/análisis , Ratas , Bazo/fisiología
18.
Mutat Res ; 528(1-2): 1-18, 2003 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-12873718

RESUMEN

Our laboratory has previously reported a flow cytometric acridine orange method for detection of micronucleus (MN) in the rat using cyclophosphamide as a test compound. To replace the manual method of scoring and satisfy Good Laboratory Practice (GLP) requirements, an extensive validation of the flow method was required. Therefore, manual scoring and flow cytometric determination of MN were compared using vincristine, chlorambucil, methotrexate, and doxorubicin compounds known to induce MN formation with various mechanisms of action. 1,2-Dimethylhydrazine (1,2-DH), a compound with negative or equivocal MN findings also was evaluated. The flow method consistently demonstrated dose- and time-dependent responses for MN production at all concentrations of vincristine, methotrexate, clorambucil, and doxorubicin. In contrast, manual scoring of slides failed to detect an increase in MN at the lowest doses of doxorubicin (1mg/kg) at 24 or 48 h, and methotrexate at 48 h, or any dose of methotrexate (50, 100, or 250 mg/kg) at 24h. Additionally, a dose-response for methotrexate at 48 h, and chlorambucil at 24 h were missed using manual scoring. For 1,2-DH, the flow method showed a low level (< 1.4-fold) increase in MN at all doses and times. In contrast, the manual method showed five-seven-fold increases at 24 h, but a < two-fold increase at 48 h in the highest dose only. These data may suggest that the flow method has a greater sensitivity and possibly accuracy than manual scoring. Significant decreases in polychromatic erythrocytes (PCE) were seen using both methods at approximately the same dose for all compounds. However, absolute flow cytometric PCE values were consistently higher than manual. Additional cytotoxicity parameters obtained by the flow method allowed a more complete assessment of cytotoxicity than PCE alone. Furthermore, data reported here combined with improved throughput, shortened data turnaround and reporting times, and possibly better precision due to evaluation of much larger numbers of cells clearly demonstrate the usefulness of flow cytometry method in the routine micronucleus evaluation.


Asunto(s)
Naranja de Acridina , Citometría de Flujo , Pruebas de Micronúcleos , 1,2-Dimetilhidrazina/toxicidad , Administración Oral , Animales , Clorambucilo/toxicidad , Relación Dosis-Respuesta a Droga , Doxorrubicina/toxicidad , Masculino , Metotrexato/toxicidad , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Vincristina/toxicidad
19.
J Pharm Pharmacol ; 50(10): 1147-53, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9821662

RESUMEN

The compound CI-1007 (R-(+)-1,2,3,6-tetrahydro-4-phenyl-1 [(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine maleate) has been identified as a partial dopamine agonist and putative antipsychotic in in-vitro and in-vivo neurochemical, neurophysiological and behavioural tests. By use of microdialysis in conjunction with high-performance liquid chromatography (HPLC) with electrochemical detection, the effects of the drug on brain dopamine release, previously observed in anaesthetized animals, were shown to occur in awake animals also. Detection of peripherally administered CI-1007 in the brain, i.e. evidence of the drug's ability to penetrate the blood-brain barrier, was achieved by use of in-vivo brain microdialysis in awake, freely moving rats and capillary HPLC in combination with tandem mass spectrometry (HPLC/MS/MS). Intravenous administration of CI-1007 (40 mg kg-1) significantly inhibits dopamine release in the nucleus accumbens, a region associated with dopamine hyperactivity in schizophrenia, while having a non-significant impact on the striatal dopamine neurotransmission which is critical to regular motor function. The differential neurochemical profile of the drug indicates its potential usefulness in treating positive disease symptoms and implies that its extrapyramidal side effects are lower than those of typical antipsychotics.


Asunto(s)
1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/análogos & derivados , Antipsicóticos/farmacología , Agonistas de Dopamina/farmacología , Dopamina/metabolismo , Núcleo Accumbens/efectos de los fármacos , Corteza Visual/efectos de los fármacos , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacocinética , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Antipsicóticos/farmacocinética , Barrera Hematoencefálica , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Cromatografía , Agonistas de Dopamina/farmacocinética , Masculino , Espectrometría de Masas , Microdiálisis , Núcleo Accumbens/metabolismo , Ratas , Ratas Sprague-Dawley , Corteza Visual/metabolismo
20.
Chemosphere ; 45(4-5): 589-98, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11680755

RESUMEN

In this study, the pulse-amplitude-modulation (PAM)-fluorometric method was used to evaluate the difference in the sensitivity to mercury (Hg) and metolachlor of six algal species: Ankistrodesmus falcatus, Selenastrum capricornutum, Chlorella vulgaris, Nannoplankton (PLS), Microcystis aeruginosa and Pediastrum biwae. We found that the fluorescence parameters (phiM, the maximal photosystem II (PSII) quantum yield, phi'M, the operational PSII quantum yield at steady state of electron transport, Q(P), the photochemical quenching value, and Q(N), the non-photochemical quenching value) were appropriate indicators for inhibitory effects of mercury but only phi'M and Q(N) were useful for metolachlor. The examined algal species showed very different levels of sensitivity to the effect of Hg and of metolachlor. The most sensitive species to Hg and metolachlor were respectively M. aeruginosa and A. falcatus, while the least sensitive were C. vulgaris and P. biwae. We interpreted these differences by the action mode of pollutants and by the different metabolism properties and morphological characteristics between algal species. These results related to fluorescence parameters may offer useful tool to be used in bioassay for different pollutants. Heterogeneous algal sensitivity to the same pollutant suggests the need to use a battery of species to evaluate the effects of mixtures of pollutants in aquatic systems.


Asunto(s)
Acetamidas/efectos adversos , Exposición a Riesgos Ambientales , Eucariontes , Herbicidas/efectos adversos , Mercurio/efectos adversos , Contaminantes Químicos del Agua/efectos adversos , Bioensayo , Fluorescencia , Medición de Riesgo
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