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1.
Phys Rev E ; 109(5): L053002, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38907479

RESUMEN

In amorphous materials, plasticity is localized and occurs as shear transformations. It was recently shown by Wu et al. that these shear transformations can be predicted by applying topological defect concepts developed for liquid crystals to an analysis of vibrational eigenmodes [Z. W. Wu et al., Nat. Commun. 14, 2955 (2023)10.1038/s41467-023-38547-w]. This study relates the -1 topological defects to the displacement fields expected of an Eshelby inclusion, which are characterized by an orientation and the magnitude of the eigenstrain. A corresponding orientation and magnitude can be defined for each defect using the local displacement field around each defect. These parameters characterize the plastic stress relaxation associated with the local structural rearrangement and can be extracted using the fit to either the global displacement field or the local field. Both methods provide a reasonable estimation of the molecular-dynamics-measured stress drop, confirming the localized nature of the displacements that control both long-range deformation and stress relaxation.

2.
Cytotechnology ; 75(2): 135-141, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36969572

RESUMEN

Mycoplasma contamination is a significant problem in cell culture replication and maintenance. From more than 200 known species, a limited number of Mycoplasma species have been detected in cell cultures, representing new species or variants that can escape detection systems. A qPCR commercial kit was used for Mycoplasma detection in cell cultures. Furthermore, an amplified Mycoplasma species was sequenced and summited for sequence assembly, clustering, and evolutionary analysis study. Our work has identified a new and unusual variant or species of Mycoplasma that possesses a high degree of homology with species related with M. mycoides cluster. This variant is usually associated with cattle but has been detected contaminating a cell culture. Mycoplasma testing (even for unusual species) in cell cultures is essential to ensure the validity and reproducibility of research that uses cell cultures and to ensure the quality of cell line deposits in biobanks. For this reason, it is necessary to perform continuous checks for the absence of Mycoplasma in cell cultures and engage in the continuous adaptation of relevant detection systems.

3.
Persoonia ; 39: 143-174, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29503474

RESUMEN

During various surveys of Phytophthora diversity in Europe, Chile and Vietnam slow growing oomycete isolates were obtained from rhizosphere soil samples and small streams in natural and planted forest stands. Phylogenetic analyses of sequences from the nuclear ITS, LSU, ß-tubulin and HSP90 loci and the mitochondrial cox1 and NADH1 genes revealed they belong to six new species of a new genus, officially described here as Nothophytophthora gen. nov., which clustered as sister group to Phytophthora. Nothophytophthora species share numerous morphological characters with Phytophthora: persistent (all Nothophytophthora spp.) and caducous (N. caduca, N. chlamydospora, N. valdiviana, N. vietnamensis) sporangia with variable shapes, internal differentiation of zoospores and internal, nested and extended (N. caduca, N. chlamydospora) and external (all Nothophytophthora spp.) sporangial proliferation; smooth-walled oogonia with amphigynous (N. amphigynosa) and paragynous (N. amphigynosa, N. intricata, N. vietnamensis) attachment of the antheridia; chlamydospores (N. chlamydospora) and hyphal swellings. Main differing features of the new genus are the presence of a conspicuous, opaque plug inside the sporangiophore close to the base of most mature sporangia in all known Nothophytophthora species and intraspecific co-occurrence of caducity and non-papillate sporangia with internal nested and extended proliferation in several Nothophytophthora species. Comparisons of morphological structures of both genera allow hypotheses about the morphology and ecology of their common ancestor which are discussed. Production of caducous sporangia by N. caduca, N. chlamydospora and N. valdiviana from Valdivian rainforests and N. vietnamensis from a mountain forest in Vietnam suggests a partially aerial lifestyle as adaptation to these humid habitats. Presence of tree dieback in all forests from which Nothophytophthora spp. were recovered and partial sporangial caducity of several Nothophytophthora species indicate a pathogenic rather than a saprophytic lifestyle. Isolation tests from symptomatic plant tissues in these forests and pathogenicity tests are urgently required to clarify the lifestyle of the six Nothophytophthora species.

4.
Faraday Discuss ; 180: 11-33, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26079195

RESUMEN

The increase in the rate of hydrogen evolution (HE) on dissolving Mg surfaces with increasing anodic current density or potential, which is sometimes called the negative difference effect, has been the topic of much discussion in recent years. A review of the very recent contributions to this subject is given in this paper. Increased catalytic activity of the corrosion product layer, either from the accumulated impurities or from the Mg oxy-hydroxide itself, is shown to have a minor influence on the anodic HE observed on dissolving Mg at high anodic current densities and potentials. Al exhibits similar characteristics during anodic polarization in concentrated HCl, although the anodic HE rate on Al is less than on Mg. Possible mechanisms for the anodic hydrogen are provided and implications in the area of intergranular corrosion and environmental cracking are discussed.

5.
Dement Geriatr Cogn Dis Extra ; 2(1): 332-42, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22962557

RESUMEN

OBJECTIVE: Our aim was to evaluate clinical and neuropsychological features to identify pre-dementia Alzheimer's disease (PAD) among mild cognitive impairment (MCI) patients. METHODS: A longitudinal prospective study of 89 consecutive patients affected with MCI was conducted. Clinical evaluation consisted of a clinical interview protocol, neuropsychological evaluation, standard laboratory tests, and CT scan. A 6-month clinical check-up was made to determine whether patients remained in MCI, improved or progressed to AD or another dementia. RESULTS: At 3-year follow-up, 47% patients developed AD dementia. Seventeen variables were significant and were evaluated by logistic regression analysis to identify the remaining optimal diagnostic criteria: age, gender, repeating comments, difficulties in understanding explanations, time of symptom evolution, history of depression, and word fluency (with animals) were identified with a sensitivity of 100% and a specificity of 93%. A computer application was developed with all these variables which we have named Clinical Approach to Diagnosis of PAD (CAD-PAD). CONCLUSIONS: These results suggest that CAD-PAD can help in the clinical diagnosis of PAD.

6.
Ars pharm ; 51(supl.3): 541-548, jul. 2010. ilus, tab
Artículo en Español | IBECS | ID: ibc-99514

RESUMEN

La acetilación de residuos de lisina en las histonas está mediada por las enzimas denominadas histona acetiltransferasas (HAT). Los grupos acetilo son eliminados de las e-N-acetil-lisinas por la actividadde las histonas desacetilasas (HDAC). El balance entre las actividades opuestas de las HAT y las HDAC regula el estado de acetilación de las histonas. Este tipo de modificaciones regulan en la célula procesos fundamentales clave en respuesta a señales extracelulares. En general, altos niveles de acetilación (hiperacetilación) se asocian a un incremento de la actividad transcripcional, mientras que bajos niveles de acetilación (hipoacetilación) se asocian a la represión de la expresión genética. Actualmente se conocen diversos tipos de inhibidores de las HDAC que pueden reactivar la expresión genética e inhibir el crecimiento de las células tumorales, por lo que se investiga su uso en el tratamiento frente al cáncer. Sería deseable identificar nuevos inhibidores de las enzimas HDAC para su utilización en el tratamiento o profilaxis de enfermedades en las que la inhibición de dichas enzimas HDAC está implicada. Se han obtenido 10 nuevos inhibidores de las HDAC y se ha evaluado su actividad frente a HDAC aislada. Se discute la importancia de las modificaciones realizadas en el espaciador(AU)


Lysine residues acetylation on histones is mediated by histone acetyltransferase (HAT). The acetyl groups are removed from e-N-acetyl-lysine by the histone deacetylase (HDAC) activity. The balance between the HATs and HDACs activities regulates the histone acetylation status. Such changes regulate key processes in the cell in response to extracellular signals. Mostly, high levels of acetylation(hyperacetylation) are associated with increased transcriptional activity. Low levels of acetylation (hypoacetylation) are associated with repression of gene expression. Currently, different types of HDAC inhibitors are known to reactivate gene expression and inhibit tumor cell growth. We aim at identifying novel HDAC inhibitors for the treatment or prophylaxis of cancer diseases. Ten new HDAC inhibitors have been obtained and their potency as HDAC inhibitors has been evaluated. A structure-activity relationship discussion has been focused on the structural changes made in the spacer(AU)


Asunto(s)
Acetiltransferasa de Residuos Dihidrolipoil-Lisina/análisis , Acetiltransferasa de Residuos Dihidrolipoil-Lisina/síntesis química , Acetiltransferasa de Residuos Dihidrolipoil-Lisina , Histona Acetiltransferasas/análisis , Histona Acetiltransferasas/síntesis química , Histona Acetiltransferasas/farmacología , Acetilación , Enzimas/aislamiento & purificación , Enzimas/farmacología , Enzimas/farmacocinética , Acetiltransferasa de Residuos Dihidrolipoil-Lisina/farmacología , Acetiltransferasa de Residuos Dihidrolipoil-Lisina/farmacocinética , Histona Acetiltransferasas , Histona Acetiltransferasas/farmacocinética
7.
Am J Physiol Endocrinol Metab ; 291(5): E913-21, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16757552

RESUMEN

In previous work, we demonstrated that a 65% protein calorie food restriction started during the third trimester of gestation in rats caused a reduced beta-cell mass at 4 days of life that persisted until adult age. In this study with adult undernourished (U) rats, we investigated 1) whether undernutrition affects the beta-cell growth potential and both beta-cell proliferation and differentiation and 2) the implication of the IGFs, highly responsive to nutritional status, in these processes. To this end, we used the 90% pancreatectomy (Px) procedure in U and control (C) adult rats. The results show that, on day 2 after Px, beta-cell replication was significantly higher in C rats, whereas the beta-cell neogenesis was markedly increased in U/Px rats. Both the serum levels of IGF-I and the liver IGF-I mRNA expression were reduced in adult U rats before and after Px compared with C rats. Pancreatic IGF-I mRNA expression was reduced in U animals on day 0. However, on day 2 after Px, the increase of pancreatic IGF-I mRNA expression was significantly higher in U rats than in C rats. These data suggest that beta-cells still have the capacity to regenerate in the adult U rats, with a higher efficiency than C rats on day 2, and that both beta-cell neogenesis and beta-cell replication are stimulated. The increased pancreatic IGF-I mRNA may be instrumental in these processes.


Asunto(s)
Trastornos Nutricionales en el Feto/patología , Células Secretoras de Insulina/citología , Islotes Pancreáticos/embriología , Pancreatectomía , Regeneración/fisiología , Factores de Edad , Animales , Restricción Calórica , Diferenciación Celular , División Celular , Femenino , Trastornos Nutricionales en el Feto/fisiopatología , Expresión Génica/fisiología , Edad Gestacional , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Islotes Pancreáticos/citología , Islotes Pancreáticos/cirugía , Hígado/embriología , Hígado/fisiología , Masculino , Conductos Pancreáticos/citología , Conductos Pancreáticos/embriología , Embarazo , ARN Mensajero/metabolismo , Ratas
8.
Drug Dev Ind Pharm ; 32(1): 107-13, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16455609

RESUMEN

The influence of sucrose laureate and sucrose oleate on the in vivo percutaneous penetration of octyl methoxycinnamate (OMC) formulated in i) colloidal suspensions (nano-emulsions and nanocapsules), and ii) conventional o/w emulsions was evaluated. The results showed that nano-emulsions formulated with sucrose laureate exhibited the highest penetration in the stratum corneum compared to the other formulations. A two-fold increase in OMC skin deposition was observed with the nano-emulsion containing sucrose laureate when compared to the control. The data obtained suggest that the total amount of OMC detected in the stratum corneum and the penetration depth are strongly dependent upon the formulation's nature, the particle size, and the type of enhancer.


Asunto(s)
Cinamatos/administración & dosificación , Nanoestructuras , Absorción Cutánea , Sacarosa/análogos & derivados , Adulto , Química Farmacéutica , Cinamatos/farmacocinética , Emulsiones , Humanos , Tamaño de la Partícula , Sacarosa/farmacología
9.
Heredity (Edinb) ; 90(4): 302-7, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12692583

RESUMEN

Island differentiation and relationships with congenerics were investigated in the endemic Canary Island bat Plecotus teneriffae, based on approximately 1 kb of mtDNA from the 16S rRNA and cytochrome b genes. P. teneriffae had closer affinities with P. austriacus than with P. auritus. Levels of differentiation between Canary Islands were quite high relative to Pipistrelle-like bats, consistent with philopatric behaviour in the Plecotus genus. Cladogenesis within P. teneriffae appears to have occurred after the emergence of the islands of El Hierro and La Palma during the Pleistocene. An intraspecific network shows that haplotypes from the younger islands of La Palma and El Hierro are connected to the Tenerife haplotype by a similarly large number of mutational steps. This suggests that they were both colonised at a similar time from the much older island of Tenerife. The other Plecotine bat species, Barbastellus barbastellus shows close affinities with B. barbastellus from mainland Spain, with levels of mtDNA divergence being comparable with intraspecific variation within other mammal species.


Asunto(s)
Quirópteros/genética , ADN Mitocondrial/genética , Filogenia , Animales , Islas del Atlántico , Secuencia de Bases , Cartilla de ADN , Geografía , Haplotipos/genética , Funciones de Verosimilitud , Modelos Genéticos , Datos de Secuencia Molecular
10.
Rev Neurol ; 36(8): 756-62, 2003.
Artículo en Español | MEDLINE | ID: mdl-12717656

RESUMEN

OBJECTIVE: To develop a neuropsychological test battery in Spanish for the cognitive evaluation of HIV 1 infected patients. DEVELOPMENT: Departing from the suggestions presented by the work group of the National Institute of Mental Health (USA), a neuropsychological assessment battery was developed. It was named HUMANS (HIV/University of Miami Annotated Neuropsychological test battery in Spanish). This battery includes the following domains: 1) attention and speed of processing information, 2) memory, 3) executive function, 4) language, 5) visuospacial/visuoconstructive abilities, and 6) motor abilities. Administration takes about 3 4 hours. The English parallel version of this battery has been successfully used in English for over a decade with HIV 1 infected patients. In the paper the development and adaptation to Spanish language of the HUMANS neuropsychology section is presented. CONCLUSIONS: HUMANS neuropsychological test battery fulfill the recommendations presented by the work group of the National Institute of Mental Health for evaluating HIV 1 infected patients. Studies regarding validity and reliability are still required.


Asunto(s)
Infecciones por VIH/fisiopatología , VIH-1 , Pruebas Neuropsicológicas , Humanos , Lenguaje , National Institute of Mental Health (U.S.) , Estados Unidos
11.
Rev. neurol. (Ed. impr.) ; 36(8): 756-762, 16 abr., 2003. tab
Artículo en Es | IBECS | ID: ibc-27583

RESUMEN

Objetivo. Desarrollar una batería de diagnóstico neuropsicológico en español para la evaluación cognitiva de pacientes infectados con VIH-1.Desarrollo. Se parte de las sugerencias presentadas por el grupo de trabajo del Instituto Nacional de Salud Mental de EE.UU. y se desarrolla una batería de diagnóstico neuropsicológico, denominada HUMANS (delinglés, HIV/ University of Miami Annotated Neuropsychological test battery in Spanish). Esta batería incluye las siguientes áreas: 1) atención y velocidad de procesamiento de la información, 2) memoria, 3) función ejecutiva, 4) lenguaje, 5) habilidades visuoespaciales /visuoconstruccionales, y 6) habilidades motoras. Su realización requiere aproximadamente 3-4 horas. La versión paralela en inglés de esta batería se ha utilizado con éxito durante más de una década con pacientes VIH-1 positivos. En este artículo se presenta la sección neuropsicológica de la batería HUMANS y se explica el proceso de desarrollo y su adaptación al español. Conclusiones. La batería HUMANS cumple con las recomendaciones hechas por el grupo de trabajo del Instituto Nacional de Salud Mental de los EE.UU. para la evaluación de los cambios cognitivos en pacientes infectados con VIH-1. Sin embargo, todavía se requieren estudios relativos a su validez y confiabilidad (AU)


Objective. To develop a neuropsychological test battery in Spanish for the cognitive evaluation of HIV-1 infected patients. Development. Departing from the suggestions presented by the work group of the National Institute of Mental Health (USA), a neuropsychological assessment battery was developed. It was named HUMANS (HIV/University of Miami Annotated Neuropsychological test battery in Spanish). This battery includes the following domains: 1) attention and speed of processing information, 2) memory, 3) executive function, 4) language, 5) visuospacial/visuoconstructive abilities, and 6) motor abilities. Administration takes about 3-4 hours. The English parallel version of this battery has been successfully used in English for over a decade with HIV-1 infected patients. In the paper the development and adaptation to Spanish language of the HUMANS neuropsychology section is presented. Conclusions. HUMANS neuropsychological test battery fulfill the recommendations presented by the work group of the National Institute of Mental Health for evaluating HIV-1 infected patients. Studies regarding validity and reliability are still required (AU)


Asunto(s)
Humanos , VIH-1 , Pruebas Neuropsicológicas , Estados Unidos , Infecciones por VIH , National Institute of Mental Health (U.S.) , Lenguaje
12.
Mol Phylogenet Evol ; 26(1): 56-63, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12470938

RESUMEN

Evolution of three Canary Island Vespertilionid bat species, Pipistrellus kuhlii, Pipistrellus maderensis, and Hypsugo savii was studied by comparison of approximately 1 kbp of mtDNA (from cytochrome b and 16S rRNA genes) between islands. mtDNA reveals that both P. kuhlii and P. maderensis exist in sympatry on Tenerife (and possibly other islands). Their morphological similarity explains why their co-occurrence had not been detected previously. Levels of sequence divergence are quite low within P. maderensis. Haplotypes were either identical or separated by /=12 mutational steps) indicating colonization of the latter from the former sometime during the last approximately 1.2 Ma, with low subsequent gene flow. Unlike P. maderensis the El Hierro population alone appears to represent an ESU. The H. savii haplotypes detected in Gran Canaria and Tenerife are identical or separated by 1 mutational step.


Asunto(s)
Quirópteros/genética , ADN Mitocondrial , Geografía , Filogenia , Animales , Grupo Citocromo b/genética
13.
Pediatr Res ; 50(4): 508-14, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11568295

RESUMEN

To characterize the thromboxane A2 (TXA2) -induced resistance to the vasodilator effects of the nitric oxide (NO)/cGMP pathway in pulmonary arteries, we have studied the effects of the NO donor sodium nitroprusside on intracellular calcium concentration ([Ca2+]i) and contractile force recorded simultaneously in isolated piglet pulmonary arteries loaded with fura-2 and contracted with norepinephrine or the TXA2 mimetic U46619 and by activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate. In the TXA2 mimetic- and phorbol 12-myristate 13-acetate plus norepinephrine-stimulated arteries, nitroprusside exhibited lower vasodilator efficacy (and lower potency in the TXA2 mimetic-stimulated arteries) but similar reductions in [Ca2+]i compared with arteries activated by norepinephrine. The nonselective serine/threonine kinase inhibitor staurosporine, but not the selective inhibitor of PKC bisindolylmaleimide, potentiated the relaxation of nitroprusside in the TXA2 mimetic-stimulated arteries. In conclusion, the resistance to NO/cGMP-induced vasodilation in arteries stimulated by TXA2 and PKC involves a reduced ability of the Ca2+-independent mechanisms for smooth muscle vasodilation. The resistance to NO in arteries stimulated by TXA2 is sensitive to staurosporine but not to bisindolylmaleimide, suggesting the involvement of an activation of a serine/threonine kinase distinct from PKC.


Asunto(s)
Señalización del Calcio/efectos de los fármacos , Óxido Nítrico/farmacología , Arteria Pulmonar/efectos de los fármacos , Tromboxano A2/farmacología , Vasoconstricción/efectos de los fármacos , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Animales , Inhibidores Enzimáticos/farmacología , Indoles/farmacología , Masculino , Maleimidas/farmacología , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Norepinefrina/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , Arteria Pulmonar/enzimología , Arteria Pulmonar/fisiología , Estaurosporina/farmacología , Porcinos , Acetato de Tetradecanoilforbol/farmacología
14.
Rev. cient. (Bogotá) ; 6(2): 69-74, jul.-dic. 2000. ilus
Artículo en Español | LILACS | ID: lil-385891

RESUMEN

El síndrome de Marshall-Smith se caracteriza por una maduración esquelética acelerada, baja estatura, dismorfismo orofacial, dificultad respiratoria, criptorquidismo, dificultad para prosperar, y retardo mental y sicomotor. Este reporte describe el caso de un niño de 7 años, sexo masculino, que presenta el síndrome de Marshall-Smith. Las características orales son paladar duro profundo, maloclusión dental, y alto riesgo de caries. Se explica el tratamiento odontológico que éste paciente ha recibido hasta el momento.


Asunto(s)
Craneosinostosis , Maloclusión
15.
Br J Pharmacol ; 128(7): 1419-26, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10602320

RESUMEN

1. The endothelial modulation of the relaxant responses to the nitric oxide (NO) donor sodium nitroprusside (SNP) and the KATP channel opener levcromakalim (LEM) and the interactions between these agents were analysed in isolated rat aorta. 2. LEM-induced relaxation was unchanged by endothelium removal or by the presence of L-NAME (10-4 M) or ODQ (10-6 M). In contrast, in KCl- (25 mM), but not in noradrenaline- (NA, 10-6 M) contracted arteries, SNP-induced relaxation was augmented by endothelium removal but not by L-NAME, indomethacin, glibenclamide nor charybdotoxin plus apamin. 3. The isobolographic analysis of the interactions between exogenously activated KATP channels and cyclic GMP using mixtures of SNP and LEM revealed that there were no interactions between both drugs at the proportions at which both drugs were active. However, the points for the SNP : LEM mixtures in proportions 10:1 and 1:10,000 (i.e. at concentrations at which LEM and SNP were inactive, respectively) fell significantly above the line of additivity indicating that there were negative interactions between both drugs at these selected proportions (about 5- and 2 fold inhibition, respectively). The former interaction was sensitive to glibenclamide, whereas the latter was insensitive ODQ. The magnitude of the 10:1 SNP:LEM interaction was smaller in endothelium-intact arteries and was absent in arteries stimulated by NA. 4. In conclusion, the relaxations induced by LEM and SNP were additive. However, the presence of endothelium and low concentrations of LEM inhibited SNP-induced relaxation. Both inhibitory effects were not additive and were only observed in KCl- and not in NA-contracted aortae.


Asunto(s)
Aorta Torácica/efectos de los fármacos , Cromakalim/farmacología , Nitroprusiato/farmacología , Vasodilatadores/farmacología , Adenosina Trifosfato/fisiología , Animales , Aorta Torácica/metabolismo , Aorta Torácica/fisiología , GMP Cíclico/antagonistas & inhibidores , GMP Cíclico/biosíntesis , GMP Cíclico/fisiología , Combinación de Medicamentos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiología , Técnicas In Vitro , Masculino , Relajación Muscular/efectos de los fármacos , Relajación Muscular/fisiología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiología , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/fisiología , Donantes de Óxido Nítrico/farmacología , Canales de Potasio/efectos de los fármacos , Canales de Potasio/fisiología , Ratas , Ratas Wistar
16.
Br J Pharmacol ; 126(4): 1025-33, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10193784

RESUMEN

1. The contribution of the relaxant mechanisms of nicorandil (NIC) were analysed by comparing its effects with those of sodium nitroprusside (SNP), levcromakalim (LEM) and mixtures (1:10, 1:30 and 1:100) of SNP:LEM in isolated endothelium-denuded rat aorta. 2. In rings precontracted with KCl (25 mM), the relative inhibitory potency of the soluble guanylate cyclase inhibitor ODQ and the K(ATP) channel inhibitor glibenclamide (GLI) on SNP:LEM mixtures showed a good correlation with the relative proportion of SNP and LEM in the mixtures. Furthermore, the degree of the inhibition by ODQ and GLI of the effects of the 1:30 SNP:LEM mixture varied as a function of the relative potency of SNP and LEM in KCl-, noradrenaline- (NA) or NA plus nifedipine-treated arteries. 3. The inhibitory effects of ODQ, GLI and ODQ plus GLI on NIC-induced relaxation was similar to that for the 1:30 SNP:LEM mixture in NA plus nifedipine-contracted arteries, but the inhibition of GLI or ODQ plus GLI was smaller in KCl-contracted arteries. 4. In conclusion, the relative importance of activation of the cyclic GMP pathway and K(ATP) channel opening in mixtures of SNP and LEM could be predicted by the proportion of the drugs in the mixtures and by the relative potency of SNP vs LEM in different experimental conditions. Furthermore, the present results suggest that besides these two mechanisms, a third ODQ- and GLI-insensitive mechanism, possibly involving Ca2+ channel blockade, also participates in the relaxant effects of NIC in KCl-induced contractions.


Asunto(s)
Aorta/efectos de los fármacos , Cromakalim/farmacología , Nicorandil/farmacología , Nitroprusiato/farmacología , Vasodilatadores/farmacología , Animales , Aorta/fisiología , GMP Cíclico/fisiología , Gliburida/farmacología , Técnicas In Vitro , Masculino , Norepinefrina/farmacología , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Vasoconstricción
17.
Graefes Arch Clin Exp Ophthalmol ; 228(4): 350-5, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2401420

RESUMEN

Intravitreal 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (DHPG) has been advocated as an alternative mode of therapy in cytomegalovirus (CMV) retinitis in the acquired immunodeficiency syndrome (AIDS) because of toxic neutropenia which is a complication of systemic intravenous DHPG. The recommended regimen requires injection of 200 micrograms DHPG intravitreally twice a week for a period of several weeks to months to control the progression of CMV retinitis. A previous study performed to determine the safe dose of intravitreal DHPG was based on a single intravitreal dose study; it does not consider the toxicity which may arise from multiple intravitreal injections of DHPG as it is utilized in the treatment of patients with CMV retinitis. In our study, intravitreal injections of 1000, 400, 200, 100, 50, and 25 micrograms DHPG were administered weekly for a period of 5 weeks in rabbit eyes. Ocular toxicity was monitored using slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and light and electron microscopy. Electroretinographic evidence of retinal toxicity was found with doses as low as 100 micrograms. Electron-micrographic studies of retinal tissue from the eyes injected with even lower doses (as low as 25 micrograms) also showed evidence of toxic vacuolization in the inner segments of the photoreceptor.


Asunto(s)
Ganciclovir/toxicidad , Retina/efectos de los fármacos , Animales , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Electrorretinografía/efectos de los fármacos , Ganciclovir/administración & dosificación , Ganciclovir/farmacocinética , Oftalmoscopía , Células Fotorreceptoras/efectos de los fármacos , Células Fotorreceptoras/ultraestructura , Conejos , Retina/ultraestructura , Cuerpo Vítreo
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